Ulcerative Colitis: Zeitz M

Stallmach A, Chan CC, Ecker KW, Feifel G, Herbst H, Schuppan D, Zeitz M. · Department of Internal Medicine II, Saarland University, Saar, Germany. · Gut. · Pubmed #10940281 links to  free full text

Abstract: BACKGROUND AND AIMS: Matrix metalloproteinases (MMPs) are implicated in the tissue destruction associated with inflammatory diseases. Proctocolectomy with ileo-anal pouch (IAP) anastomosis is associated with pouchitis, particularly in patients with ulcerative colitis (UC). The aim of this study was to quantify MMP-1 and MMP-2 in inflamed and uninflamed pouches of patients with UC compared with those with active UC. IAP patients with familial adenomatous polyposis (FAP) served as controls. METHODS: Biopsies were taken from 33 patients with IAP (UC, n=25; FAP, n=8) and from 10 UC patients. MMP-1 and MMP-2 were quantified using sandwich enzyme linked immunosorbent assays. In addition, northern and western blotting and in situ hybridisation experiments were performed. RESULTS: In pouchitis (n=11), MMP-1 and MMP-2 concentrations were increased compared with uninflamed pouches of patients with UC (n=14) or FAP (n=8) (MMP-1 17.7 ng/mg protein v 7.8 (UC) v 7.6 (FAP), p</=0.05; MMP-2 16.4 v 9.5 (UC) v 6.3 (FAP), p</=0.05). Western and northern blots revealed increased MMP-1 and MMP-2 protein and transcript concentrations in inflamed pouches. Mesenchymal cells were identified as major producers of MMP-1 and MMP-2 in pouchitis. A similar increase in MMPs was observed in tissues of patients with active UC. CONCLUSIONS: Our results support the hypothesis that MMPs are involved in mucosal destruction and crypt hyperplasia, as seen in pouchitis.

Stallmach A, Moser C, Hero-Gross R, Müller-Molaian I, Ecker KW, Feifel G, Zeitz M. · Department of Internal Medicine II, Saarland University, Homburg, Germany. · Dis Colon Rectum. · Pubmed #10528770 No free full text.

Abstract: PURPOSE: Variant pathological changes have been observed in ileoanal pouches, including inflammation, villous atrophy, and crypt hyperplasia. Therefore, we investigated the type and degree of mucosal adaptation in patients with ulcerative colitis and familial adenomatous polyposis. METHODS: Forty-two patients with ulcerative colitis and 14 patients with familial adenomatous polyposis with ileoanal pouches were assessed. Samples were taken from three months to eight years after creation of an ileoanal pouch. Mucosal architecture was examined by morphometry after microdissection. RESULTS: Structural changes of the mucosa can be categorized into three groups. Compared with preoperative values, patients without pouchitis (73 percent) has only minor decrease of villous length (402 microm vs. 540 microm) and increase in crypt depth (274.5 microm vs. 177 microm). In patients with acute pouchitis (20 percent), a slight increase in villous length (477 microm vs. 402 microm) and pronounced crypt hyperplasia (376 microm vs. 274.5 microm) was observed compared with noninflamed ileoanal pouches. In contrast, in patients with chronic pouchitis (7 percent), severe villous atrophy (62.5 microm) and crypt hyperplasia (543 microm) was found. CONCLUSIONS: Minor structural changes of ileoanal pouch mucosa develop early as an adaptive response to a new environment. Only in a small group of patients with chronic pouchitis does severe villous atrophy and crypt hyperplasia of the ileoanal pouch mucosa develop, most likely as a consequence of mucosal inflammation.

Stallmach A, van Look M, Scheiffele F, Ecker KW, Feifel G, Duchmann R, Zeitz M. · Clinic for Internal Medicine II, Saarland University, Homburg/Saar, Germany. · Int J Colorectal Dis. · Pubmed #10207728 No free full text.

Abstract: Pouchitis is the most significant long-term complication in patients with ileoanal pouch anastomosis (IAP) and is especially frequent in patients with ulcerative colitis. There is an urgent need for simple and objective parameters to assess the presence and activity of pouchitis. Whole-gut lavage fluid (WGLF) was collected from 34 patients [8 with pouchitis (PDAI > or = 7 points) and 26 without pouchitis (Pouchitis Disease Activity Index, PDAI, < 7)]. Patients with active ulcerative colitis (n = 8) served as controls. Concentrations of IgG and sCD44 in WGLF were measured by enzyme-linked immunosorbent assays and those of albumin by immunoturbidimetry. Similar to the case in active ulcerative colitis, concentrations of IgG, albumin, and sCD44 in WGLF were significantly increased in acute pouchitis and reached high specificity (IgG 96%, albumin 96%, sCD44 100%) and acceptable sensitivity (75%) for the diagnosis of acute pouchitis. These parameters were also closely correlated with disease activity as determined by PDAI and endoscopic scoring indices. Assay of protein concentrations in WGLF is thus a simple and objective means for grading inflammation of the pouch and may be useful as a quantitative index of disease activity in clinical studies.