Antibiotic combination therapy in patients with chronic, treatment-resistant pouchitis.
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BACKGROUND: Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. About 15% of patients have a chronic, treatment-resistant disease. AIMS: To evaluate the efficacy of an antibiotic combination for chronic active, treatment-resistant pouchitis. PATIENTS AND METHODS: Eighteen patients were treated orally with rifaximin 1 g b.d. + ciprofloxacin 500 mg b.d. for 15 days. Symptoms assessment, endoscopic and histological evaluations were performed at screening and after 15 days using the Pouchitis Disease Activity Index (PDAI). Improvement was defined as a decrease of at least 3 points in PDAI score, and remission as a PDAI score of 0. Systemic absorption of rifaximin was determined by high performance liquid chromatography. Faecal samples were collected before and after antibiotic treatment for stool culture. RESULTS: Sixteen out of 18 patients (88.8%) either improved (n=10) or went into remission (n=6); the median PDAI scores before and after therapy were 11 (range 9-17) and 4 (range 0-16), respectively (P < 0.002). No side-effects were reported. Rifaximin plasma levels and urinary excretion were negligible, confirming its mainly topical activity. A significant decrease in total anaerobes and aerobes, enterococci, lactobacilli, bifidobacteria and bacteroides in faecal samples was observed, while the reduction in number of coliforms and Clostridium perfringens did not reach a statistical significance. CONCLUSIONS: A combination of rifaximin and ciprofloxacin was effective in patients with active chronic, treatment-resistant pouchitis, suggesting the need, in these patients, for treatment using antibiotic agents with wide antibacterial spectrum of activity. (+info)
Ileoanal anastomosis with reservoirs: complications and long-term results.
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OBJECTIVE: To determine the rate of complications of ileoanal pouch anastomosis, their treatment and their influence on a successful outcome. DESIGN: A computerized database and chart review. SETTING: Three academic tertiary care health centres. PATIENTS: All 239 patients admitted for surgery between 1981 and 1994 with a diagnosis of ulcerative colitis and familial adenomatosis coli. INTERVENTIONS: Sphincter-saving total proctocolectomy and construction of either S-type of J-type ileoanal reservoir. OUTCOME MEASURES: Indications, early and late complications, incidence of pouch excision. RESULTS: Of the 239 patients, 228 (95.4%) were operated on for ulcerative colitis and 11 (4.6%) for familial polyposis coli. One patient in each group was found to have a carcinoma not previously diagnosed. Twenty-eight patients had poor results: in 17 (7.1%) the ileostomy was never closed or was re-established because of pelvic sepsis or complex fistulas, sclerosing cholangitis or severe diarrhea; 11 (4.6%) patients required excision of the pouch because of anal stenosis, perirectal abscess-fistula or rectovaginal fistula. Three patients died--of suicide, and complications of liver transplantation and HIV infection. Thus, 208 patients maintained a functioning pouch. The early complication rate (within 30 days of operation) was 57.7% (138 patients) and the late complication rate was 52.3% (125 patients). Pouchitis alone did not lead to failure or pouch excision. Emptying difficulties in 25 patients with anal stenosis were helped in 2 by resorting to intermittent catheterization. Patients with indeterminate colitis had a higher rate of anorectal septic complications, and all patients having Crohn's disease after pouch construction had complicated courses. CONCLUSIONS: The complication rate associated with ileoanal pouch anastomosis continues to be relatively high despite increasing experience with this technique. Overall, however, a satisfactory outcome was obtained in 87% of patients. (+info)
Pouchitis: extracolonic manifestation of ulcerative colitis?
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Pouchitis is the most frequent complication of ileal pouch-anal anastomosis for treatment of ulcerative colitis. There are several possible explanations. Among them, we focus on the one that considers pouchitis as an extracolonic manifestation of ulcerative colitis. The aim of this study was to investigate the association between pouchitis and extra-intestinal manifestations (EIM), which are frequent in these patients. Sixty patients underwent restorative proctocolectomy with an ileal J pouch (IPAA) from September 1984 to December 1998. Pouchitis was defined by clinical, endoscopic, and histologic criteria. The following extra-intestinal manifestations were studied: articular, cutaneous, hepatobiliary, ocular, genitourinary, and growth failure. Thirteen patients, of which 10 were female (76.9%), developed one or more episodes of pouchitis. Twelve patients of this group (92.3%) presented some kind of extra-intestinal manifestation, 4 pre-operatively (exclusively), 2 post-operatively (exclusively), and 6 both pre- and post-operatively (1.7 per patient). Twenty patients (42.7%) of the 47 without pouchitis did not present extra-intestinal manifestations; 10/35 (28. 5%) of females had pouchitis, compared to 3/35 (12.0%) of men. Pouchitis was more frequent among females, though not statistically significant. EIM increases the risk of pouchitis. Pouchitis is related to EIM in 92.3 % of cases, corroborating the hypothesis that it could be an extracolonic manifestation of ulcerative colitis. (+info)
Comparable expression of matrix metalloproteinases 1 and 2 in pouchitis and ulcerative colitis.
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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+info)
Activation of signal-transducer and activator of transcription 1 (STAT1) in pouchitis.
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Activation of signal transducer and activator of transcription 1 (STAT1) is a hallmark of IFN-gamma receptor signal transduction but is also part of the signalling pathway of other cytokines/growth factor receptors. In ulcerative colitis, high levels of activation and expression of STAT1 have been observed in comparison with both Crohn's Disease and normal controls. Pouchitis develops in some patients after Ileal-Pouch-Anal-Anastomosis (IPAA). The pathophysiology and aetiology of pouchitis is still unclear. Recent studies have shown an increased production of proinflammatory cytokines including IFN-gamma. To investigate the expression and activation of STAT1 in pouchitis and the influence of treatment, patients were followed longitudinally from pouch operation. Diagnosis of pouchitis was made by clinical, endoscopic and histological criteria. Biopsies were obtained during routine endoscopy and snap frozen in liquid nitrogen. Nuclear and cytosolic extracts were prepared and the expression and activation of specific transcription factors were assessed by Western blot, electrophoretic mobility shift assay and immunofluorescence. Patients who develop pouchitis show highly increased levels of STAT1 alpha as well as STAT1 beta expression and activation in comparison with both normal pouch and normal ileal mucosa. Improvement of pouchitis during antibiotic therapy relates to a normalization of STAT1 expression and activation. We conclude that activation of STAT1 correlates to clinical disease activity and therefore STAT1 could play an important role in the pathophysiology of pouchitis. Similarities in the pattern of activation of STAT1 in pouchitis and ulcerative colitis may suggest a common pathway in the immunopathophysiology of both diseases. (+info)
Functional results and visceral perception after ileo neo-rectal anastomosis in patients: a pilot study.
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INTRODUCTION: To reduce pouch related complications after restorative proctocolectomy, an alternative procedure was developed, the ileo neo-rectal anastomosis (INRA). This technique consists of rectal mucosa replacement by ileal mucosa and straight ileorectal anastomosis. Our study provides a detailed description of the functional results after INRA. PATIENTS AND METHODS: Eleven patients underwent an INRA procedure with a temporary ileostomy. Anorectal function tests were performed two months prior to and six and 12 months after closure of the ileostomy and comprised: anal manometry, ultrasound examination, rectal balloon distension, and transmucosal electrical nerve stimulation (TENS). Function was subsequently related to the histopathology of rectal biopsy samples. RESULTS: Median stool frequency decreased from 15/24 hours (10-25) to 6/24 hours (4-11) at one year. All patients reported full continence. Anal sensibility, and resting and squeeze pressures did not change after INRA. Rectal compliance decreased (2.1 (0.7-2.8) v 1.5 (0.4-2.2) and 1.4 (0.8-3.7) ml/mm Hg (p=0.03)) but the maximum tolerated volume increased (70 (50-118) v 96 (39-176) (NS) and 122 (56-185) ml (p=0.03)). Decreasing rectal sensitivity was found: the maximum tolerated pressure increased (14 (8-24) v 22 (8-34) (NS) and 26 (14-40) (p=0.02)) and the rectal threshold for TENS displayed a similar tendency. All patients displayed a low grade chronic inflammatory infiltrate in neorectal biopsy samples before closure of the ileostomy, with no change during follow up. CONCLUSIONS: The technique of INRA provides a safe alternative for restorative surgery. Stool frequency after INRA improves with time and seems to be related to decreasing sensitivity and not to histopathological changes in the neorectum. Furthermore, after the INRA procedure, all patients reported full continence. (+info)
Ulcer associated cell lineage glands expressing trefoil peptide genes are induced by chronic ulceration in ileal pouch mucosa.
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BACKGROUND: Chronic ulcerative conditions in the gastrointestinal tract result in the appearance of the ulcer associated cell lineage (UACL). The glands of this new cell lineage secrete epidermal growth factor, transforming growth factor alpha, and the trefoil factor family (TFF) peptides, which are known to participate in repair processes. Pouchitis is the most frequent complication of ileal pouch-anal anastomosis. AIM: Our aim was to determine whether the mucosal ulceration present in pouchitis can induce the development of UACL glands. METHODS: Biopsies from ileal pouches with pouchitis (n=10), healthy pouches (n=5), and normal terminal ileum (n=5) were studied. Expression of TFF mRNA was assessed by in situ hybridisation. TFF1 and TFF2 proteins were localised by immunochemistry. RESULTS: UACL glands containing TFF1 and TFF2 were observed in six patients with pouchitis. In some glands, there was TFF3 mRNA as has been reported for Crohn's UACL. None of the biopsies from ileal reservoirs without pouchitis showed UACL glands (p<0.05). Neither TFF1 nor TFF2 expression was detected in ileal reservoirs without pouchitis. CONCLUSION: UACL glands arise de novo in ileal pouch mucosa of patients with pouchitis and express all three TFF peptide genes. Chronic inflammation alone, present in healthy pouches, is not enough to stimulate the growth of the UACL, and additional stimuli consequent on ulceration may be needed. (+info)
Clinical use of Infliximab in Crohn's disease: the Edinburgh experience.
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Infliximab is an established treatment for steroid-resistant and fistulating Crohn's disease. Although efficacy has been shown in clinical trials, financial implications often limit its use and limited data exist regarding clinical practice. AIMS: To audit the clinical effectiveness of Infliximab. METHODS: We prospectively audited 50 consecutive patients [28 females; median age, 34 years (17-70 years)]. Disease activity and response rates were assessed by the Harvey-Bradshaw index. Clinical and disease data were collected and blood was taken for inflammatory markers, complement and double-stranded DNA antibodies. Patients received Infliximab at 5 mg/kg and were followed for 12 weeks. RESULTS: Indications for Infliximab were refractory Crohn's disease in 39 patients, fistulating Crohn's disease in six, pyoderma gangrenosum in one, pouchitis in two and coeliac disease in two. Thirty-one (79%) of the refractory Crohn's disease patients and four (66%) of the fistulating patients responded at 4 weeks. Twenty-one (54%) of the refractory Crohn's disease patients had a continued response at 12 weeks. Perianal disease was more prevalent in non-responders (7/8 vs. 12/31, P < 0.02). CONCLUSIONS: Response rates to Infliximab in our group are comparable to those of clinical trials. Despite the expense, it remains a useful adjunct to treatment in this otherwise difficult group of patients. Patients with perianal disease responded less well in our cohort. (+info)