No abstract

Ulcerative colitis (UC) and, to a lesser extent, Crohn's disease (CD) are associated with a reduction of the protective mucus layer in the large intestine; the role of this alteration in the pathogenesis of either disease is, however, not clear. To learn more about the molecular mechanism of the alteration of the mucus layer, the expression of the main intestinal mucin, MUC2, was investigated in relation to inflammation and dysplasia. Formalin‐fixed, paraffin‐embedded biopsies from 70 patients with UC and 16 patients with CD, and 13 biopsies from normal colonic mucosa, were used for detection of MUC2 mRNA by in situ hybridization with the SMUC41 probe, and MUC2 protein by immunohistochemistry with the antibody CCP58. The steady‐state concentration of MUC2 mRNA was not affected by UC or CD. By contrast, the amount of the detectable MUC2 protein, assessed as the immunoreactive score (IRS), was significantly (p < 0·0001) increased in UC (IRS = 8·0 ± 3·8) and CD (8·0 ± 3·7), compared with the normal colonic mucosa (IRS = 2·0 ± 1·5). This alteration occurred in the inactive phase of inflammation and persisted in the active phase of the disease. It was also observed during bacterial or protozoal inflammation (n = 7). The IRS values did not correlate with the grade of inflammation or dysplasia. Simultaneous histochemistry with high iron diamine and immunohistochemistry indicated that the increase of detectable MUC2 is concomitant with low mucin sulphation in the same cells. These data indicate that the strong MUC2 protein staining in colonic mucosa of patients with UC or CD is due to a long‐term alteration of the post‐transcriptional modification of the MUC2 molecule, leading to its better detectability by the anti‐MUC2 antibody CCP58. This alteration, induced by the inflammatory process, may affect the gel thickness and may contribute to a protracted autoimmune response. Copyright © 1999 John Wiley & Sons, Ltd.

Epstein-Barr virus (EBV) is associated with several lymphoid and epithelial human malignancies. The latter include gastric adenocarcinomas, while sporadic colorectal adenocarcinomas (CRCs) have been reported to be EBV-negative. Recently, increased numbers of EBV-infected B lymphocytes have been detected in intestinal mucosal samples affected by ulcerative colitis (UC) and, to a lesser extent, Crohn's disease (CD). Both CRC and colorectal non-Hodgkin's lymphoma (NHL) are recognized complications of inflammatory bowel disease (IBD), but it is unclear to what extent EBV contributes to the development of these neoplasms. Seventeen cases of IBD-associated CRC and nine cases of IBD-associated colorectal NHL were therefore studied for the presence of EBV by in situ hybridization. EBV-positive cases were further studied for the expression of the EBV-encoded nuclear antigen (EBNA) 2 and the latent membrane protein (LMP) 1 of EBV by immunohistochemistry. Four out of seven cases of colorectal NHL associated with UC were shown to be EBV-positive. In addition, two of two colorectal NHLs developing in patients with CD were EBV-positive. Of the EBV-positive lymphomas, three displayed a pattern of EBV latent gene expression consistent with type I latency (EBNA2(-)/LMP1(-)), two a type II pattern (EBNA2(-)/LMP1(+)), and one a type III pattern (EBNA2(+)/LMP1(+)). These findings suggest that EBV infection is involved in the pathogenesis of a proportion of colorectal NHLs developing in IBD. Iatrogenic immunosuppression may contribute to the development of these lymphomas. By contrast, all 17 IBD-associated CRCs were EBV-negative, including a case of CRC occurring synchronously with an EBV-positive NHL. In conjunction with previous reports on sporadic CRCs, this suggests that EBV is not involved in the pathogenesis of CRC.

On the basis of 3 of our own cases, we describe unusually intense forms of filiform polyposis and local giant polyposis as a consequence of chronic inflammatory bowel disease. The patients are: A 52-year-old woman who for 7 years has been known to have Crohn's disease (CD); a 55-year-old man who for 14 years has been known to have chronic inflammatory bowel disease, which was first thought to have been ulcerative colitis, but, as a result of the findings on the subtotal colectomy specimen, had to be classified as Crohn's disease or colitis indeterminate; and a 53-year-old woman known to have had ulcerative colitis for 37 years. From the literature on the subject, we drew up a chronological list of a total of 43 cases with similar or completely identical findings. The clinical significance of the findings in their particularly massive intensity results from their necessary differentiation--in the context of differential diagnosis--from a malignant tumor, in particular from a carcinoma in association with chronic inflammatory bowel disease, or from a villous adenoma. The indication of a need to operate results from the impossibility of being able definitely to rule out a malignant degeneration by means of clinical methods. Also, experience shows that with massive findings of the kind described a spontaneous disappearance cannot be expected. Finally, too, the clinical symptoms and the patients subjective complaints necessitate balanced surgical treatment, taking into consideration the site and the extent of the lesion.

HIV-associated malignant lymphomas are a common complication in late HIV infection, and there is a high percentage of gastrointestinal tract involvement. Non-Hodgkin’s lymphoma was found in 108 of 2,750 HIV-positive patients (3.9%) in our institution, whereas gastrointestinal manifestation was diagnosed in 48 of 108 patients (44.4%). 44 of these cases were found during endoscopy of the upper and lower gastrointestinal tract (or by laparotomy or laparoscopy in 4 cases). Endoscopy is a reliable procedure for the diagnosis of lymphoma. Unusual manifestations such as oral, esophageal or perianal lesions and multifocal disease were common findings. Life-threatening complications such as gastrointestinal bleeding, perforation, and obstruction occurred in 37.5%. High-grade B-cell lymphomas were found in all cases including mainly lymphoblastic, immunoblastic, centroblastic and Burkitt subtypes. 52% of the patients had disseminated lymphoma with Ann Arbor stage III or IV. Standard chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisone was started in 25 patients and resulted in a mean survival time of 4.8 months. The prognosis of AIDS patients presenting with malignant gastrointestinal lymphoma depends mainly on the presence or absence of previous AIDS-defining diseases, not CD4 cells, lymphoma-associ-ated gastrointestinal complications or the histopathologic lymphoma type at the time of diagnosis.