Ulcerative Colitis: Svrcek M

Svrcek M, Tiret E, Bennis M, Guyot P, Fléjou JF. · Service d'Anatomie et Cytologie Pathologiques, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France. · Dis Colon Rectum. · Pubmed #19273971 No free full text.

Abstract: Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), has been identified in all four forms of Kaposi's sarcoma (classic, endemic, HIV-associated and iatrogenic). We report the rare case of an intestinal (small intestine and rectosigmoid) Kaposi's sarcoma in a 62-year-old HIV-negative man with ulcerative colitis. This patient was receiving immunosuppressive therapy with steroids and azathioprine. To date, the causative role of KSHV/HHV8 in the pathophysiology of Kaposi's sarcoma associated with ulcerative colitis has only been proven for cutaneous lesions but not for intestinal lesions of Kaposi's sarcoma. We report for the first time, the expression of HHV8 (by using immunohistochemistry) in colonic Kaposi's sarcoma in a patient with an ulcerative colitis-related tumor. The patient underwent a total proctocolectomy. At laparotomy, numerous Kaposi's sarcoma lesions were found in the small intestine, which were left in situ. Forty months after surgery and following withdrawal of immunosuppressive therapy, the patient had no evidence of any disease and a normal abdominal and thoracic CT scan. Cases of colorectal Kaposi's sarcoma complicating inflammatory bowel disease should be managed with a conservative approach and discontinuation of the immunosuppressive treatment. However, discontinuation of the immunosuppression is not always possible and in those cases chemotherapy may be indicated.

Grijelmo C, Rodrigue C, Svrcek M, Bruyneel E, Hendrix A, de Wever O, Gespach C. · INSERM U673 and Université Pierre et Marie Curie-Paris 6, Molecular and Clinical Oncology of Solid Tumors, Hôpital Saint-Antoine, 75571 Paris Cedex 12, France. · Cell Signal. · Pubmed #17478078 No free full text.

Abstract: Recent data indicate that the Bone Morphogenetic Protein BMP-7 exhibits mucosal protection against experimental colitis in rats, suggesting that this cytokine exerts direct actions in intestinal epithelial cells during inflammatory bowel diseases and other precancerous lesions of the colon. In this study, we investigated the functional expression of BMP-7 and its receptors in normal human colon crypts, aberrant crypt foci (ACF) in sigmoiditis and colorectal tumors, and their derived cancer cell lines. Transcripts encoding BMP-7 receptors type II (BMPRII, ActRII, ActRIIB) and type I (ALK-2) were clearly detected by RT-PCR in several premalignant and carcinoma cell lines. The cytokine was identified by immunohistochemistry in surface epithelial cells and crypts in the normal colon mucosa, ACF in sigmoiditis, sporadic high grade dysplastic adenoma, and in 9 of 16 colon carcinomas (56.2%). In addition, the conditioned medium collected from the adenoma PC/AA/C1 and carcinoma HCT8/S11 and SW48 cell lines in culture contained significant levels of BMP-7 ranging from 0.17 to 0.38 ng/ml. We found that BMP-7 induced scattering and proinvasive responses (EC50=1 ng/ml) in kidney and colon cancer cell lines through SMAD4 and src -independent pathways and signaling cascades using FAK phosphorylation at Y925 and activation of ERK1/2, Rac1 and JNK. This phosphorylation of FAK on Y925 was also induced by the proinvasive agent EGF. Taken together, our findings suggest that BMP-7 exerts divergent effects in the colon mucosa, one counteracting transient inflammatory situations and the other linked to pejorative functions during chronic ulcerative diseases and the neoplastic progression.

Svrcek M, Cosnes J, Beaugerie L, Parc R, Bennis M, Tiret E, Fléjou JF. · AP-HP Hôpital Saint-Antoine, Service d'Anatomie et Cytologie Pathlogiques, Université Paris, Faculté de Médecine Pierre et Marie Curie, Paris, France. · Histopathology. · Pubmed #17394493 No free full text.

Abstract: AIMS: To determine the clinicopathological features of colorectal cancer (CRC) in Crohn's disease (CD). METHODS AND RESULTS: All histological slides from surgical specimens with inflammatory bowel disease-related colorectal neoplasia examined in our hospital between 1990 and 2005 were reviewed. We identified 18 CRCs in 16 patients with CD and compared them with 57 CRCs in 41 patients with ulcerative colitis (UC). We also studied 25 patients with dysplasia without cancer (CD 2, UC 23). When CD and UC were compared, the median age at diagnosis of cancer (CD 52 years, UC 51 years), the frequency of mucinous adenocarcinoma (CD 16.7%, UC 17.5%) and the frequency of dysplasia adjacent to and distal from cancer (CD 56.3 and 37.5%, UC 65.8 and 39%, respectively) were similar. All neoplastic lesions occurred in areas affected by inflammatory bowel disease. CONCLUSIONS: CRC complicating CD and UC shares many clinicopathological features, in particular similar frequencies of dysplasia, both adjacent and distal, with cancer. Thus, surveillance for patients with Crohn's colitis should be similar to that for patients with UC. Consideration should be given to a more extensive UC-like surgical approach instead of segmental resection of the involved area.