Ulcerative Colitis: Ecker KW

Hammond A, Andus T, Gierend M, Ecker KW, Scholmerich J, Herfarth H, Anonymous00088. · Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. · Hepatogastroenterology. · Pubmed #15362749 No free full text.

Abstract: BACKGROUND/AIMS: There is evidence of a higher quality of life with foams as compared with enemas. The purpose of this study was to assess the effect of treatment with budesonide foam or betamethasone enema on the quality of life and the clinical outcome in patients with distal ulcerative colitis. METHODOLOGY: In an open multicenter trial, patients with active distal ulcerative colitis were randomized to receive 2 mg/50 mL budesonide foam or 5 mg/100 mL betamethasone enema. Primary outcome variable was the change in the mean Life Quality Index. Therapeutic efficacy was determined by clinical activity, endoscopical and histological indices. RESULTS: 38 patients were included in the study. The decrease of the mean Life Quality Index was more pronounced in the budesonide group. No significant difference in the efficacy of treatment was observed for both groups. Betamethasone suppressed the plasma cortisol level in the majority of the patients (87%) compared to only 22% of the patients receiving budesonide. CONCLUSIONS: The quality of life is not significantly different in patients during treatment with budesonide foam or betamethasone enema for active distal ulcerative colitis. However, while having comparable clinical efficacy budesonide foam has less effect on the plasma cortisol level thus potentially minimizing steroid side effects.

Jüngling B, Kindermann I, Moser C, Püschel W, Ecker KW, Schäfers HJ, Böhm M, Zeuzem S, Giese T, Stallmach A. · Department of Internal Medicine II, Saarland University, Germany. · Z Gastroenterol. · Pubmed #15700214 No free full text.

Abstract: BACKGROUND: Cardiac transplantation has become an accepted treatment modality for end-stage heart failure. Immunosuppressive agents, which are used after transplantation, are considered as therapeutic options for inflammatory bowel disease. CASE REPORT: We report on a 53-year-old patient who was treated for 2 years with cyclosporine A, azathioprine and prednisolone after heart transplantation. He developed a distal colitis with all features of ulcerative colitis. An infectious or ischemic etiology was carefully excluded. In spite of high-dose treatment with prednisolone the patient's abdominal symptoms worsened and he developed a progression of the inflammation in the entire colon and a colectomy with ileostomy was necessary. The histology was consistent with ulcerative colitis. After colectomy he recovered and remained in a good state of health. CONCLUSIONS: This report supports the concept that new onset inflammatory bowel disease can develop in a heart transplantation recipient in spite of immunosuppression.

Stallmach A, Marth T, Adrian N, Wittig BM, Ecker KW, Schilling M, Zeitz M. · Department of Internal Medicine II, Saarland University, 66421 Homburg, Germany. · Int J Colorectal Dis. · Pubmed #12172923 No free full text.

Abstract: BACKGROUND AND AIMS: Since interleukin-12 is pathogenetically involved in Crohn's disease (CD) but not in ulcerative colitis (UC), expression and mechanisms of induction of interleukin-12 receptor (IL-12R) subunits beta(1) and beta(2) were analyzed in lamina propria mononuclear cells (LPMNC) of patients with CD and UC. PATIENTS AND METHODS: LPMNC from patients with CD ( n=17), UC ( n=14), and controls ( n=19) were isolated by standard techniques. IL-12R beta(1) and IL-12R beta(2) transcripts were semiquantified by RT-PCR, and expression of IL-12R beta(2) chain was characterized by flow cytometry. LPMNC were activated by cross-linking with anti-CD3 antibodies and B7-1 costimulation. RESULTS: IL-12R beta(1) and IL-12R beta(2) transcript concentrations were higher in inflamed specimens than in noninflamed segments of patients with CD but not in UC. Increased percentage of mucosal CD4(+)/IL-12R beta(2)(+) cells was observed in active CD, but not UC. In vitro stimulation of LPMNC with anti-CD3 antibodies resulted in an increase in IL-12R beta(1) transcripts irrespective of B7-1 mediated costimulation (84% and 95%, respectively). However, increased expression of IL-12R beta(2) mRNA (110%) was detected only after B7-1 costimulation. CONCLUSION: Our data indicate that increased mucosal expression of IL-12R beta(2) on LPMNC in CD but not in UC may be the result of B7-1 costimulation. Modulation or inhibition of IL-12R beta(2) expression on LPMNC could provide a selective therapeutic approach in CD.

Pfister K, Wittig BM, Jüngling B, Ecker KW, Barth S, Huhn M, Sasse S, Engert A, Mueller-Molaian I, Diehl V, Zeitz M, Stallmach A. · Department of Internal Medicine II, Saarland University, Homburg/Saar, Germany. · Int J Colorectal Dis. · Pubmed #12014425 No free full text.

Abstract: BACKGROUND AND AIMS: In chronic inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis an aberrant mucosal immune regulation is observed accompanied by upregulation of proinflammatory cytokines. Lamina propria T cells of inflamed mucosa have an activated phenotype characterized by increased expression of surface markers such as CD25. We therefore determined the anti-inflammatory effect of a recombinant immunotoxin consisting of an anti-CD25 single chain variable fragment (scFv) fused to a deletion mutant of Pseudomonas exotoxin A [RFT5(scFv)ETA'] on isolated lamina propria lymphocytes of patients with IBD and in the murine model of trinitrobenzene sulfonic acid (TNBS) induced colitis. PATIENTS AND/METHODS: Lamina propria lymphocytes of 25 patients with IBD and 19 control patients were stimulated in absence or presence of RFT5(scFv)ETA'. Interferon-gamma production was determined in the supernatant by ELISA and the induction of apoptosis by flow cytometry after propidium iodide staining. BALB/c mice received TNBS intrarectally and were treated with RFT5(scFv)ETA'. RESULTS: In vitro the administration of RFT5(scFv)ETA' significantly reduced interferon-gamma production and increased apoptosis in lamina propria lymphocytes isolated of inflamed mucosa. However, this contrainflammatory regulation did not result in gain of weight or increased life span in experimental colitis in vivo. CONCLUSION: In addition to the downregulation of the proinflammatory cytokine in vitro, RFT5(scFv)ETA' induced neither a direct nor a bystander effect in an in vivo model of colitis. Therefore our data do not support potential therapeutic implications of targeting CD25 by RFT5(scFv)ETA' in chronic IBD.

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.

Ecker KW. · Abteilung für Allgemeine Chirurgie, Abdominal- und Gefässchirurgie, Chirurgische Universitätsklinik, Homburg/Saar. · Chirurg. · Pubmed #10427449 No free full text.

Abstract: Over a period of 12 years, 73 patients received a continent ileostomy. 19 Kock pouches were primarily constructed due to contraindications against the ileoanal pouch, 30 ileostomies were converted due to psychological rejection of the incontinent stoma and 9 ileoanal pouches for dysfunction. 15 Kock pouches had to be corrected for nipple valve complications. Perioperative complications (14/73) were related to the Kock pouch in only one third of cases. Surgical late complications of the nipple valve function decreased with technical modifications from 41.1% to 20.0% and then to 4.8%. They could always be dealt with surgically. Pouchitis was observed in 26.8% of cases of ulcerative colitis (11/41), and in 6/15 patients with Crohn's disease (40.0%) complicated ileal recurrences developed. The definitive rate of success over the time was 98.1% in ulcerative colitis and familial adenomatous polyposis (53/54) and 63.2% in other conditions (12/19). Continent ileostomy has become universal and safe method for conversion of any previous operation.

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.