Progressive dysphagia in a dog caused by a scirrhous, poorly differentiated perioesophageal carcinoma.

Investigation of canine dysphagia is performed by a combination of diagnostic imaging, direct visualisation of the upper gastrointestinal tract, and ancillary diagnostic testing to differentiate between structural and functional causes. Video fluoroscopy may be especially helpful. The case of a seven-year-old Border collie that presented with a history of progressive pharyngeal dysphagia is described. Fluoroscopic investigation was initially suggestive of functional pharyngeal disease, but magnetic resonance imaging and surgical exploration demonstrated the presence of a diffuse, scirrhous, poorly differentiated carcinoma with extensive oesophageal involvement. This case highlights that, in some circumstances, fluoroscopy may occasionally be of limited use in the investigation of dysphagia in the dog.

Development and biological analysis of peritoneal metastasis mouse models for human scirrhous stomach cancer.

The number of published studies on peritoneal dissemination of scirrhous gastric carcinoma is very small as a result of the unavailability of highly reproducible animal models. Orthotopic implantation of HSC-44PE and HSC-58 (scirrhous gastric carcinoma-derived cell lines) cells into nude mice led to dissemination of the tumor cells to the greater omentum, mesenterium, peritoneum and so on, and caused ascites in a small number of animals. Cycles of isolation of the ascitic tumor cells and orthotopic inoculation of these cells were repeated in turn to animals. This was to isolate highly metastatic cell lines with a strong capability of inducing the formation of ascites (44As3 from HSC-44PE; 58As1 and 58As9 from HSC-58). All three cell lines induced tumor formation at the site of orthotopic injection, and caused fatal cancerous peritonitis and bloody ascites in 90-100% of the animals approximately 3-5 weeks after the inoculation. When the parent cells were implanted, the animals became moribund in approximately 12-18 weeks, however, none of the animals developed ascites. Complementary DNA microarray and immunohistochemical analyses revealed differences in the expression levels of genes coding for the matrix proteinase, cell adhesion, motility, angiogenesis and proliferation between the highly metastatic- and parent-cell lines. The usefulness of this model for the evaluation of drugs was assessed by analyzing the stability of the metastatic potential of the cells and the reproducibility. Animals intravenously treated with CPT-11 and GEM showed suppressed tumor growth and significantly prolonged survival. The metastatic cell lines and the in vivo model established in the present study are expected to serve as a model of cancerous peritonitis developing from primary lesions, and as a useful means of clarifying the pathophysiology of peritoneal dissemination of scirrhous gastric carcinoma and the development of drugs for its treatment.

Establishment of two cell lines from human gastric scirrhous carcinoma that possess the potential to metastasize spontaneously in nude mice.

Few experimental studies have been conducted to clarify the mechanism of development of metastasis in scirrhous carcinoma of the stomach. In the present study, we attempted to establish gastric carcinoma cell lines by incubation of cancer cells collected from the body fluids of patients with gastric cancer. At the same time, xenografting of these cells to nude mice was performed. It was found that, of the gastric carcinoma cell lines thus established, two cell lines, designated as HSC-44PE and HSC-58, formed s.c. tumors with a high infiltrative potential (often invading the lymphatics around the cancer tissue) when implanted. Metastasis to the lymph nodes and lungs was observed in 20-40% of all the animals, indicating that the two cell lines are also capable of metastasizing spontaneously. Through repeated selection, i.e., repeated cycles of removal, culture, and implantation of the HSC cancer cells from metastatic lesions, we obtained 5 subclones of HSC-44PE and HSC-58 (designated as m2509, m2615, m2792, m2917, and m2691), which, when implanted orthotopically, exhibited the following characteristics as compared to the parent cells: (1) a higher percentage take (survival), similar frequency of metastasis, shorter time to metastasis (less than 100 days), and consistent metastasizing potential; (2) a relatively high frequency of metastasis to lymph nodes, including distant metastasis to axillary lymph nodes; (3) the potential to cause occasional bloody ascites; (4) enhanced expression of dysadherin, CD44, and other molecules. This is the first report of cultured scirrhous gastric carcinoma cells showing the potential for spontaneous metastasis.

Scirrhous gastric carcinoma with mediastinal invasion in a dog.

An 8-year-old male Rottweiler was presented for recurrent episodes of dysphagia and vomiting with chronic weight loss. Radiography revealed a mediastinal mass in the heart base region. Necropsy revealed a firm, white mediastinal mass extending along the distal esophagus, through the diaphragm, to the gastric cardia, leftward to the convex visceral aspect of the fundus, and rightward along the lesser curvature of the stomach to the pyloric antrum. The gastric lymph node was enlarged and the omentum contained several nodules. Histologically, deep fundic mucosa contained pleomorphic, vacuolated cells with intracytoplasmic mucin, which was hyaluronidase resistant. Neoplastic cells were cytokeratin positive and vimentin negative. Transmural invasion was evidenced by the presence of cytokeratin-positive cells between smooth muscle bundles of the gastric wall. The mediastinal mass was composed of clusters of neoplastic cells in a stroma of dense and loose connective tissue. Neoplastic cells were also within blood and lymphatic vessels, tracheobronchial and gastric lymph nodes, and around peripheral nerves. This carcinoma most likely arose from the gastric fundus and extended to the cardia, from where it advanced proximally to the mediastinum as well as further rightward along the lesser curvature, demonstrating an anatomic continuity suggestive of a direct invasion. Metastasis, evidenced by the presence of lymphatic, blood, and perineural tumor emboli, also occurred.

Colonic adenocarcinoma in rhesus macaques.

Colon cancer is the second most common cause of cancer mortality in human beings, but relatively few cases have been described in macaques. The present report documents two fatal cases of colon cancer in aged rhesus macaques. Case 1 was a 20-year-old female in which extensive invasion of the caecum by a scirrhous adenocarcinoma led to perforation and a severe fibrinopurulent peritonitis. Case 2 was a 32-year-old male with a stricture at the ileocaecal junction, also caused by a scirrhous adenocarcinoma, which had metastasized to a regional lymph node. Both neoplasms showed aggressive local involvement of the proximal large bowel, which appears to be a predilection site in rhesus monkeys. Descriptions of spontaneous cases of colon cancer in non-human primates may lead to the development of models for certain aspects of the disease in man.

Scirrhous adenocarcinoma of the rectum in a cow.

Clinical and pathological examinations were performed on a 3-year-old Holstein-Friesian cow with scirrhous adenocarcinoma of the rectum. Hemorrhagic diarrhea causing rectal stenosis was a principal clinical manifestation. Microscopically, cancerous transformation of the intestinal epithelium was observed in the rectal crypts. Irregular glandular arrangements containing PAS positive and eosinophilic mucus were observed in the lumen, which were surrounded by scirrhous collagenous fibers. The neoplastic epithelial cell had round or ovoid nucleus and slightly eosinophilic cytoplasm. Metastatic lesions were localized in the marginal and medullary sinuses of the anorectal lymph nodes.

Intracavitary cisplatin chemotherapy experience with six dogs.

Six dogs with a median age of 7 years (range = 5-14 years) were presented for signs referable to thoracic or abdominal effusion associated with neoplasia of the body cavities. Intracavitary cisplatin was administered at 50 mg/m2 every 4 weeks for a median of 2.5 treatments (mean = 3, range = 1-6). Three dogs with pleural mesothelioma had complete resolution of effusion for 289, 129, and greater than 306 days without evidence of tumor growth. Resolution of effusion occurred after one treatment in two dogs and after two treatments in one dog. In three dogs with carcinomatosis of unknown origin, complete responses was seen in two dogs after one treatment for 255 and greater than 807 days, respectively. Intracavitary chemotherapy with cisplatin was associated with palliation and control of malignant pleural and/or abdominal effusion in five of six dogs. Toxicity was minimal, and this method of therapy should be further explored in dogs with similar malignancies.

Extrahepatic biliary carcinoma in sloth bears.

Extrahepatic biliary carcinoma was found in each of 5 adult sloth bears that died between 1970 and 1984 while on exhibit in Ohio zoos. The tumor was characterized by numerous mucin-producing neoplastic glands scattered throughout abundant fibrous stroma. The cause of the tumor was not determined.

A schirrhous anaplastic carcinoma in two dogs resembling mesothelioma.

The clinical, laboratory, radiographic and pathological findings of two dogs with similar neoplasms are described. Both dogs were mature males of a large breed and had pleural and abdominal effusions containing neoplastic cells. Diffuse scirrhous thickening of the pleura and serosal surfaces was a prominent feature. A fibrous layer containing nests of neoplastic, epithelial-like cells was present on serosal surfaces. The morphological appearance of the cells was suggestive of either an atypical sclerosing mesothelioma or a scirrhous carcinoma. On the basis of ultrastructural and differential staining characteristics, a diagnosis of a scirrhous carcinoma of undetermined primary origin was made in one case and of prostatic urethral origin in the other case.