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Phenotypic modulation of hepatocarcinogenesis and reduction in N-nitrosomorpholine-induced hemangiosarcoma and adrenal lesion development in Sprague-Dawley rats by dehydroepiandrosterone.

Dietary administration of 0.25% dehydroepiandrosterone (DHEA) during and subsequent to 7 weeks treatment with N-nitrosomorpholine (NNM) resulted in significantly reduced development of adrenal cortical lesions and hemangiosarcomas in the liver. In addition, distinct phenotypic modulation of hepatocellular tumours was observed after combined hormone and carcinogen treatment. Thus the neoplasms were characterized by a higher degree of differentiation, lower mitotic rate and reduced potential for metastasis as compared to tumours observed after NNM alone. The data clearly indicate that DHEA exerts an inhibitory effect on both adrenal and hepatocarcinogenesis similar to that earlier reported for neoplasia in lung, thyroid, colon and skin.

Adenoma↗

Azoxymethane-induced liver hemangiosarcomas in inbred strain-2 guinea pigs.

Intrarectal administration of 0.5 ml of a 0.2% solution of azoxymethane twice weekly for 33 weeks to female inbred strain-2 guinea pigs specifically induced multiple liver hemangiosarcomas in 15 of 16 animals 32-54 weeks after the first treatment. No neoplasms and preneoplastic changes were found in the large intestine.

Animals↗

Functional asplenia and portal hypertension in a patient with primary splenic hemangiosarcoma.

A 60-year-old man with primary splenic hemangiosarcoma (PSH) presented with weakness, weight loss, abdominal pain, and anemia. Physical examination revealed hepatomegaly, ascites, and firm, huge splenomegaly. Ultrasonography showed many nodular structures characterized by hypoechogenic and hyperechogenic areas. The patient also had portal hypertension, which was confirmed by physical findings and by measurement of portal vein pressure during operation. A liver-spleen scan using Tc-99m sulfur colloid and Tc-99m labeled heat denatured erythrocytes failed to demonstrate any splenic uptake, a reliable feature of functional asplenia. Although on a total body scan with Ga-67 citrate there was no splenic uptake, there was gallium uptake in the liver, where the presence of the metastatic lesion was histopathologically verified and confirmed by operation. There was also uptake in the middle zones of the lungs. Ga-67 citrate imaging appears to be helpful in the diagnosis of metastasis of PSH, and PSH can rarely cause portal hypertension.

Gallium Radioisotopes↗

Hemangiosarcoma of the breast.--Case report with scanning electron microscopic study.

Hemangiosarcoma of the breast in a 22-year-old female was presented. She died of massive pulmonary metastasis and apparent internal hemorrhage from the involved liver by metastasis after 40 months of the illness. Intense scanning electron microscopic (SEM) study was undertaken on this lesion. At the same time, in order to compare SEM findings of angiosarcoma with several other benign disorders, the following lesions were chosen, namely, chronically-inflamed veins in the gastric submucosa, benign cavernous hemangiomas of the skin and liver, and organizing thrombi with papillary structures. Some of these lesions exhibited focal similarities in surface structures to those from angiosarcoma. Besides various characteristics by SEM in angiosarcoma, cell clusters protruding into the vascular cavity were found to be the most unique feature which we have never observed in any other lesions.

Adult↗

Hemangiosarcoma subsequent to radiotherapy for a hemangioma in infancy.

A case is presented of a 31-year-old white man who developed a hemangiosarcoma in the very place where 30 years ago a hemangioma had been treated by radiotherapy. The rarity of such an occurrence is attested to by the fact that only two similar cases were found in the English medical literature.

Adolescent↗

Intracranial lesions in dogs with hemangiosarcoma.

A retrospective analysis of 85 dogs with hemangiosarcoma (HSA) that underwent complete necropsy, including gross examination of the brain, was conducted. Grossly identifiable intracranial lesions were present in 17 dogs. Twelve of 85 dogs (14.2%) had brain metastases. Four of 85 dogs (4.7%) had hemorrhagic lesions and/or ischemic necrosis without identifiable tumor. One dog had a primary central nervous system tumor. Signs of intracranial disease were present in six of 85 dogs (7.1%) with HSA; four had brain metastases and two had nonneoplastic lesions. Metastases had a propensity for cerebrum and gray matter. Dogs with brain metastases had more widely disseminated disease than dogs without brain metastases (P less than 0.001). Dogs with pulmonary metastases were at greater risk for developing brain metastases than dogs without pulmonary metastases (odds ratio = 8.31). Although thoracic radiography accurately identified ten of 12 dogs (83%) with pulmonary metastases, too few cases were available to assess the applicability/accuracy of thoracic radiography in predicting the presence or absence of brain metastases in dogs with malignancy and signs of intracranial disease.

Animals↗

Chemotherapy of canine hemangiosarcoma with doxorubicin and cyclophosphamide.

Sixteen dogs with a histologic diagnosis of hemangiosarcoma were treated with surgery and doxorubicin/cyclophosphamide. The patients' characteristics, ie, age, size, and breed, were similar to those of previous studies. Historic controls for surgery alone were used to evaluate efficacy of the chemotherapy. The results show a trend of improved survival in dogs with localized disease (Stage I) receiving combination therapy. The median survival was 250 days, with a mean of 403 days. The survival times for dogs with stage I, II, and III disease was also improved with combination therapy, when compared to historical controls treated with surgery alone. The overall median survival was 202 days with a mean of 285 days. Toxicities included mild to moderate neutropenia (9 of 16) and clinical signs, such as lethargy, anorexia, vomiting, diarrhea, and fever (13 of 16). Three dogs had severe neutropenia requiring hospitalization and supportive care. One dog died from sepsis and related complications. Chemotherapy with doxorubicin and cyclophosphamide appears to improve survival with acceptable morbidity in patients with early stage disease.

Animals↗

Hemangiosarcoma of the spleen and liver metastases: angiographic manifestations.

The arteriographic findings in two cases of hemangiosarcoma of the spleen with liver metastases are described. These are the second and third reported cases of angiographically demonstrated malignant splenic tumors of vascular origin. Despite the absence of tumor vessels, there were multiple vascular takes in the arterial through the venous phase, mimicking benign cavernous hemangioma. Multiple metastases in the liver were the only clue to malignancy. Arteriography combined with liver-spleen scintigraphy not only provides information which is valuable in the preoperative diagnosis but also aids in management of the patient.

Adult↗

Hemangiosarcoma of the bone. Problems arising from the heterogeneity of malignant vascular tumors of the bone.

BACKGROUND: Hemangioendothelioma of the bone is a rare vasoformative tumor of the bone with an intermediately aggressive nature. The tumor is said to have a long clinical course depending on the sites involved. Diagnosis is particularly difficult since vascular tumors of the bone often present heterogeneous differentiation. CASE REPORT: We report on a 65-year-old female patient who had been diagnosed with an epitheloid hemangioendothelioma of the iliac bone and who underwent wide local excision. Although the initial biopsy specimens had clearly shown an epitheloid hemangioendothelioma, the final pathological analysis revealed a heterogeneous tumor, partially with some characteristics of an epitheloid hemangiosarcoma. The patient subsequently developed pulmonary metastasis, received a multimodality treatment, but died 14 months after the initial diagnosis from pulmonary insufficiency due to pleural sarcomatosis. CONCLUSION: Hemangioendothelioma of the bone needs to be discussed as a differential diagnosis of osteolytic lesions. Our case stresses the importance of multimodality treatment in centers for cancer treatment. Histopathologic evaluation is essential in the diagnosis of epitheloid hemangioendothelioma. It is particularly difficult due to the heterogeneous differentiation of vasoformative tumors of the bone.

Aged↗

[Splenohepatic hemangiosarcoma with laceration of the spleen].

A case of a 31-years-old male with pathologic rupture of the spleen and hemoperitoneum, caused by a primitive hemangiosarcoma and occurred during a weight-lifting is described. A metastatic involvement of the liver was also noted. The patient was splenectomized and died within 2 months.

Adult↗

Diffuse bilateral hemangiosarcoma of the uterus in a dog.

A 15-year-old female mongrel dog showed abdominal swelling, marked hemorrhagic ascites and vulvar discharge, and ovariohysterectomy was performed. Grossly, the uterus was enlarged bilaterally without apparent mass formation. Histologically, the uterine muscular wall was composed of proliferated sinusoidal vessels. In some areas, irregular and small vessels proliferated markedly, while in others, pleomorphic and atypical tumor cells forming irregular vascular structures were predominant. From these findings, the case was diagnosed as diffuse bilateral hemangiosarcoma of the uterus that invaded to the ovary and broad ligament. The relationship between the tumor and angiomatosis was discussed.

Animals↗

Pulmonary intravascular hemangiosarcoma in a cat.

A 9-year-old, castrated male Japanese domestic cat presented with a complaint of exertional dyspnea. Based on the radiographic findings, presumptive diagnosis of aspiration pneumonia or primary diffuse pulmonary neoplasia in the right middle lobe was made. Histologically, the pulmonary lesion was characterized by diffuse thickening of alveolar wall with the proliferation of apparently atypical irregular-shaped cells. Immunohistochemical staining using anti-human factor VIII-related antigen antiserum showed positive reaction in the cytoplasm of the atypical cells. According to the findings, the lesion was diagnosed as pulmonary intravascular hemangiosarcoma.

Animals↗

Primary hemangiosarcoma of the humerus in a Maltese dog.

A 14-year-old intact male Maltese dog was presented with a history of pain and swelling of the left upper forelimb and lameness for 3 weeks. Hematological and radiographical examinations showed regenerative anemia and osteolysis of the humerus. Fine needle aspiration biopsy detected epithelioid- and fibroblast-like anaplastic cells with blood components. A hemorrhagic and osteolytic malignant tumor was suspected, and the affected forelimb was amputated. Histopathologically, the dog was diagnosed with primary hemangiosarcoma of the humerus. Thereafter, metastatic lesions appeared in the skin, and the dog was euthanized 1 month after the operation.

Animals↗

Assessment of cyclooxygenase-2 expression in canine hemangiosarcoma, histiocytic sarcoma, and mast cell tumor.

To determine whether cyclooxygenase-2 (COX-2) is expressed in canine hemangiosarcoma (HSA), histiocytic sarcoma (HS), and grade-II mast cell tumor (MCT), we performed immunohistochemistry using COX-2 antibodies in the aforementioned tumors. Twenty cases of each tumor type were selected initially from the Laboratory of Pathology archives of cases submitted through the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania. Immunohistochemistry was performed, using a polyclonal antiprostaglandin endoperoxide synthase immunoglobulin G COX-2 antibody. Sections from the kidneys of young dogs, in which the macula densa stains positive for COX-2, served as positive controls. Slides were reviewed by a single pathologist (M. H. Goldschmidt) and graded for COX-2 expression according to previously established scales. Descriptive data is given for each tumor type. COX-2 expression was identified in 0 of 19 HSA, 1 of 20 HS, and 1 of 17 grade-II MCT. Although COX-2 has been shown to be overexpressed in selected human sarcomas and hematopoeitic tumors, these results indicate that canine HSA, HS, and MCT do not express COX-2 in any appreciable fashion.

Animals↗

Treatment of canine hemangiosarcoma: 2000 and beyond.

Canine hemangiosarcoma (HSA) is an aggressive and malignant neoplasia with a grave prognosis. Surgery and chemotherapy have limited success in prolonging survival times and increasing quality of life in dogs with HSA. 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 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.

Adjuvants, Immunologic↗

Plasma vascular endothelial growth factor concentrations in healthy dogs and dogs with hemangiosarcoma.

Vascular endothelial growth factor (VEGF) is a dimeric glycosylated polypeptide growth factor with potent angiogenic, mitogenic, and vascular permeability-enhancing properties specific for endothelial cells. In humans, VEGF seems to play a major role in tumor growth, and plasma concentrations correlate with tumor burden, response to therapy, and disease progression. This study compared plasma VEGF concentrations in healthy client-owned dogs (n = 17) to dogs with hemangiosarcoma (HSA; n 16). Dogs with HSA were significantly more likely to have detectable concentrations of plasma VEGF (13/17) compared to healthy dogs (1/17; P < .001). The median plasma VEGF concentration for dogs with HSA was 17.2 pg/mL (range, < 1.0-66.7 pg/mL). Plasma VEGF concentrations in dogs with HSA did not correlate with stage of disease or tumor burden, but 1 dog had undetectable VEGF during chemotherapy that subsequently increased with disease progression.

Animals↗

Efficacy and toxicity of a dose-intensified doxorubicin protocol in canine hemangiosarcoma.

The purpose of this study was to evaluate the efficacy and toxicity of a single-agent, dose-intensified doxorubicin protocol in canine hemangiosarcoma (HSA). Canine HSA is a highly malignant tumor, and most affected dogs die within 6 months of diagnosis. Doxorubicin is the most, and possibly the only, effective chemotherapeutic drug for this malignancy, but it provides only moderate improvement in survival. On the basis of previous studies reporting similar survival in dogs treated with doxorubicin as a single agent and doxorubicin-based combination chemotherapy and the concept of summation dose intensity, a dose-intensified single-agent doxorubicin protocol was initiated. Twenty dogs with HSA were recruited to participate in this study. Workup and staging were performed according to standard practice. Chemotherapy was initiated within 3 weeks of surgery. Doxorubicin was scheduled to be administered at 30 mg/m2 i.v. every 2 weeks for a total of 5 treatments. The dogs were monitored for toxicity and signs of recurrence during and at regular intervals after chemotherapy. The protocol was tolerated well. No dogs were hospitalized because of adverse effects or developed clinical signs consistent with doxorubicin-induced cardiomyopathy. There was a significant difference in survival in dogs with stage I and I1 HSA compared with dogs with stage III HSA. with median survival times of 257, 210, and 107 days, respectively. These results are slightly better than the historical control with respect to toxicity and efficacy but are not statistically different from what is achieved with standard treatments. There was no association between dose intensity and outcome.

Animals↗

Comparative aspects and clinical outcomes of canine renal hemangiosarcoma.

BACKGROUND: Hemangiosarcoma (HSA) is a common solid tumor of the spleen, heart, and skin of dogs. Renal HSA represents an uncommon anatomic variant, with little reported about its biologic behavior and clinical outcome. HYPOTHESIS: That renal HSA is associated with longer survival than other visceral forms of HSA. ANIMALS: 14 dogs with renal HSA. METHODS: Medical records from 1999 to 2004 were searched for dogs with histopathologically confirmed renal HSA, and data relevant to clinical signs, treatments, and outcomes were abstracted. RESULTS: Clinical signs were nonspecific, and the median duration of clinical signs before diagnosis was 60 days. Two dogs presented in cardiovascular collapse secondary to hemoperitoneum. Common hematologic and biochemical abnormalities were anemia (9/14), hematuria (7/14), and proteinuria (7/14). One dog had pulmonary metastasis at diagnosis. All dogs had evidence of a renal mass visualized by abdominal radiography (14/14), ultrasound (9/14), or both. All dogs underwent nephrectomy, and 4/14 dogs also received adjunctive chemotherapy. Median survival time of all dogs was 278 days (range 0-1,005 days), and dogs with hemoperitoneum had significantly shorter survival times than dogs without hemoperitoneum (62 days versus 286 days, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate that hemoperitoneum and distant metastasis at diagnosis appear to occur less frequently in dogs with renal HSA compared with other visceral forms of HSA. Furthermore, dogs with renal HSA have protracted disease progression, with improved 1-year survival rates and longer median survival time compared to dogs with splenic, cardiac, and retroperitoneal HSA.

Animals↗