Ulcerative Colitis: Hop WC

Gosselink MP, Schouten WR, van Lieshout LM, Hop WC, Laman JD, Ruseler-van Embden JG. · Colorectal Research Group of the Department of Surgery, Erasmus MC, Rotterdam, The Netherlands. · Dis Colon Rectum. · Pubmed #15486751 No free full text.

Abstract: PURPOSE: Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Metronidazole and ciprofloxacin are commonly used for treatment; however, nothing is known about the effects on the pouch flora during and after pouchitis episodes. This study was designed to evaluate the effect of both antibiotics on eradication of pathogens and the restoration of normal pouch flora. METHODS: The fecal flora obtained from 13 patients with ulcerative colitis was examined at the beginning of a pouchitis episode before treatment, during treatment with metronidazole or ciprofloxacin, and during pouchitis-free periods. Some patients experienced more than one pouchitis episode. Therefore, a total of 104 samples was obtained. Each sample was cultured under aerobic and anaerobic conditions and the isolated bacteria were identified. Furthermore, the clinical response to both antibiotics was compared using the Pouchitis Disease Activity Index score. RESULTS: During pouchitis-free periods, the patients had a flora characterized by high numbers of anaerobes and no or low numbers of pathogens. This flora resembles normal colon flora. During pouchitis episodes, we found a significant decrease of anaerobes ( P = 0.01), a significant increase of aerobic bacteria ( P = 0.01), and significantly more numbers of pathogens, such as Clostridium perfringens (in 95 percent of the samples; P < 0.01) and hemolytic strains of Escherichia coli (in 57 percent of the samples; P = 0.05). Treatment with metronidazole resulted in a complete eradication of the anaerobic flora, including C. perfringens. However, no changes in the numbers of E. coli were found. In contrast, when the patient was treated with ciprofloxacin, not only C. perfringens, but also all coliforms including hemolytic strains of E. coli disappeared. The larger part of the anaerobic flora was left undisturbed during the administration of ciprofloxacin. Patients treated with ciprofloxacin experienced significant larger reductions in Pouchitis Disease Activity Index score compared with patients treated with metronidazole ( P = 0.04). CONCLUSIONS: This study strongly suggests a role of pathogenic bacteria ( C. perfringens and/or hemolytic strains of E. coli) in pouchitis. From a microbiologic and a clinical point of view, ciprofloxacin is preferable to metronidazole, because treatment with ciprofloxacin eradicates both pathogens and results in an optimal restoration of normal pouch flora.

Vleggaar FP, van Buuren HR, van Berge Henegouwen GP, Hop WC, van Erpecum KJ. · Department of Hepatology and Gastroenterology, University Hospital, Rotterdam, The Netherlands. · Eur J Gastroenterol Hepatol. · Pubmed #11246617 No free full text.

Abstract: BACKGROUND/AIMS: Smoking is associated with a decreased risk of primary sclerosing cholangitis. We aimed to explore the therapeutic efficacy of and tolerance for transdermal nicotine treatment in this disease. METHODS: Twelve patients (11 males; 37 +/- 6 years; six with ulcerative colitis) who did not achieve complete biochemical remission on ursodeoxycholic acid (14 mg/ kg/day) were treated in a randomized cross-over trial with transdermal nicotine (15 mg/day) or a placebo, each for 8 weeks (4-week washout period between treatments). RESULTS: One patient developed de novo ulcerative colitis and two did not complete the entire protocol because of intercurrent bacterial cholangitis. Baseline values [mean (range)] were: bilirubin, 1.3 (0.5-2.6); alkaline phosphatase (APh), 2.5 (1.4-4.7); gamma-glutamyl transpeptidase (gammaGT), 7.7 (0.7-38); aspartate aminotransferase (AST), 1.9 (0.5-3.2); alanine aminotransferase (ALT), 2.4 (0.4-7.3); and bile salts, 10.9 (2.1 -39) times the upper limit of normal. No significant effect on pruritus or fatigue was noted during either period, but a small increase in bodyweight was observed during placebo treatment. No significant differences were observed between the two treatment modalities after 8 weeks in bilirubin (nicotine versus placebo, +13% versus -6% change from baseline), APh (-3% versus -17%), gammaGT (-11% versus -13%), AST (+2% versus -10%), ALT (-1% versus -11%) or bile salts (+36% versus -3%). CONCLUSION: Transdermal nicotine does not seem to have a clear short-term beneficial effect in primary sclerosing cholangitis treated with ursodeoxycholic acid.

Damen GM, Hol J, de Ruiter L, Bouquet J, Sinaasappel M, van der Woude J, Laman JD, Hop WC, Büller HA, Escher JC, Nieuwenhuis EE. · Department of Pediatric Gastroenterology and Laboratory of Pediatrics, Erasmus MC-Sophia Children's Hospital, University Medical Center, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. · J Pediatr Gastroenterol Nutr. · Pubmed #16456405 No free full text.

Abstract: OBJECTIVES: Inflammatory bowel diseases (IBD) represent an aberrant immune response by the mucosal immune system to luminal bacteria. Because the oral mucosa harbors the first epithelial cells that interact with microorganisms, we assessed the immunologic activity of buccal epithelium in children with IBD and adults with Crohn disease. METHODS: Buccal epithelial cells were obtained from 17 children and 14 adults with Crohn disease, 18 children with ulcerative colitis, and 40 controls. Cells were cultured with and without microbial stimulation. Chemokine levels were determined in culture supernatants by cytometric bead array and enzyme-linked immunoabsorbent assay. CXCL-8 production was studied by immunohistochemical analysis of these cells. CXCL-8 production by lipopolysaccharide stimulated monocyte-derived dendritic cells from these patients was determined. RESULTS: Compared with controls, pediatric ulcerative colitis patients, and adult Crohn disease patients, only in children with Crohn disease did buccal epithelial cells exhibit enhanced production of CXCL-8, CXCL-9, and CXCL-10. In vitro stimulation with lipopolysaccharide or zymosan resulted in a further increase of chemokine levels only in cells from pediatric Crohn disease patients. CXCL-8 production by stimulated monocyte-derived dendritic cells from children with Crohn disease was equal to that of children with ulcerative colitis. CONCLUSIONS: Buccal epithelium of children with Crohn disease is immunologically active, even in the absence of oral lesions. The enhanced chemokine production is associated with pediatric Crohn disease and appears restricted to cells derived from the epithelial barrier. Assessment of chemokine production by buccal epithelial cells may become a new, rapid, noninvasive test for screening and classification of IBD in children.

Gosselink MP, Schouten WR, van Lieshout LM, Hop WC, Laman JD, Ruseler-van Embden JG. · Department of Surgery, Erasmus MC, Rotterdam, The Netherlands. · Dis Colon Rectum. · Pubmed #15108026 No free full text.

Abstract: PURPOSE: Proctocolectomy with ileal pouch-anal anastomosis is the operation of choice for patients with refractory or fulminant ulcerative colitis. The most common long-term complication in these patients is pouchitis. This study was designed to investigate the efficacy of probiotic Lactobacillus rhamnosus GG in long-term delaying the first onset of pouchitis. METHODS: Between 1989 and 2001, a consecutive series of 127 patients presenting with ulcerative colitis underwent an ileal pouch-anal anastomosis at the Erasmus Medical Center in Rotterdam. Histopathologic investigation of the resected specimens revealed unsuspected Crohn's disease in five patients. Postoperative complications resulted in pouch excision in five patients. The remaining 117 patients were included in this study. All episodes of pouchitis occurring in this group were analyzed. Pouchitis was diagnosed on the basis of clinical symptoms and endoscopic and histologic features. The 39 patients, who underwent an ileal pouch-anal anastomosis between 1996 and 2001, started immediately after the operation with the daily intake of L. rhamnosus GG in a fermented product. The 78 patients, in whom an ileal pouch-anal anastomosis was performed between 1989 and 1996, received no L. rhamnosus GG. RESULTS: Except for the duration of follow-up, the patient characteristics, indications for proctocolectomy, number of postoperative complications, and functional outcome were similar in both groups. First episodes of pouchitis were observed less frequently in patients with a daily intake of L. rhamnosus GG (cumulative risk at 3 years: 7 vs. 29 percent; P = 0.011). CONCLUSIONS: Daily intake of fermented products containing L. rhamnosus GG provides significant clinical benefit, without side effects. Based on the results of this study, we recommend a daily intake of Lactobacillus rhamnosus GG (dose 1-2 x 10(10) bacteria) to delay the first onset of pouchitis.