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Neurological signs in a horse due to metastases of an intestinal adenocarcinoma.

A 22-year-old Dutch Warmblood mare was referred to Utrecht University with progressive left hind limb paresis and hyporeflexia. The preliminary clinical diagnosis was the neurological form of equine herpes virus (EHV-1) infection. Within 1 day of admission, the mare became recumbent and deteriorated rapidly. Postmortem examination revealed an adenocarcinoma of the caecum, with metastases in all regional lymph nodes and extending from the lumbar nodes into the vertebral canal, causing spinal cord compression and destruction of the left 4th and 5th lumbar nerves.

Adenocarcinoma↗

Spontaneous internal jugular vein thrombosis: primary manifestation of a colorectal adenocarcinoma in a very old woman.

We report the history of a very old woman with a spontaneous internal jugular vein thrombosis as the presenting feature of an occult adenocarcinoma of the caecum. Spontaneous internal jugular vein thrombosis is an unusual form of venous thrombosis. Doppler ultrasound and Computed Tomography or Magnetic Resonance Imaging should confirm signs and symptoms suggesting thrombosis. Immediate anticoagulation with heparin followed by oral anticoagulation is mandatory to reduce associated mortality and morbidity. If no risk factors for internal jugular vein thrombosis are present, a work-up for hypercoagulable states and a careful search for distant malignancy should been obtained. If screening shows no obvious malignancy, further follow-up is necessary.

Adenocarcinoma↗

Laparoscopic "radical appendectomy" is an effective alternative to endoscopic removal of cecal polyps.

BACKGROUND: The endoscopic removal of cecal polyps can be complicated by hemorrhage, perforation, or incomplete resection. Laparoscopic radical appendectomy represents a safe alternative for the definitive resection and accurate pathologic evaluation of selected cecal polyps. METHODS: Patients with cecal cap polyps not involving the ileocecal valve were candidates for laparoscopic radical appendectomy. Intraoperative colonoscopy and resection of the appendix and cecum to the level of the ileocecal valve were accomplished via three midline ports. For each patient, histologic evaluation by frozen section ruled out malignancy and ensured complete resection. RESULTS: Five patients, four of whom had significant medical comorbidities, presented with large adenomatous polyps contained within the cecum. Each polyp was determined to be unresectable endoscopically; therefore, a laparoscopic radical appendectomy was performed. One patient with cirrhosis also underwent intraoperative liver ultrasonography and biopsies, which contributed to the longest operative time and hospital stay. The histologic diagnosis by frozen section was benign for each patient. The mean operative time was 95 minutes, and the mean length of hospital stay was 1.8 days. No postoperative complications were observed during a mean follow-up of 6 months. CONCLUSION: Laparoscopic "radical appendectomy" is an effective treatment for selected cecal adenomatous polyps. Our ability to resect the polyps completely and avoid a standard right hemicolectomy supports this approach.

Adenomatous Polyps↗

Angiogenesis and growth of murine colon carcinoma are dependent on infiltrating leukocytes.

We determined whether the angiogenesis and growth of murine colon carcinomas growing in the wall of the cecum is dependent on infiltrating leukocytes. Syngeneic BALB/c or SCID mice were treated with a myelosuppressive, maximally tolerated dose of doxorubicin. Parental or multidrug resistant CT-26 colon carcinoma cells were implanted into the cecal wall 3 days after the second intravenous injection of doxorubicin. Control mice developed large, well-vascularized tumors, whereas doxorubicin-pretreated mice did not. Intravenous injection of spleen cells from normal BALB/c or SCID mice one day prior to tumor cell implantation reversed the decreased vascularity and tumorigenicity. The production of proangiogenic molecules and microvessel density in tumors directly correlated with the number of infiltrating leukocytes, suggesting that tumor-infiltrating leukocytes are essential to angiogenesis of murine colon carcinomas.

Animals↗

Inflammatory fibroid polyps of the intestine.

The clinical and pathologic features of 64 inflammatory fibroid polyps of the large and small bowel in 63 patients are reported. Six of the lesions in the small bowel were studied by electron microscopy. Follow-up information was obtained from 39 patients. The lesion was always benign, occurred at all ages, and had a world-wide distribution. The lesions were polypoid, sessile, originated in the submucosa, infiltrated the muscularis propria, and most closely resembled granulation tissue. The principal mesenchymal cell by electron microscopy was the fibroblast. No associated medical conditions were identified and the cause remains unknown.

Adolescent↗

o-Nitrotoluene-induced large intestinal tumors in B6C3F1 mice model human colon cancer in their molecular pathogenesis.

In the previous 500 2-year chemical bioassays within the National Toxicology Program, large intestinal tumors (cecal carcinomas) related to chemical exposure have not been observed in B6C3F1 mice. The recently completed o-nitrotoluene study provided the first cecal tumor response and an opportunity to evaluate the morphology and molecular profile of oncogenes and tumor suppressor genes that are relevant to humans. Morphologically, the carcinomas were gland-forming tumors lined by tall columnar epithelial cells that were positive for cytokeratin 20 and negative for cytokeratin 7. Using immunohistochemistry beta-catenin (encoded by Catnb) protein accumulation was detected in 80% (8/10) of the cecal carcinomas, while increased cyclin D1 and p53 protein expression was detected in 73% (8/11), respectively. There was no difference in adenomatous polyposis protein expression between normal colon and cecal carcinomas. All tumors examined exhibited mutations in exon 2 (corresponds to exon 3 in humans) in the Catnb gene. Mutations in p53 were identified in nine of 11 carcinomas, and all were in exon 7. Analysis of the K-ras gene revealed mutations in 82% (9/11) of carcinomas; all had specific G --> T transversions (Gly --> Val) at codons 10 or 12. The alterations in cancer genes and proteins found in the mouse large intestinal tumors included mutations that activate signal transduction pathways (K-ras and Catnb) and changes that disrupt the cell-cycle and bypass G(1) arrest (p53, cyclin D1). These alterations, which are hallmarks of human colon cancer, probably contributed to the pathogenesis of the large intestinal carcinomas in mice following o-nitrotoluene exposure.

Animals↗

Dietary maltitol decreases the incidence of 1,2-dimethylhydrazine-induced cecum and proximal colon tumors in rats.

Maltitol is fermented in the colon due to only partial hydrolysis in the small intestine. In the present study, we examined effects of dietary maltitol on dimethylhydrazine-induced intestinal tumor in rats. In experiment 1, rats were fed a fiber-free diet or diets supplemented with 1 or 5 g/100 g maltitol for 27 wk. Each group of rats was injected with dimethylhydrazine or vehicle alone for the first 14 wk of the experimental period. Maltitol supplementation at 1 g/100 g of the diet significantly reduced tumor incidence in the cecum and the 5% supplement reduced tumor incidence in both the cecum and proximal colon in dimethylhydrazine-treated rats. In experiment 2, we investigated the effect of the 1 g/100 g maltitol diet on the short chain fatty acid concentrations in cecal contents of placebo and dimethylhydrazine-treated rats. Intake of the 1 g/100 g maltitol diet doubled (P < 0.05) the concentration of butyrate but did not affect acetate or propionate in the cecal contents. These results suggest that dietary maltitol has a protective effect against dimethylhydrazine-induced tumors in rat cecum and proximal colon and that butyrate produced by bacterial fermentation of maltitol in the cecum may be involved in the protection.

1,2-Dimethylhydrazine↗

Murine colon adenocarcinoma: syngeneic orthotopic transplantation and subsequent hepatic metastases.

Syngeneic murine colon adenocarcinoma (MCA-38) cells were transplanted in the submucosa of distal colon, proximal colon, cecum, ileum, jejunum, and duodenum of male C57BL/6 mice, with local lymphoid follicles used as points of entry. The tumor grew best at the cecum and led to liver and mesenteric lymph node metastases in 8 and 9 weeks, respectively, after transplantation. Histologically, a local inflammatory reaction involving polymorphonuclear leukocytes was observed within 48-72 hours following transplantation; after this time, the microscopic tumor foci began to grow progressively. Mononuclear lymphoid cells of the gut-associated lymphoid tissue did not infiltrate the progressively growing tumor; however, polymorphonuclear leukocytes were constantly observed at the tumor periphery in the lamina propria. The studies indicated that orthotopic transplantation as a model system can provide a means of examining the role of the local immune response as a focus of host resistance and as a factor in metastatic tumor spread. The findings also suggested the usefulness of this model in immunotherapeutic and chemotherapeutic studies of secondary hepatic disease.

Adenocarcinoma↗