George A. Poultsides, MD, MS, FACS
Professor of Surgery (General Surgery) at the Stanford University Medical Center
Surgery - General Surgery
Practices at Stanford Hospital and Clinics
Web page: http://med.stanford.edu/profiles/George_Poultsides/
Dr. Poultsides is Section Chief of Surgical Oncology and Professor of Surgery at Stanford University. He is an oncologic surgeon specializing in the removal of liver, pancreatic, and other abdominal tumors. He joined Stanford in 2009 after completing fellowship training in Surgical Oncology at Memorial Sloan Kettering and in Hepato-Pancreato-Biliary (HPB) Surgery at Johns Hopkins.
Dr. Poultsides serves as Physician Lead of the GI Oncology Clinical Research Program at the Stanford Cancer Institute. His research program focuses on outcomes analysis following multidisciplinary treatment of hepatic, pancreatic and gastrointestinal malignancies. He has received a Masters Degree in Epidemiology from Stanford University and has led several nationwide, multi-institutional clinical research collaborations across several academic medical centers in the US. Within Stanford, Dr. Poultsides has developed a novel interdisciplinary research program assessing the completeness of surgical resection for pancreatic cancer. He has been the principal investigator in two, first in human, prospective clinical trials evaluating the role of mass spectrometric and intraoperative fluorescent imaging during surgery for pancreatic cancer. These research efforts were funded through the 2012 Stanford Hospital Cancer Innovation Fund award and the 2016 Stanford Cancer Institute translational research award. In addition, Dr. Poultsides sits on the guidelines panel of the National Comprehensive Cancer Network for gastric and esophageal cancer.
For his contributions to the education of the next generation of surgeons, Dr. Poultsides received the John Austin Collins, MD annual teaching award from the Stanford Surgery residents in 2013 and the Best Rotation award from the Stanford Surgery chief residents in 2012, 2016, 2017, and 2018.
Cancer > GI Oncology
Liver Neoplasms
Pancreas Neoplasms
Gastric Neoplasms
Bile Duct Neoplasms
Gallbladder Neoplasms
Adrenal Neoplasms
Professor - University Medical Line, Surgery - General Surgery
Chief, Section of Surgical Oncology, Stanford University (2019 - Present)
Lead, Gastrointestinal Oncology Clinical Research Program, Stanford Cancer Institute (2019 - Present)
Program Director, Stanford University Complex General Surgical Oncology (CGSO) Fellowship (2019 - Present)
Instructor in Surgery, Johns Hopkins University School of Medicine (2008 - 2009)
Bay Area Top Doctors, Castle Connolly (2018)
Best PGY-5 Rotation Award, Stanford General Surgery Chief Residents (2018)
James Foster Visiting Professor, University of Connecticut School of Medicine, Department of Surgery (2017)
Translational Research Award, Stanford Cancer Institute (2016)
John Austin Collins, MD Memorial Award for Outstanding Teaching and Dedication to Resident Training, Department of Surgery, Stanford University (2013)
Cancer Innovation Fund Award, Stanford Hospital and Clinics (2012)
Henry Mannix, Jr, MD Award for Clinical and Academic Excellence, Saint Francis Hospital & Medical Center, University of Connecticut School of Medicine (2007)
Ludwig J. Pyrtek, MD Prize for Clinical and Scientific Capabilities, Department of Surgery, Hartford Hospital, University of Connecticut School of Medicine (2007)
Andrew Canzonetti, MD Award, Outstanding 4th Year Surgery Resident, Department of Surgery, University of Connecticut School of Medicine (2006)
Charles Polivy, MD Memorial Award, Department of Surgery, Hartford Hospital, University of Connecticut School of Medicine (2005)
Editorial Board, Annals of Surgical Oncology (2018 - Present)
Editorial Board, Journal of Gastrointestinal Surgery (2018 - Present)
Editorial Board, Journal of Surgical Oncology (2017 - Present)
Associate Editor, BMC Cancer (2015 - 2020)
Residency: University of Connecticut School of Medicine Registrar (2007) CT
Internship: University of Connecticut School of Medicine Registrar (2003) CT
Fellowship: Johns Hopkins University School of Medicine (2009) MD
Fellowship: Memorial Sloan-Kettering Cancer Center (2008) NY
MS, Stanford University, Epidemiology (2011)
Board Certification: American Board of Surgery, General Surgery (2008)
Medical Education: University of Athens Medical School (2000) Greece
gpoultsides@stanford.edu
University - Faculty Department:&nbspSurgery - General Surgery Position: Professor-Univ Med Line
Alternate Contact April Leyson Administrative Associate aleyson@stanford.edu
Clinical Surgical Oncology 875 Blake Wilbur Dr Clinic F MC 6560 Stanford, CA 94305
Clinical Stanford Cancer Center 875 Blake Wilbur Dr Rm 2313 MC 6560 Stanford, CA 94309
Stanford Surgical Oncology
New Stanford Surg Onc Chief
Clinical trials of experimental diagnostics and therapeutics; outcomes analysis following combined modality treatment of hepatic, pancreatic, and gastrointestinal malignancies.
Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer Recruiting
This phase III trial compares perioperative chemotherapy (given before and after surgery) versus adjuvant chemotherapy (given after surgery) for the treatment of pancreatic cancer that can be removed by surgery (removable/resectable). Chemotherapy drugs, such as fluorouracil, irinotecan, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before and after surgery (perioperatively) may work better in treating patients with pancreatic cancer compared to giving chemotherapy after surgery (adjuvantly).
Cetuximab-IRDye 800CW and Intraoperative Imaging in Finding Pancreatic Cancer in Patients Undergoing Surgery Not Recruiting
This phase 1-2 trial studies the side effects and best dose of cetuximab-IRDye 800CW when used with intraoperative imaging, to determine the utility of cetuximab-IRDye 800CW to identify and assess pancreatic cancer in patients undergoing surgery to remove the tumor. Cetuximab-IRDye 800CW may help doctors better identify cancer in the operating room by making the cancer visible when viewed through a fluorescent imaging system.
Stanford is currently not accepting patients for this trial. For more information, please contact Alifia Hasan, 650-721-4088.
Panitumumab-IRDye800 in Patients With Pancreatic Cancer Undergoing Surgery Not Recruiting
This phase I/II trial studies the side effects and best dose of panitumumab-IRDye800 and to see how well it works in finding cancer in patients with pancreatic cancer who are undergoing surgery. Panitumumab-IRDye800 is a combination of the antibody drug panitumumab and IRDye800CW, an investigational dye that can be seen using a special camera. Panitumumab-IRDye800 may attach to tumor cells and make them more visible during surgery in patients with pancreatic cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Nick Oberhelman, 650-724-3866.
Pilot Study of 89-Zr Panitumumab in Pancreas Cancer Not Recruiting
The main purpose of the study is to assess the safety of 89Zr-panitumumab as a molecular imaging agent in patients with (metastatic) pancreas cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Alexander A Valencia, 650-498-5185.
Prognostic Value of Baseline Computed Tomography (CT) Perfusion Parameters of Pancreatic Cancer for Patients Undergoing Stereotactic Body Radiotherapy or Surgical Resection Not Recruiting
The purpose of this study is first, to determine whether baseline perfusion characteristics of pancreatic cancer, as characterized by CT perfusion studies, can predict tumor response to treatment by stereotactic body radiotherapy (SBRT). The second goal of this study is to determine whether baseline perfusion characteristics in those patients with resectable pancreatic cancer correlate with immunohistologic markers of angiogenesis such as microvessel density and vascular endothelial growth factor (VEGF) expression.
Stanford is currently not accepting patients for this trial. For more information, please contact Lindee Burton, (650) 725 - 4712.
Directed Reading in Surgery
SURG 299 (Aut, Win, Spr, Sum)
M. Usman Ahmad
Epidemiology (Masters Program)
Extremity Soft Tissue Sarcoma: A Multi-Institutional Validation of Prognostic Nomograms. Annals of surgical oncology Squires, M. H., Ethun, C. G., Donahue, E. E., Benbow, J. H., Anderson, C. J., Jagosky, M. H., Manandhar, M., Patt, J. C., Kneisl, J. S., Salo, J. C., Hill, J. S., Ahrens, W., Prabhu, R. S., Livingston, M. B., Gower, N. L., Needham, M., Trufan, S. J., Fields, R. C., Krasnick, B. A., Bedi, M., Votanopoulos, K., Chouliaras, K., Grignol, V., Roggin, K. K., Tseng, J., Poultsides, G., Tran, T. B., Cardona, K., Howard, J. H. 1800
BACKGROUND: Prognostic nomograms for patients with resected extremity soft tissue sarcoma (STS) include the Sarculator and Memorial Sloan Kettering (MSKCC) nomograms. We sought to validate these two nomograms within a large, modern, multi-institutional cohort of resected primary extremity STS patients.METHODS: Resected primary extremity STS patients from 2000 to 2017 were identified across nine high-volume U.S. institutions. Predicted 5- and 10-year overall survival (OS) and distant metastases cumulative incidence (DMCI), and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated with Sarculator and MSKCC nomograms, respectively. Predicted survival probabilities stratified in quintiles were compared in calibration plots to observed survival assessed by Kaplan-Meier estimates. Cumulative incidence was estimated for DMCI. Harrell's concordance index (C-index) assessed discriminative ability of nomograms.RESULTS: A total of 1326 patients underwent resection of primary extremity STS. Common histologies included: undifferentiated pleomorphic sarcoma (35%), fibrosarcoma (13%), and leiomyosarcoma (9%). Median tumor size was 8.0 cm (IQR 4.5-13.0). Tumor grade distribution was: Grade 1 (13%), Grade 2 (9%), Grade 3 (78%). Median OS was 172 months, with estimated 5- and 10-year OS of 70% and 58%. C-indices for 5- and 10-year OS (Sarculator) were 0.72 (95% CI 0.70-0.75) and 0.73 (95% CI 0.70-0.75), and 0.72 (95% CI 0.69-0.75) for 5- and 10-year DMCI. C-indices for 4-, 8-, and 12-year DSS (MSKCC) were 0.71 (95% CI 0.68-0.75). Calibration plots showed good prognostication across all outcomes.CONCLUSIONS: Sarculator and MSKCC nomograms demonstrated good prognostic ability for survival and recurrence outcomes in a modern, multi-institutional validation cohort of resected primary extremity STS patients. External validation of these nomograms supports their ongoing incorporation into clinical practice.
Detection of MDM2 amplification by shallow whole genome sequencing of cell-free DNA of patients with dedifferentiated liposarcoma. PloS one Przybyl, J., Spans, L., Ganjoo, K., Bui, N., Mohler, D., Norton, J., Poultsides, G., Debiec-Rychter, M., van de Rijn, M. 2022; 17 (1): e0262272
High-level amplification of MDM2 and other genes in the 12q13-15 locus is a hallmark genetic feature of well-differentiated and dedifferentiated liposarcomas (WDLPS and DDLPS, respectively). Detection of this genomic aberration in plasma cell-free DNA may be a clinically useful assay for non-invasive distinction between these liposarcomas and other retroperitoneal tumors in differential diagnosis, and might be useful for the early detection of disease recurrence. In this study, we performed shallow whole genome sequencing of cell-free DNA extracted from 10 plasma samples from 3 patients with DDLPS and 1 patient with WDLPS. In addition, we studied 31 plasma samples from 11 patients with other types of soft tissue tumors. We detected MDM2 amplification in cell-free DNA of 2 of 3 patients with DDLPS. By applying a genome-wide approach to the analysis of cell-free DNA, we also detected amplification of other genes that are known to be recurrently affected in DDLPS. Based on the analysis of one patient with DDLPS with longitudinal plasma samples available, we show that tracking MDM2 amplification in cell-free DNA may be potentially useful for evaluation of response to treatment. The patient with WDLPS and patients with other soft tissue tumors in differential diagnosis were negative for the MDM2 amplification in cell-free DNA. In summary, we demonstrate the feasibility of detecting amplification of MDM2 and other DDLPS-associated genes in plasma cell-free DNA using technology that is already routinely applied for other clinical indications. Our results may have clinical implications for improved diagnosis and surveillance of patients with retroperitoneal tumors.
Surgical treatment of gastric adenocarcinoma: Are we achieving textbook oncologic outcomes for our patients? Journal of surgical oncology Spolverato, G., Paro, A., Capelli, G., Dalmacy, D., Poultsides, G. A., Fields, R. C., Weber, S. M., Votanopoulos, K. I., He, J., Maithel, S. K., Pucciarelli, S., Pawlik, T. M. 1800
BACKGROUND AND OBJECTIVES: Composite measures are increasingly used to assess quality of care in surgical oncology. We sought to define the incidence of "textbook oncologic outcome" (TOO) following resection of gastric adenocarcinoma among a large, international cohort of patients.METHODS: Gastric adenocarcinoma patients undergoing resection between 2000 and 2020 were identified from an international database. TOO was defined as margin-negative resection, examination of ≥16 lymph nodes, no prolonged length-of-stay (LOS), no 30-day mortality, and stage-appropriate receipt of chemotherapy.RESULTS: Among a total of 910 patients, 321 patients (35.3%) achieved a postoperative TOO. While failure to evaluate ≥16 lymph nodes (n=591, 65.0%) and receipt of chemotherapy (n=651, 71.5%) had the greatest negative impact on the ability to obtain a TOO, no 30-day mortality (n=880, 96.7%), margin-negative resection (n=831, 91.3%), and no extended LOS (n=706, 77.6%) were more commonly achieved. No postoperative complications (OR: 0.44;95% CI:0.31-0.63) and T1a/T1b-stage disease (OR: 2.87;95% CI:1.59-5.18) were independently associated with achieving a TOO (p<0.05). The odds of achieving a TOO improved over time (p-trend<0.05), which was largely attributable to improved odds of evaluating≥16 lymph nodes (2010-2014 vs. 2000-2004:OR,5.21;95% CI: 3.22-8.45).CONCLUSIONS: Only about onein threepatients achieved a TOO following resection of gastric adenocarcinoma. Odds of TOO increased over time, largely due to improved lymph node evaluation.
View details for DOI 10.1002/jso.26778
Dynamic Prediction of Survival after Curative Resection of Gastric Adenocarcinoma: A landmarking-based analysis. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology Spolverato, G., Azzolina, D., Paro, A., Lorenzoni, G., Gregori, D., Poultsides, G., Fields, R. C., Weber, S. M., Votanopoulos, K., Maithel, S. K., Pucciarelli, S., Pawlik, T. M. 1800
BACKGROUND: Accurate estimation of survival and recurrence are important to inform decisions regarding therapy and surveillance. We sought to design and validate a dynamic prognostic model for patients undergoing resection for gastric adenocarcinoma.METHODS: Patients who underwent curative-intent surgery for gastric adenocarcinoma between 2000 and 2020 were identified using a multi-institutional database. Landmark analysis was used to create dynamic OS and DFS prediction models. Model performance was internally cross-validated via bootstrap resampling.RESULTS: Among 895 patients, 507 (57.2%) patients underwent partial gastrectomy (n=507, 57.2%) while 380 (42.8%) had total gastrectomy. Median tumor size was 40mm (IQR: 25-65), most tumors were located in the antrum (n=344, 39.5%) and infiltrated the subserosa (T3 tumors: n=283, 31.9%) or serosa (T4 tumors: n=253, 28.5%); lymph node metastasis occurred in 528 (59.1%) patients. Median OS and DFS were 17.5 (IQR: 7.5-42.8) and 14.3 months (IQR: 6.5-39.9), respectively. The impact of age, sex, preoperative comorbidities, tumor size and location, extent of lymphadenectomy and total number of lymph nodes examined, Lauren class, T and N category, postoperative complications, and tumor recurrence varied over time (all p<0.05). An online tool to predict dynamic OS and DFS based on patient survival relative to time survived was developed and made available for clinical use. Discrimination ability of OS and DFS was excellent (C-index: 0.84 and 0.86, respectively) and calibration plots revealed good prediction.CONCLUSIONS: An online dynamic prognostic tool was developed and validated to predict OS and DFS following resection of gastric adenocarcinoma. Landmark analysis to predict long-term outcomes based on follow-up time may be helpful to surgeons and patients.
View details for DOI 10.1016/j.ejso.2021.11.127
Non-transplantable Recurrence After Resection for Transplantable Hepatocellular Carcinoma: Implication for Upfront Treatment Choice. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Zhang, X., Xue, F., Bagante, F., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Lv, Y., Pawlik, T. M. 2021
OBJECTIVES: To identify the preoperative risk factors for prediction of non-transplantable recurrence (NTR) after tumor resection for early-stage hepatocellular carcinoma (HCC) to assist in patient selection relative toupfront liver resection (LR) versus livertransplantation (LT).METHODS: Patients who underwent curative resection for transplantable HCC and chronic liver disease were identified from an international multi-institutional database. NTR was defined as recurrence beyond the Milan or UCSF criteria, and the preoperative risk factors of NTR were investigated.RESULTS: Among 293 patients with transplantable HCC within Milan criteria and 320 within UCSF criteria, 113 (38.6%) and 131 (40.9%) patients developed tumor recurrence, respectively. Among patients who recurred, NTR was present in 32 (28.3%) patients within Milan and 35 (26.7%) within UCSF criteria. When either Milan or UCSF criteria was adopted, three preoperative risk factors including liver cirrhosis, tumor size>3cm, and multiple lesions were consistently identified as risk factors associated with NTR after curative resection. By summing up the three factors, a scoring model was established and the incidence of NTR among patients with 0,1 or≥2 risk factors incrementally increased from 4.5%, 13.3% to 20.5% when Milan criteria was used, and from 4.5%, 12.4% to 33.9% when UCSF criteria was adopted. The model demonstratedvery good discriminatory power on internal validation (n=5,000) (c-index 0.689 for Milan criteria, and 0.715 for UCSF criteria).CONCLUSIONS: Whereas surgical resection may be optimal first-line treatment forpatients with no or one risk factor, patients with≥2 risk factors should be considered for upfront liver transplantation.
Resection Status Does Not Impact Recurrence in Well-Differentiated Liposarcoma of the Extremity AMERICAN SURGEON Olson, C. R., Suarez-Kelly, L. P., Ethun, C. G., Shelby, R. D., Yu, P. Y., Hughes, T. M., Palettas, M., Tran, T. B., Poultsides, G., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B. A., Fields, R. C., King, D. M., Bedi, M., Pollock, R. E., Grignol, V. P., Cardona, K., Howard, J. 2021: 31348211054536
Well-differentiated liposarcoma (WDLPS) is a low-grade soft tissue sarcoma with a propensity for local recurrence. The necessity of obtaining microscopically free surgical margins (R0) to minimize local recurrence is not clear. This study evaluates recurrence-free survival (RFS) of extremity WDLPS in relation to resection margin status.A retrospective review of adult patients with primary extremity WDLPS at seven US institutions from 2000 to 2016 was performed. Patients with recurrent tumors or incomplete resection (R2) were excluded. Clinicopathologic factors were analyzed to assess impact on local RFS.97 patients with primary extremity WDLPS were identified. The majority of patients had deep, lower extremity tumors. Mean tumor size was 18.2±8.9cm. Patients were treated with either radical (76.3%) or excisional (23.7%) resections; 64% had R0 and 36% had microscopically positive (R1) resection margins. Ten patients received radiation therapy with no difference in receipt of radiation between R0 vs R1 groups. Thirteen patients (13%) developed a local recurrence with no difference in RFS between R0 vs R1 resection. Five-year RFS was 59.5% for R0 vs 85.2% for R1. Only one patient died of disease after developing dedifferentiation and distant metastasis despite originally having an R0 resection.In this large multi-institutional study of surgical resection of extremity WDLPS, microscopically positive margins were not associated with an increased risk of recurrence. Positive microscopic margin resection for extremity WDLPS may yield similar rates of local control while avoiding a radical approach to obtain microscopically negative margins.
View details for DOI 10.1177/00031348211054536
Predictors of Desmoid Recurrence after Surgical Management from the US Sarcoma Collaborative Chouliaras, K., Ethun, C. G., Poultsides, G. A., Howard, J., Clarke, C. N., Roggin, K. K., Fields, R. C., Levine, E. A., Cardona, K., Votanopoulos, K. I. ELSEVIER SCIENCE INC. 2021: S239-S240
More Than an ERAS Pathway is Needed to Meet Target Length of Stay After Pancreaticoduodenectomy. The Journal of surgical research Ayala, C. I., Li, A. Y., Lu, A., Wilson, A., Bergquist, J. R., Poultsides, G. A., Norton, J. A., Visser, B. C., Dua, M. M. 2021; 270: 195-202
BACKGROUND: Enhanced Recovery After Surgery (ERAS) protocols have been successfully instituted for pancreaticoduodenectomy (PD). This study evaluates reasons patients fail to meet length of stay (LOS) and areas for pathway improvement.MATERIALS AND METHODS: A multidisciplinary team developed and implemented an ERAS protocol for open PD in 2017. The study includes a medical record review of all patients who were perioperatively managed with the ERAS protocol and failed to meet LOS after PD procedures. Target LOS was defined as 7 d.RESULTS: From 2017 to 2020, 44% (93 of 213) of patients using ERAS protocol after PD procedures failed to meet target LOS. The most common reason to fail target LOS was ileus or delayed gastric emptying (47 of 93, LOS 11). Additional reasons included work-up of leukocytosis or pancreatic leak (17 of 93, LOS 14), additional "night" of observation (14 of 93, LOS 8), and orthostatic hypotension (3 of 93, LOS 10). Of these additional 46 patients, 19 patients underwent computed tomography (on or after POD 7) and only four patients received additional inpatient intervention.CONCLUSIONS: The most common reason for PD pathway failure included slow return of gastrointestinal function, a known complication after PD. The remaining patients were often kept for observation without additional intervention. This group represents an actionable cohort to target for improving LOS through surgeon awareness rather than protocol modification.
View details for DOI 10.1016/j.jss.2021.08.034
Mutant KRAS as a prognostic biomarker after hepatectomy for rectal cancer metastases: does the primary disease site matter? Journal of hepato-biliary-pancreatic sciences Amini, N., Andreatos, N., Margonis, G. A., Buettner, S., Wang, J., Galjart, B., Wagner, D., Sasaki, K., Angelou, A., Sun, J., Kamphues, C., Beer, A., Morioka, D., Marie Loes, I., Antoniou, E., Imai, K., Pikoulis, E., He, J., Kaczirek, K., Poultsides, G., Verhoef, C., Lonning, P. E., Endo, I., Baba, H., Kornprat, P., NAucejo, F., Kreis, M. E., Wolfgang, C. L., Weiss, M. J., Safar, B., Burkhart, R. A. 2021
BACKGROUND: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown.METHODS: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed.RESULTS: A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio (HR): 1.58, 95%CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95%CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95%CI 1.22-1.99; codon 13, HR 2.10 95%CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy.CONCLUSIONS: While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.
View details for DOI 10.1002/jhbp.1054
ASO Visual Abstract: Development of a Prognostic Nomogram and Nomogram Software Application Tool to Predict Overall Survival and Disease-Free Survival After Curative-Intent Gastrectomy for Gastric Cancer. Annals of surgical oncology Spolverato, G., Capelli, G., Lorenzoni, G., Gregori, D., Squires, M. H., Poultsides, G. A., Fields, R. C., Bloomston, M. P., Weber, S. M., Votanopoulos, K. I., Acher, A. W., Jin, L. X., Hawkins, W. G., Schmidt, C. R., Kooby, D. A., Worhunsky, D. J., Saunders, N. D., Levine, E. A., Cho, C. S., Maithel, S. K., Pucciarelli, S., Pawlik, T. M. 2021
View details for DOI 10.1245/s10434-021-10853-x
Development of a Prognostic Nomogram and Nomogram Software Application Tool to Predict Overall Survival and Disease-Free Survival After Curative-Intent Gastrectomy for Gastric Cancer. Annals of surgical oncology Spolverato, G., Capelli, G., Lorenzoni, G., Gregori, D., Squires, M. H., Poultsides, G. A., Fields, R. C., Bloomston, M. P., Weber, S. M., Votanopoulos, K. I., Acher, A. W., Jin, L. X., Hawkins, W. G., Schmidt, C. R., Kooby, D. A., Worhunsky, D. J., Saunders, N. D., Levine, E. A., Cho, C. S., Maithel, S. K., Pucciarelli, S., Pawlik, T. M. 2021
BACKGROUND: We sought to derive and validate a prediction model of survival and recurrence among Western patients undergoing resection of gastric cancer.METHODS: Patients who underwent curative-intent surgery for gastric cancer at seven US institutions and a major Italian center from 2000 to 2020 were included. Variables included in the multivariable Cox models were identified using an automated model selection procedure based on an algorithm. Best models were selected using the Bayesian information criterion (BIC). The performance of the models was internally cross-validated via the bootstrap resampling procedure. Discrimination was evaluated using the Harrell's Concordance Index and accuracy was evaluated using calibration plots. Nomograms were made available as online tools.RESULTS: Overall, 895 patients met inclusion criteria. Age (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.17-1.84), presence of preoperative comorbidities (HR 1.66, 95% CI 1.14-2.41), lymph node ratio (LNR; HR 1.72, 95% CI 1.42-2.01), and lymphovascular invasion (HR 1.81, 95% CI 1.33-2.45) were associated with overall survival (OS; all p<0.01), whereas tumor location (HR 1.93, 95% CI 1.23-3.02), T category (Tis-T1 vs. T3: HR 0.31, 95% CI 0.14-0.66), LNR (HR 1.82, 95% CI 1.45-2.28), and lymphovascular invasion (HR 1.49; 95% CI 1.01-2.22) were associated with disease-free survival (DFS; all p<0.05) The models demonstrated good discrimination on internal validation relative to OS (C-index 0.70) and DFS (C-index 0.74).CONCLUSIONS: A web-based nomograms to predict OS and DFS among gastric cancer patients following resection demonstrated good accuracy and discrimination and good performance on internal validation.
ASO Visual Abstract: Postoperative Infectious Complications Worsen Long-term Survival After Curative-Intent Resection for Hepatocellular Carcinoma. Annals of surgical oncology Wei, T., Zhang, X., Bagante, F., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2021
Postoperative Infectious Complications Worsen Long-Term Survival After Curative-Intent Resection for Hepatocellular Carcinoma. Annals of surgical oncology Wei, T., Zhang, X., Bagante, F., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2021
BACKGROUND: Postoperative infectious complications may be associated with a worse long-term prognosis for patients undergoing surgery for a malignant indication. The current study aimed to characterize the impact of postoperative infectious complications on long-term oncologic outcomes among patients undergoing resection for hepatocellular carcinoma (HCC).METHODS: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The relationship between postoperative infectious complications, overall survival (OS), and recurrence-free survival (RFS) was analyzed.RESULTS: Among 734 patients who underwent HCC resection, 269 (36.6%) experienced a postoperative complication (Clavien-Dindo grade 1 or 2 [n = 197, 73.2%] vs grade 3 and 4 [n = 69, 25.7%]). An infectious complication was noted in 81 patients (11.0%) and 188 patients (25.6%) had non-infectious complications. The patients with infectious complications had worse OS (median: infectious complications [46.5 months] vs no complications [106.4 months] [p < 0.001] and non-infectious complications [85.7 months] [p < 0.05]) and RFS (median: infectious complications [22.1 months] vs no complications [45.5 months] [p < 0.05] and non-infectious complications [38.3 months] [p = 0.139]) than the patients who had no complication or non-infectious complications. In the multivariable analysis, infectious complications remained an independent risk factor for OS (hazard ratio [HR], 1.7; p = 0.016) and RFS (HR, 1.6; p = 0.013). Among the patients with infectious complications, patients with non-surgical-site infection (SSI) had even worse OS and RFS than patients with SSI (median OS: 19.5 vs 70.9 months [p = 0.010]; median RFS: 12.8 vs 33.9 months [p = 0.033]).CONCLUSION: Infectious complications were independently associated with an increased long-term risk of tumor recurrence and death. Patients with non-SSI versus SSI had a particularly worse oncologic outcome.
A novel preoperative risk score to guide patient selection for resection of soft tissue sarcoma lung metastases: An analysis from the United States Sarcoma Collaborative. Journal of surgical oncology Lee, R. M., Ethun, C. G., Gamboa, A. C., Turgeon, M. K., Tran, T., Poultsides, G., Grignol, V., Bedi, M., Mogal, H., Clarke, C. N., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B. A., Fields, R. C., Oskouei, S. V., Monson, D. K., Reimer, N. B., Maithel, S. K., Pickens, A., Cardona, K. 2021
BACKGROUND: Surgical resection for sarcoma lung metastases has been associated with improved overall survival (OS).METHODS: Patients who underwent curative-intent resection of sarcoma lung metastases (2000-2016) were identified from the US Sarcoma Collaborative. Patients with extrapulmonary metastatic disease or R2 resections of primary tumor or metastases were excluded. Primary endpoint was OS.RESULTS: Three hundred and fifty-twopatients met inclusion criteria. Location ofprimary tumor was truncal/extremity in 85% (n=270) and retroperitoneal in 15% (n=49). Forty-nine percent (n=171) of patients had solitary and 51% (n=180) had multiple lung metastasis. Median OS was 49 months; 5-year OS 42%. Age ≥55 (HR1.77), retroperitoneal primary (HR 1.67), R1 resection of primary (HR 1.72), and multiple (≥2) lung metastases (HR 1.77) were associated with decreased OS(all p<0.05). Assigning one point for each factor, we developed a risk score from 0 to 4. Patients were then divided into two risk groups: low (0-1 factor) and high (2-4 factors). The low-risk group (n=159) had significantly better 5-year OS compared to the high-risk group (n=108) (51% vs.16%,p<0.001).CONCLUSION: We identified four characteristics that in aggregate portend a worse OS and created a novel prognostic risk score for patients with sarcoma lung metastases. Given that patients in the high-risk group have a projected OS of <20% at 5 years, this risk score, after external validation, will be an important tool to aid in preoperative counseling and consideration for multimodal therapy.
Impact of Tumor Burden Score on Conditional Survival after Curative-Intent Resection for Hepatocellular Carcinoma: A Multi-Institutional Analysis. World journal of surgery Elfadaly, A. N., Tsilimigras, D. I., Hyer, J. M., Paro, A., Bagante, F., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2021
BACKGROUND: The impact of tumor burden score (TBS) on conditional survival (CS) among patients undergoing curative-intent resection of hepatocellular carcinoma (HCC) has not been examined to date.METHODS: Patients who underwent liver resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS and other clinicopathologic factors on 3-year conditional survival (CS3) was examined.RESULTS: Among 1,040 patients, 263 (25.3%) patients had low TBS, 668 (64.2%) had medium TBS and 109 (10.5%) had high TBS. TBS was strongly associated with OS; 5-year OS was 39.0% among patients with high TBS compared with 61.1% and 79.4% among patients with medium and low TBS, respectively (p<0.001). While actuarial survival decreased as time elapsed from resection, CS increased over time irrespective of TBS. The largest differences between 3-year actuarial survival and CS3 were noted among patients with high TBS (5-years postoperatively; CS3: 78.7% vs. 3-year actuarial survival: 30.7%). The effect of adverse clinicopathologic factors including high TBS, poor/undifferentiated tumor grade, microvascular invasion, liver capsule involvement, and positive margins on prognosis decreased over time.CONCLUSIONS: CS rates among patients who underwent resection for HCC increased as patients survived additional years, irrespective of TBS. CS estimates can be used to provide important dynamic information relative to the changing survival probability after resection of HCC.
A multi-institutional validation study of prognostic nomograms for retroperitoneal sarcoma JOURNAL OF SURGICAL ONCOLOGY Squires, M. H., Ethun, C. G., Donahue, E. E., Benbow, J. H., Anderson, C. J., Jagosky, M. H., Salo, J. C., Hill, J. S., Ahrens, W., Prabhu, R. S., Livingston, M. B., Gower, N. L., Needham, M., Trufan, S. J., Fields, R. C., Krasnick, B. A., Bedi, M., Abbott, D. E., Schwartz, P., Votanopoulos, K., Chouliaras, K., Grignol, V., Roggin, K. K., Tseng, J., Poultsides, G., Tran, T. B., Cardona, K., Howard, J. 2021
Prognostic nomograms for patients undergoing resection of retroperitoneal sarcoma (RPS) include the Sarculator and Memorial Sloan Kettering (MSK) sarcoma nomograms. We sought to validate the Sarculator and MSK nomograms within a large, modern multi-institutional cohort of patients with primary RPS undergoing resection.Patients who underwent resection of primary RPS between 2000 and 2017 across nine high-volume US institutions were identified. Predicted 7-year disease-free (DFS) and overall survival (OS) and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated from the Sarculator and MSK nomograms, respectively. Nomogram-predicted survival probabilities were stratified in quintiles and compared in calibration plots to observed survival outcomes assessed by Kaplan-Meier estimates. Discriminative ability of nomograms was quantified by Harrell's concordance index (C-index).Five hundred and two patients underwent resection of primary RPS. Histologies included leiomyosarcoma (30%), dedifferentiated liposarcoma (23%), and well-differentiated liposarcoma (15%). Median tumor size was 14.0 cm (interquartile range [IQR], 8.5-21.0 cm). Tumor grade distribution was: Grade 1 (27%), Grade 2 (17%), and Grade 3 (56%). Median DFS was 31.5 months; 7-year DFS was 29%. Median OS was 93.8 months; 7-year OS was 51%. C-indices for 7-year DFS, and OS by the Sarculator nomogram were 0.65 (95% confidence interval [CI]: 0.62-0.69) and 0.69 (95%CI: 0.65-0.73); plots demonstrated good calibration for predicting 7-year outcomes. The C-index for 4-, 8-, and 12-year DSS by the MSK nomogram was 0.71 (95%CI: 0.67-0.75); plots demonstrated similarly good calibration ability.In a diverse, modern validation cohort of patients with resected primary RPS, both Sarculator and MSK nomograms demonstrated good prognostic ability, supporting their ongoing adoption into clinical practice.
Patient-derived ex vivo TME-models and single-cell sequencing reveal transcriptional responses to immunotherapy. Sathe, A., Chen, J., Grimes, S. M., Ayala, C. I., Poultsides, G., Ji, H. P. AMER ASSOC CANCER RESEARCH. 2021
ASO Visual Abstract: Prediction of Extrahepatic Recurrence (EHR) After Curative-Intent Resection of Hepatocellular Carcinoma. Annals of surgical oncology Wei, T., Zhang, X., Xue, F., Bagante, F., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2021
View details for DOI 10.1245/s10434-021-10201-z
Surgical Strategies for Bismuth Type I and II Hilar Cholangiocarcinoma: Impact on Long-Term Outcomes. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Zhang, X., Zhang, N., Tsilimigras, D. I., Weber, S. M., Poultsides, G., Hatzaras, I., Fields, R. C., He, J., Scoggins, C., Idrees, K., Shen, P., Maithel, S. K., Pawlik, T. M. 2021
BACKGROUND: The surgical approach to treat Bismuth type I and II hilar cholangiocarcinoma (HCCA) has been a topic of debate. We sought to characterize whether bile duct resection (BDR) with or without concomitant hepatic resection (HR) was associated with R0 margin status, as well asdefine the impact of HR+BDR versus BDR alone on long-term survival.METHODS: Patients who underwent curative-intent HR+BDR for HCCA between 2000 and 2014 were identified from a multi-institutional database. Perioperative and long-term outcomes were compared among patients who underwent BDR only, BDR+left hepatic resection (LHR), and BDR+right hepatic resection (RHR) for Bismuth type I and II HCCA.RESULTS: Among 257 patients with HCCA, 61 (23.7%) patients had aBismuth type I (n=25, 41.0%) or II (n=36, 59.0%) lesion. The incidence ofR0 resection after BDR only was the same as among patients after LHR and RHR (BDR 70.0% vs. BDR+LHR 71.4% vs. BDR+RHR 76.5%, p=0.891). In contrast, severe complications were more likely after LHR and RHR than BDR only (BDR 21.4% vs. BDR+LHR 60.0% and BDR+RHR 50.0%, p=0.041). Overall (median: BDR 20.9 vs. BDR+LHR 23.2 and BDR+RHR 25.0 months, p=0.213) and recurrence-free (median: BDR 13.4 vs. BDR+LHR 15.3 and BDR+RHR 25.0, p= 0.109) survivalwere comparable. On multivariable analysis, while CA19-9>37.0U/ml (Ref. CA19-9≤37.0U/ml, HR 3.2, 95% CI 1.1-9.4, p=0.035) and AJCC T3-T4 disease (Ref. T1-T2, HR 4.6, 95% CI 1.5-13.7, p=0.007) were associated with long-term survival, surgical approach was not (BDR+LHR: HR 1.0, 95% CI 0.5-2.2, p=0.937; BDR+RHR: HR 0.6, 95% CI 0.3-1.3, p=0.197).CONCLUSION: R0 resection, overall survival, and recurrence-free survival were comparableamong well-selectedpatients who had BDR versus BDR+HR for Bismuth type I and II HCCA.
Prediction of pancreatic cancer surgical outcomes and prognosis based on an objective resectability scoring system 2018 Gastrointestinal Cancers Sysmposium (GI-ASCO) Toesca, D. A., Jeffrey, B., von Eyben, R., Poullos, P. D., Poultsides, G. A., Fisher, G. A., Visser, B. C., Koong, A. C., Chang, D. T. 2018: 446
View details for DOI 10.1200/JCO.2018.36.4_suppl.446
Radiographical assessment of tumour stroma and treatment outcomes using deep learning: a retrospective, multicohort study LANCET DIGITAL HEALTH Jiang, Y., Liang, X., Han, Z., Wang, W., Xi, S., Li, T., Chen, C., Yuan, Q., Li, N., Yu, J., Xie, Y., Xu, Y., Zhou, Z., Poultsides, G. A., Li, G., Li, R. 2021; 3 (6): E371-E382
Multi-Institutional Development and External Validation of a Nomogram for Prediction of Extrahepatic Recurrence After Curative-Intent Resection for Hepatocellular Carcinoma. Annals of surgical oncology Wei, T., Zhang, X., Xue, F., Bagante, F., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2021
BACKGROUNDS: Extrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection is associated with unfavorable prognosis. The objectives of the current study were to identify the risk factors and develop a nomogram for the prediction of extrahepatic recurrence after initial curative surgery.METHODS: A total of 635 patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The clinicopathological characteristics, risk factors, and long-term survival of patients with extrahepatic recurrence were analyzed. A nomogram for the prediction of extrahepatic recurrence was established and validated in 144 patients from an external cohort.RESULTS: Among the 635 patients in the derivative cohort, 283 (44.6%) experienced recurrence. Among patients who recurred, 80 (28.3%) patients had extrahepatic ± intrahepatic recurrence, whereas 203 (71.7%) had intrahepatic recurrence only. Extrahepatic recurrence was associated with more advanced initial tumor characteristics, early recurrence, and worse prognosis versus non-extrahepatic recurrence. A nomogram for the prediction of extrahepatic recurrence was developed using the beta-coefficients from the identified risk factors, including neutrophil-to-lymphocyte ratio, multiple lesions, tumor size, and microvascular invasion. The nomogram demonstrated good ability to predict extrahepatic recurrence (c-index: training cohort 0.786; validation cohort: 0.845). The calibration plots demonstrated good agreement between estimated and observed extrahepatic recurrence (p=0.658).CONCLUSIONS: An externally validated nomogram was developed with good accuracy to predict extrahepatic recurrencefollowing curative-intent resection of HCC. Thisnomogram may help identify patients at high risk of extrahepatic recurrence and guide surveillance protocols as well as adjuvant treatments.
Identifying Risk Factors and Patterns for Early Recurrence of Pancreatic Neuroendocrine Tumors: A Multi-Institutional Study CANCERS Heidsma, C. M., Tsilimigras, D. I., Rocha, F., Abbott, D. E., Fields, R., Poultsides, G. A., Cho, C. S., Lopez-Aguiar, A. G., Kanji, Z., Fisher, A. V., Krasnick, B. A., Idrees, K., Makris, E., Beems, M., van Eijck, C. J., Nieveen van Dijkum, E. M., Maithel, S. K., Pawlik, T. M. 2021; 13 (9)
View details for DOI 10.3390/cancers13092242
Serum alpha-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular Carcinoma. Annals of surgical oncology Tsilimigras, D. I., Moris, D., Hyer, J. M., Bagante, F., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2021
INTRODUCTION: Although preoperative alpha-fetoprotein (AFP) has been recognized as an important tumor marker among patients with hepatocellular carcinoma (HCC), the predictive value of AFP levels at the time of recurrence (rAFP) on post-recurrence outcomes has not been well examined.METHODS: Patients undergoing curative-intent resection of HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of rAFP on post-recurrence survival, as well as the impact of rAFP relative to the timing and treatment of HCCrecurrence wereexamined.RESULTS: Among 852 patients who underwent resection of HCC, 307 (36.0%) individuals developed a recurrence. The median rAFP level was 8ng/mL (interquartile range 3-100). Among the 307 patients who developed recurrence, 3-year post-recurrence survival was 48.5%. Patients with rAFP>10ng/mL had worse 3-year post-recurrence survival compared with individuals with rAFP<10ng/mL (28.7% vs. 65.5%, p<0.001). rAFP correlated with survival among patients who had early (3-year survival; rAFP>10 vs. <10ng/mL: 30.1% vs. 60.2%, p<0.001) or late (18.0% vs. 78.7%, p=0.03) recurrence. Furthermore, rAFP levels predicted 3-year post-recurrence survival among patients independent of the therapeutic modality used to treat the recurrent HCC (rAFP>10 vs.<10ng/mL; ablation: 41.1% vs. 76.0%; intra-arterial therapy: 12.9% vs. 46.1%; resection: 37.5% vs. 100%; salvage transplantation: 60% vs. 100%; all p<0.05). After adjusting for competing risk factors, patients with rAFP>10ng/mL had a twofold higher hazard of death in the post-recurrence setting (hazard ratio 1.96, 95% confidence interval 1.26-3.04).CONCLUSION: AFP levels at the time of recurrence following resection of HCC predicted post-recurrence survival independent of the secondary treatment modality used. Evaluating AFP levels at the time of recurrence can help inform post-recurrence risk stratification of patients with recurrent HCC.
Performance of two prognostic scores that incorporate genetic information to predict long-term outcomes following resection of colorectal cancer liver metastases: an external validation of the MD Anderson and JHH-MSK scores. Journal of hepato-biliary-pancreatic sciences Sasaki, K., Gagniere, J., Dupre, A., Ardiles, V., O Connor, J., Wang, J., Moro, A., Morioka, D., Buettner, S., Gau, L., Ribeiro, M., Wagner, D., Andreatos, N., Marie Loes, I., Fitschek, F., Kaczirek, K., Lonning, P., Kornprat, P., Poultsides, G., Kamphues, C., Imai, K., Baba, H., Endo, I., Kwon, C., Aucejo, F. N., Santibanes, E., Kreis, M. E., Margonis, G. 2021
INTRODUCTION: Two novel clinical risk scores (CRS) that incorporate KRAS mutation status (modified CRS (mCRS) and GAME score) were developed. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS.METHODS: Patients undergoing hepatectomy for CRLM (2000-2018) in ten centers were included. The discriminatory abilities of mCRS, GAME, and Fong CRS were evaluated using Harrel's C-index and Akaike's Information Criterion.RESULTS: In the entire cohort, the C-index of the GAME score (0.61) was significantly higher than those of Fong score (0.57) and mCRS (0.54), while the C-Index of mCRS was significantly lower than that of Fong score. When we compared the models in the various geographical regions, the C-index of GAME score was significantly higher than that of mCRS in North America, Europe, and South America. The AIC of Fong score, mCRS, and GAME score were 14405, 14447, and 14319, respectively.CONCLUSION: In conclusion, using the largest and most heterogenous population of CRLM patients with known KRAS status, this independent, external validation demonstrated that the GAME score outperforms both the traditional Fong score and mCRS.
View details for DOI 10.1002/jhbp.963
Recurrence of Non-functional Pancreatic Neuroendocrine Tumors After Curative Resection: A Tumor Burden-Based Prediction Model. World journal of surgery Dong, D., Zhang, X., Lopez-Aguiar, A. G., Poultsides, G., Rocha, F., Weber, S., Fields, R., Idrees, K., Cho, C., Maithel, S. K., Pawlik, T. M. 2021
BACKGROUND: Patients can experience recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs). We sought to develop a nomogram to risk stratify patients relative to recurrence following resection of NF-pNETs.METHODS: Patients who underwent curative-intent resection for NF-pNETs between 1997 and 2016 were identified from a multi-institutional database. The impact of clinicopathologic factors, including tumor burden score (TBS) (TBS2=(maximum tumor diameter)2+(number of tumors)2), was assessed relative to recurrence-free survival (RFS), and a nomogram was developed and internally validated.RESULTS: With a median follow-up of 31.0months (IQR 11.3-56.6months), 66 (15.8%) out of 416 patients in the cohort experienced tumor recurrence. Overall, 3-, 5-, and 10-year RFS following curative-intent resection was 83.2%, 74.0%, and 44.7%, respectively. Several factors were associated with risk of recurrence including tumor grade (referent G1: G2, HR 4.07, 95% CI 2.29-7.26, p<0.001; G3, HR 10.83, 95% CI 3.72-31.53, p<0.001), lymph node metastasis (LNM) (HR 4.71, 95% CI 2.69-8.26, p<0.001), as well as TBS (referent low: medium, HR 4.36, 95% CI 2.06-9.24, p<0.001; high, HR 6.04, 95% CI 2.96-12.31, p<0.001). A weighted nomogram including tumor grade (G1 0, G2 54.19, G3 100), LNM (N0 0, N1 42.06), and TBS (low 0, medium 44.07, high 56.48) was developed. The discriminatory power of the nomogram was very good with a C-index of 0.75 (95% CI, 0.66-0.79) in the training cohort and 0.71 (95% CI, 0.65-0.75) in the validation cohort. In addition, the nomogram performed better than the current 8th edition of AJCC TNM staging system, which had a C-index of 0.67 (95% CI, 0.60-0.73).CONCLUSIONS: A nomogram that incorporated tumor grade, LNM, and TBS was established that had good discrimination and calibration. The nomogram may be an effective tool to stratify patients relative to recurrence risk following resection of NF-pNETs.
Proposed modification of the eighth edition of the AJCC staging system for intrahepatic cholangiocarcinoma. HPB : the official journal of the International Hepato Pancreato Biliary Association Zhang, X., Xue, F., He, J., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Itaru, E., Lv, Y., Pawlik, T. M. 2021
BACKGROUND: To improve the prognostic accuracy of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma (ICC) with establishment and validation of a modified TNM (mTNM) staging system.METHODS: Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide (n=643). An external validation dataset was obtained from the SEER registry (n=797). The mTNM staging system was proposed by redefining T categories, and incorporating the recently proposed N status as N0 (no lymph node metastasis [LNM]), N1 (1-2 LNM) and N2 (≥3 LNM).RESULTS: The 8th AJCC TNM staging system failed to stratify overall survival (OS) of stage II versus IIIA, stage IIIB versus IV, as well as overall stage III versus IV among all patients from the two databases, as well as stage I versus II, and stage III versus III among patients who had ≥6 LNs examined. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the multi-institutional (Median OS, stage I 69.8 vs. II 37.1 vs. III 18.9 vs. IV 16.4 months, all p<0.05), and SEER (Median OS, stage I 87.0 vs. II 29.3 vs. III 17.7 vs. IV 14.2 months, all p<0.05) datasets, which was also verified among patients who had ≥6 lymph node harvested from both databases.CONCLUSION: The modified TNM staging system for ICC using the new T and N definitions provided an improved means to stratify patients relative to long-term OS versus the 8th AJCC staging.
View details for DOI 10.1016/j.hpb.2021.02.009
Defining the Risk of Early Recurrence Following Curative-Intent Resection for Distal Cholangiocarcinoma. Annals of surgical oncology Sahara, K., Tsilimigras, D. I., Toyoda, J., Miyake, K., Ethun, C. G., Maithel, S. K., Abbott, D. E., Poultsides, G. A., Hatzaras, I., Fields, R. C., Weiss, M., Scoggins, C., Isom, C. A., Idrees, K., Shen, P., Yabushita, Y., Matsuyama, R., Endo, I., Pawlik, T. M. 2021
BACKGROUND: Although multidisciplinary treatments including the use of adjuvant therapy (AT) have been adopted for biliary tract cancers, patients with distal cholangiocarcinoma (DCC) can still experience recurrence. We sought to characterize the incidence and predictors of early recurrence (ER) that occurred within 12 months following surgeryfor DCC.PATIENTS AND METHODS: Patients who underwent resection for DCC between 2000 and 2015 were identified from the US multi-institutional database. Cox regression analysis was used to identify clinicopathological factors to develop anER risk score, and the predictive model was validated in an external dataset.RESULTS: Among 245 patients included in the analysis, 67 patients (27.3%) developed ER. No difference was noted in ER rates between patients who did and did not receive AT (28.7% vs. 25.0%, p = 0.55). Multivariable analysis revealed that neutrophil-to-lymphocyte ratio (NLR), peak total bilirubin (T-Bil), major vascular resection (MVR), lymphovascular invasion, and R1 surgical margin status were associated with a higher ER risk. A DIstal Cholangiocarcinoma Early Recurrence Score was developed according to each factor available prior to surgery [NLR > 9.0 (2 points); peak T-bil > 1.5 mg/dL (1 points); MVR (2 points)]. Cumulative ER rates incrementally increased among patients who were low (0 points; 10.6%), intermediate (1-2 points; 26.8%), or high (3-5 points; 57.6%) risk (p < 0.001) in the training dataset, as well as in the validation dataset [low (0 points); 3.4%, intermediate (1-2 points); 32.7%, or high risk (3-5 points); 55.6% (p < 0.001)].CONCLUSIONS: Among patients undergoing resection for DCC, 1 in 4 patients experienced an ER. Alternative treatment strategies such as neoadjuvant chemotherapy may be considered especially among individuals deemed to be at high risk for ER.
Trends and outcomes of simultaneous versus staged resection of synchronous colorectal cancer and colorectal liver metastases. Surgery Tsilimigras, D. I., Sahara, K., Hyer, J. M., Diaz, A., Moris, D., Bagante, F., Guglielmi, A., Ruzzenente, A., Alexandrescu, S., Poultsides, G., Sasaki, K., Aucejo, F., Ejaz, A., Cloyd, J. M., Pawlik, T. M. 2021
BACKGROUND: The objective of this study was to assess trends in the use as well as the outcomes of patients undergoing simultaneous versus staged resection for synchronous colorectal liver metastases.METHODS: Patients undergoing resection for colorectal liver metastases between 2008 and 2018 were identified using a multi-institutional database. Trends in use and outcomes of simultaneous resection of colorectal liver metastases were examined over time and compared with that of staged resection after propensity score matching.RESULTS: Among 1,116 patients undergoing resection for colorectal liver metastases, 690 (61.8%) patients had synchronous disease. Among them, 314 (45.5%) patients underwent simultaneous resection, while 376 (54.5%) had staged resection. The proportion of patients undergoing simultaneous resection for synchronous colorectal liver metastases increased over time (2008: 37.2% vs 2018: 47.4%; ptrend= 0.02). After propensity score matching (n= 201 per group), patients undergoing simultaneous resection for synchronous colorectal liver metastases had a higher incidence of overall (44.8% vs 34.3%; P= .03) and severe complications (Clavien-Dindo ≥III) (16.9% vs 7.0%; P= .002) yet comparable 90-day mortality (3.5% vs 1.0%; P= .09) compared with patients undergoing staged resection. The incidence of severe morbidity decreased over time (2008: 50% vs 2018: 11.1%; ptrend= 0.02). Survival was comparable among patients undergoing simultaneous versus staged resection of colorectal liver metastases (3-year overall survival: 66.1% vs 62.3%; P= .67). Following simultaneous resection, severe morbidity and mortality increased incrementally based on the extent of liver resection and complexity of colectomy.CONCLUSION: While simultaneous resection was associated with increased morbidity, the incidence of severe morbidity decreased over time. Long-term survival was comparable after simultaneous resection versus staged resection of colorectal liver metastases.
View details for DOI 10.1016/j.surg.2021.01.041
Cumulative GRAS Score as a Predictor of Survival After Resection for Adrenocortical Carcinoma: Analysis From the U.S. Adrenocortical Carcinoma Database. Annals of surgical oncology Baechle, J. J., Marincola Smith, P., Solorzano, C. C., Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J., Pawlik, T., Wang, T. S., Glenn, J., Hatzaras, I., Shenoy, R., Phay, J. E., Shirley, L. A., Fields, R. C., Jin, L., Abbott, D. E., Ronnekleiv-Kelly, S., Sicklick, J. K., Yopp, A., Mansour, J., Duh, Q., Seiser, N., Votanopoulos, K., Levine, E. A., Poultsides, G., Kiernan, C. M. 2021
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection.METHODS: A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥3 or Ki67 ≥20%), resection status (micro- or macroscopically positive margin), age (≥50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan-Meier method and log-rank test.RESULTS: Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection.CONCLUSION: In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.
Synergistic Impact of Alpha-Fetoprotein and Tumor Burden on Long-Term Outcomes Following Curative-Intent Resection of Hepatocellular Carcinoma. Cancers Tsilimigras, D. I., Hyer, J. M., Diaz, A., Bagante, F., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2021; 13 (4)
INTRODUCTION: The prognostic role of tumor burden score (TBS) relative to pre-operative alpha -fetoprotein (AFP) levels among patients undergoing curative-intent resection of HCC has not been examined.METHODS: Patients who underwent curative-intent resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS on overall survival (OS) and cumulative recurrence relative to serum AFP levels was assessed.RESULTS: Among 898 patients, 233 (25.9%) patients had low TBS, 572 (63.7%) had medium TBS and 93 (10.4%) had high TBS. Both TBS (5-year OS; low TBS: 76.9%, medium TBS: 60.9%, high TBS: 39.1%) and AFP (>400 ng/mL vs. <400 ng/mL: 48.5% vs. 66.1%) were strong predictors of outcomes (both p < 0.001). Lower TBS was associated with better OS among patients with both low (5-year OS, low-medium TBS: 68.0% vs. high TBS: 47.7%, p < 0.001) and high AFP levels (5-year OS, low-medium TBS: 53.7% vs. high TBS: not reached, p < 0.001). Patients with low-medium TBS/high AFP had worse OS compared with individuals with low-medium TBS/low AFP (5-year OS, 53.7% vs. 68.0%, p = 0.003). Similarly, patients with high TBS/high AFP had worse outcomes compared with patients with high TBS/low AFP (5-year OS, not reached vs. 47.7%, p = 0.015). Patients with high TBS/low AFP and low TBS/high AFP had comparable outcomes (5-year OS, 47.7% vs. 53.7%, p = 0.24). The positive predictive value of certain TBS groups relative to the risk of early recurrence and 5-year mortality after HCC resection increased with higher AFP levels.CONCLUSION: Both TBS and serum AFP were important predictors of prognosis among patients with resectable HCC. Serum AFP and TBS had a synergistic impact on prognosis following HCC resection with higher serum AFP predicting worse outcomes among patients with HCC of a certain TBS class.
Identification of patients who may benefit the most from adjuvant chemotherapy following resection of incidental gallbladder carcinoma. Journal of surgical oncology Xiang, J., Zhang, X., Weber, S. M., Poultsides, G., Fields, R. C., Hatzaras, I., Weiss, M., Scoggins, C., Idrees, K., Shen, P., Maithel, S. K., Pawlik, T. M. 2021
BACKGROUND: To develop a scoring system to identify the subset of patients who may benefit the most from adjuvant chemotherapy following curative-intent resection for incidental gallbladder cancer (IGBC).METHODS: A novel scoring system was utilized to stratify patients relative to overall survival (OS), as well as potential benefit from adjuvant chemotherapy following curative resection for IGBC.RESULTS: Among 266 patients with IGBC, a total of 99 (37.2%) patients received adjuvant chemotherapy. Five risk factors were used to develop an integer-based score to predict OS. Risk of death at 5-years incrementally increased among patients in the low (n=42, 69.0%), medium (n=64, 56.3%) and high-risk groups (n=40, 30.0%) (median OS, 99.4 vs. 33.5 vs. 15.6 months, all p<.001). Use of adjuvant chemotherapy did not provide a survival benefit among patients in the low-risk group (median survival, 99.4 vs. 60.7 months, p=.56). In contrast, utilization of adjuvant chemotherapy was associated with an improvement in survival among medium- (median survival, 21.7 vs. 59.5 months, p=.04) and high-risk patients (median survival, 11.6 vs. 20.1 months, p=.01).CONCLUSIONS: While low-risk patients did not benefit from adjuvant chemotherapy, individuals with medium or high-risk scores had an improved survival with the utilization of adjuvant chemotherapy.
Regional lymph node sampling in hepatoma resection: insight into prognosis. HPB : the official journal of the International Hepato Pancreato Biliary Association Bergquist, J. R., Li, A. Y., Javadi, C. S., Lee, B., Norton, J. A., Poultsides, G. A., Dua, M. M., Visser, B. C. 2021
BACKGROUND: The importance of regional lymph node sampling (LNS) during resection of hepatocellular carcinoma (HCC) is poorly understood. This study sought to ameliorate this knowledge gap through a nationwide population-based analysis.METHODS: Patients who underwent liver resection (LR) for HCC were identified from Surveillance, Epidemiology and End Results (SEER-18) database (2003-2015). Cohort-based clinicopathologic comparisons were made based on completion of regional LNS. Propensity-score matching reduced bias. Overall and disease-specific survival (OS/DSS) were analyzed.RESULTS: Among 5395 patients, 835 (15.4%) underwent regional LNS. Patients undergoing LNS had larger tumors (7.0vs4.8cm) and higher T-stage (30.9 vs. 17.6% T3+, both p<0.001). Node-positive rate was 12.0%. Median OS (50 months for both) and DSS (28 vs. 29 months) were similar between cohorts, but node-positive patients had decreased OS/DSS (20/16 months, p<0.01). Matched patients undergoing LNS had equivalent OS (46 vs. 43 months, p=0.869) and DSS (27 vs. 29 months, p=0.306) to non-LNS patients. The prognostic impact of node positivity persisted after matching (OS/DSS 24/19 months, p<0.01). Overall disease-specific mortality were both independently elevated (overall HR 1.71-unmatched, 1.56-matched, p<0.01; disease-specific HR 1.40-unmatched, p<0.01, 1.25-matched, p=0.09).CONCLUSION: Regional LNS is seldom performed during resection for HCC, but it provides useful prognostic information. As the era of adjuvant therapy for HCC begins, surgeons should increasingly consider performing regional LNS to facilitate optimal multidisciplinary management.
The optimal cut-off values for tumor size, number of lesions, and CEA levels in patients with surgically treated colorectal cancer liver metastases: An international, multi-institutional study. Journal of surgical oncology Kamphues, C., Andreatos, N., Kruppa, J., Buettner, S., Wang, J., Sasaki, K., Wagner, D., Morioka, D., Fitschek, F., Loes, I. M., Imai, K., Sun, J., Poultsides, G., Kaczirek, K., Lonning, P. E., Endo, I., Baba, H., Kornprat, P., Aucejo, F. N., Wolfgang, C. L., Kreis, M. E., Weiss, M. J., Margonis, G. A. 2021
BACKGROUND AND OBJECTIVES: Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen(CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established.METHODS: Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut-offs in the surgical literature.RESULTS: A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut-offs were identified: 2.95cm for tumor size, 1.5 for tumor number and 6.15ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut-offs.CONCLUSION: The current study was able to identify optimal cut-offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut-offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores.
Long-Term Outcomes after Spleen-Preserving Distal Pancreatectomy for Pancreatic Neuroendocrine Tumors: Results from the US Neuroendocrine Study Group. Neuroendocrinology Sahara, K. n., Tsilimigras, D. I., Moro, A. n., Mehta, R. n., Dillhoff, M. n., Heidsma, C. M., Lopez-Aguiar, A. G., Maithel, S. K., Rocha, F. G., Kanji, Z. n., Abbott, D. E., Fisher, A. n., Fields, R. C., Krasnick, B. A., Idrees, K. n., Smith, P. M., Poultsides, G. A., Makris, E. n., Cho, C. S., Beems, M. n., Endo, I. n., Pawlik, T. M. 2021; 111 (1-2): 129–38
The adoption of spleen-preserving distal pancreatectomy (SPDP) for malignant disease such as pancreatic neuroendocrine tumors (pNETs) has been controversial. The objective of the current study was to assess the impact of SPDP on outcomes of patients with pNETs.Patients undergoing a distal pancreatectomy for pNET between 2002 and 2016 were identified in the US Neuroendocrine Tumor Study Group database. Propensity score matching (PSM) was used to compare short- and long-term outcomes of patients undergoing SPDP versus distal pancreatectomy with splenectomy (DPS).Among 621 patients, 103 patients (16.6%) underwent an SPDP. Patients who underwent SPDP were more likely to have lower BMI (median, 27.5 [IQR 24.0-31.2] vs. 28.7 [IQR 25.7-33.6]; p = 0.005) and have undergone minimally invasive surgery (n = 56, 54.4% vs. n = 185, 35.7%; p < 0.001). After PSM, while the median total number of lymph nodes examined among patients who underwent an SPDP was lower compared with DPS (3 [IQR 1-8] vs. 9 [5-13]; p < 0.001), 5-year overall survival (OS) and recurrence-free survival (RFS) were comparable (OS: 96.8 vs. 92.0%, log-rank p = 0.21, RFS: 91.1 vs. 84.7%, log-rank p = 0.93). In addition, patients undergoing SPDP had less intraoperative blood loss (median, 100 mL [IQR 10-250] vs. 150 mL [IQR 100-400]; p = 0.001), lower incidence of serious complications (n = 13, 12.8% vs. n = 28, 27.5%; p = 0.014), and shorter length of stay (median: 5 days [IQR 4-7] vs. 6 days [IQR 5-13]; p = 0.049) compared with patients undergoing DPS.SPDP for pNET was associated with acceptable perioperative and long-term outcomes that were comparable to DPS. SPDP should be considered for patients with pNET.
View details for DOI 10.1159/000506399
Radiographical assessment of tumour stroma and treatment outcomes using deep learning: a retrospective, multicohort study. The Lancet. Digital health Jiang, Y., Liang, X., Han, Z., Wang, W., Xi, S., Li, T., Chen, C., Yuan, Q., Li, N., Yu, J., Xie, Y., Xu, Y., Zhou, Z., Poultsides, G. A., Li, G., Li, R. 2021; 3 (6): e371-e382
The tumour stroma microenvironment plays an important part in disease progression and its composition can influence treatment response and outcomes. Histological evaluation of tumour stroma is limited by access to tissue, spatial heterogeneity, and temporal evolution. We aimed to develop a radiological signature for non-invasive assessment of tumour stroma and treatment outcomes.In this multicentre, retrospective study, we analysed CT images and outcome data of 2209 patients with resected gastric cancer from five independent cohorts recruited from two centres (Nanfang Hospital of Southern Medical University [Guangzhou, China] and Sun Yat-sen University Cancer Center [Guangzhou, China]). Patients with histologically confirmed gastric cancer, at least 15 lymph nodes harvested, preoperative abdominal CT available, and complete clinicopathological and follow-up data were eligible for inclusion. Tumour tissue was collected for patients in the training cohort (321 patients), internal validation cohort one (246 patients), and external validation cohort one (128 patients). Four stroma classes were defined according to the protein expression of α-smooth muscle actin and periostin assessed by immunohistochemistry. The primary objective was to predict the histologically based stroma classes by using preoperative CT images. We trained a deep convolutional neural network model using the training cohort and tested the model in the internal and external validation cohort one. We evaluated the model's association with prognosis in the training cohort, two internal, and two external validation cohorts and compared outcomes of patients who received or did not receive adjuvant chemotherapy.The deep-learning model achieved a high diagnostic accuracy for assessing tumour stroma in both internal validation cohort one (area under the receiver operating characteristic curve [AUC] 0·96-0·98]) and external validation cohort one (AUC 0·89-0·94). The stromal imaging signature was significantly associated with disease-free survival and overall survival in all cohorts (p<0·0001). The predicted stroma classes remained an independent prognostic factor adjusting for clinicopathological variables including tumour size, stage, differentiation, and Lauren histology. In patients with stage II or III disease in predicted stroma classes one and two subgroups, patients who received adjuvant chemotherapy had improved survival compared with those who did not (in those with stage II disease hazard ratio [HR] 0·48 [95% CI 0·29-0·77], p=0·0021; and in those with stage III disease HR 0·70 [0·57-0·85], p=0·00042). However, in the other two subgroups adjuvant chemotherapy was not associated with survival and might even be detrimental in the predicted stroma class 4 subgroup (HR 1·48 [1·08-2·03], p=0·013).The deep-learning model could allow for accurate and non-invasive evaluation of tumour stroma from CT images in gastric cancer. The radiographical model predicted chemotherapy outcomes and could be used in combination with clinicopathological criteria to refine prognosis and inform treatment decisions of patients with gastric cancer.None.
Identifying Risk Factors and Patterns for Early Recurrence of Pancreatic Neuroendocrine Tumors: A Multi-Institutional Study. Cancers Heidsma, C. M., Tsilimigras, D. I., Rocha, F., Abbott, D. E., Fields, R., Poultsides, G. A., Cho, C. S., Lopez-Aguiar, A. G., Kanji, Z., Fisher, A. V., Krasnick, B. A., Idrees, K., Makris, E., Beems, M., van Eijck, C. H., Nieveen van Dijkum, E. J., Maithel, S. K., Pawlik, T. M. 2021; 13 (9)
Identifying patients at risk for early recurrence (ER) following resection for pancreatic neuroendocrine tumors (pNETs) might help to tailor adjuvant therapies and surveillance intensity in the post-operative setting.Patients undergoing surgical resection for pNETs between 1998-2018 were identified using a multi-institutional database. Using a minimum p-value approach, optimal cut-off value of recurrence-free survival (RFS) was determined based on the difference in post-recurrence survival (PRS). Risk factors for early recurrence were identified.Among 807 patients who underwent curative-intent resection for pNETs, the optimal length of RFS to define ER was identified at 18 months (lowest p-value of 0.019). Median RFS was 11.0 months (95% 8.5-12.60) among ER patients (n = 49) versus 41.0 months (95% CI: 35.0-45.9) among non-ER patients (n = 77). Median PRS was worse among ER patients compared with non-ER patients (42.6 months vs. 81.5 months, p = 0.04). On multivariable analysis, tumor size (OR: 1.20, 95% CI: 1.05-1.37, p = 0.007) and positive lymph nodes (OR: 4.69, 95% CI: 1.41-15.58, p = 0.01) were independently associated with ER.An evidence-based cut-off value for ER after surgery for pNET was defined at 18 months. These data emphasized the importance of close follow-up in the first two years after surgery.
Surgical resection of leiomyosarcoma of the inferior vena cava: A case series and literature review. Surgical oncology Zhou, M., Javadi, C., Charville, G. W., Bui, N. Q., Harris, E. J., Poultsides, G. A., Norton, J. A., Visser, B., Lee, B., Dua, M. M., Ganjoo, K. N. 2021; 39: 101670
We review our institution's experience in treating leiomyosarcomas involving the inferior vena cava, and we offer guidance on the management.A text-based search was performed to identify all patients who underwent surgical resection between January 2002 and October 2020. Clinicopathologic data, intraoperative variables, and outcomes were extracted from chart review.Twelve of 16 patients (75%) had localized disease; the remaining had limited metastatic disease. Seven of 16 patients (44%) received neoadjuvant chemotherapy or radiation; three patients had partial responses, and four patients had stable disease using RECIST 1.1 criteria. IVC reconstruction was performed in 14 of 16 patients (88%); IVC was ligated for the remaining two patients. Half of all patients had R0 resection on final pathology; the remaining had R1 resections. Progression-free survival (PFS) and overall survival (OS) were not statistically different between patients with R0 and R1 resection. Median PFS was 1.8 years (95% CI 0.89 - not reached); median OS was 6.5 years (1.8 - not reached). Only one patient (6%) experienced local disease recurrence; 4 of 16 patients (25%) experienced disease recurrence distally without local recurrence.Resection of IVC leiomyosarcomas at a sarcoma referral center with experience in vascular reconstruction can lead to many years of recurrence-free survival. Surgical resection should be offered to patients with a low volume of metastatic disease to reduce local complications from the primary tumor, many of which exert significant mass effect on surrounding organs. For patients with metastatic disease or large, high-risk tumors, neoadjuvant chemotherapy can provide a biologic test of disease stability prior to resection.
View details for DOI 10.1016/j.suronc.2021.101670
Subtle endoscopic manifestations of diffuse signet cell gastric adenocarcinoma in patients with CDH1 mutations. Gastrointestinal endoscopy Ladabaum, U., Ford, J. M., Poultsides, G., Norton, J. 2021
View details for DOI 10.1016/j.gie.2021.08.006
Correction to: Laparoscopic Duodenojejunostomy for Superior Mesenteric Artery Syndrome. Digestive diseases and sciences Magee, G. A., Slater, B. J., Lee, J. T., Poultsides, G. A. 2021
Advances in the surgical management of gastric and gastroesophageal junction cancer. Translational gastroenterology and hepatology Narayan, R. R., Poultsides, G. A. 2021; 6: 16
Since Theodore Billroth and Cesar Roux perfected the methods of post-gastrectomy reconstruction in the late 19th century, surgical management of gastric and gastroesophageal cancer has made incremental progress. The majority of patients with localized disease are treated with perioperative combination chemotherapy or neoadjuvant chemoradiation. Staging laparoscopy before initiation of treatment or before surgical resection has improved staging accuracy and can drastically inform treatment decisions. The longstanding and contentious debate on the optimal extent of lymph node dissection for gastric cancer appears to have settled in favor of D2 dissection with the recently published 15-year follow-up of the Dutch randomized trial. Minimally invasive gastric and gastroesophageal resections are performed routinely in most centers affording faster recovery and equivalent oncologic outcomes. Pylorus-preserving distal (central) gastrectomy has emerged as a less invasive, function-preserving option for T1N0 middle-third gastric cancers, while randomized data on its oncologic adequacy are pending. Multi-visceral resections and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy has been utilized selectively for patients with locally advanced tumors who have demonstrated disease control on preoperative chemotherapy. This review summarizes the current standard of surgical care for gastroesophageal junction and gastric cancer as well as highlights recent and upcoming advances to the field.
View details for DOI 10.21037/tgh.2020.02.06
Advances in the surgical management of gastric and gastroesophageal junction cancer TRANSLATIONAL GASTROENTEROLOGY AND HEPATOLOGY Narayan, R. R., Poultsides, G. A. 2021; 6
Tumor Burden Dictates Prognosis Among Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma: A Tool to Guide Post-Resection Adjuvant Chemotherapy? Annals of surgical oncology Tsilimigras, D. I., Hyer, J. M., Paredes, A. Z., Moris, D., Sahara, K., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Soubrane, O., Koerkamp, B. G., Endo, I., Sasaki, K., Aucejo, F., Zhang, X., Pawlik, T. M. 2020
INTRODUCTION: While tumor burden (TB) has been associated with outcomes among patients with hepatocellular carcinoma, the role of overall TB in intrahepatic cholangiocarcinoma (ICC) remains poorly defined.METHODS: Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified from a multi-institutional database. The impact of TB on overall (OS) and disease-free survival (DFS) was evaluated in the multi-institutional database and validated externally.RESULTS: Among 1101 patients who underwent curative-intent resection of ICC, 624 (56.7%) had low TB, 346 (31.4%) medium TB, and 131 (11.9%) high TB. OS incrementally worsened with higher TB (5-year OS; low TB: 48.3% vs medium TB: 29.8% vs high TB: 17.3%, p<0.001). Similarly, patients with low TB had better DFS compared with medium and high TB patients (5-year DFS: 38.3% vs 18.7% vs 6.9%, p<0.001). On multivariable analysis, TB was independently associated with OS (medium TB: HR=1.40, 95% CI 1.14-1.71; high TB: HR=1.89, 95% CI 1.46-2.45) and DFS (medium TB, HR=1.61, 95% CI 1.33-1.96; high TB: HR=2.03, 95% CI 1.56-2.64). Survival analysis revealed an excellent prognostic discrimination using the TB among the external validation cohort (3-year OS; low TB: 44.8%, medium TB: 29.3%; high TB: 23.3%, p=0.03; 3-year DFS: low TB: 32.7%, medium TB: 10.7%; high TB: 0%, p<0.001). While neoadjuvant chemotherapy was not associated with survival across the TB groups, receipt of adjuvant chemotherapy was associated with increased survival among patients with high TB (5-year OS: 24.4% vs 13.4%, p=0.02).CONCLUSION: Overall TB dictated prognosis among patients with resectable ICC. TB may be used as a tool to help guide post-resection treatment strategies.
Tumor Necrosis Impacts Prognosis of Patients Undergoing Curative-Intent Hepatocellular Carcinoma. Annals of surgical oncology Wei, T., Zhang, X., Bagante, F., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2020
BACKGROUND: The impact of tumor necrosis relative to prognosis among patients undergoing curative-intent resection for hepatocellular carcinoma (HCC) remains ill-defined.METHODS: Patients who underwent curative-intent resection for HCC without any prior treatment between 2000 and 2017 were identified from an international multi-institutional database. Tumor necrosis was graded as absent, moderate (<50% area), or extensive (≥50% area) on histological examination. The relationship between tumor necrosis, clinicopathologic characteristics, and long-term survival were analyzed.RESULTS: Among 919 patients who underwent curative-intent resection for HCC, the median tumor size was 5.0cm (IQR, 3.0-8.5). Tumor necrosis was present in 367 (39.9%) patients (no necrosis: n=552, 60.1% vs<50% necrosis: n=256, 27.9% vs≥50% necrosis: n=111, 12.1%). Extent of tumor necrosis was also associated with more advanced tumor characteristics. HCC necrosis was associated with OS (median OS: no necrosis, 84.0months vs<50% necrosis, 73.6months vs≥50% necrosis: 59.3months; p<0.001) and RFS (median RFS: no necrosis, 49.6months vs<50% necrosis, 38.3months vs≥50% necrosis: 26.5months; p<0.05). Patients with T1 tumors with extensive≥50% necrosis had an OS comparable to patients with T2 tumors (median OS, 62.9 vs 61.8months; p=0.645). In addition, patients with T2 disease with necrosis had long-term outcomes comparable to patients with T3 disease (median OS, 61.8 vs 62.4months; p=0.713).CONCLUSION: Tumor necrosis was associated with worse OS and RFS, as well as T-category upstaging of patients. A modified AJCC T classification that incorporates tumor necrosis should be considered in prognostic stratification of HCC patients.
Impact of time-to-surgery on outcomes of patients undergoing curative-intent liver resection for BCLC-0, A and B hepatocellular carcinoma. Journal of surgical oncology Tsilimigras, D. I., Hyer, J. M., Diaz, A., Moris, D., Bagante, F., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2020
BACKGROUND: The impact of a prolonged time-to-surgery (TTS) among patients with resectable hepatocellular carcinoma (HCC) is not well defined.METHODS: Patients who underwent curative-intent hepatectomy for BCLC-0, A and B HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of prolonged TTS on overall survival (OS) and disease-free survival (DFS) was examined.RESULTS: Among 775 patients who underwent resection for HCC, 537 (69.3%) had early surgery (TTS<90 days) and 238 (30.7%) patients had a delayed surgery (TTS≥90 days). Patient- and tumor-related characteristics were similar between the two groups except for a higher proportion of patients undergoing major liver resection in the early surgery group (31.3% vs. 23.8%, p=.04). The percentage of patients with delayed surgery varied from 8.8% to 59.1% among different centers (p<.001). Patients with TTS<90 days had similar 5-year OS (63.7% vs. 64.9; p=.79) and 5-year DFS (33.5% vs. 42.4; p=.20) with that of patients with TTS≥90 days. On multivariable analysis, delayed surgery was not associated with neither worse OS (BCLC-0/A: adjusted hazards ratio [aHR]=0.90; 95% confidence interval [CI]: 0.65-1.25 and BCLC-B: aHR=0.72; 95%CI: 0.30-1.74) nor DFS (BCLC-0/A: aHR=0.78; 95%CI: 0.60-1.01 and BCLC-B: aHR=0.67; 95% CI: 0.36-1.25).CONCLUSION: Approximately one in three patients diagnosed with resectable HCC had a prolonged TTS. Delayed surgery was not associated with worse outcomes among patients with resectable HCC.
Impact of resection margin on outcomes in high-grade soft tissue sarcomas of the extremity-A USSC analysis. Journal of surgical oncology Chouliaras, K., Patel, N., Senehi, R., Ethun, C. G., Poultsides, G., Grignol, V., Gamblin, T. C., Roggin, K. K., Fields, R. C., D'Agostino, R. J., Levine, E. A., Cardona, K., Votanopoulos, K. 2020
BACKGROUND: The optimal margin of resection for high-grade extremity sarcomas and its impact on survival has long been questioned in the setting of adjuvant radiotherapy. The objective of this study was to investigate the impact of resection status on recurrence and survival.METHODS: All patients with primary, nonmetastatic, high-grade extremity sarcomas that underwent surgical resection from January 2000 to April 2016 in the U.S. Sarcoma Collaborative (USSC) were retrospectively reviewed. Recurrence patterns, recurrence-free survival (RFS), and overall survival (OS) were examined in multivariate analyses (MVA).RESULTS: A cohort of 959 patients was identified with a median follow-up of 34.7 months from diagnosis. R0 resection was achieved in 86.7% (831) while R1 resection in 13.3% (128). Locoregional recurrence for R0 and R1 groups occurred in 9.1% (76) versus 14.8% (19; p=.05) while distant recurrence occurred in 24.7% (205) versus 26.6% (34; p=.65), respectively. Median RFS was 171.2 versus 48.5 (p=.01) while median OS was 149.8 versus 71.5 months (p=.02) for the R0 versus R1 group, respectively. On MVA, female gender (hazard ratio [HR]=0.69, p=.007) and adjuvant radiotherapy (0.7, p=.04) were associated with improved OS, whereas older age (HR=1.03, p<.001) and tumor size (HR=1.01, p<.001) were associated with worse OS. R0 resection status was associated with improved locoregional RFS (HR=0.56, p=.03) but not with distant RFS (HR=0.84, p=.4) or OS (HR=0.7, p=.052).CONCLUSIONS: In high-grade extremity sarcomas, tumor size and gender are predictive of OS while R0 resection status is associated with improved locoregional recurrence rate without a significant impact on distant RFS or OS.
Prediction of tumor recurrence by alpha-fetoprotein model after curative resection for hepatocellular carcinoma. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology Ding, H., Zhang, X., Bagante, F., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Lv, Y., Pawlik, T. M. 2020
BACKGROUND: Preoperative alpha-fetoprotein (AFP) level levels may help select patients with hepatocellular carcinoma (HCC) for surgery. The objective of the current study was to assess an AFP model to predict tumor recurrence and patient survival after curative resection for HCC.METHODS: Patients undergoing curative-intent resection for HCC between 2000 and 2017 were identified from a multi-institutional database. AFP score was calculated based on the last evaluation before surgery. Probabilities of tumor recurrence and overall survival (OS) were compared according to an AFP model.RESULTS: A total of 825 patients were included. An optimal cut-off AFP score of 2 was identified with an AFP score ≥3 versus ≤2 independently predicting tumor recurrence and OS. Net reclassification improvements indicated the AFP model was superior to the Barcelona Clinic Liver Cancer (BCLC) system to predict recurrence (p<0.001). Among patients with BCLC B-C, AFP score ≤2 identified a subgroup of patients with AFP levels of ≤100ng/mL with a low 5-year recurrence risk (≤2 45.2% vs. ≥3 61.8%, p=0.046) and favorable 5-year OS (≤2 54.5% vs. ≥3 39.4%, p=0.035). In contrast, among patients within BCLC 0-A, AFP score ≥3 identified a subgroup of patients with AFP values>1000ng/mL with a high 5-year recurrence (≥3 47.9% vs. ≤2% 38.4%, p=0.046) and worse 5-year OS (≥3 47.8% vs. ≤2 65.9%, p<0.001). In addition, the AFP score independently correlated with vascular invasion, tumor differentiation and capsule invasion.CONCLUSIONS: The AFP model was more accurate than the BCLC system to identify which HCC patients may benefit the most from surgical resection.
Tumor Burden Dictates Prognosis among Patients Undergoing Curative-Intent Resection of Intrahepatic Cholangiocarcinoma: An International, Multi-Institutional Analysis Tsilimigras, D. I., Moris, D., Paredes, A., Weiss, M. J., Bauer, T. W., Poultsides, G. A., Maithel, S., Martel, G., Pawlik, T. ELSEVIER SCIENCE INC. 2020: S173
ASO Author Reflections: Refining the Surgical Management of Pancreatic Neuroendocrine Tumors. Annals of surgical oncology Cloyd, J. M., Poultsides, G. A. 2020
Defining and Predicting Early Recurrence after Resection for Gallbladder Cancer. Annals of surgical oncology Sahara, K., Tsilimigras, D. I., Kikuchi, Y., Ethun, C. G., Maithel, S. K., Abbott, D. E., Poultsides, G. A., Hatzaras, I., Fields, R. C., Weiss, M., Scoggins, C., Isom, C. A., Idrees, K., Shen, P., Yabushita, Y., Matsuyama, R., Endo, I., Pawlik, T. M. 2020
BACKGROUND: The optimal time interval to define early recurrence (ER) among patients who underwent resection of gallbladder cancer (GBC) is not well defined. We soughtto develop and validate a novel GBC recurrence risk (GBRR) score to predict ER among patients undergoing resection for GBC.PATIENTS AND METHODS: Patients who underwent curative-intent resection for GBC between 2000 and 2018 were identified from the US Extrahepatic Biliary Malignancy Consortiumdatabase. A minimum p value approach in the log-rank test was used to define the optimal cutoff forER. A risk stratification model was developed to predict ER based on relevant clinicopathological factors and was externally validated.RESULTS: Among 309 patients, 103 patients (33.3%) had a recurrence at a median follow-up period of 15.1months. The optimal cutoff for ER was defined at 12months (p=3.04*10-18). On multivariable analysis, T3/T4 disease (HR: 2.80; 95% CI 1.58-5.11) and poor tumordifferentiation (HR: 1.91; 95% CI 1.11-3.25) were associated with greater hazards of ER. The GBRR score was developed using beta-coefficients of variables in the final model, and patients were classified into three distinct groups relative to the risk forER (12-month RFS; low risk: 88.4%, intermediate risk: 77.9%, high risk: 37.0%, p<0.001). The external validation demonstrated good model generalizability with good calibration (n=102: 12-month RFS; low risk: 94.2%, intermediate risk: 59.8%, high risk: 42.0%, p<0.001). The GBRR score is available online at https://ktsahara.shinyapps.io/GBC_earlyrec/ .CONCLUSIONS: A novel online calculator was developed to help clinicians predict the probability of ER after curative-intent resection for GBC. The proposed web-based tool may help in the optimization of surveillance intervals and the counselling of patients about their prognosis.
View details for DOI 10.1245/s10434-020-09108-y
Islet Tumors: Resect or Follow? Advances in surgery Sinclair, T. J., Poultsides, G. A. 2020; 54: 69–88
View details for DOI 10.1016/j.yasu.2020.04.004
A closer look at the natural history and recurrence patterns of high-grade truncal/extremity leiomyosarcomas: A multi-institutional analysis from the US Sarcoma Collaborative. Surgical oncology Lee, R. M., Ethun, C. G., Zaidi, M. Y., Tran, T. B., Poultsides, G. A., Grignol, V. P., Howard, J. H., Bedi, M., Gamblin, T. C., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B. A., Fields, R. C., Oskouei, S. V., Monson, D. K., Reimer, N. B., Maithel, S. K., Cardona, K. 2020; 34: 292–97
BACKGROUND/OBJECTIVE: Natural history and outcomes for truncal/extremity (TE) soft tissue sarcoma (STS) is derived primarily from studies investigating all histiotypes as one homogenous cohort. We aimed to define the recurrence rate (RR), recurrence patterns, and response to radiation of TE leiomyosarcomas (LMS).METHODS: Patients from the US Sarcoma Collaborative database with primary, high-grade TE STS were identified. Patients were grouped into LMS or other histology (non-LMS). Primary endpoints were locoregional recurrence-free survival (LR-RFS), distant-RFS (D-RFS), and disease specific survival (DSS).RESULTS: Of 1215 patients, 93 had LMS and 1122 non-LMS. In LMS patients, median age was 63 and median tumor size was 6cm. In non-LMS patients, median age was 58 and median tumor size was 8cm. In LMS patients, overall RR was 42% with 15% LR-RR and 29% D-RR. The 3yr LR-RFS, D-RFS, and DSS were 84%, 65%, and 76%, respectively. When considering high-risk (>5cm and high-grade, n=49) LMS patients, the overall RR was 45% with 12% LR-RR and 35% D-RR. 61% received radiation. The 3yr LR-RFS (78vs93%, p=0.39), D-RFS (53vs63%, p=0.27), and DSS (67vs91%, p=0.17) were similar in those who did and did not receive radiation. High-risk, non-LMS patients had a similar overall RR of 42% with 15% LR-RR and 30% D-RR. 60% of non-LMS patients received radiation. There was an improved 3yr LR-RFS (82vs75%, p=0.030) and DSS (77vs65%,p=0.007) in non-LMS patients who received radiation.CONCLUSIONS: In our cohort, patients with LMS have a low local recurrence rate (12-15%) and modest distant recurrence rate (29-35%). However, LMS patients had no improvement in local control or long-term outcomes with radiation. The value of radiation in these patients merits further investigation.
View details for DOI 10.1016/j.suronc.2020.06.003
A Novel Machine-Learning Approach to Predict Recurrence After Resection of Colorectal Liver Metastases. Annals of surgical oncology Paredes, A. Z., Hyer, J. M., Tsilimigras, D. I., Moro, A., Bagante, F., Guglielmi, A., Ruzzenente, A., Alexandrescu, S., Makris, E. A., Poultsides, G. A., Sasaki, K., Aucejo, F. N., Pawlik, T. M. 2020
BACKGROUND: Surgical resection of hepatic metastases remains the only potentially curative treatment option for patients with colorectal liver metastases (CRLM). Widely adopted prognostic tools may oversimplify the impact of model parameters relative to long-term outcomes.METHODS: Patients with CRLM who underwent a hepatectomy between 2001 and 2018 were identified in an international, multi-institutional database. Bootstrap resampling methodology used in tandem with multivariable mixed-effects logistic regression analysis was applied to construct a prediction model that was validated and compared with scores proposed by Fong and Vauthey.RESULTS: Among 1406 patients who underwent hepatic resection of CRLM, 842 (59.9%) had recurrence. The full model (based on age, sex, primary tumor location, T stage, receipt of chemotherapy before hepatectomy, lymph node metastases, number of metastatic lesions in the liver, size of the largest hepatic metastases, carcinoembryonic antigen [CEA] level and KRAS status) had good discriminative ability to predict 1-year (area under the receiver operating curve [AUC], 0.693; 95% confidence interval [CI], 0.684-0.704), 3-year (AUC, 0.669; 95% CI, 0.661-0.677), and 5-year (AUC, 0.669; 95% CI, 0.661-0.679) risk of recurrence. Studies analyzing validation cohorts demonstrated similar model performance, with excellent model accuracy. In contrast, the AUCs for the Fong and Vauthey scores to predict 1-year recurrence were only 0.527 (95% CI, 0.514-0.538) and 0.525 (95% CI, 0.514-0.533), respectively. Similar trends were noted for 3- and 5-year recurrence.CONCLUSION: The proposed clinical score, derived via machine learning, which included clinical characteristics and morphologic data, as well as information on KRAS status, accurately predicted recurrence after CRLM resection with good discrimination and prognostic ability.
Indications and outcomes of enucleation versus formal pancreatectomy for pancreatic neuroendocrine tumors. HPB : the official journal of the International Hepato Pancreato Biliary Association Heidsma, C. M., Tsilimigras, D. I., van Dieren, S., Rocha, F., Abbott, D. E., Fields, R., Smith, P. M., Poultsides, G. A., Cho, C., Dillhoff, M., Lopez-Aguiar, A. G., Kanji, Z., Fisher, A., Krasnick, B. A., Idrees, K., Makris, E., Beems, M., van Eijck, C. H., Nieveen van Dijkum, E. J., Maithel, S. K., Pawlik, T. M. 2020
BACKGROUND: Pancreatoduodenectomy (PD) or distal pancreatectomy (DP) are common procedures for patients with a pancreatic neuroendocrine tumor (pNET). Nevertheless, certain patients may benefit from a pancreas-preserving resection such as enucleation (EN). The aim of this study was to define the indications and differences in long-term outcomes among patients undergoing EN and PD/DP.METHODS: Patients undergoing resection of a pNET between 1992 and 2016 were identified. Indications and outcomes were evaluated, and propensity score matching (PSM) analysis was performed to compare long-term outcomes between patients who underwent EN versus PD/DP.RESULTS: Among 1034 patients, 143 (13.8%) underwent EN, 304 (29.4%) PD, and 587 (56.8%) DP. Indications for EN were small size (1.5cm, IQR:1.0-1.9), functional tumors (58.0%) that were mainly insulinomas (51.7%). After PSM (n=109 per group), incidence of postoperative pancreatic fistula (POPF) grade B/C was higher after EN (24.5%) compared with PD/DP (14.0%) (p=0.049). Median recurrence-free survival (RFS) was comparable among patients who underwent EN (47 months, 95% CI:23-71) versus PD/DP (37 months, 95% CI: 33-47, p=0.480).CONCLUSION: Comparable long-term outcomes were noted among patients who underwent EN versus PD/DP for pNET. The incidence of clinically significant POPF was higher after EN.
High neutrophil-lymphocyte ratio is not independently associated with worse survival or recurrence in patients with extremity soft tissue sarcoma. Surgery Strong, E. A., Park, S. H., Ethun, C. G., Chow, B., King, D., Bedi, M., Charlson, J., Mogal, H., Tsai, S., Christians, K., Tran, T. B., Poultsides, G., Grignol, V., Howard, J. H., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Cullinan, D., Fields, R. C., Gamblin, T. C., Cardona, K., Clarke, C. N. 2020
BACKGROUND: Soft tissue sarcomas are a heterogenous group of neoplasms without well-validated biomarkers. Cancer-related inflammation is a known driver of tumor growth and progression. Recent studies have implicated a high circulating neutrophil-lymphocyte ratio as a surrogate marker for the inflammatory tumor microenvironment and a poor prognosticator in multiple solid tumors, including colorectal and pancreatic cancers. The impact of circulating neutrophil-lymphocyte ratio in soft tissue sarcomas has yet to be elucidated.METHODS: We performed a retrospective analysis of patients undergoing curative resection for primary or recurrent extremity soft tissue sarcomas at academic centers within the US Sarcoma Collaborative. Neutrophil-lymphocyte ratio was calculated retrospectively in treatment-naive patients using blood counts at or near diagnosis.RESULTS: A high neutrophil-lymphocyte ratio (≥4.5) was associated with worse survival on univariable analysis in patients with extremity soft tissue sarcomas (hazard ratio 2.07; 95% confidence interval, 1.54-2.8; P < .001). On multivariable analysis, increasing age (hazard ratio 1.03; 95% confidence interval, 1.02-1.04; P < .001), American Joint Committee on Cancer T3 (hazard ratio 1.89; 95% confidence interval, 1.16-3.09; P= .011), American Joint Committee on Cancer T4 (hazard ratio 2.36; 95% confidence interval, 1.42-3.92; P= .001), high tumor grade (hazard ratio 4.56; 95% confidence interval, 2.2-9.45; P < .001), and radiotherapy (hazard ratio 0.58; 95% confidence interval, 0.41-0.82; P= .002) were independently predictive of overall survival, but a high neutrophil-lymphocyte ratio was not predictive of survival (hazard ratio 1.26; 95% confidence interval, 0.87-1.82; P= .22).CONCLUSION: Tumor inflammation as measured by high pretreatment neutrophil-lymphocyte ratio was not independently associated with overall survival in patients undergoing resection for extremity soft tissue sarcomas.
Analysis of textbook outcomes among patients undergoing resection of retroperitoneal sarcoma: A multi-institutional analysis of the US Sarcoma Collaborative. Journal of surgical oncology Wiseman, J. T., Ethun, C. G., Cloyd, J. M., Shelby, R., Suarez-Kelly, L., Tran, T., Poultsides, G., Mogal, H., Clarke, C., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B., Fields, R., Walle, K. V., Ronnekleiv-Kelly, S., Howard, J. H., Cardona, K., Grignol, V. 2020
BACKGROUND: The novel composite metric textbook outcome (TO) has increasingly been used as a quality indicator but has not been reported among patients undergoing surgical resection for retroperitoneal sarcoma (RPS) using multi-institutional collaborative data.METHODS: All patients who underwent resection for RPS between 2000 to 2016 from eight academic institutions were included. TO was defined as a patient with R0/R1 resection that discharged to home and was without transfusion, reoperation, grade ≥2 complications, hospital-stay >50th percentile, or 90-day readmission or mortality. Univariate and multivariable analyses were performed.RESULTS: Among 627 patients, 56.1% were female and the median age was 59 years. A minority of patients achieved a TO (34.9%). Factors associated with achieving a TO were tumor size <20cm and low tumor grade, while ASA class ≥3, history of a prior cardiac event, resection of left colon/rectum, distal pancreatic resection, major venous resection and drain placement were associated with not achieving a TO (all P<.05). Achievement of a TO was associated with improved survival (median:12.7 vs 5.9 years, P<.01).CONCLUSIONS: Among patients undergoing resection for RPS, failure to achieve TO is common and associated with significantly worse survival. The use of TO may inform patient expectations and serve as a measure for patient-level hospital performance.
Predicting Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Tsilimigras, D. I., Sahara, K., Paredes, A. Z., Moro, A., Mehta, R., Moris, D., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Soubrane, O., Koerkamp, B. G., Endo, I., Pawlik, T. M. 2020
BACKGROUND: The objective of the current study was to develop a model to predict the likelihood of occult lymph node metastasis (LNM) prior to resection of intrahepatic cholangiocarcinoma (ICC).METHODS: Patients who underwent hepatectomy for ICC between 2000 and 2017 were identified using a multi-institutional database. A novel model incorporating clinical and preoperative imaging data was developed to predict LNM.RESULTS: Among 980 patients who underwent resection of ICC, 190 (19.4%) individuals had at least one LNM identified on final pathology. An enhanced imaging model incorporating clinical and imaging data was developed to predict LNM ( https://k-sahara.shinyapps.io/ICC_imaging/ ). The performance of the enhanced imaging model was very good in the training data set (c-index 0.702), as well as the validation data set with bootstrapping resamples (c-index 0.701) and outperformed the preoperative imaging alone (c-index 0.660). The novel model predicted both 5-year overall survival (OS) (low risk 48.4% vs. high risk 18.4%) and 5-year disease-specific survival (DSS) (low risk 51.9% vs. high risk 25.2%, both p < 0.001). When applied among Nx patients, 5-year OS and DSS of low-risk Nx patients was comparable with that of N0 patients, while high-risk Nx patients had similar outcomes to N1 patients (p > 0.05).CONCLUSION: This tool may represent an opportunity to stratify prognosis of Nx patients and can help inform clinical decision-making prior to resection of ICC.
Prognostic factors differ according to KRAS mutational status: A classification and regression tree model to define prognostic groups after hepatectomy for colorectal liver metastasis. Surgery Moro, A., Mehta, R., Tsilimigras, D. I., Sahara, K., Paredes, A. Z., Bagante, F., Guglielmi, A., Alexandrescu, S., Poultsides, G. A., Sasaki, K., Aucejo, F. N., Pawlik, T. M. 2020
BACKGROUND: Although KRAS mutation status is known to affect the prognosis of patients with colorectal liver metastasis, the hierarchical association between other prognostic factors and KRAS status is not fully understood.METHODS: Patients who underwent a hepatectomy for colorectal liver metastasis were identified in a multi-institutional international database. A classification and regression tree model was constructed to investigate the hierarchical association between prognostic factors and overall survival relative to KRAS status.RESULTS: Among 1,123 patients, 29.9% (n= 336) had a KRAS mutation. Among wtKRAS patients, the classification and regression tree model identified presence of metastatic lymph nodes as the most important prognostic factor, whereas among mtKRAS patients, carcinoembryonic antigen level was identified as the most important prognostic factor. Among patients with wtKRAS, the highest 5-year overall survival (68.5%) was noted among patients with node negative primary colorectal cancer, solitary colorectal liver metastases, size <4.3 cm. In contrast, among patients with mtKRAS colorectal liver metastases, the highest 5-year overall survival (57.5%) was observed among patients with carcinoembryonic antigen <6 mg/mL. The classification and regression tree model had higher prognostic accuracy than the Fong score (wtKRAS [Akaike's Information Criterion]: classification and regression tree model 3334 vs Fong score 3341; mtKRAS [Akaike's Information Criterion]: classification and regression tree model 1356 vs Fong score 1396).CONCLUSION: Machine learning methodology outperformed the traditional Fong clinical risk score and identified different factors, based on KRAS mutational status, as predictors of long-term prognosis.
Pancreatic Cancer Prognostication: From Trousseau to Thrombelastography. Annals of surgery Poultsides, G. A. 2020
View details for DOI 10.1097/SLA.0000000000004139
Recurrence beyond the Milan criteria after curative-intent resection of hepatocellular carcinoma: A novel tumor-burden based prediction model. Journal of surgical oncology Tsilimigras, D. I., Mehta, R., Guglielmi, A., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2020
BACKGROUND: Accurate prediction of recurrence patterns of hepatocellular carcinoma (HCC) may allow for prioritization of patients for resection or transplantation as well as guide post-resection surveillance strategies.METHODS: Patients who underwent curative-intent R0 resection for HCC between 2000 and 2017 were identified using a multi-institutional database. A prognostic model that incorporated HCC tumor burden score (TBS) to predict recurrence beyond the Milan criteria (MC) was developed and validated.RESULTS: Among 718 patients who underwent R0 resection for HCC, 185 (25.8%) recurred within and 110 (15.3%) beyond the MC. On multivariable analysis, AFP more than 400ng/mL (hazard ratio [HR]=2.26; 95% confidence interval [CI]: 1.27-4.02), lymphovascular invasion (HR=2.00; 95% CI: 1.14-3.50), and TBS (HR=1.08; 95% CI: 1.03-1.12) were associated with recurrence beyond the MC. A weighted TBS-based score was constructed: [0.074*TBS+0.692*lymphovascular invasion (yes: 1, no: 0)+0.816*AFP>400 (yes:1, no:0)]. Patients with a low, medium, and high TBS-based risk score had a 5-year incidence of recurring beyond the MC of 16.2%, 28.6%, and 47.2%, respectively (P<.001). The predictive accuracy of the model was very good in the training (C-index: 0.761) and validation (C-index: 0.706) datasets and outperformed the previously reported clinical risk score (CRS; C-index: 0.680).CONCLUSION: A TBS-based model accurately predicted recurrence beyond MC after curative-intent resection of HCC and outperformed the CRS. Incorporating TBS allows for better risk stratification and identifies patients in need of closer surveillance.
Predicting Pancreatic Cancer Resectability and Outcomes Based on an Objective Quantitative Scoring System. Pancreas Toesca, D. A., Jeffrey, R. B., von Eyben, R. n., Pollom, E. L., Poullos, P. D., Poultsides, G. A., Fisher, G. A., Visser, B. C., Koong, A. C., Chang, D. T. ; 48 (5): 622–28
To quantitatively assess the probability of tumor resection based on measurements of tumor contact with the major peripancreatic vessels.This is a retrospective cohort study of pancreatic cancer patients treated between January 2001 and December 2015 in a single academic comprehensive cancer center. Radiographic measurements of the circumferential degree and length of solid tumor contact with major peripancreatic vessels were obtained from diagnostic pancreatic protocol computed tomography images and tested for correlation with tumor resection and margin status.Of 294 patients analyzed, 113 (38%) were resected, with 71 (63%) with negative margins. Based on the individual measurements of vascular involvement, a resectability scoring system (RSS) was created. The RSS correlated strongly with resection (P < 0.0001) and R0 resection (P < 0.0001) probabilities. Moreover, the RSS correlated with overall survival (P < 0.0001) and metastasis-free survival (P < 0.0001), being able to substratify resectable (P = 0.022) and unresectable patients (P = 0.014) into subgroups with different prognosis based on RSS scores.Based on a comprehensive and systematic quantitative approach, we developed a scoring system that demonstrated excellent accuracy to predict tumor resection, surgical margin status, and prognosis.
Multi-institutional Development and External Validation of a Nomogram Predicting Recurrence After Curative Liver Resection for Neuroendocrine Liver Metastasis. Annals of surgical oncology Xiang, J., Zhang, X., Weiss, M., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S. K., Marques, H. P., Pawlik, T. M. 2020
OBJECTIVES: To establish and externally validate a novel nomogram to predict recurrence of patients undergoing curative liver resection for neuroendocrine liver metastasis (NELM).METHODS: A total of 279 patients who underwent curative liver resection for NELM identified from an international multicenter database were utilized to develop a nomogram to predict recurrence; 98 cases from two different institutions were used to externally validate the nomogram.RESULTS: Among 279 patients in the development cohort, median age was 57years, and 50.5% were male. On multivariate analysis, primary tumor location (pancreatic vs nonpancreatic, HR 2.1, p=0.004), tumor grade (Ref. well, moderate HR 1.9, p=0.022; poor HR 1.6, p=0.238), lymph node metastasis (positive vs negative, HR 2.6, p=0.002), and extent of resection (major vs parenchymal-sparing resection, HR 0.3, p=0.001) were independently associated with recurrence-free survival. The beta coefficients from the final multivariable model were utilized to develop a nomogram. The nomogram demonstrated good ability to predict risk of recurrence (training cohort, C-index 0.754; validation cohort, C-index 0.748). The calibrated nomogram predicted recurrence-free survival that closely corresponded to actual recurrence. Decision curve analysis demonstrated that the nomogram had a good net benefit for most of the threshold probabilities, especially between 20 and 60%, in both development and validation cohorts.CONCLUSIONS: The externally validated novel nomogram predicted 3- and 5-year recurrence-free survival among patients with NELM. Prediction of individual recurrence risk may help guide personalized estimates of prognosis, as well as surveillance protocols and consideration of adjuvant therapies.
Tumour-specific fluorescence-guided surgery for pancreatic cancer using panitumumab-IRDye800CW: a phase 1 single-centre, open-label, single-arm, dose-escalation study. The lancet. Gastroenterology & hepatology Lu, G., van den Berg, N. S., Martin, B. A., Nishio, N., Hart, Z. P., van Keulen, S., Fakurnejad, S., Chirita, S. U., Raymundo, R. C., Yi, G., Zhou, Q., Fisher, G. A., Rosenthal, E. L., Poultsides, G. A. 2020
BACKGROUND: Complete surgical resection remains the primary curative option for pancreatic ductal adenocarcinoma, with positive margins in 30-70% of patients. In this study, we aimed to evaluate the use of intraoperative tumour-specific imaging to enhance a surgeon's ability to detect visually occult cancer in real time.METHODS: In this single-centre, open-label, single-arm study, done in the USA, we enrolled patients who had clinically suspicious or biopsy-confirmed pancreatic ductal adenocarcinomas and were scheduled for curative surgery. Eligible patients were 19 years of age or older with a life expectancy of more than 12 weeks and a Karnofsky performance status of at least 70% or an Eastern Cooperative Oncology Group or Zubrod level of one or lower, who were scheduled to undergo curative surgery. Patients were sequentially enrolled into each dosing group and 2-5 days before surgery, patients were intravenously infused with 100 mg of unlabelled panitumumab followed by 25 mg, 50 mg, or 75 mg of the near-infrared fluorescently labelled antibody (panitumumab-IRDye800CW). The primary endpoint was to determine the optimal dose of panitumumab-IRDye800CW in identifying pancreatic ductal adenocarcinomas as measured by tumour-to-background ratio in all patients. The tumour-to-background ratio was defined as the fluorescence signal of the tumour divided by the fluorescence signal of the surrounding healthy tissue. The dose-finding part of this study has been completed. This study is registered with ClinicalTrials.gov, NCT03384238.FINDINGS: Between April, 2018, and July, 2019, 16 patients were screened for enrolment onto the study. Of the 16 screened patients, two (12%) patients withdrew from the study and three (19%) were not eligible; 11 (69%) patients completed the trial, all of whom were clinically diagnosed with pancreatic ductal adenocarcinoma. The mean tumour-to-background ratio of primary tumours was 3·0 (SD 0·5) in the 25 mg group, 4·0 (SD 0·6) in the 50 mg group, and 3·7 (SD 0·4) in the 75 mg group; the optimal dose was identified as 50 mg. Intraoperatively, near-infrared fluorescence imaging provided enhanced visualisation of the primary tumours, metastatic lymph nodes, and small (<2 mm) peritoneal metastasis. Intravenous administration of panitumumab-IRDye800CW at the doses of 25 mg, 50 mg, and 75 mg did not result in any grade 3 or higher adverse events. There were no serious adverse events attributed to panitumumab-IRDye800CW, although four possibly related adverse events (grade 1 and 2) were reported in four patients.INTERPRETATION: To our knowledge, this study presents the first clinical use of panitumumab-IRDye800CW for detecting pancreatic ductal adenocarcinomas and shows that panitumumab-IRDye800CW is safe and feasible to use during pancreatic cancer surgery. Tumour-specific intraoperative imaging might have added value for treatment of patients with pancreatic ductal adenocarcinomas through improved patient selection and enhanced visualisation of surgical margins, metastatic lymph nodes, and distant metastasis.FUNDING: National Institutes of Health and the Netherlands Organization for Scientific Research.
Assessing Textbook Outcomes Following Liver Surgery for Primary Liver Cancer Over a 12-Year Time Period at Major Hepatobiliary Centers. Annals of surgical oncology Tsilimigras, D. I., Sahara, K., Moris, D., Mehta, R., Paredes, A. Z., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Weiss, M., Bauer, T. W., Maithel, S. K., Pulitano, C., Shen, F., Koerkamp, B. G., Endo, I., Pawlik, T. M. 2020
INTRODUCTION: The objective of the current study was to comprehensively assess the change of practice in hepatobiliary surgery by determining the rates and the trends of textbook outcomes (TO) among patients undergoing surgery for primary liver cancerover time.METHODS: Patients undergoing curative-intent resection for primary liver malignancies, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) between 2005 and 2017 were analyzed using a large, international multi-institutional dataset. Rates of TO were assessed over time. Factors associated with achieving a TO and the impact of TO on long-term survival were examined.RESULTS: Among 1829 patients, 944 (51.6%) and 885 (48.4%) individuals underwent curative-intent resection for HCC and ICC, respectively. Over time, patients were older, more frequently had ASAclass>2, albumin-bilirubin grade 2/3, major vascular invasion and more frequently underwent major liver resection (all p<0.05). Overall, a total of 1126 (62.0%) patients achieved a TO. No increasing trends in TO rates were noted over the years (ptrend=0.90). In addition, there was no increasing trend in the TO rates among patients undergoing either major (ptrend=0.39) or minor liver resection (ptrend=0.63) over the study period. Achieving a TO was independently associated with 26% and 37% decreased hazards of death among ICC (HR 0.74, 95%CI 0.56-0.97) and HCC patients (HR 0.63, 95%CI 0.46-0.85), respectively.CONCLUSION: Approximately 6 in 10 patients undergoing surgery for primary liver tumors achieved a TO. While TO rates did not increase over time, TO was associated with better long-term outcomes following liver resection for both HCC and ICC.
Recurrence Patterns and Outcomes after Resection of Hepatocellular Carcinoma within and beyond the Barcelona Clinic Liver Cancer Criteria. Annals of surgical oncology Tsilimigras, D. I., Bagante, F., Moris, D., Hyer, J. M., Sahara, K., Paredes, A. Z., Mehta, R., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2020
BACKGROUND: Several investigators have advocated for extending the Barcelona Clinic Liver Cancer (BCLC) resection criteria to select patients with BCLC-B and even BCLC-C hepatocellular carcinoma (HCC). The objective of the current study wasto define the outcomes and recurrence patterns after resection within and beyond the current resection criteria.PATIENTS AND METHODS: Patients who underwent resection for HCC within (i.e., BCLC 0/A) and beyond (i.e. BCLC B/C) the current resection criteria between 2005 and 2017 were identified from an international multi-institutional database. Overall survival (OS), disease-free survival (DFS), as well as patterns of recurrence of patients undergoing HCC resection within and beyond the BCLC guidelines were examined.RESULTS: Among 756 patients, 602 (79.6%) patients were BCLC 0/A and 154 (20.4%) were BCLC B/C. Recurrences were mostly intrahepatic (within BCLC: 74.3% versus beyond BCLC: 70.8%, p = 0.80), with BCLC B/C patients more often having multiple tumors at relapse (69.6% versus 49.4%, p = 0.001) and higher rates of early (< 2 years) recurrence (88.0% versus 75.5%, p = 0.011). During the first postoperative year, annual recurrence was 38.3% and 21.3% among BCLC B/C and BCLC 0/A patients, respectively; 5-year OS among BCLC 0/A and BCLC B/C patients was 76.9% versus 51.6% (p = 0.003). On multivariable analysis, only a-fetoprotein (AFP) > 400ng/mL(HR = 1.84, 95% CI 1.07-3.15) and R1 resection (HR = 2.36, 95% CI 1.32-4.23) were associated with higher risk of recurrence among BCLC B/C patients.CONCLUSIONS: Surgery can provide acceptable outcomes among select patients with BCLC B/C HCC. The data emphasize the need to further refine the BCLC treatment algorithm as well as highlight the need for surveillance protocols with a particular focus on the liver, especially for patients undergoing resection outside the BCLC criteria.
Neoadjuvant radiation improves margin-negative resection rates in extremity sarcoma but not survival. Journal of surgical oncology Shelby, R. D., Suarez-Kelly, L. P., Yu, P. Y., Hughes, T. M., Ethun, C. G., Tran, T. B., Poultsides, G., King, D. M., Bedi, M., Mogal, H., Clarke, C., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B. A., Fields, R. C., Pollock, R. E., Howard, J. H., Cardona, K., Grignol, V. 2020
BACKGROUND AND OBJECTIVES: Radiation improves limb salvage in extremity sarcomas. Timing of radiation therapy remains under investigation. We sought to evaluate the effects of neoadjuvant radiation (NAR) on surgery and survival of patients with extremity sarcomas.MATERIALS AND METHODS: A multi-institutional database was used to identify patients with extremity sarcomas undergoing surgical resection from 2000-2016. Patients were categorized by treatment strategy: surgery alone, adjuvant radiation (AR), or NAR. Survival, recurrence, limb salvage, and surgical margin status was analyzed.RESULTS: A total of 1483 patients were identified. Most patients receiving radiotherapy had high-grade tumors (82% NAR vs 81% AR vs 60% surgery; P<.001). The radiotherapy groups had more limb-sparing operations (98% AR vs 94% NAR vs 87% surgery; P<.001). NAR resulted in negative margin resections (90% NAR vs 79% surgery vs 75% AR; P<.0001). There were fewer local recurrences in the radiation groups (14% NAR vs 17% AR vs 27% surgery; P=.001). There was no difference in overall or recurrence-free survival between the three groups (OS, P=.132; RFS, P=.227).CONCLUSION: In this large study, radiotherapy improved limb salvage rates and decreased local recurrences. Receipt of NAR achieves more margin-negative resections however this did not improve local recurrence or survival rates over.
The Impact of Preoperative CA19-9 and CEA on Outcomes of Patients with Intrahepatic Cholangiocarcinoma. Annals of surgical oncology Moro, A., Mehta, R., Sahara, K., Tsilimigras, D. I., Paredes, A. Z., Farooq, A., Hyer, J. M., Endo, I., Shen, F., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Soubrane, O., Koerkamp, B. G., Sasaki, K., Pawlik, T. M. 2020
BACKGROUND: The objective of the current study was to assess the impact of serum CA19-9 and CEA and their combination on survival among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC).METHODS: Patients who underwent curative-intent resection of ICC between 1990 and 2016 were identified using a multi-institutional database. Patients were categorized into four groups based on combinations of serum CA19-9 and CEA (low vs. high). Factors associated with 1-year mortality after hepatectomy were examined.RESULTS: Among 588 patients, 5-year OS was considerably better among patients with low CA19-9/low CEA (54.5%) compared with low CA19-9/high CEA (14.6%), high CA19-9/low CEA (10.0%), or high CA19-9/high CEA (0%) (P<0.001). No difference in 1-year OS existed between patients who had either high CA19-9 (high CA19-9/low CEA:70.4%) or high CEA levels (low CA19-9/high CEA:72.5%) (P=0.92). Although patients with the most favorable tumor marker profile (low CA19-9/low CEA) had the best 1-year survival (87.9%), 15.1% (n=39) still died within a year of surgery. Among patients with low CA19-9/low CEA, a high neutrophil-to-lymphocyte ratio (NLR) (odds ratio 1.09; 95% confidence interval 1.03-1.64) and large size tumor (odds ratio 3.34; 95% confidence interval 1.40-8.10) were associated with 1-year mortality (P<0.05).CONCLUSIONS: Patients with either a high CA19-9 and/or high CEA had poor 1-year survival. High NLR and large tumor size were associated with a greater risk of 1-year mortality among patients with favorable tumor marker profile.
Incidence and impact of Textbook Outcome among patients undergoing resection of pancreatic neuroendocrine tumors: Results of the US Neuroendocrine Tumor Study Group. Journal of surgical oncology Heidsma, C. M., Hyer, M., Tsilimigras, D. I., Rocha, F., Abbott, D. E., Fields, R., Smith, P. M., Poultsides, G. A., Cho, C., Maithel, S. K., Pawlik, T. M., Other Members of the US Neuroendocrine Tumor Study Group 2020
BACKGROUND AND OBJECTIVES: We sought to define the incidence and impact of Textbook Outcome (TO) on disease-freesurvival [DFS] among patients undergoing resection of pancreatic neuroendocrine tumors (PNET).METHODS: Patients undergoing resection of a PNET between 2000 and 2016 were identified using a multi-institutional database. TO was defined as no postoperative severe complications (Clavien-Dindo grade≥III), no 90-day mortality, no prolonged length-of-hospital stay (LOS) (ie, >75th percentile), no 90-day readmission after discharge, and R0 resection. The 5-year DFS was calculated and the association with TO was examined.RESULTS: Among 821 patients with a PNET, median tumor size was 2.1cm (IQR 1.4-14.6). Resection consisted of pancreatoduodenectomy (PD) (n=231, 28.1%), distal pancreatectomy (DP) (n=492, 59.9%), and enucleation (EN) (n=98, 11.9%). Overall TO rate was 49.3% (n=405). The incidence of TO varied by procedure type (PD: 32.5% vs DP: 56.7% vs EN: 52.0%; P<.001). After adjusting for all competing factors, achievement of a TO was independently associated with improved DFS (hazard ratio: 0.54, 95% CI, 0.35-0.81; P=.003).CONCLUSIONS: Only one in two patients undergoing resection of a PNET achieved a TO, which varied markedly based on procedure type. Achievement of a TO was associated with improved DFS.
Outcomes of palliative-intent surgery in retroperitoneal sarcoma-Results from the US Sarcoma Collaborative. Journal of surgical oncology Thalji, S. Z., Tsai, S., Gamblin, T. C., Clarke, C., Christians, K., Charlson, J., Ethun, C. G., Poultsides, G., Grignol, V. P., Roggin, K. K., Votanopoulos, K., Fields, R. C., Abbott, D. E., Cardona, K., Mogal, H., other members of the US Sarcoma Collaborative 2020
BACKGROUND AND OBJECTIVES: Outcomes of palliative-intent surgery in retroperitoneal sarcomas (RPS) are not well understood. This study aims to define indications for and outcomes after palliative-intent RPS resection.METHODS: Using a retrospective 8-institution database, patients undergoing resection of primary/recurrent RPS with palliative intent were identified. Logistic regression and Cox-proportional hazards models were constructed to analyze factors associated with postoperative complications and overall survival (OS).RESULTS: Of 3088 patients, 70 underwent 87 palliative-intent procedures. Most common indications were pain (26%) and bowel obstruction (21%). Dedifferentiated liposarcoma (n=17, 24%), leiomyosarcoma (n=13, 19%) were predominant subtypes. Median OS was 10.69 months (IQR, 3.91-23.23). R2 resection (OR, 8.60; CI, 1.42-52.15; P=.019), larger tumors (OR, 10.87; CI, 1.44-82.11; P=.021) and low preoperative albumin (OR, 0.14; CI, 0.04-0.57; P=.006) were associated with postoperative complications. Postoperative complications (HR, 1.95; CI, 1.02-3.71; P=.043) and high-grade histology (HR, 6.56; CI, 1.72-25.05; P=.006) rather than resection status were associated with reduced OS. However, in R2-resected patients, development of postoperative complications significantly reduced survival (P=.042).CONCLUSIONS: Postoperative complications and high-grade histology rather than resection status impacts survival in palliative-intent RPS resections. Given the higher incidence of postoperative complications which may diminish survival, palliative-intent R2 resection should be offered only after cautious consideration.
Adjuvant therapy following resection of gastroenteropancreatic neuroendocrine tumors provides no recurrence or survival benefit. Journal of surgical oncology Barrett, J. R., Rendell, V., Pokrzywa, C., Lopez-Aguiar, A. G., Cannon, J., Poultsides, G. A., Rocha, F., Crown, A., Beal, E., Michael Pawlik, T., Fields, R., Panni, R. Z., Smith, P., Idrees, K., Cho, C., Beems, M., Maithel, S., Weber, S., Erik Abbott, D. 2020
BACKGROUND AND OBJECTIVES: Lack of high-level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non-standard of care use.METHODS: Patients with primary GEP NETs who underwent curative-intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence-free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts.RESULTS: In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five-year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P<.01). RFS with somatostatin analog therapy (compared to none) was lower (P<.01), as was OS (P=.01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor-specific characteristics (RFS P<.01).CONCLUSIONS: Our data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high-risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.
Neoadjuvant Capecitabine/Temozolomide for Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors. Pancreas Squires, M. H., Worth, P. J., Konda, B., Shah, M. H., Dillhoff, M. E., Abdel-Misih, S., Norton, J. A., Visser, B. C., Dua, M., Pawlik, T. M., Schmidt, C. R., Poultsides, G., Cloyd, J. M. 2020
OBJECTIVES: The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established.METHODS: The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed.RESULTS: Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%.CONCLUSIONS: Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.
View details for DOI 10.1097/MPA.0000000000001500
Neoadjuvant Capecitabine/Temozolomide for Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors Squires, M., Worth, P., Konda, B., Dillhoff, M., Abdel-Misih, S., Pawlik, T., Schmidt, C., Poultsides, G., Cloyd, J. LIPPINCOTT WILLIAMS & WILKINS. 2020: 488
Is a Nomogram Able to Predict Postoperative Wound Complications in Localized Soft-tissue Sarcomas of the Extremity? Clinical orthopaedics and related research Bedi, M., Ethun, C. G., Charlson, J., Tran, T. B., Poultsides, G., Grignol, V., Howard, J. H., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Cullinan, D., Fields, R. C., Cardona, K., King, D. M. 2020; 478 (3): 550–59
BACKGROUND: Postoperative wound complications are challenging in patients with localized extremity soft-tissue sarcomas. Various factors have been associated with wound complications, but there is no individualized predictive model to allow providers to counsel their patients and thus offer methods to mitigate the risk of complications and implement appropriate measures.QUESTIONS/PURPOSES: We used data from multiple centers to ask: (1) What risk factors are associated with postoperative wound complications in patients with localized soft-tissue sarcomas of the extremity? (2) Can we create a predictive nomogram that will assess the risk of wound complications in individual patients after resection for soft-tissue sarcoma?METHODS: From 2000 to 2016, 1669 patients undergoing limb-salvage resection for a localized primary or recurrent extremity soft-tissue sarcoma with at least 120 days of follow-up at eight participating United States Sarcoma Collaborative institutions were identified. Wound complications included superficial wounds with or without drainage, deep wounds with drainage because of dehiscence, and intentional opening of the wound within 120 days postoperatively. Sixteen variables were selected a priori by clinicians and statisticians as potential risk factors for wound complications. A univariate analysis was performed using Fisher's exact tests for categorical predictors, and Wilcoxon's rank-sum tests were used for continuous predictors. A multiple logistic regression analysis was used to train the prediction model that was used to create the nomogram. The prediction performance of the datasets was evaluated using a receiver operating curve, area under the curve, and calibration plot.RESULTS: After controlling for potential confounding factors such as comorbidities, functional status, albumin level, and chemotherapy use, we found that increasing age (odds ratio 1.02; 95% confidence interval, 1.00-1.03; p = 0.008), BMI (OR 1.05; 95% CI, 1.02-1.09; p = 0.004), lower-extremity location (OR 6; 95% CI, 2.87-12.69; p < 0.001), and neoadjuvant radiation (OR 2; 95% CI, 1.47-3.16; p < 0.001) were associated with postoperative wound complications (area under the curve 69.2% [range 62.8%-75.6%]).CONCLUSIONS: We found that age, BMI, tumor location, and timing of radiation are associated with the risk of wound complications. Based on these factors, a validated nomogram has been established that can provide an individualized prediction of wound complications in patients with a resected soft-tissue sarcoma of the extremity. This may allow for proactive management with nutrition and surgical techniques, and help determine the delivery of radiation in patients with a high risk of having these complications.LEVEL OF EVIDENCE: Level III, therapeutic study.
View details for DOI 10.1097/CORR.0000000000000959
Evaluation of the ACS NSQIP Surgical Risk Calculator in Elderly Patients Undergoing Hepatectomy for Hepatocellular Carcinoma JOURNAL OF GASTROINTESTINAL SURGERY Sahara, K., Paredes, A. Z., Merath, K., Tsilimigras, D., Bagante, F., Ratti, F., Marques, H. P., Soubrane, O., Beal, E. W., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Aklile, W., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2020; 24 (3): 551–59
Survival benefit of lymphadenectomy for gallbladder cancer based on the therapeutic index: An analysis of the US extrahepatic biliary malignancy consortium. Journal of surgical oncology Sahara, K., Tsilimigras, D. I., Maithel, S. K., Abbott, D. E., Poultsides, G. A., Hatzaras, I., Fields, R. C., Weiss, M., Scoggins, C., Isom, C. A., Idrees, K., Shen, P., Endo, I., Pawlik, T. M., and the US Extrahepatic Biliary Malignancy Consortium 2020
BACKGROUND: The survival benefit of lymphadenectomy among patients with gallbladder cancer (GBC) remains poorly understood.METHODS: Patients who underwent resection for GBC between 2000 and 2015 were identified from a US multi-institutional database. The therapeutic index (LNM rate multiplied by 3-year overall survival [OS]) was determined to assess the survival benefit of lymphadenectomy.RESULTS: Among 449 patients, less than half had LNM (N=183, 40.8%). The median number of evaluated and metastatic lymph nodes (LNs) was 3 (interquartile range [IQR]: 1-6) and 1 (IQR: 0-1), respectively. 3-year OS among patients with LNM in the entire cohort was 26.8%. The therapeutic index was lower among patients with T4 (5.9) or T1 (6.0) tumors as well as carbohydrate antigen (CA19-9) ≥200UI/mL (6.0). Of note, a therapeutic index difference ≥10 was noted relative to CA19-9 (<200: 18.7 vs ≥200: 6.0), American Joint Committee on Cancer T Stage (T1: 6.0 vs T2: 17.8 vs T4: 5.9) and number of LNs examined (1-2: 6.9 vs ≥6: 16.9). Concomitant common bile duct resection was not associated with a higher therapeutic index among patients with either T2 or T3 disease.CONCLUSION: Certain clinicopathological factors including T1 or T4 tumor and CA19-9 ≥200UI/mL were associated with a low therapeutic index. Resection of six or more LNs was associated with a meaningful therapeutic index benefit among patients with LNM.
Development and Validation of a Laboratory Risk Score (LabScore) to Predict Outcomes after Resection for Intrahepatic Cholangiocarcinoma. Journal of the American College of Surgeons Tsilimigras, D. I., Mehta, R. n., Aldrighetti, L. n., Poultsides, G. A., Maithel, S. K., Martel, G. n., Shen, F. n., Koerkamp, B. G., Endo, I. n., Pawlik, T. M. 2020
Estimating prognosis in the preoperative setting is challenging as most survival risk scores rely exclusively on postoperative factors. We sought to develop a composite score that incorporated preoperative liver, tumor, nutritional and inflammatory markers to predict long-term outcomes following resection of intrahepatic cholangiocarcinoma (ICC).Patients who underwent curative-intent hepatectomy for ICC between 2000-2017 were identified using an international multi-institutional database. Clinico-pathologic factors were assessed using bivariate and multivariable analysis and a prognostic model to estimate overall survival (OS) based only on preoperative laboratory values (LabScore) was developed and validated.Among 660 patients, median and 5-year OS were 43.2 months and 42.4%, respectively. On multivariable analysis, laboratory values associated with OS included carbohydrate antigen (CA) 19-9 (HR=1.16, 95%CI 1.05-1.27), neutrophil-to-lymphocyte ratio (NLR)(HR=1.09, 95%CI 1.05-1.13), platelet count (PLT)(HR=1.01, 95%CI 1.00-1.01) and albumin (HR=0.75, 95%CI 0.62-0.92). A weighted LabScore was constructed based on the formula: (8.2 + 1.45*lnCA19-9 + 0.84*NLR + 0.03*PLT-2.83*Albumin). Patients with a LabScore of 0-9 (n=223), 10-19 (n=353) and >20 (n=88) had an incrementally worse 5-year OS of 54.9%, 38.2% and 21.6%, respectively (p<0.001). The model demonstrated good performance in both the test (c-index: 0.70) and validation cohorts (c-index: 0.67), as well as outperformed individual laboratory markers, the prognostic nutritional index (c-index: 0.58) and 8th edition AJCC staging (c-index: 0.60).A preoperative LabScore was able to predict long-term outcomes of patients following resection for ICC better than AJCC staging system. The LabScore can be used to preoperatively identify patients who will benefit the most from upfront surgery or alternative treatment options including neoadjuvant chemotherapy prior to resection.
View details for DOI 10.1016/j.jamcollsurg.2019.12.025
PLR and NLR Are Poor Predictors of Survival Outcomes in Sarcomas: A New Perspective From the USSC. The Journal of surgical research Schwartz, P. B., Poultsides, G. n., Roggin, K. n., Howard, J. H., Fields, R. C., Clarke, C. N., Votanopoulos, K. n., Cardona, K. n., Winslow, E. R. 2020; 251: 228–38
Elevations in inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), are reportedly associated with decreased overall survival (OS) or recurrence-free survival (RFS) in patients with numerous cancers. A large multicenter sarcoma data set was used to determine if elevated NLR or PLR was associated with worse survival and can guide treatment selection.A total of 409 patients with a primary retroperitoneal sarcoma (n = 268) or truncal (n = 141) sarcoma from 2000 to 2015 were analyzed using the US Sarcoma Collaboration database. Binary NLR and PLR values were developed using receiver operating characteristic curves. Kaplan-Meier model and Cox proportional hazards model identified predictors of decreased OS and RFS. Point biserial analyses were used to correlate binary and continuous data.Neither elevated NLR nor PLR was predictive of decreased OS or RFS. These findings persisted despite exclusion of comorbid inflammatory conditions. Further, NLR and PLR were not correlated with tumor grade. In multivariate models, decreased RFS was associated with tumor factors (e.g., positive margins, tumor grade, tumor size, necrosis, positive nodes); decreased OS was associated with histologic subtype, male gender, and nodal involvement.Although several small studies have suggested that elevated NLR and PLR are associated with decreased survival in patients with abdominal or truncal sarcoma, this large multicenter study demonstrates no association with decreased OS, decreased RFS, or tumor grade. Rather, survival outcomes are best predicted using previously established tumoral factors.
Specific Growth Rate as a Predictor of Survival in Pancreatic Neuroendocrine Tumors: A Multi-institutional Study from the United States Neuroendocrine Study Group. Annals of surgical oncology Baechle, J. J., Marincola Smith, P. n., Tan, M. n., Solórzano, C. C., Lopez-Aguiar, A. G., Dillhoff, M. n., Beal, E. W., Poultsides, G. n., Makris, E. n., Rocha, F. G., Crown, A. n., Cho, C. n., Beems, M. n., Winslow, E. R., Rendell, V. R., Krasnick, B. A., Fields, R. n., Maithel, S. K., Bailey, C. E., Idrees, K. n. 2020
Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate (SGR) has been predictive of survival in other malignancies but has not been examined in PNETs.A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database. Patients with ≥ 2 preoperative cross-sectional imaging studies at least 30 days apart were included in our analysis (N = 288). Patients were grouped as "high SGR" or "low SGR." Demographic and clinical factors were compared between the groups. Kaplan-Meier and log-rank analysis were used for survival analysis. Cox proportional hazard analysis was used to assess the impact of various clinical factors on overall survival (OS).High SGR was associated with higher T stage at resection, shorter doubling time, and elevated HbA1c (all P ≤ 0.01). Patients with high SGR had significantly decreased 5-year OS (63 vs 80%, P = 0.01) and disease-specific survival (72 vs 91%, P = 0.03) compared to those with low SGR. In patients with small (≤ 2 cm) tumors (N = 106), high SGR predicted lower 5-year OS (79 vs 96%, P = 0.01). On multivariate analysis, high SGR was independently associated with worse OS (hazard ratio 2.67, 95% confidence interval 1.05-6.84, P = 0.04).High SGR is associated with worse survival in PNET patients. Evaluating PNET SGR may enhance clinical decision-making, particularly when weighing expectant management versus surgery in patients with small tumors.
The systemic immune-inflammation index predicts prognosis in intrahepatic cholangiocarcinoma: an international multi-institutional analysis. HPB : the official journal of the International Hepato Pancreato Biliary Association Tsilimigras, D. I., Moris, D. n., Mehta, R. n., Paredes, A. Z., Sahara, K. n., Guglielmi, A. n., Aldrighetti, L. n., Weiss, M. n., Bauer, T. W., Alexandrescu, S. n., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G. n., Pulitano, C. n., Shen, F. n., Soubrane, O. n., Koerkamp, B. G., Endo, I. n., Pawlik, T. M. 2020
The objective of this study was to examine whether the systemic immune inflammation index (SII) was associated with prognosis among patients following resection of intrahepatic cholangiocarcinoma (ICC).The impact of SII on overall (OS) and cancer-specific survival (CSS) following resection of ICC was assessed. The performance of the final multivariable models that incorporated inflammatory markers (i.e. neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR] and SII [platelets∗NLR]) was assessed using the Harrell's concordance index.Patients with high SII had worse 5-year OS (37.7% vs 46.6%, p < 0.001) and CSS (46.1% vs 50.1%, p < 0.001) compared with patients with low SII. An elevated SII (HR = 1.70, 95% CI 1.23-2.34) and NLR (HR = 1.58, 95% CI 1.10-2.27) independently predicted worse OS, whereas high PLR (HR = 1.17, 95% CI 0.85-1.60) was no longer associated with prognosis. Only SII remained an independent predictor of CSS (HR = 1.55, 95% CI 1.09-2.21). The SII multivariable model outperformed models that incorporated PLR and NLR relative to OS (c-index; 0.696 vs 0.689 vs 0.692) and CSS (c-index; 0.697 vs 0.689 vs 0.690).SII independently predicted OS and CSS among patients with resectable ICC. SII may be a better predictor of outcomes compared with other markers of inflammatory response among patients with resectable ICC.
Correction to: Trends in the Number of Lymph Nodes Evaluated Among Patients with Pancreatic Neuroendocrine Tumors in the United States: A Multi-Institutional and National Database Analysis. Annals of surgical oncology Sahara, K. n., Tsilimigras, D. I., Mehta, R. n., Moro, A. n., Paredes, A. Z., Lopez-Aguiar, A. G., Rocha, F. n., Kanji, Z. n., Weber, S. n., Fisher, A. n., Fields, R. C., Krasnick, B. A., Idrees, K. n., Smith, P. M., Poultsides, G. A., Makris, E. n., Cho, C. n., Beems, M. n., Dillhoff, M. n., Maithel, S. K., Endo, I. n., Pawlik, T. M. 2020
In the original article, Ryan C. Fields' middle initial is missing.
Minimally Invasive Versus Open Liver Resection for Hepatocellular Carcinoma in the Setting of Portal Vein Hypertension: Results of an International Multi-institutional Analysis. Annals of surgical oncology Ruzzenente, A. n., Bagante, F. n., Ratti, F. n., Alaimo, L. n., Marques, H. P., Silva, S. n., Soubrane, O. n., Endo, I. n., Sahara, K. n., Beal, E. W., Lam, V. n., Poultsides, G. A., Makris, E. A., Popescu, I. n., Alexandrescu, S. n., Martel, G. n., Workneh, A. n., Hugh, T. J., Guglielmi, A. n., Aldrighetti, L. n., Pawlik, T. M. 2020
Patients with hepatocellular carcinoma (HCC) and portal vein hypertension assessed with platelet count (PVH-PLT; platelet count < 100,000/mL) are often denied surgery even when the disease is technically resectable. Short- and long-term outcomes of patients undergoing minimally invasive surgery (MIS) versus open resection for HCC and PVH-PLT were compared.Propensity score matching (PSM) was used to balance the clinicopathological differences between MIS and non-MIS patents. Univariate comparison and standard survival analyses were utilized.Among 1974 patients who underwent surgery for HCC, 13% had a PVH-PLT and 33% underwent MIS. After 1:1 PSM, 407 MIS and 407 non-MIS patients were analyzed. Incidence of complications and length-of-stay (LoS) were higher among non-MIS versus MIS patients (both p ≤ 0.002). After PSM, among 178 PVH-PLT patients (89 MIS and 89 non-MIS), patients who underwent a non-MIS approach had longer LoS (> 7 days; non-MIS: 55% vs. MIS: 29%), as well as higher morbidity (non-MIS: 42% vs. MIS: 29%) [p <0.001]. In contrast, long-term oncological outcomes were comparable, including 3-year overall survival (non-MIS: 66.2% vs. MIS: 72.9%) and disease-free survival (non-MIS: 47.3% vs. MIS: 50.2%) [both p ≥ 0.08].An MIS approach was associated with improved short-term outcomes, but similar long-term outcomes, compared with open liver resection for patients with HCC and PVH-PLT. An MIS approach for liver resection should be considered for patients with HCC, even those individuals with PVH-PLT.
Overall Tumor Burden Dictates Outcomes for Patients Undergoing Resection of Multinodular Hepatocellular Carcinoma Beyond the Milan Criteria. Annals of surgery Tsilimigras, D. I., Mehta, R. n., Paredes, A. Z., Moris, D. n., Sahara, K. n., Bagante, F. n., Ratti, F. n., Marques, H. P., Silva, S. n., Soubrane, O. n., Lam, V. n., Poultsides, G. A., Popescu, I. n., Grigorie, R. n., Alexandrescu, S. n., Martel, G. n., Workneh, A. n., Guglielmi, A. n., Hugh, T. n., Aldrighetti, L. n., Endo, I. n., Spolverato, G. n., Umberto, C. n., Pawlik, T. M. 2020; 272 (4): 574–81
The objective of the current study was to define surgical outcomes after resection of multinodular hepatocellular carcinoma (HCC) beyond the Milan criteria, and develop a prediction tool to identify which patients likely benefit the most from resection.Liver resection for multinodular HCC, especially beyond the Milan criteria, remains controversial. Rigorous selection of the best candidates for resection is essential to achieve optimal outcomes after liver resection of advanced tumors.Patients who underwent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Patients were categorized according to Milan criteria status. Pre- and postoperative overall survival (OS) prediction models that included HCC tumor burden score (TBS) among patients with multinodular HCC beyond Milan criteria were developed and validated.Among 1037 patients who underwent resection for HCC, 164 (15.8%) had multinodular HCC beyond the Milan criteria. Among patients with multinodular HCC, 25 (15.2%) patients experienced a serious complication and 90-day mortality was 3.7% (n = 6). Five-year OS after resection of multinodular HCC beyond Milan criteria was 52.8%. A preoperative TBS-based model (5-year OS: low-risk, 73.7% vs intermediate-risk, 45.1% vs high-risk, 13.1%), and postoperative TBS-based model (5-year OS: low-risk, 80.1% vs intermediate-risk, 37.2% vs high-risk, not reached) categorized patients into distinct prognostic groups relative to long-term prognosis (both P < 0.001). Pre- and postoperative models could accurately stratify OS in an external validation cohort (5-year OS; low vs medium vs high risk; pre: 66.3% vs 25.2% vs not reached, P = 0.012; post: 61.4% vs 42.5% vs not reached, P = 0.045) Predictive accuracy of the pre- and postoperative models was good in the training (c-index; pre: 0.68; post: 0.71), internal validation (n = 2000 resamples) (c-index, pre: 0.70; post: 0.72) and external validation (c-index, pre: 0.67; post 0.68) datasets. TBS alone could stratify patients relative to 5-year OS after resection of multinodular HCC beyond Milan criteria (c-index: 0.65; 5-year OS; low TBS: 70.2% vs medium TBS: 54.7% vs high TBS: 16.7%; P < 0.001). The vast majority of patients with low and intermediate TBS were deemed low or medium risk based on both the preoperative (98.4%) and postoperative risk scores (95.3%).Prognosis of patients with multinodular HCC was largely dependent on overall tumor burden. Liver resection should be considered among patients with multinodular HCC beyond the Milan criteria who have a low- or intermediate-TBS.
The Landmark Series: Pancreatic Neuroendocrine Tumors. Annals of surgical oncology Cloyd, J. M., Poultsides, G. A. 2020
Pancreatic neuroendocrine tumors (PNETs) comprise a heterogeneous group of neoplasms arising from pancreatic islet cells that remain relatively rare but are increasing in incidence worldwide. While significant advances have been made in recent years with regard to systemic therapies for patients with advanced disease, surgical resection remains the standard of care for most patients with localized tumors. Although formal pancreatectomy with regional lymphadenectomy is the standard approach for most PNETs, pancreas-preserving approaches without formal lymphadenectomy are acceptable for smaller tumors at low risk for lymph node metastases. Furthermore, observation of small, asymptomatic, low-grade PNETs is a safe, initial strategy and is generally recommended for tumors < 1 cm in size. In this Landmark Series review, we highlight the critical studies that have defined the surgical management of PNETs.
Development and Validation of a Modified Eighth AJCC Staging System for Primary Pancreatic Neuroendocrine Tumors. Annals of surgery Zhang, X. F., Xue, F. n., Wu, Z. n., Lopez-Aguiar, A. G., Poultsides, G. n., Makris, E. n., Rocha, F. n., Kanji, Z. n., Weber, S. n., Fisher, A. n., Fields, R. n., Krasnick, B. A., Idrees, K. n., Smith, P. M., Cho, C. n., Beems, M. n., Lyu, Y. n., Maithel, S. K., Pawlik, T. M. 2020
To improve the prognostic accuracy of the eighth edition of AJCC staging system for pNETs with establishment and validation of a new staging system.Validation of the updated eighth AJCC staging system for pNETs has been limited and controversial.Data from the SEER registry (1975-2016) (n = 3303) and a multi-institutional database (2000-2016) (n = 825) was used as development and validation cohorts, respectively. A mTNM was proposed by maintaining the eighth AJCC T and M definitions, and the recently proposed N status as N0 (no LNM), N1 (1-3 LNM), and N2 (≥4 LNM), but adopting a new stage classification.The eighth TNM staging system failed to stratify patients with stage I versus IIA, stage IIB versus IIIA, and overall stage I versus II relative to long-term OS in both database. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the SEER (5-year OS, stage I 87.0% vs stage II 80.3% vs stage III 72.9% vs stage IV 57.2%, all P < 0.001), and multi-institutional (5-year OS, stage I 97.6% vs stage II 82.7% vs stage III 78.4% vs stage IV 50.0%, all P < 0.05) datasets. On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the 2 cohorts.A mTNM pNETs clinical staging system using N0, N1, N2 nodal categories was better at stratifying patients relative to long-term OS than the eighth AJCC staging.
Renal Function After Retroperitoneal Sarcoma Resection with Nephrectomy: A Matched Analysis of the United States Sarcoma Collaborative Database. Annals of surgical oncology Stahl, C. C., Schwartz, P. B., Ethun, C. G., Marka, N. n., Krasnick, B. A., Tran, T. B., Poultsides, G. A., Roggin, K. K., Fields, R. C., Clarke, C. N., Votanopoulos, K. I., Cardona, K. n., Abbott, D. E. 2020
Nephrectomy often is required during en bloc resection of a retroperitoneal sarcoma (RPS) to achieve an R0 or R1 resection. The impact of nephrectomy on postoperative renal function in this patient population, who also may benefit from subsequent nephrotoxic systemic therapy, is not well described.The United States Sarcoma Collaborative (USSC) database was queried for patients undergoing RPS resection between 2000 and 2016. Patients with missing pre- or postoperative measures of renal function were excluded. A matched cohort was created using coarsened exact matching. Weighted logistic regression was used to control further for differences between the nephrectomy and non-nephrectomy cohorts. The primary outcomes were postoperative acute kidney injury (AKI), acute renal failure (ARF), and dialysis.The initial cohort consisted of 858 patients, 3 (0.3%) of whom required postoperative dialysis. The matched cohort consisted of 411 patients, 108 (26%) of whom underwent nephrectomy. The patients who underwent nephrectomy had higher rates of postoperative AKI (14.8% vs 4.3%; p < 0.01) and ARF (4.6% vs 1.3%; p = 0.04), but no patients required dialysis postoperatively. Logistic regression modeling showed that the risk of AKI (odds ratio [OR], 5.16; p < 0.01) and ARF (OR 5.04; p < 0.01) after nephrectomy persisted despite controlling for age and preoperative renal function.Nephrectomy is associated with an increased risk of postoperative AKI and ARF after RPS resection. This study was unable to statistically assess the impact of nephrectomy on postoperative dialysis, but the risk of postoperative dialysis is 0.5% or less regardless of nephrectomy status.
A Novel Classification of Intrahepatic Cholangiocarcinoma Phenotypes Using Machine Learning Techniques: An International Multi-Institutional Analysis. Annals of surgical oncology Tsilimigras, D. I., Hyer, J. M., Paredes, A. Z., Diaz, A. n., Moris, D. n., Guglielmi, A. n., Aldrighetti, L. n., Weiss, M. n., Bauer, T. W., Alexandrescu, S. n., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G. n., Pulitano, C. n., Shen, F. n., Soubrane, O. n., Koerkamp, B. G., Endo, I. n., Pawlik, T. M. 2020
Patients with intrahepatic cholangiocarcinoma (ICC) generally have a poor prognosis, yet there can be heterogeneity in the patterns of presentation and associated outcomes. We sought to identify clusters of ICC patients based on preoperative characteristics that may have distinct outcomes based on differing patterns of presentation.Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified using a multi-institutional database. A cluster analysis was performed based on preoperative variables to identify distinct patterns of presentation. A classification tree was built to prospectively assign patients into cluster assignments.Among 826 patients with ICC, three distinct presentation patterns were noted. Specifically, Cluster 1 (common ICC, 58.9%) consisted of individuals who had a small-size ICC (median 4.6 cm) and median carbohydrate antigen (CA) 19-9 and neutrophil-to-lymphocyte ratio (NLR) levels of 40.3 UI/mL and 2.6, respectively; Cluster 2 (proliferative ICC, 34.9%) consisted of patients who had larger-size tumors (median 9.0 cm), higher CA19-9 levels (median 72.0 UI/mL), and similar NLR (median 2.7); Cluster 3 (inflammatory ICC, 6.2%) comprised of patients with a medium-size ICC (median 6.2 cm), the lowest range of CA19-9 (median 26.2 UI/mL), yet the highest NLR (median 13.5) (all p < 0.05). Median OS worsened incrementally among the three different clusters {Cluster 1 vs. 2 vs. 3; 60.4 months (95% confidence interval [CI] 43.0-77.8) vs. 27.2 months (95% CI 19.9-34.4) vs. 13.3 months (95% CI 7.2-19.3); p < 0.001}. The classification tree used to assign patients into different clusters had an excellent agreement with actual cluster assignment (κ = 0.93, 95% CI 0.90-0.96).Machine learning analysis identified three distinct prognostic clusters based solely on preoperative characteristics among patients with ICC. Characterizing preoperative patient heterogeneity with machine learning tools can help physicians with preoperative selection and risk stratification of patients with ICC.
Evaluation of Outcomes Following Surgery for Locally Advanced Pancreatic Neuroendocrine Tumors. JAMA network open Titan, A. L., Norton, J. A., Fisher, A. T., Foster, D. S., Harris, E. J., Worhunsky, D. J., Worth, P. J., Dua, M. M., Visser, B. C., Poultsides, G. A., Longaker, M. T., Jensen, R. T. 2020; 3 (11): e2024318
Although outcome of surgical resection of liver metastases from pancreatic neuroendocrine tumors (PNETs) has been extensively studied, little is known about surgery for locally advanced PNETs; it was listed recently by the European neuroendocrine tumor society as a major unmet need.To evaluate the outcome of patients who underwent surgery for locally aggressive PNETs.This retrospective single-center case series reviewed consecutive patients who underwent resection of T3/T4 PNETs at a single academic institution. Data collection occurred from 2003 to 2018. Data analysis was performed in August 2019.Disease-free survival (primary outcome) and overall mortality (secondary outcome) were assessed with Kaplan-Meier analysis. Recurrence risk (secondary outcome, defined as identification of tumor recurrence on imaging) was assessed with Cox proportional hazard models adjusting for covariates.In this case series, 99 patients with locally advanced nondistant metastatic PNET (56 men [57%]) with a mean (SEM) age of 57.0 (1.4) years and a mean (SEM) follow-up of 5.3 (0.1) years underwent surgically aggressive resections. Of those, 4 patients (4%) underwent preoperative neoadjuvant treatment (including peptide receptor radionuclide therapy and chemotherapy); 18 patients (18%) underwent pancreaticoduodenectomy, 68 patients (69%) had distal or subtotal pancreatic resection, 10 patients (10%) had total resection, and 3 patients (3%) had other pancreatic procedures. Additional organ resection was required in 86 patients (87%): spleen (71 patients [71%]), major blood vessel (17 patients [17%]), bowel (2 patients [2%]), stomach (4 patients [4%]), and kidney (2 patients [2%]). Five-year disease-free survival was 61% (61 patients) and 5-year overall survival was 91% (91 patients). Of those living, 75 patients (76%) had an Eastern Cooperative Oncology Group score of less than or equal to 1 at last followup. Lymph node involvement (HR, 7.66; 95% CI, 2.78-21.12; P < .001), additional organ resected (HR, 6.15; 95% CI, 1.61-23.55; P = .008), and male sex (HR, 3.77; 95% CI, 1.68-8.97; P = .003) were associated with increased risk of recurrence. Functional tumors had a lower risk of recurrence (HR, 0.23; CI, 0.06-0.89; P = .03). Required resection of blood vessels was not associated with a significant increase recurrence risk.In this case series, positive lymph node involvement and resection of organs with tumor involvement were associated with an increased recurrence risk. These subgroups may require adjuvant systemic treatment. These findings suggest that patients with locally advanced PNETs who undergo surgical resection have excellent disease-free and overall survival.
View details for DOI 10.1001/jamanetworkopen.2020.24318
Clinical relevance of performing endoscopic ultrasound-guided fine-needle biopsy for pancreatic neuroendocrine tumors less than 2 cm. Journal of surgical oncology Heidsma, C. M., Tsilimigras, D. I., Rocha, F. n., Abbott, D. E., Fields, R. n., Smith, P. M., Poultsides, G. A., Cho, C. n., van Eijck, C. n., van Dijkum, E. N., Maithel, S. K., Pawlik, T. M. 2020
We sought to define the diagnostic yield and concordance rates between endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) and surgical pathology specimen following resection of pancreatic neuroendocrine tumors (pNET) less than 2 cm.Patients with a pNET less than 2 cm who underwent EUS-FNA were identified using a multi-institutional international database. Tumor differentiation, and Ki-67 index, as determined through EUS-FNA were examined and concordance rates between EUS-FNA and the surgical pathology were assessed.Among 628 patients with a pNET less than 2 cm, 57.2% of patients had an EUS-FNA performed. Patients who underwent EUS had slightly smaller size tumors (1.3 vs 1.4 cm), and the pNETs were less likely to be functional (15.3% vs 26.8%) or symptomatic (48.5% vs 56.5%) (both P < .05). Among 314 patients with a pNET less than 2 cm who had an EUS-FNA performed at the time of diagnosis, 243 (73.2%) had the diagnosis confirmed by preoperative EUS-FNA. Tumor differentiation and Ki-67 could be determined by EUS-FNA in only 26.4% and 20.1% of patients, respectively. Concordance rate between EUS-FNA and pathology was high relative to tumor differentiation (92.7%) and Ki-67 (81.0%).Tumor differentiation and Ki-67 index could be determined by EUS-FNA in only 26.4% and 20.1% of cases, respectively. Further studies should focus on EUS techniques to optimize diagnostic yield and cell extraction in the preoperative setting.
Early Versus Late Recurrence of Hepatocellular Carcinoma After Surgical Resection Based on Post-recurrence Survival: an International Multi-institutional Analysis. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Wei, T. n., Zhang, X. F., Bagante, F. n., Ratti, F. n., Marques, H. P., Silva, S. n., Soubrane, O. n., Lam, V. n., Poultsides, G. A., Popescu, I. n., Grigorie, R. n., Alexandrescu, S. n., Martel, G. n., Workneh, A. n., Guglielmi, A. n., Hugh, T. n., Lv, Y. n., Aldrighetti, L. n., Pawlik, T. M. 2020
To define early versus late recurrence based on post-recurrence survival (PRS) among patients undergoing curative resection for hepatocellular carcinoma (HCC).Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The optimal cut-off time point to discriminate early versus late recurrence was determined relative to PRS.Among 1004 patients, 443 (44.1%) patients experienced recurrence with a median recurrence-free survival time of 12 months. A cut-off time point of 8 months was defined as the optimal threshold based on sensitivity analyses relative to PRS for early (n = 165, 37.2%) versus late relapse (n = 278, 62.8%) (p = 0.008). Early recurrence was associated with worse PRS (median PRS, 27.0 vs. 43.0 months, p = 0.019), as well as overall survival (OS) (median OS, 32.0 versus 74.0 months, p < 0.001) versus late recurrence. In addition, patients who recurred early were more likely to recur at extra- ± intrahepatic (35.5% vs. 19.8%, p = 0.003) sites and were less likely to have the recurrence treated with curative intent (33.8% vs. 45.7%, p = 0.08). Patients undergoing curative re-treatment of late recurrence had a comparable OS with patients who had no recurrence (median OS, 139.0 vs. 140.0 months); patients with early recurrence had inferior OS after curative re-treatment versus patients with no recurrence (median OS, 69.0 vs. 140.0 months, p = 0.036), yet still better than patients who received palliative treatment for early recurrence (median OS, 69.0 vs. 21.0 months, p < 0.001).Eight months was identified as the cut-off value to differentiate early versus late recurrence. Curative-intent treatment for recurrent intrahepatic tumors was associated with reasonable long-term outcomes.
Single cell genomic characterization reveals the cellular reprogramming of the gastric tumor microenvironment. Clinical cancer research : an official journal of the American Association for Cancer Research Sathe, A. n., Grimes, S. M., Lau, B. T., Chen, J. n., Suarez, C. n., Huang, R. J., Poultsides, G. A., Ji, H. P. 2020
The tumor microenvironment (TME) consists of a heterogenous cellular milieu that can influence cancer cell behavior. Its characteristics havean impact on treatments such as immunotherapy. These features can be revealed with single-cell RNA sequencing (scRNA-seq). We hypothesized that scRNA-seq analysis ofgastric cancer (GC) together with paired normal tissue and peripheral blood mononuclear cells (PBMCs) would identify critical elements of cellular deregulation not apparent with other approaches.scRNA-seq was conducted on seven patients with GC and one patient with intestinal metaplasia. We sequenced 56,167 cells comprising GC (32,407 cells), paired normal tissue (18,657 cells) and PBMCs (5,103 cells). Protein expression was validated by multiplex immunofluorescence.Tumor epithelium had copy number alterations, a distinct gene expression program from normal, with intra-tumor heterogeneity. GC TME was significantly enriched for stromal cells, macrophages, dendritic cells (DCs) and Tregs. TME-exclusive stromal cells expressed distinct extracellular matrix components than normal. Macrophages were transcriptionally heterogenous and did not conform to a binary M1/M2 paradigm. Tumor-DCs had a unique gene expression program compared to PBMC DCs. TME-specific cytotoxic T cells were exhausted with two heterogenous subsets. Helper, cytotoxic T, Treg and NK cells expressed multiple immune checkpoint or costimulatory molecules. Receptor-ligand analysis revealed TME-exclusive inter-cellular communication.Single-cell gene expression studies revealed widespread reprogramming across multiple cellular elements in the GC TME. Cellular remodeling was delineated by changes in cell numbers, transcriptional states and inter-cellular interactions. This characterization facilitates understanding of tumor biology and enables identification of novel targets including for immunotherapy.
View details for DOI 10.1158/1078-0432.CCR-19-3231
Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging. Molecular imaging and biology Pei, J. n., Juniper, G. n., van den Berg, N. S., Nisho, N. n., Broadt, T. n., Welch, A. R., Yi, G. S., Raymundo, R. C., Chirita, S. U., Lu, G. n., Krishnan, G. n., Lee, Y. J., Kapoor, S. n., Zhou, Q. n., Colevas, A. D., Lui, N. S., Poultsides, G. A., Li, G. n., Zinn, K. R., Rosenthal, E. L. 2020
The development of molecularly targeted tracers is likely to improve the accuracy of diagnostic, screening, and therapeutic tools. Despite the many therapeutic antibodies that are FDA-approved with known toxicity, only a limited number of antibody-dye conjugates have been introduced to the clinic. Thorough evaluation of the safety, stability, and pharmacokinetics of antibody conjugates in the clinical setting compared with their parental components could accelerate the clinical approval of antibodies as agents for molecular imaging. Here we investigate the safety and stability of a near-infrared fluorescent dye (IRDye800CW) conjugated panitumumab, an approved therapeutic antibody, and report on the product stability, pharmacokinetics, adverse events, and QTc interval changes in patients.Panitumumab-IRDye800CW was made under good manufacturing practice (GMP) conditions in a single batch on March 26, 2014, and then evaluated over 4.5 years at 0, 3, and 6 months, and then at 6-month intervals thereafter. We conducted early phase trials in head and neck, lung, pancreas, and brain cancers with panitumumab-IRDye800CW. Eighty-one patients scheduled to undergo standard-of-care surgery were infused with doses between 0.06 to 2.83 mg/kg of antibody. Patient ECGs, blood samples, and adverse events were collected over 30-day post-infusion for analysis.Eighty-one patients underwent infusion of the study drug at a range of doses. Six patients (7.4 %) experienced an adverse event that was considered potentially related to the drug. The most common event was a prolonged QTc interval which occurred in three patients (3.7 %). Panitumumab-IRDye800CW had two OOS results at 42 and 54 months while meeting all other stability testing criteria.Panitumumab-IRDye800CW was safe and stable to administer over a 54-month window with a low rate of adverse events (7.4 %) which is consistent with the rate associated with panitumumab alone. This data supports re-purposing therapeutic antibodies as diagnostic imaging agents with limited preclinical toxicology studies.
Resection of Colorectal Liver Metastasis: Prognostic Impact of Tumor Burden vs KRAS Mutational Status. Journal of the American College of Surgeons Tsilimigras, D. I., Hyer, J. M., Bagante, F. n., Guglielmi, A. n., Ruzzenente, A. n., Alexandrescu, S. n., Poultsides, G. n., Sasaki, K. n., Aucejo, F. n., Pawlik, T. M. 2020
Prognostic impact of colorectal liver metastasis (CRLM) morphologic characteristics relative to KRAS mutational status following hepatic resection remains ill-defined.Patients undergoing hepatectomy for CRLM between 2001-2018 were identified using an international multi-institutional database. Tumor burden score (TBS) was defined as distance from origin on a Cartesian plane that incorporated maximum tumor size (x-axis) and number of lesions (y-axis). Impact of TBS on overall survival (OS) relative to KRAS status [wild type (wtKRAS) versus mutated (mutKRAS)] was assessed.Among 1,361 patients, median number of metastatic lesions was 2 (IQR:1-3) and median size of largest metastatic lesion was 3.0cm (IQR:2.0-5.0cm) resulting in a median TBS of 4.1(IQR:2.8-6.1); KRAS status was wtKRAS (n=420, 30.9%), mutKRAS (n=251, 18.4%), and unknown (n=690, 50.7%). Overall median and 5-year OS were 49.5 months (95%CI: 45.2-53.8) and 43.2%, respectively. In examining the entire cohort, TBS was associated with long-term prognosis (5-year OS, low TBS:49.4% vs. high TBS:36.7%), as was KRAS mutational status (5-year OS, wtKRAS:48.2% vs. mutKRAS:31.1%; unknown-KRAS:44.0%)(both p<0.01). Among patients with wtKRAS tumors, TBS was strongly associated with improved OS (5-year OS, low TBS: 59.1% vs. high TBS: 38.4%, p=0.002); however, TBS failed to discriminate long-term prognosis among patients with mutKRAS tumors (5-year OS, low TBS: 37.4% vs. high TBS: 26.7%, p=0.19). In fact, patients with high TBS/wtKRAS CRLM had comparable outcomes as patients with low TBS/mutKRAS tumors (5-year OS, 38.4% vs. 37.4%, respectively; p=0.59). On multivariable analysis, while TBS was associated with OS among patients with wt-KRAS CRLM (HR 1.43, 95%CI 1.02-2.00; p=0.03), TBS was not an independent predictor of survival among patients with mutKRAS CRLM (HR 1.36, 95%CI 0.92-1.99; p=0.12).While TBS was associated with survival among patients with wtKRAS tumors, CRLM morphology was not predictive of long-term outcomes among patients with mutKRAS CRLM.
Retroperitoneal sarcoma perioperative risk stratification: A United States Sarcoma Collaborative evaluation of the ACS-NSQIP risk calculator. Journal of surgical oncology Schwartz, P. B., Stahl, C. C., Ethun, C. n., Marka, N. n., Poultsides, G. A., Roggin, K. K., Fields, R. C., Howard, J. H., Clarke, C. N., Votanopoulos, K. I., Cardona, K. n., Abbott, D. E. 2020
The ACS-NSQIP risk calculator predicts perioperative risk. This study tested the calculator's ability to predict risk for outcomes following retroperitoneal sarcoma (RPS) resection.The United States Sarcoma Collaborative database was queried for adults who underwent RPS resection. Estimated risk for outcomes was calculated twice in the risk calculator, once using sarcoma-specific CPT codes and once using codes indicative of most comorbid organ resection (eg nephrectomy). ROC curves were generated, with area under the curve (AUC) and Brier scores reported to assess discrimination and calibration. An AUC < 0.6 was considered ineffective discrimination. A negative ▲ Brier indicated improved performance relative to baseline outcome rates.In total, 482 patients were identified with a 42.3% 90-day complication rate. Discrimination was poor for all outcomes except "all complications" and "renal failure." Baseline outcome rates were better predictors than calculator estimates except for "discharge to nursing or rehab facility" and "renal failure." Replacing sarcoma-specific CPT codes with resection-specific codes did not improve performance.The ACS-NSQIP risk calculator poorly predicted outcomes following RPS resection. Changing sarcoma-specific CPT to resection-specific codes did not improve performance. Comorbidities in the calculator may not effectively capture perioperative risk. Future work should evaluate a sarcoma-specific calculator.
Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors. Annals of surgical oncology Marincola Smith, P. n., Baechle, J. n., Tan, M. C., Solórzano, C. C., Lopez-Aguiar, A. G., Dillhoff, M. n., Beal, E. W., Poultsides, G. n., Cannon, J. G., Rocha, F. G., Crown, A. n., Cho, C. S., Beems, M. n., Winslow, E. R., Rendell, V. R., Krasnick, B. A., Fields, R. C., Maithel, S. K., Bailey, C. E., Idrees, K. n. 2020
Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear.A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS).The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006].Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.
Very Early Recurrence After Liver Resection for Intrahepatic Cholangiocarcinoma: Considering Alternative Treatment Approaches. JAMA surgery Tsilimigras, D. I., Sahara, K. n., Wu, L. n., Moris, D. n., Bagante, F. n., Guglielmi, A. n., Aldrighetti, L. n., Weiss, M. n., Bauer, T. W., Alexandrescu, S. n., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G. n., Pulitano, C. n., Shen, F. n., Soubrane, O. n., Koerkamp, B. G., Moro, A. n., Sasaki, K. n., Aucejo, F. n., Zhang, X. F., Matsuyama, R. n., Endo, I. n., Pawlik, T. M. 2020
Although surgery offers the best chance of a potential cure for patients with localized, resectable intrahepatic cholangiocarcinoma (ICC), prognosis of patients remains dismal largely because of a high incidence of recurrence.To predict very early recurrence (VER) (ie, recurrence within 6 months after surgery) following resection for ICC in the pre- and postoperative setting.Patients who underwent curative-intent resection for ICC between May 1990 and July 2016 were identified from an international multi-institutional database. The study was conducted at The Ohio State University in collaboration with all other participating institutions. The data were analyzed in December 2019.Two logistic regression models were constructed to predict VER based on pre- and postoperative variables. The final models were used to develop an online calculator to predict VER and the tool was internally and externally validated.Among 880 patients (median age, 59 years [interquartile range, 51-68 years]; 388 women [44.1%]; 428 [50.2%] white; 377 [44.3%] Asian; 27 [3.2%] black]), 196 (22.3%) developed VER. The 5-year overall survival among patients with and without VER was 8.9% vs 49.8%, respectively (P < .001). A preoperative model was able to stratify patients relative to the risk for VER: low risk (6-month recurrence-free survival [RFS], 87.7%), intermediate risk (6-month RFS, 72.3%), and high risk (6-month RFS, 49.5%) (log-rank P < .001). The postoperative model similarly identified discrete cohorts of patients based on probability for VER: low risk (6-month RFS, 90.0%), intermediate risk (6-month RFS, 73.1%), and high risk (6-month RFS, 48.5%) (log-rank, P < .001). The calibration and predictive accuracy of the pre- and postoperative models were good in the training (C index: preoperative, 0.710; postoperative, 0.722) as well as the internal (C index: preoperative, 0.715; postoperative, 0.728; bootstrapping resamples, n = 5000) and external (C index: postoperative, 0.672) validation data sets.An easy-to-use online calculator was developed to help clinicians predict the chance of VER after curative-intent resection for ICC. The tool performed well on internal and external validation. This tool may help clinicians in the preoperative selection of patients for neoadjuvant therapy as well as during the postoperative period to inform surveillance strategies.
View details for DOI 10.1001/jamasurg.2020.1973
Number and Station of Lymph Node Metastasis After Curative-intent Resection of Intrahepatic Cholangiocarcinoma Impact Prognosis. Annals of surgery Zhang, X. F., Xue, F. n., Dong, D. H., Weiss, M. n., Popescu, I. n., Marques, H. P., Aldrighetti, L. n., Maithel, S. K., Pulitano, C. n., Bauer, T. W., Shen, F. n., Poultsides, G. A., Soubrane, O. n., Martel, G. n., Koerkamp, B. G., Itaru, E. n., Lv, Y. n., Pawlik, T. M. 2020
To determine the prognostic implication of the number and station of LNM, and the minimal number of LNs needed for evaluation to accurately stage patients with intrahepatic cholangiocarcinoma (ICC).Impact of the number and station of LNM on long-term survival, and the minimal number of LNs needed for accurate staging of ICC patients remain poorly defined.Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide. External validation was performed using the SEER registry. Primary outcomes included overall (OS), disease-specific, and recurrence-free survival.Among 603 patients who underwent curative-intent resection, median and 5-year OS were 30.6 months and 30.4%. Patients with 1 or 2 LNM had comparable worse OS versus patients with no nodal disease (median OS, 1 LNM 18.0, 2 LNM 20.0 vs no LNM 45.0 months, both P < 0.001), yet better OS versus patients with 3 or more LNM (median OS, 1-2 LNM 19.8 vs ≥3 LNM 16.0 months, P < 0.01). On multivariable analysis, a proposed new nodal staging with N1 (1-2 LNM) (Ref. N0, HR 2.40, P < 0.001) and N2 (≥3 LNM) [Ref. N0, hazard ratio (HR) 3.85, P < 0.001] categories were independently associated with incrementally worse OS. Patients with no nodal metastasis, 1-2 LNM and ≥3 LNM also had an increasingly worse disease-specific survival, and recurrence-free survival (both P < 0.05). Total number of LNs examined ≥6 had the greatest discriminatory power relative to OS among patients with 1-2 LNM, and patients with ≥3 LNM in both the multi-institutional (area under the curve 0.780) and SEER database (area under the curve 0.820) (n = 1036). Among patients who underwent an adequate regional lymphadenectomy (total number of LNs examined ≥6), LNM beyond the HDL was associated with worse OS versus LNM within the HDL only (median OS, 14.0 vs 24.0 months, HR 2.41, P = 0.003).Standard lymphadenectomy of at least 6 LNs is strongly recommended and should include examination beyond station 12 to have the greatest chance of accurate staging. The proposed new nodal staging of N0, N1, and N2 should be considered to stratify outcomes among patients after curative-intent resection of ICC.
Laparoscopic hepatic lobectomy for symptomatic polycystic liver disease. HPB : the official journal of the International Hepato Pancreato Biliary Association Li, A. Y., Bergquist, J. R., August, A. T., Dua, M. M., Poultsides, G. A., Visser, B. C. 2020
Laparoscopic fenestration has largely replaced open fenestration of liver cysts. However, most hepatectomies for polycystic liver disease (PCLD) are performed open. Outcomes data on laparoscopic hepatectomy for PCLD are lacking.Patients who underwent surgery for PCLD at a single institution between 2010 and 2019 were reviewed and grouped by operative approach. Pre- and post-operative volumes were calculated for patients who underwent resection. Primary outcomes were: volume reduction, re-admission and postoperative complications.Twenty-six patients were treated for PCLD: 13 laparoscopic fenestration, nine laparoscopic hepatectomy, three open hepatectomy and one liver transplantation. Median length of stay for patients after laparoscopic resection was 3 days (IQR 2-3). The only complication was post-operative atrial fibrillation in one patient. There were no readmissions. Overall volume reduction was 51% (range 22-69) for all resections, 32% (range 22-46) after open resection and 56% (range 39-69) after laparoscopic resection.Volume reduction achieved through laparoscopic approach exceeded open volume reduction at this institution and is comparable to volume reduction in previously published open resection series. Adequate volume reduction can be accomplished by laparoscopic means with acceptable postoperative morbidity.
Long-term outcomes after curative resection of HCV-positive versus non-hepatitis related hepatocellular carcinoma: an international multi-institutional analysis. HPB : the official journal of the International Hepato Pancreato Biliary Association Wei, T. n., Zhang, X. F., Bagante, F. n., Ratti, F. n., Marques, H. P., Soubrane, O. n., Lam, V. n., Poultsides, G. A., Popescu, I. n., Alexandrescu, S. n., Martel, G. n., Workneh, A. n., Guglielmi, A. n., Hugh, T. n., Aldrighetti, L. n., Pawlik, T. M. 2020
To define the chronological changes of long-term survival among patients with non-hepatitis-related hepatocellular carcinoma (Non-Hep-HCC) versus hepatitis C-related HCC (HCV-HCC) over the last two decades.Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Overall (OS) and recurrence-free survival (RFS) were analyzed and compared among Non-Hep-HCC versus HCV-HCC patients. Propensity score matching (PSM) was utilized to mitigate residual bias.Among 617 patients, 196 (31.8%) patients had HCV-HCC, whereas 421 (68.2%) patients had Non-Hep-HCC. While patients with HCV-HCC had an improvement in OS over time (5-year OS, 2000-2009 55% vs. 2010-2017 67%, p = 0.034), OS among patients with Non-Hep-HCC remain unchanged (5-year OS, 2000-2009 53% vs. 2010-2017 52%, p = 0.905). In the matched cohort, patients with HCV-HCC had a worse OS versus patients with Non-Hep-HCC during 2000 and 2009 (5-year OS, 12% vs. 63%, p = 0.029), but significantly better OS from 2010 to 2017 than patients with Non-Hep-HCC (5-year OS, 86% vs. 73%, p = 0.035). The recurrence timing, patterns and re-treatments were comparable among Non-Hep-HCC and HCV-HCC patients.While OS of patients with HCV-HCC improved over time, the long-term survival of patients with Non-Hep-HCC patients remained unchanged and was more unfavorable.
Surgical outcomes of patients with duodenal vs pancreatic neuroendocrine tumors following pancreatoduodenectomy. Journal of surgical oncology Dong, D. H., Zhang, X. F., Lopez-Aguiar, A. G., Poultsides, G. n., Rocha, F. n., Weber, S. n., Fields, R. n., Idrees, K. n., Cho, C. n., Spolverato, G. n., Maithel, S. K., Pawlik, T. M. 2020
To investigate the short- and long-term outcomes of patients undergoing pancreaticoduodenectomy (PD) for duodenal neuroendocrine tumors (dNETs) vs pancreatic neuroendocrine tumors (pNETs).Patients undergoing PD for dNETs or pNETs between 1997 and 2016 were identified from a multi-institutional database. Overall survival (OS) and recurrence-free survival (RFS) were evaluated.Among 276 patients who underwent PD, 244 (88.4%) patients had a primary pNET, whereas 32 (11.6%) patients had a dNET. Following PD, postoperative morbidity and mortality were comparable. While the total number of lymph nodes examined was similar between the two groups (median, dNETs 15.0 vs pNETs 13.0; P= .648), patients with dNETs had a higher incidence of lymph node metastasis (LNM) (60.0% vs 38.2%; P = .022) and a larger number of metastatic nodes (median, 3.5 vs 2.0; P = .039). No differences in OS or RFS were noted among patients with dNETs vs pNETs in both unadjusted and adjusted analyses. Among patients who recurred after PD, patients with dNETs were more likely to recur early (within 2 years, 100% vs 49.2%; P = .029) and at an extrahepatic site (intrahepatic-only recurrence, 20.0% vs 54.1%; P = 0.142) vs patients with pNETs.Patients with dNETs and pNETs had a similar prognosis following PD. Data on differences in the incidence of LNM, as well as in recurrence time and patterns may help to inform the treatment of these patients.
Redefining Conditional Overall and Disease-Free Survival After Curative Resection for Intrahepatic Cholangiocarcinoma: a Multi-institutional, International Study of 1221 patients. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Hu, L., Zhang, X., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Itaru, E., Lv, Y., Pawlik, T. M. 2019
OBJECTIVES: To assess conditional survival (CS) according to recurrence status, as well as conditional disease-free survival (cDFS) among patients with intrahepatic cholangiocarcinoma (ICC).METHODS: CS and cDFS were evaluated among ICC patients who underwent curative-intent resection for ICC by using a multi-institutional database. Five-year CS (CS5) at "x" years was calculated separately for patients who did and did not experience recurrence. The cDFS3 at "x" years was defined as the chance to be disease-free for an additional 3 years after not having experienced a recurrence for "x" years postoperatively.RESULTS: Among 1221 patients, median OS was 36.8 months. While estimated actuarial OS decreased over time, CS5 increased as patients survived over longer periods of time and reached 93.9% at 4 years among 139 patients who did not experience a recurrence. Among the 725 (59.4%) patients who did experience a tumor recurrence, CS5 decreased to 17.7% the first postoperative year; however, CS5 subsequently increased to 79.7% for 81 patients who had survived 4 years after surgery. While actuarial DFS decreased from 54.6% at 1 year to 28.2% at 5 years, estimated cDFS3 following liver resection increased over time. Of note, patients with known risk factors for recurrence had even more marked improvements in cDFS3 over subsequent years versus patients without risk factors for recurrence.CONCLUSION: CS and cDFS changed over time according to the presence of disease-specific risk factors, as well as the presence of recurrence.
Tumor burden score predicts tumor recurrence of non-functional pancreatic neuroendocrine tumors after curative resection. HPB : the official journal of the International Hepato Pancreato Biliary Association Dong, D., Zhang, X., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Schmidt, C. R., Dillhoff, M., Maithel, S. K., Pawlik, T. M. 2019
BACKGROUND: To investigate the feasibility of Tumor Burden Score (TBS) to predict tumor recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs).METHOD: The TBS cut-off values were determined by a statistical tool, X-tile. The influence of TBS on recurrence-free survival (RFS) was examined.RESULTS: Among 842 NF-pNETs patients, there was an incremental worsening of RFS as the TBS increased (5-year RFS, low, medium, and high TBS: 92.0%, 73.3%, and 59.3%, respectively; P<0.001). TBS (AUC 0.74) out-performed both maximum tumor size (AUC 0.65) and number of tumors (AUC 0.5) to predict RFS (TBS vs. maximum tumor size, p=0.05; TBS vs. number of tumors, p<0.01). The impact of margin (low TBS: R0 80.4% vs. R1 71.9%, p=0.01 vs. medium TBS: R0 55.8% vs. R1 37.5%, p=0.67 vs. high TBS: R0 31.9% vs. R1 12.0%, p=0.11) and nodal (5-year RFS, low TBS: N0 94.9% vs. N1 68.4%, p<0.01 vs. medium TBS: N0 81.8% vs. N1 55.4%, p<0.01 vs. high TBS: N0 58.0% vs. N1 54.2%, p=0.15) status on 5-year RFS outcomes disappeared among patients who had higher TBS.CONCLUSIONS: TBS was strongly associated with risk of recurrence and outperformed both tumor size and number alone.
Evaluating the ACS-NSQIP Risk Calculator in Primary GI Neuroendocrine Tumor: Results from the United States Neuroendocrine Tumor Study Group AMERICAN SURGEON Armstrong, E. A., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Cannon, J. G., Rocha, F., Crown, A., Barrett, J., Ronnkleiv-Kelly, S., Fields, R. C., Krasnick, B. A., Idrees, K., Smith, P., Nathan, H., Beems, M., Maithel, S. K., Schmidt, C. R., Pawlik, T. M., Dillhoff, M. 2019; 85 (12): 1334–40
Evaluating the ACS-NSQIP Risk Calculator in Primary GI Neuroendocrine Tumor: Results from the United States Neuroendocrine Tumor Study Group. The American surgeon Armstrong, E. A., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Cannon, J. G., Rocha, F., Crown, A., Barrett, J., Ronnkleiv-Kelly, S., Fields, R. C., Krasnick, B. A., Idrees, K., Smith, P. M., Nathan, H., Beems, M. V., Maithel, S. K., Schmidt, C. R., Pawlik, T. M., Dillhoff, M. 2019; 85 (12): 1334–40
The ACS established an online risk calculator to help surgeons make patient-specific estimates of postoperative morbidity and mortality. Our objective was to assess the accuracy of the ACS-NSQIP calculator for estimating risk after curative intent resection for primary GI neuroendocrine tumors (GI-NETs). Adult patients with GI-NET who underwent complete resection from 2000 to 2017 were identified using a multi-institutional database, including data from eight academic medical centers. The ability of the NSQIP calculator to accurately predict a particular outcome was assessed using receiver operating characteristic curves and the area under the curve (AUC). Seven hundred three patients were identified who met inclusion criteria. The most commonly performed procedures were resection of the small intestine with anastomosis (N = 193, 26%) and partial colectomy with anastomosis (N = 136, 18%). The majority of patients were younger than 65 years (N = 482, 37%) and ASA Class III (N = 337, 48%). The most common comorbidities were diabetes (N = 128, 18%) and hypertension (N = 395, 56%). Complications among these patients based on ACS NSQIP definitions included any complication (N = 132, 19%), serious complication (N = 118, 17%), pneumonia (N = 7, 1.0%), cardiac complication (N = 1, 0.01%), SSI (N = 80, 11.4%), UTI (N = 17, 2.4%), venous thromboembolism (N = 18, 2.5%), renal failure (N = 16, 2.3%), return to the operating room (N = 27, 3.8%), discharge to nursing/rehabilitation (N = 22, 3.1%), and 30-day mortality (N = 9, 1.3%). The calculator provided reasonable estimates of risk for pneumonia (AUC = 0.721), cardiac complication (AUC = 0.773), UTI (AUC = 0.716), and discharge to nursing/rehabilitation (AUC = 0.779) and performed poorly (AUC < 0.7) for all other complications Fig. 1). The ACS-NSQIP risk calculator estimates a similar proportion of risk to actual events in patients with GI-NET but has low specificity for identifying the correct patients for many types of complications. The risk calculator may require modification for some patient populations.
Appendiceal Neuroendocrine Tumors: Does Colon Resection Improve Outcomes? Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Crown, A., Simianu, V. V., Kennecke, H., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G. A., Makris, E., Idrees, K., Smith, P. M., Nathan, H., Beems, M., Abbott, D., Barrett, J., Fields, R. C., Davidson, J., Maithel, S. K., Rocha, F. G. 2019
BACKGROUND: Appendiceal neuroendocrine tumors (A-NETs) are rare neoplasms of the GI tract. They are typically managed according to tumor size; however, the impact of surgical strategy on the short- and long-term outcomes is unknown.METHODS: All patients who underwent resection of A-NET at 8 institutions from 2000 to 2016 were analyzed retrospectively. Patient clinicopathologic features and outcomes were stratified according to resection type.RESULTS: Of 61 patients identified with A-NET, mean age of presentation was 44.7 ± 16.0 years and patients were predominantly Caucasian (77%) and female (56%). Mean tumor size was 1.2 ± 1.3 cm with a median of 0.8 cm. Thirty-one patients (51%) underwent appendectomy and 30 (49%) underwent colonic resection. The appendectomy group had more T1 tumors (87% vs 42%, p < 0.01) than the colon resection group. Of patients in the colon resection group, 27% had positive lymph nodes and 3% had M1 disease. R0 resections were achieved in 90% of appendectomy patients and 97% of colon resection patients. Complications occurred with a higher frequency in the colon resection group (30%) compared with those in the appendectomy group (6%, p = 0.02). The colon resection group also had a longer length of stay, higher average blood loss, and longer average OR time. Median RFS and OS were similar between groups.CONCLUSION: A-NET RFS and OS are equivalent regardless of surgical strategy. Formal colon resection is associated with increased length of stay, OR time, higher blood loss, and more complications. Further study is warranted to identify patients that are likely to benefit from more aggressive surgery.
Utilizing Machine Learning for Pre- and Postoperative Assessment of Patients Undergoing Resection for BCLC-0, A and B Hepatocellular Carcinoma: Implications for Resection Beyond the BCLC Guidelines. Annals of surgical oncology Tsilimigras, D. I., Mehta, R., Moris, D., Sahara, K., Bagante, F., Paredes, A. Z., Farooq, A., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019
BACKGROUND: There is anongoing debate about expanding the resection criteria for hepatocellular carcinoma (HCC) beyond the Barcelona Clinic Liver Cancer (BCLC) guidelines. We sought to determine the factors that held the most prognostic weight in the pre- and postoperative setting for each BCLC stage by applying a machine learning method.METHODS: Patients who underwent resection for BCLC-0, A and B HCC between 2000 and 2017 were identified from an international multi-institutional database. A Classification and Regression Tree (CART) model was used to generate homogeneous groups of patients relative to overall survival (OS) based on pre- and postoperative factors.RESULTS: Among 976 patients, 63 (6.5%) had BCLC-0, 745 (76.3%) had BCLC-A, and 168 (17.2%) had BCLC-B HCC. Five-year OS among BCLC-0/A and BCLC-B patients was 64.2% versus 50.2%, respectively (p=0.011). The preoperative CART model selected alpha-fetoprotein (AFP) and Charlson comorbidity score (CCS) as the first and second most important preoperative factors of OS among BCLC-0/A patients, whereas radiologic tumor burden score (TBS) was the best predictor of OS among BCLC-B patients. The postoperative CART model revealed lymphovascular invasion as the best postoperative predictor of OS among BCLC-0/A patients, whereas TBS remained the best predictor of long-term outcomes among BCLC-B patients in the postoperative setting. On multivariable analysis, pathologic TBS independently predicted worse OS among BCLC-0/A (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.02-1.07) and BCLC-B patients (HR 1.13, 95% CI 1.06-1.19) undergoing resection.CONCLUSION: Prognostic stratification of patients undergoing resection for HCC within and beyond the BCLC resection criteria should include assessment of AFP and comorbidities for BCLC-0/A patients, as well as tumor burden for BCLC-B patients.
Duodenal neuroendocrine tumors: Impact of tumor size and total number of lymph nodes examined. Journal of surgical oncology Zhang, X., Wu, X., Tsilimigras, D. I., Poultsides, G., Rocha, F., Abbott, D. E., Fields, R., Idrees, K., Cho, C., Maithel, S. K., Pawlik, T. M., other members of the US Neuroendocrine Tumor Study Group 2019
BACKGROUND: The current study sought to investigate the impact of tumor size and total number of LN examined (TNLE) on the incidence of lymph node metastasis (LNM) among patients with duodenal neuroendocrine tumor (dNET).METHODS: Patients who underwent curative resection for dNETs between 1997-2016 were identified from 8 high-volume US centers. Risk factors associated with overall survival and LNM were identified and the optimal cut-off of TNLE relative to LNM was determined.RESULTS: Among 162 patients who underwent resection of dNETs, median patient age was 59 (interquartile range [IQR], 51-68) years and median tumor size was 1.2cm (IQR, 0.7-2.0cm); a total of 101 (62.3%) patients underwent a concomitant LND at the time of surgery. Utilization of lymphadenectomy (LND) increased relative to tumor size (≤1cm:52.2% vs 1-2cm:61.4% vs >2cm:93.8%; P<.05). Similarly, the incidence of LNM increased with dNET size (≤1cm: 40.0% vs 1-2cm:65.7% vs >2cm:80.0%; P<.05). TNLE≥8 had the highest discriminatory power relative to the incidence of LNM (area under the curve=0.676). On multivariable analysis, while LNM was not associated with prognosis (hazard ratio [HR]=0.9; 95% confidence intervals [95%CI], 0.4-2.3), G2/G3 tumor grade was (HR=1.5; 95%CI, 1.0-2.1).CONCLUSIONS: While the incidence of LNM directly correlated with tumor size, patients with dNETs≤1cm had a 40% incidence of LNM. Regional lymphadenectomy of a least 8 LN was needed to stage patients accurately.
Evaluating the ACS NSQIP Risk Calculator in Primary Pancreatic Neuroendocrine Tumor: Results from the US Neuroendocrine Tumor Study Group JOURNAL OF GASTROINTESTINAL SURGERY Dave, A., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F. G., Kanji, Z., Ronnekleiv-Kelly, S., Rendell, V. R., Fields, R. C., Krasnick, B. A., Idrees, K., Smith, P., Nathan, H., Beems, M., Maithel, S. K., Pawlik, T. M., Schmidt, C. R., Dillhoff, M. E. 2019; 23 (11): 2225–31
KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: a study from the International Genetic Consortium for Liver Metastases Margonis, G. A., Amini, N., Andreatos, N., Sasaki, K., Mcvey, J., Mirza, M. B., Warner, S., Buettner, S., Barbon, C., Wang, J., Pulvirenti, A., Angelou, A., Kamphues, C., Antoniou, E., Pikoulis, E., Pawlik, T. M., Kaczirek, K., Poultsides, G., Wagner, D., Endo, I., Imai, K., Aucejo, F., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. ELSEVIER SCI LTD. 2019: 1527–34
Is hepatectomy safe following Yttrium-90 therapy? A multi-institutional international experience Melstrom, L. G., Eng, O. S., Raoof, M., Singh, G., Fong, Y., Latorre, K., Choi, G. H., Salem, R., Bentrem, D. J., Lewandowski, R., Makris, E., Poultsides, G., Dhar, V. K., Chadalavada, S., Shah, S. A., Johnson, A. C., Sekhar, A., Kies, D., Maithel, S. K., Rocha, F., Alseidi, A., Hagendoorn, J., Rinkes, I., Fisher, A. V., Ronnekleiv-Kelly, S., Weber, S. M., Winslow, E. R., Abbott, D. E. ELSEVIER SCI LTD. 2019: 1520–26
Survival after Resection of Multiple Tumor Foci of Intrahepatic Cholangiocarcinoma Buettner, S., ten Cate, D. G., Bagante, F., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T., Maithel, S. K., Pulitano, C., Margonis, G., Weiss, M., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J., IJzermans, J. M., Pawlik, T. M., Koerkamp, B. SPRINGER. 2019: 2239–46
Evaluation of integrin alphavbeta6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis. Nature communications Kimura, R. H., Wang, L., Shen, B., Huo, L., Tummers, W., Filipp, F. V., Guo, H. H., Haywood, T., Abou-Elkacem, L., Baratto, L., Habte, F., Devulapally, R., Witney, T. H., Cheng, Y., Tikole, S., Chakraborti, S., Nix, J., Bonagura, C. A., Hatami, N., Mooney, J. J., Desai, T., Turner, S., Gaster, R. S., Otte, A., Visser, B. C., Poultsides, G. A., Norton, J., Park, W., Stolowitz, M., Lau, K., Yang, E., Natarajan, A., Ilovich, O., Srinivas, S., Srinivasan, A., Paulmurugan, R., Willmann, J., Chin, F. T., Cheng, Z., Iagaru, A., Li, F., Gambhir, S. S. 2019; 10 (1): 4673
Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin alphavbeta6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin alphavbeta6.
Defining the chance of cure after resection for hepatocellular carcinoma within and beyond the Barcelona Clinic Liver Cancer guidelines: A multi-institutional analysis of 1,010 patients. Surgery Tsilimigras, D. I., Bagante, F., Moris, D., Merath, K., Paredes, A. Z., Sahara, K., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019
BACKGROUND: Surgery is considered the only potentially curative treatment option for patients with hepatocellular carcinoma. However, the chance that patients will eventually be "cured" after liver resection for hepatocellular carcinoma remains ill defined.METHODS: Patients who underwent curative-intent hepatectomy for hepatocellular carcinoma between 1998 and 2017 were identified using an international multi-institutional database. A nonmixture cure model was used with disease-free survival as a primary measure to estimate cure fractions after matching patients with the general population by age, race, and sex.RESULTS: Among 1,010 patients, the median and 5-year disease-free survival were 2.8 years and 36.6%, respectively. The probability of being cured after hepatocellular carcinoma resection was 42.2% and the median time to cure was 3.35 years. The multivariable cure model revealed preoperative alpha-fetoprotein level, tumor size, tumor number, and margin status as independent predictors of cure. The cure fraction for patients with an alpha-fetoprotein level ≤ 10 ng/mL, largest tumor size ≤5 cm, ≤3 nodules, and R0 resection was 61.6%. In contrast, patients who had all 4 unfavorable prognostic factors (ie, alpha-fetoprotein >11 ng/mL, nodules ≥4, size >5cm, R1 resection) had a cure fraction of 15.8%. Although the probability of cure was 47.6% among Barcelona Clinic Liver Cancer-A patients, patients undergoing resection for Barcelona Clinic Liver Cancer-B hepatocellular carcinoma had a 37.6% cure fraction. Only alpha-fetoprotein levels predicted the probability of cure among Barcelona Clinic Liver Cancer-B patients.CONCLUSION: Roughly 4 in 10 patients could be considered "cured" after liver resection for hepatocellular carcinoma. Although cure was achieved more often after resection for Barcelona Clinic Liver Cancer-A hepatocellular carcinoma, surgery still provided a reasonable probability of cure among select patients with Barcelona Clinic Liver Cancer-B hepatocellular carcinoma.
Postoperative Outcomes of Laparoscopic vs Robotic Distal Pancreatectomy: A Propensity-Matched Analysis Jensen, C. W., Baiocchi, M., Dua, M. M., Poultsides, G. A., Norton, J. A., Worth, P. J., Visser, B. C. ELSEVIER SCIENCE INC. 2019: S181–S182
Prognostic Impact of KRAS Mutational Status in Patients with Colorectal Cancer Liver Metastases Differs According to the Location of the Primary Tumor Amini, N., Margonis, G., Kreis, M. E., Poultsides, G. A., Sasaki, K., Wagner, D., Pikoulis, E., Weiss, M. J., Wolfgang, C. L., Safar, B. ELSEVIER SCIENCE INC. 2019: S69–S70
Role of Adjuvant Radiation Therapy for Retroperitoneal Sarcomas: An 8-Institution Study from the US Sarcoma Collaborative Chouliaras, K., Cardona, K., Poultsides, G. A., Grignol, V. P., Clarke, C. N., Roggin, K., Fields, R. C., Weber, S. M., Johnson, E., Votanopoulos, K. ELSEVIER SCIENCE INC. 2019: S274
Impact of tumor size and nodal status on recurrence of nonfunctional pancreatic neuroendocrine tumors ≤2cm after curative resection: A multi-institutional study of 392 cases. Journal of surgical oncology Dong, D., Zhang, X., Poultsides, G., Rocha, F., Weber, S., Fields, R., Idrees, K., Cho, C., Maithel, S. K., Pawlik, T. M., other members of the US Neuroendocrine Tumor Study Group 2019
BACKGROUND: The current study sought to define the impact of lymph node metastasis (LNM) relative to tumor size on tumor recurrence after curative resection for nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) ≤2cm.METHODS: Patients who underwent curative resection for ≤2-cm NF-pNETs were identified from a multi-institutional database. Risk factors associated with tumor recurrence as well as LNM were identified. Recurrence-free survival (RFS) was compared among patients with or without LNM.RESULTS: A total of 392 ≤2-cm NF-pNETs patients were identified. Among the 328 patients who had lymph node dissection and evaluation, 42 (12.8%) patients had LNM. LNM was associated with tumor recurrence (hazard ratio, 3.06; P=.026) after surgery. RFS was worse among LNM vs no LNM patients (5-year RFS, 81.7% vs 94.1%; P=.019). Patients with tumors measuring 1.5-2cm had a two-fold increase in the incidence of LNM vs patients with tumors <1.5cm (17.9% vs 8.7%, odds ratio, 2.59; P=.022), as well as a higher risk of advanced tumor grade and higher Ki-67 levels (both P<.01). After curative resection, a total of 14 (8.0%) patients with a tumor of 1.5-2cm and 10 (4.5%) patients with tumor <1.5cm developed tumor recurrence.CONCLUSION: Surgical resection with lymphadenectomy should be considered for patients with NF-pNETs ≥1.5-2.0cm.
Role of radiation therapy for retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative. Journal of surgical oncology Chouliaras, K., Senehi, R., Ethun, C. G., Poultsides, G., Grignol, V., Clarke, C. N., Roggin, K. K., Fields, R. C., Schwartz, P. B., Ronnekleiv-Kelly, S. M., D'Agostino, R. J., Johnson, E. N., Levine, E. A., Cardona, K., Votanopoulos, K. I. 2019
BACKGROUND: The use of radiation therapy in the treatment of retroperitoneal sarcomas has increased in recent years. Its impact on survival and recurrence is unclear.METHODS: A retrospective propensity score matched (PSM) analysis of patients with primary retroperitoneal soft tissue sarcomas, who underwent resection from 2000 to 2016 at eight institutions of the US Sarcoma Collaborative, was performed. Patients with metastatic disease, desmoid tumors, and palliative resections were excluded.RESULTS: Total 425 patients were included, 56 in the neoadjuvant radiation group (neo-RT), 75 in the adjuvant radiation group (adj-RT), and 294 in the no radiotherapy group (no-RT). Median age was 59.5 years, 186 (43.8%) were male with a median follow up of 31.4 months. R0 and R1 resection was achieved in 253 (61.1%) and 143 (34.5%), respectively. Overall 1:1 match of 46 adj-RT and 59 neo-RT patients was performed using histology, sex, age, race, functional status, tumor size, grade, resection status, and chemotherapy. Unadjusted recurrence-free survival (RFS) was 35.9 months (no-RT) vs 33.5 months (neo-RT) and 27.2 months (adj-RT), P=.43 and P=.84, respectively. In the PSM, RFS was 17.6 months (no-RT) vs 33.9 months (neo-RT), P=.28 and 19 months (no-RT) vs 27.2 months (adj-RT), P=.1.CONCLUSIONS: Use of radiotherapy, both in adjuvent or neoadjuvent setting, was not associated with improved survival or reduced recurrence rate.
Response to preoperative chemotherapy: impact of change in total burden score and mutational tumor status on prognosis of patients undergoing resection for colorectal liver metastases HPB Ruzzenente, A., Bagante, F., Ratti, F., Beal, E. W., Alexandrescu, S., Merath, K., Makris, E. A., Poultsides, G. A., Margonis, G. A., Weiss, M. J., Popescu, I., Aldrighetti, L., Guglielmi, A., Pawlik, T. M. 2019; 21 (9): 1230–39
Complications after liver surgery: a benchmark analysis HPB Bagante, F., Ruzzenente, A., Beal, E. W., Campagnaro, T., Merath, K., Conci, S., Akgul, O., Alexandrescu, S., Marques, H. P., Lam, V., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Iacono, C., Guglielmi, A., Pawlik, T. M. 2019; 21 (9): 1139–49
Discordance in prediction of prognosis among patients with intrahepatic cholangiocarcinoma: A preoperative vs postoperative perspective JOURNAL OF SURGICAL ONCOLOGY Moro, A., Paredes, A. Z., Farooq, A., Sahara, K., Tsilimigras, D., Mehta, R., Endo, I., Guglielmi, A., Aldrighetti, L., Alexandrescu, S., Marques, H. P., Shen, F., Koerkamp, B. G., Sasaki, K., Pawlik, T. M., Weiss, M., Bauer, T. W., Poultsides, G. A., Maithel, S. K., Martel, G., Pulitano, C., Soubrane, O., Int Intrahepatic Cholangiocarcinom 2019
The objective of the current study was to characterize patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent surgery with discordant preoperative and postoperative prediction scores and determine factors associated with prediction discrepancy.Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified in a multi-institutional international database. Preoperative and postoperative prognostic models were designed and discordant prognostic scores were identified. A multivariable logistic regression analysis was completed to determined factors associated with score discordance.Among 1149 patients, those who had concordant prediction scores were older (median age, 60 vs 56), and more likely to have a smaller median tumor size (6.0 vs 7.5 cm) (all P < .05). On multivariable logistic analysis, patients with higher neutrophil-lymphocyte ratio (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.09-1.19), higher CEA levels (OR, 1.25; 95% CI, 1.04-1.50), larger tumors (OR, 1.10; 95% CI, 1.04-1.15) and suspicious lymph nodes (OR, 2.05; 95% CI, 1.25-3.36) were more likely to have preoperative and postoperative score discordance. Older patients had decreased odds of having score discordance (OR, 0.98; 95% CI, 0.96-0.99). Patients with score discordance had worse overall survival compared with patients with concordant scores (median:15.9 vs 21.7 months, P < .05).Score discordance may reflect an aggressive variant of ICC that would benefit from early integration of multidisciplinary treatment strategies.
Interaction of race and pathology for neuroendocrine tumors: Epidemiology, natural history, or racial disparity? Journal of surgical oncology DePalo, D. K., Lee, R. M., Lopez-Aguiar, A. G., Gamboa, A. C., Rocha, F., Poultsides, G., Dillhoff, M., Fields, R. C., Idrees, K., Nathan, H., Abbott, D., Maithel, S. K., Russell, M. C., other members of the United States Neuroendocrine Tumor Study Group 2019
BACKGROUND AND OBJECTIVES: Although minority race has been associated with worse cancer outcomes, the interaction of race with pathologic variables and outcomes of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is not known.METHODS: Patients from the US Neuroendocrine Study Group (2000-2016) undergoing curative-intent resection of GEP-NETs were included. Given few patients of other races, only Black and White patients were analyzed.RESULTS: A total of 1143 patients were included. Median age was 58years, 49% were male, 14% Black, and 86% White. Black patients were more likely to be uninsured (7% vs 2%, P=.011), and to have symptomatic bleeding (13% vs 7%, P=.009), emergency surgery (7% vs 3%, P=.006), and positive lymph nodes (LN) (47% vs 36%, P=.021). However, Black patients had improved 5-year recurrence-free survival (RFS) (90% vs 80%, P=.008). Quality of care was comparable between races, seen by similar LN yield, R0 resections, postoperative complications, and need for reoperation/readmission (all P>.05). While both races were more likely to have pancreas-NETs, Black patients had more small bowel-NETs (22% vs 13%, P<.001). LN positivity was prognostic for pancreas-NETs (5-year RFS 67% vs 83%, P=.001) but not for small-bowel NETs.CONCLUSIONS: Black patients with GEP-NETs had more adverse characteristics and higher LN positivity. Despite this, Black patients have improved RFS. This may be attributed to the epidemiologic differences in the primary site of GEP-NETs and variable prognostic value of LN-positive disease.
The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status: A Study By the International Genetic Consortium for Colorectal Liver Metastasis. Annals of surgery Margonis, G. A., Amini, N., Buettner, S., Kim, Y., Wang, J., Andreatos, N., Wagner, D., Sasaki, K., Beer, A., Kamphues, C., Morioka, D., Loes, I. M., Imai, K., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P. E., Burkhart, R., Endo, I., Baba, H., Mischinger, H. J., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019
OBJECTIVE: To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status.BACKGROUND: Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors.METHODS: Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status.RESULTS: 277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38).CONCLUSIONS: This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.
Minimally invasive versus open distal pancreatectomy for pancreatic neuroendocrine tumors: An analysis from the US neuroendocrine tumor study group JOURNAL OF SURGICAL ONCOLOGY Zhang, X., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Schmidt, C. R., Maithel, S. K., Pawlik, T. M., United States Neuroendocrine Tumor 2019; 120 (2): 231–40
Prognostic utility of albumin-bilirubin grade for short- and long-term outcomes following hepatic resection for intrahepatic cholangiocarcinoma: A multi-institutional analysis of 706 patients JOURNAL OF SURGICAL ONCOLOGY Tsilimigras, D. I., Hyer, J., Moris, D., Sahara, K., Bagante, F., Guglielmi, A., Aldrighetti, L., Alexandrescu, S., Marques, H. P., Shen, F., Koerkamp, B., Endo, I., Pawlik, T. M., Merath, K., Paredes, A. Z., Weiss, M., Bauer, T. W., Poultsides, G. A., Maithel, S. K., Martel, G., Pulitano, C., Soubrane, O., Int Intrahepatic 2019; 120 (2): 206–13
The objective of the current study was to define the impact of albumin-bilirubin (ALBI) grade on short- as well as long-term outcomes among patients with intrahepatic cholangiocarcinoma (ICC).Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified using an international multi-institutional database. Clinicopathologic factors including ALBI score were assessed using bivariate and multivariable analyses, as well as standard survival analyses.Among 706 patients, 453 (64.2%) patients had ALBI grade 1, 231 (32.7%) ALBI grade 2, and 22 (3.1%) had ALBI grade 3. After adjusting for all competing factors, patients with ALBI grade 2/3 had higher odds of a prolonged length-of-stay (>10 days, odds ratio [OR] = 2.37, 95% confidence interval [CI]:1.47-3.80), perioperative transfusion (OR = 2.15, 95% CI:1.45-3.18) and 90-day mortality (OR = 2.50, 95% CI:1.16-5.38). Median and 5-year overall survival (OS) for the entire cohort was 41.5 months (IQR:15.7-107.8) and 39.8%, respectively. Of note, median OS incrementally worsened with increased ALBI grade: grade 1, 49.6 months (IQR:18.3-NR) vs grade 2, 29.6 months (IQR:12.6-98.4) vs grade 3, 16.9 months (IQR:6.5-32.4; P < 0.001). On multivariable analysis, higher ALBI grade remained associated with higher hazards of death (grade 2/3: hazard ratio = 1.36, 95% CI:1.04-1.78).The ALBI score was associated with both short- and long-term outcomes following resection for ICC and could prove a useful surrogate marker to identify patients at risk for adverse outcomes.
Recurrence Patterns and Timing Courses Following Curative-Intent Resection for Intrahepatic Cholangiocarcinoma ANNALS OF SURGICAL ONCOLOGY Hu, L., Zhang, X., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Itaru, E., Pawlik, T. M. 2019; 26 (8): 2549–57
Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group Lopez-Aguiar, A. G., Zaidi, M. Y., Beal, E. W., Dillhoff, M., Cannon, J. D., Poultsides, G. A., Kanji, Z. S., Rocha, F. G., Smith, P., Idrees, K., Beems, M., Cho, C. S., Fisher, A. V., Weber, S. M., Krasnick, B. A., Fields, R. C., Cardona, K., Maithel, S. K. SPRINGER. 2019: 2517–24
New Nodal Staging for Primary Pancreatic Neuroendocrine Tumors: A Multi-institutional and National Data Analysis. Annals of surgery Zhang, X., Xue, F., Dong, D., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Lv, Y., Maithel, S. K., Pawlik, T. M. 2019
OBJECTIVE: To determine the prognostic role of metastatic lymph node (LN) number and the minimal number of LNs for optimal staging of patients with pancreatic neuroendocrine tumors (pNETs).BACKGROUND: Prognosis relative to number of LN metastasis (LNM), and minimal number of LNs needed to evaluate for accurate staging, have been poorly defined for pNETs.METHODS: Number of LNM and total number of LN evaluated (TNLE) were assessed relative to recurrence-free survival (RFS) and overall survival (OS) in a multi-institutional database. External validation was performed using Surveillance, Epidemiology and End Results (SEER) registry.RESULTS: Among 854 patients who underwent resection, 233 (27.3%) had at least 1 LNM. Patients with 1, 2, or 3 LNM had a comparable worse RFS versus patients with no nodal metastasis (5-year RFS, 1 LNM 65.6%, 2 LNM 68.2%, 3 LNM 63.2% vs 0 LNM 82.6%; all P < 0.001). In contrast, patients with ≥4 LNM (proposed N2) had a worse RFS versus patients who either had 1 to 3 LNM (proposed N1) or node-negative disease (5-year RFS, ≥4 LNM 43.5% vs 1-3 LNM 66.3%, 0 LNM 82.6%; all P < 0.05) [C-statistics area under the curve (AUC) 0.650]. TNLE ≥8 had the highest discriminatory power relative to RFS (AUC 0.713) and OS (AUC 0.726) among patients who had 1 to 3 LNM, and patients who had ≥4 LNM in the multi-institutional and SEER database (n = 2764).CONCLUSIONS: Regional lymphadenectomy of at least 8 lymph nodes was necessary to stage patients accurately. The proposed nodal staging of N0, N1, and N2 optimally staged patients.
Assessing the Role of Neoadjuvant Chemotherapy in Primary High-Risk Truncal/Extremity Soft Tissue Sarcomas: An Analysis of the Multi-institutional U.S. Sarcoma Collaborative. Annals of surgical oncology Zaidi, M. Y., Ethun, C. G., Tran, T. B., Poultsides, G., Grignol, V. P., Howard, J. H., Bedi, M., Mogal, H., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B., Fields, R. C., Oskouei, S., Reimer, N., Monson, D., Maithel, S. K., Cardona, K. 2019
BACKGROUND: The role of neoadjuvant chemotherapy (NCT) for high-risk soft tissue sarcoma (STS) is questioned. This study aimed to define which patients may experience a survival advantage with NCT.METHODS: All the patients from the U.S. Sarcoma Collaborative database (2000-2016) who underwent curative-intent resection of high-grade, primary truncal/extremity STS size 5cm or larger were included in this study. The primary end points were recurrence-free survival (RFS) and overall survival (OS).RESULTS: Of the 4153 patients, 770 were included in the study. The median tumor size was 10cm, and 669 of the patients (87%) had extremity tumors. The most common histology was undifferentiated pleomorphic sarcoma (UPS), found in 42% of the patients. Of the 770 patients, 216 (28%) received NCT. The patients who received NCT had deeper, larger tumors (p<0.001). Of the patients with tumors 5cm or larger and 8cm or larger, NCT was not associated with improved RFS or OS. However for the patients with tumors 10cm or larger, NCT was associated with improved 5-year RFS (51% vs 40%; p=0.053) and 5-year OS (58% vs 47%; p=0.043). By location, the patients with extremity tumors 10cm or larger but not truncal tumors had improved 5-yearr RFS (54% vs 42%; p=0.042) and 5-year OS (61% vs 47%; p=0.015) with NCT. According to histology, no subtype had improved RFS or OS with NCT, although the patients with UPS had a trend toward improved 5-year RFS (56% vs 42%; p=0.092) and 5-year OS (66% vs 52%; p=0.103) with NCT.CONCLUSION: For the patients with high-grade STS, NCT was associated with improved RFS and OS when tumors were 10cm or larger and located in the extremity. However, no histiotype-specific advantage was identified. Future studies assessing the efficacy of NCT may consider focusing on these patients, with added focus on histology-specific strategies.
Intrahepatic cholangiocarcinoma tumor burden: A classification and regression tree model to define prognostic groups after resection. Surgery Bagante, F., Spolverato, G., Merath, K., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Guglielmi, A., Endo, I., Pawlik, T. M. 2019
BACKGROUND: Tumor burden is an important factor in defining prognosis among patients with primary and secondary liver cancers. Although the eighth edition of the American Joint Committee on Cancer staging system has changed the criteria for staging patients with intrahepatic cholangiocarcinoma to better define the effect of tumor burden on prognosis, the impact of intrahepatic cholangiocarcinoma tumor burden on overall survival has not been examined using a machine-learning tool.METHODS: Patients who underwent resection of intrahepatic cholangiocarcinoma at 1 of 14 participating international hospitals between 1990 and 2015 were identified. Classical survival models and the Classification and Regression Tree model were used to identify groups of patients with a homogeneous risk of death and investigate the hierarchical association between variables and overall survival.RESULTS: Among 1,116 patients included in the analysis, tumor size was ≤5 cm in 447 (40.1%) patients and >5 cm in 669 (59.9%) patients. Although 82.9% (n= 926) of patients had a single intrahepatic cholangiocarcinoma, 9.9% (n= 110) and 7.2% (n= 80) of patients had 2 and ≥3 tumors, respectively. Patients with intrahepatic cholangiocarcinoma tumors ≤5 cm and >5 cm had a 5-year overall survival of 51.7% and 32.6%, respectively (P < 0.001). Five-year overall survival decreased from 44.6% among patients with a single intrahepatic cholangiocarcinoma to 28.1% and 14.2% among patients with 2 and ≥3 intrahepatic cholangiocarcinomas, respectively (P < 0.001). Among the combinations of tumor size and intrahepatic cholangiocarcinoma tumor number used to estimate tumor burden, logarithmic transformation of tumor size (log tumor size) and intrahepatic cholangiocarcinoma tumor number had the highest concordance index. The Classification and Regression Tree model identified 8 classes of patients with a homogeneous risk of death, illustrating the hierarchical relationship between tumor burden (log tumor size and number of intrahepatic cholangiocarcinomas) and other factors associated with prognosis.CONCLUSION: Intrahepatic cholangiocarcinoma tumor size and number demonstrated a strong nonlinear association with survival after resection of intrahepatic cholangiocarcinoma. A log-model Classification and Regression Tree-derived tumor burden score may be a better tool to estimate prognosis of patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma.
A Novel Validated Recurrence Risk Score to Guide a Pragmatic Surveillance Strategy After Resection of Pancreatic Neuroendocrine Tumors: An International Study of 1006 Patients. Annals of surgery Zaidi, M. Y., Lopez-Aguiar, A. G., Switchenko, J. M., Lipscomb, J., Andreasi, V., Partelli, S., Gamboa, A. C., Lee, R. M., Poultsides, G. A., Dillhoff, M., Rocha, F. G., Idrees, K., Cho, C. S., Weber, S. M., Fields, R. C., Staley, C. A., Falconi, M., Maithel, S. K. 2019
OBJECTIVE: Despite heterogeneous biology, similar surveillance schemas are utilized after resection of all pancreatic neuroendocrine tumors (PanNETs). Given concerns regarding excess radiation exposure and financial burden, our aim was to develop a prognostic score for disease recurrence to guide individually tailored surveillance strategies.METHODS: All patients with primary nonfunctioning, nonmetastatic well/moderately differentiated PanNETs who underwent curative-intent resection at 9-institutions from 2000 to 2016 were included (n = 1006). A Recurrence Risk Score (RRS) was developed from a randomly selected derivation cohort comprised of 67% of patients and verified on the validation-cohort comprised of the remaining 33%.RESULTS: On multivariable analysis, patients within the derivation cohort (n = 681) with symptomatic tumors (jaundice, pain, bleeding), tumors >2 cm, Ki67 >3%, and lymph node (LN) (+) disease had increased recurrence. Each factor was assigned a score based on their weighted odds ratio that formed a RRS of 0 to 10: symptomatic = 1, tumor >2 cm = 2, Ki67 3% to 20% = 1, Ki67 >20% = 6, LN (+) = 1. Patients were grouped into low- (RRS = 0-2; n = 247), intermediate-(RRS = 3-5; n = 204), or high (RRS = 6-10; n = 9)-risk groups. At 24 months, 33% of high RRS recurred, whereas only 2% of low and 14% of intermediate RRS recurred. This persisted in the validation cohort (n = 325).CONCLUSIONS: This international, novel, internally validated RRS accurately stratifies recurrence-free survival for patients with resected PanNETs. Given their unique recurrence patterns, surveillance intervals of 12, 6, and 3 months are proposed for low, intermediate, and high RRS patients, respectively, to minimize radiation exposure and optimize cost/resource utilization.
Prognosis After Resection of Barcelona Clinic Liver Cancer (BCLC) Stage 0, A, and B Hepatocellular Carcinoma: A Comprehensive Assessment of the Current BCLC Classification. Annals of surgical oncology Tsilimigras, D. I., Bagante, F., Sahara, K., Moris, D., Hyer, J. M., Wu, L., Ratti, F., Marques, H. P., Soubrane, O., Paredes, A. Z., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019
BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have questioned the prognostic stratification of this classification schema, as well as the proposed treatment allocation of patients with a single large tumor.METHODS: Patients who underwent curative-intent hepatectomy for histologically proven hepatocellular carcinoma (HCC) between 1998 and 2017 were identified using an international multi-institutional database. Overall survival (OS) among patients with BCLC stage 0, A, and B was examined. Patients with a single large tumor were classified as BCLC stage A1 and were independently assessed.RESULTS: Among 814 patients, 68 (8.4%) were BCLC-0, 310 (38.1%) were BCLC-A, 279 (34.3%) were BCLC-A1, and 157 (19.3%) were BCLC-B. Five-year OS among patients with BCLC stage 0, A, A1, and B HCC was 86.2%, 69.0%, 56.9%, and 49.9%, respectively (p<0.001). Among patients with very early- and early-stage HCC (BCLC 0, A, and A1), patients with BCLC stage A1 had the worstOS (p=0.0016). No difference in survival was noted among patients undergoing surgery for BCLC stage A1 and B HCC (5-year OS: 56.9% vs. 49.9%; p=0.259) even after adjusting for competing factors (hazard ratio 0.83, 95% confidence interval 0.54-1.28; p=0.40).CONCLUSION: Prognosis following liver resection among patients with BCLC-A1 HCC was similar to patients presenting with BCLC-B tumors. Surgery provided acceptable long-term outcomes among select patients with BCLC-B HCC. Designation into BCLC stage B should not be considered an a priori contraindication to surgery.
The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management Lopez-Aguiar, A. G., Ethun, C. G., Zaidi, M. Y., Rocha, F. G., Poultsides, G. A., Dillhoff, M., Fields, R. C., Idrees, K., Cho, C. S., Abbott, D. E., Cardona, K., Maithel, S. K. MOSBY-ELSEVIER. 2019: 15–21
Esophageal and Esophagogastric Junction Cancers, Version 2.2019 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ajani, J. A., D'Amico, T. A., Bentrem, D. J., Chao, J., Corvera, C., Das, P., Denlinger, C. S., Enzinger, P. C., Fanta, P., Farjah, F., Gerdes, H., Gibson, M., Glasgow, R. E., Hayman, J. A., Hochwald, S., Hofstetter, W. L., Ilson, D. H., Jaroszewski, D., Johung, K. L., Keswani, R. N., Kleinberg, L. R., Leong, S., Ly, Q. P., Matkowskyj, K. A., McNamara, M., Mulcahy, M. F., Paluri, R. K., Park, H., Perry, K. A., Pimiento, J., Poultsides, G. A., Roses, R., Strong, V. E., Wiesner, G., Willett, C. G., Wright, C. D., McMillian, N. R., Pluchino, L. A. 2019; 17 (7): 855–83
Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.
View details for DOI 10.6004/jnccn.2019.0033
Should Utilization of Lymphadenectomy Vary According to Morphologic Subtype of Intrahepatic Cholangiocarcinoma? ANNALS OF SURGICAL ONCOLOGY Zhang, X., Lv, Y., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Itaru, E., Pawlik, T. M. 2019; 26 (7): 2242–50
Comprehensive characterization of gastric cancer at single-cell resolution Chen, J., Sathe, A., Grimes, S., Greer, S., Lau, B., Renschler, A., Poultsides, G., Suarez, C., Ji, H. AMER ASSOC CANCER RESEARCH. 2019
View details for DOI 10.1158/1538-7445.SABCS18-151
Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer HPB Tummers, W. S., Miller, S. E., Teraphongphom, N. T., van den Berg, N. S., Hasan, A., Longacre, T. A., Fisher, G. A., Bonsing, B. A., Vahrmeijer, A. L., Gambhir, S. S., Swijnenburg, R., Rosenthal, E. L., Poultsides, G. A. 2019; 21 (7): 883–90
Features of synchronous versus metachronous metastasectomy in adrenal cortical carcinoma: Analysis from the US adrenocortical carcinoma database. Surgery Prendergast, K. M., Smith, P. M., Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J. D., Pawlik, T. M., Wang, T. S., Glenn, J., Hatzaras, I., Shenoy, R., Phay, J. E., Shirley, L. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Solorzano, C. C., Kiernan, C. M. 2019
BACKGROUND: Adrenocortical carcinoma is a rare, aggressive cancer. We compared features of patients who underwent synchronous versus metachronous metastasectomy.METHODS: Adult patients who underwent resection for metastatic adrenocortical carcinoma from 1993 to 2014 at 13 institutions of the US adrenocortical carcinoma group were analyzed retrospectively. Patients were categorized as synchronous if they underwent metastasectomy at the index adrenalectomy or metachronous if they underwent resection after recurrence of the disease. Factors associated with overall survival were assessed by univariate analysis.RESULTS: In the study, 84 patients with adrenocortical carcinoma underwent metastasectomy; 26 (31%) were synchronous and 58 (69%) were metachronous. Demographics were similar between groups. The synchronous group had more T4 tumors at the index resection (42 vs 3%, P < .001). The metachronous group had prolonged median survival after the index resection (86.3 vs 17.3 months, P < .001) and metastasectomy (36.9 vs 17.3 months, P= .007). Synchronous patients with R0 resections had improved survival compared to patients with R1/2 resections (P= .008). Margin status at metachronous metastasectomy was not associated with survival (P= .452).CONCLUSION: Select patients with metastatic adrenocortical carcinoma may benefit from metastasectomy. Patients with metachronous metastasectomy have a more durable survival benefit than those undergoing synchronous metastasectomy. This study highlights need for future studies examining differences in tumor biology that could explain outcome disparities in these distinct patient populations.
Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming GUT Koutsioumpa, M., Hatziapostolou, M., Polytarchou, C., Tolosa, E. J., Almada, L. L., Mahurkar-Joshi, S., Williams, J., Belen Tirado-Rodriguez, A., Huerta-Yepez, S., Karavias, D., Kourea, H., Poultsides, G. A., Struhl, K., Dawson, D. W., Donahue, T. R., Fernandez-Zapico, M. E., Iliopoulos, D. 2019; 68 (7): 1271–86
View details for DOI 10.1136/gutjnl-2017-315690
Recurrence patterns after resection of retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative. Journal of surgical oncology Chouliaras, K., Senehi, R., Ethun, C. G., Poultsides, G., Tran, T., Grignol, V., Gamblin, T. C., Roggin, K. K., Tseng, J., Fields, R. C., Weber, S. M., Russell, G. B., Levine, E. A., Cardona, K., Votanopoulos, K. 2019
BACKGROUND AND OBJECTIVES: Resection of primary retroperitoneal sarcomas (RPS) has a high incidence of recurrence. This study aims to identify patterns of recurrence and its impact on overall survival.METHODS: Adult patients with primary retroperitoneal soft tissue sarcomas who underwent resection in 2000-2016 at eight institutions of the US Sarcoma Collaborative were evaluated.RESULTS: Four hundred and ninety-eight patients were analyzed, with 56.2% (280 of 498) having recurrences. There were 433 recurrences (1-8) in 280 patients with 126 (25.3%) being locoregional, 82 (16.5%) distant, and 72 (14.5%) both locoregional and distant. Multivariate analyses revealed the following: Patient age P=.0002), tumor grade (P=.02), local recurrence (P=.0003) and distant recurrence (P<.0001) were predictors of disease-specific survival. The 1-, 3-, and 5-year survival rate for patients who recurred vs not was 89.6% (standard error [SE] 1.9) vs 93.5% (1.8), 66.0% (3.2) vs 88.4% (2.6), and 51.8% (3.6) vs 83.9% (3.3), respectively, P<.0001. Median survival was 5.3 years for the recurrence vs 11.3+ years for the no recurrence group (P<.0001). Median survival from the time of recurrence was 2.5 years.CONCLUSIONS: Recurrence after resection of RPS occurs in more than half of patients independently of resection status or perioperative chemotherapy and is equally distributed between locoregional and distant sites. Recurrence is primarily related to tumor biology and is associated with a significant decrease in overall survival.
Effect of Surgical Margin Width on Patterns of Recurrence among Patients Undergoing R0 Hepatectomy for T1 Hepatocellular Carcinoma: An International Multi-Institutional Analysis. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Tsilimigras, D. I., Sahara, K., Moris, D., Hyer, J. M., Paredes, A. Z., Bagante, F., Merath, K., Farooq, A. S., Ratti, F., Marques, H. P., Soubrane, O., Azoulay, D., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019
INTRODUCTION: Although a positive surgical margin is a known prognostic factor for recurrence, the optimal surgical margin width in the context of an R0 resection for early-stage hepatocellular carcinoma (HCC) is still debated. The aim of the current study was to examine the impact of wide (>1cm) versus narrow (<1cm) surgical margin status on the incidence and recurrence patterns among patients with T1 HCC undergoing an R0 hepatectomy.METHODS: Between 1998 and 2017, patients with T1 HCC who underwent R0 hepatectomy for stage T1 HCC were identified using an international multi-institutional database. Recurrence-free survival (RFS) was estimated, and recurrence patterns were examined based on whether patients had a wide versus narrow resection margins.RESULTS: Among 404 patients, median patient age was 66years (IQR: 58-73). Most patients (n=326, 80.7%) had surgical margin <1cm, while 78 (19.3%) patients had a >1cm margin. The majority of patients had early recurrences (<24months) in both margin width groups (<1cm: 70.3% vs >1cm: 85.7%, p=0.141); recurrence site was mostly intrahepatic (<1cm: 77% vs >1cm: 61.9%, p=0.169). The 1-, 3-, and 5-year RFS among patients with margin <1cm were 77%, 48.9%, and 35.3% versus 81.7%, 65.8%, and 60.7% for patients with margin >1cm, respectively (p=0.02). Among patients undergoing anatomic resection, resection margin did not impact RFS (3-year RFS: <1cm: 49.2% vs >1cm: 58.9%, p=0.169), whereas in the non-anatomic resection group, margin width >1cm was associated with a better 3-year RFS compared to margin <1cm (86.7% vs 47.3%, p=0.017). On multivariable analysis, margin >1cm remained protective against recurrence (HR=0.50, 95%CI 0.28-0.89), whereas Child-Pugh B (HR=2.13, 95%CI 1.09-4.15), AFP >20 ng/mL (HR=1.71, 95%CI 1.18-2.48), and presence of microscopic lymphovascular invasion (HR=1.48, 95%CI 1.01-2.18) were associated with a higher hazard of recurrence.CONCLUSION: Resection margins >1cm predicted better RFS among patients undergoing R0 hepatectomy for T1 HCC, especially small (<5cm) HCC. Although resection margin width did not influence outcomes after anatomic resection, wider margins were more important among patients undergoing non-anatomic liver resections.
Resection of pancreatic neuroendocrine tumors: defining patterns and time course of recurrence. HPB : the official journal of the International Hepato Pancreato Biliary Association Dong, D., Zhang, X., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Dillhoff, M., Maithel, S. K., Pawlik, T. M. 2019
BACKGROUND: To define recurrence patterns and time course, as well as risk factors associated with recurrence following curative resection of pNETs.METHOD: Patients who underwent curative-intent resection for pNET between 1997 and 2016 were identified from the US Neuroendocrine Tumor Study Group. Data on baseline and tumor-specific characteristics, overall survival (OS), timing and first-site of recurrence, predictors and recurrence management were analyzed.RESULTS: Among 1020 patients, 154 (15.1%) patients developed recurrence. Among patients who experienced recurrence, 76 (49.4%) had liver-only recurrence, while 35 (22.7%) had pancreas-only recurrence. The proportion of liver-only recurrence increased from 54.3% within one-year after surgery to 61.5% from four-to-six years after surgery; whereas the proportion of pancreas-only recurrence decreased from 26.1% to 7.7% over these time periods. While liver-only recurrence was associated with tumor characteristics, pancreas-only recurrence was only associated with surgical margin status. Patients undergoing curative resection of recurrence had comparable OS with patients who had no recurrence (median OS, pancreas-only recurrence, 133.9 months; liver-only recurrence, not attained; no recurrence, 143.0 months, p=0.499) CONCLUSIONS: Different recurrence patterns and timing course, as well as risk factors suggest biological heterogeneity of pNET recurrence. A personalized approach to postoperative surveillance and treatment of recurrence disease should be considered.
A Multi-institutional International Analysis of Textbook Outcomes Among Patients Undergoing Curative-Intent Resection of Intrahepatic Cholangiocarcinoma JAMA SURGERY Merath, K., Chen, Q., Bagante, F., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Weiss, M. J., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Cloyd, J. M., Pawlik, T. M. 2019; 154 (6)
Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases A Multi-institutional, International Analysis of 1099 Patients ANNALS OF SURGERY Margonis, G., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Barbon, C., Beer, A., Kamphues, C., Loes, I., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P., Cameron, J. L., Mischinger, H., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019; 269 (6): 1129–37
What Is the Best Operation for Proximal Gastric Cancer and Distal Esophageal Cancer? SURGICAL CLINICS OF NORTH AMERICA Mazer, L. M., Poultsides, G. A. 2019; 99 (3): 457-+
View details for DOI 10.1016/j.suc.2019.02.003
Association of Perioperative Transfusion with Recurrence and Survival After Resection of Distal Cholangiocarcinoma: A 10-Institution Study from the US Extrahepatic Biliary Malignancy Consortium Lopez-Aguiar, A. G., Ethun, C. G., Pawlik, T. M., Tran, T., Poultsides, G. A., Isom, C. A., Idrees, K., Krasnick, B. A., Fields, R. C., Salem, A., Weber, S. M., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H. D., Beal, E. W., Schmidt, C., Shenoy, R., Hatzaras, I., Maithel, S. K. SPRINGER. 2019: 1814–23
Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases: A Multi-institutional, International Analysis of 1099 Patients. Annals of surgery Margonis, G. A., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Barbon, C., Beer, A., Kamphues, C., Loes, I. M., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P. E., Cameron, J. L., Mischinger, H. J., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019; 269 (6): 1129–37
OBJECTIVE: To evaluate the changing impact of genetic and clinicopathologic factors on conditional overall survival (CS) over time in patients with resectable colorectal liver metastasis.BACKGROUND: CS estimates account for the changing likelihood of survival over time and may reveal the changing impact of prognostic factors as time accrues from the date of surgery.METHODS: CS analysis was performed in 1099 patients of an international, multi-institutional cohort. Three-year CS (CS3) estimates at the "xth" year after surgery were calculated as follows: CS3 = CS (x + 3)/CS (x). The standardized difference (d) between CS3 rates was used to estimate the changing prognostic power of selected variables over time. A d < 0.1 indicated very small differences between groups, 0.1 ≤ d < 0.3 indicated small differences, 0.3 ≤ d < 0.5 indicated moderate differences, and d ≥ 0.5 indicated strong differences.RESULTS: According to OS estimates calculated at the time of surgery, the presence of BRAF and KRAS mutations, R1 margin status, resected extrahepatic disease, patient age, primary tumor lymph node metastasis, tumor number, and carcinoembryonic antigen levels independently predicted worse survival. However, when temporal changes in the prognostic impact of these variables were considered using CS3 estimates, BRAF mutation dominated prognosis during the first year (d = 0.48), whereas surgeon-related variables (ie, surgical margin and resected extrahepatic disease) determined prognosis thereafter (d ≥ 0.5). Traditional clinicopathologic factors affected survival constantly, but only to a moderate degree (0.3 ≤ d < 0.5).CONCLUSIONS: The impact of genetic, surgery-related, and clinicopathologic factors on OS and CS3 changed dramatically over time. Specifically, BRAF mutation status dominated prognosis in the first year, whereas positive surgical margins and resected extrahepatic disease determined prognosis thereafter.
Impact of body mass index on tumor recurrence among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma- a multi-institutional international analysis EJSO Merath, K., Mehta, R., Hyer, J., Bagante, F., Sahara, K., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Weiss, M. J., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Ejaz, A., Pawlik, T. M. 2019; 45 (6): 1084–91
Gastric carcinoids: Does type of surgery or tumor affect survival? AMERICAN JOURNAL OF SURGERY Crown, A., Kennecke, H., Kozarek, R., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G. A., Makris, E., Idrees, K., Smith, P., Nathan, H., Beems, M., Abbott, D., Fisher, A., Fields, R. C., Davidson, J., Maithel, S. K., Rocha, F. G. 2019; 217 (5): 937–42
View details for DOI 10.1016/j.amjsurg.2018.12.057
Predicting Pancreatic Cancer Resectability and Outcomes Based on an Objective Quantitative Scoring System Toesca, D. S., Jeffrey, R., von Eyben, R., Pollom, E. L., Poullos, P. D., Poultsides, G. A., Fisher, G. A., Visser, B. C., Koong, A. C., Chang, D. T. LIPPINCOTT WILLIAMS & WILKINS. 2019: 622–28
Recurrence Patterns and Timing Courses Following Curative-Intent Resection for Intrahepatic Cholangiocarcinoma. Annals of surgical oncology Hu, L., Zhang, X., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Itaru, E., Pawlik, T. M. 2019
BACKGROUND: Recurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common.OBJECTIVE: The aim of this study was to investigate the patterns, timing and risk factors of disease recurrence after curative-intent resection for ICC.METHODS: Patients undergoing curative resection for ICC were identified from a multi-institutional database. Data on clinicopathological and initial operation information, timing and first sites of recurrence, recurrence management, and long-term outcomes were analyzed.RESULTS: A total of 920 patients were included. With a median follow-up of 38months, 607 patients (66.0%) experienced ICC recurrence. In the cohort, 145 patients (23.9%) recurred at the surgical margin, 178 (29.3%) recurred within the liver away from the surgical margin, 90 (14.8%) recurred at extraheptatic sites, and 194 (32.0%) developed both intrahepatic and extrahepatic recurrence. Intrahepatic margin recurrence (median 6.0m) and extrahepatic-only recurrence (median 8.0m) tended to occur early, while intrahepatic recurrence at non-margin sites occurred later (median 14.0m; p<0.05). On multivariate analysis, surgical margin<10mm was associated with increased margin recurrence (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.11-2.60; p=0.014), whereas female sex (HR 2.12, 95% CI 1.40-3.22; p<0.001) and liver cirrhosis (HR 2.36, 95% CI 1.31-4.25; p=0.004) were both associated with an increased risk of intrahepatic recurrence at other sites. Median survival after recurrence was better among patients who underwent repeat curative-intent surgery (48.7months) versus other treatments (9.7months) [p<0.001].CONCLUSIONS: Different recurrence patterns and timing of recurrence suggest biological heterogeneity of ICC tumor recurrence. Understanding timing and risk factors associated with different types of recurrence can hopefully inform discussions around adjuvant therapy, surveillance, and treatment of recurrent disease.
Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group. Annals of surgical oncology Lopez-Aguiar, A. G., Zaidi, M. Y., Beal, E. W., Dillhoff, M., Cannon, J. G., Poultsides, G. A., Kanji, Z. S., Rocha, F. G., Marincola Smith, P., Idrees, K., Beems, M., Cho, C. S., Fisher, A. V., Weber, S. M., Krasnick, B. A., Fields, R. C., Cardona, K., Maithel, S. K. 2019
BACKGROUND: Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined.METHODS: Patients who underwent curative-intent resection of non-functional PanNETs at eight institutions from 2000 to 2016 were analyzed. Preoperative factors associated with LN metastases were identified. A procedure-specific target for LN retrieval to accurately stage patients was determined.RESULTS: Of 695 patients who underwent resection, 33% of tumors were proximal (head/uncinate) and 67% were distal (neck/body/tail). Twenty-six percent of patients (n=158) had LN-positive disease, which was associated with a worse 5-year recurrence-free survival (RFS; 60% vs. 86%; p<0.001). The increasing number of positive LNs was not associated with worse RFS. Preoperative factors associated with positive LNs included tumor size≥2cm (odds ratio [OR] 6.6; p<0.001), proximal location (OR 2.5; p<0.001), moderate versus well-differentiation (OR 2.1; p=0.006), and Ki-67≥3% (OR 3.1; p<0.001). LN metastases were also present in tumors without these risk factors:<2cm (9%), distal location (19%), well-differentiated (23%), and Ki-67<3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage patients was not identified. However, for DP, removal of less than seven LNs failed to discriminate 5-year RFS between LN-positive and LN-negative patients (less than seven LNs: 72% vs. 83%, p=0.198; seven or more LNs: 67% vs. 86%; p=0.002).CONCLUSIONS: Tumor size≥2cm, proximal location, moderate differentiation, and Ki-67≥3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9-23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. PD inherently includes sufficient LN retrieval, while DP should aim to remove seven or more LNs for accurate staging.
Minimally invasive versus open distal pancreatectomy for pancreatic neuroendocrine tumors: An analysis from the U.S. neuroendocrine tumor study group. Journal of surgical oncology Zhang, X., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Schmidt, C. R., Maithel, S. K., Pawlik, T. M., United States Neuroendocrine Tumor Study Group 2019
BACKGROUND: To determine short- and long-term oncologic outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for the treatment of pancreatic neuroendocrine tumor (pNET).METHODS: The data of the patients who underwent curative MIDP or ODP for pNET between 2000 and 2016 were collected from a multi-institutional database. Propensity score matching (PSM) was used to generate 1:1 matched patients with MIDP and ODP.RESULTS: A total of 576 patients undergoing curative DP for pNET were included. Two hundred and fourteen (37.2%) patients underwent MIDP, whereas 362 (62.8%) underwent ODP. MIDP was increasingly performed over time (2000-2004: 9.3% vs 2013-2016: 54.8%; P<0.01). In the matched cohort (n=141 in each group), patients who underwent MIDP had less blood loss (median, 100 vs 200mL, P<0.001), lower incidence of Clavien-Dindo≥III complications (12.1% vs 24.8%, P=0.026), and a shorter hospital stay versus ODP (median, 4 versus 7 days, P=0.026). Patients who underwent MIDP had a lower incidence of recurrence (5-year cumulative recurrence, 10.1% vs 31.1%, P<0.001), yet equivalent overall survival (OS) rate (5-year OS, 92.1% vs 90.9%, P=0.550) compared with patients who underwent OPD.CONCLUSION: Patients undergoing MIDP over ODP in the treatment of pNET had comparable oncologic surgical metrics, as well as similar long-term OS.
Is hepatectomy safe following Yttrium-90 therapy? A multi-institutional international experience. HPB : the official journal of the International Hepato Pancreato Biliary Association Melstrom, L. G., Eng, O. S., Raoof, M., Singh, G., Fong, Y., Latorre, K., Choi, G. H., Salem, R., Bentrem, D. J., Lewandowski, R., Makris, E., Poultsides, G., Dhar, V. K., Chadalavada, S., Shah, S. A., Johnson, A. C., Sekhar, A., Kies, D., Maithel, S. K., Rocha, F., Alseidi, A., Hagendoorn, J., Borel Rinkes, I. H., Fisher, A. V., Ronnekleiv-Kelly, S., Weber, S. M., Winslow, E. R., Abbott, D. E. 2019
BACKGROUND: Single institution reports demonstrate variable safety profiles when liver-directed therapy with Yttrium-90 (Y-90) is followed by hepatectomy. We hypothesized that in well-selected patients, hepatectomy after Y90 is feasible and safe.METHODS: Nine institutions contributed data for patients undergoing Y90 followed by hepatectomy (2008-2017). Clinicopathologic and perioperative data were analyzed, with 90-day morbidity and mortality as primary endpoints.RESULTS: Forty-seven patients were included. Median age was 59 (20-75) and 62% were male. Malignancies treated included hepatocellular cancer (n=14; 30%), colorectal cancer (n=11; 23%), cholangiocarcinoma (n=8; 17%), neuroendocrine (n=8; 17%) and other tumors (n=6). The distribution of Y-90 treatment was: right (n=30; 64%), bilobar (n=14; 30%), and left (n=3; 6%). Median future liver remnant (FLR) following Y90 was 44% (30-78). Resections were primarily right (n=16; 34%) and extended right (n=14; 30%) hepatectomies. The median time to resection from Y90 was 196 days (13-947). The 90-day complication rate was 43% and mortality was 2%. Risk factors for Clavien-Dindo Grade>3 complications included: number of Y-90-treated lobes (OR 4.5; 95% CI1.14-17.7; p=0.03), extent of surgery (p=0.04) and operative time (p=0.009).CONCLUSIONS: These data demonstrate that hepatectomy following Y-90 is safe in well-selected populations. This multi-disciplinary treatment paradigm should be more widely studied, and potentially adopted, for patients with inadequate FLR.
KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: a study from the International Genetic Consortium for Liver Metastases. HPB : the official journal of the International Hepato Pancreato Biliary Association Margonis, G. A., Amini, N., Andreatos, N., Sasaki, K., McVey, J., Mirza, M. B., Warner, S., Buettner, S., Barbon, C., Wang, J., Pulvirenti, A., Angelou, A., Kamphues, C., Antoniou, E., Pikoulis, E., Pawlik, T. M., Kaczirek, K., Poultsides, G., Wagner, D., Endo, I., Imai, K., Aucejo, F., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019
BACKGROUND: A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined.METHODS: Pathologic response was characterized as minor or major depending on the percentage of remnant viable cells (>50% vs <50%, respectively). Multivariable logistic regression was used to identify factors associated with major response.RESULTS: 319 patients met inclusion criteria. 229 patients had a KRAS wild-type (wtKRAS) tumor and 90 harbored KRAS mutations (mutKRAS). A major pathologic response was more commonly noted in patients with wtKRAS compared to mutKRAS (48.5% vs 33.3%, P=0.01) and wtKRAS status remained independently associated with a major response (P=0.04). On a codon-specific level, major pathologic response occurred less frequently in those with codon 13 mutations (17.7%) compared to those with codon 12 (35.4%), and other KRAS mutations (33.3%). Importantly, codon 13 mutations were independently associated with minor pathologic response (P=0.023).CONCLUSIONS: Patients with wtKRAS tumors appear to have the highest likelihood of experiencing a major response after preoperative chemotherapy. Future studies in "all-comer" cohorts are needed to confirm these findings and further investigate the response of codon 13 mutations.
Evaluating the ACS NSQIP Risk Calculator in Primary Pancreatic Neuroendocrine Tumor: Results from the US Neuroendocrine Tumor Study Group. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Dave, A., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F. G., Kanji, Z., Ronnekleiv-Kelly, S., Rendell, V. R., Fields, R. C., Krasnick, B. A., Idrees, K., Smith, P. M., Nathan, H., Beems, M., Maithel, S. K., Pawlik, T. M., Schmidt, C. R., Dillhoff, M. E. 2019
BACKGROUND: In a changing health care environment where patient outcomes will be more closely scrutinized, the ability to predict surgical complications is becoming increasingly important. The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) online risk calculator is a popular tool to predict surgical risk. This paper aims to assess the applicability of the ACS NSQIP calculator to patients undergoing surgery for pancreatic neuroendocrine tumors (PNETs).METHODS: Using the US Neuroendocrine Tumor Study Group (USNET-SG), 890 patients who underwent pancreatic procedures between 1/1/2000-12/31/2016 were evaluated. Predicted and actual outcomes were compared using C-statistics and Brier scores.RESULTS: The most commonly performed procedure was distal pancreatectomy, followed by standard and pylorus-preserving pancreaticoduodenectomy. For the entire group of patients studied, C-statistics were highest for discharge destination (0.79) and cardiac complications (0.71), and less than 0.7 for all other complications. The Brier scores for surgical site infection (0.1441) and discharge to nursing/rehabilitation facility (0.0279) were below the Brier score cut-off, while the rest were equal to or above and therefore not useful for interpretation.CONCLUSION: This work indicates that the ACS NSQIP risk calculator is a valuable tool that should be used with caution and in coordination with clinical assessment for PNET clinical decision-making.
Evaluation of the ACS NSQIP Surgical Risk Calculator in Elderly Patients Undergoing Hepatectomy for Hepatocellular Carcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Sahara, K., Paredes, A. Z., Merath, K., Tsilimigras, D. I., Bagante, F., Ratti, F., Marques, H. P., Soubrane, O., Beal, E. W., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Aklile, W., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019
BACKGROUND: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator (SRC) aims to help predict patient-specific risk for morbidity and mortality. The performance of the SRC among an elderly population undergoing curative-intent hepatectomy for hepatocellular carcinoma (HCC) remains unknown.METHODS: Patients >70years of age who underwent hepatectomy for HCC between 1998 and 2017 were identified using a multi-institutional international database. To estimate the performance of SRC, 12 observed postoperative outcomes were compared with median SRC-predicted risk, and C-statistics and Brier scores were calculated.RESULTS: Among 500 patients, median age was 75years (IQR 72-78). Most patients (n=324, 64.8%) underwent a minor hepatectomy, while 35.2% underwent a major hepatectomy. The observed incidence of venous thromboembolism (VTE) (3.2%) and renal failure (RF) (4.4%) exceeded the median predicted risk (VTE, 1.8%; IQR 1.5-3.1 and RF, 1.0%; IQR 0.5-2.0). In contrast, the observed incidence of 30-day readmission (7.0%) and non-home discharge (2.5%) was lower than median-predicted risk (30-day readmission, 9.4%; IQR 7.4-12.8 and non-home discharge, 5.7%; IQR 3.3-11.7). Only 57.8% and 71.2% of patients who experienced readmission (C-statistic, 0.578; 95%CI 0.468-0.688) or mortality (C-statistic, 0.712; 95%CI 0.508-0.917) were correctly identified by the model.CONCLUSION: Among elderly patients undergoing hepatectomy for HCC, the SRC underestimated the risk of complications such as VTE and RF, while being no better than chance in estimating the risk of readmission. The ACS SRC has limited clinical applicability in estimating perioperative risk among elderly patients being considered for hepatic resection of HCC.
Predictive Value of Chromogranin A and a Pre-Operative Risk Score to Predict Recurrence After Resection of Pancreatic Neuroendocrine Tumors Fisher, A. V., Lopez-Aguiar, A. G., Rendell, V. R., Pokrzywa, C., Rocha, F. G., Kanji, Z. S., Poultsides, G. A., Makris, E. A., Dillhoff, M. E., Beal, E. W., Fields, R. C., Panni, R. Z., Idrees, K., Smith, P., Cho, C. S., Beems, M. V., Maithel, S. K., Winslow, E. R., Abbott, D. E., Weber, S. M. SPRINGER. 2019: 651-658
Should Utilization of Lymphadenectomy Vary According to Morphologic Subtype of Intrahepatic Cholangiocarcinoma? Annals of surgical oncology Zhang, X., Lv, Y., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Itaru, E., Pawlik, T. M. 2019
OBJECTIVE: We sought to evaluate the utilization of lymphadenectomy (LND) and the incidence of lymph node metastasis (LNM) among different morphologic types of intrahepatic cholangiocarcinoma (ICC).METHODS: Clinical data of patients undergoing curative-intent resection for ICC between 1990 and 2017 were collected and analyzed. The preoperative nodal status was evaluated by imaging studies, and the morphologic and lymph node (LN) status was collected on final pathology report.RESULTS: Overall, 1032 patients had a mass-forming (MF) or intraductal growth (IG) ICC subtype, whereas 150 patients had a periductal infiltrating (PI) or MF+PI subtype. Among the 924 patients with MF/IG ICC subtype who had nodal assessment on preoperative imaging, 747 (80.8%) were node-negative, whereas 177 (19.2%) patients were suspicious for metastatic nodal disease. On final pathological analysis, 71 of 282 (25.2%) patients who had preoperative node-negative disease ultimately had LNM. In contrast, 79 of 135 (58.5%) patients with preoperative suspicious/metastatic LNs had pathologically confirmed LNM (odds ratio [OR] 4.2, p<0.001). Among the 129 patients with PI/MF+PI ICC subtype and preoperative nodal information, 72 (55.8%) were node-negative on preoperative imaging. In contrast, 57 (44.2%) patients had suspicious/metastatic LNs. On final pathologic examination, 45.3% (n=24) of patients believed to be node-negative on preoperative imaging had LNM; 68.0% (n=34) of patients who had suspicious/positive nodal disease on imaging ultimately had LNM (OR 2.6, p=0.009).CONCLUSION: Given the low accuracy of preoperative imaging evaluation of nodal status, routine LND should be performed at the time of resection for both MF/IG and PI/MF+PI ICC subtypes.
Survival after Resection of Multiple Tumor Foci of Intrahepatic Cholangiocarcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Buettner, S., Ten Cate, D. W., Bagante, F., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Margonis, G. A., Weiss, M., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., IJzermans, J. N., Pawlik, T. M., Koerkamp, B. G. 2019
BACKGROUND: Multiple tumor foci of intrahepatic cholangiocarcinoma (ICC) are often considered a contra-indication for resection. We sought to define long-term outcomes after resection of ICC in patients with multiple foci.METHODS: Patients who underwent resection for ICC between 1990 and 2017 were identified from 12 major HPB centers. Outcomes of patients with solitary lesions, multiple lesions (ML), and oligometastases (OM) were compared. OM were defined as extrahepatic metastases spread to a single organ.RESULTS: One thousand thirteen patients underwent resection of ICC. On final pathology, 185 patients (18.4%) had ML and 27 (2.7%) had OM. Median survival of patients with a solitary tumor was 43.2months, while the median survival of patients with 2 tumors was 21.2months; the median survival of patients with 3 or more tumors was 15.3months (p<0.001). Five-year survival was 43.3%, 28.0%, and 8.6%, respectively. The median survival of patients without OM was 37.8months versus 14.9months among patients with OM (p<0.001); estimated 5-year survival was 39.3% and 10.6%, respectively. In multivariable analysis, the presence of two lesions was not an independent poor prognostic factor for OS (HR 1.19; 95%CI 0.90-1.57; p=0.229). However, the presence of three or more tumors was an independent poor prognostic factor for OS (HR 1.97; 95%CI 1.48-2.64; p<0.001).CONCLUSION: Resection of multiple liver tumors for patients with ICC did not preclude 5-year survival: in particular, estimated 5-year OS for resection of two tumors was 28.0%.
Association of Perioperative Transfusion with Recurrence and Survival After Resection of Distal Cholangiocarcinoma: A 10-Institution Study from the US Extrahepatic Biliary Malignancy Consortium. Annals of surgical oncology Lopez-Aguiar, A. G., Ethun, C. G., Pawlik, T. M., Tran, T., Poultsides, G. A., Isom, C. A., Idrees, K., Krasnick, B. A., Fields, R. C., Salem, A., Weber, S. M., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Beal, E. W., Schmidt, C., Shenoy, R., Hatzaras, I., Maithel, S. K. 2019
BACKGROUND: Perioperative allogeneic blood transfusion is associated with poor oncologic outcomes in multiple malignancies. The effect of blood transfusion on recurrence and survival in distal cholangiocarcinoma (DCC) is not known.METHODS: All patients with DCC who underwent curative-intent pancreaticoduodenectomy at 10 institutions from 2000 to 2015 were included. Primary outcomes were recurrence-free (RFS) and overall survival (OS).RESULTS: Among 314 patients with DCC, 191 (61%) underwent curative-intent pancreaticoduodenectomy. Fifty-three patients (28%) received perioperative blood transfusions, with a median of 2 units. There were no differences in baseline demographics or operative data between transfusion and no-transfusion groups. Compared with no-transfusion, patients who received a transfusion were more likely to have (+) margins (28 vs 14%; p=0.034) and major complications (46 vs 16%; p<0.001). Transfusion was associated with worse median RFS (19 vs 32months; p=0.006) and OS (15 vs 29months; p=0.003), which persisted on multivariable (MV) analysis for both RFS [hazard ratio (HR) 1.8; 95% confidence interval (CI) 1.1-3.0; p=0.031] and OS (HR 1.9; 95% CI 1.1-3.3; p=0.018), after controlling for portal vein resection, estimated blood loss (EBL), grade, lymphovascular invasion (LVI), and major complications. Similarly, transfusion of≥2 pRBCs was associated with lower RFS (17 vs 32months; p<0.001) and OS (14 vs 29months; p<0.001), which again persisted on MV analysis for both RFS (HR 2.6; 95% CI 1.4-4.5; p=0.001) and OS (HR 4.0; 95% CI 2.2-7.5; p<0.001). The RFS and OS of patients transfused 1 unit was comparable to patients who were not transfused.CONCLUSION: Perioperative blood transfusion is associated with decreased RFS and OS after resection for distal cholangiocarcinoma, after accounting for known adverse pathologic factors. Volume of transfusion seems to exert an independent effect, as 1 unit was not associated with the same adverse effects as≥2 units.
Impact of body mass index on tumor recurrence among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma- a multi-institutional international analysis. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology Merath, K., Mehta, R., Hyer, J. M., Bagante, F., Sahara, K., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Weiss, M. J., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Guglielmi, A., Itaru, E., Ejaz, A., Pawlik, T. M. 2019
BACKGROUND: The association between body mass index (BMI) and long-term outcomes of patients with ICC has not been well defined. We sought to define the presentation and oncologic outcomes of patients with ICC undergoing curative-intent resection, according to their BMI category.METHODS: Patients who underwent resection of ICC were identified in a multi-institutional database. Patients were categorized as normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (BMI≥30 kg/m2) according to the World Health Organization (WHO) definition. Impact of clinico-pathological factors on recurrence-free survival (RFS) was assessed using Cox proportional hazards model among patients in the three BMI categories.RESULTS: Among a total of 790 patients undergoing curative-intent resection of ICC in the analytic cohort, 399 (50.5%) had normal weight, 274 (34.7%) were overweight and 117 (14.8%) were obese. Caucasian patients were more likely to be obese (66.7%, n = 78) and overweight (47.1%, n = 129) compared with Asian (obese: 18.8%, n = 22; overweight: 46%, n = 126) and other races (obese: 14.5%, n = 17; overweight: 6.9%, n = 19)(p < 0.001). There were no differences in the presence of cirrhosis (10.9%, vs. 12.8%, vs. 12.9%), preoperative jaundice (8.6% vs. 9.5% vs. 12.0%), or levels of CA 19-9 (75, IQR 24.6-280 vs. 50.9, IQR 17.9-232 vs. 43, IQR 16.9-192.7) among the BMI groups (all p > 0.05). On multivariable analysis, increased BMI was an independent risk factor for tumor recurrence (OR 1.16, 95% CI 1.02-1.32, for every 5 unit increase).CONCLUSION: Increasing BMI was associated with incremental increases in the risk of recurrence following curative-intent resection of ICC. Future studies should aim to achieve a better understanding of BMI-related factors relative to prognosis of patients with ICC.
The Impact of Extent of Liver Resection Among Patients with Neuroendocrine Liver Metastasis: an International Multi-institutional Study JOURNAL OF GASTROINTESTINAL SURGERY Sham, J. G., Ejaz, A., Gage, M. M., Bagante, F., Reames, B. N., Maithel, S., Poultsides, G. A., Bauer, T. W., Fields, R. C., Weiss, M. J., Marques, H., Aldrighetti, L., Pawlik, T. M., He, J. 2019; 23 (3): 484–91
Liver resection in patients with neuroendocrine liver metastasis (NELM) provides a survival benefit, yet the optimal extent of resection remains unknown. We sought to examine outcomes of patients undergoing non-anatomic (NAR) versus anatomic liver resection (AR) for NELM using a large international cohort of patients.Two hundred and fifty-eight patients who underwent curative intent liver resection from January 1990 to December 2016 were identified from eight institutions. Patients were excluded if they underwent concurrent ablation, had extrahepatic disease, underwent a debulking operation, or had mixed anatomic and non-anatomic resections. Overall (OS) and recurrence-free (RFS) survival were compared among patients based on the extent of liver resection (AR vs. NAR).Most primary tumors were located in the pancreas (n = 117, 45.4%) or the small intestine (n = 65, 25.2%). Liver resection consisted of NAR (n = 126, 48.8%) or AR (n = 132, 51.2%) resection. The overwhelming majority of patients who underwent NAR had an estimated liver involvement of < 50% (NAR 109, 97.3% vs. AR n = 82, 65.6%; P < 0.001). Patients who underwent NAR also had higher rates of primary tumor lymph node metastasis (NAR n = 79, 71.2% vs. AR n = 37, 33.6%; P < 0.001) and microscopically positive margins (R1) (NAR n = 29, 25.7% vs. AR n = 16, 12.5%; P = 0.009). After a median follow-up of 47.7 months, 48 (18.6%) patients died and 37.0% (n = 95) had evidence of disease recurrence. Patients who underwent AR had both longer median OS (not reached) and RFS (not reached) versus patients who underwent NAR (median OS 138.3 months; median RFS 31.3 months) (both P < 0.01). After controlling for patient and disease-related factors, extent of liver resection was independently associated with an increased risk of recurrence (HR 2.39, 95% CI 1.04-5.48; P = 0.04) but not death (HR 1.92, 95% CI 0.40-9.28; P = 0.42).NAR was independently associated with a higher incidence of recurrence versus patients who undergo a formal anatomic hepatectomy among patients with NELM.
Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor after curative resection: Results from the US Neuroendocrine Tumor Study Group SURGERY Zhang, X., Wu, Z., Cloyd, J., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Schmidt, C. R., Dillhoff, M., Maithel, S. K., Pawlik, T. M. 2019; 165 (3): 548–56
Influence of carcinoid syndrome on the clinical characteristics and outcomes of patients with gastroenteropancreatic neuroendocrine tumors undergoing operative resection SURGERY Kimbrough, C. W., Beal, E. W., Dillhoff, M. E., Schmidt, C. R., Pawlik, T. M., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F. G., Crown, A., Abbott, D. E., Fisher, A. V., Fields, R. C., Krasnick, B. A., Idrees, K., Marincola-Smith, P., Cho, C. S., Beems, M., Maithel, S. K., Cloyd, J. M. 2019; 165 (3): 657-663
Staging laparoscopy among three subtypes of extra-hepatic biliary malignancy: a 15-year experience from 10 institutions JOURNAL OF SURGICAL ONCOLOGY Davidson, J. T., Jin, L. X., Krasnick, B., Ethun, C. G., Pawlik, T. M., Poultsides, G. A., Idrees, K., Weber, S. M., Martin, R. G., Shen, P., Hatzaras, I., Maithel, S. K., Fields, R. C., Hawkins, W. G., Strasberg, S. M., Chapman, W. C., Doyle, M., Beal, E., Schmidt, C. R., Thuy Tran, Isom, C. A., Salem, A., Scoggins, C., Mogal, H., Shenoy, R., US Extrahepatic Biliary Malignancy 2019; 119 (3): 288-294
Response to preoperative chemotherapy: impact of change in total burden score and mutational tumor status on prognosis of patients undergoing resection for colorectal liver metastases. HPB : the official journal of the International Hepato Pancreato Biliary Association Ruzzenente, A., Bagante, F., Ratti, F., Beal, E. W., Alexandrescu, S., Merath, K., Makris, E. A., Poultsides, G. A., Margonis, G. A., Weiss, M. J., Popescu, I., Aldrighetti, L., Guglielmi, A., Pawlik, T. M. 2019
BACKGROUND: Progression of colorectal liver metastasis (CRLM) on preoperative chemotherapy has been associated with a worse prognosis compared with patients who have responsive disease. Defining response can be challenging as traditional criteria largely assess only tumor size.METHODS: Patients who underwent hepatectomy between 2010 and 2017 were identified using a multi-centric database. This study aimed to define the impact of preoperative chemotherapy response relative to initial tumor burden score (TBS) and determine impact of clinico-pathological variables on overall survival (OS).RESULTS: Among 784 patients who received preoperative chemotherapy, the regimen was oxaliplatin- (66%) or irinotecan-based (34%). Among patients with a TBS<6at diagnosis, genetic status was the most important prognostic variable. Patients with a TBS<6, 5-year OS was 55%, 35%, and 0% for patients with KRAS/NRAS/BRAF wild-type, KRAS/NRAS, and BRAF mutations, respectively. Among patients who presented with CRLM with a TBS≥6, only Delta-TBS was prognostically important and patients with a Delta-TBS≥-10% had a 5-year OS of 27% compared with 49% for patients with a Delta-TBS<-10%.CONCLUSIONS: Prognostic stratification of patients with CRLM receiving preoperative chemotherapy should be multi-faceted and include consideration of initial tumor burden, change in tumor burden due to chemotherapy, and tumor genetic status.
Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer. HPB : the official journal of the International Hepato Pancreato Biliary Association Tummers, W. S., Miller, S. E., Teraphongphom, N. T., van den Berg, N. S., Hasan, A., Longacre, T. A., Fisher, G. A., Bonsing, B. A., Vahrmeijer, A. L., Gambhir, S. S., Swijnenburg, R., Rosenthal, E. L., Poultsides, G. A. 2019
BACKGROUND: Although most patients with PDAC experience distant failure after resection, a significant portion still present with local recurrence. Intraoperative fluorescent imaging can potentially facilitate the visualization of involved peritumoral LNs and guide the locoregional extent of nodal dissection. Here, the efficacy of targeted intraoperative fluorescent imaging was examined in the detection of metastatic lymph nodes (LNs) during resection of pancreatic ductal adenocarcinoma (PDAC).METHODS: A dose-escalation prospective study was performed to assess feasibility of tumor detection within peripancreatic LNs using cetuximab-IRDye800 in PDAC patients. Fluorescent imaging of dissected LNs was analyzed exvivo macroscopically and microscopically and fluorescence was correlated with histopathology.RESULTS: A total of 144 LNs (72 in the low-dose and 72 in the high-dose cohort) were evaluated. Detection of metastatic LNs by fluorescence was better in the low-dose (50mg) cohort, where sensitivity and specificity was 100% and 78% macroscopically, and 91% and 66% microscopically. More importantly, this method was able to detect occult foci of tumor (measuring<5mm) with a sensitivity of 88% (15/17 LNs).CONCLUSION: This study provides proof of concept that intraoperative fluorescent imaging with cetuximab-IRDye800 can facilitate the detection of peripancreatic lymph nodes often containing subclinical foci of disease.
Interaction of race and pathology for neuroendocrine tumors: Epidemiology, natural history, or racial disparity? Lee, R. M., DePalo, D. K., Lopez-Aguiar, A. G., Zaidi, M., Rocha, F. G., Kanji, Z. S., Poultsides, G. A., Makris, E., Dillhoff, M., Beal, E. W., Fields, R., Panni, R. Z., Idrees, K., Smith, P., Nathan, H., Beems, M., Abbott, D., Rendell, V., Maithel, S. K., Russell, M. C. AMER SOC CLINICAL ONCOLOGY. 2019
Prognostic Role of Lymph Node Positivity and Number of Lymph Nodes Needed for Accurately Staging Small-Bowel Neuroendocrine Tumors JAMA SURGERY Zaidi, M. Y., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E., Poultsides, G., Makris, E., Rocha, F., Crown, A., Idrees, K., Smith, P., Nathan, H., Beems, M., Abbott, D., Barrett, J. R., Fields, R. C., Davidson, J., Cardona, K., Maithel, S. K. 2019; 154 (2): 134-140
Actual 5-Year Survivors After Surgical Resection of Hilar Cholangiocarcinoma Tran, T. B., Ethun, C. G., Pawlik, T. M., Schmidt, C., Beal, E. W., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H. D., Idrees, K., Isom, C. A., Hatzaras, I., Shenoy, R., Maithel, S. K., Poultsides, G. A. SPRINGER. 2019: 611-618
Complications after liver surgery: a benchmark analysis. HPB : the official journal of the International Hepato Pancreato Biliary Association Bagante, F., Ruzzenente, A., Beal, E. W., Campagnaro, T., Merath, K., Conci, S., Akgul, O., Alexandrescu, S., Marques, H. P., Lam, V., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Iacono, C., Guglielmi, A., Pawlik, T. M. 2019
BACKGROUND: The best achievable short-term outcomes after liver surgery have not been identified. Several factors may influence the post-operative course of patients undergoing hepatectomy increasing the risk of post-operative complications. We sought to identify risk-adjusted benchmark values [BMV] for liver surgery.METHODS: The National Surgery Quality Improvement Program (NSQIP) database was used to develop Bayesian models to estimate risk-adjusted BMVs for overall and liver related (post-hepatectomy liver failure [PHLF], biliary leakage [BL]) complications. A separate international multi-institutional database was used to validate the risk-adjusted BMVs.RESULTS: Among the 11,243 patients included in the NSQIP database, the incidence of complications, PHLF, and BL was 36%, 5%, and 8%, respectively. The risk-adjusted BMVs for complication (range, 16-72%), PHLF (range, 1%-20%), and BL (range, 4%-22%) demonstrated a high variability based on patients characteristics. When tested using an international database including nine institutes, the risk-adjusted BMVs for complications ranged from 26% (Institute-4) to 43% (Institute-1), BMVs for PHLF between 3% (Institute-3) and 12% (Institute-5), while BMVs for BL ranged between 5% (Institute-4) and 9% (Institute-7).CONCLUSIONS: Multiple factors influence the risk of complications following hepatectomy. Risk-adjusted BMVs are likely much more applicable and appropriate in assessing "acceptable" benchmark outcomes following liver surgery.
Resection margin distance in extrahepatic cholangiocarcinoma: How much is enough? Rahnemai-Azar, A. A., Ronnekleiv-Kelly, S., Abbott, D., Ethun, C., Poultsides, G. A., Thuy Tran, Fields, R., Krasnick, B., Martin, R. G., Scoggins, C., Idrees, K., Isom, C. A., Hatzaras, I., Shenoy, R., Shen, P., Perkins, J. D., Pawlik, T. M., Maithel, S. K., Weber, S. M. AMER SOC CLINICAL ONCOLOGY. 2019
Predictive Value of Chromogranin A and a Pre-Operative Risk Score to Predict Recurrence After Resection of Pancreatic Neuroendocrine Tumors. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Fisher, A. V., Lopez-Aguiar, A. G., Rendell, V. R., Pokrzywa, C., Rocha, F. G., Kanji, Z. S., Poultsides, G. A., Makris, E. A., Dillhoff, M. E., Beal, E. W., Fields, R. C., Panni, R. Z., Idrees, K., Smith, P. M., Cho, C. S., Beems, M. V., Maithel, S. K., Winslow, E. R., Abbott, D. E., Weber, S. M. 2019
INTRO: Chromogranin A (CgA) may be prognostic for patients with neuroendocrine tumors; however, the clinical utility of this test is unclear.METHODS: Patients undergoing resection for pancreatic neuroendocrine tumors (pNET) were selected from the eight institutions of the US Neuroendocrine Tumor Study Group database. Cox regression was used to identify pre-operative variables that predicted recurrence-free survival (RFS), and those with p<0.1 were included in a risk score. The risk score was tested in a unique subset of the overall cohort.RESULTS: In the entire cohort of 287 patients, median follow-up time was 37months, and 5-year RFS was 73%. Cox regression analysis identified four variables for inclusion in the risk score: CgA >5x ULN (HR 4.3, p=0.01), tumor grade 2/3 (HR 3.7, p=0.01), resection for recurrent disease (HR 6.2, p<0.01), and tumor size >4cm (HR 4.5, p=0.1). Each variable was assigned 1 point. Risk-score testing in the unique validation cohort of 63 patients revealed a 95% negative predictive value for recurrence in patients with zero points.DISCUSSION: This simple pre-operative risk scoring system resulted in a high degree of specificity for identifying patients at low-risk for tumor recurrence. This test can be utilized pre-operatively to aid informed decision-making.
Hospital variation in Textbook Outcomes following curative-intent resection of hepatocellular carcinoma: an international multi-institutional analysis. HPB : the official journal of the International Hepato Pancreato Biliary Association Tsilimigras, D. I., Mehta, R. n., Merath, K. n., Bagante, F. n., Paredes, A. Z., Farooq, A. n., Ratti, F. n., Marques, H. P., Silva, S. n., Soubrane, O. n., Lam, V. n., Poultsides, G. A., Popescu, I. n., Grigorie, R. n., Alexandrescu, S. n., Martel, G. n., Workneh, A. n., Guglielmi, A. n., Hugh, T. n., Aldrighetti, L. n., Endo, I. n., Pawlik, T. M. 2019
Composite measures such as "Textbook Outcome" (TO) may be superior to individual quality metrics to assess surgical care and hospital performance. However, the incidence and factors associated with TO after resection of HCC remain poorly defined.Hospital variation in the rates of TO, factors associated with achieving a TO and the impact of TO on long-term survival following resection for HCC were examined using an international multi-institutional database.Among 605 patients who underwent curative-intent resection of HCC, the unadjusted incidence of TO ranged from 50.9% to 77.7%. While achievement of each individual quality metric was relatively high (range, 74.5-98.0%), an overall TO was achieved among only 62.3% (n = 377) of patients. At the hospital level, TO ranged from 54.3% to 72.9%. Patients with BCLC-0 HCC (referent BCLC-B/C; OR: 4.17, 95%CI: 1.62-10.7) and ALBI grade 1 (referent ALBI grade 2/3; OR: 1.49, 95%CI: 1.06-2.11) had higher odds of achieving a TO. On multivariable analysis, TO was associated with improved overall survival (HR: 0.60, 95% CI: 0.42-0.85).Roughly 6 in 10 patients achieved a TO following resection for HCC. When achieved, TO was associated with better long-term outcomes. TO is a simple composite measure of both short- and long-term outcomes among patients undergoing resection for HCC.
Surgery Provides Long-Term Survival in Patients with Metastatic Neuroendocrine Tumors Undergoing Resection for Non-Hormonal Symptoms Chakedis, J., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F. G., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Marincola-Smith, P., Cho, C., Beems, M., Pawlik, T. M., Maithel, S. K., Schmidt, C. R., Dillhoff, M. SPRINGER. 2019: 122-134
Impact of microvascular invasion on clinical outcomes after curative-intent resection for intrahepatic cholangiocarcinoma JOURNAL OF SURGICAL ONCOLOGY Hu, L., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Itaru, E., Pawlik, T. M. 2019; 119 (1): 21-29
The impact of failure to achieve symptom control after resection of functional neuroendocrine tumors: An 8-institution study from the US Neuroendocrine Tumor Study Group JOURNAL OF SURGICAL ONCOLOGY Zaidi, M. Y., Lopez-Aguiar, A. G., Poultsides, G. A., Dillhoff, M., Rocha, F. G., Idrees, K., Nathan, H., Winslow, E. R., Fields, R. C., Cardona, K., Maithel, S. K., US Neuroendocrine Tumor Study 2019; 119 (1): 5-11
Outcomes of Elderly Patients Undergoing Curative Resection for Retroperitoneal Sarcomas: Analysis From the US Sarcoma Collaborative JOURNAL OF SURGICAL RESEARCH Wilkinson, K., Ethun, C. G., Hembrook, M., Bedi, M., Charlson, J., Mogal, H., Tsai, S., Christians, K., Tran, T. B., Poultsides, G., Grignol, V., Howard, J., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Cullinan, D., Fields, R. C., Weber, S., Gamblin, T., Cardona, K., Clarke, C. N. 2019; 233: 154-162
Therapeutic index of lymphadenectomy among patients with pancreatic neuroendocrine tumors: A multi-institutional analysis. Journal of surgical oncology Wu, L. n., Sahara, K. n., Tsilimigras, D. I., Maithel, S. K., Poultsides, G. A., Rocha, F. G., Weber, S. M., Fields, R. C., Idrees, K. n., Cho, C. S., Shen, F. n., Pawlik, T. M. 2019
The benefit derived from lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) based on clinicopathological characteristics remains unclear.Patients undergoing surgery for pNET between 1997 and 2016 were identified using a multi-institutional dataset. The therapeutic index of LND relative to patient characteristics was calculated.Among 647 patients, the median number of lymph nodes (LNs) evaluated was 10 (interquartile range: 4-16) and approximately one quarter of patients had lymph node metastasis (LNM) (N = 159, 24.6%). Among patients with LNM, 5-year recurrence-free survival was 56.0%, reflecting a therapeutic index value of 13.8. The therapeutic index was highest among patients with a moderately/poorly-differentiated pNET (21.5), Ki-67 ≥ 3% (20.1), tumor size ≥2.0 cm (20.0), and tumor location at the head of the pancreas (20.0). Patients with ≥8 LNs evaluated had a higher therapeutic index than patients who had 1 to 7 LNs evaluated (≥8: 17.9 vs 1-7: 7.5; difference of index: 11.4).LND was mostly beneficial among patients with pNETs >2 cm, Ki-67 ≥ 3%, and lesions located at the pancreatic head as identification of LNM was most common among individuals with these tumor characteristics. Evaluation of ≥8 LNs was associated with a higher likelihood of identifying LNM as well as a higher therapeutic index, and therefore this number of LNs should be considered the goal.
Correction to: Neuroendocrine Liver Metastasis: Prognostic Implications of Primary Tumor Site on Patients Undergoing Curative Intent Liver Surgery. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Spolverato, G. n., Bagante, F. n., Aldrighetti, L. n., Poultsides, G. n., Bauer, T. W., Fields, R. C., Marques, H. P., Weiss, M. n., Maithel, S. K., Pawlik, T. M. 2019
There is an error in an author's name in this paper, Ryan C. Field should be Ryan C. Fields. The correct author list is above.
Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group. HPB : the official journal of the International Hepato Pancreato Biliary Association Marincola Smith, P. n., Baechle, J. n., Solórzano, C. C., Tan, M. n., Lopez-Aguiar, A. G., Dillhoff, M. n., Beal, E. n., Poultsides, G. n., Cannon, J. G., Rocha, F. G., Crown, A. n., Cho, C. n., Beems, M. n., Winslow, E. R., Rendell, V. R., Krasnick, B. A., Fields, R. C., Maithel, S. K., Bailey, C. E., Idrees, K. n. 2019
Packed red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection.A retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan-Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression.Of 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia.PRBC transfusion is associated with worse survival for patients undergoing PNET resection.
View details for DOI 10.1016/j.hpb.2019.10.2441
Conditional disease-free survival after curative-intent liver resection for neuroendocrine liver metastasis. Journal of surgical oncology Sahara, K. n., Merath, K. n., Tsilimigras, D. I., Hyer, J. M., Guglielmi, A. n., Aldrighetti, L. n., Weiss, M. n., Fields, R. C., Poultsides, G. A., Maithel, S. K., Endo, I. n., Pawlik, T. M., Other Members Of The U S Neuroendocrine Tumor Study Group, n. n. 2019
Neuroendocrine liver metastases (NELM) are typically associated with high recurrence rates following surgical resection. Conditional disease-free survival (CDFS) estimates may be more clinically relevant compared to actuarial survival estimates.CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with disease-free survival (DFS). Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as CDFS3 = DFS(x + 3)/DFS(x).A total of 521 patients met the inclusion criteria. While actuarial 3-year DFS gradually decreased from 49% at 1 year to 39% at 5 years, CDFS3 increased over time. CDFS3 at 5 years was estimated as 89% vs actuarial 8-year DFS of 39% (P < .001). The probability of remaining disease-free at 5 years after resection increased as patients remained disease-free. For example, the probability of being disease-free for an additional 3 years was 66.3% and 88.8% for patients who lived 2 and 5 years, respectively. Overall, CDFS3 in each subgroup increased postoperatively as years elapsed, however, the impact of each prognostic factor on CDFS3 changed over time.CDFS of patients who underwent resection of NELM exponentially improved as patients survived additional years without recurrence. CDFS provides more accurate prognostic measures compared with traditional DFS measures.
Trends in the Number of Lymph Nodes Evaluated Among Patients with Pancreatic Neuroendocrine Tumors in the United States: A Multi-Institutional and National Database Analysis. Annals of surgical oncology Sahara, K. n., Tsilimigras, D. I., Mehta, R. n., Moro, A. n., Paredes, A. Z., Lopez-Aguiar, A. G., Rocha, F. n., Kanji, Z. n., Weber, S. n., Fisher, A. n., Fields, R. n., Krasnick, B. A., Idrees, K. n., Smith, P. M., Poultsides, G. A., Makris, E. n., Cho, C. n., Beems, M. n., Dillhoff, M. n., Maithel, S. K., Endo, I. n., Pawlik, T. M. 2019
The role of routine lymphadenectomy in the surgical treatment of pancreatic neuroendocrine tumors (pNET) remains poorly defined. The objective of the current study was to investigate trends in the number of lymph nodes (LN) evaluated for pNET treatment at a nationwide level.Patients undergoing surgery for pNET between 2000 and 2016 were identified in the U.S. Neuroendocrine Tumor Study Group (US-NETSG) database as well as the Surveillance, Epidemiology, and End Results (SEER) database. The number of LNs examined was evaluated over time.The median number of evaluated LNs increased roughly fourfold over the study period (US-NETSG, 2000: 3 LNs vs. 2016: 13 LNs; SEER, 2000: 3 LNs vs. 2016: 11 LNs, both p < 0.001). While no difference in 5-year OS and RFS was noted among patients who had 1-3 lymph node metastases (LNM) vs. ≥ 4 LNM between 2000-2007 (OS 73.5% vs. 69.9%, p = 0.12; RFS: 64.9% vs. 40.1%, p = 0.39), patients who underwent resection and LN evaluation during the period 2008-2016 had an incrementally worse survival if the patient had node negative disease, 1-3 LNM and ≥ 4 LNM (OS 86.8% vs. 82.7% vs. 74.9%, p < 0.001; RFS: 86.3% vs. 64.7% vs. 50.4%, p < 0.001). On multivariable analysis, a more recent year of diagnosis, pancreatic head tumor location, and tumor size > 2 cm were associated with 12 or more LNs evaluated in both US-NETSG and SEER databases.The number of LNs examined nearly quadrupled over the last decade. The increased number of LNs examined suggested a growing adoption of the AJCC staging manual recommendations regarding LN evaluation in the treatment of pNET.
A Machine-Based Approach to Preoperatively Identify Patients with the Most and Least Benefit Associated with Resection for Intrahepatic Cholangiocarcinoma: An International Multi-institutional Analysis of 1146 Patients. Annals of surgical oncology Tsilimigras, D. I., Mehta, R. n., Moris, D. n., Sahara, K. n., Bagante, F. n., Paredes, A. Z., Moro, A. n., Guglielmi, A. n., Aldrighetti, L. n., Weiss, M. n., Bauer, T. W., Alexandrescu, S. n., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G. n., Pulitano, C. n., Shen, F. n., Soubrane, O. n., Koerkamp, B. G., Endo, I. n., Pawlik, T. M. 2019
Accurate risk stratification and patient selection is necessary to identify patients who will benefit the most from surgery or be better treated with other non-surgical treatment strategies. We sought to identify which patients in the preoperative setting would likely derive the most or least benefit from resection of intrahepatic cholangiocarcinoma (ICC).Patients who underwent curative-intent resection for ICC between 1990 and 2017 were identified from an international multi-institutional database. A machine-based classification and regression tree (CART) was used to generate homogeneous groups of patients relative to overall survival (OS) based on preoperative factors.Among 1146 patients, CART analysis revealed tumor number and size, albumin-bilirubin (ALBI) grade and preoperative lymph node (LN) status as the strongest prognostic factors associated with OS among patients undergoing resection for ICC. In turn, four groups of patients with distinct outcomes were generated through machine learning: Group 1 (n = 228): single ICC, size ≤ 5 cm, ALBI grade I, negative preoperative LN status; Group 2 (n = 708): (1) single tumor > 5 cm, (2) single tumor ≤ 5 cm, ALBI grade 2/3, and (3) single tumor ≤ 5 cm, ALBI grade 1, metastatic/suspicious LNs; Group 3 (n = 150): 2-3 tumors; Group 4 (n = 60): ≥ 4 tumors. 5-year OS among Group 1, 2, 3, and 4 patients was 60.5%, 35.8%, 27.5%, and 3.8%, respectively (p < 0.001). Similarly, 5-year disease-free survival (DFS) among Group 1, 2, 3, and 4 patients was 47%, 27.2%, 6.8%, and 0%, respectively (p < 0.001).The machine-based CART model identified distinct prognostic groups of patients with distinct outcomes based on preoperative factors. Survival decision trees may be useful as guides in preoperative patient selection and risk stratification.
Therapeutic Index Associated with Lymphadenectomy Among Patients with Intrahepatic Cholangiocarcinoma: Which Patients Benefit the Most from Nodal Evaluation? Annals of surgical oncology Sahara, K. n., Tsilimigras, D. I., Merath, K. n., Bagante, F. n., Guglielmi, A. n., Aldrighetti, L. n., Weiss, M. n., Bauer, T. W., Alexandrescu, S. n., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G. n., Pulitano, C. n., Shen, F. n., Soubrane, O. n., Koerkamp, B. G., Matsuyama, R. n., Endo, I. n., Pawlik, T. M. 2019
Although lymph node metastasis (LNM) is an important prognostic indicator for patients with intrahepatic cholangiocarcinoma (ICC), the benefit and indication for lymphadenectomy remain unclear.Patients diagnosed with ICC between 1990 and 2016 were identified in the international multi-institutional dataset. To determine the survival benefit from lymphadenectomy, the therapeutic index was calculated by multiplying the frequency of LNM in a particular group of patients by the 3-year cancer-specific survival (CSS) rate of patients with LNM in that subgroup.Among 471 patients who met the inclusion criteria, approximately half had LNM (n = 205, 43.5%). The median number of resected and metastatic LNs were 4 [interquartile range (IQR) 2-8] and 0 (IQR 0-1), respectively. Three-year CSS in the entire cohort was 29.9%, reflecting a therapeutic index value of 13.0. The therapeutic index was lower among patients with major vascular invasion (5.4), preoperative carcinoembryonic antigen (CEA) > 5.0 (8.2), and LNM in areas other than the hepatoduodenal ligament (5.2). Of note, a therapeutic index difference of more than 10 points was noted only when examining the number of LNs harvested [1-2 (4.1) vs. 3-6 (16.1) vs. ≥ 7 (17.8)].The survival benefit derived from lymphadenectomy was poor among patients with major vascular invasion, CEA > 5.0, and LNM in areas other than the hepatoduodenal ligament. Resection of three or more LNs was associated with the highest therapeutic value among patients with LNM.
The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management. Surgery Lopez-Aguiar, A. G., Ethun, C. G., Zaidi, M. Y., Rocha, F. G., Poultsides, G. A., Dillhoff, M. n., Fields, R. C., Idrees, K. n., Cho, C. S., Abbott, D. E., Cardona, K. n., Maithel, S. K. 2019
Management of <2-cm pancreatic neuroendocrine tumors is controversial. Although often indolent, the oncologic heterogeneity of these tumors particularly related to lymph node metastases poses challenges when deciding between resection versus surveillance.We analyzed all patients who underwent resection of primary nonfunctional <2-cm with curative-intent at 8 institutions of the US Neuroendocrine Tumor Study Group from 2000 to 2016. Pancreatic neuroendocrine tumors with poor differentiation and Ki-67 > 20% were excluded. Our primary aim was to create a lymph node risk score that predicted lymph node metastases accurately for <2-cm pancreatic neuroendocrine tumors, utilizing readily available preoperative data.Of 695 patients with resected pancreatic neuroendocrine tumors, 309 were <2 cm. Of these small pancreatic neuroendocrine tumors, 25% were proximal (head/uncinate), 23% had a Ki-67 > 3%, and only 8% were moderately differentiated. Also, only 9% of all <2-cm pancreatic neuroendocrine tumors were lymph node (+). Indeed lymph node positivity was associated with worse 5-year recurrence-free survival compared with lymph node (-) disease (80% vs 96%; P = .007). Factors known preoperatively to be associated with lymph node metastases were proximal location (odds ratio 4.0; P = .002) and Ki-67 >3% (odds ratio 2.7; P = .05). Moderate differentiation was not associated with lymph node (+) disease. Location and Ki-67 were assigned a value weighted by their odds ratio: (distal= 1, proximal= 4, and Ki-67 < 3% = 1 and Ki-67 > 3% = 3), which formed a lymph node risk score ranging 1-7. Scores were categorized into low (1-2), intermediate (3-4), and high (5-7) risk groups. Incidence of lymph node metastases increased progressively based on risk group, with low = 3.2%, intermediate = 13.8%, and high = 20.5%. Only 3.4% of pancreatic neuroendocrine tumors with a Ki-67 < 3% in the distal pancreas were lymph node (+) compared with 21.4% of pancreatic neuroendocrine tumors with a Ki-67 > 3% in the head/uncinate.This simple and novel lymph node risk score utilizes readily available preoperative factors (tumor location and Ki-67) to stratify risk of lymph node metastases accurately s for < 2-cm pancreatic neuroendocrine tumors and may help guide management strategy.
A Multi-Institutional International Analysis of Textbook Outcomes Among Patients Undergoing Curative-Intent Resection of Intrahepatic Cholangiocarcinoma. JAMA surgery Merath, K. n., Chen, Q. n., Bagante, F. n., Alexandrescu, S. n., Marques, H. P., Aldrighetti, L. n., Maithel, S. K., Pulitano, C. n., Weiss, M. J., Bauer, T. W., Shen, F. n., Poultsides, G. A., Soubrane, O. n., Martel, G. n., Koerkamp, B. G., Guglielmi, A. n., Itaru, E. n., Cloyd, J. M., Pawlik, T. M. 2019: e190571
Composite measures may be superior to individual measures for the analysis of hospital performance and quality of surgical care.To determine the incidence of a so-called textbook outcome, a composite measure of the quality of surgical care, among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma.This cohort study involved an analysis of a multinational, multi-institutional cohort of patient from 15 major hepatobiliary centers in North America, Europe, Australia, and Asia who underwent curative-intent resection of intrahepatic cholangiocarcinoma between 1993 and 2015. Data analysis was conducted from April 2018 to May 2018.Hospital variation in the composite end point of textbook outcome, defined as negative margins, no perioperative transfusion, no postoperative surgical complications, no prolonged length of stay, no 30-day readmissions, and no 30-day mortality. Secondary end points were factors associated with achieving textbook outcomes.Among 687 patients (of whom 370 [53.9%] were men; median patient age, 61 [range, 18-86] years) undergoing curative-intent resection of intrahepatic cholangiocarcinoma, a textbook outcome was achieved in 175 patients (25.5%). Being 60 years or younger (odds ratio [OR], 1.61 [95% CI, 1.04-2.49]; P = .03), absence of preoperative jaundice (OR, 4.40 [95% CI, 1.28-15.15]; P = .02), no neoadjuvant chemotherapy (OR, 2.57 [95% CI, 1.05-6.29]; P = .04), T1a/T1b-stage disease (OR, 1.58 [95% CI, 1.01-2.49]; P = .049), N0 status (OR, 3.89 [95% CI, 1.77-8.54]; P = .001), and no bile duct resection (OR, 2.46 [95% CI, 1.25-4.84]; P = .009) were independently associated with achieving a textbook outcome after resection. A prolonged length of stay had the greatest negative association with a textbook outcome. A nomogram to assess the probability of textbook outcome was developed and had good accuracy in both the training data set (area under the curve, 0.755) and validation data set (area under the curve, 0.763).In this study, while hepatic resection for intrahepatic cholangiocarcinoma was performed with less than 5% mortality in specialized centers, a textbook outcome was achieved in only approximately 26% of patients. A textbook outcome may be useful for the reporting of patient-level hospital performance and hospital variation, leading to quality improvement efforts after resection of intrahepatic cholangiocarcinoma.
Outcomes of Elderly Patients Undergoing Curative Resection for Retroperitoneal Sarcomas: Analysis From the US Sarcoma Collaborative. The Journal of surgical research Wilkinson, K. H., Ethun, C. G., Hembrook, M., Bedi, M., Charlson, J., Mogal, H., Tsai, S., Christians, K., Tran, T. B., Poultsides, G., Grignol, V., Howard, J. H., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Cullinan, D., Fields, R. C., Weber, S., Gamblin, T. C., Cardona, K., Clarke, C. N. 2019; 233: 154–62
BACKGROUND: The postoperative outcomes of elderly patients undergoing resection of retroperitoneal sarcomas (RPS) have not been widely studied.METHODS: Patients undergoing surgical resection for primary or recurrent RPS between 2000 and 2015 at participating US Sarcoma Collaborative institutions were identified. Patient demographics, perioperative morbidity, mortality, length of stay, discharge to home, disease-specific survival, and disease-free survival were compared between elderly (≥70y, n=171) and nonelderly (<70y, n=494) patients.RESULTS: There was no difference in perioperative morbidity (total and major complications elderly versus nonelderly: 39% versus 35%; P=0.401 and 18% versus 17%; P=0.646, respectively) or mortality between elderly and nonelderly patients with each group experiencing a 1% 30-d mortality rate. Length of stay and 30-d readmission rates were similar (elderly versus nonelderly; 7d interquartile range [IQR: 5-9] versus 6d [IQR: 4-9], P=0.528 and 11% versus 12%, P=0.667). Elderly patients were more likely to be discharged to a skilled nursing or rehabilitation facility (elderly versus nonelderly; 19% versus 7%, P<0.001). There was no difference in 3-y disease-free survival between the elderly and nonelderly patients (41% versus 43%, P=0.65); however, elderly patients had a lower 3-y disease-specific survival (60% versus 76%, P<0.001). In elderly patients, the presence of multiple comorbidities and high-grade tumors were most predictive of outcomes.CONCLUSIONS: Advanced age was not associated with an increased risk of perioperative morbidity and mortality following resection of RPS in this multi-institutional review. Although short-term oncologic outcomes were similar in both groups, the risk of death after sarcoma recurrence was higher in elderly patients and may be related to comorbidity burden and tumor histology.
The role of radiation therapy and margin width in localized soft-tissue sarcoma: Analysis from the US Sarcoma Collaborative. Journal of surgical oncology Gannon, N. P., King, D. M., Ethun, C. G., Charlson, J. n., Tran, T. B., Poultsides, G. n., Grignol, V. n., Howard, J. H., Tseng, J. n., Roggin, K. K., Votanopoulos, K. n., Krasnick, B. n., Fields, R. C., Cardona, K. n., Bedi, M. n. 2019
Soft-tissue sarcomas (STSs) are often treated with resection and radiation (RT)±chemotherapy. The role of RT in decreasing resection width to achieve local control is unclear. We evaluated RT on margin width to achieve local control and local recurrence (LR).From 2000 to 2016, 514 patients with localized STS were identified from the US Sarcoma Collaborative database. Patients were stratified by a margin and local control was compared amongst treatment groups.LR was 9% with positive, 4.2% with ≤1 mm, and 9.3% with >1 mm margins (P = .315). In the ≤1 mm group, LR was 5.7% without RT, 0% with preoperative RT, and 0% with postoperative RT (P < .0001). In the >1 mm group, LR was 10.2%, 0%, and 3.7% in the no preoperative and postoperative RT groups, respectively (P = .005). RT did not influence LR in patients with positive margins. In stage I-III and II-III patients, local recurrence-free survival was higher following RT (P = .008 and P = .05, respectively).RT may play a larger role in minimizing LR than margin status. In patients with positive margins, RT may decrease LR to similar rates as a negative margin without RT and may be considered to decrease the risk of LR with anticipated close/positive margins.
The impact of unplanned excisions of truncal/extremity soft tissue sarcomas: A multi-institutional propensity score analysis from the US Sarcoma Collaborative. Journal of surgical oncology Zaidi, M. Y., Ethun, C. G., Liu, Y. n., Poultsides, G. n., Howard, J. H., Mogal, H. n., Tseng, J. n., Votanopoulos, K. n., Fields, R. C., Cardona, K. n. 2019
Our aim was to compare outcomes in patients who underwent unplanned excisions (UE) of soft-tissue sarcomas (STS) against patients with planned excisions (PE).The retrospective 7-institution US Sarcoma Collaborative database was used. Patients with curative-intent resection of truncal/extremity STS between 2000 and 2016 were included. Propensity score weighting analysis (PSWA) was performed. Endpoints were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-specific survival (DSS).One thousand five hundred and ninety-six patients were included. Eighty-two percent (n = 1315) underwent PE and 18% (n = 281) underwent UE. Compared with PE, patients with UE were younger with smaller tumors with similar tumor grade. Unmatched analysis revealed PE was associated with worse DMFS (hazard ratio [HR] 1.95, P = .009) and DSS (HR 1.78, P = .039), but not LRFS compared with UE. On PSWA, UE had earlier LRFS (3-year LRFS: 80.5% vs 89.8%, P = .039), but not DMFS or DSS. By grade, patients with high-grade tumors and UE had worse LRFS (1-year LRFS: 90% vs 94%, P = .015), but similar DMFS and DSS compared with PE. In low-grade patients, UE and PE had similar LRFS, DMFS, or DSS.UE of STS is not associated with worse prognosis compared to PE, though UE is associated with earlier locoregional recurrence in patients with high-grade tumors. Multimodality therapy is needed to achieve improved outcomes in these patients.
Association of preoperative monocyte-to-lymphocyte and neutrophil-to-lymphocyte ratio with recurrence-free and overall survival after resection of pancreatic neuroendocrine tumors (US-NETSG). Journal of surgical oncology Panni, R. Z., Lopez-Aguiar, A. G., Liu, J. n., Poultsides, G. A., Rocha, F. G., Hawkins, W. G., Strasberg, S. M., Trikalinos, N. A., Maithel, S. n., Fields, R. C. 2019
Preoperative systemic inflammatory response plays a crucial role in tumorigenesis, progression, and prognosis; and neutrophil, monocyte, and lymphocyte counts serve as important biomarkers. An altered monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with a favorable prognosis for certain hematologic malignancies and breast cancer. The aim of this study was to investigate the prognostic significance of MLR, NLR in patients with resectable PNETs.Patients undergoing surgery for PNETs between 2000 and 2016 were identified using a large, multi-center database. NLR and MLR were calculated and Contal and O'Quigley analysis was used to determine the optimal cutoff value.A total of 620 patients were included in the analytic cohort. The prognostic implications of blood count parameters were evaluated in both univariate and multivariate analysis. The univariate analysis revealed that low MLR and NLR is associated with significantly improved overall survival (OS; P < .01) and recurrence-free survival (RFS; P < .01). On multivariate analysis, in addition to tumor size and grade, NLR was an independent predictor of improved OS and RFS.In addition to established tumor-specific factors, preoperative NLR levels can serve as a valuable biomarker that can be used as a predictor of OS and RFS after resection of PNETs.
Management of Ileal Neuroendocrine Tumors with Liver Metastases. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Fisher, A. T., Titan, A. L., Foster, D. S., Worth, P. J., Poultsides, G. A., Visser, B. C., Dua, M. M., Norton, J. A. 2019
Assessment of treating metastatic ileal neuroendocrine tumors (NETs) with complete resection of primary tumor, nodal and liver metastases, plus administration of long-acting somatostatin analogues (SSAs).A prospective database was queried for patients with ileal or pancreatic NETs with pathology-confirmed liver metastases and tumor somatostatin receptors. Patients did not have MEN-1 and had no previous treatment. The impacts of SSA treatment on the primary outcome of survival and secondary outcome of progression-free survival were assessed with Kaplan-Meier analysis. Log rank test was used to compare overall and progression-free survival among groups.Seventeen ileal NET patients and 36 pancreatic NET patients who underwent surgical resection between 2001 and 2018, who had pathology-confirmed liver metastases and confirmed tumor somatostatin receptors, did not have MEN-1, and had no previous treatment were identified. Median follow-up for patients with ileal NETs was 80 months (range 0-197 months) and 32 months (range 1-182 months) for pancreatic NETs. Five-year survival was 93% and 72% for ileal and pancreatic NET, respectively. Progression-free 5-year survival was 70% and 36% for ileal and pancreatic NET, respectively. Overall 5-year survival for pNETs was greater in those patients treated with SSA (79%) compared to those who underwent surgery alone (34%, p < 0.01). The average ECOG score was low for surviving patients with ileal (0.15) and pancreatic NET (0.73) indicating a good quality of life.Resection of primary lymph node and liver metastatic ileal or pancreatic NETs followed with continued SSAs is associated with an excellent progression-free and overall survival and minimal side effects.
Lung Surveillance Strategy for High-Grade Soft Tissue Sarcomas: Chest X-Ray or CT Scan? Journal of the American College of Surgeons Gamboa, A. C., Ethun, C. G., Switchenko, J. M., Lipscomb, J. n., Poultsides, G. A., Grignol, V. n., Howard, J. H., Gamblin, T. C., Roggin, K. K., Votanopoulos, K. n., Fields, R. C., Maithel, S. K., Delman, K. A., Cardona, K. n. 2019
Given the propensity for lung metastases (LM), NCCN guidelines recommend lung surveillance (LS) with either CXR or CT in high-grade soft tissue sarcoma (HG-STS). Considering survival, diagnostic sensitivity and cost, the optimal modality is unknown.The US Sarcoma Collaborative database (2000-2016) was reviewed for patients who underwent resection of a primary HG-STS. Primary outcome was overall survival (OS). Cost analysis was performed.Among 909pts, 83% had truncal/extremity, 17% had retroperitoneal (RP) tumors. Recurrence occurred in 48% of which 54% were LM. LS was performed with CT in 80% and CXR in 20%. Both groups were clinically similar although CT patients had more RP tumors and recurrences. Regardless of modality, 85-90% of LM were detected within the first 2yrs with a similar re-intervention rate. When considering age, tumor size, location, margin status, and receipt of radiation, LM was independently associated with worse OS(HR:4.26; p<0.01) while imaging modality was not(HR:1.01; p=0.97). CXR patients did not have an inferior 5-year OS compared to CT(71vs60%, p<0.01). When analyzing patients in whom no LM was detected, both cohorts had a similar 5-year OS(73vs74%, p=0.42), suggesting CXR was not missing clinically relevant lung nodules. When adhering to a guideline-specified protocol for 2018 projected 4,406 cases, surveillance with CXR for 5yrs results in savings of $5-8M/year to the US healthcare system.In this large multicenter study, LS with CXR did not result in worse overall survival when compared to CT. With considerable savings, a CXR-based protocol may optimize resource utilization for LS in HG-STS; prospective trials are needed.
Trends in the Use of Adjuvant Chemotherapy for High-Grade Truncal and Extremity Soft Tissue Sarcomas. The Journal of surgical research Squires, M. H., Ethun, C. G., Suarez-Kelly, L. P., Yu, P. Y., Hughes, T. M., Shelby, R. D., Tran, T. B., Poultsides, G. n., Charlson, J. n., Gamblin, T. C., Tseng, J. n., Roggin, K. K., Chouliaras, K. n., Votanopoulos, K. n., Krasnick, B. A., Fields, R. C., Pollock, R. E., Grignol, V. n., Cardona, K. n., Howard, J. H. 2019; 245: 577–86
In the randomized controlled trial (RCT) EORTC 62931, adjuvant chemotherapy failed to show improvement in relapse-free survival (RFS) or overall survival (OS) for patients with resected high-grade soft tissue sarcoma (STS). We evaluated whether the negative results of this 2012 RCT have influenced multidisciplinary treatment patterns for patients with high-grade STS undergoing resection at seven academic referral centers.The U.S. Sarcoma Collaborative database was queried to identify patients who underwent curative-intent resection of primary high-grade truncal or extremity STS from 2000 to 2016. Patients with recurrent tumors, metastatic disease, and those receiving neoadjuvant chemotherapy were excluded. Patients were divided by treatment era into early (2000-2011, pre-European Organisation for Research and Treatment of Cancer [EORTC] trial) and late (2012-2016, post-EORTC trial) cohorts for analysis. Rates of adjuvant chemotherapy and clinicopathologic variables were compared between the two cohorts. Univariate and multivariate regression analyses were used to determine factors associated with OS and RFS.949 patients who met inclusion criteria were identified, with 730 patients in the early cohort and 219 in the late cohort. Adjuvant chemotherapy rates were similar between the early and late cohorts (15.6% versus 14.6%; P = 0.73). Patients within the early and late cohorts demonstrated similar median OS (128 months versus median not reached, P = 0.84) and RFS (107 months versus median not reached, P = 0.94). Receipt of adjuvant chemotherapy was associated with larger tumor size (13.6 versus 8.9 cm, P < 0.001), younger age (53.3 versus 63.7 years, P < 0.001), and receipt of adjuvant radiation (P < 0.001). On multivariate regression analysis, risk factors associated with decreased OS were increasing American Society of Anesthesiologists class (P = 0.02), increasing tumor size (P < 0.001), and margin-positive resection (P = 0.01). Adjuvant chemotherapy was not associated with OS (P = 0.88). Risk factors associated with decreased RFS included increasing tumor size (P < 0.001) and margin-positive resection (P = 0.03); adjuvant chemotherapy was not associated with RFS (P = 0.23).Rates of adjuvant chemotherapy for resected high-grade truncal or extremity STS have not decreased over time within the U.S. Sarcoma Collaborative, despite RCT data suggesting a lack of efficacy. In this retrospective multi-institutional analysis, adjuvant chemotherapy was not associated with RFS or OS on multivariate analysis, consistent with the results from EORTC 62931. Rates of adjuvant chemotherapy for high-grade STS were low in both cohorts but may be influenced more by selection bias based on clinicopathologic variables such as tumor size, margin status, and patient age than by prospective, randomized data.
Predictors of Disease-Free and Overall Survival in Retroperitoneal Sarcomas: A Modern 16-Year Multi-Institutional Study from the United States Sarcoma Collaboration (USSC). Sarcoma Schwartz, P. B., Vande Walle, K., Winslow, E. R., Ethun, C. G., Tran, T. B., Poultsides, G., Tseng, J., Roggin, K., Grignol, V., Howard, J. H., Krasnick, B. A., Fields, R. C., Mogal, H., Clarke, C. N., Senehi, R., Votanopoulos, K., Cardona, K., Abbott, D. E. 2019; 2019: 5395131
Background: Retroperitoneal sarcomas (RPS) comprise approximately 15% of all soft-tissue sarcomas and frequently associated with significant morbidity and as little as 30% 5-year survival. Here, we provide a large, contemporary, and multi-institutional experience to determine which tumor, patient, and treatment characteristics are associated with long-term outcomes in RPS.Methods: 571 patients with primary RPS were identified from the United States Sarcoma Collaboration (USSC). RPS patients who underwent resection from January 2000 to April 2016 were included with patient, tumor, and treatment-specific variables investigated as independent predictors of survival. Survival analyses for disease-free and overall survival were conducted using Kaplan-Meier and Cox proportional hazards model methods.Results: The study cohort was 55% female, with a median age of 58.9years (IQR: 48.6-70.0). The most common tumor histiotypes were liposarcoma (34%) and leiomyosarcoma (28%). Median follow-up was 30.6months (IQR: 11.2-60.4). Median disease-free survival was 35.3months (95% CI: 27.6-43.0), with multivariate predictors of poorer disease-free survival including higher grade tumors, nodal-positive disease, and multivisceral resection. Median overall survival was 81.6months (95% CI: 66.3-96.8). Multivariate predictors of shorter overall survival included higher grade tumors, nodal-positive and multifocal disease, systemic chemotherapy, and grossly positive margins (R2) following resection.Conclusions: The strongest predictors of disease-free and overall survival are tumor-specific characteristics, while surgical factors are less impactful. Nonsurgical therapies are not associated with improved outcomes despite persistent interest and utilization. Complete macroscopic resection (R0/R1) remains a persistent potentially modifiable risk factor associated with improved overall survival in patients with retroperitoneal sarcomas.
View details for DOI 10.1155/2019/5395131
What Is the Best Operation for Proximal Gastric Cancer and Distal Esophageal Cancer? The Surgical clinics of North America Mazer, L. M., Poultsides, G. A. 2019; 99 (3): 457–69
Cancer of the gastroesophageal junction (GEJ) is increasing in incidence, likely as a result of rising obesity and gastroesophageal reflux disease rates. The tumors that arise here share features of esophageal and gastric cancer, and are classified based on their location in relationship to the GEJ. The definition of the GEJ itself, as well as optimal resection strategy, extent of lymph node dissection, resection margin length, and reconstruction methods are still very much a subject of debate. This article summarizes the available evidence on this topic, and highlights specific areas for further research.
Gastric carcinoids: Does type of surgery or tumor affect survival? American journal of surgery Crown, A., Kennecke, H., Kozarek, R., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G. A., Makris, E., Idrees, K., Smith, P. M., Nathan, H., Beems, M., Abbott, D., Fisher, A. V., Fields, R. C., Davidson, J., Maithel, S. K., Rocha, F. G. 2018
BACKGROUND: Gastric carcinoids are rare neuroendocrine tumors of the gastrointestinal tract. They are typically managed according to their etiology. However, there is little known about the impact of surgical strategy on the long-term outcomes of these patients.METHODS: All patients who underwent resection of gastric carcinoids at 8 institutions from 2000 to 2016 were analyzed retrospectively. Tumors were stratified according to subtype (I, II, III, IV) and resection type (local resection, LR or formal gastrectomy, FG). Clinicopathological parameters, recurrence-free (RFS) and overall survival (OS) were compared between groups.RESULTS: Of 79 patients identified with gastric carcinoids, 34 had type I lesions associated with atrophic gastritis, 4 had type II lesions associated with a gastrinoma, 37 had type III sporadic lesions, and 4 had type IV poorly-differentiated lesions. The mean age of presentation was 56 years in predominantly Caucasian (77%) and female (63%) patients. Mean tumor size was 2.4 cm and multifocal tumors were found in 24 (30%) of patients with the majority occurring in those with type I tumors. Lymph node positive tumors were seen in 15 (19%) patients and 7 (8%) had M1 disease; both most often in type IV followed by type III tumors. R0 resection was achieved in 56 (71%) patients while 15 (19%) had R1 resections and 6 (8%) R2 resections. Patients with type I and III tumors were equally likely to have a LR (50% and 43% respectively) compared to FG while those with type II and IV all had FG with one exception. Type IV tumors had the poorest RFS and OS while Type II tumors had the most favorable RFS and OS (p < 0.04 and p < 0.0004, respectively). While there was no difference in RFS in those patients undergoing FG versus LR, OS was worse in the FG group (p < 0.017). This trend persisted when type II and type IV groups were excluded (p < 0.045).CONCLUSION: Gastric carcinoid treatment should be tailored to tumor type, as biologic behavior rather than resection technique is the more important factor contributing to long-term outcomes.
Staging laparoscopy among three subtypes of extra-hepatic biliary malignancy: a 15-year experience from 10 institutions. Journal of surgical oncology Davidson, J. T., Jin, L. X., Krasnick, B., Ethun, C. G., Pawlik, T. M., Poultsides, G. A., Idrees, K., Weber, S. M., Martin, R. C., Shen, P., Hatzaras, I., Maithel, S. K., Fields, R. C., and the U.S. Extrahepatic Biliary Malignancy Consortium,, 2018
BACKGROUND: Staging laparoscopy (SL) is used to avoid resection failure and thus increase the curative resection rate. SL utilization in extra-hepatic biliary tumors (EHBT) is variable.METHODS: Data from 1090 patients with potentially resectable EHBT including gallbladder (GBC), distal (DC), and hilar (HC) subtypes were retrospectively collected from 10 academic centers (2000-2015).RESULTS: The SL utilization rate increased over time and was significantly higher in GBC than DC and HC. SL yield was 16.8% and did not differ between groups or over time. In patients undergoing attempted resection with prior SL, the curative resection rate did not differ between subtypes. In patients undergoing attempted resection without prior SL, the curative resection rate was less in GBC compared with DC or HC. After matching cohorts by inverse probability weighting, prior SL was associated with curative resection in GBC only (odds ratio [OR], 2.41, 95% CI, 1.36-4.27). On multivariable regression analysis, elevated carbohydrate antigen 19-9 (CA 19-9), low serum albumin, and GBC were strong predictors of distant disease on SL. After categorizing patients undergoing SL into low, intermediate, and high-risk groups based on these parameters, SL yield improved progressively from 10.0% to 19.6% to 52.6%.CONCLUSIONS: We recommend routine SL for patients with GBC, particularly with elevated CA19-9 level and/or decreased serum albumin.
Actual 5-Year Survivors After Surgical Resection of Hilar Cholangiocarcinoma. Annals of surgical oncology Tran, T. B., Ethun, C. G., Pawlik, T. M., Schmidt, C., Beal, E. W., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Idrees, K., Isom, C. A., Hatzaras, I., Shenoy, R., Maithel, S. K., Poultsides, G. A. 2018
BACKGROUND: The prevalence and characteristics of actual 5-year survivors after surgical treatment of hilar cholangiocarcinoma (HC) have not been described previously.METHODS: Patients who underwent resection for HC from 2000 to 2015 were analyzed through a multi-institutional registry from 10 U.S. academic medical centers. The clinicopathologic characteristics and both the perioperative and long-term outcomes for actual 5-year survivors were compared with those for non-survivors (patients who died within 5years after surgery). Patients alive at last encounter who had a follow-up period shorter than 5years were excluded from the study.RESULTS: The study identified 257 patients with HC who underwent curative-intent resection with an actuarial 5-year survival of 19%. Of 194 patients with a follow-up period longer than 5years, 23 (12%) were 5-year survivors. Compared with non-survivors, the 5-year survivors had a lower median pretreatment CA 19-9 level (116 vs. 34 U/L; P=0.008) and a lower rate of lymph node involvement (42% vs. 15%; P=0.027) and R1 margins (39% vs. 17%; P=0.042). However, the sole presence of these factors did not preclude a 5-year survival after surgery. The frequencies of bile duct resection alone, major hepatectomy, caudate lobe resection, portal vein or hepatic artery resection, preoperative biliary sepsis, intraoperative blood transfusion, serious postoperative complications, and receipt of adjuvant chemotherapy were comparable between the two groups.CONCLUSIONS: One in eight patients with HC reaches the 5-year survival milestone after resection. A 5-year survival can be achieved even in the presence of traditionally unfavorable clinicopathologic factors (elevated CA 19-9, nodal metastasis, and R1 margins).
Long-term outcomes of patients with intraductal growth sub-type of intrahepatic cholangiocarcinoma HPB Bagante, F., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Guglielmi, A., Itaru, E., Pawlik, T. M. 2018; 20 (12): 1189–97
Intraductal-growth (IG) type of intrahepatic cholangiocarcinoma (ICC) may be associated with a favorable prognosis compared with mass-forming (MF) and periductal-infiltrating (PI) ICC.The clinico-pathological characteristics and long-term outcomes of 1206 patients undergoing liver resection for ICC were compared based on the ICC morphological classification.Compared with MF patients, IG patients had a higher incidence of poor/un-differentiated tumor, lympho-vascular, and perineural invasion (poor/un-differentiated: MF, 18% vs. IG, 24%; lympho-vascular invasion: MF, 30% vs. IG, 35%; perineural invasion: MF, 17% vs. IG, 33%; all p > 0.05). The pattern of recurrence was different among MF patients (intrahepatic only: 63%; extrahepatic only: 22%; both intra- and extrahepatic: 16%) versus IG patients (intrahepatic only: 46%; extrahepatic: 25%; both intra- and extrahepatic: 29%) (p < 0.001). Moreover, while 78% of patients with MF had an early recurrence (<18 months from surgery), 59% of IG patients had and early recurrence (p = 0.039). On multivariable analysis, after controlling for competing risk factors, IG patients had a similar prognosis as MF patients (HR 0.90, p = 0.69).While IG patients more frequently presented with more adverse pathological characteristics, the prognosis of IG patients was comparable with MF patients after controlling for all these adverse factors.
A novel, simplified, externally validated staging system for truncal/extremity soft tissue sarcomas: An analysis of the US Sarcoma Collaborative database JOURNAL OF SURGICAL ONCOLOGY Johnson, A. C., Ethun, C. G., Liu, Y., Poultsides, G., Howard, J. H., Bedi, M., Charlson, J., Tseng, J., Roggin, K. K., Votanopoulos, K., Cullinan, D., Fields, R. C., Maithel, S. K., Cardona, K., US Sarcoma Collaborative 2018; 118 (7): 1135–41
The prognosis of colorectal cancer liver metastases associated with inflammatory bowel disease: An exploratory analysis JOURNAL OF SURGICAL ONCOLOGY Margonis, G., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Galjart, B., Kamphues, C., Pawlik, T. M., Poultsides, G., Kaczirek, K., Lonning, P., Verhoef, C., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2018; 118 (7): 1074-1080
ASO Author Reflections: Fluorescent-Guided Surgery to Augment Pancreatic Cancer Surgery ANNALS OF SURGICAL ONCOLOGY Tummers, W. S., Rosenthal, E. L., Vahrmeijer, A. L., Poultsides, G. A. 2018; 25: 820-821
The prognostic significance of adrenocortical carcinomas identified incidentally JOURNAL OF SURGICAL ONCOLOGY Rossfeld, K. K., Maithel, S. K., Prescott, J., Wang, T. S., Fields, R. C., Weber, S. M., Sicklick, J. K., Yopp, A. C., Quan-Yang Duh, Solorzano, C. C., Votanopoulos, K. I., Hatzaras, I., Poultsides, G. A., Shirley, L. A., U S Adrenocortical Carcinoma Study 2018; 118 (7): 1155-1162
ASO Author Reflections: Fluorescent-Guided Surgery to Augment Pancreatic Cancer Surgery (vol 25, pg 820, 2018) ANNALS OF SURGICAL ONCOLOGY Tummers, W. S., Rosenthal, E. L., Vahrmeijer, A. L., Poultsides, G. A. 2018; 25: 999
Hepatic Resection for Non-functional Neuroendocrine Liver Metastasis: Does the Presence of Unresected Primary Tumor or Extrahepatic Metastatic Disease Matter? ANNALS OF SURGICAL ONCOLOGY Xiang, J., Zhang, X., Beal, E. W., Weiss, M., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S., Marques, H. P., Pawlik, T. M. 2018; 25 (13): 3928–35
The objective of this study was to assess the impact of unresected primary tumor, as well as extrahepatic metastasis, on the long-term prognosis of patients undergoing hepatic resection for non-functional neuroendocrine liver metastasis (NF-NELM).Patients who underwent hepatic resection for NF-NELM were identified from a multi-institutional database. Data on clinical and pathological details, as well as the long-term overall survival (OS) were obtained and compared. Propensity score matching was performed to generate matched pairs of patients.Among the 332 patients with NF-NELM, 281 (84.6%) underwent primary tumor resection, while 51 (15.4%) did not. Patients who underwent primary resection were more likely to have a pancreatic primary and metachronous NELM. The long-term OS of patients who did and did not have the primary neuroendocrine tumor (NET) resected was comparable on both unmatched (10-year survival rate 66.8% vs. 54.0%, p = 0.192) and matched (10-year survival rate 75.7% vs. 60.4%, p = 0.271) analyses. In contrast, patients with NF-NELM and extrahepatic metastasis had a worse OS following resection compared with patients who had intrahepatic-only metastasis on unmatched (10-year survival rate 37.5% vs. 69.3%, p = 0.002) and matched (10-year survival rate 37.5% vs. 86.3%, p = 0.011) analyses. On multivariable analysis, while resection of the primary NET was not associated with OS (hazard ratio [HR] 0.7, 95% confidence interval [CI] 0.4-1.2, p = 0.195), the presence of extrahepatic metastasis was independently associated with long-term risk of death (HR 3.9, 95% CI 1.7-9.2, p = 0.002).While surgery should be considered for patients with NF-NELM who have an unresectable primary tumor, operative resection of NF-NELM may not be as beneficial in patients with extrahepatic disease.
The impact of failure to achieve symptom control after resection of functional neuroendocrine tumors: An 8-institution study from the US Neuroendocrine Tumor Study Group. Journal of surgical oncology Zaidi, M. Y., Lopez-Aguiar, A. G., Poultsides, G. A., Dillhoff, M., Rocha, F. G., Idrees, K., Nathan, H., Winslow, E. R., Fields, R. C., Cardona, K., Maithel, S. K., and other members of the US Neuroendocrine Tumor Study Group 2018
BACKGROUND: The goals of resection of functional neuroendocrine tumors (NETs) are two-fold: Oncological benefit and symptom control. The interaction between the two is not well understood.METHODS: All patients with functional NETs of the pancreas, duodenum, and ampulla who underwent curative-intent resection between 2000 and 2016 were identified. Using Cox regression analysis, factors associated with reduced recurrence-free survival (RFS) were identified.RESULTS: Two-hundred and thirty patients underwent curative-intent resection. Fifty-three percent were insulinomas, 35% gastrinomas, and 12% were other types. Twenty-one percent had a known genetic syndrome, 23% had lymph node (LN) positivity, 80% underwent an R0 resection, and 14% had no postoperative symptom improvement (SI). Factors associated with reduced RFS included noninsulinoma histology, the presence of a known genetic syndrome, LN positivity, R1 margin, and lack of SI. On multivariable analysis, only the failure to achieve SI following resection was associated with reduced RFS. Considering only those patients with an R0 resection, failure to achieve SI was associated with worse 3-year RFS compared with patients having SI (36% vs 80%; P=0.006).CONCLUSIONS: Failure to achieve symptomatic improvement after resection of functional NETs is associated with worse RFS. These patients may benefit from short-interval surveillance imaging postoperatively to assess for earlier radiographical disease recurrence.
Impact of microvascular invasion on clinical outcomes after curative-intent resection for intrahepatic cholangiocarcinoma. Journal of surgical oncology Hu, L., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Itaru, E., Pawlik, T. M. 2018
BACKGROUND: Microvascular invasion (MiVI) is a histological feature of intrahepatic cholangiocarcinoma (ICC) that may be associated with biological behavior. We sought to investigate the impact of MiVI on long-term survival of patients undergoing curative-intent resection for ICC.METHODS: A total of 1089 patients undergoing curative-intent resection for ICC were identified. Data on clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) were compared among patients with no vascular invasion (NoVI), MiVI, and macrovascular invasion (MaVI).RESULTS: A total of 249 (22.9%) patients had MiVI, while 149 (13.7%) patients had MaVI (±MiVI). MiVI was associated with higher incidence of perineural, biliary and adjacent organ invasion, and satellite lesions (all P<0.01). On multivariable analysis, MiVI was an independent risk factor of DFS (hazard ratios [HR] 1.5; 95%confidence intervals [CI], 1.3-1.9; P<0.001), but not OS (HR 1.1; 95%CI, 0.9-1.3; P=0.379). While MiVI and MaVI patients had similar DFS (median, MiVI 14.0 vs MaVI 12.0 months, HR 0.9; 95%CI, 0.7-1.2; P=0.377), OS was better among MiVI patients (median, MiVI 39.0 vs MaVI 21.0 months, HR 0.7; 95%CI, 0.5-0.8; P=0.002). Whereas nodal metastasis, R1 margin, and postoperative morbidity were associated with early death (≤18 months) among patients with MiVI, only nodal metastasis was associated with late (>18 months) prognosis.CONCLUSIONS: Roughly 1 out of 5 patients with resected ICC had MiVI. MiVI was associated with advanced tumor characteristics and a higher risk of tumor recurrence.
Correction to: ASO Author Reflections: Fluorescent-Guided Surgery to Augment Pancreatic Cancer Surgery. Annals of surgical oncology Tummers, W. S., Rosenthal, E. L., Vahrmeijer, A. L., Poultsides, G. A. 2018
In the original version of this article, George A. Poultsides's middle initial was incorrect.
Isolated pancreatic tail remnants after transgastric necrosectomy can be observed. The Journal of surgical research Dua, M. M., Jensen, C. W., Friedland, S., Worth, P. J., Poultsides, G. A., Norton, J. A., Park, W. G., Visser, B. C. 2018; 231: 109–15
BACKGROUND: Severe necrotizing pancreatitis may result in midbody necrosis and ductal disruption leaving an isolated pancreatic tail. The purpose of this study was to characterize outcomes among patients with an isolated tail remnant who underwent transgastric drainage or necrosectomy (endoscopic or surgical) and determine the need for subsequent operative management.MATERIALS AND METHODS: Patients with necrotizing pancreatitis and retrogastric walled-off collections treated by surgical transgastric necrosectomy or endoscopic cystgastrostomy± necrosectomy between 2009 and 2017 were identified by a retrospective chart review. All available preprocedure and postprocedure imaging was reviewed for evidence of isolated distal pancreatic tail remnants.RESULTS: Seventy-four patients were included (40 surgical and 34 endoscopic). All the patients in the surgical group underwent laparoscopic transgastric necrosectomy; the endoscopic group consisted of 26 patients for pseudocyst drainage and eight patients for necrosectomy. A disconnected pancreatic tail was identified in 22 (29%) patients (13 laparoscopic and nine endoscopic). After the creation of the "cystgastrostomy," there were no external fistulas despite the viable tail. Of the 22 patients, four patients developed symptoms at a median of 23months (two, recurrent episodic pancreatitis; two, intractable pain). Two patients (both initially in endoscopic group) ultimately required distal pancreatectomy and splenectomy at 24 and 6months after index procedure.CONCLUSIONS: Patients with a walled-off retrogastric collection and an isolated viable tail are effectively managed by a transgastric approach. Despite this seemingly "unstable anatomy," the creation of an internal fistula via surgical or endoscopic "cystgastrostomy" avoids external fistulas/drains and the short-term necessity of surgical distal pancreatectomy. A very small subset requires intervention for late symptoms.
Monitoring gastric myoelectric activity after pancreaticoduodenectomy for diet "readiness" AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Dua, M. M., Navalgund, A., Axelrod, S., Axelrod, L., Worth, P. J., Norton, J. A., Poultsides, G. A., Triadafilopoulos, G., Visser, B. C. 2018; 315 (5): G743–G751
View details for DOI 10.1152/ajpgi.00074.2018
Isolated pancreatic tail remnants after transgastric necrosectomy can be observed JOURNAL OF SURGICAL RESEARCH Dua, M. M., Jensen, C. W., Friedland, S., Worth, P. J., Poultsides, G. A., Norton, J. A., Park, W. G., Visser, B. C. 2018; 231: 109–15
Perioperative chemotherapy is not associated with improved survival in high-grade truncal sarcoma JOURNAL OF SURGICAL RESEARCH Yu, P. Y., Beal, E. W., Hughes, T. M., Suarez-Kelly, L. P., Shelby, R. D., Ethun, C. G., Tran, T. B., Poultsides, G., Charlson, J., Gamblin, T., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B. A., Fields, R. C., Pollock, R. E., Grignol, V., Cardona, K., Howard, J. 2018; 231: 248–56
The treatment benefit of perioperative chemotherapy (CTX) for truncal soft tissue sarcoma (STS) is not well established. This study evaluates the association of CTX with survival for patients with resected primary high-grade truncal STS.Adult patients with high-grade truncal STS who had curative-intent resection from 2000 to 2016 at seven U.S. institutions were evaluated retrospectively. Patients were stratified by receipt of CTX. Kaplan-Meier curves with log-rank tests were used to compare overall survival (OS) and recurrence-free survival. Logistic regression models were used to evaluate characteristics associated with OS.Of patients with primary high-grade truncal STS, 235 underwent curative-intent resections. The most common histology was undifferentiated pleomorphic sarcoma and mean tumor size was 7.8 cm. Thirty percent of the patients received CTX (n = 70). Among patients receiving CTX, 34% (n = 24) had neoadjuvant CTX, 44% (n = 31) adjuvant CTX, and 21% (n = 15) had neoadjuvant and adjuvant CTX. Patients receiving CTX were more likely to receive radiation (51% versus 34%, P = 0.01), have deep tumors (86% versus 73%, P = 0.037) and solid organ invasion (14% versus 3%, P = 0.001). On univariate analysis, patients who received CTX had worse OS (P < 0.01) and a trend toward worse recurrence-free survival (P = 0.08). Margin status was the only variable associated with improved OS on multivariate analysis (odds ratio 4.36, 95% confidence interval 1.56, 12.13, P < 0.01).In this multi-institutional retrospective analysis of resected high-grade truncal STS, receipt of perioperative CTX was not associated with improved OS, which may be related to selection bias. Microscopically negative margin status was the only independent factor associated with OS.
Prognostic Role of Lymph Node Positivity and Number of Lymph Nodes Needed for Accurately Staging Small Bowel Neuroendocrine Tumors. JAMA surgery Zaidi, M. Y., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E., Poultsides, G., Makris, E., Rocha, F., Crown, A., Idrees, K., Marincola Smith, P., Nathan, H., Beems, M., Abbott, D., Barrett, J. R., Fields, R. C., Davidson, J., Cardona, K., Maithel, S. K. 2018
Importance: Little information is available regarding the minimum number of lymph nodes needed to accurately stage patients when performing a mesenteric lymphadenectomy for small-bowel neuroendocrine tumors.Objectives: To determine the prognostic role of lymph node positivity and the ideal number of lymph nodes for accurately staging patients with small-bowel neuroendocrine tumors.Design, Setting, and Participants: This case series from the US Neuroendocrine Tumor Study Group, a collaboration among 8 US-based, academic tertiary care referral centers, obtained demographic, perioperative, and pathologic data from the group's database, Social Security Death Index, and publicly available obituaries. All patients in these institutions with small-bowel neuroendocrine tumors who underwent curative-intent surgical resection of a primary tumor between January 1, 2000, and December 31, 2015, were included (n=199). Patients with duodenal or ampullary tumors, other nonneuroendocrine concurrent malignant neoplasms, mortality of fewer than 30 days after the surgical procedure, and distant metastatic disease were excluded. Data analysis was conducted from September 1, 2017, to December 1, 2017.Main Outcomes and Measures: Primary study outcome was recurrence-free survival. Hypothesis was generated after data collection and data entry into the US Neuroendocrine Tumor Study Group database.Results: Of the 199 patients included, 112 (56.3%) were male and 87 (43.7%) female with a mean (SD) age of 60.3 (12.5) years and a mean (SD) body mass index of 29.5 (6.0). One hundred fifty-four patients (77.4%) had lymph node-positive disease. No difference in 3-year recurrence-free survival was found between patients with lymph node-positive and lymph node-negative disease. Patients with 4 positive lymph nodes had a worse 3-year recurrence-free survival compared with those with 1 to 3 or 0 positive lymph nodes (81.6% vs 91.4% vs 92.1%; P=.01). When examining patients with fewer than 8 resected lymph nodes, no difference in 3-year recurrence-free survival was observed among patients with 4 or more, 1 to 3, or 0 positive lymph nodes (100% vs 93.8% vs 91.7%; P=.87). Retrieval of 8 or more lymph nodes, however, accurately discriminated patients with 4 or more, 1 to 3, or 0 positive lymph nodes (3-year recurrence-free survival: 79.9% vs 89.6% vs 92.9%; P=.05).Conclusions and Relevance: The findings from this study suggest that, for patients undergoing curative-intent resection of small-bowel neuroendocrine tumors, accurate lymph node staging requires a minimum of 8 lymph nodes for examination, and 4 or more positive lymph nodes are associated with decreased 3-year recurrence-free survival compared with 1 to 3 or 0 positive lymph nodes; a thorough regional lymphadenectomy may be critical for accurate staging and management of this disease.
Influence of carcinoid syndrome on the clinical characteristics and outcomes of patients with gastroenteropancreatic neuroendocrine tumors undergoing operative resection. Surgery Kimbrough, C. W., Beal, E. W., Dillhoff, M. E., Schmidt, C. R., Pawlik, T. M., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F. G., Crown, A., Abbott, D. E., Fisher, A. V., Fields, R. C., Krasnick, B. A., Idrees, K., Marincola-Smith, P., Cho, C. S., Beems, M., Maithel, S. K., Cloyd, J. M. 2018
BACKGROUND: The incidence, clinical characteristics, and long-term outcomes of patients with gastroenteropancreatic neuroendrocrine tumors and carcinoid syndrome undergoing operative resection have not been well characterized.METHODS: Patients undergoing resection of primary or metastatic gastroenteropancreatic neuroendrocrine tumors between 2000 and 2016 were identified from an 8-institution collaborative database. Clinicopathologic and postoperative characteristics as well as overall survival and disease-free survival were compared among patients with and without carcinoid syndrome.RESULTS: Among 2,182 patients who underwent resection, 139 (6.4%) had preoperative carcinoid syndrome. Patients with carcinoid syndrome were more likely to have midgut primary tumors (44.6% vs 21.4%, P < .001), lymph node metastasis (63.4% vs 44.3%, P < .001), and metastatic disease (62.8% vs 26.7%, P < .001). There was no difference in tumor differentiation, grade, or Ki67 status. Perioperative carcinoid crisis was rare (1.6% vs 0%, P < .01), and the presence of preoperative carcinoid syndrome was not associated with postoperative morbidity (38.8% vs 45.5%, P = .129). Substantial symptom improvement was reported in 59.5% of patients who underwent curative-intent resection, but occurred in only 22.7% who underwent debulking. Despite an association on univariate analysis (P = .04), carcinoid syndrome was not independently associated with disease-free survival after controlling for confounding factors (hazard ratio 0.97, 95% confidence interval 0.64-1.45). Preoperative carcinoid syndrome was not associated with overall survival on univariate or multivariate analysis.CONCLUSION: Among patients undergoing operative resection of gastroenteropancreatic neuroendrocrine tumors, the prevalence of preoperative carcinoid syndrome was low. Although operative intervention with resection or especially debulking in patients with carcinoid syndrome was disappointing and often failed to improve symptoms, after controlling for markers of tumor burden, carcinoid syndrome was not independently associated with worse disease-free survival or overall survival.
Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming. Gut Koutsioumpa, M., Hatziapostolou, M., Polytarchou, C., Tolosa, E. J., Almada, L. L., Mahurkar-Joshi, S., Williams, J., Tirado-Rodriguez, A. B., Huerta-Yepez, S., Karavias, D., Kourea, H., Poultsides, G. A., Struhl, K., Dawson, D. W., Donahue, T. R., Fernandez-Zapico, M. E., Iliopoulos, D. 2018
OBJECTIVE: Despite advances in the identification of epigenetic alterations in pancreatic cancer, their biological roles in the pathobiology of this dismal neoplasm remain elusive. Here, we aimed to characterise the functional significance of histone lysine methyltransferases (KMTs) and demethylases (KDMs) in pancreatic tumourigenesis.DESIGN: DNA methylation sequencing and gene expression microarrays were employed to investigate CpG methylation and expression patterns of KMTs and KDMs in pancreatic cancer tissues versus normal tissues. Gene expression was assessed in five cohorts of patients by reverse transcription quantitative-PCR. Molecular analysis and functional assays were conducted in genetically modified cell lines. Cellular metabolic rates were measured using an XF24-3 Analyzer, while quantitative evaluation of lipids was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Subcutaneous xenograft mouse models were used to evaluate pancreatic tumour growth in vivo.RESULTS: We define a new antitumorous function of the histone lysine (K)-specific methyltransferase 2D (KMT2D) in pancreatic cancer. KMT2D is transcriptionally repressed in human pancreatic tumours through DNA methylation. Clinically, lower levels of this methyltransferase associate with poor prognosis and significant weight alterations. RNAi-based genetic inactivation of KMT2D promotes tumour growth and results in loss of H3K4me3 mark. In addition, KMT2D inhibition increases aerobic glycolysis and alters the lipidomic profiles of pancreatic cancer cells. Further analysis of this phenomenon identified the glucose transporter SLC2A3 as a mediator of KMT2D-induced changes in cellular, metabolic and proliferative rates.CONCLUSION: Together our findings define a new tumour suppressor function of KMT2D through the regulation of glucose/fatty acid metabolism in pancreatic cancer.
Surgery Provides Long-Term Survival in Patients with Metastatic Neuroendocrine Tumors Undergoing Resection for Non-Hormonal Symptoms. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Chakedis, J., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F. G., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Marincola-Smith, P., Cho, C., Beems, M., Pawlik, T. M., Maithel, S. K., Schmidt, C. R., Dillhoff, M. 2018
INTRODUCTION: Patients with metastatic neuroendocrine tumor (NET) often have an indolent disease course yet the outcomes for patients with metastatic NET undergoing surgery for non-hormonal (NH) symptoms of GI obstruction, bleeding, or pain is not known.METHODS: We identified patients with metastatic gastroenteropancreatic NET who underwent resection from 2000 to 2016 at 8 academic institutions who participated in the US Neuroendocrine Tumor Study Group.RESULTS: Of 581 patients with metastatic NET to liver (61.3%), lymph nodes (24.1%), lung (2.1%), and bone (2.5%), 332 (57.1%) presented with NH symptoms of pain (n=223, 67.4%), GI bleeding (n=54, 16.3%), GI obstruction (n=49, 14.8%), and biliary obstruction (n=22, 6.7%). Most patients were undergoing their first operation (85.4%) within 4weeks of diagnosis. The median overall survival was 110.4months, and operative intent predicted survival (p<0.001) with 66.3% undergoing curative resection. Removal of all metastatic disease was associated with the longest median survival (112.5months) compared to debulking (89.2months), or palliative resection (50.0months; p<0.001). The 1-, 3-, and 12-month mortality was 3.0%, 4.5%, and 9.0%, respectively. Factors associated with 1-year mortality included palliative operations (OR 6.54, p=0.006), foregut NET (5.62, p=0.042), major complication (4.91, p=0.001), and high tumor grade (11.2, p<0.001). The conditional survival for patients who lived past 1year was 119months.CONCLUSIONS: Patients with metastatic NET and NH symptoms that necessitate surgery have long-term survival, and goals of care should focus on both oncologic and quality of life impact. Surgical intervention remains a critical component of multidisciplinary care of symptomatic patients.
The prognostic significance of adrenocortical carcinomas identified incidentally. Journal of surgical oncology Rossfeld, K. K., Maithel, S. K., Prescott, J., Wang, T. S., Fields, R. C., Weber, S. M., Sicklick, J. K., Yopp, A. C., Duh, Q., Solorzano, C. C., Votanopoulos, K. I., Hatzaras, I., Poultsides, G. A., Shirley, L. A., and the U.S. Adrenocortical Carcinoma Study Group,, 2018
BACKGROUND AND OBJECTIVES: Little is known regarding the difference in prognosis among patients who have an incidentally discovered adrenocortical carcinoma (ACC)vs those who present with signs or symptoms. We aimed to explore differences in the outcomes of these two populations.METHODS: Data were collected on patients who underwent resection of ACC at 1 of 13 institutions between January 1993 and December 2014. Presentations were categorized as incidental vs symptomatic and outcomes were compared.RESULTS: Among 227 patients, 100 were diagnosed incidentally while 127 patients presented with symptoms/signs. Clinical and pathological features were comparable among incidental vs nonincidental patients with ACC following the exceptions. Patients with incidentalomas were more likely to have a T1/T2 tumor (55.8% vs 34.8%; P<0.01) and less likely to have a functional tumor (33.7% vs 47.9%; P=0.04). Patients with an incidental ACC had improved median recurrence-free survival (RFS; 29.4 months) compared with patients with a nonincidental ACC (13.0 months; P=0.03); however, on multivariable analysis, incidental ACC was not an independent predictor of survival.CONCLUSIONS: Patients with resected ACC identified incidentally had an improved RFS compared with the patients who presented with symptoms or signs. This difference may be related to the patients with incidental tumors having earlier T-stage disease.
ASO Author Reflections: Fluorescent-Guided Surgery to Augment Pancreatic Cancer Surgery. Annals of surgical oncology Tummers, W. S., Rosenthal, E. L., Vahrmeijer, A. L., Poultsides, G. P. 2018
Perioperative Management in Hepatic Resections: Comparative Effectiveness of Neuraxial Anesthesia and Disparity of Care Patterns ANESTHESIA AND ANALGESIA Zerillo, J., Agarwal, P., Poeran, J., Zubizarreta, N., Poultsides, G., Schwartz, M., Memtsoudis, S., Mazumdar, M., DeMaria, S. 2018; 127 (4): 855–63
Complication rates after hepatic resection can be affected by management decisions of the hospital care team and/or disparities in care. This is true in many other surgical populations, but little study has been done regarding patients undergoing hepatectomy.Data from the claims-based national Premier Perspective database were used for 2006 to 2014. The analytical sample consisted of adults undergoing partial hepatectomy and total hepatic lobectomy with anesthesia care consisting of general anesthesia (GA) only or neuraxial and GA (n = 9442). The key independent variable was type of anesthesia that was categorized as GA versus GA + neuraxial. The outcomes examined were clinical complications and health care resource utilization. Unadjusted bivariate and adjusted multivariate analyses were conducted to examine the effects of the different types of anesthesia on clinical complications and health care resource utilization after controlling for patient- and hospital-level characteristics.Approximately 9% of patients were provided with GA + neuraxial anesthesia during hepatic resection. In multivariate analyses, no association was observed between types of anesthesia and clinical complications and/or health care utilization (eg, admission to intensive care unit). However, patients who received blood transfusions were significantly more likely to have complications and intensive care unit stays. In addition, certain disparities of care, including having surgery in a rural hospital, were associated with poorer outcomes.Neuraxial anesthesia utilization was not associated with improvement in clinical outcome or cost among patients undergoing hepatic resections when compared to patients receiving GA alone. Future research may focus on prospective data sources with more clinical information on such patients and examine the effects of GA + neuraxial anesthesia on various complications and health care resource utilization.
Serum tumor markers enhance the predictive power of the AJCC and LCSGJ staging systems in resectable intrahepatic cholangiocarcinoma HPB Sasaki, K., Margonis, G. A., Andreatos, N., Chen, Q., Barbon, C., Bagante, F., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Endo, I., Aucejo, F. N., Pawlik, T. M. 2018; 20 (10): 956–65
While several prognostic models have been developed to predict long-term outcomes in resectable intrahepatic cholangiocarcinoma (ICC), their prognostic discrimination remains limited. The addition of tumor markers might improve the prognostic power of the classification schemas proposed by the AJCC 8th edition and the Liver Cancer Study Group of Japan (LCSGJ).The prognostic discrimination of the AJCC and the LCSGJ were compared before and after the addition of CA 19-9 and CEA, using Harrell's C-index, net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) in an international, multi-institutional cohort.Eight hundred and five surgically treated patients with ICC that met the inclusion criteria were identified. On multivariable analysis, CEA5 ng/mL, 100IU/mL CA 19-9< 500IU/mL and CA 19-9500 IU/mL were associated with worse overall survival. The C-index of the AJCC and the LCSGJ improved from 0.540 to 0.626 and 0.553 to 0.626, respectively following incorporation of CA 19-9 and CEA. The NRI and IDI metrics confirmed the superiority of the modified AJCC and LCSGJ, compared to the original versions.The inclusion of preoperative CA 19-9 and CEA in the AJCC and LCSGJ staging schemas may improve prognostic discrimination among surgically treated patients with ICC.
Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor after curative resection: Results from the US Neuroendocrine Tumor Study Group. Surgery Zhang, X., Wu, Z., Cloyd, J., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Schmidt, C. R., Dillhoff, M., Maithel, S. K., Pawlik, T. M. 2018
BACKGROUND: The impact of margin status on resection of primary pancreatic neuroendocrine tumors has been poorly defined. The objectives of the present study were to determine the impact of margin status on long-term survival of patients with pancreatic neuroendocrine tumors after curative resection and evaluate the impact of reresection to obtain a microscopically negative margin.METHODS: Patients who underwent curative-intent resection for pancreatic neuroendocrine tumors between 2000 and 2016 were identified at 8 hepatobiliary centers. Overall and recurrence-free survival were analyzed relative to surgical margin status using univariable and multivariable analyses.RESULTS: Among 1,020 patients, 866 (84.9%) had an R0 (>1 mm margin) resection, whereas 154 (15.1%) had an R1 (≤1 mm margin) resection. R1 resection was associated with a worse recurrence-free survival (10-year recurrence-free survival, R1 47.3% vs R0 62.8%, hazard ratio 1.8, 95% confidence interval 1.2-2.7, P = .002); residual tumor at either the transection margin (R1t) or the mobilization margin (R1m) was associated with increased recurrence versus R0 (R1t versus R0: hazard ratio 1.8, 95% confidence interval 1.0-3.0, P = .033; R1m versus R0: hazard ratio 1.3, 95% confidence interval 1.0-1.7, P = .060). In contrast, margin status was not associated with overall survival (10-year overall survival, R1 71.1% vs R0 71.8%, P = .392). Intraoperatively, 539 (53.6%) patients had frozen section evaluation of the surgical margin; 49 (9.1%) patients had a positive margin on frozen section analysis; 38 of the 49 patients (77.6%) had reresection, and a final R0 (secondary R0) margin was achieved in 30 patients (78.9%). Extending resection to achieve an R0 status remained associated with worse overall survival (hazard ratio 3.1, 95% confidence interval 1.6-6.2, P = .001) and recurrence-free survival (hazard ratio 2.6, 95% confidence interval 1.4-5.0, P = .004) compared with primary R0 resection. On multivariable analyses, tumor-specific factors, such as cellular differentiation, perineural invasion, Ki-67 index, and major vascular invasion, rather than surgical margin, were associated with long-term outcomes.CONCLUSION: Margin status was not associated with long-term survival. The reresection of an initially positive surgical margin to achieve a negative margin did not improve the outcome of patients with pancreatic neuroendocrine tumors. Parenchymal-sparing pancreatic procedures for pancreatic neuroendocrine tumors may be appropriate when feasible.
A novel, simplified, externally validated staging system for truncal/extremity soft tissue sarcomas: An analysis of the US Sarcoma Collaborative database. Journal of surgical oncology Johnson, A. C., Ethun, C. G., Liu, Y., Poultsides, G., Howard, J. H., Bedi, M., Charlson, J., Tseng, J., Roggin, K. K., Votanopoulos, K., Cullinan, D., Fields, R. C., Maithel, S. K., Cardona, K., and other members of the US Sarcoma Collaborative 2018
BACKGROUND: The 8th edition AJCC staging system for truncal/extremity soft tissue sarcoma (STS) offers significant changes from the 7th. However the complexity of both limits their clinical utility.METHODS: Patients with truncal/extremity STS undergoing resection from 2000 to 2016 at seven institutions of the US Sarcoma Collaborative were analyzed. The proposed staging system was externally validated using the National Cancer Database (NCDB).RESULTS: Of 1318 patients, mean age was 59 years, and 54% were male. Median tumor size was 9cm; 72% were high grade. Applying 8th edition staging, there was no differentiation between stages IA/IB ( P=0.92), and clinically similar outcomes between stages II/IIIA. Receiver operating characteristic (ROC) analysis identified 7.5cm as the ideal tumor size discriminating 5-year OS for high-grade tumors. Therefore, a simplified staging system defining all low-grade tumors as stage I, high-grade<7.5cm as stage II, high-grade>7.5cm as stage III, and metastatic disease as stage IV improved stratification (all P<0.05). The C-statistic was noninferior to the 8th edition. External validation in the NCDB confirmed optimal stratification (all P<0.01).CONCLUSIONS: Our proposed staging system maintains prognostic significance between stages within a simplified system. For high-grade tumors, a cutoff of 7.5cm, instead of 5cm, maintains discrimination for survival and could be a more clinically applicable cutoff for future clinical trials.
Early recurrence of well-differentiated (G1) neuroendocrine liver metastasis after curative-intent surgery: Risk factors and outcome. Journal of surgical oncology Xiang, J., Zhang, X., Weiss, M., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S. K., Marques, H. P., Pawlik, T. M. 2018
BACKGROUND: The objective of the current study was to identify the risk of early vs late recurrence of well-differentiated (G1) neuroendocrine liver metastasis (NELM) after curative-intent resection.METHODS: Patients who underwent curative-intent resection for well-differentiated NELM were identified from a multi-institutional database. Clinicopathological details, as well as the long-term overall (OS) and recurrence free survival (RFS) were obtained and compared. The optimal cutoff value to differentiate early and late recurrence was determined to be 1 year based on trend curve analysis.RESULTS: Among the 548 patients undergoing curative resection for NELM, 162 patients had a well-differentiated NELM. After a median follow-up of 69 months, 59 (36.4%) patients had tumor recurrence; 23 (39.0%) patients recurred within 1 year (early recurrence) after surgery, while 36 (61.0%) recurred after 1 year (late recurrence). Early recurrence was associated with worse outcome vs late recurrence (5-year OS, 72.4% vs 92.0%; P=0.020) and no recurrence (5-year OS, 72.4% vs 100.0%; P<0.001). In addition, postrecurrence survival was worse within 36 months after recurrence among patients who recurred early compared with patients who recurred late (survival after recurrence at 36 months: early recurrence, 71.6% vs late recurrence, 91.4%; P=0.047), although survival was comparable at 60 months (early recurrence, 71.6% vs late recurrence, 70.0%; P=0.304). On multivariable analysis, nonfunctional neuroendocrine tumors (hazard ratio [HR], 4.4; 95% confidence interval [CI], 1.2-16.7; P=0.029) and lymph node metastasis (HR, 3.6; 95% CI, 1.1-11.1; P=0.028) were independent risk factors for early recurrence, whereas lymph node metastasis (HR, 3.0; 95% CI, 1.2-7.8; P=0.020) and R1 resection (HR, 3.9; 95% CI, 1.4-10.5; P=0.008) were independently associated with late recurrence.CONCLUSIONS: Roughly, one-third of patients with well-differentiated NELM experienced a recurrence following curative-intent surgery. Among patients who recurred, two out of five patients recurred within 1 year after surgery. Early recurrence of well-differentiated NELM was associated with the hormone functional status and lymph node metastasis.
The prognosis of colorectal cancer liver metastases associated with inflammatory bowel disease: An exploratory analysis. Journal of surgical oncology Margonis, G. A., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Galjart, B., Kamphues, C., Pawlik, T. M., Poultsides, G., Kaczirek, K., Lonning, P. E., Verhoef, C., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2018
BACKGROUND AND OBJECTIVES: In contrast with sporadic colorectal cancer liver metastases (CRLM), inflammatory bowel disease (IBD)-related CRLM have not been studied to date.METHODS: Patients who underwent resection for IBD-related and sporadic CRLM from 2000 to 2015 were identified from an international registry and matched for pertinent prognostic variables. Overall survival (OS) and recurrence-free survival (RFS) were subsequently assessed.RESULTS: Twenty-eight patients had IBD-related CRLM. Synchronous extrahepatic disease was more common in IBD-related CRLM patients than patients with sporadic CRLM (28.6% vs 8.3%; P<0.001), most commonly located in the lungs. In multivariable analysis, IBD did not have a significant influence on OS ( P=0.835), and had a hazard ratio (HR) close to 1 (HR, 0.95; 95% confidence interval [CI], 0.57-1.57). IBD was also not associated with inferior RFS (HR, 1.07; 95%CI, 0.68-1.68; P=0.780). Among patients with IBD-related CRLM, 9(50%) had isolated intrahepatic recurrence and 8(44.4%) isolated extrahepatic recurrence, while only 1(5.6%) developed combined recurrence. Of those who experienced recurrence after resection of IBD-related CRLM, 10 had their recurrence treated with curative intent.CONCLUSIONS: Patients with IBD-related CRLM had similar survival compared with patients with sporadic CRLM, even though they more often present with extrahepatic disease. In addition, patients with IBD-related CRLM may experience patterns of recurrence different from patients with sporadic CRLM.
Defining Early Recurrence of Hilar Cholangiocarcinoma After Curative-intent Surgery: A Multi-institutional Study from the US Extrahepatic Biliary Malignancy Consortium WORLD JOURNAL OF SURGERY Zhang, X., Beal, E. W., Chakedis, J., Chen, Q., Lv, Y., Ethun, C. G., Salem, A., Weber, S. M., Tran, T., Poultsides, G., Son, A. Y., Hatzaras, I., Jin, L., Fields, R. C., Buettner, S., Scoggins, C., Martin, R. G., Isom, C. A., Idrees, K., Mogal, H. D., Shen, P., Maithel, S. K., Schmidt, C. R., Pawlik, T. M. 2018; 42 (9): 2919–29
Time to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection.A total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA. Data on clinicopathologic characteristics, pre-, intra-, and postoperative details and overall survival (OS) were analyzed. The slope of the curves identified by linear regression was used to categorize recurrences as early versus late.With a median follow-up of 18.0 months, 99 (44.0%) patients experienced a tumor recurrence. According to the slope of the curves identified by linear regression, the functions of the two straight lines were y = -0.465x + 16.99 and y = -0.12x + 7.16. The intercept value of the two lines was 28.5 months, and therefore, 30 months (2.5 years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority (n = 80, 80.8%) occurred within the first 2.5 years (early recurrence), while 19.2% of recurrences occurred beyond 2.5 years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, p = 0.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4 months, p < 0.001). On multivariable analysis, poor tumor differentiation (HR 10.3, p = 0.021), microvascular invasion (HR 3.3, p = 0.037), perineural invasion (HR 3.9, p = 0.029), lymph node metastases (HR 5.0, p = 0.004), and microscopic positive margin (HR 3.5, p = 0.046) were independent risk factors associated with early recurrence.Early recurrence of HCCA after curative resection was common (~35.6%). Early recurrence was strongly associated with aggressive tumor characteristics, increased risk of distant metastatic recurrence and a worse long-term survival.
Preoperative prognostic nutritional index predicts survival of patients with intrahepatic cholangiocarcinoma after curative resection JOURNAL OF SURGICAL ONCOLOGY Akguel, O., Bagante, F., Olsen, G., Cloyd, J. M., Weiss, M., Merath, K., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2018; 118 (3): 422–30
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy. We sought to examine the association between preoperative prognostic nutritional index (PNI) and long-term overall survival among patients with ICC who underwent curative-intent resection.Patients who underwent hepatectomy for ICC between 1990 and 2015 were identified using an international multi-institutional database. Clinic-pathological characteristics and long-term outcomes of patients with PNI ≥ 40 and <40 were compared using univariable and multivariable analyses.Among 637 patients, 53 patients had PNI < 40 (8.3%) and 584 patients had PNI ≥ 40 (91.7%). While there was no difference between PNI groups with regard to tumor size (P = .87), patients with PNI < 40 were more likely to have multifocal disease (PNI < 40, n = 16, 30.2% vs PNI ≥ 40, n = 65, 11.1%; P < 0.001), poorly differentiated or undifferentiated ICC (PNI < 40, n = 13, 25.5% vs PNI ≥ 40, n = 75, 13.1%; P = 0.020) and T2/T3/T4 disease vs patients with PNI ≥ 40 (PNI < 40, n = 38, 71.7% vs PNI ≥ 40, n = 265, 45.4%; P < 0.001). Patients with PNI ≥ 40 had better OS vs patients with PNI < 40 (5-year OS: PNI ≥ 40: 47.5%, 95% CI, 42.2 to 52.6% vs PNI < 40: 24.6%, 95% CI, 12.1 to 39.6%; P < 0.001). On multivariable analysis, PNI < 40 remained associated with increase risk of death (HR, 1.71; 95% CI, 1.15 to 2.53; P = 0.008).A low preoperative PNI was associated with a more aggressive ICC phenotype. After controlling for these factors, PNI remained independently associated with a markedly worse prognosis.
Circulating tumor DNA (ctDNA) in B-cell lymphoma Scherer, F., Kurtz, D. M., Newman, A. M., Stehr, H., Craig, A. M., Esfahani, M. S., Lovejoy, A. F., Chabon, J. J., Klass, D. M., Green, M. R., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G. A., Advani, R. H., Maeda, L. S., Gupta, N. K., Davis, R., Levy, R., Ohgami, R. S., Kunder, C. A., Rossi, D., Westin, J., Diehn, M., Alizadeh, A. A. WILEY. 2018: 16–17
The impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio among patients with intrahepatic cholangiocarcinoma Buettner, S., Spolverato, G., Kimbrough, C. W., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T., Maithel, S. K., Pulitano, C., Weiss, M., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J., IJzermans, J. M., Koerkamp, B., Pawlik, T. M. MOSBY-ELSEVIER. 2018: 411–18
Neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio may be host factors associated with prognosis. We sought to determine whether neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio were associated with overall survival among patients undergoing surgery for intrahepatic cholangiocarcinoma.Patients who underwent resection for intrahepatic cholangiocarcinoma between 1990 and 2015 were identified from 12 major centers. Clinicopathologic factors and overall survival were compared among patients stratified by neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio. Risk factors identified on multivariable analysis were included in a prognostic model and the discrimination was assessed using Harrell's concordance index (C index).A total of 991 patients were identified. Median neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio were 2.7 (interquartile range [IQR]: 2.0-4.0) and 109.6 (IQR: 72.4-158.8), respectively. Preoperative neutrophil-to-lymphocyte ratio was elevated (≥5) in 100 patients (10.0%) and preoperative platelets-to-lymphocyte ratio (≥190) in 94 patients (15.2%). Patients with low and high neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio generally had similar baseline characteristics with regard to tumor characteristics. Overall survival was 37.7 months (95% confidence interval [CI]: 32.7-42.6); 1-, 3-, and 5-year overall survival was 78.8%, 51.6%, and 39.3%, respectively. Patients with an neutrophil-to-lymphocyte ratio <5 had a median survival of 47.1 months (95% CI: 37.9-53.3) compared with a median survival of 21.9 months (95% CI: 4.8-39.1) among patients with an neutrophil-to-lymphocyte ratio ≥5 (P = .001). In contrast, patients who had a platelets-to-lymphocyte ratio <190 vs platelets-to-lymphocyte ratio ≥190 had comparable long-term survival (P > .05). On multivariable analysis, an elevated neutrophil-to-lymphocyte ratio was independently associated with decreased overall survival (hazard ratio: 1.04, 95% CI: 1.01-1.07; P = .002). Patients could be stratified into low- versus high-risk groups based on standard tumor-specific factors such as lymph node status, tumor size, number, and vascular invasion (C index 0.62). When neutrophil-to-lymphocyte ratio was added to the prognostic model, the discriminatory ability of the model improved (C index 0.71).Elevated neutrophil-to-lymphocyte ratio was independently associated with worse overall survival and improved the prognostic estimation of long-term survival among patients with intrahepatic cholangiocarcinoma undergoing resection.
Studying a Rare Disease Using Multi-Institutional Research Collaborations vs Big Data: Where Lies the Truth? JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Johnson, A. C., Ethun, C. G., Liu, Y., Lopez-Aguiar, A. G., Tran, T. B., Poultsides, G., Grignol, V., Howard, J., Bedi, M., Gamblin, T., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Cullinan, D., Fields, R. C., Delman, K. A., Wood, W. C., Cardona, K., Maithel, S. K. 2018; 227 (3): 357-+
Multi-institutional collaborations provide granularity lacking in epidemiologic data sets to enable in-depth study of rare diseases. For patients with superficial, high-grade soft tissue sarcomas of the trunk and extremity, the value of radiation therapy (RT) is not clear. We aimed to use the 7-institution US Sarcoma Collaborative (USSC) and the National Cancer Database (NCDB) to investigate this issue.All adult patients with superficial truncal and extremity high-grade soft tissue sarcomas who underwent primary curative-intent resection from 2000 to 2016 at USSC institutions or were included in the NCDB from 2004 to 2013 were analyzed. Propensity score matching was performed. End points were locoregional recurrence-free survival (LRFS), overall survival (OS), and disease-specific survival (DSS).Of 4,153 patients in the USSC, 169 patients with superficial high-grade tumors underwent primary curative-intent resection, 38% of which received RT. On multivariable Cox-regression analysis, RT was not associated with improved LRFS (p = 0.56), OS (p = 0.31), or DSS (p = 0.20). On analysis of 51 propensity score-matched pairs, RT was still not associated with increased LRFS, OS, or DSS. Analysis of 631 propensity score-matched pairs in the NCDB demonstrated improved 5-year OS rate associated with RT (80% vs 70%; p = 0.02). The LRFS and DSS rates were not evaluable.Granular data afforded by collaborative research enables in-depth analysis of patient outcomes. The NCDB, although powered with large numbers, cannot assess many relevant outcomes (eg recurrence, DSS, or complications). In this study, the approaches yielded conflicting results. The USSC data suggested no value of radiation and the NCDB demonstrated improved OS, contradicting all randomized controlled trials in sarcoma. The pros and cons of either approach must be considered when applying results to clinical practice, and underscore the importance of randomized controlled trials.
Role of Additional Organ Resection in Adrenocortical Carcinoma: Analysis of 167 Patients from the US Adrenocortical Carcinoma Database ANNALS OF SURGICAL ONCOLOGY Smith, P., Kiernan, C. M., Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J., Pawlik, T., Wang, T. S., Glenn, J., Hatzaras, I., Shenoy, R., Phay, J., Shirley, L. A., Fields, R. C., Jin, L., Weber, S., Salem, A., Sicklick, J., Gad, S., Yopp, A., Mansour, J., Duh, Q., Seiser, N., Votanopoulos, K., Levine, E. A., Poultsides, G., Solorzano, C. C. 2018; 25 (8): 2308–15
Adrenocortical carcinoma (ACC) is a rare and aggressive cancer. This report describes factors and outcomes associated with resection of extra-adrenal organs en bloc during index adrenalectomy.Patients who underwent ACC resection for non-metastatic disease from 1993 to 2014 at 13 participating institutions of the US-ACC Group were included in the study. Factors associated with en bloc resection were assessed by uni- and multivariate analysis. The primary end point was overall survival.In this study, 167 patients were included and categorized as adrenalectomy with en bloc resection (AdEBR) if they had extra-adrenal organs removed or adrenalectomy (Ad) if they did not. The demographics were similar between the AdEBR (n = 68, 40.7%) and Ad groups, including age, gender, race, American Society of Anesthesiology (ASA) class, and body mass index (BMI). The AdEBR group had larger tumors (13 vs. 10 cm), more open operations (97.1 vs. 63.6%), and more lymph node dissections (LNDs) (36.8 vs. 12.1%). The most common organs removed were kidney (55.9%), liver (27.9%), and spleen (23.5%). Multiple organs were removed in 38.2% (n = 26) of the patients. Margin-negative resections were similar between the two groups. In the multivariate Cox regression adjusted for T and N stages, LND, margin, size, and hormone hypersecretion, en bloc resection was not associated with improved survival (hazard ratio [HR], 1.42; p = 0.323).The study findings validated current practice by showing that en bloc resection should occur at index adrenalectomy for ACC when a T4 lesion is suspected pre- or intraoperatively, or when it is necessary to avoid tumor rupture. However, in this study, when a negative margin resection was otherwise achieved, removal of extra-adrenal organs en bloc was not associated with additional survival benefit.
Surgical Management of Intrahepatic Cholangiocarcinoma in Patients with Cirrhosis: Impact of Lymphadenectomy on Peri-Operative Outcomes WORLD JOURNAL OF SURGERY Bagante, F., Spolverato, G., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Ruzzenente, A., Pawlik, T. M. 2018; 42 (8): 2551–60
The consequences of lymphadenectomy (LND) on cirrhotic patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) have not been investigated. We sought to analyze the impact of LND on morbidity among patients undergoing resection for ICC.A total of 1005 patients who underwent hepatectomy for ICC at one of the 14 participating institutions between 1990 and 2015 were identified. A propensity score match analysis was performed to reduce confounding biases between cirrhosis and non-cirrhosis groups.Cirrhosis was diagnosed in 118 (11.7%) patients. Among non-cirrhotic patients, 63% underwent major liver resection versus only 20% among patients with cirrhosis (p < 0.001). LND was also less common among cirrhotic versus non-cirrhotic patients (19 vs. 50%, p < 0.001). The incidence of complications was 41 and 30% among patients who did not and did have cirrhosis, respectively (p = 0.022). The propensity-matched cohort included 150 patients. The incidence of complications was 71% among patients who underwent lymphadenectomy versus 23% among patients who did not undergo lymphadenectomy (OR 8.39) (p < 0.001). In the propensity-matched analysis, the median HLN was comparable among patients independent of cirrhosis status (median HLN: non-cirrhosis, 2.5 vs. cirrhosis, 2) (p = 0.95). While lymphadenectomy was associated with a higher risk of infections (non-cirrhosis, 0% vs. cirrhosis, 21%, p < 0.001) among patients with cirrhosis, infections were not associated with lymphadenectomy among non-cirrhotic patients (p = 0.19).Lymphadenectomy was associated with an increased risk of complications among patients with cirrhosis undergoing surgery for ICC. The benefit of lymphadenectomy in cirrhotic patients should be considered in light of the higher risk of postoperative complications compared with non-cirrhotic patients.
Monitoring Gastric Myoelectric Activity After Pancreaticoduodenectomy for Diet "Readiness". American journal of physiology. Gastrointestinal and liver physiology Dua, M. M., Navalgund, A., Axelrod, S., Axelrod, L., Worth, P. J., Norton, J. A., Poultsides, G. A., Triadafilopoulos, G., Visser, B. C. 2018
INTRODUCTION: Post-operative delayed gastric emptying (DGE) is a frustrating complication of pancreaticoduodenectomy (PD). We studied whether monitoring of post-operative gastric motor activity using a novel wireless patch system can identify patients at risk for DGE.METHODS: Eighty-one patients were prospectively studied since 2016; 75 patients were analyzed for this study. After PD, battery-operated wireless patches (G-Tech Medical) that acquire gastrointestinal myoelectrical signals are placed on the abdomen and transmit data by Bluetooth. Patients were divided into EARLY and LATE groups, by diet tolerance of 7 days (ERAS goal). Subgroup analysis was done of patients included after ERAS initiation.RESULTS: The EARLY and LATE groups had 50 and 25 patients, respectively, with length of stay (LOS) 7 and 11 days (p<0.05). Nasogastric insertion was required in 44% of the LATE group. Tolerance of food was noted by 6 vs 9 days in the EARLY vs LATE group (p<0.05) with higher cumulative gastric myoelectrical activity. Diminished gastric myoelectrical activity accurately identified delayed tolerance to regular diet in a logistical regression analysis (area under the curve (AUC), 0.81; 95% CI, 0.74-0.92). The gastric myoelectrical activity also identified delayed LOS status with an AUC of 0.75 (95% CI, 0.67-0.88). Stomach signal continued to be predictive in 90% of the ERAS cohort despite earlier oral intake.CONCLUSIONS: Measurement of gastric activity after PD can distinguish patients with shorter or longer times to diet. This non-invasive technology provides data to identify patients at risk for DGE and may guide timing of oral intake by gastric "readiness."
Association of BRAF Mutations With Survival and Recurrence in Surgically Treated Patients With Metastatic Colorectal Liver Cancer JAMA SURGERY Margonis, G., Buettner, S., Andreatos, N., Kim, Y., Wagner, D., Sasaki, K., Beer, A., Schwarz, C., Loes, I., Smolle, M., Kamphues, C., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P., Cameron, J. L., Burkhart, R. A., Gerger, A., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2018; 153 (7): e180996
BRAF mutations are reportedly associated with aggressive tumor biology. However, in contrast with primary colorectal cancer, the association of V600E and non-V600E BRAF mutations with survival and recurrence after resection of colorectal liver metastases (CRLM) has not been well studied.To investigate the prognostic association of BRAF mutations with survival and recurrence independently and compared with other prognostic determinants, such as KRAS mutations.In this cohort study, all patients who underwent resection for CRLM with curative intent from January 1, 2000, through December 31, 2016, at the institutions participating in the International Genetic Consortium for Colorectal Liver Metastasis and had data on BRAF and KRAS mutational status were retrospectively identified. Multivariate Cox proportional hazards regression models were used to assess long-term outcomes.Hepatectomy in patients with CRLM.The association of V600E and non-V600E BRAF mutations with disease-free survival (DFS) and overall survival (OS).Of 853 patients who met inclusion criteria (510 men [59.8%] and 343 women [40.2%]; mean [SD] age, 60.2 [12.4] years), 849 were included in the study analyses. Forty-three (5.1%) had a mutated (mut) BRAF/wild-type (wt) KRAS (V600E and non-V600E) genotype; 480 (56.5%), a wtBRAF/wtKRAS genotype; and 326 (38.4%), a wtBRAF/mutKRAS genotype. Compared with the wtBRAF/wtKRAS genotype group, patients with a mutBRAF/wtKRAS genotype more frequently were female (27 [62.8%] vs 169 [35.2%]) and 65 years or older (22 [51.2%] vs 176 [36.9%]), had right-sided primary tumors (27 [62.8%] vs 83 [17.4%]), and presented with a metachronous liver metastasis (28 [64.3%] vs 229 [46.8%]). On multivariable analysis, V600E but not non-V600E BRAF mutation was associated with worse OS (hazard ratio [HR], 2.76; 95% CI, 1.74-4.37; P < .001) and DFS (HR, 2.04; 95% CI, 1.30-3.20; P = .002). The V600E BRAF mutation had a stronger association with OS and DFS than the KRAS mutations (β for OS, 10.15 vs 2.94; β for DFS, 7.14 vs 2.27).The presence of the V600E BRAF mutation was associated with worse prognosis and increased risk of recurrence. The V600E mutation was not only a stronger prognostic factor than KRAS but also was the strongest prognostic determinant in the overall cohort.
Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging ANNALS OF SURGICAL ONCOLOGY Tummers, W. S., Miller, S. E., Teraphongphom, N. T., Gomez, A., Steinberg, I., Huland, D. M., Hong, S., Kothapalli, S., Hasan, A., Ertsey, R., Bonsing, B. A., Vahrmeijer, A. L., Swijnenburg, R., Longacre, T. A., Fisher, G. A., Gambhir, S. S., Poultsides, G. A., Rosenthal, E. L. 2018; 25 (7): 1880–88
Characterization of colorectal liver metastasis at single-cell resolution reveals dynamic interplay in the tumor microenvironment Sathe, A., Chen, J., Wood-Bouwens, C., Almeda, A., Lau, B., Grimes, S. M., Poultsides, G. A., Ji, H. AMER ASSOC CANCER RESEARCH. 2018
View details for DOI 10.1158/1538-7445.AM2018-2126
Integrated single-cell DNA and RNA analysis of intratumoral heterogeneity and immune lineages in colorectal and gastric tumor biopsies Lau, B., Andor, N., Sathe, A., Wood-Bouwens, C., Poultsides, G., Ji, H. AMER ASSOC CANCER RESEARCH. 2018
Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. Annals of surgical oncology Tummers, W. S., Miller, S. E., Teraphongphom, N. T., Gomez, A., Steinberg, I., Huland, D. M., Hong, S., Kothapalli, S., Hasan, A., Ertsey, R., Bonsing, B. A., Vahrmeijer, A. L., Swijnenburg, R., Longacre, T. A., Fisher, G. A., Gambhir, S. S., Poultsides, G. A., Rosenthal, E. L. 2018; 25 (7): 1880–88
BACKGROUND: Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor.METHODS: A dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50mg or 100mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo.RESULTS: Seven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09±0.06) versus surrounding normal pancreatic tissue (0.02±0.01), and pancreatitis (0.04±0.01; p<0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue.CONCLUSIONS: The safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.
Association of perioperative transfusion with survival and recurrence after resection of gallbladder cancer: A 10-institution study from the US Extrahepatic Biliary Malignancy Consortium JOURNAL OF SURGICAL ONCOLOGY Lopez-Aguiar, A. G., Ethun, C. G., McInnis, M. R., Pawlik, T. M., Poultsides, G., Thuy Tran, Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B. A., Weber, S. M., Salem, A., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Cardona, K., Maithel, S. K. 2018; 117 (8): 1638–47
Perioperative blood transfusion is associated with poor outcomes in several malignancies. Its effect in gallbladder cancer (GBC) is unknown.All patients with GBC who underwent curative-intent resection at 10-institutions from 2000 to 2015 were included. The effect of blood transfusion on overall survival (OS) and recurrence-free (RFS) was evaluated.Of 262 patients with curative-intent resection for GBC, 61 patients (23%) received blood transfusions. Radical cholecystectomy was the most common procedure (80%), but major hepatectomy was more frequent in the transfusion versus no-transfusion group (13% vs 4%; P = 0.02). The transfusion group was less likely to have incidentally discovered disease (57% vs 74%) and receive adjuvant therapy (29% vs 48%), but more likely to have preoperative jaundice (23% vs 11%), T3/T4 tumors (60% vs 39%), LVI (71% vs 40%), PNI (71% vs 48%), and major complications (39% vs 12%) (all P < 0.05). Transfusion was associated with lower median OS compared to no-transfusion (20 vs 32 mos; P < 0.001), which persisted on multivariable (MV) analysis (HR:1.9; 95%CI 1.1-3.5; P = 0.035), controlling for comorbidities, serum albumin, INR, preoperative jaundice, major hepatectomy, incidental discovery, margin status, T-Stage, LN status, and major complications. Median RFS of transfused patients was 13mo compared to 49mo for non-transfused patients (P = 0.1). Transfusion, however, was an independent predictor of decreased RFS on MV analysis (HR:2.3; 95%CI 1.1-5.1; P = 0.035).Perioperative blood transfusion is associated with decreased OS and RFS after resection for GCC, accounting for other adverse factors. Transfusions should thus be administered with well-defined protocols.
Clinical Trigonometry: Right Hepatic Trisegmentectomy After Radiation Trisegmentectomy for Hepatocellular Carcinoma DIGESTIVE DISEASES AND SCIENCES Titan, A. L., Devereaux, K., Louie, J. D., Poultsides, G. A. 2018; 63 (6): 1419–23
Perioperative and long-term outcome of intrahepatic cholangiocarcinoma involving the hepatic hilus after curative-intent resection: comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma SURGERY Zhang, X., Bagante, F., Chen, Q., Beal, E. W., Lv, Y., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2018; 163 (5): 1114–20
Intrahepatic cholangiocarcinoma with hepatic hilus involvement has been either classified as intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma. The present study aimed to investigate the clinicopathologic characteristics and short- and long-term outcomes after curative resection for hilar type intrahepatic cholangiocarcinoma in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.A total of 912 patients with mass-forming peripheral intrahepatic cholangiocarcinoma, 101 patients with hilar type intrahepatic cholangiocarcinoma, and 159 patients with hilar cholangiocarcinoma undergoing curative resection from 2000 to 2015 were included from two multi-institutional databases. Clinicopathologic characteristics and short- and long-term outcomes were compared among the 3 groups.Patients with hilar type intrahepatic cholangiocarcinoma had more aggressive tumor characteristics (eg, higher frequency of vascular invasion and lymph nodes metastasis) and experienced more extensive resections in comparison with either peripheral intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma patients. The odds of lymphadenectomy and R0 resection rate among patients with hilar type intrahepatic cholangiocarcinoma were comparable with hilar cholangiocarcinoma patients, but higher than peripheral intrahepatic cholangiocarcinoma patients (lymphadenectomy incidence, 85.1% vs 42.5%, P < .001; R0 rate, 75.2% vs 88.8%, P < .001). After curative surgery, patients with hilar type intrahepatic cholangiocarcinoma experienced a higher rate of technical-related complications compared with peripheral intrahepatic cholangiocarcinoma patients. Of note, hilar type intrahepatic cholangiocarcinoma was associated with worse disease-specific survival and recurrence-free survival after curative resection versus peripheral intrahepatic cholangiocarcinoma (median disease-specific survival, 26.0 vs 54.0 months, P < .001; median recurrence-free survival, 13.0 vs 18.0 months, P = .021) and hilar cholangiocarcinoma (median disease-specific survival, 26.0 vs 49.0 months, P = .003; median recurrence-free survival, 13.0 vs 33.4 months, P < .001).Mass-forming intrahepatic cholangiocarcinoma with hepatic hilus involvement is a more aggressive type of cholangiocarcinoma, which showed distinct clinicopathologic characteristics, worse long-term outcomes after curative resection, in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.
Diagnostic staging laparoscopy in gastric cancer treatment: A cost-effectiveness analysis JOURNAL OF SURGICAL ONCOLOGY Li, K., Cannon, J. D., Jiang, S. Y., Sambare, T. D., Owens, D. K., Bendavid, E., Poultsides, G. A. 2018; 117 (6): 1288–96
Double KRAS and BRAF Mutations in Surgically Treated Colorectal Cancer Liver Metastases: An International, Multi-institutional Case Series ANTICANCER RESEARCH Deshwar, A., Margonis, G., Andreatos, N., Barbon, C., Wang, J., Buettner, S., Wagner, D., Sasaki, K., Beer, A., Loes, I., Pikoulis, E., Damaskos, C., Garmpis, N., Kamphues, K., He, J., Kaczirek, K., Poultsides, G., Lonning, P., Mischinger, H., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weis, M. J. 2018; 38 (5): 2891–95
While previously believed to be mutually exclusive, concomitant mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS)- and V-raf murine sarcoma b-viral oncogene homolog B1 (BRAF)-mutated colorectal carcinoma (CRC), has been described in rare instances and been associated with advanced-stage disease. The present case series is the first to report on the implications of concurrent KRAS/BRAF mutations among surgically treated patients, and the largest set of patients with surgically treated colorectal liver metastasis (CRLM) and data on KRAS/BRAF mutational status thus far described.We present cases from an international, multi-institutional cohort of patients that underwent hepatic resection for CRLM between 2000-2015 at seven tertiary centers. The incidence of KRAS/BRAF mutation in patients with CRLM was 0.5% (4/820). Of these cases, patient 1 (T2N1 primary, G13D/V600E), patient 2 (T3N1 primary, G12V/V600E) and patient 3 (T4N2 primary, G13D/D594N) succumbed to their disease within 485, 236 and 79 days respectively, post-hepatic resection. Patient 4 (T4 primary, G12S/G469S) was alive 416 days after hepatic resection.The present case series suggests that the incidence of concomitant KRAS/BRAF mutations in surgical cohorts may be higher than previously hypothesized, and associated with more variable survival outcomes than expected.
Oncologic effects of preoperative biliary drainage in resectable hilar cholangiocarcinoma: Percutaneous biliary drainage has no adverse effects on survival JOURNAL OF SURGICAL ONCOLOGY Zhang, X., Beal, E. W., Merath, K., Ethun, C. G., Salem, A., Weber, S. M., Thuy Tran, Poultsides, G., Son, A. Y., Hatzaras, I., Jin, L., Fields, R. C., Weiss, M., Scoggins, C., Martin, R. G., Isom, C. A., Idrees, K., Mogal, H. D., Shen, P., Maithel, S. K., Schmidt, C. R., Pawlik, T. M. 2018; 117 (6): 1267–77
The objective of the current study was to define long-term survival of patients with resectable hilar cholangiocarcinoma (HCCA) after preoperative percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD).Between 2000 and 2014, 240 patients who underwent curative-intent resection for HCCA were identified at 10 major hepatobiliary centers. Postoperative morbidity and mortality, as well as disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed among patients.The median decrease in total bilirubin levels after biliary drainage was similar comparing PTBD (n = 104) versus EBD (n = 92) (mg/dL, 4.9 vs 4.9, P = 0.589) before surgery. There was no difference in baseline demographic characteristics, type of surgical procedure performed, final AJCC tumor stage or postoperative morbidity among patients who underwent EBD only versus PTBD (all P > 0.05). Patients who underwent PTBD versus EBD had a comparable long-term DSS (median, 43.7 vs 36.9 months, P = 0.802) and RFS (median, 26.7 vs 24.0 months, P = 0.571). The overall pattern of recurrence relative to regional or distant disease was also the same among patients undergoing PTBD and EBD (P = 0.669) CONCLUSIONS: Oncologic outcomes including DSS and RFS were similar among patients who underwent PTBD versus EBD with no difference in tumor recurrence location.
Transplantation Versus Resection for Hilar Cholangiocarcinoma An Argument for Shifting Treatment Paradigms for Resectable Disease Ethun, C. G., Lopez-Aguiar, A. G., Anderson, D. J., Adams, A. B., Fields, R. C., Doyle, M. B., Chapman, W. C., Krasnick, B. A., Weber, S. M., Mezrich, J. D., Salem, A., Pawlik, T. M., Poultsides, G., Tran, T. B., Idrees, K., Isom, C. A., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Cardona, K., Maithel, S. K. LIPPINCOTT WILLIAMS & WILKINS. 2018: 797–805
To investigate the influence of type of surgery (transplant vs resection) on overall survival (OS) in patients with hilar cholangiocarcinoma (H-CCA).Outcomes after resection for H-CCA are poor, yet transplantation is currently only reserved for well-selected patients with unresectable disease.All patients with H-CCA who underwent resection from 2000 to 2015 at 10 institutions were included. Three institutions additionally had active H-CCA transplant protocols with similar selection criteria over similar time periods.Of 304 patients with suspected H-CCA, 234 underwent attempted resection and 70 were enrolled in a transplant protocol. Excluding incomplete/R2 resections (n = 43), patients who were enrolled, but did not undergo transplant (n = 24), and transplants without confirmed H-CCA diagnoses (n = 5), 191 patients underwent curative-intent resection and 41 curative-intent transplant. Compared with resection, transplant patients were younger (52 vs 65 years; P < 0.001), and more frequently had primary sclerosing cholangitis (PSC; 61% vs 2%; P < 0.001) and received chemotherapy and/or radiation (98% vs 57%; P < 0.001). Groups were otherwise similar in demographics and comorbidities. Patients who underwent transplant for confirmed H-CCA diagnosis had improved OS compared with resection (3-year: 72% vs 33%; 5-year: 64% vs 18%; P < 0.001). Among patients who underwent resection for tumors <3 cm with lymph-node negative disease, and excluding PSC patients, transplant was still associated with improved OS (3-year: 54% vs 44%; 5-year: 54% vs 29%; P = 0.03). Transplant remained associated with improved survival on intention-to-treat analysis, even after accounting for tumor size, lymph node status, and PSC (P = 0.049).Resection for hilar cholangiocarcinoma that meets criteria for transplantation (<3 cm, lymph-node negative disease) is associated with substantially decreased survival compared to transplant for the same criteria with unresectable disease. Prospective trials are needed and justified.
The Impact of Intraoperative Re-Resection of a Positive Bile Duct Margin on Clinical Outcomes for Hilar Cholangiocarcinoma ANNALS OF SURGICAL ONCOLOGY Zhang, X., Squires, M. H., Bagante, F., Ethun, C. G., Salem, A., Weber, S. M., Thuy Tran, Poultsides, G., Son, A. Y., Hatzaras, I., Jin, L., Fields, R. C., Weiss, M., Scoggins, C., Martin, R. G., Isom, C. A., Idrees, K., Mogal, H. D., Shen, P., Maithel, S. K., Schmidt, C. R., Pawlik, T. M. 2018; 25 (5): 1140–49
The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA.Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status.Among 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p > 0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5 months and 7.9%, respectively, for patients with an R1 resection (p = 0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p = 0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0-1.7; p = 0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4-2.3; p = 0.829).Additional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA.
Nomogram predicting the risk of recurrence after curative-intent resection of primary non-metastatic gastrointestinal neuroendocrine tumors: An analysis of the US Neuroendocrine Tumor Study Group Merath, K., Bagante, F., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Schmidt, C. R., Dillhoff, M., Maithel, S. K., Pawlik, T. M. WILEY. 2018: 868–78
The risk of recurrence after resection of non-metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) is poorly defined. We developed/validated a nomogram to predict risk of recurrence after curative-intent resection.A training set to develop the nomogram and test set for validation were identified. The predictive ability of the nomogram was assessed using c-indices.Among 1477 patients, 673 (46%) were included in the training set and 804 (54%) in y the test set. On multivariable analysis, Ki-67, tumor size, nodal status, and invasion of adjacent organs were independent predictors of DFS. The risk of death increased by 8% for each percentage increase in the Ki-67 index (HR 1.08, 95% CI, 1.05-1.10; P < 0.001). GEP-NET invading adjacent organs had a HR of 1.65 (95% CI, 1.03-2.65; P = 0.038), similar to tumors ≥3 cm (HR 1.67, 95% CI, 1.11-2.51; P = 0.014). Patients with 1-3 positive nodes and patients with >3 positive nodes had a HR of 1.81 (95% CI, 1.12-2.87; P = 0.014) and 2.51 (95% CI, 1.50-4.24; P < 0.001), respectively. The nomogram demonstrated good ability to predict risk of recurrence (c-index: training set, 0.739; test set, 0.718).The nomogram was able to predict the risk of recurrence and can be easily applied in the clinical setting.
Clinicopathologic score predicting lymph node metastasis in T1 gastric cancer Tran, T. B., Worhunsky, D. J., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Weber, S. M., Schmidt, C., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Norton, J. A., Poultsides, G. A. MOSBY-ELSEVIER. 2018: 889–93
Prospective Evaluation of Results of Reoperation in Zollinger-Ellison Syndrome ANNALS OF SURGERY Norton, J. A., Krampitz, G. W., Poultsides, G. A., Visser, B. C., Fraker, D. L., Alexander, H., Jensen, R. T. 2018; 267 (4): 782–88
The impact of caudate lobe resection on margin status and outcomes in patients with hilar cholangiocarcinoma: a multi-institutional analysis from the US Extrahepatic Biliary Malignancy Consortium SURGERY Bhutiani, N., Scoggins, C. R., McMasters, K. M., Ethun, C. G., Poultsides, G. A., Pawlik, T. M., Weber, S. M., Schmidt, C. R., Fields, R. C., Idrees, K., Hatzaras, L., Shen, P., Maithel, S. K., Martin, R. G. 2018; 163 (4): 726–31
The objective of this study was to determine the impact of caudate resection on margin status and outcomes during resection of extrahepatic hilar cholangiocarcinoma.A database of 1,092 patients treated for biliary malignancies at institutions of the Extrahepatic Biliary Malignancy Consortium was queried for individuals undergoing curative-intent resection for extrahepatic hilar cholangiocarcinoma. Patients who did versus did not undergo concomitant caudate resection were compared with regard to demographic, baseline, and tumor characteristics as well as perioperative outcomes.A total of 241 patients underwent resection for a hilar cholangiocarcinoma, of whom 85 underwent caudate resection. Patients undergoing caudate resection were less likely to have a final positive margin (P = .01). Kaplan-Meier curve of overall survival for patients undergoing caudate resection indicated no improvement over patients not undergoing caudate resection (P = .16). On multivariable analysis, caudate resection was not associated with improved overall survival or recurrence-free survival, although lymph node positivity was associated with worse overall survival and recurrence-free survival, and adjuvant chemoradiotherapy was associated with improved overall survival and recurrence-free survival.Caudate resection is associated with a greater likelihood of margin-negative resection in patients with extrahepatic hilar cholangiocarcinoma. Precise preoperative imaging is critical to assess the extent of biliary involvement, so that all degrees of hepatic resections are possible at the time of the initial operation.
Preoperative Risk Score and Prediction of Long-Term Outcomes after Hepatectomy for Intrahepatic Cholangiocarcinoma Sasaki, K., Margonis, G. A., Andreatos, N., Bagante, F., Weiss, M., Barbon, C., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Aucejo, F. N., Pawlik, T. M. ELSEVIER SCIENCE INC. 2018: 393–405
Accurate prediction of prognosis for patients with intrahepatic cholangiocarcinoma (ICC) remains a challenge. We sought to define a preoperative risk tool to predict long-term survival after resection of ICC.Patients who underwent hepatectomy for ICC at 1 of 16 major hepatobiliary centers between 1990 and 2015 were identified. Clinicopathologic data were analyzed and a prognostic model was developed based on the regression β-coefficients on data in training set. The model was subsequently assessed using a validation set.Among 538 patients, most patients had a solitary tumor (median tumor number 1; interquartile range 1 to 2) and median tumor size was 5.7 cm (interquartile range 4.0 to 8.0 cm). Median and 5-year overall survival was 39.0 months and 39.0%, respectively. On multivariable analyses, preoperative factors associated with long-term survival included tumor size (hazard ratio [HR] 1.12; 95% CI 1.06 to 1.18), natural logarithm carbohydrate antigen 19-9 level (HR 1.33; 95% CI 1.22 to 1.45), albumin level (HR 0.76; 95% CI 0.55 to 0.99), and neutrophil to lymphocyte ratio (HR 1.05; 95% CI 1.02 to 1.09). A weighted composite prognostic score was constructed based on these factors: [9 + (1.12 × tumor size) + (2.81 × natural logarithm carbohydrate antigen 19-9) + (0.50 × neutrophil to lymphocyte ratio) + (-2.79 × albumin)]. The model demonstrated good performance in the testing (area under the curve 0.696) and validation (0.691) datasets. The model performed better than both the T categories (area under the curve 0.532) and the cumulative stage classifications in the American Joint Committee on Cancer staging manual, 8th edition (area under the curve 0.559). When assessing risk of death within 1 year of operation, a risk score ≥25 had a positive predictive value of 59.8% compared with a positive predictive value of 35.3% for American Joint Committee on Cancer staging manual, 8th edition T4 disease and 31.8% for stage IIIB disease.Postsurgical long-term outcomes could be predicted using a composite weighted scoring system based on preoperative clinical parameters. The preoperative risk model can be used to inform patient to provider conversations and expectations before operation.
Outcomes after vascular resection during curative-intent resection for hilar cholangiocarcinoma: a multi-institution study from the US extrahepatic biliary malignancy consortium Schimizzi, G. V., Jin, L. X., Davidson, J. T., Krasnick, B. A., Ethun, C. G., Pawlik, T. M., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Weber, S. M., Salem, A., Hawkins, W. G., Strasberg, S. M., Doyle, M. B., Chapman, W. C., Martin, R. G., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Fields, R. C. ELSEVIER SCI LTD. 2018: 332–39
Surgical resection is the cornerstone of curative-intent therapy for patients with hilar cholangiocarcinoma (HC). The role of vascular resection (VR) in the treatment of HC in western centres is not well defined.Utilizing data from the U.S. Extrahepatic Biliary Malignancy Consortium, patients were grouped into those who underwent resection for HC based on VR status: no VR, portal vein resection (PVR), or hepatic artery resection (HAR). Perioperative and long-term survival outcomes were analyzed.Between 1998 and 2015, 201 patients underwent resection for HC, of which 31 (15%) underwent VR: 19 patients (9%) underwent PVR alone and 12 patients (6%) underwent HAR either with (n = 2) or without PVR (n = 10). Patients selected for VR tended to be younger with higher stage disease. Rates of postoperative complications and 30-day mortality were similar when stratified by vascular resection status. On multivariate analysis, receipt of PVR or HAR did not significantly affect OS or RFS.In a modern, multi-institutional cohort of patients undergoing curative-intent resection for HC, VR appears to be a safe procedure in a highly selected subset, although long-term survival outcomes appear equivalent. VR should be considered only in select patients based on tumor and patient characteristics.
Clinicopathologic score predicting lymph node metastasis in T1 gastric cancer. Surgery Tran, T. B., Worhunsky, D. J., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Weber, S. M., Schmidt, C., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Norton, J. A., Poultsides, G. A. 2018; 163 (4): 889–93
BACKGROUND: Although gastrectomy with adequate regional nodal examination is considered the standard of care for invasive gastric adenocarcinoma, endoscopic resection has been adopted increasingly in select patients with T1 gastric cancer. The objective of this study was to identify preoperative predictors of lymph node metastasis in patients in the United States with T1 gastric cancer.METHODS: Patients who underwent operative resection for T1 gastric cancer between 2000 and 2012 were identified from a multi-institutional database. Clinicopathologic predictors of lymph node metastasis were determined using univariate and multivariate logistic regression. A preoperative score was created, assigning points based on each variable's regression coefficient.RESULTS: Among 835 patients with gastric cancer undergoing curative-intent surgical resection, 176 patients (20.5%) had T1 disease confirmed on final pathology. Of those, 38 patients (22%) had lymph node metastasis. Independent predictors of lymph node involvement on multivariate analysis were poor differentiation, T1b stage, lymphovascular invasion, and tumor size >2cm. A clinicopathologic risk score composed of these 4 variables was created. Receiver operating curve analysis showed excellent discrimination (area under the curve=0.79) and 100% sensitivity in detecting lymph node metastasis when only one of the aforementioned factors was present.CONCLUSIONS: In this cohort of U.S. patients with T1 gastric adenocarcinoma, the lack of lymph node involvement could be predicted by the absence of several unfavorable factors, including T stage, poor differentiation, lymphovascular invasion, and size >2cm.
Prospective Evaluation of Results of Reoperation in Zollinger-Ellison Syndrome. Annals of surgery Norton, J. A., Krampitz, G. W., Poultsides, G. A., Visser, B. C., Fraker, D. L., Alexander, H. R., Jensen, R. T. 2018; 267 (4): 782–88
OBJECTIVE: To determine the role of reoperation in patients with persistent or recurrent Zollinger-Ellison Syndrome (ZES).BACKGROUND: Approximately, 0% to 60% of ZES patients are disease-free (DF) after an initial operation, but the tumor may recur.METHODS: A prospective database was queried.RESULTS: A total of 223 patients had an initial operation for possible cure of ZES and then were subsequently evaluated serially with cross sectional imaging-computed tomography, magnetic resonance imaging, ultrasound, more recently octreoscan-and functional studies for ZES activity. The mean age at first surgery was 49 years and with an 11-year mean follow-up 52 patients (23%) underwent reoperation when ZES recurred with imageable disease. Results in this group are analyzed in the current report. Reoperation occurred on a mean of 6 years after the initial surgery with a mean number of reoperations of 1 (range 1-5). After reoperation 18/52 patients were initially DF (35%); and after a mean follow-up of 8 years, 13/52 remained DF (25%). During follow-up, 9/52 reoperated patients (17%) died, of whom 7 patients died a disease-related death (13%). The overall survival from first surgery was 84% at 20 years and 68% at 30 years. Multiple endocrine neoplasia type 1 status did not affect survival, but DF interval and liver metastases did.CONCLUSIONS: These results demonstrate that a significant proportion of patients with ZES will develop resectable persistent or recurrent disease after an initial operation. These patients generally have prolonged survival after reoperation and 25% can be cured with repeat surgery, suggesting all ZES patients postresection should have systematic imaging, and if tumor recurs, advise repeat operation.
Implications of Intrahepatic Cholangiocarcinoma Etiology on Recurrence and Prognosis after Curative-Intent Resection: a Multi-Institutional Study WORLD JOURNAL OF SURGERY Zhang, X., Chakedis, J., Bagante, F., Beal, E. W., Lv, Y., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2018; 42 (3): 849–57
We sought to investigate the prognosis of patients following curative-intent surgery for intrahepatic cholangiocarcinoma (ICC) stratified by hepatitis B (HBV-ICC), hepatolithiasis (Stone-ICC), and no identifiable cause (conventional ICC) etiologic subtype.986 patients with HBV-ICC (n = 201), stone-ICC (n = 103), and conventional ICC (n = 682) who underwent curative-intent resection were identified from a multi-institutional database. Propensity score matching (PSM) was used to mitigate residual bias.HBV-ICC patients more often had cirrhosis, earlier stage tumors, a mass-forming lesion, well-to-moderate tumor differentiation, and an R0 resection versus stone-ICC or conventional ICC patients. Five-year recurrence-free survival among HBV-ICC and conventional ICC patients was 23.9 and 17.8%, respectively, versus a recurrence-free of only 8.3% among patients with stone-ICC. Similarly, 5-year overall survival among patients with stone-ICC was only 18.3% compared with 48.9 and 38.0% for patients with HBV-ICC and conventional ICC, respectively. On PSM, patients with stone-ICC group had equivalent long-term outcomes as HBV-ICC patients. In contrast, on PSM, stone-ICC patients had a median overall survival of only 18.0 months versus 44.0 months for patients with conventional ICC. Median overall survival after intrahepatic-only recurrence among patients who had stone-ICC (6.0 months) was worse than OS among HBV-ICC (13.0 months) or conventional ICC (12.0 months) (p = 0.006 and p = 0.082, respectively).While HBV-ICC had a better prognosis on unadjusted analyses, these differences were mitigated on PSM suggesting no stage-for-stage differences in outcomes compared with stone-ICC or conventional ICC. In contrast, patients with stone-ICC had worse long-term outcomes. These data highlight the relative importance of ICC etiology relative to established clinicopathological factors in the prognosis of patients with ICC.
Incidence and Prognosis of Primary Gastrinomas in the Hepatobiliary Tract JAMA SURGERY Norton, J. A., Foster, D. S., Blumgart, L. H., Poultsides, G. A., Visser, B. C., Fraker, D. L., Alexander, H., Jensen, R. T. 2018; 153 (3): e175083
Accuracy of the ACS NSQIP Online Risk Calculator Depends on How You Look at It: Results from the United States Gastric Cancer Collaborative AMERICAN SURGEON Beal, E. W., Saunders, N. D., Kearney, J. F., Lyon, E., Wei, L., Squires, M. H., Jin, L. X., Worhunsky, D. J., Votanopoulos, K. I., Ejaz, A., Poultsides, G., Fields, R. C., Swords, D., Acher, A. W., Weber, S. M., Maithel, S. K., Pawlik, T., Schmidt, C. R. 2018; 84 (3): 358–64
The objective of this study is to assess the accuracy of the American College of Surgeons National Surgical Quality Improvement Program online risk calculator for estimating risk after operation for gastric cancer using the United States Gastric Cancer Collaborative. Nine hundred and sixty-five patients who underwent resection of gastric adenocarcinoma between January 2000 and December 2012 at seven academic medical centers were included. Actual complication rates and outcomes for patients were compared. Most of the patients underwent total gastrectomy with Roux-en-Y reconstruction (404, 41.9%) and partial gastrectomy with gastrojejunostomy (239, 24.8%) or Roux-en-Y reconstruction (284, 29.4%). The C-statistic was highest for venous thromboembolism (0.690) and lowest for renal failure at (0.540). All C-statistics were less than 0.7. Brier scores ranged from 0.010 for venous thromboembolism to 0.238 for any complication. General estimates of risk for the cohort were variable in terms of accuracy. Improving the ability of surgeons to estimate preoperative risk for patients is critically important so that efforts at risk reduction can be personalized to each patient. The American College of Surgeons National Surgical Quality Improvement Program risk calculator is a rapid and easy-to-use tool and validation of the calculator is important as its use becomes more common.
Adjuvant therapy is associated with improved survival after curative resection for hilar cholangiocarcinoma: A multi-institution analysis from the US extrahepatic biliary malignancy consortium JOURNAL OF SURGICAL ONCOLOGY Krasnick, B. A., Jin, L. X., Davidson, J. T., Sanford, D. E., Ethun, C. G., Pawlik, T. M., Poultsides, G. A., Thuy Tran, Idrees, K., Hawkins, W. G., Chapman, W. C., Doyle, M. M., Weber, S. M., Strasberg, S. M., Salem, A., Martin, R. G., Isom, C. A., Scoggins, C., Schmidt, C. R., Shen, P., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Fields, R. C. 2018; 117 (3): 363–71
Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection.We reviewed patients with resected HC between 2000 and 2015 from the ten institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium. We analyzed the impact of AT on RFS and OS. The probability of RFS and OS were calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis.A total of 249 patients underwent curative resection for HC. Patients who received AT and those who did not had similar demographic and preoperative features. In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.58, P = 0.013), and this was maintained in a propensity matched analysis (HR 0.66, P = 0.033). The protective effect of AT remained significant when node negative patients were excluded (HR 0.28, P = 0.001), while it disappeared (HR 0.76, P = 0.260) when node positive patients were excluded.AT should be strongly considered after curative-intent resection for HC, particularly in patients with node positive disease.
Cytoreductive debulking surgery among patients with neuroendocrine liver metastasis: a multi-institutional analysis HPB Ejaz, A., Reames, B. N., Maithel, S., Poultsides, G. A., Bauer, T. W., Fields, R. C., Weiss, M. J., Marques, H. P., Aldrighetti, L., Pawlik, T. M. 2018; 20 (3): 277–84
Management of neuroendocrine liver metastasis (NELM) in the setting of unresectable disease is poorly defined and the role of debulking remains controversial. The objective of the current study was to define outcomes following non-curative intent liver-directed therapy (debulking) among patients with NELM.612 patients were identified who underwent liver-directed therapy of NELM from a multi-institutional database. Outcomes were stratified according to curative (R0/R1) versus non-curative ≥ 80% debulking (R2).179 (29.2%) patients had an R2/debulking procedure. Patients undergoing debulking more commonly had more aggressive high-grade tumors (R0/R1: 12.8% vs. R2: 35.0%; P < 0.001) or liver disease burden that was bilateral (R0/R1: 52.8% vs. R2: 75.6%; P < 0.001). After a median follow-up of 51 months, median (R0/R1: not reached vs. R2: 87 months; P < 0.001) and 5-year survival (R0/R1: 85.2% vs. R2: 60.7%; P < 0.001) was higher among patients who underwent an R0/R1 resection compared with patients who underwent a debulking operation. Among patients with ≥50% NELM liver involvement, median and 5-year survival following debulking was 55.4 months and 40.6%, respectively.Debulking operations for NELM provided reasonable long-term survival. Hepatic debulking for patients with NELM is a reasonable therapeutic option for patients with grossly unresectable disease that may provide a survival benefit.
The Limitations of Standard Clinicopathologic Features to Accurately Risk-Stratify Prognosis after Resection of Intrahepatic Cholangiocarcinoma JOURNAL OF GASTROINTESTINAL SURGERY Bagante, F., Merath, K., Squires, M. H., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2018; 22 (3): 477–85
The ability to provide accurate prognostic data after hepatectomy for intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and validate a nomogram to predict survival, as well as investigate the clinical implications of underestimating patients' risk of recurrence.Patients undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major hepatobiliary centers were included. Variables significant on multivariable analysis were used to construct a nomogram to predict disease-free survival (DFS). The nomogram assigned a score to each variable included in the model and calculated the risk of recurrence.Eight hundred ninety-seven patients are included in the analytic cohort. On multivariable Cox regression analysis, tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13; p < 0.001), multifocal ICC (HR 1.64, 95% CI 1.32-2.03; p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25-2.11; p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89; p < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09-1.83; p = 0.008) were independent adverse risk factors associated with decreased DFS. The Harrell's c-index for the nomogram was 0.633 (with n = 5000 bootstrapping resamples) and the plot comparing predicted and actuarial DFS demonstrated a good calibration of the model. A subset of patients (n = 282) had a DFS worse than predicted (ΔPredicted DFS - Actuarial DFS > 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered "favorable."A nomogram based on standard clinicopathologic characteristics was suboptimal in its ability to predict accurately risk of recurrence among patients with ICC after curative-intent liver resection. Particularly, the risk of underestimating patient risk of recurrence was highest among patients with historically favorable characteristics. Over one third of patients recurred > 6 months earlier than the DFS predicted by the nomogram.
A Novel T-Stage Classification System for Adrenocortical Carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group Poorman, C. E., Ethun, C. G., Postlewait, L. M., Tran, T. B., Prescott, J. D., Pawlik, T. M., Wang, T. S., Glenn, J., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Staley, C. A., Poultsides, G. A., Maithel, S. K. SPRINGER. 2018: 520–27
The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC.Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS).Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001).Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.
Gastric carcinoids: Does type of surgery or tumor affect survival? Crown, A., Kanji, Z. S., Lopez-Aguiar, A. G., Dillhoff, M., Poultsides, G. A., Makris, E., Idrees, K., Smith, P., Nathan, H., Beems, M., Weber, S. M., Fisher, A. V., Fields, R., Davidson, J., Maithel, S., Rocha, F. G. AMER SOC CLINICAL ONCOLOGY. 2018
Association of preoperative monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio with overall survival after resection of pancreatic neuroendocrine tumors. Panni, R. Z., Davidson, J. T., Krasnick, B. A., McGilvray, M., Rodriguez, J., Lopez-Aguiar, A. G., Dillhoff, M., Poultsides, G. A., Winslow, E., Rocha, F. G., Idrees, K., Hammill, C., Cho, C., Doyle, M., Chapman, W. C., Hawkins, W. G., Strasberg, S. M., Trikalinos, N. A., Maithel, S., Fields, R. AMER SOC CLINICAL ONCOLOGY. 2018
Defining the number of lymph nodes needed to accurately stage small bowel neuroendocrine tumors: An 8-institution study from the US neuroendocrine tumor study group. Zaidi, M., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G. A., Makris, E., Rocha, F. G., Crown, A., Idrees, K., Smith, P., Nathan, H., Beems, M., Abbott, D., Barrett, J., Fields, R. C., Davidson, J. T., Cardona, K., Maithel, S. AMER SOC CLINICAL ONCOLOGY. 2018
Microsatellite instability in resectable colorectal liver metastasis: An international multi-institutional analysis. Margonis, G., Buettner, S., Wagner, D., McVey, J., Andreatos, N., Beer, A., Sasaki, K., He, J., Kaczirek, K., Poultsides, G. A., Cameron, J. L., Mischinger, H., Aucejo, F., Wolfgang, C., Weiss, M. J. AMER SOC CLINICAL ONCOLOGY. 2018
Prognostic value of neutrophil-to-lymphocyte ratio (NLR) in intestinal neuroendocrine tumors: An analysis of the US Neuroendocrine Tumor Study Group. Krasnick, B. A., Davidson, J. T., Panni, R. Z., McGilvray, M., Rodriguez, J., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G. A., Makris, E., Rocha, F. G., Crown, A., Idrees, K., Hawkins, W. G., Strasberg, S. M., Hammill, C., Chapman, W. C., Doyle, M., Maithel, S., Fields, R. AMER SOC CLINICAL ONCOLOGY. 2018
Defining the role of lymphadenectomy for pancreatic neuroendocrine tumors: An eight institution study of 695 patients from the US Neuroendocrine Tumor Study Group. Lopez-Aguiar, A. G., Zaidi, M., Dillhoff, M., Beal, E. W., Poultsides, G. A., Makris, E., Rocha, F. G., Kanji, Z. S., Idrees, K., Smith, P., Cho, C., Beems, M., Weber, S. M., Fisher, A. V., Fields, R. C., Krasnick, B. A., Cardona, K., Maithel, S. AMER SOC CLINICAL ONCOLOGY. 2018
Impact of insurance status on survival in neuroendocrine tumors: A multi-institutional Study from the US Neuroendocrine Study Group. Smith, P., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G. A., Makris, E., Rocha, F. G., Crown, A., Cho, C., Beems, M., Winslow, E., Rendell, V., Krasnick, B. A., Fields, R., Maithel, S., Idrees, K. AMER SOC CLINICAL ONCOLOGY. 2018
Timing of disease occurrence and hepatic resection on long-term outcome of patients with neuroendocrine liver metastasis JOURNAL OF SURGICAL ONCOLOGY Zhang, X., Beal, E. W., Weiss, M., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S. K., Marques, H. P., Pawlik, T. M. 2018; 117 (2): 171–81
The objective of the study was to evaluate the impact of timing of disease occurrence and hepatic resection on long-term outcome of neuroendocrine liver metastasis (NELM).A total of 420 patients undergoing curative-intent resection for NELM were identified from a multi-institutional database. Date of primary resection, NELM detection and resection, intraoperative details, disease-specific (DSS), and recurrence-free survival (RFS) were obtained.A total of 243 (57.9%) patients had synchronous NELM, while 177 (42.1%) developed metachronous NELM. On propensity score matching (PSM), patients with synchronous versus metachronous NELM had comparable DSS (10-year DSS, 76.2% vs 85.9%, P = 0.105), yet a worse RFS (10-year RFS, 34.1% vs 59.8%, P = 0.008). DSS and RFS were comparable regardless of operative approach (simultaneous vs staged, both P > 0.1). Among patients who developed metachronous NELM, no difference in long-term outcomes were identified between early (≤2 years, n = 102, 57.6%) and late (>2 years, n = 68, 42.4%) disease on PSM (both P > 0.1).Patients with synchronous NELM had a higher risk of tumor recurrence after hepatic resection versus patients with metachronous disease. The time to development of metachronous NELM did not affect long-term outcome. Curative-intent hepatic resection should be considered for patients who develop NELM regardless of the timing of disease presentation.
Management of Borderline Resectable Pancreatic Cancer. International journal of radiation oncology, biology, physics Toesca, D. A., Koong, A. J., Poultsides, G. A., Visser, B. C., Haraldsdottir, S. n., Koong, A. C., Chang, D. T. 2018; 100 (5): 1155–74
With the rapid development of imaging modalities and surgical techniques, the clinical entity representing tumors that are intermediate between resectable and unresectable pancreatic adenocarcinoma has been identified has been termed "borderline resectable" (BR). These tumors are generally amenable for resection but portend an increased risk for positive margins after surgery and commonly necessitate vascular resection and reconstruction. Although there is a lack of consensus regarding the appropriate definition of what constitutes a BR pancreatic tumor, it has been demonstrated that this intermediate category carries a particular prognosis that is in between resectable and unresectable disease. In order to downstage the tumor and increase the probability of clear surgical margins, neoadjuvant therapy is being increasingly utilized and studied. There is a lack of high-level evidence to establish the optimal treatment regimen for BR tumors. When resection with negative margins is achieved after neoadjuvant therapy, the prognosis for BR tumors approaches and even exceeds that for resectable disease. This review presents the current definitions, different treatment approaches, and the clinical outcomes of BR pancreatic cancer.
Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases: A Multi-institutional, International Analysis of 1099 Patients. Annals of surgery Margonis, G. A., Buettner, S. n., Andreatos, N. n., Wagner, D. n., Sasaki, K. n., Barbon, C. n., Beer, A. n., Kamphues, C. n., Løes, I. M., He, J. n., Pawlik, T. M., Kaczirek, K. n., Poultsides, G. n., Lønning, P. E., Cameron, J. L., Mischinger, H. J., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2018
To evaluate the changing impact of genetic and clinicopathologic factors on conditional overall survival (CS) over time in patients with resectable colorectal liver metastasis.CS estimates account for the changing likelihood of survival over time and may reveal the changing impact of prognostic factors as time accrues from the date of surgery.CS analysis was performed in 1099 patients of an international, multi-institutional cohort. Three-year CS (CS3) estimates at the "xth" year after surgery were calculated as follows: CS3 = CS (x + 3)/CS (x). The standardized difference (d) between CS3 rates was used to estimate the changing prognostic power of selected variables over time. A d < 0.1 indicated very small differences between groups, 0.1 ≤ d < 0.3 indicated small differences, 0.3 ≤ d < 0.5 indicated moderate differences, and d ≥ 0.5 indicated strong differences.According to OS estimates calculated at the time of surgery, the presence of BRAF and KRAS mutations, R1 margin status, resected extrahepatic disease, patient age, primary tumor lymph node metastasis, tumor number, and carcinoembryonic antigen levels independently predicted worse survival. However, when temporal changes in the prognostic impact of these variables were considered using CS3 estimates, BRAF mutation dominated prognosis during the first year (d = 0.48), whereas surgeon-related variables (ie, surgical margin and resected extrahepatic disease) determined prognosis thereafter (d ≥ 0.5). Traditional clinicopathologic factors affected survival constantly, but only to a moderate degree (0.3 ≤ d < 0.5).The impact of genetic, surgery-related, and clinicopathologic factors on OS and CS3 changed dramatically over time. Specifically, BRAF mutation status dominated prognosis in the first year, whereas positive surgical margins and resected extrahepatic disease determined prognosis thereafter.
Performance of prognostic scores and staging systems in predicting long-term survival outcomes after surgery for intrahepatic cholangiocarcinoma JOURNAL OF SURGICAL ONCOLOGY Buettner, S., Galjart, B., van Vugt, J. A., Bagante, F., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T., Maithel, S. K., Pulitano, C., Margonis, G. A., Weiss, M., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J., IJzermans, J. M., Koerkamp, B., Pawlik, T. M. 2017; 116 (8): 1085–95
We sought to validate the commonly used prognostic models and staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi-center patient cohort.The overall (OS) and disease free survival (DFS) prognostic discriminatory ability of various commonly used models were assessed in a large retrospective cohort. Harrell's concordance index (c-index) was used to determine accuracy of model prediction.Among 1054 ICC patients, median OS was 37.7 months and 1-, 3-, and 5-year survival, were 78.8%, 51.5%, and 39.3%, respectively. Recurrence of disease occurred in 454 (43.0%) patients with a median DFS of 29.6 months. One-, 3- and 5- year DFS were 64.6%, 46.5 % and 44.4%, respectively. The prognostic models associated with the best OS prediction were the Wang nomogram (c-index 0.668) and the Nathan staging system (c-index 0.639). No model was proficient in predicting DFS. Only the Wang nomogram exceeded a c-index of 0.6 for DFS (c-index 0.602). The c-index for the AJCC staging system was 0.637 for OS and 0.582 for DFS.While the Wang nomogram had the best discriminatory ability relative to OS and DFS, no ICC staging system or nomogram demonstrated excellent prognostic discrimination. The AJCC staging for ICC performed reasonably, although its overall discrimination was only modest-to-good.
The impact of extrahepatic disease among patients undergoing liver-directed therapy for neuroendocrine liver metastasis JOURNAL OF SURGICAL ONCOLOGY Ejaz, A., Reames, B. N., Maithel, S., Poultsides, G. A., Bauer, T. W., Fields, R. C., Weiss, M., Marques, H., Aldrighetti, L., Pawlik, T. M. 2017; 116 (7): 841–47
Predictors and Prognostic Implications of Perioperative Chemotherapy Completion in Gastric Cancer Karagkounis, G., Squires, M., Melis, M., Poultsides, G. A., Worhunsky, D., Jin, L. X., Fields, R. C., Spolverato, G., Pawlik, T. M., Votanopoulos, K. I., Levine, E. A., Schmidt, C., Bloomston, M., Cho, C. S., Weber, S., Masi, A., Berman, R., Pachter, H., Staley, C. A., Newman, E., Maithel, S. K., Hatzaras, I. SPRINGER. 2017: 1984–92
Perioperative chemotherapy in gastric cancer is increasingly used since the "MAGIC" trial, while clinical practice data outside of trials remain limited. We sought to evaluate the predictors and prognostic implications of perioperative chemotherapy completion in patients undergoing curative-intent gastrectomy across multiple US institutions.Patients who underwent curative-intent resection of gastric adenocarcinoma between 2000 and 2012 in eight institutions of the US Gastric Cancer Collaborative were identified. Patients who received preoperative chemotherapy were included, while those who died within 90 days or with unknown adjuvant chemotherapy status were excluded. Predictors of chemotherapy completion and survival were identified using multivariable logistic regression and Cox proportional hazards.One hundred sixty three patients were included (median age 63.3, 36.8% female). The postoperative component of perioperative chemotherapy was administered in 112 (68.7%) patients. Factors independently associated with receipt of adjuvant chemotherapy were younger age (odds ratio (OR) 2.73, P = 0.03), T3 tumors (OR 14.3, P = 0.04), lymph node metastasis (OR 5.82, P = 0.03), and D2 lymphadenectomy (OR 4.12, P = 0.007), and, inversely, postoperative complications (OR 0.25, P = 0.008). Median overall survival (OS) was 25.1 months and 5-year OS was 36.5%. Predictors of OS were preexisting cardiac disease (hazard ratio (HR) 2.7, 95% CI 1.13-6.46), concurrent splenectomy (HR 4.11, 95% CI 1.68-10.0), tumor stage (reference stage I; stage II HR 2.62; 95% CI 0.99-6.94; stage III HR 4.86, 95% CI 1.81-13.02), and D2 lymphadenectomy (HR 0.43, 95% CI 0.19-0.95). After accounting for these factors, adjuvant chemotherapy administration was associated with improved OS (HR 0.33, 95% CI 0.14-0.82).Completion of perioperative chemotherapy was successful in two thirds of patients with gastric cancer and was independently associated with improved survival.
The Effects of Travel Burden on Outcomes After Resection of Extrahepatic Biliary Malignancies: Results from the US Extrahepatic Biliary Consortium O'Connor, S. C., Mogal, H., Russell, G., Ethun, C., Fields, R. C., Jin, L., Hatzaras, I., Vitiello, G., Idrees, K., Isom, C. A., Martin, R., Scoggins, C., Pawlik, T. M., Schmidt, C., Poultsides, G., Tran, T. B., Weber, S., Salem, A., Maithel, S., Shen, P. SPRINGER. 2017: 2016–24
Surgical resection of extrahepatic biliary malignancies has been increasingly centralized at high-volume tertiary care centers. While this has improved outcomes overall, increased travel burden has been associated with worse survival for many other malignancies. We hypothesized that longer travel distances are associated with worse outcomes for these patients as well.Data was analyzed from the US Extrahepatic Biliary Consortium database, which retrospectively reviewed patients who received resection of extrahepatic biliary malignancies at 10 high-volume centers. Driving distance to the patient's treatment center was measured for 1025 patients. These were divided into four quartiles for analysis: < 24.5, 24.5-57.2, 57.2-117, and < 117 mi. Cox proportional hazard models were then used to measure differences in overall survival.No difference was found between the groups in severity of disease or post-operative complications. The median overall survival in each quartile was as follows: 1st = 1.91, 2nd = 1.60, 3rd = 1.30, and 4th = 1.39 years. Patients in the 3rd and 4th quartile had a significantly lower median household income (p = 0.0001) and a greater proportion Caucasian race (p = 0.0001). However, neither of these was independently associated with overall survival. The two furthest quartiles were found to have decreased overall survival (HR = 1.39, CI = 1.12-1.73 and HR = 1.3, CI = 1.04-1.62), with quartile 3 remaining significant after multivariate analysis (HR = 1.45, CI = 1.04-2.0, p = 0.028).Longer travel distances were associated with decreased overall survival, especially in the 3rd quartile of our study. Patients traveling longer distances also had a lower household income, suggesting that these patients have significant barriers to care.
Neuroendocrine Liver Metastasis: Prognostic Implications of Primary Tumor Site on Patients Undergoing Curative Intent Liver Surgery Spolverato, G., Bagante, F., Aldrighetti, L., Poultsides, G., Bauer, T. W., Field, R. C., Marques, H. P., Weiss, M., Maithel, S. K., Pawlik, T. M. SPRINGER. 2017: 2039–47
Neuroendocrine tumors typically arise from pancreatic (PNET) vs. gastrointestinal or thoracic origins (non-PNET). The impact of primary tumor site on long-term prognosis following resection of neuroendocrine liver metastasis (NELM) remains poorly defined. The objective of the current study was to define the association of primary tumor location on prognosis of patients undergoing curative intent liver resection for NELM.Between 1990 and 2014, 421 patients who underwent resection of NELM were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified and analyzed by location of the primary tumor (PNET vs. non-PNET). A propensity score-matched analysis was utilized to assess the impact of primary tumor location on long-term survival.Among the 421 patients, 197 (46.8%) patients had NELM from a PNET primary while 224 (53.2%) had a non-PNET primary (small bowel, n = 145; rectal, n = 10; bronchial, n = 22; other, n = 47). There were no differences in tumor burden and tumor site, while presence of extrahepatic disease was more common among patients with non-PNET NELM (extrahepatic disease, PNET NELM, n = 11 27.5% vs. non-PNET NELM, n = 29 72.5%; p = 0.010). Patients with PNET NELM were more likely to have non-functional disease compared with patients who had non-PNET NELM (non-functional, PNET NELM, n = 117 54.9% vs. non-PNET NELM, n = 96 45.1%; p = 0.011). On the final pathological specimen of the resected NELM, patients with PNET NELM were more likely to have a moderately differentiated tumor (59.3%), while patients with non-PNET NELM were more likely to have a poorly differentiated tumor (67.8%) (p = 0.005). Patients with PNET NELM had a worse 5-year DFS and 5-year OS compared with patients who had non-PNET NELM (DFS, PNET 36.2% vs. non-PNET 55.2%; p = 0.001 and OS, PNET 79.5% vs. non-PNET 83.4%; p = 0.008). After propensity score matching, both 5-year DFS and 5-year OS of the PNET and non-PNET groups were comparable (DFS, PNET 46.2% vs. non-PNET 55.9%; p = 0.22 and OS, PNET 81.5% vs. non-PNET 84.3%; p = 0.19).PNET patients more often present with non-functional NELM and moderately differentiated tumors. On propensity-matched analysis, factors such as extrahepatic disease and tumor grade, but not primary tumor location, were associated with prognosis of patients undergoing curative intent liver surgery for NELM.
Evaluating the American College of Surgeons National Surgical Quality Improvement project risk calculator: results from the US Extrahepatic Biliary Malignancy Consortium Beal, E. W., Lyon, E., Kearney, J., Wei, L., Ethun, C. G., Black, S. M., Dillhoff, M., Salem, A., Weber, S. M., Tran, T. B., Poultsides, G., Shenoy, R., Hatzaras, I., Krasnick, B., Fields, R. C., Buttner, S., Scoggins, C. R., Martin, R. G., Isom, C. A., Idrees, K., Mogal, H. D., Shen, P., Maithel, S. K., Pawlik, T. M., Schmidt, C. R. ELSEVIER SCI LTD. 2017: 1104–11
The objective of this study is to evaluate use of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) online risk calculator for estimating common outcomes after operations for gallbladder cancer and extrahepatic cholangiocarcinoma.Subjects from the United States Extrahepatic Biliary Malignancy Consortium (USE-BMC) who underwent operation between January 1, 2000 and December 31, 2014 at 10 academic medical centers were included in this study. Calculator estimates of risk were compared to actual outcomes.The majority of patients underwent partial or major hepatectomy, Whipple procedures or extrahepatic bile duct resection. For the entire cohort, c-statistics for surgical site infection (0.635), reoperation (0.680) and readmission (0.565) were less than 0.7. The c-statistic for death was 0.740. For all outcomes the actual proportion of patients experiencing an event was much higher than the median predicted risk of that event. Similarly, the group of patients who experienced an outcome did have higher median predicted risk than those who did not.The ACS NSQIP risk calculator is easy to use but requires further modifications to more accurately estimate outcomes for some patient populations and operations for which validation studies show suboptimal performance.
Transgastric pancreatic necrosectomy-expedited return to prepancreatitis health JOURNAL OF SURGICAL RESEARCH Dua, M. M., Worhunsky, D. J., Malhotra, L., Park, W. G., Poultsides, G. A., Norton, J. A., Visser, B. C. 2017; 219: 11–17
The best operative strategy for necrotizing pancreatitis remains controversial. Traditional surgical necrosectomy is associated with significant morbidity; endoscopic and percutaneous strategies require repeated interventions with prolonged hospitalizations. We have developed a transgastric approach to pancreatic necrosectomy to overcome the shortcomings of the other techniques described.Patients with necrotizing pancreatitis treated from 2009 to 2016 at an academic center were retrospectively reviewed. Open or laparoscopic transgastric necrosectomy was performed if the area of necrosis was walled-off and in a retrogastric position on cross-sectional imaging. Study endpoints included postoperative complications and mortality.Forty-six patients underwent transgastric necrosectomy (nine open and 37 laparoscopic). Median (interquartile range) preoperative Acute Physiologic and Chronic Health Evaluation II score was 6 (3-12). Seventy percent of patients had >30% necrosis on preoperative imaging; infected necrosis was present in 35%. Median total length of stay (LOS) was 6 (3-12) d. No patient required a second operative debridement; four patients (9%) had short-term postoperative percutaneous drainage for residual fluid collections. Median follow-up was 1 y; there were no fistula or wound complications. Six patients (13%) had postoperative bleeding; five patients received treatment by image-guided embolization. There was one death in the cohort.Transgastric pancreatic necrosectomy allows for effective debridement with a single definitive operation. When anatomically suitable, this operative strategy offers expedited recovery and avoids long-term morbidity associated with fistulas and prolonged drainage.
Surgical Site Infection Is Associated with Tumor Recurrence in Patients with Extrahepatic Biliary Malignancies JOURNAL OF GASTROINTESTINAL SURGERY Buettner, S., Ethun, C. G., Poultsides, G., Thuy Tran, Idrees, K., Isom, C. A., Weiss, M., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Koerkamp, B., Maithel, S. K., Pawlik, T. M. 2017; 21 (11): 1813–20
Surgical site infections (SSI) are one of the most common complications after hepato-pancreato-biliary surgery. Infectious complications may lead to an associated immune-modulatory effect that inhibits the body's response to cancer surveillance. We sought to define the impact of SSI on long-term prognosis of patients undergoing surgical resection of extrahepatic biliary malignancies (EHBM).Patients undergoing surgery for EHBM between 2000 and 2014 were identified using a large, multi-center, national cohort dataset. Recurrence free survival (RFS) was calculated and a multivariable Cox proportional hazards model was utilized to identify potential risk factors for RFS including SSI.Seven hundred twenty-eight patients included in the analytic cohort; 236 (32.4%) patients had perihilar cholangiocarcinoma, 241 (33.1%) gallbladder cancer, and 251 (34.5%) distal cholangiocarcinoma. A major resection, liver resection, was performed in 205 (28.3%) patients, while 110 (15.2%) patients had a pancreaticoduodenectomy. The overall incidence of morbidity was 55.8%; among the 397 patients who experienced a complication, 161 patients specifically had an SSI. The SSI occurred as an infection of the surgical site (n = 70, 9.6%) or formation of an abscess in the operative bed (n = 91, 12.5%). SSI was associated with long-term survival as patients who experienced an SSI had a median RFS of 19.5 months compared with 30.5 months for those patients who did not have an SSI (HR 1.40, 95% CI 1.08-1.80; p = 0.01). Among 279 patients who had EHBM that had no associated lymph node metastases, well-to-moderate tumor differentiation, as well as an R0 resection margin, SSI remained associated with worse RFS (HR 1.84, 95% CI 1.03-3.29; p = 0.038), as well as overall survival (HR 1.87, 95% CI 1.18-2.97; p = 0.008).SSI was a relatively common occurrence following surgery for EHBM as 1 in 10 patients experienced an SSI. In addition to standard tumor-specific factors, the occurrence of postoperative SSI was adversely associated with long-term survival.
Yttrium-90 Radioembolization for Unresectable Combined Hepatocellular-Cholangiocarcinoma (vol 40, pg 1383, 2017) CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY Chan, L. S., Sze, D. Y., Poultsides, G. A., Louie, J. D., Abdelrazek Mohammed, M. A., Wang, D. S. 2017; 40 (10): 1657
Management of Postoperative Pancreatic Fistula: Drain Position Matters Malhotra, L., Dua, M. M., Leal, J. N., Poultsides, G. A., Norton, J. A., Visser, B. C. ELSEVIER SCIENCE INC. 2017: E123–E124
Blood Transfusion and Survival for Resected Adrenocortical Carcinoma: A Study from the United States Adrenocortical Carcinoma Group AMERICAN SURGEON Poorman, C. E., Postlewait, L. M., Ethun, C. G., Tran, T. B., Prescott, J. D., Pawlik, T. M., Wang, T. S., Glenn, J., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Staley, C. A., Poultsides, G. A., Maithel, S. K. 2017; 83 (7): 761-768
Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P < 0.001), inferior vena cava involvement (24.6% vs 5.4%, P = 0.002), additional organ resection (78.9% vs 36.3%, P < 0.001), and major complications (29% vs 2%, P < 0.001). Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P < 0.001). On univariate Cox regression, transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7-5.9, P < 0.001), and hormonal hypersecretion (HR = 2.6, 95% CI = 1.5-4.2, P < 0.001) were associated with worse RFS. When applying this model to OS, similar associations were seen (transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1-12.4, P < 0.001; hormonal hypersecretion HR = 3.5, 95% CI = 1.9-6.4, P < 0.001). There was no difference in outcomes between patients who received 1 to 2 units versus >2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Perioperative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.
Pathologic and Prognostic Implications of Incidental versus Nonincidental Gallbladder Cancer: A 10-Institution Study from the United States Extrahepatic Biliary Malignancy Consortium AMERICAN SURGEON Ethun, C. G., Le, N., Lopez-Aguiar, A. G., Pawlik, T. M., Poultsides, G., Thuy Tran, Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B. A., Weber, S. M., Salem, A., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Russell, M. C., Maithel, S. K. 2017; 83 (7): 679-686
Most gallbladder cancers (GBCs) are discovered incidentally after routine cholecystectomy. The influence of timing of diagnosis on disease stage, treatment, and prognosis is not known. Patients with GBC who underwent resection at 10 institutions from 2000 to 2015 were included. Patients diagnosed incidentally (IGBC) and nonincidentally (non-IGBC) were compared. Primary outcome was overall survival (OS). Of 445 patients with GBC, 266 (60%) were IGBC and 179 (40%) were non-IGBC. Compared with IGBC, non-IGBC patients were more likely to have R2 resections (43% vs 19%; P < 0.001), advanced T-stage (T3/T4: 70% vs 40%; P < 0.001), high-grade tumors (50% vs 31%; P < 0.001), lymphovascular invasion (64% vs 45%; P = 0.01), and positive lymph nodes (60% vs 43%; P = 0.009). Receipt of adjuvant chemotherapy was similar between groups (49% vs 49%). Non-IGBC was associated with worse median OS compared with IGBC (17 vs 32 months; P < 0.001), which persisted among stage III patients (12 vs 29 months; P < 0.001), but not stages I, II, or IV. Despite accounting for other adverse pathologic factors (grade, T-stage, lymphovascular invasion, margin, lymph node), adjuvant chemotherapy was associated with improved OS only in stage III IGBC, but not in non-IGBC. Compared with incidental discovery, non-IGBC is associated with reduced OS, which is most evident in stage III disease. Despite being well matched for other adverse pathologic factors, adjuvant chemotherapy was associated with improved survival only in stage III patients with incidentally discovered cancer. This underscores the importance of timing of diagnosis in GBC and suggests that these two groups may represent a distinct biology of disease, and the same treatment paradigm may not be appropriate.
Impact of lymph node ratio in selecting patients with resected gastric cancer for adjuvant therapy. Surgery Kim, Y., Squires, M. H., Poultsides, G. A., Fields, R. C., Weber, S. M., Votanopoulos, K. I., Kooby, D. A., Worhunsky, D. J., Jin, L. X., Hawkins, W. G., Acher, A. W., Cho, C. S., Saunders, N., Levine, E. A., Schmidt, C. R., Maithel, S. K., Pawlik, T. M. 2017
The impact of adjuvant chemotherapy and chemo-radiation therapy in the treatment of resectable gastric cancer remains varied. We sought to define the clinical impact of lymph node ratio on the relative benefit of adjuvant chemotherapy or chemo-radiation therapy among patients having undergone curative-intent resection for gastric cancer.Using the multi-institutional US Gastric Cancer Collaborative database, 719 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2013 were identified. Patients with metastasis or an R2 margin were excluded. The impact of lymph node ratio on overall survival among patients who received chemotherapy or chemo-radiation therapy was evaluated.Median patient age was 65 years, and the majority of patients were male (56.2%). The majority of patients underwent either subtotal (40.6%) or total gastrectomy (41.0%), with the remainder undergoing distal gastrectomy or wedge resection (18.4%). On pathology, median tumor size was 4 cm; most patients had a T3 (33.0%) or T4 (27.9%) lesion with lymph node metastasis (59.7%). Margin status was R0 in 92.5% of patients. A total of 325 (45.2%) patients underwent resection alone, 253 (35.2%) patients received 5-FU or capecitabine-based chemo-radiation therapy, whereas the remaining 141 (19.6%) received chemotherapy. Median overall survival was 40.9 months, and 5-year overall survival was 40.3%. According to lymph node ratio categories, 5-year overall survival for patients with a lymph node ratio of 0, 0.01-0.10, >0.10-0.25, >0.25 were 54.1%, 53.1 %, 49.1 % and 19.8 %, respectively. Factors associated with worse overall survival included involvement of the gastroesophageal junction (hazard ratio 1.8), T-stage (3-4: hazard ratio 2.1), lymphovascular invasion (hazard ratio 1.4), and lymph node ratio (>0.25: hazard ratio 2.3; all P < .05). In contrast, receipt of adjuvant chemo-radiation therapy was associated with an improved overall survival in the multivariable model (versus resection alone: hazard ratio 0.40; versus chemotherapy: hazard ratio 0.45, both P < .001). The benefit of chemo-radiation therapy for resected gastric cancer was noted only among patients with lymph node ratio >0.25 (versus resection alone: hazard ratio R 0.34; versus chemotherapy: hazard ratio 0.45, both P < .001). In contrast, there was no noted overall survival benefit of chemotherapy or chemo-radiation therapy among patients with lymph node ratio ≤0.25 (all P > .05).Adjuvant chemotherapy or chemo-radiation therapy was utilized in more than one-half of patients undergoing curative-intent resection for gastric cancer. Lymph node ratio may be a useful tool to select patients for adjuvant chemo-radiation therapy, because the benefit of chemo-radiation therapy was isolated to patients with greater degrees of lymphatic spread (ie, lymph node ratio >0.25).
Survival after resection of perihilar cholangiocarcinoma in patients with lymph node metastases. HPB Buettner, S., van Vugt, J. L., Gaspersz, M. P., Coelen, R. J., Roos, E., Labeur, T. A., Margonis, G. A., Ethun, C. G., Maithel, S. K., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B. A., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., IJzermans, J. N., van Gulik, T. M., Pawlik, T. M., Groot Koerkamp, B. 2017
The aim of this study was to compare patients with PHC with lymph node metastases (LN+) who underwent a resection with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy.Consecutive LN+ patients who underwent a resection for PHC in 12 centers were compared with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy in 2 centers.In the resected cohort of 119 patients, the median overall survival (OS) was 19 months and the estimated 1-, 3- and 5-year OS was 69%, 27% and 13%, respectively. In the non-resected cohort of 113 patients, median OS was 12 months and the estimated 1-, 3- and 5-year OS was 49%, 7%, and 3%, respectively. OS was better in the resected LN+ cohort (p < 0.001). Positive resection margin (hazard ratio [HR]: 1.54; 95%CI: 0.97-2.45) and lymphovascular invasion (LVI) (HR: 1.71; 95%CI: 1.09-2.69) were independent poor prognostic factors in the resected cohort.Patients with PHC who underwent a resection for LN+ disease had better OS than patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. LN+ PHC does not preclude 5-year survival after resection.
Management and outcomes of patients with recurrent neuroendocrine liver metastasis after curative surgery: An international multi-institutional analysis. Journal of surgical oncology Spolverato, G., Bagante, F., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S. K., Marques, H. P., Weiss, M., Pawlik, T. M. 2017
We sought to characterize the treatment, as well as define the long-term outcomes, of patients with recurrent neuroendocrine liver metastasis (NELM).Between 1990 and 2014, 322 patients undergoing curative intent liver surgery for NELM were identified from a multi-institutional database. Recurrences were classified as intrahepatic, extrahepatic, and both intra- and extra-hepatic.Overall, median, 1-, 5-, 10-year DFS were 3.1 years, 75.5%, 40.4%, and 32.1%, respectively. After curative intent liver surgery, 209 patients (64.9%) recurred within a median follow-up of 4.5 years, while 113 (35.1%) patients were alive without disease with a follow-up time ≥3 years. The site of recurrence was intrahepatic only (n = 111, 65.7%), extrahepatic only (n = 19, 11.2%), or intra- and extra-hepatic (n = 39, 23.1%). Compared with intrahepatic only recurrence, extrahepatic only, and combined intra- and extra-hepatic recurrence were associated with a worse long-term outcome (10-year OS: intrahepatic only, 42.5%, 95%CI, 24.9-59.0 vs extrahepatic only, 0% and combined intra- and extra-hepatic, 21.5%, 95%CI, 5.3-44.0) (P < 0.001). Most patients were treated with repeat surgery (n = 49, 36.6%), while 34 (23.5%) patients received a somatostatin analogue, 27 (18.6%) systemic cytotoxic chemotherapy, and 27 (21.4%) patients had intra-arterial therapy. Ten-year OS among patients who underwent repeat surgery or intra-arterial treatments was 60.3% (95%CI, 34.1-78.8) and 52.0% (95%CI, 30.6-69.9), respectively. Patients who received somatostatin analogues (45.9% 95%CI, 22.3-66.9) or systemic chemotherapy (0%) had a shorter long-term survival (P = 0.001).Recurrence after surgery for NELM occurred among half of patients. Repeat liver resection for recurrence may offer a reasonable 5-year survival benefit.
Gallbladder Cancer Presenting with Jaundice: Uniformly Fatal or Still Potentially Curable? Journal of gastrointestinal surgery Tran, T. B., Norton, J. A., Ethun, C. G., Pawlik, T. M., Buettner, S., Schmidt, C., Beal, E. W., Hawkins, W. G., Fields, R. C., Krasnick, B. A., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Idrees, K., Isom, C. A., Hatzaras, I., Shenoy, R., Maithel, S. K., Poultsides, G. A. 2017
Jaundice as a presenting symptom of gallbladder cancer has traditionally been considered to be a sign of advanced disease, inoperability, and poor outcome. However, recent studies have demonstrated that a small subset of these patients can undergo resection with curative intent.Patients with gallbladder cancer managed surgically from 2000 to 2014 in 10 US academic institutions were stratified based on the presence of jaundice at presentation (defined as bilirubin ≥4 mg/ml or requiring preoperative biliary drainage). Perioperative morbidity, mortality, and overall survival were compared between jaundiced and non-jaundiced patients.Of 400 gallbladder cancer patients with available preoperative data, 108 (27%) presented with jaundice while 292 (73%) did not. The fraction of patients who eventually underwent curative-intent resection was much lower in the presence of jaundice (n = 33, 30%) than not (n = 218, 75%; P < 0.001). Jaundiced patients experienced higher perioperative morbidity (69 vs. 38%; P = 0.002), including a much higher need for reoperation (12 vs. 1%; P = 0.003). However, 90-day mortality (6.5 vs. 3.6%; P = 0.35) was not significantly higher. Overall survival after resection was worse in jaundiced patients (median 14 vs. 32 months; P < 0.001). Further subgroup analysis within the jaundiced patients revealed a more favorable survival after resection in the presence of low CA19-9 < 50 (median 40 vs. 12 months; P = 0.003) and in the absence of lymphovascular invasion (40 vs. 14 months; P = 0.014).Jaundice is a powerful preoperative clinical sign of inoperability and poor outcome among gallbladder cancer patients. However, some of these patients may still achieve long-term survival after resection, especially when preoperative CA19-9 levels are low and no lymphovascular invasion is noted pathologically.
View details for DOI 10.1007/s11605-017-3440-z
Impact of Morphological Status on Long-Term Outcome Among Patients Undergoing Liver Surgery for Intrahepatic Cholangiocarcinoma. Annals of surgical oncology Bagante, F., Spolverato, G., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Groot Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2017
The influence of morphological status on the long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) is poorly defined. We sought to study the impact of morphological status on overall survival (OS) of patients undergoing curative-intent resection for ICC.A total of 1083 patients who underwent liver resection for ICC between 1990 and 2015 were identified. Data on clinicopathological characteristics, operative details, and morphological status were recorded and analyzed. A propensity score-matched analysis was performed to reduce confounding biases.Among 1083 patients, 941(86.9%) had a mass-forming (MF) or intraductal-growth (IG) type, while 142 (13.1%) had a periductal-infiltrating (PI) or MF with PI components (MF + PI) ICC. Patients with an MF/IG ICC had a 5-year OS of 41.8% (95% confidence interval [CI] 37.7-45.9) compared with 25.5% (95% CI 17.3-34.4) for patients with a PI/MF + PI (p < 0.001). Morphological type was found to be an independent predictor of OS as patients with a PI/MF + PI ICC had a higher hazard of death (hazard ratio [HR] 1.42, 95% CI 1.11-1.82; p = 0.006) compared with patients who had an MF/IG ICC. Compared with T1a-T1b-T2 MF/IG tumors, T1a-T1b-T2 PI/MF + PI and T3-T4 PI/MF + PI tumors were associated with an increased risk of death (HR 1.47 vs. 3.59). Conversely, patients with T3-T4 MF/IG tumors had a similar risk of death compared with T1a-T1b-T2 MF/IG patients (p = 0.95).Among patients undergoing curative-intent resection of ICC, morphological status was a predictor of long-term outcome. Patients with PI or MF + PI ICC had an approximately 45% increased risk of death long-term compared with patients who had an MF or IG ICC.
View details for DOI 10.1245/s10434-017-5870-y
A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the US Extrahepatic Biliary Malignancy Consortium ANNALS OF SURGICAL ONCOLOGY Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T. M., Buettner, S., Poultsides, G., Thuy Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Merchant, N., Cardona, K., Maithel, S. K. 2017; 24 (5): 1343-1350
This study was designed to develop a more robust predictive model, beyond T-stage alone, for incidental gallbladder cancer (IGBC) for discovering locoregional residual (LRD) and distant disease (DD) at reoperation, and estimating overall survival (OS). T-stage alone is currently used to guide treatment for incidental gallbladder cancer. Residual disease at re-resection is the most important factor in predicting outcomes.All patients with IGBC who underwent reoperation at 10 institutions from 2000 to 2015 were included. Routine pathology data from initial cholecystectomy was utilized to create the gallbladder cancer predictive risk score (GBRS).Of 449 patients with gallbladder cancer, 262 (58 %) were incidentally discovered and underwent reoperation. Advanced T-stage, grade, and presence of lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of DD and LRD and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well-diff: 1, mod-diff: 2, poor-diff: 3; LVI-neg: 1, LVI-pos: 2; PNI-neg: 1, PNI-pos: 2), which added to a total GBRS score from 3 to 10. The scores were separated into three risk-groups (low: 3-4, intermediate: 5-7, high: 8-10). Each progressive GBRS group was associated with an increased incidence LRD and DD at the time of re-resection and reduced OS.By accounting for subtle pathologic variations within each T-stage, this novel predictive risk-score better stratifies patients with incidentally discovered gallbladder cancer. Compared with T-stage alone, it more accurately identifies patients at risk for locoregional-residual and distant disease and predicts long-term survival as it redistributes T1b, T2, and T3 disease across separate risk-groups based on additional biologic features. This score may help to optimize treatment strategy for patients with incidentally discovered gallbladder cancer.
Yttrium-90 Radioembolization for Unresectable Combined Hepatocellular-Cholangiocarcinoma. Cardiovascular and interventional radiology Chan, L. S., Sze, D. Y., Poultsides, G. A., Louie, J. D., Abdelrazek Mohammed, M. A., Wang, D. S. 2017
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare mixed cell type primary liver cancer with limited data to guide management. Transarterial radioembolization with yttrium-90 microspheres (RE) is an emerging treatment option for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. This study explored the safety and efficacy of RE for unresectable cHCC-CC.Patients with histopathologically confirmed cHCC-CC treated with RE were retrospectively evaluated. Clinical and biochemical toxicities were assessed using the Common Toxicity Criteria for Adverse Events v4.03. Radiological response was analyzed using the Response Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST criteria. Survival times were calculated and prognostic variables identified.Ten patients (median age 59 years; six men, four women) with unresectable cHCC-CC underwent 14 RE treatments with resin (n = 6 patients) or glass (n = 4 patients) microspheres. Clinical toxicities were limited to grade 1-2 fatigue, anorexia, nausea, or abdominal pain. No significant biochemical toxicities were observed. Median overall survivals from the first RE treatment and from initial diagnosis were 10.2 and 17.7 months, respectively. Six of seven patients with elevated tumor biomarker levels before RE showed decreased levels after treatment (median decrease of 72%, range 13-80%). Best hepatic radiological response was 60% partial response and 40% stable disease by modified RECIST, and 100% stable disease by RECIST v1.1. Poor performance status and the presence of macrovascular invasion were identified as predictors of reduced survival after RE.RE appears to be a safe and promising treatment option for patients with unresectable cHCC-CC.Level 4.
Assessment of the Lymph Node Status in Patients Undergoing Liver Resection for Intrahepatic Cholangiocarcinoma: the New Eighth Edition AJCC Staging System. Journal of gastrointestinal surgery Bagante, F., Spolverato, G., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Groot Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2017
The role of routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal staging. We sought to define outcome and risk of death among patients who were staged with ≥6 HLNs versus <6 HLNs.Patients undergoing hepatectomy for ICC between 1990 and 2015 at 1 of the 14 major hepatobiliary centers were identified.Among 1154 patients undergoing hepatectomy for ICC, 515 (44.6%) had lymphadenectomy. On final pathology, 200 (17.3%) patients had metastatic lymph node (MLN), while 315 (27.3%) had negative lymph node (NLN). Among NLN patients, HLN was associated with 5-year OS (p = 0.098). While HLN did not impact 5-year OS among MLN patients (p = 0.71), the number of MLN was associated with 5-year OS (p = 0.02). Among the 317 (27.5%) patients staged according the AJCC eighth edition staging system, N1 patients had a 3-fold increased risk of death compared with N0 patients (hazard ratio 3.03; p < 0.001).Only one fourth of patients undergoing hepatectomy for ICC had adequate nodal staging according to the AJCC eighth edition. While the six HLN cutoff value impacted prognosis of N0 patients, the number of MLN rather than HLN was associated with long-term survival of N1 patients.
Surgical Management of Pancreatic Cysts: A Shifting Paradigm Toward Selective Resection. Digestive diseases and sciences Gerry, J. M., Poultsides, G. A. 2017
Due to the widespread use of high-quality cross-sectional imaging, pancreatic cystic neoplasms are being diagnosed with increasing frequency. Clinicians are therefore asked to counsel a growing number of patients with pancreatic cysts diagnosed incidentally at an early, asymptomatic stage. Over the last two decades, accumulating knowledge on the biologic behavior of these neoplasms along with improved diagnostics through imaging and endoscopic cyst fluid analysis have allowed for a selective therapeutic approach toward these neoplasms. On one end of the management spectrum, observation is recommended for typically benign lesions (serous cystadenoma), and on the other end, upfront resection is recommended for likely malignant lesions (main duct IPMN, mucinous cystadenoma, solid pseudopapillary tumor, and cystic pancreatic neuroendocrine tumors). In between, management of premalignant lesions (branch duct IPMN) is dictated by the presence of high-risk features. In general, resection should be considered whenever the risk of malignancy is higher than the risk of the operation. This review aims to describe the evolution and current status of evidence guiding the selection of patients with pancreatic cystic neoplasms for surgical resection, along with a specific discussion on the type of resection required and expected outcomes.
Impact of major vascular resection on outcomes and survival in patients with intrahepatic cholangiocarcinoma: A multi-institutional analysis. Journal of surgical oncology Reames, B. N., Ejaz, A., Koerkamp, B. G., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Martel, G., Marsh, J. W., Pawlik, T. M. 2017
Major vascular involvement (IVC or portal vein) for intrahepatic cholangiocarcinoma (ICC) has traditionally been considered a contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing hepatectomy with major vascular resection in a large international multi-institutional database.A total of 1087 ICC patients who underwent curative-intent hepatectomy between 1990 and 2016 were identified from 13 institutions. Multivariable logistic and cox regressions were used to determine the impact of major vascular resection on perioperative and survival outcomes.Of 1087 patients who underwent resection, 128 (11.8%) also underwent major vascular resection (21 [16.4%] IVC resections, 98 [76.6%] PV resections, 9 [7.0%] combined resections). Despite more advanced disease, major vascular resection was not associated with the risk of any complication (OR = 0.68, 95%CI 0.32-1.45) or major complications (OR = 0.95, 95%CI 0.49-2.00). Post-operative mortality was also comparable between groups (OR = 1.05, 95%CI 0.32-3.47). In addition, median recurrence-free (14.0 vs 14.7 months, HR = 0.737, 95%CI 0.49-1.10) and overall (33.4 vs 40.2 months, HR = 0.71, 95%CI 0.359-1.40) survival were similar among patients who did and did not undergo major vascular resection (both P > 0.05).Among patients with ICC, major vascular resection was not associated with worse perioperative or oncologic outcomes. Concurrent major vascular resection should be considered in appropriately selected patients with ICC undergoing hepatectomy.
Surrogate End Points for Overall Survival in Metastatic, Locally Advanced, or Unresectable Pancreatic Cancer: A Systematic Review and Meta-Analysis of 24 Randomized Controlled Trials. Annals of surgical oncology Makris, E. A., MacBarb, R., Harvey, D. J., Poultsides, G. A. 2017
Overall survival (OS) has traditionally been the primary end point in studies evaluating the clinical benefit of first-line chemotherapy in metastatic, locally advanced, or unresectable pancreatic cancer (MLAUPC). Given the prolonged follow-up assessment required to obtain OS and its potential to be confounded by second-line treatments, this study sought to determine whether progression-free survival (PFS), response rate (RR), or disease control rate (DCR) can serve as a reliable surrogate for OS.A systematic review and meta-analysis was performed including all phase 3 clinical trials for MLAUPC, with gemcitabine as the control arm of the trial. The hazard ratios (HRs) for OS and PFS and odds ratios (ORs) for RR and DCR were recorded. A weighted Pearson correlation coefficient was estimated for the association between OS and the other outcomes. The primary analysis used a random effects weighting model, whereas the secondary analyses used a fixed effects- or sample size-weighted approach.For the study, 24 randomized controlled trials were identified. The Pearson correlation coefficient between OS and PFS was 0.86 (95% confidence interval [CI] 0.67-0.94; p < 0.001). Sensitivity analysis of the studies with little to no crossover further showed a correlation coefficient of 0.91 (95% CI 0.76-0.97; p < 0.001). The correlation coefficient between OS and RR was 0.45 (95% CI 0.07-0.72; p = 0.02) and between OS and DCR was 0.74 (95% CI 0.38-0.90; p < 0.001).First-line chemotherapy trials for MLAUPC show a robust correlation between OS and PFS, affirming its role as a surrogate of OS.
Surgical Considerations in the Management of Gastric Adenocarcinoma SURGICAL CLINICS OF NORTH AMERICA Makris, E. A., Poultsides, G. A. 2017; 97 (2): 295-?
Since Theodor Billroth and César Roux perfected the methods of postgastrectomy reconstruction in as early as the late nineteenth century, surgical management of gastric cancer has made incremental progress. The longstanding and contentious debate on the optimal extent of lymph node dissection for gastric cancer seems to have settled in favor of D2 dissection. Pylorus-preserving distal (central) gastrectomy has emerged as a less invasive, function-preserving option for T1N0 middle-third gastric cancers. Frozen section analysis of margins seems partially helpful in this direction. Last, the role of palliative gastrectomy in patients with metastatic seems less important than initially thought.
Fukuoka and AGA Criteria Have Superior Diagnostic Accuracy for Advanced Cystic Neoplasms than Sendai Criteria. Digestive diseases and sciences Sighinolfi, M., Quan, S. Y., Lee, Y., Ibaseta, A., Pham, K., Dua, M. M., Poultsides, G. A., Visser, B. C., Norton, J. A., Park, W. G. 2017; 62 (3): 626-632
The aim of this study was to compare the American Gastroenterological Association guidelines (AGA criteria), the 2012 (Fukuoka criteria), and 2006 (Sendai criteria) International Consensus Guidelines for the diagnosis of advanced pancreatic cystic neoplasms.All patients who underwent surgical resection of a pancreatic cyst from August 2007 through January 2016 were retrospectively analyzed at a single tertiary academic center. Relevant clinical and imaging variables along with pathology results were collected to determine appropriate classification for each guideline. Advanced pancreatic cystic neoplasms were defined by the presence of either high-grade dysplasia or cystic adenocarcinoma. Diagnostic accuracy was measured by ROC analysis.A total of 209 patients were included. Both the AGA and Fukuoka criteria had a higher diagnostic accuracy for advanced neoplastic cysts than the Sendai criteria: AGA ROC 0.76 (95% CI 0.69-0.81), Fukuoka ROC 0.78 (95% CI 0.74-0.82), and Sendai ROC 0.65 (95% CI 0.61-0.69) (p < 0.0001). There was no difference between the Fukuoka and the AGA criteria. While the sensitivity was higher in the Fukuoka criteria compared to the AGA criteria (97.7 vs. 88.6%), the specificity was higher in the AGA criteria compared to the Fukuoka criteria (62.4 vs. 58.2%).In a surgical series of patients with pancreatic cysts, the AGA and Fukuoka criteria had superior diagnostic accuracy for advanced neoplastic cysts compared to the original Sendai criteria.
Routine port-site excision in incidentally discovered gallbladder cancer is not associated with improved survival: A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium. Journal of surgical oncology Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T. M., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B. A., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Cardona, K., Maithel, S. K. 2017
Current data on the utility of port-site excision (PSE) during re-resection for incidentally discovered gallbladder cancer (IGBC) in the US are conflicting and limited to single-institution series.All patients with IGBC who underwent curative re-resection at 10 institutions from 2000 to 2015 were included. Patients with and without PSE were compared. Primary outcome was overall survival (OS).Of 449 pts with GBC, 266 were incidentally discovered, of which 193(73%) underwent curative re-resection and had port-site data; 47 pts(24%) underwent PSE, 146(76%) did not. The PSE rate remained similar over time (2000-2004: 33%; 2005-2009: 22%; 2010-2015:22%; P = 0.36). Both groups had similar demographics, operative procedures, and post-operative complications. There was no difference in T-stage (T1: 9 vs. 11%; T2: 52 vs. 52%; T3: 39 vs. 38%; P = 0.96) or LN involvement (36 vs. 41%; P = 0.7) between groups. A 3-year OS was similar between PSE and no PSE groups (65 vs. 43%; P = 0.07). On univariable analysis, residual disease at re-resection (HR = 2.1, 95% CI 1.4-3.3; P = 0.001), high tumor grade, and advanced T-stage were associated with decreased OS. Only grade and T-stage, but not PSE, persisted on multivariable analysis. Distant disease recurrence-rate was identical between PSE and no PSE groups (80 vs. 81%; P = 1.0).Port-site excision during re-resection for IGBC is not associated with improved overall survival and has the same distant disease recurrence compared to no port-site excision. Routine port-site excision is not recommended.
Comparative performances of the 7th and the 8th editions of the American Joint Committee on Cancer staging systems for intrahepatic cholangiocarcinoma. Journal of surgical oncology Spolverato, G., Bagante, F., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Guglielmi, A., Itaru, E., Pawlik, T. M. 2017
We sought to evaluate and validate the 8th edition of the AJCC classification using a multi-institutional cohort of patients with intrahepatic cholangiocarcinoma (ICC).Patients undergoing curative-intent hepatic resection for ICC between 1990 and 2015 at 14 major hepatobiliary centers were included and were staged according to 7th and 8th editions AJCC criteria.A total of 1154 patients underwent liver resection for ICC. When patients were staged using the AJCC 7th edition, T2a, T2b, and T4 patients had a higher hazard ratio (HR) of death compared with T1 (T2a, HR 1.43, P = 0.004; T2b, HR 1.99, P < 0.001; T4, HR 2.20, P < 0.001). T3 patients had a higher HR of death compared with T1 patients (HR 1.30, P = 0.029) but lower than T2a and T2b. According to AJCC 8th edition, T1b, T2, and T4 patients were at higher risk of death compared with T1a patients (T1b, HR 1.91, P < 0.001; T2, HR 2.29, P < 0.001; T4, HR 4.16, P < 0.001). As in the AJCC 7th edition, AJCC 8th edition T3 patients had a higher HR of death compared with T1 patients (HR 1.65, P = 0.001) but lower than T1b and T2. AJCC 8th edition. T-category performed slightly better than AJCC 7th edition with a C-index of 0.609 versus 0.590.A staging system that perfectly discriminates between stages has not yet been developed, but the AJCC 8th edition was able to better stratify the risk of death of Stage III and T3 patients.
Association of Optimal Time Interval to Re-resection for Incidental Gallbladder Cancer With Overall Survival A Multi-Institution Analysis From the US Extrahepatic Biliary Malignancy Consortium JAMA SURGERY Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T., Buettner, S., Poultsides, G., Thuy Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Kooby, D. A., Maithel, S. K. 2017; 152 (2): 143-148
The current recommendation is to perform re-resection for select patients with incidentally discovered gallbladder cancer. The optimal time interval for re-resection for both patient selection and long-term survival is not known.To assess the association of time interval from the initial cholecystectomy to reoperation with overall survival.This cohort study was conducted from January 1, 2000, to December 31, 2014 at 10 US academic institutions. A total of 207 patients with incidentally discovered gallbladder cancer who underwent reoperation and had available data on the date of their initial cholecystectomy were included.Time interval from the initial cholecystectomy to reoperation: group A: less than 4 weeks; group B: 4 to 8 weeks; and group C: greater than 8 weeks.Primary outcome was overall survival.Of 449 patients with gallbladder cancer, 207 cases (46%) were discovered incidentally and underwent reoperation at 3 different time intervals from the date of the original cholecystectomy: group A: less than 4 weeks (25 patients, 12%); B: 4 to 8 weeks (91 patients, 44%); C: more than 8 weeks (91 patients, 44%). The mean (SD) ages of patients in groups A, B, and C were 65 (9), 64 (11), and 66 (12) years, respectively. All groups were similar for baseline demographics, extent of resection, presence of residual disease, T stage, resection margin status, lymph node involvement, and postoperative complications. Patients who underwent reoperation between 4 and 8 weeks had the longest median overall survival (group B: 40.4 months) compared with those who underwent early (group A: 17.4 months) or late (group C: 22.4 months) reoperation (log-rank P = .03). Group A and C time intervals (vs group B), presence of residual disease, an R2 resection, advanced T stage, and lymph node involvement were associated with decreased overall survival on univariable Cox regression. Only group A (hazard ratio, 2.63; 95% CI, 1.25-5.54) and group C (hazard ratio, 2.07; 95% CI, 1.17-3.66) time intervals (vs group B), R2 resection (hazard ratio, 2.69; 95% CI, 1.27-5.69), and advanced Tstage (hazard ratio, 1.85; 95% CI, 1.11-3.08) persisted on multivariable Cox regression analysis.The optimal time interval for re-resection for incidentally discovered gallbladder cancer appears to be between 4 and 8 weeks after the initial cholecystectomy.
Histologic classification and grading enhances gallbladder cancer staging: A population-based prognostic score validated by the US Extrahepatic Biliary Malignancy Consortium. Thuy Tran, Ethun, C., Pawlik, T. M., Buettner, S., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. G., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Maithel, S., Poultsides, G. A. AMER SOC CLINICAL ONCOLOGY. 2017
Impact of major vascular resection on short- and long-term outcomes in patients with intrahepatic cholangiocarcinoma. Reames, B., Pawlik, T. M., Ejaz, A., Marques, H., Aldrighetti, L., Maithel, S., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J., Popescu, I., Sandroussi, C., Clark, T. AMER SOC CLINICAL ONCOLOGY. 2017
Actual 5-year survivors following resection of hilar cholangiocarcinoma. Thuy Tran, Ethun, C., Pawlik, T. M., Buettner, S., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. G., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Maithel, S., Poultsides, G. A. AMER SOC CLINICAL ONCOLOGY. 2017
A novel t-stage classification system for adrenocortical carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group. Poorman, C., Ethun, C., Postlewait, L., Thuy Tran, Pawlik, T. M., Wang, T. S., Hatzaras, I., Phay, J. E., Fields, R. C., Weber, S. M., Sicklick, J. K., Yopp, A., Prescott, J., Duh, Q., Solorzano, C. C., Votanopoulos, K., Poultsides, G. A., Maithel, S. AMER SOC CLINICAL ONCOLOGY. 2017
The impact of extrahepatic disease among patients undergoing liver-directed therapy for neuroendocrine liver metastasis: A multi-institutional analysis. Ejaz, A., Pawlik, T. M., Reames, B., Maithel, S., Poultsides, G. A., Bauer, T. W., Fields, R. C., Weiss, M. J., Marques, H., Aldrighetti, L. AMER SOC CLINICAL ONCOLOGY. 2017
Effect of perioperative transfusion on recurrence and survival after resection of distal cholangiocarcinoma: A 10-institution study from the US Extrahepatic Biliary Malignancy Consortium. Lopez-Aguiar, A. G., Ethun, C., Pawlik, T. M., Poultsides, G. A., Thuy Tran, Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. G., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Maithel, S. AMER SOC CLINICAL ONCOLOGY. 2017
Minimally Invasive Resection of Adrenocortical Carcinoma: a Multi-Institutional Study of 201 Patients JOURNAL OF GASTROINTESTINAL SURGERY Lee, C. W., Salem, A. I., Schneider, D. F., Leverson, G. E., Tran, T. B., Poultsides, G. A., Postlewait, L. M., Maithel, S. K., Wang, T. S., Hatzaras, I., Shenoy, R., Phay, J. E., Shirley, L., Fields, R. C., Jin, L. X., Pawlik, T. M., Prescott, J. D., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Weber, S. M. 2017; 21 (2): 352-362
Minimally invasive surgery for adrenocortical carcinoma (ACC) is controversial. We sought to evaluate the perioperative and long-term outcomes following minimally invasive (MIS) and open resection (OA) of ACC in patients treated with curative intent surgery.Retrospective data from patients who underwent adrenalectomy for primary ACC at 13 tertiary care cancer centers were analyzed, including demographics, clinicopathological, and operative outcomes. Outcomes following MIS were compared to OA.A total of 201 patients were evaluated including 47 MIS and 154 OA. There was no difference in utilization of MIS approach among institutions (p = 0.24) or 30-day morbidity (29.3 %, MIS, vs. 30.9 %, OA; p = 0.839). The only preoperatively determined predictor for MIS was smaller tumor size (p < 0.001). There was no difference in rates of intraoperative tumor rupture (p = 0.612) or R0 resection (p = 0.953). Only EBL (p = 0.038) and T stage (p = 0.045) were independent prognostic indicators of overall survival after adjusting for significant factors. The surgical approach was not associated with overall or disease-free survival.MIS adrenalectomy may be utilized for preoperatively determined ACC ≤ 10.0 cm; however, OA should be utilized for adrenal masses with either preoperative or intraoperative evidence of local invasion or enlarged lymph nodes, regardless of size.
Neuroendocrine liver metastasis: The chance to be cured after liver surgery. Journal of surgical oncology Bagante, F., Spolverato, G., Merath, K., Postlewait, L. M., Poultsides, G. A., Mullen, M. G., Bauer, T. W., Fields, R. C., Lamelas, J., Marques, H. P., Aldrighetti, L., Tran, T., Maithel, S. K., Pawlik, T. M. 2017
Neuroendocrine liver metastasis tumors (NELM) are a heterogeneous group of neoplasms with varied histologic features and a wide range of clinical behaviors. We aimed to identify the fraction of patients cured after liver surgery for NELM.Cure fraction models were used to analyze 376 patients who underwent hepatectomy with curative intent for NELM.The median and 5-year disease-free survival (DFS) were 4.5 years and 46%, respectively. The probability of being cured from NELM by liver surgery was 44%; the time to cure was 5.1 years. In a multivariable cure model, type of neuroendocrine tumor (NET), grade of tumor differentiation, and rate of liver involvement resulted as independent predictors of cure. The cure fraction for patients with well differentiated NELM from gastrointestinal NET or a functional pancreatic NET, and with <50% of liver-involvement was 95%. Patients who had moderately/poorly differentiated NELM from a non-functional pancreatic NET, and with <50% of liver-involvement was 43%. In the presence of all the three unfavorable prognostic factors (nonfunctional PNET, liver involvement >50%, moderately/poorly differentiation), the cure fraction was 8%.Statistical cure after surgery for NELM is possible, and allow for a more accurate prediction of long-term outcome among patients with NELM undergoing liver resection.
The effect of preoperative chemotherapy treatment in surgically treated intrahepatic cholangiocarcinoma patients-A multi-institutional analysis. Journal of surgical oncology Buettner, S., Koerkamp, B. G., Ejaz, A., Buisman, F. E., Kim, Y., Margonis, G. A., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., IJzermans, J. N., Pawlik, T. M. 2017
While preoperative chemotherapy (pCT) is utilized in many intra-abdominal cancers, the use of pCT among patients with intrahepatic cholangiocarcinoma (ICC) remains ill defined. As such, the objective of the current study was to examine the impact of pCT among patients undergoing curative-intent resection for ICC.Patients who underwent hepatectomy for ICC were identified from a multi-institutional international cohort. The association between pCT with peri-operative and long-term clinical outcomes was assessed.Of the 1 057 patients who were identified and met the inclusion criteria, 62 patients (5.9%) received pCT. These patients were noticed to have more advanced disease. Median OS (pCT:46.9 months vs no pCT:37.4 months; P = 0.900) and DFS (pCT: 34.1 months vs no pCT: 29.1 months; P = 0.909) were similar between the two groups. In a subgroup analysis of propensity-score matched patients, there was longer OS (pCT:46.9 months vs no pCT:29.4 months) and DFS (pCT:34.1 months vs no pCT:14.0 months); however this did not reach statistical significance (both P > 0.05).In conclusion, pCT utilization among patients with ICC was higher among patients with more advanced disease. Short-term post-operative outcomes were not affected by pCT use and receipt of pCT resulted in equivalent OS and DFS following curative-intent resection.
Gastric Staging System for Gastroesophageal Junction Cancer in a Western Population. American surgeon Adeshuko, F. A., Squires, M. H., Poultsides, G., Pawlik, T. M., Weber, S. M., Schmidt, C., Votanopoulos, K., Fields, R. C., Maithel, S. K., Cardona, K. 2017; 83 (1): 82-89
Controversy exists over the staging of gastroesophageal junction (GEJ) adenocarcinomas. The aim of our study was to assess the adequacy of the American Joint Committee on Cancer 7th edition esophageal (E7) and gastric (G7) staging systems for GEJ tumors in a western population. All patients with GEJ adenocarcinoma who underwent curative resection from 2000 to 2012 were identified from the United States Gastric Cancer Collaborative database and assessed according to the E7 and G7 systems. Fifty-one patients were identified. Neither the E7 nor G7 system adequately stratified patients by T or N stage with a loss of distinctiveness between T1 to 4 and N0 to 3 tumors. On final stage analysis, the outcomes were similar between both systems; however, neither system, with the exception of the G7 stage I versus II, adequately stratified patients by stage (E7: I vs II, P = 0.07; II vs III, P = 0.23; G7: I vs II, P = 0.02; II vs III, P = 0.13). Histologic grade was not associated with survival (P = 0.27) and did not improve the ability to stratify patients in the E7 system. Our study identifies limitations in the proper stratification of patients with GEJ adenocarcinoma using either the American Joint Committee on Cancer 7th esophageal or gastric systems. The classification of GEJ adenocarcinoma within either system needs to be further studied in a larger patient population.
The impact of extrahepatic disease among patients undergoing liver-directed therapy for neuroendocrine liver metastasis. Journal of surgical oncology Ejaz, A. n., Reames, B. N., Maithel, S. n., Poultsides, G. A., Bauer, T. W., Fields, R. C., Weiss, M. n., Marques, H. P., Aldrighetti, L. n., Pawlik, T. M. 2017; 116 (7): 841–47
Management of neuroendocrine liver metastasis (NELM) in the presence of extrahepatic disease (EHD) is controversial. We sought to examine outcomes of patients undergoing liver-directed therapy (resection, ablation, or both) for NELM in the presence of EHD using a large international cohort of patients.612 patients who underwent liver-directed therapy were identified from eight institutions. Postoperative outcomes, as well as and overall (OS) were compared among patients with and without EHD.Most primary tumors were located in the pancreas (N = 254;41.8%) or the small bowel (N = 188;30.9%). Patients underwent surgery alone (N = 471;77.0%), ablation alone (N = 15;2.5%), or a combined approach (N = 126;20.6%). Patients with EHD had more high-grade tumors (EHD: 44.4% vs no EHD: 16.1%; P < 0.001). EHD was often the peritoneum (N = 29;41.4%) or lung (N = 19;27.1%). Among 70 patients with EHD, 20.0% (N = 14) underwent concurrent resection for EHD. After median follow-up of 51 months, 174 (28.4%) patients died with a median OS of 140.4 months. Patients with EHD had a shorter median OS versus patients who did not have EHD (EHD: 87 months vs no EHD: not reached; P = 0.002). EHD was independently associated with an increased risk of death (HR: 2.56, 95%CI 1.16-5.62; P = 0.02).Patients with NELM and EHD had more aggressive tumors, conferring a twofold increased risk of death. Surgical treatment of NELM among patients with EHD should be individualized.
Impact of adjuvant chemotherapy on survival in patients with intrahepatic cholangiocarcinoma: a multi-institutional analysis. HPB : the official journal of the International Hepato Pancreato Biliary Association Reames, B. N., Bagante, F. n., Ejaz, A. n., Spolverato, G. n., Ruzzenente, A. n., Weiss, M. n., Alexandrescu, S. n., Marques, H. P., Aldrighetti, L. n., Maithel, S. K., Pulitano, C. n., Bauer, T. W., Shen, F. n., Poultsides, G. A., Soubrane, O. n., Martel, G. n., Koerkamp, B. G., Guglielmi, A. n., Itaru, E. n., Pawlik, T. M. 2017; 19 (10): 901–9
The benefit of adjuvant chemotherapy for resected intrahepatic cholangiocarcinoma (ICC) is unclear. The aim of the current study was to investigate the impact of adjuvant chemotherapy on survival among patients undergoing resection of ICC using a multi-institutional database.1154 ICC patients undergoing curative-intent hepatectomy between 1990 and 2015 were identified from 14 institutions. Cox proportional hazard modeling was used to determine the impact of adjuvant chemotherapy on overall survival (OS).Following resection, 347 (30%) patients received adjuvant chemotherapy, most commonly a gemcitabine-based regimen (n = 184, 52%). Patients with T2/T3/T4 disease were more likely to receive adjuvant therapy compared with patients with T1a/T1b disease (OR 2.5, 95%CI 1.89-3.23; P < 0.001). Among patients who did and did not receive adjuvant therapy, patients with T2/T3/T4 tumors had a 5-year OS of 37% (95%CI 28.9-44.4) versus 30% (95%CI 23.8-35.6), respectively (p = 0.006). Similarly patients with N1 disease who received adjuvant chemotherapy tended to have improved 5-year OS (18.3%, 95%CI 9.0-30.1 vs. no adjuvant therapy 12%, 95%CI 3.9-24.4; P = 0.050).While adjuvant chemotherapy did not influence the prognosis of all ICC patients following surgical resection, it was associated with a potential survival benefit in subgroups of patients at increased risk for recurrence, such as those with advanced tumors.
Early Recurrence of Neuroendocrine Liver Metastasis After Curative Hepatectomy: Risk Factors, Prognosis, and Treatment. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Zhang, X. F., Beal, E. W., Chakedis, J. n., Lv, Y. n., Bagante, F. n., Aldrighetti, L. n., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S. K., Marques, H. P., Weiss, M. n., Pawlik, T. M. 2017; 21 (11): 1821–30
Early tumor recurrence after curative resection typically indicates a poor prognosis. The objective of the current study was to investigate the risk factors, treatment, and prognosis of early recurrence of neuroendocrine tumor (NET) liver metastasis (NELM) after hepatic resection.A total of 481 patients who underwent curative-intent resection for NELM were identified from a multi-institutional database. Data on clinicopathological characteristics, intraoperative details, and outcomes were documented. The optimal cutoff value to differentiate early and late recurrence was determined to be 3 years based on linear regression.With a median follow-up of 60 months, 223 (46.4%) patients developed a recurrence, including 158 (70.9%) early and 65 (29.1%) late recurrences. On multivariable analysis, pancreatic NET, primary tumor lymph node metastasis, and a microscopic positive surgical margin were independent risk factors for early intrahepatic recurrence. While recurrence patterns and treatments were comparable among patients with early and late recurrences, early recurrence was associated with worse disease-specific survival than late recurrences (10-year NELM-specific survival, 44.5 vs 75.8%, p < 0.001). Among the 34 (21.5%) patients who underwent curative treatment for early recurrence, post-recurrence disease-specific survival was better than non-curatively treated patients (10-year NELM-specific survival, 54.2 vs 26.3%, p = 0.028), yet similar to patients with late recurrences treated with curative intent (10-year NELM-specific survival, 54.2 vs 37.4%, p = 0.519).Early recurrence after surgery for NELM was associated with the pancreatic type, primary lymph node metastasis, and extrahepatic disease. Re-treatment with curative intent prolonged survival after recurrence, and therefore, operative intervention even for early recurrences of NELM should be considered.
Perioperative and Long-Term Outcome for Intrahepatic Cholangiocarcinoma: Impact of Major Versus Minor Hepatectomy. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Zhang, X. F., Bagante, F. n., Chakedis, J. n., Moris, D. n., Beal, E. W., Weiss, M. n., Popescu, I. n., Marques, H. P., Aldrighetti, L. n., Maithel, S. K., Pulitano, C. n., Bauer, T. W., Shen, F. n., Poultsides, G. A., Soubrane, O. n., Martel, G. n., Groot Koerkamp, B. n., Guglielmi, A. n., Itaru, E. n., Pawlik, T. M. 2017; 21 (11): 1841–50
The objective of the current study was to investigate both short- and long-term outcomes of patients undergoing curative-intent resection for intrahepatic cholangiocarcinoma (ICC) stratified by extent of hepatic resection relative to overall final pathological margin status.One thousand twenty-three patients with ICC who underwent curative-intent resection were identified from a multi-institutional database. Demographic, clinicopathological, and operative data, as well as overall (OS) and recurrence-free survival (RFS) were compared among patients undergoing major and minor resection before and after propensity score matching.Overall, 608 (59.4%) patients underwent major hepatectomy, while 415 (40.6%) had a minor resection. Major hepatectomy was more frequently performed among patients who had large, multiple, and bilobar tumors. Roughly half of patients (n = 294, 48.4%) developed a postoperative complication following major hepatectomy versus only one fourth of patients (n = 113, 27.2%) after minor resection (p < 0.001). In the propensity model, patients who underwent major hepatectomy had an equivalent OS and RFS versus patients who had a minor hepatectomy (median OS, 38 vs. 37 months, p = 0.556; and median RFS, 20 vs. 18 months, p = 0.635). Patients undergoing major resection had comparable OS and RFS with wide surgical margin (≥10 and 5-9 mm), but improved RFS when surgical margin was narrow (1-4 mm) versus minor resection in the propensity model. In the Cox regression model, tumor characteristics and surgical margin were independently associated with long-term outcome.Major hepatectomy for ICC was not associated with an overall survival benefit, yet was associated with increased perioperative morbidity. Margin width, rather than the extent of resection, affected long-term outcomes. Radical parenchymal-sparing resection should be advocated if a margin clearance of ≥5 mm can be achieved.
Defining Long-Term Survivors Following Resection of Intrahepatic Cholangiocarcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Bagante, F. n., Spolverato, G. n., Weiss, M. n., Alexandrescu, S. n., Marques, H. P., Aldrighetti, L. n., Maithel, S. K., Pulitano, C. n., Bauer, T. W., Shen, F. n., Poultsides, G. A., Soubrane, O. n., Martel, G. n., Groot Koerkamp, B. n., Guglielmi, A. n., Itaru, E. n., Pawlik, T. M. 2017; 21 (11): 1888–97
Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival.Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS < 5).Among the 1154 patients who underwent liver resection for ICC, 5- and 10-year OS were 39.6 and 20.3% while the actual LT survival rate was 13.3%. After excluding 475 patients who survived < 5 years, as well as patients were alive yet had < 5 years of follow-up, 153 patients (22.5%) who survived ≥ 5 years were included in the LT group, while 526 patients (77.5%) who died < 5 years from the date of surgery were included in the non-LT group. Factors associated with not surviving to 5 years included perineural invasion (OR 4.78, 95% CI, 1.92-11.8; p = 0.001), intrahepatic metastasis (OR 3.75, 95% CI, 0.85-16.6, p = 0.082), satellite lesions (OR 2.12, 95% CI, 1.15-3.90, p = 0.016), N1 status (OR 4.64, 95% CI, 1.77-12.2; p = 0.002), ICC > 5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (< 10%) who had these pathological characteristics were LT.While ICC is generally associated with a poor prognosis, some patients will be LT. In fact, even a subset of patients with traditional adverse prognostic factors survived long term.
Diagnostic staging laparoscopy in gastric cancer treatment: A cost-effectiveness analysis. Journal of surgical oncology Li, K. n., Cannon, J. G., Jiang, S. Y., Sambare, T. D., Owens, D. K., Bendavid, E. n., Poultsides, G. A. 2017
Accurate preoperative staging helps avert morbidity, mortality, and cost associated with non-therapeutic laparotomy in gastric cancer (GC) patients. Diagnostic staging laparoscopy (DSL) can detect metastases with high sensitivity, but its cost-effectiveness has not been previously studied. We developed a decision analysis model to assess the cost-effectiveness of preoperative DSL in GC workup.Analysis was based on a hypothetical cohort of GC patients in the U.S. for whom initial imaging shows no metastases. The cost-effectiveness of DSL was measured as cost per quality-adjusted life-year (QALY) gained. Drivers of cost-effectiveness were assessed in sensitivity analysis.Preoperative DSL required an investment of $107 012 per QALY. In sensitivity analysis, DSL became cost-effective at a threshold of $100 000/QALY when the probability of occult metastases exceeded 31.5% or when test sensitivity for metastases exceeded 86.3%. The likelihood of cost-effectiveness increased from 46% to 93% when both parameters were set at maximum reported values.The cost-effectiveness of DSL for GC patients is highly dependent on patient and test characteristics, and is more likely when DSL is used selectively where procedure yield is high, such as for locally advanced disease or in detecting peritoneal and superficial versus deep liver lesions.
Defining the Chance of Statistical Cure Among Patients with Extrahepatic Biliary Tract Cancer. World journal of surgery Spolverato, G., Bagante, F., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Winslow, E., Cho, C., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2017; 41 (1): 224-231
While surgery offers the best curative-intent treatment, many patients with biliary tract malignancies have poor long-term outcomes. We sought to apply a non-mixture cure model to calculate the cure fraction and the time to cure after surgery of patients with peri-hilar cholangiocarcinoma (PHCC) or gallbladder cancer (GBC).Using the Extrahepatic Biliary Malignancy Consortium, 576 patients who underwent curative-intent surgery for gallbladder carcinoma or peri-hilar cholangiocarcinoma between 1998 and 2014 at 10 major hepatobiliary institutions were identified and included in the analysis. A non-mixture cure model was adopted to compare mortality after surgery to the mortality expected for the general population matched by sex and age.The median and 5-year overall survival (OS) were 1.9 years (IQR, 0.9-4.9) and 23.9 % (95 % CI, 19.6-28.6). Among all patients with PHCC or GBC, the probability of being cured after surgery was 14.5 % (95 % CI, 8.7-23.2); the time to cure was 9.7 years and the median survival of uncured patients was 1.8 years. Determinants of cure probabilities included lymph node metastasis and CA 19.9 level (p ≤ 0.05). The cure fraction for patients with a CA 19.9 < 50 U/ml and no lymph nodes metastases were 39.0 % versus only 5.1 % among patients with a CA 19.9 ≥ 50 who also had lymph node metastasis.Examining an "all comer" cohort, <15 % of patients with PHCC or GBC could be considered cured after surgery. Factors such CA 19.9 level and lymph node metastasis independently predicted long-term outcome. Estimating the odds of statistical cure following surgery for biliary tract cancer can assist in decision-making as well as inform discussions around survivorship.
A Multi-Institutional Study Comparing the Use of the American Joint Committee on Cancer 7th Edition Esophageal versus Gastric Staging System for Gastroesophageal Junction Cancer in a Western Population AMERICAN SURGEON Adeshuko, F. A., Squires, M. H., Poultsides, G., Pawlik, T. M., Weber, S. M., Schmidt, C., Votanopoulos, K., Fields, R. C., Maithel, S. K., Cardona, K. 2017; 83 (1): 82-89
Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability ANNALS OF SURGERY Kim, Y., Margonis, G. A., Prescott, J. D., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Glenn, J. A., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2017; 265 (1): 197-204
To evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC).ACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery.CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x).One hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%).DFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.
An Untapped Resource: Left Renal Vein Interposition Graft for Portal Vein Reconstruction During Pancreaticoduodenectomy DIGESTIVE DISEASES AND SCIENCES Tran, T. B., Mell, M. W., Poultsides, G. A. 2017; 62 (1): 68-71
Oncologic Procedures Amenable to Fluorescence-guided Surgery. Annals of surgery Tipirneni, K. E., Warram, J. M., Moore, L. S., Prince, A. C., de Boer, E., Jani, A. H., Wapnir, I. L., Liao, J. C., Bouvet, M., Behnke, N. K., Hawn, M. T., Poultsides, G. A., Vahrmeijer, A. L., Carroll, W. R., Zinn, K. R., Rosenthal, E. 2016
Although fluorescence imaging is being applied to a wide range of cancers, it remains unclear which disease populations will benefit greatest. Therefore, we review the potential of this technology to improve outcomes in surgical oncology with attention to the various surgical procedures while exploring trial endpoints that may be optimal for each tumor type.For many tumors, primary treatment is surgical resection with negative margins, which corresponds to improved survival and a reduction in subsequent adjuvant therapies. Despite unfavorable effect on patient outcomes, margin positivity rate has not changed significantly over the years. Thus, patients often experience high rates of re-excision, radical resections, and overtreatment. However, fluorescence-guided surgery (FGS) has brought forth new light by allowing detection of subclinical disease not readily visible with the naked eye.We performed a systematic review of clinicatrials.gov using search terms "fluorescence," "image-guided surgery," and "near-infrared imaging" to identify trials utilizing FGS for those received on or before May 2016.fluorescence surgery for tumor debulking, wide local excision, whole-organ resection, and peritoneal metastases.fluorescence in situ hybridization, fluorescence imaging for lymph node mapping, nonmalignant lesions, nonsurgical purposes, or image guidance without fluorescence.Initial search produced 844 entries, which was narrowed down to 68 trials. Review of literature and clinical trials identified 3 primary resection methods for utilizing FGS: (1) debulking, (2) wide local excision, and (3) whole organ excision.The use of FGS as a surgical guide enhancement has the potential to improve survival and quality of life outcomes for patients. And, as the number of clinical trials rise each year, it is apparent that FGS has great potential for a broad range of clinical applications.
Distal Cholangiocarcinoma and Pancreas Adenocarcinoma: Are They Really the Same Disease? A 13-Institution Study from the US Extrahepatic Biliary Malignancy Consortium and the Central Pancreas Consortium. Journal of the American College of Surgeons Ethun, C. G., Lopez-Aguiar, A. G., Pawlik, T. M., Poultsides, G., Idrees, K., Fields, R. C., Weber, S. M., Cho, C., Martin, R. C., Scoggins, C. R., Shen, P., Schmidt, C., Hatzaras, I., Bentrem, D., Ahmad, S., Abbott, D., Kim, H. J., Merchant, N., Staley, C. A., Kooby, D. A., Maithel, S. K. 2016
Distal cholangiocarcinoma (DC) and pancreatic ductal adenocarcinoma (PDAC) are often managed as 1 entity, yet direct comparisons are lacking. Our aim was to use 2 large multi-institutional databases to assess treatment, pathologic, and survival differences between these diseases.This study included patients with DC and PDAC who underwent curative-intent pancreaticoduodenectomy from 2000 to 2015 at 13 institutions comprising the US Extrahepatic Biliary Malignancy and Central Pancreas Consortiums. Primary endpoint was disease-specific survival (DSS).Of 1,463 patients, 224 (15%) had DC and 1,239 (85%) had PDAC. Compared with PDAC, DC patients were less likely to be margin-positive (19% vs 25%; p = 0.005), lymph node (LN)-positive (55% vs 69%; p < 0.001), and receive adjuvant therapy (57% vs 71%; p < 0.001). Of DC patients treated with adjuvant therapy, 62% got gemcitabine alone and 16% got gemcitabine/cisplatin. Distal cholangiocarcinoma was associated with improved median DSS (40 months) compared with PDAC (22 months; p < 0.001), which persisted on multivariable analysis (hazard ratio 0.65; 95% CI 0.50 to 0.84; p = 0.001). Lymph node involvement was the only factor independently associated with decreased DSS for both DC and PDAC. The DC/LN-positive patients had similar DSS as PDAC/LN-negative patients (p = 0.74). Adjuvant therapy (chemotherapy ± radiation) was associated with improved median DSS for PDAC/LN-positive patients (21 vs 13 months; p = 0.001), but not for DC patients (38 vs 40 months; p = 0.62), regardless of LN status.Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are distinct entities. Distal cholangiocarcinoma has a favorable prognosis compared with PDAC, yet current adjuvant therapy regimens are only associated with improved survival in PDAC, not DC. Therefore, treatment paradigms used for PDAC should not be extrapolated to DC, despite similar operative approaches, and novel therapies for DC should be explored.
Enumeration and targeted analysis of KRAS, BRAF and PIK3CA mutations in CTCs captured by a label-free platform: Comparison to ctDNA and tissue in metastatic colorectal cancer ONCOTARGET Kidess-Sigal, E., Liu, H. E., Triboulet, M. M., Che, J., Ramani, V. C., Visser, B. C., Poultsides, G. A., Longacre, T. A., Marziali, A., Vysotskaia, V., Wiggin, M., Heirich, K., Hanft, V., Keilholz, U., Tinhofer, I., Norton, J. A., Lee, M., Sollier-Christen, E., Jeffrey, S. S. 2016; 7 (51): 85349-85364
Treatment of advanced colorectal cancer (CRC) requires multimodal therapeutic approaches and need for monitoring tumor plasticity. Liquid biopsy biomarkers, including CTCs and ctDNA, hold promise for evaluating treatment response in real-time and guiding therapeutic modifications. From 15 patients with advanced CRC undergoing liver metastasectomy with curative intent, we collected 41 blood samples at different time points before and after surgery for CTC isolation and quantification using label-free Vortex technology. For mutational profiling, KRAS, BRAF, and PIK3CA hotspot mutations were analyzed in CTCs and ctDNA from 23 samples, nine matched liver metastases and three primary tumor samples. Mutational patterns were compared. 80% of patient blood samples were positive for CTCs, using a healthy baseline value as threshold (0.4 CTCs/mL), and 81.4% of captured cells were EpCAM+ CTCs. At least one mutation was detected in 78% of our blood samples. Among 23 matched CTC and ctDNA samples, we found a concordance of 78.2% for KRAS, 73.9% for BRAF and 91.3% for PIK3CA mutations. In several cases, CTCs exhibited a mutation that was not detected in ctDNA, and vice versa. Complementary assessment of both CTCs and ctDNA appears advantageous to assess dynamic tumor profiles.
View details for DOI 10.18632/oncotarget.13350
Actual 10-Year Survivors Following Resection of Adrenocortical Carcinoma JOURNAL OF SURGICAL ONCOLOGY Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J. D., Wang, T. S., Glenn, J., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Hatzaras, I., Shenoy, R., Pawlik, T. M., Norton, J. A., Poultsides, G. A. 2016; 114 (8): 971-976
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited therapeutic options beyond surgical resection. The characteristics of actual long-term survivors following surgical resection for ACC have not been previously reported.Patients who underwent resection for ACC at one of 13 academic institutions participating in the US Adrenocortical Carcinoma Group from 1993 to 2014 were analyzed. Patients were stratified into four groups: early mortality (died within 2 years), late mortality (died within 2-5 years), actual 5-year survivor (survived at least 5 years), and actual 10-year survivor (survived at least 10 years). Patients with less than 5 years of follow-up were excluded.Among the 180 patients available for analysis, there were 49 actual 5-year survivors (27%) and 12 actual 10-year survivors (7%). Patients who experienced early mortality had higher rates of cortisol-secreting tumors, nodal metastasis, synchronous distant metastasis, and R1 or R2 resections (all P < 0.05). The need for multi-visceral resection, perioperative blood transfusion, and adjuvant therapy correlated with early mortality. However, nodal involvement, distant metastasis, and R1 resection did not preclude patients from becoming actual 10-year survivors. Ten of twelve actual 10-year survivors were women, and of the seven 10-year survivors who experienced disease recurrence, five had undergone repeat surgery to resect the recurrence.Surgery for ACC can offer a 1 in 4 chance of actual 5-year survival and a 1 in 15 chance of actual 10-year survival. Long-term survival was often achieved with repeat resection for local or distant recurrence, further underscoring the important role of surgery in managing patients with ACC. J. Surg. Oncol. 2016;114:971-976. © 2016 Wiley Periodicals, Inc.
Development and Validation of Biopsy-Free Genotyping for Molecular Subtyping of Diffuse Large B-Cell Lymphoma 58th Annual Meeting and Exposition of the American-Society-of-Hematology Scherer, F., Kurtz, D. M., Newman, A. M., Esfahani, M. S., Craig, A., Stehr, H., Lovejoy, A. F., Chabon, J. J., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Ohgami, R. S., Davis, E. R., Gaidano, G., Kunder, C. A., Rossi, D., Westin, J. R., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2016
Noninvasive Detection of BCL2, BCL6, and MYC Translocations in Diffuse Large B-Cell Lymphoma Kurtz, D. M., Scherer, F., Newman, A. M., Craig, A., Jin, M., Stehr, H., Chabon, J. J., Esfahani, M., Liu, C., Zhou, L., Glover, C., Visser, B. C., Poultsides, G., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Ohgami, R. S., Davis, R., Kunder, C. A., Westin, J. R., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2016
Lymphadenectomy for Adrenocortical Carcinoma: Is There a Therapeutic Benefit? ANNALS OF SURGICAL ONCOLOGY Gerry, J. M., Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J. D., Wang, T. S., Glenn, J. A., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Hatzaras, I., Shenoy, R., Pawlik, T. M., Norton, J. A., Poultsides, G. A. 2016; 23: S708-S713
Lymph node metastasis is an established predictor of poor outcome for adrenocortical carcinoma (ACC); however, routine lymphadenectomy during surgical resection of ACC is not widely performed and its therapeutic role remains unclear.Patients undergoing margin-negative resection for localized ACC were identified from a multi-institutional database. Patients were stratified into 2 groups based on the surgeon's effort or not to perform a lymphadenectomy as documented in the operative note. Clinical, pathologic, and outcome data were compared between the 2 groups.Of 120 patients who met inclusion criteria from 1993 to 2014, 32 (27 %) underwent lymphadenectomy. Factors associated with lymphadenectomy were tumor size (12 vs. 9.5 cm; p = .007), palpable mass at presentation (26 vs. 12 %; p = .07), suspicious lymph nodes on preoperative imaging (44 vs. 7 %; p < .001), and need for multivisceral resection (78 vs. 36 %; p < .001). Median number of lymph nodes harvested was higher in the lymphadenectomy group (5.5 vs. 0; p < .001). In-hospital mortality (0 vs. 1.3 %; p = .72) and grade 3/4 complication rates (0 vs. 12 %; p = .061) were not significantly different. Patients who underwent lymphadenectomy had improved overall survival (5-year 76 vs. 59 %; p = .041). The benefit of lymphadenectomy on overall survival persisted on multivariate analysis (HR = 0.17; p = .006) controlling for adverse preoperative and intraoperative factors associated with lymphadenectomy, such as tumor size, palpable mass, irregular tumor edges, suspicious nodes on imaging, and multivisceral resection.In this multicenter study of adrenocortical carcinoma patients undergoing R0 resection, the surgeon's effort to dissect peritumoral lymph nodes was independently associated with improved overall survival.
Lymphadenectomy for Adrenocortical Carcinoma: Is There a Therapeutic Benefit? Annals of surgical oncology Gerry, J. M., Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J. D., Wang, T. S., Glenn, J. A., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Hatzaras, I., Shenoy, R., Pawlik, T. M., Norton, J. A., Poultsides, G. A. 2016; 23: 708-713
Changing Odds of Survival Over Time among Patients Undergoing Surgical Resection of Gallbladder Carcinoma. Annals of surgical oncology Buettner, S., Margonis, G. A., Kim, Y., Gani, F., Ethun, C. G., Poultsides, G. A., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016; 23 (13): 4401-4409
While survival after malignancies is traditionally reported as actuarial survival, conditional survival (CS) may be more clinically relevant by accounting for "accrued" survival time as time progresses. We sought to compare actuarial and CS among patients with gallbladder carcinoma (GBC) .A total of 312 patients who underwent curative intent surgery for GBC between 2000 and 2014 were identified using a multi-institutional database. Overall survival (OS) was estimated using the Kaplan-Meier method. CS was calculated as the probability of surviving an additional 3 years at year "x" after surgery using the formula CS3 = S(x+3)/Sx.Among all patients, the median actuarial OS was 24.8 months (IQR 13.3-88.9). While actuarial survival decreased over time, 3-year CS (CS3) increased, with CS3 at 2 years after surgery noted to be 61.8 % compared with the 5-year actuarial OS of 31.6 %. Factors associated with reduced actuarial OS were positive margin status (HR 3.61, 95 % CI 2.47-5.26), increasing tumor size (HR = 1.02, 95 % CI 1.01-1.02), higher tumor grade (HR 2.98, 95 % CI 1.47-6.04), residual disease at repeat resection (HR = 2.78, 95 % CI 1.49-3.49, p < 0.001), and lymph node metastasis (HR = 1.95, 95 % CI 1.39-2.75, all p < 0.001). The calculated CS3 exceeded the actuarial survival within each high-risk patient subgroup. For example, patients with residual disease at repeat resection had an actuarial survival 23.1 % at 5 years versus a CS3 of 56.3 % in patients alive at 2 years (Δ = 33.2 %).CS provides a more accurate, dynamic estimate for survival, especially among high-risk patients. CS estimates can be used to accurately predict survival and guide clinical decision making.
Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA SCIENCE TRANSLATIONAL MEDICINE Scherer, F., Kurtz, D. M., Newman, A. M., Stehr, H., Craig, A. F., Esfahani, M. S., Lovejoy, A. F., Chabon, J. J., Klass, D. M., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G. A., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Ohgami, R. S., Kunder, C. A., Diehn, M., Alizadeh, A. A. 2016; 8 (364)
Patients with diffuse large B cell lymphoma (DLBCL) exhibit marked diversity in tumor behavior and outcomes, yet the identification of poor-risk groups remains challenging. In addition, the biology underlying these differences is incompletely understood. We hypothesized that characterization of mutational heterogeneity and genomic evolution using circulating tumor DNA (ctDNA) profiling could reveal molecular determinants of adverse outcomes. To address this hypothesis, we applied cancer personalized profiling by deep sequencing (CAPP-Seq) analysis to tumor biopsies and cell-free DNA samples from 92 lymphoma patients and 24 healthy subjects. At diagnosis, the amount of ctDNA was found to strongly correlate with clinical indices and was independently predictive of patient outcomes. We demonstrate that ctDNA genotyping can classify transcriptionally defined tumor subtypes, including DLBCL cell of origin, directly from plasma. By simultaneously tracking multiple somatic mutations in ctDNA, our approach outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies. In addition, we identified distinct patterns of clonal evolution distinguishing indolent follicular lymphomas from those that transformed into DLBCL, allowing for potential noninvasive prediction of histological transformation. Collectively, our results demonstrate that ctDNA analysis reveals biological factors that underlie lymphoma clinical outcomes and could facilitate individualized therapy.
View details for DOI 10.1126/scitranslmed.aai8545
A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the U.S. Extrahepatic Biliary Malignancy Consortium. Annals of surgical oncology Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T. M., Buettner, S., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Merchant, N., Cardona, K., Maithel, S. K. 2016: -?
Association of Optimal Time Interval to Re-resection for Incidental Gallbladder Cancer With Overall Survival: A Multi-Institution Analysis From the US Extrahepatic Biliary Malignancy Consortium. JAMA surgery Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T. M., Buettner, S., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Kooby, D. A., Maithel, S. K. 2016
Minimally Invasive Resection of Adrenocortical Carcinoma: a Multi-Institutional Study of 201 Patients. Journal of gastrointestinal surgery Lee, C. W., Md, A. I., Schneider, D. F., Leverson, G. E., Tran, T. B., Poultsides, G. A., Postlewait, L. M., Maithel, S. K., Wang, T. S., Hatzaras, I., Shenoy, R., Phay, J. E., Shirley, L., Fields, R. C., Jin, L. X., Pawlik, T. M., Prescott, J. D., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Weber, S. M. 2016: -?
A Comparison of Prognostic Schemes for Perihilar Cholangiocarcinoma. Journal of gastrointestinal surgery Buettner, S., van Vugt, J. L., Gani, F., Groot Koerkamp, B., Margonis, G. A., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Guglielmi, A., IJzermans, J. N., Pawlik, T. M. 2016; 20 (10): 1716-1724
Although widely used, the 7th edition American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (PHC) may be limited. Disease-specific nomograms have been proposed as a better means to predict long-term survival for individual patients. We sought to externally validate a recently proposed nomogram by Memorial Sloan Kettering Cancer Center (MSKCC) for PHC, as well as identify factors to improve the prediction of prognosis for patients with PHC.Four hundred seven patients who underwent surgery for PHC between 1988 and 2014 were identified using an international, multi-center database. Standard clinicopathologic and outcome data were collected. The predictive power of the AJCC staging system and nomogram were assessed.Median survival was 24.4 months; 3- and 5-year survival was 37.2 and 20.8 %, respectively. The AJCC 7th edition staging system (C-index 0.570) and the recently proposed PHC nomogram (C-index 0.587) both performed poorly. A revised nomogram based on age, lymphovascular invasion, perineural invasion, and lymph node metastases performed better (C-index 0.682). The calibration plot of the revised PHC nomogram demonstrated good calibration.The 7th edition AJCC staging system and the MSKCC nomogram had a poor ability to predict long-term survival for individual patients with PHC. A revised nomogram provided more accurate prediction of survival, but will need to be externally validated.
Incidence and Predictors of Readmission after Curative-Intent Resection for Extrahepatic Cholangiocarcinoma: A Multi-Institutional 15-Year Experience from the US Extrahepatic Biliary Malignancy Collaborative Hatzaras, I., Maithel, S., Shen, P., Pawlik, T. M., Idrees, K., Fields, R. C., Weber, S. M., Martin, R. G., Schmidt, C. R., Poultsides, G. A. ELSEVIER SCIENCE INC. 2016: E25
Rates, Predictors, and Prognostic Implications of Perioperative Chemotherapy Completion in Gastric Cancer Karagkounis, G., Squires, M., Poultsides, G. A., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Bloomston, M., Weber, S. M., Maithel, S. ELSEVIER SCIENCE INC. 2016: E186-E187
A Comparison of Prognostic Schemes for Perihilar Cholangiocarcinoma Buettner, S., van Vugti, J., Gani, F., Koerkamp, B., Margonis, G., Ethun, C. G., Poultsides, G., Thuy Tran, Idrees, K., Isom, C., Fields, R., Krasnick, B., Weber, S., Salem, A., Martin, R., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Maithel, S., Guglielmi, A., Uzermans, J., Pawlik, T. M. WILEY. 2016: 699A
Gastric Cancer, Version 3.2016 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ajani, J. A., D'Amico, T. A., Almhanna, K., Bentrem, D. J., Chao, J., Das, P., Denlinger, C. S., Fanta, P., Farjah, F., Fuchs, C. S., Gerdes, H., Gibson, M., Glasgow, R. E., Hayman, J. A., Hochwald, S., Hofstetter, W. L., Ilson, D. H., Jaroszewski, D., Johung, K. L., Keswani, R. N., Kleinberg, L. R., Korn, W. M., Leong, S., Linn, C., Lockhart, A. C., Ly, Q. P., Mulcahy, M. F., Orringer, M. B., Perry, K. A., Poultsides, G. A., Scott, W. J., Strong, V. E., Washington, M. K., Weksler, B., Willett, C. G., Wright, C. D., Zelman, D., McMillian, N., Sundar, H. 2016; 14 (10): 1286-1312
Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of death from cancer in the world. Several advances have been made in the staging procedures, imaging techniques, and treatment approaches. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer provide an evidence- and consensus-based treatment approach for the management of patients with gastric cancer. This manuscript discusses the recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease.
Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network Ajani, J. A., D'Amico, T. A., Almhanna, K., Bentrem, D. J., Chao, J., Das, P., Denlinger, C. S., Fanta, P., Farjah, F., Fuchs, C. S., Gerdes, H., Gibson, M., Glasgow, R. E., Hayman, J. A., Hochwald, S., Hofstetter, W. L., Ilson, D. H., Jaroszewski, D., Johung, K. L., Keswani, R. N., Kleinberg, L. R., Korn, W. M., Leong, S., Linn, C., Lockhart, A. C., Ly, Q. P., Mulcahy, M. F., Orringer, M. B., Perry, K. A., Poultsides, G. A., Scott, W. J., Strong, V. E., Washington, M. K., Weksler, B., Willett, C. G., Wright, C. D., Zelman, D., McMillian, N., Sundar, H. 2016; 14 (10): 1286-1312
Proposal for a new T-stage classification system for distal cholangiocarcinoma: a 10-institution study from the U.S. Extrahepatic Biliary Malignancy Consortium. HPB Postlewait, L. M., Ethun, C. G., Le, N., Pawlik, T. M., Buettner, S., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Vitiello, G., Cardona, K., Maithel, S. K. 2016; 18 (10): 793-799
Seventh AJCC distal cholangiocarcinoma T-stage classification inadequately separates patients by survival. This retrospective study aimed to define a novel T-stage system to better stratify patients after resection.Curative-intent pancreaticoduodenectomies for distal cholangiocarcinoma (1/2000-5/2015) at 10 US institutions were included. Relationships between tumor characteristics and overall survival (OS) were assessed and incorporated into a novel T-stage classification.176 patients (median follow-up: 24mo) were included. Current AJCC T-stage was not associated with OS (T1: 23mo, T2: 20mo, T3: 25mo, T4: 12mo; p = 0.355). Tumor size ≥3 cm and presence of lymphovascular invasion (LVI) were associated with decreased OS on univariate and multivariable analyses. Patients were stratified into 3 groups [T1: size <3 cm and (-)LVI (n = 69; 39.2%); T2: size ≥3 cm and (-)LVI or size <3 cm and (+)LVI (n = 82; 46.6%); and T3: size ≥3 cm and (+)LVI (n = 25; 14.2%)]. Each progressive proposed T-stage was associated with decreased median OS (T1: 35mo; T2: 20mo; T3: 8mo; p = 0.002).Current AJCC distal cholangiocarcinoma T-stage does not adequately stratify patients by survival. This proposed T-stage classification, based on tumor size and LVI, better differentiates patient outcomes after resection and could be considered for incorporation into the next AJCC distal cholangiocarcinoma staging system.
A Comparison of Prognostic Schemes for Perihilar Cholangiocarcinoma JOURNAL OF GASTROINTESTINAL SURGERY Buettner, S., van Vugt, J. L., Gani, F., Koerkamp, B. G., Margonis, G. A., Ethun, C. G., Poultsides, G., Thuy Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Guglielmi, A., IJzermans, J. N., Pawlik, T. M. 2016; 20 (10): 1716-1724
Laparoscopic hepatectomy in cirrhotics: safe if you adjust technique. Surgical endoscopy Worhunsky, D. J., Dua, M. M., Tran, T. B., Siu, B., Poultsides, G. A., Norton, J. A., Visser, B. C. 2016; 30 (10): 4307-4314
Minimally invasive liver surgery is a growing field, and a small number of recent reports have suggested that laparoscopic liver resection (LLR) is feasible even in patients with cirrhosis. However, parenchymal transection of the cirrhotic liver is challenging due to fibrosis and portal hypertension. There is a paucity of data regarding the technical modifications necessary to safely transect the diseased parenchyma.Patients undergoing LLR by a single surgeon between 2008 and 2015 were reviewed. Patients with cirrhosis were compared to those without cirrhosis to examine differences in surgical technique, intraoperative characteristics, and outcomes (including liver-related morbidity and general postoperative complication rates).A total of 167 patients underwent LLR during the study period. Forty-eight (29 %) had cirrhosis, of which 43 (90 %) had hepatitis C. Most had Child-Pugh class A disease (85 %). Compared to noncirrhotics, patients with cirrhosis were older, had more comorbidities, and were more likely to have hepatocellular carcinoma. Precoagulation before parenchymal transection was used more frequently in cirrhotics (65 vs. 15 %, P < 0.001), and mean portal triad clamping time was longer (32 vs. 22 min, P = 0.002). There were few conversions to open surgery, though hand-assisted laparoscopy was used as an alternative to converting to open in three patients with cirrhosis. Blood loss was relatively low for both groups. Although there were more postoperative complications among cirrhotics (38 vs. 13 %, P = 0.001), this was almost entirely due to a higher rate of minor (Clavien-Dindo I or II) complications. Liver-related morbidity, major complications, and mortality rates were similar.LLR is safe for selected patients with cirrhosis. The added complexity associated with the division of diseased liver parenchyma may be overcome with some form of technique modification, including more liberal use of precoagulation, portal triad clamping, or a hand-assist port.
Elevated NLR in gallbladder cancer and cholangiocarcinoma - making bad cancers even worse: results from the US Extrahepatic Biliary Malignancy Consortium. HPB Beal, E. W., Wei, L., Ethun, C. G., Black, S. M., Dillhoff, M., Salem, A., Weber, S. M., Tran, T., Poultsides, G., Son, A. Y., Hatzaras, I., Jin, L., Fields, R. C., Buettner, S., Pawlik, T. M., Scoggins, C., Martin, R. C., Isom, C. A., Idrees, K., Mogal, H. D., Shen, P., Maithel, S. K., Schmidt, C. R. 2016
Gallbladder and extrahepatic biliary malignancies are aggressive tumors with high risk of recurrence and death. We hypothesize that elevated preoperative Neutrophil-Lymphocyte Ratios (NLR) are associated with poor prognosis among patients undergoing resection of gallbladder or extrahepatic biliary cancers.Patients who underwent complete surgical resection between 2000-2014 were identified from 10 academic centers (n=525). Overall (OS) and recurrence-free survival (RFS) were analyzed by stratifying patients with normal (<5) versus elevated (>5) NLR.Overall, 375 patients had NLR <5 while 150 patients had NLR >5. Median OS was 24.5 months among patients with NLR<5 versus 17.0 months among patients with NLR>5 (p<0.001). NLR was also associated with OS in subgroup analysis of patients with gallbladder cancer. In fact, on multivariable analysis, NLR>5, dyspnea and preoperative peak bilirubin were independently associated with OS in patients with gallbladder cancer. Median RFS was 26.8 months in patients with NLR<5 versus 22.7 months among patients with NLR>5 (p=0.030). NLR>5 was independently associated with worse RFS for patients with gallbladder cancer.Elevated NLR was associated with worse outcomes in patients with gallbladder and extrahepatic biliary cancers after curative-intent resection. NLR is easily measured and may provide important prognostic information.
Clinical Score Predicting Long-Term Survival after Repeat Resection for Recurrent Adrenocortical Carcinoma. Journal of the American College of Surgeons Tran, T. B., Maithel, S. K., Pawlik, T. M., Wang, T. S., Hatzaras, I., Phay, J. E., Fields, R. C., Weber, S. M., Sicklick, J. K., Yopp, A. C., Duh, Q., Solorzano, C. C., Votanopoulos, K. I., Poultsides, G. A. 2016
Adrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study was to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC.Patients who underwent curative-intent repeat resection for recurrent ACC at 1 of 13 academic medical centers participating in the US ACC Study Group were identified. End points included morbidity, mortality, and overall survival.Fifty-six patients underwent repeat curative-intent resection for recurrent ACC (representing 21% of 265 patients who underwent resection for primary ACC) from 1997 to 2014. Median age was 52 years. Sites of resected recurrence included locoregional only (54%), lung only (14%), liver only (12%), combined locoregional and lung (4%), combined liver and lung (4%), and other distant sites (12%). Thirty-day morbidity and mortality rates were 40% and 5.4%, respectively. Cox regression analysis revealed that the presence of multifocal recurrence, disease-free interval <12 months, and extrapulmonary distant metastases were independent predictors of poor survival. A clinical score consisting of 1-point each for the 3 variables demonstrated good discrimination in predicting survival after repeat resection (5-year: 72% for 0 points, 32% for 1 point, 0% for 2 or 3 points; p = 0.0006, area under the curve = 0.78).Long-term survival after repeat resection for recurrent ACC is feasible when 2 of the following factors are present: solitary tumor, disease-free interval >12 months, and locoregional or pulmonary recurrence.
The significance of underlying cardiac comorbidity on major adverse cardiac events after major liver resection. HPB Tran, T. B., Worhunsky, D. J., Spain, D. A., Dua, M. M., Visser, B. C., Norton, J. A., Poultsides, G. A. 2016; 18 (9): 742-747
The risk of postoperative adverse events in patients with underlying cardiac disease undergoing major hepatectomy remains poorly characterized.The NSQIP database was used to identify patients undergoing hemihepatectomy and trisectionectomy. Patient characteristics and postoperative outcomes were evaluated.From 2005 to 2012, 5227 patients underwent major hepatectomy. Of those, 289 (5.5%) had prior major cardiac disease: 5.6% angina, 3.1% congestive heart failure, 1% myocardial infarction, 54% percutaneous coronary intervention, and 46% cardiac surgery. Thirty-day mortality was higher in patients with cardiac comorbidity (6.9% vs. 3.7%, P = 0.008), including the incidence of postoperative cardiac arrest requiring cardiopulmonary resuscitation (3.8% vs. 1.2%, P = 0.001) and myocardial infarction (1.7% vs. 0.4%, P = 0.011). Multivariate analysis revealed that functional impairment, older age, and malnutrition, but not cardiac comorbidity, were significant predictors of 30-day mortality. However, prior percutaneous coronary intervention was independently associated with postoperative cardiac arrest (OR 2.999, P = 0.008).While cardiac comorbidity is not a predictor of mortality after major hepatectomy, prior percutaneous coronary intervention is independently associated with postoperative cardiac arrest. Careful patient selection and preoperative optimization is fundamental in patients with prior percutaneous coronary intervention being considered for major hepatectomy as restrictive fluid management and low central venous pressure anesthesia may not be tolerated well by all patients.
Neuroendocrine tumors of the pancreas: Degree of cystic component predicts prognosis. Surgery Cloyd, J. M., Kopecky, K. E., Norton, J. A., Kunz, P. L., Fisher, G. A., Visser, B. C., Dua, M. M., Park, W. G., Poultsides, G. A. 2016; 160 (3): 708-713
Although most pancreatic neuroendocrine tumors are solid, approximately 10% are cystic. Some studies have suggested that cystic pancreatic neuroendocrine tumors are associated with a more favorable prognosis.A retrospective review of all patients with pancreatic neuroendocrine tumors who underwent operative resection between 1999 and 2014 at a single academic medical center was performed. Based on cross-sectional imaging performed before operation, pancreatic neuroendocrine tumors were classified according to the size of the cystic component relative to the total tumor size: purely cystic (100%), mostly cystic (≥50%), mostly solid (<50%), and purely solid (0%). Clinicopathologic characteristics and recurrence-free survival were assessed between groups.In the study, 214 patients met inclusion criteria: 8 with purely cystic tumors, 7 with mostly cystic tumors, 15 with mostly solid tumors, and 184 with purely solid tumors. The groups differed in terms of tumor size (1.5 ± 0.5, 3.0 ± 1.7, 3.7 ± 2.6, and 4.0 ± 3.5 cm), lymph node positivity (0%, 0%, 26.7%, and 34.2%), intermediate or high grade (0%, 16.7%, 20.0%, and 31.0%), synchronous liver metastases (0%, 14.3%, 20.0%, and 26.6%) and need for pancreaticoduodenectomy (0%, 0%, 6.7%, and 25.0%), respectively. No cases of purely cystic pancreatic neuroendocrine tumors were associated with synchronous liver or lymph node metastasis, intermediate/high grade, recurrence, or death due to disease. Among patients presenting without metastatic disease, 10-year recurrence-free survival was 100% in patients with purely and mostly cystic tumors versus 53.0% in patients with purely and mostly solid tumors; however, this difference did not reach statistical significance.Pancreatic neuroendocrine tumors demonstrate a spectrum of biologic behavior with an increasing cystic component being associated with more favorable clinicopathologic features and prognosis. Purely cystic pancreatic neuroendocrine tumors may represent 1 subset that can be safely observed without immediate resection.
Impact of Chemotherapy and External-Beam Radiation Therapy on Outcomes among Patients with Resected Gallbladder Cancer: A Multi-institutional Analysis. Annals of surgical oncology Kim, Y., Amini, N., Wilson, A., Margonis, G. A., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Cardona, K., Maithel, S. K., Pawlik, T. M. 2016; 23 (9): 2998-3008
Use of adjuvant chemotherapy (CTx) and chemoradiation therapy (cXRT) for the treatment of gallbladder cancer (GBC) remains varied. We sought to define the utilization and effect of adjuvant therapy for patients with GBC.Using a multi-institutional national database, 291 patients with GBC who underwent curative-intent resection between 2000 and 2015 were included. Patients with metastasis or an R2 margin were excluded.Median patient age was 66.6 years. Most patients had a T2 (46.2 %) or T3 (38.6 %) lesion, and 37.8 % of patients had lymph node (LN) metastasis. A total of 186 (63.9 %) patients underwent surgery alone, 61 (21.0 %) received CTx, and 44 (15.1 %) patients received cXRT. On multivariable analysis, factors associated with worse overall survival (OS) included T3/T4 stage [hazard ratio (HR) 1.82], LN-metastasis (HR 1.84), lymphovascular invasion (HR 2.02), perineural invasion (HR 1.42), and R1 surgical margin status (HR 2.06); all P < 0.05). In contrast, receipt of CTx/cXRT was associated with improved OS (CTx, HR 0.38; cXRT, HR 0.26; P < 0.001) compared with surgery alone. Similar results were observed for disease-free survival (DFS) (CTx, HR 0.61; cXRT, HR 0.43; P < 0.05). Of note, only patients with high-risk features, such as AJCC T3/T4 stage (HR 0.41), LN metastasis (HR 0.45), and R1 disease (HR 0.21) (all P < 0.05) derived an OS benefit from CTx/cXRT.Adjuvant CTx/cXRT was utilized in 36 % of patients undergoing curative-intent resection for GBC. After adjusted analyses, CTx/cXRT were independently associated with improved long-term outcomes, but the benefit was isolated to only patients with high-risk characteristics.
Prognostic Implications of Lymph Node Status for Patients With Gallbladder Cancer: A Multi-Institutional Study. Annals of surgical oncology Amini, N., Kim, Y., Wilson, A., Margonis, G. A., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016; 23 (9): 3016-3023
Although the American Joint Committee on Cancer (AJCC) classification is the most accepted lymph node (LN) staging system for gallbladder adenocarcinoma (GBA), other LN prognostic schemes have been proposed. This study sought to define the performance of the AJCC LN staging system relative to the number of metastatic LNs (NMLN), the log odds of metastatic LN (LODDS), and the LN ratio (LNR).Patients who underwent curative-intent resection for GBA between 2000 and 2015 were identified from a multi-institutional database. The prognostic performance of various LN staging systems was compared by Harrell's C and the Akaike information criterion (AIC).Altogether, 214 patients with a median age of 66.7 years (interquartile range [IQR] 56.5-73.1) were identified. A total of 1334 LNs were retrieved, with a median of 4 (IQR 2-8) LNs per patient. Patients with LN metastasis had an increased risk of death (hazard ratio [HR] 1.87; 95 % confidence interval [CI] 1.24-2.82; P = 0.003) and recurrence (HR 2.28; 95 % CI 1.37-3.80; P = 0.002). In the entire cohort, LNR, analyzed as either a continuous scale (C-index, 0.603; AIC, 803.5) or a discrete scale (C-index, 0.609; AIC, 802.2), provided better prognostic discrimination. Among the patients with four or more LNs examined, LODDS (C-index, 0.621; AIC, 363.8) had the best performance versus LNR (C-index, 0.615; AIC, 368.7), AJCC LN staging system (C-index, 0.601; AIC, 373.4), and NMLN (C-index, 0.613; AIC, 369.5).Both LODDS and LNR performed better than the AJCC LN staging system. Among the patients who had four or more LNs examined, LODDS performed better than LNR. Both LODDS and LNR should be incorporated into the AJCC LN staging system for GBA.
Rates and patterns of recurrence after curative intent resection for gallbladder cancer: a multi-institution analysis from the US Extra-hepatic Biliary Malignancy Consortium. HPB Margonis, G. A., Gani, F., Buettner, S., Amini, N., Sasaki, K., Andreatos, N., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016
Gallbladder cancer is a relatively rare malignancy. The current study aimed to define the incidence and patterns of recurrence following gallbladder cancer resection.Using a multi-institutional cohort we identified 217 patient undergoing curative intent surgery for gallbladder cancer. Patterns of recurrence were classified as locoregional and distant recurrence.At last follow-up, 76 patients (35.0%) had experienced a recurrence (locoregional only, n = 12, 15.8%; distant only, n = 50, 65.8%; locoregional and distant, n = 14, 18.4%). Median time to recurrence was 9.5 months (IQR 4.7-17.6) and was not associated with recurrence site (all p > 0.05). On multivariable analysis, T3 disease (HR = 8.44, p = 0.014), lymphovascular invasion (HR = 4.24, p < 0.001) and residual disease (HR = 2.04, p = 0.042) were associated with an increased risk of recurrence. Patients who recurred demonstrated a worse 1-, 3- and 5-year OS (1-year OS: 91.3% vs. 68.6%, p = 0.001, 3-year OS: 79.3% vs. 28.7%, p < 0.001, and 5-year OS: 75.9% vs. 16.0%, p < 0.001). After adjusting for other risk factors, recurrence was independently associated with a decreased OS (HR = 3.71, p = 0.006). Of note, receipt of adjuvant therapy was associated with improved OS (HR = 0.56, p = 0.027) among those patients who developed a tumor recurrence.Over one-third of patients experienced a recurrence after gallbladder cancer surgery. While chemotherapy did not decrease the rate of recurrence, patients who experienced recurrence after administration of adjuvant treatment faired better than patients who did not receive adjuvant therapy.
Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging. PLoS medicine Eberlin, L. S., Margulis, K., Planell-Mendez, I., Zare, R. N., Tibshirani, R., Longacre, T. A., Jalali, M., Norton, J. A., Poultsides, G. A. 2016; 13 (8)
Surgical resection with microscopically negative margins remains the main curative option for pancreatic cancer; however, in practice intraoperative delineation of resection margins is challenging. Ambient mass spectrometry imaging has emerged as a powerful technique for chemical imaging and real-time diagnosis of tissue samples. We applied an approach combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with the least absolute shrinkage and selection operator (Lasso) statistical method to diagnose pancreatic tissue sections and prospectively evaluate surgical resection margins from pancreatic cancer surgery.Our methodology was developed and tested using 63 banked pancreatic cancer samples and 65 samples (tumor and specimen margins) collected prospectively during 32 pancreatectomies from February 27, 2013, to January 16, 2015. In total, mass spectra for 254,235 individual pixels were evaluated. When cross-validation was employed in the training set of samples, 98.1% agreement with histopathology was obtained. Using an independent set of samples, 98.6% agreement was achieved. We used a statistical approach to evaluate 177,727 mass spectra from samples with complex, mixed histology, achieving an agreement of 81%. The developed method showed agreement with frozen section evaluation of specimen margins in 24 of 32 surgical cases prospectively evaluated. In the remaining eight patients, margins were found to be positive by DESI-MSI/Lasso, but negative by frozen section analysis. The median overall survival after resection was only 10 mo for these eight patients as opposed to 26 mo for patients with negative margins by both techniques. This observation suggests that our method (as opposed to the standard method to date) was able to detect tumor involvement at the margin in patients who developed early recurrence. Nonetheless, a larger cohort of samples is needed to validate the findings described in this study. Careful evaluation of the long-term benefits to patients of the use of DESI-MSI for surgical margin evaluation is also needed to determine its value in clinical practice.Our findings provide evidence that the molecular information obtained by DESI-MSI/Lasso from pancreatic tissue samples has the potential to transform the evaluation of surgical specimens. With further development, we believe the described methodology could be routinely used for intraoperative surgical margin assessment of pancreatic cancer.
The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: a multi-institutional analysis. HPB Margonis, G. A., Buettner, S., Sasaki, K., Kim, Y., Ratti, F., Russolillo, N., Ferrero, A., Berger, N., Gamblin, T. C., Poultsides, G., Tran, T., Postlewait, L. M., Maithel, S., Michaels, A. D., Bauer, T. W., Marques, H., Barroso, E., Aldrighetti, L., Pawlik, T. M. 2016; 18 (8): 700-705
Data on surgical management of breast liver metastasis are limited. We sought to determine the safety and long-term outcome of patients undergoing hepatic resection of breast cancer liver metastases (BCLM).Using a multi-institutional, international database, 131 patients who underwent surgery for BCLM between 1980 and 2014 were identified. Clinicopathologic and outcome data were collected and analyzed.Median tumor size of the primary breast cancer was 2.5 cm (IQR: 2.0-3.2); 58 (59.8%) patients had primary tumor nodal metastasis. The median time from diagnosis of breast cancer to metastasectomy was 34 months (IQR: 16.8-61.3). The mean size of the largest liver lesion was 3.0 cm (2.0-5.0); half of patients (52.0%) had a solitary metastasis. An R0 resection was achieved in most cases (90.8%). Postoperative morbidity and mortality were 22.8% and 0%, respectively. Median and 3-year overall-survival was 53.4 months and 75.2%, respectively. On multivariable analysis, positive surgical margin (HR 3.57, 95% CI 1.40-9.16; p = 0.008) and diameter of the BCLM (HR 1.03, 95% CI 1.01-1.06; p = 0.002) remained associated with worse OS.In selected patients, resection of breast cancer liver metastases can be done safely and a subset of patients may derive a relatively long survival, especially from a margin negative resection.
Interaction of Postoperative Morbidity and Receipt of Adjuvant Therapy on Long-Term Survival After Resection for Gastric Adenocarcinoma: Results From the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Jin, L. X., Sanford, D. E., Squires, M. H., Moses, L. E., Yan, Y., Poultsides, G. A., Votanopoulos, K. I., Weber, S. M., Bloomston, M., Pawlik, T. M., Hawkins, W. G., Linehan, D. C., Schmidt, C., Worhunsky, D. J., Acher, A. W., Cardona, K., Cho, C. S., Kooby, D. A., Levine, E. A., Winslow, E., Saunders, N., Spolverato, G., Colditz, G. A., Maithel, S. K., Fields, R. C. 2016; 23 (8): 2398-2408
Postoperative complications (POCs) can negatively impact survival after oncologic resection. POCs may also decrease the rate of adjuvant therapy completion. We evaluated the impact of complications on gastric cancer survival and analyzed the combined effect of complications and adjuvant therapy on survival.We analyzed 824 patients from 7 institutions of the U.S. Gastric Cancer Collaborative who underwent curative resection for gastric adenocarcinoma between 2000 and 2012. POC were graded using the modified Clavien-Dindo system. Survival probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression.Median follow-up was 35 months. The overall complication rate was 41 %. The 5-year overall survival (OS) and recurrence-free survival (RFS) of patients who experienced complications were 27 and 23 %, respectively, compared with 43 and 40 % in patients who did not have complications (p < 0.0001 for OS and RFS). On multivariate analysis, POC remained an independent predictor for decreased OS and RFS (HR 1.3, 95 % CI 1.1-1.6, p = 0.03 for OS; HR 1.3, 95 % CI 1.01-1.6, p = 0.03 for RFS). Patients who experienced POC were less likely to receive adjuvant therapy (OR 0.5, 95 % CI 0.3-0.7, p < 0.001). The interaction of complications and failure to receive adjuvant therapy significantly increased the hazard of death compared with patients who had neither complications nor adjuvant therapy (HR 2.3, 95 % CI 1.6-3.2, p < 0.001).Postoperative complications adversely affect long-term outcomes after gastrectomy for gastric cancer. Not receiving adjuvant therapy in the face of POC portends an especially poor prognosis following gastrectomy for gastric cancer.
Assessing Trends in Palliative Surgery for Extrahepatic Biliary Malignancies: A 15-Year Multicenter Study JOURNAL OF GASTROINTESTINAL SURGERY Buettner, S., Wilson, A., Margonis, G. A., Gani, F., Ethun, C. G., Poultsides, G. A., Thuy Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016; 20 (8): 1444-1452
Extrahepatic biliary malignancies are often diagnosed at an advanced stage. We compared patients with unresectable perihilar cholangiocarcinoma (PHCC) and gallbladder cancer (GBC) who underwent a palliative procedure versus an aborted laparotomy.Seven hundred seventy-seven patients who underwent surgery for PHCC or GBC between 2000 and 2014 were identified. Uni- and multivariable analyses were performed to identify factors associated with outcome.Utilization of preoperative imaging increased over time (CT use, 80.1 % pre-2009 vs. 90 % post-2009) (p < 0.001). The proportion of the patients undergoing curative-intent resection also increased (2000-2004, 67.0 % vs. 2005-2009, 74.5 % vs. 2010-2014, 78.8 %; p = 0.001). The planned surgery was aborted in 106 (13.7 %) patients and 94 (12.1 %) had a palliative procedure. A higher incidence of postoperative complications (19.2 vs. 3.8 %, p = 0.001) including deep surgical site infections (8.3 vs. 1.1 %), bleeding (4.8 vs. 0 %), bile leak (6.0 vs. 0 %) and longer length of stay (7 vs. 4.5 days) were observed among the patients who underwent a palliative surgical procedure versus an aborted non-therapeutic, non-palliative laparotomy (all p < 0.05). OS was comparable among the patients who underwent a palliative procedure (8.7 months) versus an aborted laparotomy (7.8 months) (p = 0.23).Increased use of advanced imaging modalities was accompanied by increased curative-intent surgery. Compared with patients in whom surgery was aborted, patients who underwent surgical palliation demonstrated an increased incidence of postoperative morbidity with comparable survival.
Assessing the impact of common bile duct resection in the surgical management of gallbladder cancer. Journal of surgical oncology Gani, F., Buettner, S., Margonis, G. A., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016; 114 (2): 176-180
Although radical re-resection for gallbladder cancer (GBC) has been advocated, the optimal extent of re-resection remains unknown. The current study aimed to assess the impact of common bile duct (CBD) resection on survival among patients undergoing surgery for GBC.Patients undergoing curative-intent surgery for GBC were identified using a multi-institutional cohort of patients. Multivariable Cox-proportional hazards regression was performed to identify risk factors for a poor overall survival (OS).Among the 449 patients identified, 26.9% underwent a concomitant CBD resection. The median number of lymph nodes harvested did not differ based on CBD resection (CBD, 4 [IQR: 2-9] vs. no CBD, 3 [IQR: 1-7], P = 0.108). While patients who underwent a CBD resection had a worse OS, after adjusting for potential confounders, CBD resection did not impact OS (HR = 1.40, 95%CI 0.87-2.27, P = 0.170). Rather, the presence of advanced disease (T3: HR = 3.11, 95%CI 1.22-7.96, P = 0.018; T4: HR = 7.24, 95%CI 1.70-30.85, P = 0.007) and the presence of disease at the surgical margin (HR = 2.58, 95%CI 1.26-5.31, P = 0.010) were predictive of a worse OS.CBD resection did not yield a higher lymph node count and was not associated with an improved survival. Routine CBD excision in the re-resection of GBC is unwarranted and should only be performed selectively. J. Surg. Oncol. 2016;114:176-180. © 2016 Wiley Periodicals, Inc.
To Roux or not to Roux: a comparison between Roux-en-Y and Billroth II reconstruction following partial gastrectomy for gastric cancer GASTRIC CANCER Tran, T. B., Worhunsky, D. J., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Cho, C. S., Weber, S. M., Schmidt, C., Levine, E. A., Bloomston, M., Fields, R. C., Pawlik, T. M., Maithel, S. K., Norton, J. A., Poultsides, G. A. 2016; 19 (3): 994-1001
Although the extent of resection frequently dictates the method of reconstruction following distal subtotal gastrectomy, it is unclear whether Roux-en-Y gastrojejunostomy compared with Billroth II gastrojejunostomy is associated with superior perioperative outcomes.Patients who underwent resection for gastric cancer with Roux-en-Y or Billroth II reconstruction between 2000 and 2012 in seven academic institutions (US Gastric Cancer Collaborative) were identified. Patients who underwent total gastrectomy, gastric wedge, or palliative resections (metastatic disease or R2 resections) were excluded.Of a total of 965 patients, 447 met the inclusion criteria. A comparison between the Roux-en-Y (n = 257) and Billroth II (n = 190) groups demonstrated no differences in patient and tumor characteristics, except for Billroth II patients having a higher proportion of antral tumors (71 % vs. 50 %, p < 0.001). Roux-en-Y operations were slightly longer (244 min vs. 212 min, p < 0.001) and associated with somewhat higher blood loss (243 ml vs. 205 ml, p = 0.033). However, there were no significant differences in the length of hospital stay (8 days vs. 7 days), readmission rate (17 % vs. 18 %), 90-day mortality (5.1 % vs. 4.7 %), incidence (39 % vs. 41 %) and severity of complications, dependency on jejunostomy tube feeding at discharge (13 % vs. 12 %), same-patient decrease in serum albumin level from the preoperative to the postoperative value at 30, 60, and 90 days, receipt of adjuvant therapy (50 % vs. 53 %), or 5-year survival (44 % vs. 41 %).Although long-term quality-of-life parameters were not compared, this study did not show an advantage of Roux-en-Y gastrojejunostomy over Billroth II gastrojejunostomy in short-term perioperative outcomes. Both techniques should be regarded as equally acceptable reconstructive options following partial gastrectomy for gastric cancer.
Defining when to offer operative treatment for intrahepatic cholangiocarcinoma: A regret-based decision curves analysis SURGERY Bagante, F., Spolverato, G., Cucchetti, A., Gani, F., Popescu, I., Ruzzenente, A., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Sandroussi, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Gugliehni, A., Pawlik, T. M. 2016; 160 (1): 106-117
Regret-based decision curve analysis (DCA) is a framework that assesses the medical decision process according to physician attitudes (expected regret) relative to disease-based factors. We sought to apply this methodology to decisions around the operative management of intrahepatic cholangiocarcinoma (ICC).Utilizing a multicentric database of 799 patients who underwent liver resection for ICC, we developed a prognostic nomogram. DCA tested 3 strategies: (1) perform an operation on all patients, (2) never perform an operation, and (3) use the nomogram to select patients for an operation.Four preoperative variables were included in the nomogram: major vascular invasion (HR = 1.36), tumor number (multifocal, HR = 1.18), tumor size (>5 cm, HR = 1.45), and suspicious lymph nodes on imaging (HR = 1.47; all P < .05). The regret-DCA was assessed using an online survey of 50 physicians, expert in the treatment of ICC. For a patient with a multifocal ICC, largest lesion measuring >5 cm, one suspicious malignant lymph node, and vascular invasion on imaging, the 1-year predicted survival was 52% according to the nomogram. Based on the therapeutic decision of the regret-DCA, 60% of physicians would advise against an operation for this scenario. Conversely, all physicians recommended an operation to a patient with an early ICC (single nodule measuring 3 cm, no suspicious lymph nodes, and no vascular invasion at imaging).By integrating a nomogram based on preoperative variables and a regret-based DCA, we were able to define the elements of how decisions rely on medical knowledge (postoperative survival predicted by a nomogram, severity disease assessment) and physician attitudes (regret of commission and omission).
Readmission Following Gastric Cancer Resection: Risk Factors and Survival JOURNAL OF GASTROINTESTINAL SURGERY Acher, A. W., Squires, M. H., Fields, R. C., Poultsides, G. A., Schmidt, C., Votanopoulos, K. I., Pawlik, T. M., Jin, L. X., Ejaz, A., Kooby, D. A., Bloomston, M., Worhunsky, D., Levine, E. A., Saunders, N., Winslow, E., Cho, C. S., Leverson, G., Maithel, S. K., Weber, S. M. 2016; 20 (7): 1284-1294
This study utilized a multi-institutional database to evaluate risk factors for readmission in patients undergoing curative gastrectomy for gastric adenocarcinoma with the intent of describing both perioperative risk factors and the relationship of readmission to survival.Patients who underwent curative resection of gastric adenocarcinoma from 2000 to 2012 from seven academic institutions of the US Gastric Cancer Collaborative were analyzed. In-hospital deaths and palliative surgeries were excluded, and readmission was defined as within 30 days of discharge. Univariate and multivariable logistic regression analyses were employed and survival analysis conducted.Of the 855 patients, 121 patients (14.2 %) were readmitted. Univariate analysis identified advanced age (p < 0.0128), American Society of Anesthesiology status ≥3 (p = 0.0045), preexisting cardiac disease (p < 0.0001), hypertension (p = 0.0142), history of smoking (p = 0.0254), increased preoperative blood urea nitrogen (BUN; p = 0.0426), concomitant pancreatectomy (p = 0.0056), increased operation time (p = 0.0384), estimated blood loss (p = 0.0196), 25th percentile length of stay (<7 days, p = 0.0166), 75th percentile length of stay (>12 days, p = 0.0256), postoperative complication (p < 0.0001), and total gastrectomy (p = 0.0167) as risk factors for readmission. Multivariable analysis identified cardiac disease (odds ratio (OR) 2.4, 95 % confidence interval (CI) 1.6-3.3, p < 0.0001), postoperative complication (OR 2.3, 95 % CI 1.6-5.4, p < 0.0001), and pancreatectomy (OR 2.2, 95 % CI 1.1-4.1, p = 0.0202) as independent risk factors for readmission. There was an association of decreased overall median survival in readmitted patients (39 months for readmitted vs. 103 months for non-readmitted). This was due to decreased survival in readmitted stage 1 (p = 0.0039), while there was no difference in survival for other stages. Stage I readmitted patients had a higher incidence of cardiac disease than stage I non-readmitted patients (58 vs. 24 %, respectively, p = 0.0002).Within this multi-institutional study investigating readmission in patients undergoing curative resection for gastric cancer, cardiac disease, postoperative complication, and concomitant pancreatectomy were identified as significant risk factors for readmission. Readmission was associated with decreased overall median survival, but on further analysis, this was driven by differences in survival for stage I disease only.
A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma BMC CANCER Palumbo, T., Poultsides, G. A., Kouraklis, G., Liakakos, T., Drakaki, A., Peros, G., Hatziapostolou, M., Iliopoulos, D. 2016; 16
Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo.A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors.The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas.Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma.
Optimal Extent of Lymphadenectomy for Gastric Adenocarcinoma: A 7-Institution Study of the US Gastric Cancer Collaborative JOURNAL OF SURGICAL ONCOLOGY Randle, R. W., Swords, D. S., Levine, E. A., Fino, N. F., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Pawlik, T. M., Jin, L. X., Spolverato, G., Schmidt, C., Worhunsky, D., Cho, C. S., Maithel, S. K., Votanopoulos, K. I. 2016; 113 (7): 750-755
The optimal extent of lymphadenectomy in the treatment of gastric adenocarcinoma is debated. We compared gastrectomy outcomes following limited (D1) or extended (D2) lymphadenectomy.Using the multi-institutional US Gastric Cancer Collaborative database, we reviewed the morbidity, mortality, recurrence, and overall survival (OS) of patients receiving D1 or D2 lymphadenectomies.Between 2000 and 2012, 266 and 461 patients received a D1 and D2 lymphadenectomy, respectively. ASA class, mean number of comorbidities, grade, and stage were similar between groups. While major morbidity was similar (P = 0.85), mortality was worse for those receiving a D1 lymphadenectomy (4.9% vs. 1.3%, P = 0.004). D2 lymphadenectomy was associated with improved median OS in stage I (4.7 years for D1 vs. not reached for D2, P = 0.003), stage II (3.6 years for D1 vs. 6.3 for D2, P = 0.42), and stage III patients (1.3 years for D1 vs. 2.1 for D2, P = 0.01). After adjusting for predictors of OS, D2 lymphadenectomy remained a significant predictor of improved survival (HR 1.5, 95%CI 1.1-2.0, P = 0.008).D2 lymphadenectomy can be performed without increased risk of morbidity and mortality. Additionally, D2 lymphadenectomy is associated with improved survival especially in early stages, and should be considered for gastric adenocarcinoma patients. J. Surg. Oncol. 2016;113:750-755. © 2016 Wiley Periodicals, Inc.
An economic analysis of pancreaticoduodenectomy: should costs drive consumer decisions? AMERICAN JOURNAL OF SURGERY Tran, T. B., Dua, M. M., Worhunsky, D. J., Poultsides, G. A., Norton, J. A., Visser, B. C. 2016; 211 (6): 991-?
Consumer groups campaign for cost transparency believing that patients will select hospitals accordingly. We sought to determine whether the cost of pancreaticoduodenectomy (PD) should be considered in choosing a hospital.Using the Nationwide Inpatient Sample database, we analyzed charges for patients who underwent PD from 2000 to 2010. Outcomes were stratified by hospital volume.A total of 15,599 PDs were performed in 1,186 hospitals. The median cost was $87,444 (interquartile range $16,015 to $144,869). High volume hospitals (HVH) had shorter hospital stay (11 vs 15 days, P < .001) and mortality (3% vs 7.6%, P < .001). PD performed at low volume hospitals had higher charges compared with HVH ($97,923 vs $81,581, P < .001). On multivariate analysis, HVH was associated with a lower risk of mortality, while extremes in hospital costs, cardiac comorbidity, and any complication were significant predictors of mortality.Although PDs performed at HVH are associated with better outcomes and lower hospital charges, costs should not be the primary determinant when selecting a hospital.
Outcomes after resection of cortisol-secreting adrenocortical carcinoma AMERICAN JOURNAL OF SURGERY Margonis, G. A., Kim, Y., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Glenn, J. A., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 211 (6): 1106-1113
We sought to define the impact of cortisol-secreting status on outcomes after surgical resection of adrenocortical carcinoma (ACC).The U.S ACC group database was queried to identify patients who underwent ACC resection between 1993 and 2014. The short-term and long-term outcomes were assessed.The incidence of all functional and cortisol-secreting tumors was 40.6% and 22.6%, respectively. On multivariable analysis, cortisol secretion remained associated with an increased risk of postoperative complications (odds ratio = 2.25, 95 % confidence interval = 1.04 to 4.88; P = .04). At a median follow-up of 17.6 months, 118 patients (50.4%) had developed a recurrence. On multivariable analysis, after adjusting for patient and disease-related factors cortisol secretion independently predicted shorter recurrence-free survival (Hazard ratio = 2.05, 95% confidence interval = 1.16 to 3.60; P = .01).Cortisol secretion was associated with an increased risk of postoperative morbidity. Recurrence remains high among patients with ACC after surgery; cortisol secretion was independently associated with a shorter recurrence-free survival. Tailoring postoperative surveillance of ACC patients based on their cortisol secreting status may be important.
Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Vorvis, C., Hatziapostolou, M., Mahurkar-Joshi, S., Koutsioumpa, M., Williams, J., Donahue, T. R., Poultsides, G. A., Eibl, G., Iliopoulos, D. 2016; 310 (11): G1124-G1137
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with low survival rates and limited therapeutic options. Thus elucidation of signaling pathways involved in PDAC pathogenesis is essential for identifying novel potential therapeutic gene targets. Here, we used a systems approach to elucidate those pathways by integrating gene and microRNA profiling analyses together with CRISPR/Cas9 technology to identify novel transcription factors involved in PDAC pathogenesis. FOXA2 transcription factor was found to be significantly downregulated in PDAC relative to control pancreatic tissues. Functional experiments revealed that FOXA2 has a tumor suppressor function through inhibition of pancreatic cancer cell growth, migration, invasion, and colony formation. In situ hybridization analysis revealed miR-199a to be significantly upregulated in pancreatic cancer. Bioinformatics and luciferase analyses showed that miR-199a negatively but directly regulates FOXA2 expression through binding in its 3'-untranslated region (UTR). Evaluation of the functional importance of miR-199a on pancreatic cancer revealed that miR-199a acts as an inhibitor of FOXA2 expression, inducing an increase in pancreatic cancer cell proliferation, migration, and invasion. Additionally, gene ontology and network analyses in PANC-1 cells treated with a small interfering RNA (siRNA) against FOXA2 revealed an enrichment for cell invasion mechanisms through PLAUR and ERK activation. FOXA2 deletion (FOXA2Δ) by using two CRISPR/Cas9 vectors in PANC-1 cells induced tumor growth in vivo resulting in upregulation of PLAUR and ERK pathways in FOXA2Δ xenograft tumors. We have identified FOXA2 as a novel tumor suppressor in pancreatic cancer and it is regulated directly by miR-199a, thereby enhancing our understanding of how microRNAs interplay with the transcription factors to affect pancreatic oncogenesis.
Conditional probability of long-term survival after resection of hilar cholangiocarcinoma HPB Buettner, S., Margonis, G. A., Kim, Y., Gani, F., Ethun, C. G., Poultsides, G., Thuy Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, L., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016; 18 (6): 510-517
While traditional survival analyses focus on factors determined at the time of surgery, conditional survival (CS) estimates prognosis relative to time following treatment. We sought to compare actuarial and CS among patients undergoing curative intent surgery for hilar cholangiocarcinoma.242 patients undergoing surgery between 2000 and 2014 were identified using a multi-institutional database. CS was calculated as the probability of surviving an additional 3 years, given that the patient had already survived "x" years from surgery.Median patient age was 67 years (IQR: 57-73) and most patients were male (n = 140, 57.9%). Lymph node metastases were noted in 79 (32.6%) patients while an R0 margin was obtained in 66.1% (n = 160). Median OS was 22.3 months. Actuarial survival decreased over time from 46.3% at 2 years following surgery to 18.2% at 5 years; in contrast, the 3-year CS (CS3) increased with time (CS3 at 2 years was 39.3% versus 54.4% at 5 years). CS3 exceeded actuarial survival for high-risk patients with patients with perineural invasion demonstrating an actuarial survival of 15.4% at 5 years versus CS3 of 37.6% at 2 years following surgery (Δ = 22.2%).CS provides a more accurate, dynamic estimate for survival, especially among high-risk patients.
The First Decade of Laparoscopic Pancreaticoduodenectomy in the United States: Costs and Outcomes Using the Nationwide Inpatient Sample SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Tran, T. B., Dua, M. M., Worhunsky, D. J., Poultsides, G. A., Norton, J. A., Visser, B. C. 2016; 30 (5): 1778-1783
Minimally invasive pancreaticoduodenectomy (PD) remains an uncommon procedure, and the safety and efficacy remain uncertain beyond single institution case series. The aim of this study is to compare outcomes and costs between laparoscopic (LPD) and open PD (OPD) using a large population-based database.The Nationwide Inpatient Sample database (a sample of approximately 20 % of all hospital discharges) was analyzed to identify patients who underwent PD from 2000 to 2010. Patient demographics, comorbidities, hospital characteristics, inflation-adjusted total charges, and complications were evaluated using univariate and multivariate logistic regression. Hospitals were categorized as high-volume hospitals (HVH) if more than 20 PD (open and laparoscopic) were performed annually, while those performing fewer than 20 PD were classified as low-volume hospitals.Of the 15,574 PD identified, 681 cases were LPD (4.4 %). Compared to OPD, patients who underwent LPD were slightly older (65 vs. 67 years; p = 0.001) and were more commonly treated at HVH (56.6 vs. 66.1 %; p < 0.001). Higher rates of complications were observed in OPD than LPD (46 vs. 39.4 %; p = 0.001), though mortality rates were comparable (5 vs. 3.8 %, p = 0.27). Inflation-adjusted median hospital charges were similar between OPD and LPD ($87,577 vs. $81,833, p = 0.199). However, hospital stay was slightly longer in the OPD group compared to LPD group (12 vs. 11 days, p < 0.001). Stratifying outcomes by hospital volume, LPD at HVH resulted in shorter hospital stays (9 vs. 13 days, p < 0.001), which translated into significantly lower median hospital charges ($76,572 vs. $106,367, p < 0.001).Contrary to fears regarding the potential for compromised outcomes early in the learning curve, LPD morbidity in its first decade is modestly reduced, while hospital costs are comparable to OPD. In high-volume pancreatic hospitals, LPD is associated with a reduction in length of stay and hospital costs.
Perihilar Cholangiocarcinoma: Number of Nodes Examined and Optimal Lymph Node Prognostic Scheme JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Bagante, F., Thuy Tran, T., Spolverato, G., Ruzzenente, A., Buttner, S., Ethun, C. G., Koerkamp, B. G., Conci, S., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Vitiello, G., IJzermans, J. N., Maithel, S. K., Poultsides, G., Guglielmi, A., Pawlik, T. M. 2016; 222 (5): 750-?
The role of routine lymphadenectomy for perihilar cholangiocarcinoma is still controversial and no study has defined the minimum number of lymph nodes examined (TNLE). We sought to assess the prognostic performance of American Joint Committee on Cancer/Union Internationale Contre le Cancer (7(th) edition) N stage, lymph node ratio, and log odds (LODDS; logarithm of the ratio between metastatic and nonmetastatic nodes) in patients with perihilar cholangiocarcinoma and identify the optimal TNLE to accurately stage patients.A multi-institutional database was queried to identify 437 patients who underwent hepatectomy for perihilar cholangiocarcinoma between 1995 and 2014. The prognostic abilities of the lymph node staging systems were assessed using the Harrell's c-index. A Bayesian model was developed to identify the minimum TNLE.One hundred and fifty-eight (36.2%) patients had lymph node metastasis. Median TNLE was 3 (interquartile range, 1 to 7). The LODDS had a slightly better prognostic performance than lymph node ratio and American Joint Committee on Cancer, in particular among patients with <4 TNLE (c-index = 0.568). For 2 TNLE, the Bayesian model showed a poor discriminatory ability to distinguish patients with favorable and poor prognosis. When TNLE was >2, the hazard ratio for N1 patients was statistically significant and the hazard ratio for N1 patients increased from 1.51 with 4 TNLE to 2.10 with 10 TNLE. Although the 5-year overall survival of N1 patients was only slightly affected by TNLE, the 5-year overall survival of N0 patients increased significantly with TNLE.Perihilar cholangiocarcinoma patients undergoing radical resection should ideally have at least 4 lymph nodes harvested to be accurately staged. In addition, although LODDS performed better at determining prognosis among patients with <4 TNLE, both lymph node ratio and LODDS outperformed compared with American Joint Committee on Cancer N stage among patients with ≥4 TNLE.
Identification of tumorigenic cells and therapeutic targets in pancreatic neuroendocrine tumors PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Krampitz, G. W., George, B. M., Willingham, S. B., Volkmer, J., Weiskopf, K., Jahchan, N., Newman, A. M., Sahoo, D., Zemek, A. J., Yanovsky, R. L., Nguyen, J. K., Schnorr, P. J., Mazur, P. K., Sage, J., Longacre, T. A., Visser, B. C., Poultsides, G. A., Norton, J. A., Weissman, I. L. 2016; 113 (16): 4464-4469
Pancreatic neuroendocrine tumors (PanNETs) are a type of pancreatic cancer with limited therapeutic options. Consequently, most patients with advanced disease die from tumor progression. Current evidence indicates that a subset of cancer cells is responsible for tumor development, metastasis, and recurrence, and targeting these tumor-initiating cells is necessary to eradicate tumors. However, tumor-initiating cells and the biological processes that promote pathogenesis remain largely uncharacterized in PanNETs. Here we profile primary and metastatic tumors from an index patient and demonstrate that MET proto-oncogene activation is important for tumor growth in PanNET xenograft models. We identify a highly tumorigenic cell population within several independent surgically acquired PanNETs characterized by increased cell-surface protein CD90 expression and aldehyde dehydrogenase A1 (ALDHA1) activity, and provide in vitro and in vivo evidence for their stem-like properties. We performed proteomic profiling of 332 antigens in two cell lines and four primary tumors, and showed that CD47, a cell-surface protein that acts as a "don't eat me" signal co-opted by cancers to evade innate immune surveillance, is ubiquitously expressed. Moreover, CD47 coexpresses with MET and is enriched in CD90(hi)cells. Furthermore, blocking CD47 signaling promotes engulfment of tumor cells by macrophages in vitro and inhibits xenograft tumor growth, prevents metastases, and prolongs survival in vivo.
Is Linitis Plastica a Contraindication for Surgical Resection: A Multi-Institution Study of the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Blackham, A. U., Swords, D. S., Levine, E. A., Fino, N. F., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Pawlik, T. M., Jin, L. X., Spolverato, G., Schmidt, C., Worhunsky, D., Cho, C. S., Maithel, S. K., Votanopoulos, K. I. 2016; 23 (4): 1203-1211
Current staging and treatment guidelines for gastric adenocarcinoma do not differentiate between linitis plastic (LP) and non-LP cancers. Significant controversy exists regarding the surgical management of LP patients.Using the multi-institutional U.S. Gastric Cancer Collaborative database, 869 gastric cancer patients who underwent resection between 2000 and 2012 were identified. Clinicopathologic and outcomes data of 58 LP patients were compared to 811 non-LP patients.Stage III/IV disease was more common at presentation in LP patients compared with non-LP patients (90 vs. 44 %, p < 0.01). Despite the fact that most LP patients underwent total gastrectomy (88 vs. 39 %, p < 0.01), final positive margins were more common in LP patients (33 vs. 7 %, p < 0.01). The use of frozen section allowed 15 intraoperative positive margins in 38 patients to be converted to negative final margins. Median overall survival (OS) was significantly worse in patients with LP (11.6 vs. 37.8 months, p < 0.01). There was no difference in median OS of LP patients based on stage (I/II, 17.3 mo; III, 10.6 mo; IV, 12.0 mo; p = 0.46). LP and non-LP patients who underwent optimal resection (negative margin and D2/3 lymphadenectomy) had better survival compared with those with nonoptimal resections. The median OS for optimally resected stage III LP (n = 22) and stage III non-LP (n = 185) patients was nearly identical (26.7 vs. 25.3 mo; p = 0.69).Future staging systems and treatment guidelines should differentiate between LP and non-LP gastric cancers. Long-term survival in select LP patients who undergo optimal resections is comparable to optimally resected non-LP patients.
Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma JAMA SURGERY Kim, Y., Margonis, G. A., Prescott, J. D., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A. I., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. 2016; 151 (4): 365-373
Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined.To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction.Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015.The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves.In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47-15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95-3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27-4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02-3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00-3.17; P = .05), positive nodal status (HR, 5.89; 95% CI, 2.05-16.87; P = .001), and R1 margin (HR, 2.83; 95% CI, 1.51-5.30; P = .001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS).Independent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation.
Stage-Specific Prognostic Effect of Race in Patients with Resectable Gastric Adenocarcinoma: An 8-Institution Study of the US Gastric Cancer Collaborative. Journal of the American College of Surgeons Wang, A., Squires, M. H., Melis, M., Poultsides, G. A., Norton, J. A., Jin, L. X., Fields, R. C., Spolverato, G., Pawlik, T. M., Votanopoulos, K. I., Levine, E. A., Schmidt, C., Bloomston, M., Cho, C. S., Weber, S., Berman, R., Pachter, H. L., Newman, E., Staley, C. A., Maithel, S. K., Hatzaras, I. 2016; 222 (4): 633-643
Gastric cancer constitutes a major public health problem. This study sought to evaluate the relevance of race in gastric cancer and its prognostic effect in the overall outcomes of patients with gastric adenocarcinoma.Patients who underwent curative intent resection of gastric adenocarcinoma in 8 institutions of the US Gastric Cancer Collaborative were included, from 2000 to 2012. Nonparametric descriptive statistics were used to evaluate characteristics of standard demographic data. Multivariate Cox proportional hazards regression was used to identify factors associated with recurrence-free survival and overall survival.There were 1,077 patients included in the study, the majority of whom were of Caucasian race (n = 698, 68%), followed by African-American (n = 164, 15%), Asian (n = 132, 12%), Hispanic (n = 34, 3.2%), and other (n = 49, 4.5%). Clinicopathologic data were similarly distributed among the 5 groups. Mean follow-up was 27.1 months. By multivariate, stage-specific analysis, Asian race was a significant predictor of recurrence (all stages hazard ratio [HR] 0.45 95% CI [0.23, 0.97], p = 0.041) and of overall survival (all stages HR 0.35 95% CI [0.18, 0.68], p = 0.002). Recurrence-free survival was significantly increased in the Asian population compared with the non-Asian population (25th percentile: 38.6 vs 17.7 months, p = 0.0096), as was overall median survival (141 vs 38.8 months, p < 0.001).Patients of Asian race undergoing curative gastrectomy for gastric adenocarcinoma appear to have a better prognosis stage for stage. Further studies are required to elucidate the underlying etiology of this phenomenon.
Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group. Journal of the American College of Surgeons Postlewait, L. M., Ethun, C. G., Tran, T. B., Prescott, J. D., Pawlik, T. M., Wang, T. S., Glenn, J., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Staley, C. A., Poultsides, G. A., Maithel, S. K. 2016; 222 (4): 480-490
Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines.Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS).Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS.When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.
Preoperative Helicobacter pylori Infection is Associated with Increased Survival After Resection of Gastric Adenocarcinoma ANNALS OF SURGICAL ONCOLOGY Postlewait, L. M., Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D., Jin, L. X., Cho, C. S., Winslow, E. R., Cardona, K., Staley, C. A., Maithel, S. K. 2016; 23 (4): 1225-1233
Limited data exist on the prognosis of preoperative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC).Patients who underwent curative-intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the United States Gastric Cancer Collaborative were included in the study. The primary end points of the study were overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS).Of 559 patients, 104 (18.6 %) who tested positive for H. pylori were younger (62.1 vs 65.1 years; p = 0.041), had a higher frequency of distal tumors (82.7 vs 71.9 %; p = 0.033), and had higher rates of adjuvant radiation therapy (47.0 vs 34.9 %; p = 0.032). There were no differences in American Society of Anesthesiology (ASA) class, margin status, grade, perineural invasion, lymphovascular invasion, nodal metastases, or tumor-node-metastasis (TNM) stage. H. pylori positivity was associated with longer OS (84.3 vs 44.2 months; p = 0.008) for all patients. This relationship with OS persisted in the multivariable analysis (HR 0.54; 95 % CI 0.30-0.99; p = 0.046). H. pylori was not associated with RFS or DSS in all patients. In the stage 3 patients, H. pylori was associated with longer OS (44.5 vs 24.7 months; p = 0.018), a trend of longer RFS (31.4 vs 21.6 months; p = 0.232), and longer DSS (44.8 vs 27.2 months; p = 0.034).Patients with and without preoperative H. pylori infection had few differences in adverse pathologic features at the time of gastric adenocarcinoma resection. Despite similar disease presentations, preoperative H. pylori infection was independently associated with improved OS. Further studies examining the interaction between H. pylori and tumor immunology and genetics are merited.
A multi-institutional analysis of elderly patients undergoing a liver resection for intrahepatic cholangiocarcinoma JOURNAL OF SURGICAL ONCOLOGY Vitale, A., Spolverato, G., Bagante, F., Gani, F., Popescu, I., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Sandroussi, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2016; 113 (4): 420-426
Little is known regarding postoperative outcomes of elderly patients undergoing liver surgery for intrahepatic cholangiocarcinoma (ICC).Five hundred and eighty-four patients undergoing liver resection for ICC between 1990 and 2015 were identified. Perioperative morbidity, mortality, overall survival (OS), and disease-free survival (DFS) were compared between elderly (>70 year, n = 129) and non-elderly (≤70 years, n = 455) patients.Older patients had a higher incidence of complications (elderly vs. non-elderly; 52.7% vs. 42.6%; P = 0.03), as well as major complications (elderly vs. non-elderly; 24.0% vs. 14.9%; P = 0.01); 30-day (0.1% vs. 3.3%; P > 0.05), and 90-day mortality (2.3% vs. 5.5%; P > 0.05) were comparable. Five-year OS and DFS were comparable between the elderly and non-elderly patients (OS, 13.3% vs. 24.4%; and DFS; 7.3% vs. 12.0%; P > 0.05). On propensity score matching, DFS and OS were also comparable among non-elderly versus elderly patients. Poor tumor grade was associated with worse DFS among elderly patients (HR = 1.6, 95%CI 1.0-2.6; P = 0.04), whereas periductal invasion (HR = 1.9, 95% CI 1.1-3.5; P = 0.03) and nodal disease (HR = 2.3, 95% CI 1.3-3.9; P = 0.003) were predictive of shorter DFS among non-elderly patients.Elderly patients undergoing liver surgery for ICC demonstrated an increased risk of perioperative complications, but comparable long-term DFS and OS compared with younger patients. Rather, tumor characteristics were more predictive of worse long-term outcomes. J. Surg. Oncol. 2016;113:420-426. © 2016 Wiley Periodicals, Inc.
Incidence of Perioperative Complications Following Resection of Adrenocortical Carcinoma and Its Association with Long-Term Survival WORLD JOURNAL OF SURGERY Margonis, G. A., Amini, N., Kim, Y., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Moses, L. E., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 40 (3): 706-714
The association of postoperative complications with long-term oncologic outcomes remains unclear. We sought to determine the incidence of complications among patients who underwent surgery for adrenocortical carcinoma (ACC) and define the relationship of morbidity with long-term survival.Patients who underwent surgery for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the US ACC group study. The incidence and type of the postoperative complications, the factors associated with them as well their association with long-term survival were analyzed.A total of 265 patients with median age of 52 years (IQR 44-63) were identified; at surgery, the majority of patients underwent an open abdominal procedure (n = 169, 66.8 %). A postoperative complication occurred in 99 patients for a morbidity of 37.4 %; five patients (1.9 %) died in hospital. Factors associated with morbidity included a thoraco-abdominal operative approach (reference: open abdominal; OR 2.85, 95 % CI 1.00-8.18), and a hormonally functional tumor (OR 3.56, 95 % CI 1.65-7.69) (all P < 0.05). Presence of any complication was associated with a worse long-term outcome (median survival: no complication, 58.9 months vs. any complication, 25.1 months; P = 0.009). In multivariate analysis, after adjusting for patient- and disease-related factors postoperative infectious complications independently predicted shorter overall survival (hazard ratio (HR) 5.56, 95 % CI 2.24-13.80; P < 0.001).Postoperative complications were independently associated with decreased long-term survival after resection for ACC. The prevention of complications may be important from an oncologic perspective.
Palliative treatment in extrahepatic biliary malignancies: A multi-institutional cohort. Wilson, A., Ethun, C., Poultsides, G. A., Thuy Tran, Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A. I., Martin, R. G., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Maithel, S., Pawlik, T. M. AMER SOC CLINICAL ONCOLOGY. 2016
Conditional survival probability of long-term survival after resection of peri-hilar cholangiocarcinoma. Buettner, S., Ethun, C., Maithel, S., Poultsides, G. A., Thuy Tran, Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A. I., Martin, R. G., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Pawlik, T. M. AMER SOC CLINICAL ONCOLOGY. 2016
A novel pathology-based preoperative risk score to predict distant and locoregional residual disease and survival for incidentally discovered gallbladder cancer: A 10-institution study from the US Extrahepatic Biliary Malignancy Consortium. Ethun, C., Postlewait, L., Pawlik, T. M., Buettner, S., Poultsides, G. A., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L., Weber, S. M., Salem, A. I., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Maithel, S. AMER SOC CLINICAL ONCOLOGY. 2016
The optimal time-interval to re-resection for incidentally discovered gallbladder cancer: A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium. Ethun, C., Postlewait, L., Pawlik, T. M., Buettner, S., Poultsides, G. A., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L., Weber, S. M., Salem, A. I., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Maithel, S. AMER SOC CLINICAL ONCOLOGY. 2016
A multi-institutional analysis of duodenal neuroendocrine tumors: Tumor biology rather than extent of resection to dictate prognosis. Margonis, G. A., Samaha, M., Kim, Y., Postlewait, L., Maithel, S., Poultsides, G. A., Thuy Tran, Gamblin, T., Berger, N., Pawlik, T. M. AMER SOC CLINICAL ONCOLOGY. 2016
A reappraisal of staging laparoscopy in three subtypes of cholangiocarcinoma: A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium. Davidson, J., Jin, L., Krasnick, B., Ethun, C., Pawlik, T. M., Poultsides, G. A., Thuy Tran, Idrees, K., Isom, C. A., Weber, S. M., Salem, A. I., Hawkins, W. G., Strasberg, S. M., Martin, R. G., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Maithel, S., Fields, R. C. AMER SOC CLINICAL ONCOLOGY. 2016
Effect of preoperative bilirubin on outcomes of completely resected hilar cholangiocarcinoma: A multi-institutional analysis Mogal, H., Dodson, R., Fino, N., Ethun, C., Pawlik, T. M., Poultsides, G. A., Thuy Tran, Idrees, K., Fields, R. C., Jin, L., Weber, S. M., Salem, A. I., Martin, R. G., Scoggins, C., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Maithel, S., Shen, P. AMER SOC CLINICAL ONCOLOGY. 2016
Rates and patterns of recurrence following complete resection of Hilar cholangiocarcinoma: Results from the US Extrahepatic Biliary Consortium Mogal, H., O'Connor, S., Fino, N., Ethun, C., Pawlik, T. M., Poultsides, G. A., Thuy Tran, Idrees, K., Isom, C. A., Fields, R. C., Jin, L., Weber, S. M., Salem, A. I., Martin, R. G., Scoggins, C., Schmidt, C., Beal, E. W., Hatzaras, I., Maithel, S., Shen, P. AMER SOC CLINICAL ONCOLOGY. 2016
Gallbladder cancer presenting with jaundice: Uniformly fatal or still potentially curable? Thuy Tran, Ethun, C., Pawlik, T. M., Buettner, S., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A. I., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Maithel, S., Poultsides, G. A. AMER SOC CLINICAL ONCOLOGY. 2016
Curative resection for hilar cholangiocarcinoma: Does adjuvant therapy impact overall survival? A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium. Krasnick, B., Jin, L., Davidson, J., Ethun, C., Pawlik, T. M., Poultsides, G. A., Tran, T., Idrees, K., Isom, C. A., Weber, S. M., Salem, A. I., Hawkins, W. G., Strasberg, S. M., Martin, R. G., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Maithel, S., Fields, R. C., Tumors, E. AMER SOC CLINICAL ONCOLOGY. 2016
Impact of chemotherapy and external beam radiation therapy on outcomes among patients with resected gallbladder cancer: A multi-institutional analysis. Kim, Y., Amini, N., Wilson, A., Ethun, C., Poultsides, G. A., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Weber, S. M., Salem, A. I., Martin, R. G., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Hatzaras, I., Shenoy, R., Maithel, S., Pawlik, T. M. AMER SOC CLINICAL ONCOLOGY. 2016
Optimal prognostic lymph node staging system for gallbladder adenocarcinoma: A multi-institutional study. Amini, N., Kim, Y., Wilson, A., Ethun, C., Maithel, S., Poultsides, G. A., Thuy Tran, Idrees, K., Isom, C. A., Fields, R. C., Weber, S. M., Salem, A., Martin, R. G., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Hatzaras, I., Shenoy, R., Pawlik, T. M. AMER SOC CLINICAL ONCOLOGY. 2016
The effect of postoperative morbidity on long-term survival after curative resection for extra-hepatic biliary tumors: A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium. Jin, L., Krasnick, B., Davidson, J., Ethun, C., Pawlik, T. M., Poultsides, G. A., Thuy Tran, Idrees, K., Isom, C. A., Weber, S. M., Salem, A. I., Scoggins, C., Shen, P., Mogal, H., Schmidt, C., Beal, E. W., Hatzaras, I., Maithel, S., Fields, R. C. AMER SOC CLINICAL ONCOLOGY. 2016
Albumin and Neutrophil-Lymphocyte Ratio (NLR) Predict Survival in Patients With Pancreatic Adenocarcinoma Treated With SBRT. American journal of clinical oncology Alagappan, M., Pollom, E. L., von Eyben, R., Kozak, M. M., Aggarwal, S., Poultsides, G. A., Koong, A. C., Chang, D. T. 2016: -?
To determine if pretreatment nutritional status and inflammatory markers correlate with survival in patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiotherapy (SBRT).We retrospectively reviewed 208 patients with newly diagnosed, locally advanced pancreatic adenocarcinoma treated with SBRT at our institution from 2002 to 2014. Laboratory values were collected before SBRT, including hemoglobin, platelets, albumin, red blood cell, white blood cell, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and tumor markers CA 19-9 and CEA. Patients were followed every 3 months with computed tomography (CT) and/or positron emission tomography-CT imaging to monitor for local recurrence and overall survival (OS).Median follow-up after SBRT was 7.5 months (interquartile range, 4.6 to 12.0 mo) for all patients. Median OS for patients with NLR>5 compared with NLR≤5 was 6.9 and 8.5 months, respectively (P=0.0057). On univariate analysis, receipt of chemotherapy (P=0.05, hazard ratio [HR]=0.69), increased albumin (P=0.002, HR=0.64), increased red blood cell (P=0.05, HR=0.75), increased lymphocyte count (P=0.002, HR=0.66), decreased CEA (P=0.01, HR=0.96), and NLR≤5 (P=0.01, HR=0.65) correlated with improved OS. On multivariate analysis, higher albumin (P=0.03, HR=0.70), receipt of chemotherapy (P=0.007, HR=0.56), and NLR≤5 (P=0.02, HR=0.66) correlated with better survival.Preradiotherapy low albumin levels and NLR>5 correlate with decreased survival in patients with locally advanced pancreatic adenocarcinoma treated with SBRT, indicating the prognostic value of systemic inflammatory markers (such as NLR) and a role of nutritional supplementation to improve outcomes in these patients. Further investigation is warranted.
Statin and Metformin Use Prolongs Survival in Patients With Resectable Pancreatic Cancer. Pancreas Kozak, M. M., Anderson, E. M., von Eyben, R., Pai, J. S., Poultsides, G. A., Visser, B. C., Norton, J. A., Koong, A. C., Chang, D. T. 2016; 45 (1): 64-70
The aim of this study was to investigate the impact of statin and metformin therapy on disease outcome for patients with pancreatic ductal adenocarcinoma (PDAC).This retrospective study included 171 PDAC patients who underwent surgical resection at the Stanford Cancer Institute between 1998 and 2013. No patients received neoadjuvant therapy. Statin and metformin use was defined as use during initial consult and continuing upon discharge from the hospital after surgery. Dose of each medication was recorded, as was the type of statin taken.The median follow-up for all patients was 11.23 months (range, 0.2-105.0 months). Among the 171 patients included in our analysis, 18 patients (10.5%) took metformin and 34 patients (19.9%) took statins. Statin use was associated with better overall survival (OS) in patients with PDAC (P = 0.011). Metformin use was also associated with better OS (P = 0.035). The use of statins remained significant on multivariate analysis for OS (P = 0.014; hazards ratio, 0.33; 95% confidence interval, 0.139-0.799), but metformin use did not (P = 0.33; hazards ratio 0.60, 95% confidence interval, 0.211-1.675).Statin and metformin use is associated with improved OS in patients with resectable PDAC. These medications should be further investigated for possible long-term use in the general population.
Management and Outcomes of Patients with Recurrent Intrahepatic Cholangiocarcinoma Following Previous Curative-Intent Surgical Resection. Annals of surgical oncology Spolverato, G. n., Kim, Y. n., Alexandrescu, S. n., Marques, H. P., Lamelas, J. n., Aldrighetti, L. n., Clark Gamblin, T. n., Maithel, S. K., Pulitano, C. n., Bauer, T. W., Shen, F. n., Poultsides, G. A., Tran, T. B., Wallis Marsh, J. n., Pawlik, T. M. 2016; 23 (1): 235–43
Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes.Patients who underwent surgery for ICC from 1990 to 2013 were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence, and recurrence-related management were recorded and analyzed.A total of 563 patients undergoing curative-intent hepatic resection for ICC who met the inclusion criteria were identified. With a median follow-up of 19 months, 400 (71.0 %) patients developed a recurrence. At initial surgery, treatment was resection only (98.8 %) or resection + ablation (1.2 %). Overall 5-year survival was 23.6 %; 400 (71.0 %) patients recurred with a median disease-free survival of 11.2 months. First recurrence site was intrahepatic only (59.8 %), extrahepatic only (14.5 %), or intra- and extrahepatic (25.7 %). Overall, 210 (52.5 %) patients received best supportive care (BSC), whereas 190 (47.5 %) patients received treatment, such as systemic chemotherapy-only (24.2 %) or repeat liver-directed therapy ± systemic chemotherapy (75.8 %). Repeat liver-directed therapy consisted of repeat hepatic resection ± ablation (28.5 %), ablation alone (18.7 %), and intra-arterial therapy (IAT) (52.8 %). Among patients who recurred, median survival from the time of the recurrence was 11.1 months (BSC 8.0 months, systemic chemotherapy-only 16.8 months, liver-directed therapy 18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 9.6 months for patients who had IAT (p < 0.001).Recurrence following resection of ICC was common, occurring in up to two-thirds of patients. When there is recurrence, prognosis is poor. Only 9 % of patients underwent repeat liver resection after recurrence, which offered a modest survival benefit.
Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence. Annals of surgical oncology Amini, N. n., Margonis, G. A., Kim, Y. n., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I. n., Shenoy, R. n., Phay, J. E., Keplinger, K. n., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A. n., Sicklick, J. K., Gad, S. n., Yopp, A. C., Mansour, J. C., Duh, Q. Y., Seiser, N. n., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 23 (1): 126–33
Adrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative-intent surgery for ACC.Patients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence.A total of 180 patients with a median age of 52 years (interquartile range 43-61) were identified. Most patients underwent open surgery (n = 111, 64.5 %) and had an R0 resection margin (n = 117, 75.0 %). At last follow-up, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06-6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19-7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01-1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70-16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional-only recurrence (3- and 5-year survival 81.4, 64.1 %) (p = 0.01).Nearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis.
Adrenocortical Carcinoma: Impact of Surgical Margin Status on Long-Term Outcomes. Annals of surgical oncology Margonis, G. A., Kim, Y. n., Prescott, J. D., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I. n., Shenoy, R. n., Phay, J. E., Keplinger, K. n., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A. n., Sicklick, J. K., Gad, S. n., Yopp, A. C., Mansour, J. C., Duh, Q. Y., Seiser, N. n., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 23 (1): 134–41
The influence of surgical margin status on long-term outcomes of patients undergoing adrenal resection for ACC remains not well defined. We studied the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ACC.A total of 165 patients who underwent adrenal resection for ACC and met inclusion criteria were identified form a multi-institutional database. Clinicopathological data, pathologic margin status, and long-term outcomes were assessed. Patients were stratified into two groups based on margin status: R0 (margin >1 mm) versus R1.R0 resection was achieved in 126 patients (76.4 %), whereas 39 patients (23.6 %) had an R1 resection. Median and 5-year OS for patients undergoing R0 resection were 96.3 months and 64.8 % versus 25.1 months and 33.8 % for patients undergoing an R1 resection (both p < 0.001). On multivariable analysis, surgical margin status was an independent predictor of worse OS (hazard ratio [HR] 2.22, 95 % confidence interval [CI] 1.03-4.77; p = 0.04). The incidence of recurrence also differed between the two groups; 5-year RFS was 30.3 % among patients with an R0 resection versus 13.8 % among patients who had an R1 resection (p = 0.03). Lymph node metastasis (N1) was an independent predictor of RFS (HR 2.70, 95 % CI 1.04-6.99; p = 0.04).A positive margin after ACC resection was associated with worse long-term survival. Patient selection and an emphasis on surgical technique to achieve R0 margins are pivotal to optimizing the best chance for long-term outcome among patients with ACC.
Adrenocortical Carcinoma: Impact of Surgical Margin Status on Long-Term Outcomes ANNALS OF SURGICAL ONCOLOGY Margonis, G. A., Kim, Y., Prescott, J. D., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 23 (1): 134-141
Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence ANNALS OF SURGICAL ONCOLOGY Amini, N., Margonis, G. A., Kim, Y., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 23 (1): 126-133
Management and Outcomes of Patients with Recurrent Intrahepatic Cholangiocarcinoma Following Previous Curative-Intent Surgical Resection ANNALS OF SURGICAL ONCOLOGY Spolverato, G., Kim, Y., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Tran, T. B., Marsh, J. W., Pawlik, T. M. 2016; 23 (1): 235-243
Gastric Remnant Cancer: A Distinct Entity or Simply Another Proximal Gastric Cancer? JOURNAL OF SURGICAL ONCOLOGY Tran, T. B., Hatzaras, I., Worhunsky, D. J., Vitiello, G. A., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Norton, J. A., Poultsides, G. A. 2015; 112 (8): 877-882
The purpose of this study was to compare outcomes following resection of gastric remnant (GRC) and conventional gastric cancer.Patients who underwent resection for gastric cancer in 8 academic institutions from 2000-2012 were evaluated to compare morbidity, mortality, and survival based on history of prior gastrectomy.Of the 979 patients who underwent gastrectomy with curative-intent during the 12-year study period, 55 patients (5.8%) presented with GRC and 924 patients (94.4%) presented with conventional gastric cancer. Patients with GRC were slightly older (median 69 vs. 66 years). GRC was associated with higher rates of complication (56% vs. 41%, P = 0.028), longer operative times (301 vs. 237 min, P < 0.001), higher intraoperative blood loss (300 vs. 200 ml, P = 0.012), and greater need for blood transfusion (43% vs. 23%, P = 0.001). There were no significant differences in 30-day (3.6% vs. 4%) or 90-day mortality (9% vs. 8%) between the two groups. Overall survival rates were similar between GRC and conventional gastric cancer (5-year 20.3% vs. 38.6%, P = 0.446). Multivariate analysis revealed that history of gastrectomy was not predictive of survival while established predictors (older age, advanced T-stage, nodal involvement, blood transfusion, multivisceral resection, and any complication) were associated with poor survival.Despite higher morbidity, prognosis after resection of gastric remnant cancer is similar to conventional gastric cancer. J. Surg. Oncol. 2015;112:877-882. © 2015 Wiley Periodicals, Inc.
Noninvasive Genotyping and Assessment of Treatment Response in Diffuse Large B Cell Lymphoma Scherer, F., Kurtz, D. M., Newman, A. M., Stehr, H., Liu, C., Zhou, L., Craig, A. M., Chabon, J. J., Lovejoy, A. F., Klass, D. M., Glover, C., Ohgami, R. S., Kunder, C. A., Visser, B. C., Poultsides, G., Levy, R., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2015
Outcomes of Gastric Cancer Resection in Octogenarians: A Multi-institutional Study of the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Tran, T. B., Worhunsky, D. J., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Norton, J. A., Poultsides, G. A. 2015; 22 (13): 4371-4379
As the U.S. population ages, an increasing number of elderly patients with gastric adenocarcinoma are being evaluated for surgical resection. This study aimed to describe the short- and long-term outcomes after gastric cancer resection for patients 80 years of age or older.Patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012 at seven U.S. academic institutions were analyzed. The main outcome measures included postoperative morbidity, mortality, survival, and failure to rescue (defined as death after any complication).Of 953 patients who underwent distal or total gastrectomy during the 12-year study period, 127 (13 %) were 80 years of age or older. Although the type of postoperative complications did not differ between the two groups, octogenarians had a higher incidence of any (54 vs 41 %; p = 0.006) and of major (28 vs 17 %; p = 0.006) postoperative complications. This translated into higher 30-day (10.2 vs 3.6 %; p = 0.001) and 90-day mortality (19.7 vs 7.9 %; p = 0.001) rates, with correspondingly higher failure-to-rescue rates (17.4 vs 8 %; p = 0.015). However, disease-specific survival after resection was equivalent between the two groups (5-year survival: 46 vs 53 %; p = 0.676). In the multivariate analysis, age of 80 years or older, blood transfusion, and albumin and creatinine levels all were independent predictors of 90-day mortality. Stage, tumor grade, race, blood transfusion, and adjuvant therapy, but not age, were independently associated with disease-specific survival.Perioperative mortality and failure-to-rescue from complications is substantial for octogenarians undergoing gastric cancer resection. However, if the operation can be performed safely, the long-term cancer-specific outcome appears similar to that for younger patients.
Intrahepatic Cholangiocarcinoma: Prognosis of Patients Who Did Not Undergo Lymphadenectomy JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Bagante, F., Gani, F., Spolverato, G., Xu, L., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 221 (6): 1031-?
The role of routine lymphadenectomy (LD) among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) remains poorly defined. This study aimed to evaluate the role of routine LD as well as to quantify the impact of not assessing nodal station on disease-specific survival (DSS) among patients undergoing liver surgery for ICC.Using data from 12 major hepatobiliary centers, 561 patients undergoing liver surgery for ICC between 1990 and 2012 were identified. The association between nodal status and DSS was assessed using Cox proportional and Aalen's linear hazards models.Among the 272 (48.5%) patients who underwent LD, 123 (45.2%) had lymph node metastasis (N1). Although differences in DSS were noted between N0 and Nx patients within the first 18 months after surgery (DSS at 18 months: N0 vs Nx, 70.2% vs 60.6%, respectively, p = 0.019) among patients who had survived to 18 months, the DSS at 60 months of Nx patients was comparable to that of N0 patients (p = 0.48). Conversely, although the DSS of N1 and Nx patients was comparable in the short-term (DSS at 18 months: p = 0.13), among patients who had survived to 18 months, N1 patients had a lower DSS compared with Nx patients (DSS at 60 months among patients who had survived to 18 months: N1 vs Nx, 15.2% vs 45.8%, respectively, p < 0.001; all p values were based on the log-rank test comparing 2 survival curves).Although Nx patients and N1 patients had comparable DSS in the short-term, Nx patients who survived past 18 months had a survival comparable to that of N0 patients. Lack of nodal staging may lead to heterogeneous and potentially incorrect prognostic classification of patients with ICC.
Value of Peritoneal Drain Placement After Total Gastrectomy for Gastric Adenocarcinoma: A Multi-institutional Analysis from the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Dann, G. C., Squires, M. H., Postlewait, L. M., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D. S., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Staley, C. A., Maithel, S. K., Cardona, K. 2015; 22: S888-S897
The effect of routine drainage after abdominal surgery with enteric anastomoses is controversial. In particular, the role of peritoneal drain (PD) placement after total gastrectomy for adenocarcinoma is not well established.Patients who underwent total gastrectomy for gastric adenocarcinoma (GAC) at seven institutions from the US Gastric Cancer Collaborative, from 2000 to 2012, were identified. The association of PD placement with postoperative outcomes was analyzed.Overall, 344 patients were identified and 253 (74 %) patients received a PD. The anastomotic leak rate was 9 %. Those with PD placement had similar American Society of Anesthesiologists score, tumor size, TNM stage, and the need for additional organ resection when compared with their counterparts. No difference was observed in the rate of any complication (54 vs. 48 %; p = 0.45), major complication (25 vs. 24 %; p = 0.90), or 30-day mortality (7 vs. 4 %; p = 0.51) between the two groups. In addition, no difference in anastomotic leak (9 vs. 10 %; p = 0.90), the need for secondary drainage (10 vs. 9 %; p = 0.92), or reoperation (13 vs. 8 %; p = 0.28) was identified. On multivariate analysis, PD placement was not associated with decreased postoperative complications. Subset analysis, stratified by patients who did not undergo concomitant pancreatectomy (n = 319) or those who experienced anastomotic leak (n = 31), similarly demonstrated no association of PD placement with reduced complications or mortality.PD placement after total gastrectomy for GAC is associated with neither a decrease in the frequency and severity of adverse postoperative outcomes, including anastomotic leak and mortality, nor a decrease in the need for secondary drainage procedures or reoperation. Routine use of PDs is not warranted.
Prognostic Performance of Different Lymph Node Staging Systems After Curative Intent Resection for Gastric Adenocarcinoma ANNALS OF SURGERY Spolverato, G., Ejaz, A., Kim, Y., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Votanopoulos, K., Acher, A. W., Jin, L. X., Hawkins, W. G., Schmidt, C., Kooby, D. A., Worhunsky, D., Saunders, N., Cho, C. S., Levine, E. A., Maithel, S. K., Pawlik, T. M. 2015; 262 (6): 991-998
To compare the prognostic performance of American Joint Committee on Cancer/International Union Against Cancer seventh N stage relative to lymph node ratio (LNR), log odds of metastatic lymph nodes (LODDS), and N score in gastric adenocarcinoma.Metastatic disease to the regional LN basin is a strong predictor of worse long-term outcome following curative intent resection of gastric adenocarcinoma.A total of 804 patients who underwent surgical resection of gastric adenocarcinoma were identified from a multi-institutional database. The relative discriminative abilities of the different LN staging/scoring systems were assessed using the Akaike's Information Criterion (AIC) and the Harrell's concordance index (c statistic).Of the 804 patients, 333 (41.4%) had no lymph node metastasis, whereas 471 (58.6%) had lymph node metastasis. Patients with ≥N1 disease had an increased risk of death (hazards ratio = 2.09, 95% confidence interval: 1.68-2.61; P < 0.001]. When assessed using categorical cutoff values, LNR had a somewhat better prognostic performance (C index: 0.630; AIC: 4321.9) than the American Joint Committee on Cancer seventh edition (C index: 0.615; AIC: 4341.9), LODDS (C index: 0.615; AIC: 4323.4), or N score (C index: 0.620; AIC: 4324.6). When LN status was modeled as a continuous variable, the LODDS staging system (C index: 0.636; AIC: 4304.0) outperformed other staging/scoring systems including the N score (C index: 0.632; AIC: 4308.4) and LNR (C index: 0.631; AIC: 4225.8). Among patients with LNR scores of 0 or 1, there was a residual heterogeneity of outcomes that was better stratified and characterized by the LODDS.When assessed as a categorical variable, LNR was the most powerful manner to stratify patients on the basis of LN status. LODDS was a better predicator of survival when LN status was modeled as a continuous variable, especially among those patients with either very low or high LNR.
Factors Associated With Recurrence and Survival in Lymph Node-negative Gastric Adenocarcinoma A 7-Institution Study of the US Gastric Cancer Collaborative ANNALS OF SURGERY Jin, L. X., Moses, L. E., Squires, M. H., Poultsides, G. A., Votanopoulos, K., Weber, S. M., Bloomston, M., Pawlik, T. M., Hawkins, W. G., Linehan, D. C., Strasberg, S. M., Schmidt, C., Worhunsky, D. J., Acher, A. W., Cardona, K., Cho, C. S., Kooby, D. A., Levine, E., Winslow, E. R., Saunders, N. D., Spolverato, G., Maithel, S. K., Fields, R. C. 2015; 262 (6): 999-1005
To determine pathologic features associated with recurrence and survival in patients with lymph node-negative gastric adenocarcinoma.Multi-institutional retrospective analysis.Lymph node status is among the most important predictors of recurrence after gastrectomy for gastric adenocarcinoma. Pathologic features predictive of recurrence in patients with node-negative disease are less well established.Patients who underwent curative resection for gastric adenocarcinoma between 2000 and 2012 from 7 institutions of the US Gastric Cancer Collaborative were analyzed, excluding 30-day mortalities and stage IV disease. Competing risks regression and multivariate Cox regression were used to determine pathologic features associated with time to recurrence and overall survival. Differences in cumulative incidence of recurrence were assessed using the Gray method (for univariate nonparametric analyses) and the Fine and Gray method (for multivariate analyses) and shown as subhazard ratios (SHRs) and adjusted subhazard ratios (aSHRs), respectively.Of 805 patients who met inclusion criteria, 317 (39%) had node-negative disease, of which 54 (17%) recurred. By 2 and 5 years, 66% and 88% of patients, respectively, experienced recurrence. On multivariate competing risks regression, only T-stage 3 or higher was associated with shorter time to recurrence [aSHR = 2.7; 95% confidence interval (CI), 1.5-5.2]. Multivariate Cox regression showed T-stage 3 or higher [hazard ratio (HR) = 1.8; 95% CI, 1.2-2.8], lymphovascular invasion (HR = 2.2; 95% CI, 1.4-3.4), and signet ring histology (HR = 2.1; 95% CI, 1.2-3.6) to be associated with decreased overall survival.Despite absence of lymph node involvement, patients with T-stage 3 or higher have a significantly shorter time to recurrence. These patients may benefit from more aggressive adjuvant therapy and postoperative surveillance regimens.
The Prognostic Value of Signet-Ring Cell Histology in Resected Gastric Adenocarcinoma ANNALS OF SURGICAL ONCOLOGY Postlewait, L. M., Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D., Jin, L. X., Cho, C. S., Winslow, E. R., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 22: S832-S839
Conflicting data exist on the prognostic implication of signet-ring cell (SRC) histology in gastric adenocarcinoma (GAC).All patients who underwent curative-intent resection of GAC from the seven institutions of the U.S. Gastric Cancer Collaborative between 2000 and 2012 were included. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Stage-specific analyses were performed.A total of 768 patients met the inclusion criteria. SRC was present in 40.6 % of patients and was associated with female sex (52.9 vs. 38.6 %; p < 0.001), younger age (61 vs. 67 years; p < 0.001), poor differentiation (94.8 vs. 50.3 %; p < 0.001), perineural invasion (PNI) (41.4 vs. 23 %; p < 0.001), microscopically positive resection margins (R1, 24.7 vs. 8.6 %; p < 0.001), distal location (82.2 vs. 70.1 %; p < 0.001), receipt of adjuvant therapy (63 vs. 51.2 %; p = 0.002), and more advanced stage (stage 3: 55.2 vs. 36.5 %; p < 0.001). SRC was associated with earlier recurrence (56.7 months vs. median not reached; p = 0.009) and decreased OS (33.7 vs. 46.6 months; p = 0.011). When accounting for other adverse pathologic features, PNI (hazard ratio [HR] 1.57; p = 0.016) and higher stage (HR 2.64; p < 0.001) were associated with decreased RFS, but SRC was not. Although PNI (HR 1.52; p = 0.007), higher stage (HR 2.11; p < 0.001), greater size (HR 1.05; p = 0.016), and adjuvant therapy (HR 0.50; p < 0.001) were associated with OS, SRC was not. Similarly, when accounting for adverse pathologic factors on multivariate analysis, stage-specific analyses showed no association between SRC and RFS or OS.SRC histology is associated with adverse pathologic features including poor differentiation, higher stage, and microscopically positive resection margins but is not independently associated with reduced RFS or OS. Identification of signet-ring histology during preoperative evaluation should not, in isolation, dictate treatment strategy.
Value of Peritoneal Drain Placement After Total Gastrectomy for Gastric Adenocarcinoma: A Multi-institutional Analysis from the US Gastric Cancer Collaborative. Annals of surgical oncology Dann, G. C., Squires, M. H., Postlewait, L. M., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D. S., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Staley, C. A., Maithel, S. K., Cardona, K. 2015; 22: 888-897
The Prognostic Value of Signet-Ring Cell Histology in Resected Gastric Adenocarcinoma. Annals of surgical oncology Postlewait, L. M., Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D., Jin, L. X., Cho, C. S., Winslow, E. R., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 22: 832-839
Incidence and Risk Factors Associated with Readmission After Surgical Treatment for Adrenocortical Carcinoma JOURNAL OF GASTROINTESTINAL SURGERY Valero-Elizondo, J., Kim, Y., Prescott, J. D., Margonis, G. A., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Glenn, J. A., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2015; 19 (12): 2154-2161
Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Given the lack of data on readmission after resection of ACC, the objective of the current study was to define the incidence of readmission, as well as identify risk factors associated with readmission among patients with ACC who underwent surgical resection.Two hundred nine patients who underwent resection of ACC between January 1993 and December 2014 at 1 of 13 major centers in the USA were identified. Demographic and clinicopathological data were collected and analyzed relative to readmission.Median patient age was 52 years, and 62 % of the patients were female. Median tumor size was 12 cm, and the majority of patients had an American Society of Anesthesiologists (ASA) class of 3-4 (n = 85, 56 %). The overall incidence of readmission within 90 days from surgery was 18 % (n = 38). Factors associated with readmission included high ASA class (odds ratio (OR), 4.88 (95 % confidence interval (CI), 1.75-13.61); P = 0.002), metastatic disease on presentation (OR, 2.98 (95 % CI, 1.37-6.46); P = 0.006), EBL (>700 mL: OR, 2.75 (95 % CI, 1.16-6.51); P = 0.02), complication (OR, 1.91 (95 % CI, 1.20-3.05); P = 0.007), and prolonged length of stay (LOS; ≥9 days: OR, 4.12 (95 % CI, 1.88-9.01); P < 0.001). On multivariate logistic regression, a high ASA class (OR, 4.01 (95 % CI, 1.44-11.17); P = 0.008) and metastatic disease on presentation (OR, 3.44 (95 % CI, 1.34-8.84); P = 0.01) remained independently associated with higher odds of readmission.Readmission following surgery for ACC was common as one in five patients experienced a readmission. Patients with a high ASA class and metastatic disease on presentation were over four and three times more likely to be readmitted after surgical treatment for ACC, respectively.
Multivisceral Resection for Gastric Cancer: Results from the US Gastric Cancer Collaborative. Annals of surgical oncology Tran, T. B., Worhunsky, D. J., Norton, J. A., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Poultsides, G. A. 2015; 22: 840-847
Resection of an adjacent organ during gastrectomy for gastric cancer is occasionally necessary to achieve margin clearance. The short- and long-term outcomes of this approach remain unclear.Patients who underwent gastric cancer resection in seven U.S. academic institutions from 2000 to 2012 were evaluated to compare perioperative morbidity, mortality, and survival outcomes, stratified by the need for and type of multivisceral resection (MVR).Of 835 patients undergoing curative-intent gastrectomy, 159 (19 %) had MVR. The most common adjacent organs resected were the spleen (48 %), pancreas (27 %), liver segments 2/3 (14 %), and colon (13 %). As extent of resection increased (gastrectomy only, n = 676; MVR without pancreatectomy, n = 116; and MVR with pancreatectomy, n = 43), perioperative morbidity was higher: any complication (45, 60, 59 %, p = 0.012), major complication (17, 31, 33 %, p = 0.001), anastomotic leak (5, 11, 19 %, p < 0.001), and respiratory failure (9, 15, 22 %, p = 0.012). However, perioperative mortality did not significantly increase (30-day: 3, 4, 2 %, p = 0.74; 90-day: 6, 8, 9 %, p = 0.61). Overall survival after resection decreased as extent of resection increased (5-year: 42, 28, 6 %). After controlling for age, race, T stage, N stage, grade, margin status, perineural invasion, adjuvant therapy, and blood transfusion, MVR with pancreatectomy (HR 1.67, p = 0.044), but not MVR without pancreatectomy (HR 0.97, p = 0.759), remained an independent predictor of poor survival.In this modern, multi-institutional cohort of gastric cancer patients, multivisceral resection was associated with higher perioperative morbidity but not significantly higher perioperative mortality. If concomitant pancreatectomy is anticipated, patients should be selected with extreme caution because long-term survival remains poor.
Multivisceral Resection for Gastric Cancer: Results from the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Tran, T. B., Worhunsky, D. J., Norton, J. A., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Poultsides, G. A. 2015; 22: S840-S847
Can hepatic resection provide a long-term cure for patients with intrahepatic cholangiocarcinoma? CANCER Spolverato, G., Vitale, A., Cucchetti, A., Popescu, I., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Sandroussi, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 121 (22): 3998-4006
A patient can be considered statistically cured from a specific disease when their mortality rate returns to the same level as that of the general population. In the current study, the authors sought to assess the probability of being statistically cured from intrahepatic cholangiocarcinoma (ICC) by hepatic resection.A total of 584 patients who underwent surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. A nonmixture cure model was adopted to compare mortality after hepatic resection with the mortality expected for the general population matched by sex and age.The median, 1-year, 3-year, and 5-year disease-free survival was 10 months, 44%, 18%, and 11%, respectively; the corresponding overall survival was 27 months, 75%, 37%, and 22%, respectively. The probability of being cured of ICC was 9.7% (95% confidence interval, 6.1%-13.4%). The mortality of patients undergoing surgery for ICC was higher than that of the general population until year 10, at which time patients alive without tumor recurrence can be considered cured with 99% certainty. Multivariate analysis demonstrated that cure probabilities ranged from 25.8% (time to cure, 9.8 years) in patients with a single, well-differentiated ICC measuring ≤5 cm that was without vascular/periductal invasion and lymph nodes metastases versus <0.1% (time to cure, 12.6 years) among patients with all 6 of these risk factors. A model with which to calculate cure fraction and time to cure was developed.The cure model indicated that statistical cure was possible in patients undergoing hepatic resection for ICC. The overall probability of cure was approximately 10% and varied based on several tumor-specific factors. Cancer 2015;121:3998-4006. © 2015 American Cancer Society.
View details for DOI 10.1002/cncr.29619
Severe acute pancreatitis in the community: confusion reigns JOURNAL OF SURGICAL RESEARCH Dua, M. M., Worhunsky, D. J., Tran, T. B., Rumma, R. T., Poultsides, G. A., Norton, J. A., Park, W. G., Visser, B. C. 2015; 199 (1): 44-50
The management of acute pancreatitis (AP) has evolved through enhanced understanding of the disease. Despite several evidence-based practice guidelines for AP, our hypothesis is that many hospitals still use historical treatments rather than adhere to the current guidelines, which have demonstrated shorter hospital stays, decreased infectious complications, decreased morbidity, and decreased mortality.Seventy-eight patients transferred to our institution with AP from 2010-2014 were retrospectively studied to compare pretransfer versus posttransfer adherence to current practice guidelines. Primary measures included use of antibiotics (abx), enteral nutrition, drainage of asymptomatic pseudocysts, and interventions for necrosis in the early phase (<4 wk).Pretransfer, abx were given to 51 patients; however, posttransfer, abx were discontinued in 33 patients and started in 6 patients within 24 h of admission (pretransfer versus posttransfer abx, 51 versus 24, P < 0.001). Empiric abx for AP were used in 36 patients pretransfer versus 9 patients posttransfer (P < 0.001). Patients were initially nil per os or on total parenteral nutrition in 89%; this was reduced to 17% within 72 h by starting a diet or enteric feeds (pretransfer versus posttransfer feeding, 9 versus 65 patients, P < 0.001). Fifteen transfer patients had pseudocysts that were believed to "require drainage"; five patients received intervention but >4 wk from initial episode of AP. Pretransfer, five patients had pancreatic debridement in the early phase, which resulted in prolonged postoperative length of stay compared with eight patients requiring debridement, which were delayed (early versus late, 56 versus 16 d, P < 0.05).There is still great confusion in the treatment of AP in community hospitals. Primary principles in the care of these patients are not routinely followed despite established guidelines. Increased dissemination is required to prevent lengthy hospitalizations and long-term morbidity.
The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma ANNALS OF SURGICAL ONCOLOGY Spolverato, G., Yakoob, M. Y., Kim, Y., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 22 (12): 4020-4028
The influence of margin status on long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) remains controversial. We sought to study the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ICC.From a multi-institutional database, 583 patients who underwent hepatic resection for ICC were identified. Demographics data, operative details, pathologic margin status, and long-term outcomes were collected and analyzed.Margin status was positive (R1) in 95 (17.8 %) patients; among patients who underwent an R0 resection (80.9 %), margin width was negative by 1-4 mm in 166 (31.0 %) patients, 5-9 mm in 100 (18.7 %) patients, and ≥1 cm in 174 (32.5 %) patients. Overall, 379 (65.0 %) patients had a recurrence: 61.5 % intrahepatic, 13.5 % extrahepatic, and 25.0 % both intra- and extrahepatic. Median and 5-year RFS and OS was 10.0 months and 9.2 %, and 26.4 months and 23.0 %, respectively. Patients who had an R1 resection had a higher risk of recurrence (hazard ratio [HR] 1.61, 95 % CI 1.15-2.27; p = 0.01) and shorter OS (HR 1.54, 95 % CI 1.12-2.11). Among patients with an R0 resection, margin width was also associated with RFS (1-4 mm: HR 1.32, 95 % CI 0.98-1.78 vs. 5-9 mm: HR 1.21, 95 % CI 0.89-1.66) and OS (1-4 mm: HR 1.95, 95 % CI 0.45-2.63 vs. 5-9 mm: HR 1.21, 95 % CI 0.88-1.68) (referent ≥1 cm; both p ≤ 0.002). Margin status and width remain independently associated with RFS and OS on multivariable analyses.For patients undergoing resection of ICC, R1 margin status was associated with an inferior long-term outcome. Moreover, there was an incremental worsening RFS and OS as margin width decreased.
Locally Advanced Intrahepatic Cholangiocarcinoma: Complete Pathologic Response to Neoadjuvant Chemotherapy Followed by Left Hepatic Trisectionectomy and Caudate Lobectomy DIGESTIVE DISEASES AND SCIENCES Tran, T. B., Bal, C. K., Schaberg, K., Longacre, T. A., Chatrath, B. S., Poultsides, G. A. 2015; 60 (11): 3226-3229
Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study ANNALS OF SURGERY Poultsides, G. A., Tran, T. B., Zambrano, E., Janson, L., Mohler, D. G., Mell, M. W., Avedian, R. S., Visser, B. C., Lee, J. T., Ganjoo, K., Harris, E. J., Norton, J. A. 2015; 262 (4): 632-640
To examine the impact of major vascular resection on sarcoma resection outcomes.En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described.Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival.From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P = 0.002), grade 3 or higher complication (38% vs. 18%, P = 0.024), and transfusion (66% vs. 33%, P < 0.001) were all more common in the VASC group. Thirty-day (2% vs. 0%, P = 0.30) or 90-day mortality (6% vs. 2%, P = 0.24) were not significantly higher. Local recurrence (5-year, 51% vs. 54%, P = 0.11) and overall survival after resection (5-year, 59% vs. 53%, P = 0.67) were similar between the 2 groups. Within the VASC group, overall survival was not affected by the type of vessel involved (artery vs. vein) or the presence of histology-proven vessel wall invasion.Vascular resection and reconstruction during sarcoma resection significantly increases perioperative morbidity and requires meticulous preoperative multidisciplinary planning. However, the oncologic outcome appears equivalent to cases without major vascular involvement. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma resection.
Identification of Tumorigenic Cells and Therapeutic Targets in Pancreatic Neuroendocrine Cancers Krampitz, G. W., Willingham, S. B., Volkmer, J. P., Weiskopf, K. A., George, B. M., Sage, J., Visser, B. C., Poultsides, G. A., Norton, J. A., Weissman, I. L. ELSEVIER SCIENCE INC. 2015: S59–S60
The Effect of Chronic Kidney Disease on Postoperative Outcomes after Major Hepatectomy: Results from the National Surgical Quality Improvement Program Tran, T. B., Dua, M. M., Spain, D. A., Poultsides, G. A., Norton, J. A., Visser, B. C. ELSEVIER SCIENCE INC. 2015: S94–S95
Hepato-pancreatectomy: perioperative and long term outcomes of synchronous hepatic and pancreatic resection Tran, T. B., Dua, M. M., Visser, B. C., Norton, J. A., Poultsides, G. A. ELSEVIER SCIENCE INC. 2015: E95
Hepato-pancreatectomy: how morbid? Results from the national surgical quality improvement project HPB Tran, T. B., Dua, M. M., Spain, D. A., Visser, B. C., Norton, J. A., Poultsides, G. A. 2015; 17 (9): 763-769
Simultaneous resection of both the liver and the pancreas carries significant complexity. The objective of this study was to investigate peri-operative outcomes after a synchronous hepatectomy and pancreatectomy (SHP).The American College of Surgeons National Surgical Quality Improvement Project database was queried to identify patients who underwent SHP. Resections were categorized as '< hemihepatectomy', '≥ hemihepatectomy' (hemihepatectomy and trisectionectomy), 'PD' (pancreaticoduodenectomy and total pancreatectomy) and 'distal' (distal pancreatectomy and enucleation).From 2005 to 2013, 480 patients underwent SHP. Patients were stratified based on the extent of resection: '< hemihepatectomy + distal (n = 224)', '≥ hemihepatectomy + distal' (n = 49), '< hemihepatectomy + PD' (n = 83) and '≥ hemihepatectomy + PD' (n = 24). Although the first three groups had a reasonable and comparable safety profile (morbidity 33-51% and mortality 0-6.6%), the '≥ hemihepatectomy + PD' group was associated with an 87.5% morbidity (organ space infection 58.3%, re-intubation 12.5%, reoperation 25% and septic shock 25%), 8.3% 30-day mortality and 18.2% in-hospital mortality.A synchronous hemihepatectomy (or trisectionectomy) with PD remains a highly morbid combination and should be reserved for patients who have undergone extremely cautious selection.
View details for DOI 10.1111/hpb.12426
Hepato-pancreatectomy: how morbid? Results from the national surgical quality improvement project. HPB Tran, T. B., Dua, M. M., Spain, D. A., Visser, B. C., Norton, J. A., Poultsides, G. A. 2015; 17 (9): 763-769
Effect of Perioperative Transfusion on Recurrence and Survival after Gastric Cancer Resection: A 7-Institution Analysis of 765 Patients from the US Gastric Cancer Collaborative JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Staley, C. A., Maithel, S. K. 2015; 221 (3): 767-777
The prognostic effect of perioperative blood transfusion on recurrence and survival in patients undergoing resection of gastric adenocarcinoma (GAC) remains controversial.All patients who underwent resection for GAC from 2000 to 2012 at the 7 institutions of the US Gastric Cancer Collaborative were identified. The effect of transfusion on recurrence-free (RFS) and overall survival (OS) in the context of adverse clinicopathologic variables was examined by univariate and multivariate regression analyses.Of 965 patients, 765 underwent curative intent R0 resection. Median follow-up was 44 months; 30-day mortalities were excluded. Median estimated blood loss (EBL) was 200 mL, and 168 patients (22%) received perioperative allogeneic blood transfusions. Transfused patients were less likely to receive adjuvant therapy (44% vs 56%; p = 0.01). Transfusion was associated with significantly decreased median RFS (13.5 vs 37.2 months, p < 0.001). Median OS was similarly decreased in patients receiving transfusions (18.6 vs 49.8 months, p < 0.001). On multivariate analysis, transfusion remained an independent risk factor for decreased RFS (hazard ratio [HR] 1.63; 95% CI 1.13 to 2.37; p = 0.010) and decreased OS (HR 1.79; 95% CI 1.21 to 2.67; p = 0.004), regardless of EBL or need for splenectomy. Timing (intraoperative vs postoperative) and volume of transfusion did not alter the negative prognostic effect of transfusion on survival.Perioperative allogeneic blood transfusion is associated with decreased RFS and OS after resection of gastric cancer, independent of adverse clinicopathologic factors. This supports the judicious use of perioperative transfusion during resection of gastric cancer.
Effect of Perioperative Transfusion on Recurrence and Survival after Gastric Cancer Resection: A 7-Institution Analysis of 765 Patients from the US Gastric Cancer Collaborative. Journal of the American College of Surgeons Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Staley, C. A., Maithel, S. K. 2015; 221 (3): 767-777
Pancreatectomy with vein reconstruction: technique matters HPB Dua, M. M., Tran, T. B., Klausner, J., Hwa, K. J., Poultsides, G. A., Norton, J. A., Visser, B. C. 2015; 17 (9): 824-831
A variety of techniques have been described for portal vein (PV) and/or superior mesenteric vein (SMV) resection/reconstruction during a pancreatectomy. The ideal strategy remains unclear.Patients who underwent PV/SMV resection/reconstruction during a pancreatectomy from 2005 to 2014 were identified. Medical records and imaging were retrospectively reviewed for operative details and outcomes, with particular emphasis on patency.Ninety patients underwent vein resection/reconstruction with one of five techniques: (i) longitudinal venorrhaphy (LV, n = 17); (ii) transverse venorrhaphy (TV, n = 9); (iii) primary end-to-end (n = 28); (iv) patch venoplasty (PV, n = 17); and (v) interposition graft (IG, n = 19). With a median follow-up of 316 days, thrombosis was observed in 16/90 (18%). The rate of thrombosis varied according to technique. All patients with primary end-to-end or TV remained patent. LV, PV and IG were all associated with significant rates of thrombosis (P = 0.001 versus no thrombosis). Comparing thrombosed to patent, there were no differences with respect to pancreatectomy type, pre-operative knowledge of vein involvement and neoadjuvant therapy. Prophylactic aspirin was used in 69% of the total cohort (66% of patent, 81% of thrombosed) and showed no protective benefit.Primary end-to-end and TV have superior patency than the alternatives after PV/SMV resection and should be the preferred techniques for short (<3 cm) reconstructions.
Pancreatectomy with vein reconstruction: technique matters. HPB Dua, M. M., Tran, T. B., Klausner, J., Hwa, K. J., Poultsides, G. A., Norton, J. A., Visser, B. C. 2015; 17 (9): 824-831
Non-functional neuroendocrine tumors of the pancreas: Advances in diagnosis and management. World journal of gastroenterology Cloyd, J. M., Poultsides, G. A. 2015; 21 (32): 9512-9525
Nonfunctional neuroendocrine tumors of the pancreas (NF-PNETs) are a heterogeneous group of neoplasms. Although rare, the incidence of NF-PNETs is increasing significantly. The classification of PNETs has evolved over the past decades and is now based on a proliferation grading system. While most NF-PNETs are slow growing, tumors with more aggressive biology may become incurable once they progress to unresectable metastatic disease. Tumors of higher grade can be suspected preoperatively based on the presence of calcifications, hypoenhancement on arterial phase computed tomography, positron emission technology avidity and lack of octreotide scan uptake. Surgery is the only curative treatment and is recommended for most patients for whom complete resection is possible. Liver-directed therapies (thermal ablation, transarterial embolization) can be useful in controlling unresectable hepatic metastatic disease. In the presence of unresectable progressive disease, somatostatin analogues, everolimus and sunitinib can prolong progression-free survival. This article provides a comprehensive review of NF-PNETs with special emphasis on recent advances in diagnosis and management.
View details for DOI 10.3748/wjg.v21.i32.9512
Impact of Complications on Long-Term Survival After Resection of Intrahepatic Cholangiocarcinoma CANCER Spolverato, G., Yakoob, M. Y., Kim, Y., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 121 (16): 2730-2739
The impact of postoperative complications on the long-term outcomes of patients undergoing surgery for cancer is unclear. The objective of the current study was to define the incidence of complications among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) and identify the association between morbidity and long-term outcomes.A total of 583 patients undergoing surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. The association between the occurrence and severity of postoperative complications on long-term survival was analyzed.The median age of the patients was 59.9 years and the majority of patients were male (52.3%). A total of 91 patients (15.6%) and 153 patients (26.2%) developed a major and minor postoperative complication, respectively; 18 patients (3.5%) died within 90 days of surgery. Median, 1-year, 3-year, and 5-year recurrence-free survival were 10.0 months, 43.3%, 16.7%, and 11.1%, respectively. Postoperative complications (hazard ratio [HR], 1.37, 95% confidence interval [95% CI], 1.08-1.73 [P = .01]) and severity of complications (major vs none: HR, 1.55; 95% CI, 1.14-2.11 [P = .01]; minor vs none: HR, 1.30; 95% CI, 0.99-1.70 [P = .06]) independently predicted shorter recurrence-free survival. Median, 1-year, 3-year, and 5-year overall survival was 27.8 months, 76.8%, 39.0%, and 23.4%, respectively. Postoperative complications (HR, 1.64; 95% CI, 1.30-2.08 [P<.001]) and severity of complications (major vs none: HR, 1.79; 95% CI, 1.31-2.44 [P<.001]; minor vs none: HR, 1.50; 95% CI, 1.15-1.95 [P<.01]) independently predicted shorter overall survival.Postoperative complications were found to be independent predictors of worse long-term outcomes. The prevention and management of postoperative complications is crucial to increase both short-term and long-term survival. Cancer 2015;121:2730-2739. © 2015 American Cancer Society.
An assessment of feeding jejunostomy tube placement at the time of resection for gastric adenocarcinoma: A seven-institution analysis of 837 patients from the US gastric cancer collaborative JOURNAL OF SURGICAL ONCOLOGY Dann, G. C., Squires, M. H., Postlewait, L. M., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 112 (2): 195-202
Jejunostomy feeding tubes (J-tubes) are often placed during resection for gastric adenocarcinoma (GAC). Their effect on postoperative complications and receipt of adjuvant therapy is unclear.Patients who underwent curative-intent resection of GAC at seven institutions of the U.S. Gastric Cancer Collaborative from 2000 to 2012 were identified. The associations of J-tubes with postoperative complications and receipt of adjuvant therapy were determined.Of 837 patients, 265 (32%) received a J-tube. Patients receiving J-tubes demonstrated greater incidence of preoperative weight loss, lower BMI, greater extent of resection, and more advanced TNM stage. J-tube placement was associated with increased infectious complications (36% vs. 19%; P < 0.001), including surgical-site (14% vs. 6%; P < 0.001) and deep intra-abdominal (11% vs. 4%; P < 0.001) infections. On multivariate analysis, J-tubes remained independently associated with increased risk of infectious complications (all: HR = 1.93; P = 0.001; surgical-site: HR = 2.85; P = 0.001; deep intra-abdominal: HR = 2.13; P = 0.04). J-tubes were not associated with increased receipt of adjuvant therapy (HR = 0.82; P = 0.34). Subset analyses of patients undergoing total and subtotal gastrectomy similarly demonstrated an association of J-tubes with increased risk of infectious outcomes and no association with increased receipt of adjuvant therapy.J-tube placement after resection of gastric adenocarcinoma is associated with increased postoperative infectious outcomes and is not associated with increased receipt of adjuvant therapy. Selective use of J-tubes is recommended.
The importance of the proximal resection margin distance for proximal gastric adenocarcinoma: A multi-institutional study of the US Gastric Cancer Collaborative JOURNAL OF SURGICAL ONCOLOGY Postlewait, L. M., Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D., Jin, L. X., Cho, C. S., Winslow, E. R., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 112 (2): 203-207
A 5 cm margin is advocated for distal gastric adenocarcinoma (GAC). The optimal proximal resection margin (PM) length for proximal GAC is not established.Patients who underwent curative-intent resection for proximal GAC from 2000 to 2012 at 7 centers in the US Gastric Cancer Collaborative were included. PM length was sequentially dichotomized and analyzed at 0.5 cm increments (0.5-6.5 cm). Outcomes after negative margin (R0) and positive microscopic margin (R1) resections were compared. Primary endpoints were local recurrence (LR) and overall survival (OS).All patients (n = 162) had R0 distal margins. 151 (93.2%) had an R0-PM with mean length of 2.6 cm (median:1.7 cm; range:0.1-15 cm). A greater PM distance was not associated with LR or OS. An R1-PM was associated with higher N-stage (N3:73% vs. 26%; P = 0.007) and increased LR (HR6.1; P = 0.009) but not associated with decreased OS. On multivariate analysis, an R1-PM was also not independently associated with LR.For resection of proximal gastric adenocarcinoma, proximal margin length is not associated with local recurrence or overall survival. An R1 margin is associated with advanced N-stage but is not independently associated with recurrence or survival. When performing resection of proximal gastric adenocarcinoma, efforts to achieve a specific margin distance, especially if it necessitates an esophagectomy, should be abandoned.
Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Gholami, S., Janson, L., Worhunsky, D. J., Tran, T. B., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S. M., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Efron, B., Norton, J. A., Poultsides, G. A. 2015; 221 (2): 291-299
Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection.We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be "true N0-2," based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased.The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival.
Prognostic relevance of lymph node ratio and total lymph node count for small bowel adenocarcinoma SURGERY Tran, T. B., Qadan, M., Dua, M. M., Norton, J. A., Poultsides, G. A., Visser, B. C. 2015; 158 (2): 486-493
Nodal metastasis is a known prognostic factor for small bowel adenocarcinoma. The goals of this study were to evaluate the number of lymph nodes (LNs) that should be retrieved and the impact of lymph node ratio (LNR) on survival.Surveillance, Epidemiology, and End Results was queried to identify patients with small bowel adenocarcinoma who underwent resection from 1988 to 2010. Survival was calculated with the Kaplan-Meier method. Multivariate analysis identified predictors of survival.A total of 2,772 patients underwent resection with at least one node retrieved, and this sample included equal numbers of duodenal (n = 1,387) and jejunoileal (n = 1,386) adenocarcinomas. There were 1,371 patients with no nodal metastasis (N0, 49.4%), 928 N1 (33.5%), and 474 N2 (17.1%). The median numbers of LNs examined for duodenal and jejunoileal cancers were 9 and 8, respectively. Cut-point analysis demonstrated that harvesting at least 9 for jejunoileal and 5 LN for duodenal cancers resulted in the greatest survival difference. Increasing LNR at both sites was associated with decreased overall median survival (LNR = 0, 71 months; LNR 0-0.02, 35 months; LNR 0.21-0.4, 25 months; and LNR >0.4, 16 months; P < .001). Multivariate analysis confirmed number of LNs examined, T-stage, LN positivity, and LNR were independent predictors of survival.LNR has a profound impact on survival in patients with small bowel adenocarcinoma. To achieve adequate staging, we recommend retrieving a minimum of 5 LN for duodenal and 9 LN for jejunoileal adenocarcinomas.
Neutrophil-lymphocyte and platelet-lymphocyte ratio as predictors of disease specific survival after resection of adrenocortical carcinoma JOURNAL OF SURGICAL ONCOLOGY Bagante, F., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2015; 112 (2): 164-172
The systemic inflammatory response may be associated with tumor progression. We sought to analyze the impact of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on recurrence-free survival (RFS) and disease-specific survival (DSS) among patients who underwent surgery for adrenocortical carcinoma (ACC).Patients undergoing surgery for ACC were identified from a multi-center database. Cut-off values of 5 and 190 were defined as elevated NLR and PLR, respectively, and long-term outcome was assessed.Among 84 patients with ACC, 29 (34.%) had NLR > 5 while 32 (40.5%) had PLR > 190. NLR and PLR were associated with larger tumors (NLR > 5: ≤ 5 cm, 0% vs. >5 cm, 39.7%; PLR > 190: ≤ 5cm, 0% vs. >5 cm, 45.7%), as well as need to resect of other organs (NLR > 5: other organ resected 48.8% vs. not resected 20.9%; PLR > 190: other organ resected 25.0% vs. not resected 56.4%)(all P < 0.05). Five-year RFS was associated with an elevated NLR (NLR ≤ 5, 14.2% vs. NLR> 5, 10.5%) and PLR (PLR ≤ 190: 19.4% vs. PLR > 190: 5.2%) (both P < 0.05). On multivariate survival analyses, PLR remained a predictor of RFS (HR 1.72), while NLR was associated with both DSS (HR 2.21) and RFS (HR 1.99) (both P < 0.05).Immune markers such as NLR and PLR may be useful to stratify patients with regards to prognosis following surgery for ACC.
Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway BMC CANCER Drakaki, A., Hatziapostolou, M., Polytarchou, C., Vorvis, C., Poultsides, G. A., Souglakos, J., Georgoulias, V., Iliopoulos, D. 2015; 15
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors.MicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets.A high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3'UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3'UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels.Taken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis.
Is Hepatic Resection for Large or Multifocal Intrahepatic Cholangiocarcinoma Justified? Results from a Multi-Institutional Collaboration ANNALS OF SURGICAL ONCOLOGY Spolverato, G., Kim, Y., Alexandrescu, S., Popescu, I., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Miura, J., Maithel, S. K., Squires, M. H., Pulitano, C., Sandroussi, C., Mentha, G., Bauer, T. W., Newhook, T., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 22 (7): 2218-2225
The role of surgical resection for patients with large or multifocal intrahepatic cholangiocarcinoma (ICC) remains unclear. This study evaluated the long-term outcome of patients who underwent hepatic resection for large (≥7 cm) or multifocal (≥2) ICC.Between 1990 and 2013, 557 patients who underwent liver resection for ICC were identified from a multi-institutional database. Clinicopathologic characteristics, operative details, and long-term survival data were evaluated.Of the 557 patients, 215 (38.6 %) had a small, solitary ICC (group A) and 342 (61.4 %) had a large or multifocal ICC (group B). The patients in group B underwent an extended hepatectomy more frequently (16.9 vs. 30.4 %; P < 0.001). At the final pathology exam, the patients in group B were more likely to show evidence of vascular invasion (22.5 vs. 38.5 %), direct invasion of contiguous organs (6.5 vs. 12.9 %), and nodal metastasis (13.3 vs. 21.0 %) (all P < 0.05). Interestingly, the incidences of postoperative complications (39.3 vs. 46.8 %) and hospital mortality (1.1 vs. 3.7 %) were similar between the two groups (both P > 0.05). The group A patients had better rates for 5-year overall survival (OS) (30.5 vs. 18.7 %; P < 0.05) and disease-free survival (DFS) (22.6 vs. 8.2 %; P < 0.05) than the group B patients. For the patients in group B, the factors associated with a worse OS included more than three tumor nodules [hazard ratio (HR), 1.56], nodal metastasis (HR, 1.47), and poor differentiation (HR, 1.48).Liver resection can be performed safely for patients with large or multifocal ICC. The long-term outcome for these patients can be stratified on the basis of a prognostic score that includes tumor number, nodal metastasis, and poor differentiation.
Readmission After Liver Resection for Intrahepatic Cholangiocarcinoma: a Multi-Institutional Analysis JOURNAL OF GASTROINTESTINAL SURGERY Spolverato, G., Maqsood, H., Vitale, A., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G., Maithel, S., Marsh, J. W., Pawlik, T. M. 2015; 19 (7): 1334-1341
The objective of the current study was to define the incidence of 30-day readmission after hepatic resection for intrahepatic cholangiocarcinoma (ICC). In particular, we sought to identify risk factors associated with a higher risk of readmission among patients undergoing resection for ICC.Patients who underwent hepatic resection for ICC at 12 major hepatobiliary centers in the USA, Europe, Australia, and Asia between 1990 and 2013 were identified. Thirty-day readmission and clinicopathologic characteristics associated with higher risk of readmission were examined.Among 602 patients, 401 (68.3 %) patients underwent a major hepatectomy and 256 (43.3 %) experienced at least one post-operative complication. Overall 30-day readmission was 7.8 % (n = 47). Risk factors associated with readmission included pre-operative jaundice (odds ratio (OR) 2.45) and the presence of a major complication (OR 3.38). In fact, 95.7 % of readmitted patients had experienced a post-operative complication versus only 38.8 % of non-readmitted patients (P < 0.001). Among patients who were readmitted, repeat hospitalization was associated with a median LOS of 6.5 days (interquartile range (IQR) 4.0-11.5) and one patient died during readmission.Readmission after hepatic resection for ICC occurred in 1 in 13 patients. Patients with pre-operative jaundice and those who experienced a complication had over a threefold higher risk of being readmitted.
Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts. American journal of gastroenterology Zikos, T., Pham, K., Bowen, R., Chen, A. M., Banerjee, S., Friedland, S., Dua, M. M., Norton, J. A., Poultsides, G. A., Visser, B. C., Park, W. G. 2015; 110 (6): 909-914
Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip.Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed.Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00).Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.
View details for DOI 10.1038/ajg.2015.148
Conditional Probability of Long-term Survival After Liver Resection for Intrahepatic Cholangiocarcinoma A Multi-institutional Analysis of 535 Patients JAMA SURGERY Spolverato, G., Kim, Y., Ejaz, A., Alexandrescu, S., Marques, H., Aldrighetti, L., Gamblin, C., Pulitano, C., Bauer, T. W., Shen, F., Sandroussi, C., Poultsides, G., Maithel, S. K., Pawlik, T. M. 2015; 150 (6): 538-545
Whereas conventional actuarial overall survival (OS) estimates rely exclusively on static factors determined around the time of surgery, conditional survival (CS) estimates take into account the years that a patient has already survived.To define the CS of patients following liver resection for intrahepatic cholangiocarcinoma (ICC).Between January 1, 1990, and December 31, 2013, a total of 535 patients who underwent resection of ICC were identified from an international multi-institutional database. In this retrospective international study conducted from January to June 2014, clinicopathological characteristics, operative details, and long-term survival data were analyzed. Conditional survival estimates were calculated as the probability of survival for an additional 3 years.Resection of ICC.Overall survival and CS.While actuarial OS decreased over time from 39% at 3 years to 16% at 8 years (P = .002), the 3-year CS (CS3) increased over time among those patients who survived. The CS3 at 5 years-the probability of surviving to postoperative year 8 after having already survived to postoperative year 5-was 65% compared with 8-year OS of 16% (P = .002). Factors that were associated with worse OS included larger tumor size (hazard ratio [HR], 1.02; 95% CI, 1.00-1.05; P = .05), multifocal disease (HR, 1.49; 95% CI, 1.19-1.86; P = .01), lymph node metastasis (HR, 2.21; 95% CI, 1.67-2.93; P < .01), and vascular invasion (HR, 1.39; 95% CI, 1.10-1.75; P = .006). The calculated CS3 exceeded the actuarial survival for all high-risk subgroups. For example, patients with lymph node metastasis had an actuarial OS of 11% at 6 years vs a CS3 of 49% at 3 years (Δ38%). Similarly, patients with vascular invasion had an actuarial OS of 15% at 6 years compared with a CS3 of 50% at 3 years (Δ35%).Conditional survival estimates may provide critical quantitative information about the changing probability of survival over time among patients undergoing liver resection for ICC. Therefore, such estimates can be of significant value to patients and health care professionals.
Presentation and Clinical Outcomes of Choledochal Cysts in Children and Adults A Multi-institutional Analysis JAMA SURGERY Soares, K. C., Kim, Y., Spolverato, G., Maithel, S., Bauer, T. W., Marques, H., Sobral, M., Knoblich, M., Tran, T., Aldrighetti, L., Jabbour, N., Poultsides, G. A., Gamblin, T. C., Pawlik, T. M. 2015; 150 (6): 577-584
Choledochal cysts (CCs) are rare, with risk of infection and cancer.To characterize the natural history, management, and long-term implications of CC disease.A total of 394 patients who underwent resection of a CC between January 1, 1972, and April 11, 2014, were identified from an international multi-institutional database. Patients were followed up through September 27, 2014. Clinicopathologic characteristics, operative details, and outcome data were analyzed from May 1, 2014, to October 14, 2014.Resection of CC.Management, morbidity, and overall survival.Among 394 patients, there were 135 children (34.3%) and 318 women (80.7%). Adults were more likely to present with abdominal pain (71.8% vs 40.7%; P < .001) and children were more likely to have jaundice (31.9% vs 11.6%; P < .001). Preoperative interventions were more commonly performed in adults (64.5% vs 31.1%; P < .001), including endoscopic retrograde pancreatography (55.6% vs 27.4%; P < .001), percutaneous transhepatic cholangiography (17.4% vs 5.9%; P < .001), and endobiliary stenting (18.1% vs 4.4%; P < .001)). Type I CCs were more often seen in children vs adults (79.7% vs 64.9%; P = .003); type IV CCs predominated in the adult population (23.9% vs 12.0%; P = .006). Extrahepatic bile duct resection with hepaticoenterostomy was the most frequently performed procedure in both age groups (80.3%). Perioperative morbidity was higher in adults (35.1% vs 16.3%; P < .001). On pathologic examination, 10 patients (2.5%) had cholangiocarcinoma. After a median follow-up of 28 months, 5-year overall survival was 95.5%. On follow-up, 13 patients (3.3%), presented with biliary cancer.Presentation of CC varied between children and adults, and resection was associated with a degree of morbidity. Although concomitant cancer was uncommon, it occurred in 3.0% of the patients. Long-term surveillance is indicated given the possibility of future development of biliary cancer after CC resection.
Extracorporeal Pringle for laparoscopic liver resection SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Dua, M. M., Worhunsky, D. J., Hwa, K., Poultsides, G. A., Norton, J. A., Visser, B. C. 2015; 29 (6): 1348-1355
A primary concern during laparoscopic liver resection (lapLR) is hemorrhage during parenchymal transection. Intermittent pedicle clamping is an effective method to minimize blood loss during open liver surgery; however, inflow occlusion techniques are challenging to reproduce during laparoscopy. The purpose of this study is to describe the safety and efficacy of a facile method for Pringle maneuver during lapLR.154 patients who underwent lapLR from 2007 to 2013 were retrospectively reviewed. For Pringle, the hepatoduodenal ligament is encircled with an umbilical tape which is externalized through a flexible Rumel tourniquet running alongside a port used for the operation. The internal end of the catheter is close to the pedicle and the external end is extracorporeal, allowing for easy external occlusion. Patients who underwent Pringle Maneuver (PM, n = 88) were compared to patients who had "No Occlusion" (NO, n = 66) with respect to patient characteristics, operative outcomes, changes in postoperative liver function, and complications.Annual placement of the tourniquet and vascular occlusion increased from 35.7 to 82.8 % (p = 0.004) and 21.4 to 62.1 % (p = 0.02), respectively. Median occlusion time was 24 min (IQR 15-34.3, min 5, max 70). Peak transaminase levels were comparable between groups (AST 298 ± 32 vs 405 ± 47 U/L, p = 0.15; ALT 272 ± 27 vs 372 ± 34 U/L, p = 0.14, NO and PM, respectively). Postoperative transaminase and bilirubin levels for both groups were not significantly different with similar recovery to baseline. Subgroup analysis of cirrhotic patients who underwent Pringle demonstrated similar transaminase profiles compared to non-cirrhotic patients. There were two conversions (1.3 %) and postoperative 30-day mortality was 0.65 %.Extracorporeal tourniquet placement in lapLR is a quick and safe method of gaining control for inflow occlusion. Routine adoption of laparoscopic Pringle maneuver facilitates low conversion rates without liver injury.
A Nomogram to Predict Overall Survival and Disease-Free Survival After Curative Resection of Gastric Adenocarcinoma ANNALS OF SURGICAL ONCOLOGY Kim, Y., Spolverato, G., Ejaz, A., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Votanopoulos, K., Acher, A. W., Jin, L. X., Hawkins, W. G., Schmidt, C., Kooby, D., Worhunsky, D., Saunders, N., Levine, E. A., Cho, C. S., Maithel, S. K., Pawlik, T. M. 2015; 22 (6): 1828-1835
The American Cancer Society projects there will be over 22,000 new cases, resulting in nearly 11,000 deaths, related to gastric adenocarcinoma in the US in 2014. The aim of the current study was to find clinicopathologic variables associated with disease-free survival (DFS) and overall survival (OS) following curative resection of gastric adenocarcinoma, and create a nomogram for individual risk prediction.A nomogram to predict DFS and OS following surgical resection of gastric adenocarcinoma was constructed using a multi-institutional cohort of patients who underwent surgery for primary gastric adenocarcinoma at seven major institutions in the US between January 2000 and August 2013. Discrimination and calibration of the nomogram were tested by C-statistic, Kaplan-Meier curves, and calibration plots.A total of 719 patients who underwent surgery for primary gastric adenocarcinoma were included in the study. Using the backward selection of clinically relevant variables with Akaike information criteria, age, sex, tumor site, depth of invasion, and lymph node ratio (LNR) were selected as factors predictive of OS, while age, tumor site, depth of invasion, and LNR were incorporated in the prediction of DFS. A nomogram was constructed to predict OS and DFS using these variables. Discrimination and calibration of the nomogram revealed good predictive abilities (C-index, DFS 0.711; OS 0.702).Independent predictors of recurrence and death following surgery for primary gastric adenocarcinoma were used to create a nomogram to predict DFS and OS. The nomogram was able to stratify patients into prognostic groups, and performed well on internal validation.
Predictive Factors for Surgery Among Patients with Pancreatic Cysts in the Absence of High-Risk Features for Malignancy JOURNAL OF GASTROINTESTINAL SURGERY Quan, S. Y., Visser, B. C., Poultsides, G. A., Norton, J. A., Chen, A. M., Banerjee, S., Friedland, S., Park, W. G. 2015; 19 (6): 1101-1105
Without a reliable biopsy technique for pancreatic cysts, consensus-based guidelines are used to guide surgical utilization. The primary objective of this study was to characterize the proportion of operations performed outside of these guidelines.A 5-year retrospective review between July 1, 2007, and June 30, 2012, was performed of consecutive patients seen at a single tertiary medical center for a pancreatic cyst. Manual chart review for relevant clinical variables and cyst characteristics was performed.During this period, 148 patients underwent surgery, and of these, 23 (16 %) patients had no high-risk criteria by the 2006 Sendai criteria. None of these harbored high-grade dysplastic or cancerous lesions. A high cyst carcinoembryonic antigen (CEA) level (35 %), patient anxiety (26 %), and physician concern (22 %) were explicit reasons to proceed to surgery. An elevated cyst CEA level >192 ng/ml was the most significant predictor (OR 5.14 (95 % confidence interval (CI) 1.47-18.0) for surgery without high-risk criteria.A high cyst CEA level was significantly associated with the decision to operate outside of consensus-based guidelines. The misuse of cyst CEA in the management of pancreatic cysts negatively impacts patient anxiety, increases physician uncertainty, and leads to surgery with minimal benefit.
Leiomyosarcoma: One Disease or Distinct Biologic Entities Based on Site of Origin? JOURNAL OF SURGICAL ONCOLOGY Worhunsky, D. J., Gupta, M., Gholami, S., Tran, T. B., Ganjoo, K. N., van de Rijn, M., Visser, B. C., Norton, J. A., Poultsides, G. A. 2015; 111 (7): 808-812
Leiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin.Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.From 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease-specific survival, recurrence-free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P < 0.001), but not site of origin, size, grade, or margin status, were independently associated with worse DSS. A significant number of recurrences and disease-related deaths were noted beyond 5 years.Although larger and higher grade, retroperitoneal and uterine LMS share similar survival and recurrence patterns with their trunk and extremity counterparts. LMS of various anatomic sites may not represent distinct disease processes based on clinical outcomes. The presence of metastatic disease remains the most important prognostic factor for LMS.
Impact of body mass index on perioperative outcomes and survival after resection for gastric cancer JOURNAL OF SURGICAL RESEARCH Ejaz, A., Spolverato, G., Kim, Y., Poultsides, G. A., Fields, R. C., Bloomston, M., Cho, C. S., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2015; 195 (1): 74-82
Among patients undergoing resection for gastric cancer, the impact of body mass index (BMI) on outcomes is not well understood. We sought to define the impact of non-normal BMI on short- and long-term outcomes after gastric cancer resection.We identified 775 patients who underwent gastrectomy for adenocarcinoma between 2000 and 2012 from the multi-institutional US Gastric Cancer Collaborative. Clinicopathologic characteristics, operative details, and oncologic outcomes were collected, and patients were stratified according to BMI.Most patients in the cohort were classified as having normal BMI (n = 338, 43.6%), followed by overweight (n = 229, 29.6%), obese (n = 153, 19.7%), and underweight (n = 55, 7.1%). After stratifying by BMI, there were no significant differences in the incidence of postoperative blood transfusions, perioperative morbidity, postoperative infectious complications, length of stay, perioperative 30-d in-hospital death, or readmission across groups (all P > 0.05). BMI did not impact overall or recurrence-free survival after stratifying by stage (all P > 0.05). However, underweight patients with low preoperative albumin levels had worse overall survival (OS) compared with that of patients of normal BMI.BMI did not impact perioperative morbidity, recurrence-free, or OS in patients undergoing gastric resection for adenocarcinoma. Underweight patients with BMI <18.5 kg/m(2) and low preoperative albumin levels, however, had a significantly decreased OS after gastrectomy for cancer. These high-risk patients should have their nutritional status optimized both before and after gastrectomy in an attempt to modify this risk factor and, in turn, achieve better outcomes.
Minimally Invasive Resection of Choledochal Cyst: a Feasible and Safe Surgical Option JOURNAL OF GASTROINTESTINAL SURGERY Margonis, G. A., Spolverato, G., Kim, Y., Marques, H., Poultsides, G., Maithel, S., Aldrighetti, L., Bauer, T. W., Jabbour, N., Gamblin, T. C., Soares, K., Pawlik, T. M. 2015; 19 (5): 858-865
The use of minimally invasive surgery (MIS) for choledochal cyst (CC) has not been well documented. We sought to define the overall utilization and outcomes associated with the use of the open versus MIS approach for CC. We examined the factors associated with receipt of MIS for CC, as well as characterized perioperative and long-term outcomes following open versus MIS for CC.Between 1972 and 2014, a total of 368 patients who underwent resection for CC were identified from an international, multicenter database. A 2:1 propensity score matching was used to create comparable cohorts of patients to assess the effect of MIS on short-term outcomes.Three hundred thirty-two patients had an open procedure, whereas 36 patients underwent an MIS approach. Children were more likely to be treated with a MIS approach (children, 24.0 % vs. adults, 2.1 %; P<0.001). Conversely, patients who had any medical comorbidity were less likely to undergo MIS surgery (open, 26.2 % vs. MIS, 2.8 %; P=0.002). In the propensity-matched cohort, MIS resection was associated with decreased length of stay (open, 7 days vs. MIS, 5 days), lower estimated blood loss (open, 50 mL vs. MIS, 17.5 mL), and longer operative time (open, 237 min vs. MIS, 301 min) compared with open surgery (all P<0.05). The overall and degree of complication did not differ between the open (grades I-II, n=13; grades III-IV, n=15) versus MIS (grades I-II, n=5; grades III-IV, n=5) cohorts (P=0.85). Five-year overall survival was 98.6 % (open, 98.0 % vs. MIS, 100.0 %; P=0.45); no patient who underwent MIS developed a subsequent cholangiocarcinoma.MIS resection of CC was demonstrated to be a feasible and safe approach with acceptable short-term outcomes in the pediatric population. MIS for benign CC disease was associated with similar perioperative morbidity but a shorter length of stay and a lower blood loss when compared with open resection.
Is It Time to Abandon the 5-cm Margin Rule During Resection of Distal Gastric Adenocarcinoma? A Multi-Institution Study of the U.S. Gastric Cancer Collaborative. Annals of surgical oncology Squires Iii, M. H., Kooby, D. A., Poultsides, G. A., Pawlik, T. M., Weber, S. M., Schmidt, C. R., Votanopoulos, K. I., Fields, R. C., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Bloomston, M., Winslow, E. R., Russell, M. C., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 22 (4): 1243-1251
A proximal margin distance of 5 cm is advocated for resection of gastric adenocarcinoma (GAC). We assessed the prognostic value of proximal margin (PM) distance on survival outcomes after resection of distal GAC.All patients who underwent resection of distal GAC (antrum/body) from 2000 to 2012 at seven institutions of the U.S. Gastric Cancer Collaborative were included. Patients with positive distal margins or macroscopic residual disease were excluded. The prognostic value of PM distance (assessed in 0.5-cm increments) on overall (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier and multivariate regression analysis.A total of 465 patients underwent resection of distal GAC. Of these, 435 had R0 resections; 30 patients had a positive PM. 143 patients had stage I, and 322 had stage II-III tumors. Median follow-up was 44 months. Average PM distance was 4.8 cm. Median OS for patients with PM of 3.1-5.0 cm (n = 110) was superior to patients with PM ≤ 3.0 cm (n = 176) (48.1 vs. 29.3 months; p = 0.01), while a margin >5.0 cm (n = 179) offered equivalent survival to PM 3.1-5.0 cm (50.6 months, p = 0.72). The prognostic value of margin distance was stage specific. On multivariate analysis of stage I patients, PM 3.1-5.0 cm remained associated with improved OS [hazard ratio (HR), 0.16; 95 % confidence interval (95 % CI), 0.04-0.60; p = 0.01]. In stage II-III, neither PM 3.1-5.0 cm nor PM > 5.0 cm was significantly associated with OS; OS was dictated by T stage and nodal involvement.The prognostic value of proximal margin distance after resection of distal gastric cancer appears stage specific. In stage I, a 3.1- to 5.0-cm proximal margin is associated with the same improved OS as a > 5.0-cm margin. In stage II-III disease, other adverse pathologic factors more strongly impact survival than proximal margin distance.
Clinicopathological features and prognosis of gastric cardia adenocarcinoma: A multi-institutional U.S. study. Journal of surgical oncology Amini, N., Spolverato, G., Kim, Y., Squires, M. H., Poultsides, G. A., Fields, R., Schmidt, C., Weber, S. M., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2015; 111 (3): 285-292
Potential differences in presentation and outcome of patients with gastric cardia adenocarcinoma (GCA) and non-cardia adenocarcinoma may exist. The aim of the present study was to compare the clinicopathological characteristics and the prognosis of GCA versus non-cardia