Dog HemangiosarcomaCanine hemangiosarcoma is an incurable tumor of cells that line blood vessels (endothelial cells). Based on current estimates of the lifetime risk of cancer in dogs and the prevalence of hemangiosarcoma, we predict that of 65 million pet dogs living in the United States today, as many as two million may get this cancer and die from it. Although dogs of any age and breed are susceptible to hemangiosarcoma, it occurs more commonly in dogs beyond middle age, and in breeds such as Golden Retrievers, German Shepherd Dogs, Portuguese Water Dogs, and Skye Terriers, among others.
Hemangiosarcoma develops slowly and is essentially painless – so clinical signs are usually not evident until the advanced stages when the tumors are resistant to most treatments. Less than 50% of dogs treated with standard-of-care for this tumor (surgery and intensive chemotherapy) survive more than six months. Many dogs die from severe internal bleeding before there is an opportunity to institute treatment.
Because these tumors arise in internal organs there is often little
warning that they are present prior to time they cause severe clinical
signs of disease. A common estimate of the average time from discovery
of the tumor until death occurs in affected dogs is six to eight weeks
but death occurs more rapidly than this in a number of cases.
In most instances tumors of this size in this location are found on
physical exam. In other cases the tumor affects the heart and is hard
to find on a physical exam and even easy to miss or X-rays. Sometimes
there are hundreds of small tumors spread throughout the body and
surgical exploration or an autopsy are the only ways to identify the
Visible bleeding, usually in the form of nosebleeds, and signs
associated with blood loss, such as tiring easily, episodes of
unexplained weakness, pale color to the mucous membranes of the mouth
and eyes, increased respiratory rates, abdominal swelling and
depression are the most common presenting signs for patients with
hemangiosarcoma. A few dogs just suddenly die with no clinical signs
having been noted by their families prior to death. Bleeding disorders
associated with hemangiosarcoma are sometimes confused with immune
mediated hemolytic anemia (IMHA) because the type of anemia caused by
the two conditions is very similar and early clinical signs are often
very similar, as well. Hemangiosarcomas can cause very large tumors,
sometimes as large as ten or more pounds, when they affect the spleen.
The blood disorder that most commonly accompanies the presence of hemangiosarcoma tumors is disseminated intravascular coagulation (DIC). This is blood clotting that is occurring inappropriately inside the blood vessels. It uses up all of the blood clotting elements rapidly and dogs with this condition usually have platelet deficiencies, increased blood clotting times, decrease in fibrin content in the blood and an increase in fibrin degradation products (FDPs). This is probably the cause of death in most dogs affected with hemangiosarcoma.
Diagnosis of hemangiosarcoma can be accomplished in a number of ways. Identification of a tumor in the spleen or heart raises a high degree of suspicion for this tumor. Abdominal swelling is also highly suggestive in an older large breed dog. If fluid is aspirated from the abdomen and it looks like blood it is even more suggestive of hemangiosarcoma. If blood is drawn and will not clot when left in the syringe it is another sign that a dog may have this tumor. In some cases careful evaluation of the type of bleeding disorder present is necessary to raise the suspicion of hemangiosarcoma.
Canine hemangiosarcoma is among the most challenging and mysterious diseases encountered in veterinary practice. It is an incurable tumor of cells that line blood vessels, called vascular endothelial cells. Hemangiosarcoma is relatively common in dogs; it is estimated that this type of cancer accounts for 5-7% of all tumors seen in dogs. Considering the lifetime risk of cancer for dogs is between 1 in 2 and 1 in 3, we can calculate that 1.5 to 2.5 million of the ~72 million pet dogs in the United States today will get hemangiosarcoma and succumb from it. (WHAT!?)
Although dogs of any age and breed are susceptible to hemangiosarcoma, it occurs more commonly in dogs beyond middle age (older than 6 years), and in breeds such as Golden Retrievers, German Shepherd Dogs, Portuguese Water Dogs, Bernese Mountain Dogs, Flat Coated Retrievers, Boxers and Skye Terriers, among others. According to the Golden Retriever Health Study published in 2000, the estimated lifetime risk of hemangiosarcoma in this breed is 1 in 5, illustrating the magnitude of this problem.
Unlike other cancers, hemangiosarcoma is almost an exclusive disease of dogs. In dogs, the common primary sites for hemangiosarcoma are the spleen, the right atrium of the heart, and the subcutis, which is the tissue beneath the skin. The pattern of growth for these tumors involves infiltration into normal tissues surrounding the tumor as well as distant spread (metastasis). The disease is indolent; in other words, it does not cause pain and the rate of growth in the early stages is relatively slow. Dogs harboring even large hemangiosarcomas may show no clinical signs or evidence that they have a life threatening disease. Generally, the tumor cells retain some normal aspects of behavior, so they try to make blood vessels. But these vessels are tortuous and malformed, and blood cells tend to pool in them and clot. The clots then prevent blood and nutrients from reaching tumor cells, in turn causing them to die. This creates small ruptures in the tumor through which blood may escape into the abdomen, heart sac, chest, or subcutaneous space. Depending on the amount of blood lost, affected dogs may show non-specific (constitutional) signs such as lethargy and weakness, but these are transient and resolve as dogs reabsorb the blood components and make new blood cells. The clinical signs are recurrent, but they also are subtle enough to go unnoticed for some time. Since hemangiosarcoma tends to metastasize aggressively to lungs, liver, intestines, and the membranous connective tissue that supports the intestines), distant spread (either microscopic or macroscopic) has inevitably occurred once the disease is finally diagnosed. The eventual outcome for patients with this disease often follows the rupture of a large or rapidly growing tumor, which results in acute, severe hemorrhage, collapse, shock, and death.
What Causes Hemangiosarcoma
We do not precisely know what causes canine hemangiosarcoma. The observations that the disease occurs more commonly in dogs than in other animals, and that some breeds are at higher risk than others tell us that heritable factors must contribute to risk. Tumors arise when cells accumulate mutations that eliminate normal constraints of growth and genetic integrity. These mutations provide cells a selective growth advantage within their environment, essentially the same evolutionary phenomenon that we call natural selection, albeit on a microscopic scale. Most mutations arise because the enzymes that control cell division are not foolproof.
Fortunately, most of these mutations are silent (they neither help nor hurt the cell or the organism), and the body has mechanisms to eliminate most cells that acquire deleterious mutations.
We have identified some of the fundamental properties of canine hemangiosarcoma, and it is possible one or more of these may prove to be an “Achilles heel” for the tumor. For example, most of these tumors make growth factors that they need to survive, or they “coerce” cells in their environment to do this for them. One of these growth factors is vascular endothelial growth factor-A or VEGF, which acts by binding specific receptors on the hemangiosarcoma cells. New drugs under development by various pharmaceutical companies are designed specifically to interfere with the signals transmitted by these receptors. The reliance of hemangiosarcoma cells on VEGF signals to survive should make them more sensitive than normal cells to these drugs. Several groups are working to bring these drugs into the clinic, but the process is slow because testing must be done in a careful, deliberate way to ensure the compounds are safe and effective.
Standard Treatment for Canine Hemangiosarcoma
Standard Treatment and prognosis for Hemangiosarcoma vary by location. Cutaneous Hemangiosarcoma is often curable with surgery alone, provided the lesion is small and confined to the dermis. Cutaneous Hemangiosarcoma often occur in areas of glabrous skin on lightly pigmented dogs and arise as a result of sunlight exposure.Lesions that are larger or deeper may be either primary or metastatic lesions and warrant more aggressive treatment. Treatment of splenic, atrial, or subcutaneous Hemangiosarcoma consists of surgical excision of the primary tumor and adjuvant chemotherapy. Recommended chemotherapy for Hemangiosarcoma is single-agent doxorubicin, intravenously given every 3 weeks. Use of an indwelling catheter is important because of the catastrophic tissue slough that occurs after doxorubicin extravasation. Owners should be warned of the potential of cardiotoxicity. A total of 4-6 doses of doxorubicin are recommended. Median survival time after surgery alone is reported to be 2-3 months, with the addition of chemotherapy increasing the median survival time to 4-6 months. The VAC protocol may be useful; however it has a higher morbidity rate with no increase in survival time. Dogs with splenic Hemangiosarcoma that have ruptured may have a poorer prognosis than those not ruptured. Currently several drugs are being investigated for their antiangiogenic properties, and may be useful for treatment of Hemangiosarcoma in the future. Follow-up for Hemangiosarcoma should include monthly thoracic radiographs and physical examinations.
Regrettably, the standard-of-care for this disease has not seen significant advancement over the past 20 or 30 years. There is presently no readily available, effective test for early diagnosis of hemangiosarcoma. Careful analysis of blood samples by experienced pathologists may hint at the presence of chronic hemorrhage and blood vessel abnormalities that are suggestive of hemangiosarcoma. However, this method is neither sensitive nor specific to confirm the diagnosis. Non-invasive imaging methods are useful aids to diagnose the disease. In particular, ultrasound is moderately specific, but it is not sensitive, and the tumor must be large enough to be grossly visible. In addition, biopsies are required for confirmation of imaging results. Repeated biopsies of tissues where the tumors may arise (without other evidence for the presence of a tumor) are of little use to provide early diagnosis, and considering the fact that there is some risk to these procedures, such an approach is practically and ethically unacceptable.
The options for therapy of canine hemangiosarcoma are limited, largely because the disease is not diagnosed until the late stages. The conventional standard treatment consists of surgery to shrink or remove the primary tumor, when possible, followed by intensive chemotherapy. In some cases, surgery is not feasible, or it can be impractical or inappropriate (for example, if there is evidence of extensive metastatic spread to sites beyond the primary tumor). Median survival for dogs treated with surgery alone is approximately 90 days, and that is extended to approximately 180 days by the addition of chemotherapy using one of several protocols available. Because the goal for chemotherapy in pet dogs is to extend life with good quality, toxicity is generally not a major issue of concern(WHAT?!), and when it occurs it is most often managed without much difficulty.
Surgery and chemotherapy have limited success in prolonging survival times and increasing quality of life in dogs with HSA. Splenectomy alone gives an average survival time of 1–3 months. Advances in medical oncology are resulting in increased survival rates and a better quality of life for veterinary cancer patients. An understanding of mechanisms of metastasis has led to the development of new treatments designed to delay or inhibit tumor spread. Promising new treatment options include novel delivery systems (inhalation or intracavitary chemotherapy); use of immunomodulators such as liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine; antimetastatic agents such as inhibitors of angiogenesis (interferons, thalidomide), matrix metalloproteinase inhibitors, and minocycline; dietary modifications; and gene therapy. Inhibitors of angiogenesis (meaning anti-angiogenesis) seem to be safe and, unlike conventional chemotherapy, do not induce drug resistance. Although many of the newer approaches are still under development and review, the use of multimodality therapy incorporating innovative treatment modalities may offer the best therapeutic option for dogs affected with HSA.
The nature of hemangiosarcoma itself draws attention to the prolific formation of blood vessels through the tumors. These vessels typically rupture causing loss of blood internally. Yun Nan Bai Yao herbs really helps slow the bleeding. As another integral part of natural healing for hemangiosarcoma is to help prevent the formation of new blood vessels with anti-angiogenesis supplements. Powerful medicinal mushrooms have been shown to discourage the rapid growth of these blood vessels and support the immune system.
A basic start I have seen people using is:
Mushrooms have been used in traditional Chinese medicine for more than 2,000 years. The compound in the mushroom that is believed to have immune-boosting properties is polysaccharopeptide, or PSP. In the last two decades, some studies have suggested that PSP Beta glucans also has a tumor-fighting effect. Read about medicinal Mushrooms and Beta Glucans below.
Many dose dogs at 800-1600mg twice a day.
More then any other cancer I work with I think this is the most important one to make sure you have a good holistic vet on board. I know, I know I have said that a few times already.
"I saw this thread and just joined the boards so I could give you a little information. Our lab was diagnosed with this disease on March 8. He was given 1 month to live (large spleen tumor and spread to the liver) but has been doing okay. No additional bleeding, no weight loss, pink gums etc. The oncologist said we could have the spleen removed (but the cancer would remain since it had spread) and do chemo (they would not do chemo without the surgery); this might extend his life by a few months but we felt the pain and stress with little extension of live was not worth it for him. The vet oncologist put him on a Chinese herb called Yunnan payio/baiyo that inhibits bleeding (2 capsules 2 times a day for an 80 lb dog). We can get this from the vet or order online (cheaper). We also give many other supplements and feed a high protein, no grain diet with supplements of omega 3 fatty acids. Other supplements include milk thistle (for the liver), immune support, anemia meds, medicinal mushrooms, and others. "
Mushroom Derived Compound Lengthens Survival in Dogs With Cancer
Mushroom-Derived Compound Lengthens Survival in Dogs With Cancer, Study Suggests
Dogs with hemangiosarcoma that were treated with a compound of Beta glucans derived from the Coriolus versicolor mushroom had the longest survival times ever reported for dogs with the disease. These promising findings offer hope that the compound may one day offer cancer patients -- human and canine alike -- a viable alternative or complementary treatment to traditional chemotherapies.
The study was conducted by two University of Pennsylvania School of Veterinary Medicine faculty. They published their findings in an open-access article in the journal Evidence-Based Complementary and Alternative Medicine.
The Coriolus versicolor mushroom, known commonly as the Yunzhi or Turkey Tail mushroom, has been used in traditional Chinese medicine for more than 2,000 years. The compound in the mushroom that is believed to have immune-boosting properties is polysaccharopeptide, or PSP. In the last two decades, some studies have suggested that PSP Beta glucans also has a tumor-fighting effect.
"There have been a series of studies looking at groups of people with cancer," "The issue with those studies is that they weren't necessarily measuring what most people would think is the most clinically important result, which is, do people taking PSP Beta glucans live longer?"
To address this critical question,University of Pennsylvania School of Veterinary Medicine pursued a study in dogs with naturally occurring hemangiosarcoma, an aggressive, invasive cancer that arises from the blood cells and typically affects the spleen. It commonly strikes golden retrievers and German shepherds.
Fifteen dogs that had been diagnosed with hemangiosarcoma participated in the trial. Divided into three groups of five, each group received a different dose -- 25, 50 or 100 mg/kg/day -- of (Beta glucans), a formulation of PSP.
The owners were instructed to give their dog capsules of (Beta glucans), compounded by Penn pharmacists, daily. Each month, the owners brought their dogs to Penn's Ryan Veterinary Hospital for follow-up visits. There, the researchers took blood samples and conducted ultrasounds to determine the extent that tumors developed or grew and spread in the dogs' bodies.
Based on the ultimate endpoints -- how quickly the tumors progressed and how long the dogs actually lived -- the results of the researchers' trial suggest that the Beta glucans was effectively fighting the tumors.
"We were shocked," University of Pennsylvania School of Veterinary Medicine said. "Prior to this, the longest reported median survival time of dogs with hemangiosarcoma of the spleen that underwent no further treatment was 86 days. We had dogs that lived beyond a year with nothing other than this mushroom as treatment."
There were not statistically significant differences in survival between the three dosage groups, though the median survival time was highest in the 100 mg group, at 199 days, eclipsing the previously reported median survival time.
The results were so surprising, in fact, that the researchers asked Penn Vet pathologists to recheck the dogs' tissue biopsies to make sure that the dogs really had the disease.
"They reread the samples and said, yes, it's really hemangiosarcoma," University of Pennsylvania School of Veterinary Medicine said.
Chemotherapy is available for treating hemangiosarcoma, but many owners opt not to pursue that treatment once their dog is diagnosed. "It doesn't hugely increase survival, it's expensive and it means a lot of back and forth to the vet for the dog," Cimino Brown said. "So you have to figure in quality of life."
As an added benefit, University of Pennsylvania School of Veterinary Medicine have found no evidence of adverse effects from the Beta glucans treatment.
"Although hemangiosarcoma is a very sad and devastating disease, in the long term, if we prove that this works, this treatment can be a really nice alternative for owners to have increased quality time with their pet at the end of its life."
Evid Based Complement Alternat Med. 2012;2012:384301. doi: 10.1155/2012/384301. Epub 2012 Sep 5.Single agent polysaccharopeptide delays metastases and improves survival in naturally occurring hemangiosarcoma.
Brown DC, Reetz J.
SourceVeterinary Clinical Investigations Center, Department of Clinical Studies, School of Veterinary Medicine and University of Pennsylvania, 3900 Delancey Street, Philadelphia, PA 19104-6010, USA.
The 2008 World Health Organization World Cancer Report describes global cancer incidence soaring with many patients living in countries that lack resources for cancer control. Alternative treatment strategies that can reduce the global disease burden at manageable costs must be developed. Polysaccharopeptide (PSP) is the bioactive agent from the mushroom Coriolus versicolor. Studies indicate PSP has in vitro antitumor activities and inhibits the growth of induced tumors in animal models. The investment of resources required to complete large-scale, randomized controlled trials of PSP in cancer patients is more easily justified if antitumor and survival benefits are documented in a complex animal model of a naturally occurring cancer that parallels human disease. Because of its high metastatic rate and vascular origin, canine hemangiosarcoma is used for investigations in antimetastatic and antiangiogenic therapies. In this double-blind randomized multidose pilot study, high-dose PSP Beta Glucans significantly delayed the progression of metastases and afforded the longest survival times reported in canine hemangiosarcoma. These data suggest that, for those cancer patients for whom advanced treatments are not accessible, PSP as a single agent might offer significant improvements in morbidity and mortality.
- [Study on effects of Astragalus, Angelica and their combination on vascular endothelial cell proliferation in vitro].
Lei Y, Gao Q, Li YS.
Xiyuan Hospital, China Academy of TCM, Beijing 100091.
OBJECTIVE:To study the effects of Astragalus membranaceus (AM), Angelica sinensis (AS) and their combination on human umbilical vein endothelial cell (HUVEC) proliferation and cells cycle.
METHODS:The effects were observed and studied by means of taking the cultured HUVECs as model to determine the cell proliferation with MTT method, cell cycle was analyzed with cytometry, and vascular endothelial growth factor (VEGF) expression with SABC method. The regulatory effects of AM, AS and their combination on the HUVEC proliferation promoting were observed and studied.
RESULTS:AM and AS, used singly or in combination, could promote the growth of endothelial cells, increase the cell population in S phase, the effects showed more significant when used in combination (P < 0.05 or P < 0.001). Meanwhile, VEGF expression in all the medicated group was up-regulated, but in the PBS control group, it showed only weak expression (P < 0.05 or P < 0.01).
CONCLUSION:AM and AS have effect in promoting vascular endothelial cell proliferation and DNA synthesis, and showed synergistic effect when they were used in combination, suggesting that these two Chinese herbs could have certain effect on the genesis and development of neogenetic vascularization in ischemic myocardium.