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At least 235 records · Page 13Linked to original sources
PubMed2006

Differential expression of toll-like receptor 3 and 5 in ileal pouch mucosa of ulcerative colitis patients.

BACKGROUND AND AIMS: The pathogenesis of pouchitis, major complication after restorative proctocolectomy, and ileal J pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is still unclear. Changes in intraluminal bacterial colonization and correlated changes of pouch mucosa are thought to play an important role. Toll-like receptors (TLRs) as part of the innate immune system are capable of recognizing bacterial antigens. Their activation can lead to secretion of proinflammatory mediators. In this study, TLR2, 3, 4, and 5 expression profiles in the pouch mucosa of patients with UC and IPAA were analyzed and correlated with pouchitis. MATERIALS AND METHODS: Clinical symptoms, endoscopy, and histology were assessed in 35 patients using the Heidelberg Pouchitis Activity Score to classify patients as either having pouchitis or not. TLR mRNA expression in normal ileal mucosa and pouch mucosa was investigated by performing semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The results of RT-PCR were associated with the pouchitis score. RESULTS: In the analysis of all patients, TLR3 expression was decreased significantly whereas TLR5 expression was increased significantly in pouch mucosa compared to normal ileal mucosa (p-values 0.0076 and 0.016, respectively). A more detailed analysis upon dividing the patients into patients with and without pouchitis showed decreased TLR3 expression in the pouch mucosa only of patients without pouchitis (p-value=0.0067). TLR5 expression was increased in the pouch mucosa only of patients with pouchitis (p-value=0.023). No differences in TLR2 and 4 expression were found in either group. CONCLUSION: Differential expression of TLR3 and 5 suggests bacterial involvement in the pathogenesis of pouchitis in patients with UC.

Adult↗
PubMed1994

Mucosal concentrations of interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha in pelvic ileal pouches.

Concentrations of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) were determined by solid-phase ELISA in tissue homogenates of mucosal biopsy specimens obtained from pelvic ileal pouches in 13 patients with pouchitis (reservoir ileitis) and 17 with pouches without pouchitis. Normal ileal mucosa was used as a control. IL-1 beta was detected in all tissue homogenates from patients with pouchitis compared with only 29% from pouches without pouchitis and none from controls. IL-6 and IL-8 were present in all pouchitis specimens, in 70% of the specimens from nonpouchitis and only 30% of specimens from controls. TNF-alpha was undetectable in all specimens examined. The concentrations of IL-1 beta, IL-6, and IL-8 were significantly greater (P < 0.001) in biopsy specimens from pouchitis compared to those from pouches without pouchitis or normal ileal mucosa and in patients with pouchitis tissue levels of IL-1 beta significantly correlated with IL-6 (P < 0.05) and IL-8 (P < 0.01). Furthermore IL-1 and IL-8 levels were significantly higher in tissue specimens from nonpouchitis pouches than in those from normal ileal mucosa (P < 0.02). These results suggest that an enhanced cellular immunity operates in vivo at the mucosal level in pouchitis as in the case of ulcerative colitis.

Adult↗
PubMed1998

Antineutrophil cytoplasmic antibody subtypes in children and adolescents after ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies occur frequently in adult patients with chronic pouchitis after colectomy and ileal pouch-anal anastomosis for ulcerative colitis. The purpose of the study was to determine the prevalence of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in children and adolescents who undergo colectomy and ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis. METHODS: Five groups of children and adolescents (age, <20 years) were studied, with the following histories: acute pouchitis and history of ulcerative colitis; chronic pouchitis and history of ulcerative colitis; pouchitis with Crohn's disease features and a history of ulcerative colitis; no pouchitis and a history of ulcerative colitis; and familial adenomatous polyposis, with or without pouchitis. Antineutrophil cytoplasmic antibody levels and titers were detected in postoperative sera by enzyme-linked immunosorbent assay, and positive results were subtyped by indirect immunofluorescence. RESULTS: The frequency of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in patients with a history of ulcerative colitis were 67% and 15%, compared with a 0% presence in patients with familial adenomatous polyposis (p < 0.001). There was no significant correlation between the frequency of perinuclear antineutrophil cytoplasmic antibodies and ulcerative colitis patient subgroups (patients with and without pouchitis, 66% and 75%). Similarly, there was no significant correlation between the frequency of cytoplasmic antineutrophil cytoplasmic antibodies among ulcerative colitis patient subgroups (patients with and without pouchitis, 19% and 8%). The frequency of cytoplasmic antineutrophil cytoplasmic antibody in patients with Crohn's disease features (50%), was increased, but this difference was not significant. CONCLUSIONS: There is a high frequency of perinuclear antineutrophil cytoplasmic antibodies in children and adolescents who undergo ileal pouch-anal anastomosis for ulcerative colitis, whether or not they have pouchitis. The frequency of cytoplasmic antineutrophil cytoplasmic antibody is lower in this patient population. Additional studies will be required to determine whether the presence of cytoplasmic antineutrophil cytoplasmic antibody is associated with the postoperative development of features of Crohn's disease.

Adenomatous Polyposis Coli↗
PubMed2006

Serum biochemical evaluation of patients with functional pouches ten to 20 years after restorative proctocolectomy.

BACKGROUND: Restorative proctocolectomy with an ileal pouch-anal anastomosis is a surgical treatment of choice for ulcerative colitis and familial adenomatous polyposis (FAP). Pouchitis is a significant enigmatic morbidity. In the long-term, these patients, we anticipated, would experience biochemical profiling alterations after years of retaining functionally acceptable pouches. This pilot study was aimed at assessing results of essential biochemical variables more than 10 years after surgery. METHODS: The investigation was carried out in 91 patients; 39 were women. Eight-eight had ulcerative colitis, while three had FAPs. The hand-sewn ileal reservoirs after mucoso-proctocolectomy were 66 S and 25 J. The analyses were compared short-term vs long-term. Patients were investigated and were their own control. RESULTS: Long-term, incidence of acute and chronic pouchitis was 2 and 13%. Eleven and 4% of patients had hypomagnesaemia and hypocalcaemia. Mean levels were significantly enhanced (p<0.01 and p<0.0002). Hypomagnesaemia corresponded to episodes of pouchitis and was corrected with oral magnesium and antibiotics. Hypoferric anaemia was diagnosed in 7% and treated with oral iron tablets. Chronic pouchitis and recurrent pouch mucosa bleeding were the cause. Hypohemoglobinemia and hypocyanocobalaminemia were noted in 5% and 5%, respectively. Erythrocyte sedimentation rate and white blood cells were supra-normal in 13 and 10%, which corresponded with pouchitis. A significant (p<0.03) steady rise of mean serum immunoglobulin G without correlation to pouchitis was noted. CONCLUSION: Long-term functional results did not deteriorate. Pouchitis was a significant enigmatic morbidity. Severe or chronic pouchitis complicated hypoferric and vitamin B(12) anemia and hypomagnesaemia.

Blood Proteins↗
PubMed1991

Lymphocyte and macrophage subpopulations in pelvic ileal pouches.

This study aimed to characterise the mucosal cellular infiltrate in ileal reservoirs with and without pouchitis (reservoir ileitis). Intraepithelial lymphocyte counts were performed in biopsy specimens obtained from ileal pouches and compared with counts in normal ileum and normal colon. T lymphocyte and macrophage subpopulations were characterised immunohistochemically in pouch biopsy specimens using a panel of monoclonal antibodies. Normal ileum was used as a control. Intraepithelial lymphocyte densities (expressed as intraepithelial lymphocyte/100 epithelial cells) in pouches with and without pouchitis were significantly less than in normal ileum, and approached counts found in normal colon. There was no significant increase in counts even in pouchitis. There were no significant differences in the helper/inducer to suppressor/cytotoxic T cell (CD4:CD8) ratios between normal ileum and pouches with or without pouchitis, either in the epithelium or in the lamina propria. The proportions of RFD9+ (epithelioid cells and tingible body macrophages) and 3G8+ (CD16) macrophages were significantly higher in pouchitis compared with pouches without pouchitis or normal ileum. There were no significant differences between the three groups in the proportions of cells positive for the other macrophage markers (CD68, RFD1-dendritic cells, and RFD7-mature macrophages). The significance of low intraepithelial lymphocyte counts in ileal pouches is unknown, but this may be an adaptive response to the new luminal environment. Since an increase in RFD9+ macrophages occurs in inflammatory bowel disease, but does not occur as a non-specific response to an acute infective process, their presence in pouchitis suggests that effector mechanisms similar to those triggering the original ulcerative colitis may be operating in pouchitis.

Adolescent↗
PubMed2002

Irritable pouch syndrome: a new category of diagnosis for symptomatic patients with ileal pouch-anal anastomosis.

OBJECTIVE: Pouchitis often is diagnosed based on symptoms alone. However, increased stool frequency, urgency, and abdominal pain could be due to a condition resembling irritable bowel syndrome. This study was designed to assess the etiology of bowel symptoms using the Pouchitis Disease Activity Index (PDAI). METHODS: Symptoms, endoscopy, and histology were assessed in 61 consecutive symptomatic patients with ulcerative colitis after ileal pouch-anal anastomosis. Pouchitis was defined as a PDAI score of > or = 7, cuffitis was defined as endoscopic and histological inflammation of the rectal cuff and no inflammation of the pouch, and irritable pouch syndrome (IPS) was defined as symptoms with a PDAI of <7 and the absence of cuffitis. RESULTS: Thirty-one patients (50.8%) had pouchitis, four (6.5%) had cuffitis, and 26 (42.6%) had IPS. Demographics were similar in the three groups. Increased stool frequency, urgency, and abdominal cramps were the most common symptoms in the three groups. Rectal bleeding was seen only in cuffitis (p < 0.001). No patient in the three groups had fever. Twenty-seven patients (87.1%) with pouchitis responded to a 2-wk course of ciprofloxacin or metronidazole with a reduction in PDAI scores of > or = 3. All four patients with cuffitis responded to topical hydrocortisone or mesalamine with a reduction in the PDAI symptom component score of > or = 1. Twelve patients with IPS (46.2%) responded to antidiarrheal, anticholinergic, and/or antidepressant therapies with a reduction in the PDAI symptom component score of > or = 1, whereas the remaining patients had persistent symptoms despite therapy. CONCLUSIONS: A substantial number of symptomatic patients after ileal pouch-anal anastomosis do not meet the diagnostic criteria for either pouchitis or cuffitis and have been classified as having IPS. There is an overlap of symptoms among patients with pouchitis, cuffitis, and IPS, and endoscopic evaluation can differentiate among these groups. Distinction between these three groups has therapeutic implications.

Adult↗
PubMed2001

Ulcer associated cell lineage glands expressing trefoil peptide genes are induced by chronic ulceration in ileal pouch mucosa.

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.

Autoradiography↗
PubMed2000

Mucosal changes in ileal pouches after restorative proctocolectomy for ulcerative and Crohn's colitis.

PURPOSE: Inflammation and dysplasia may affect the ileal pouch after restorative proctocolectomy and ileal pouch-anal anastomosis. The aim of this prospective study was to evaluate the morphologic changes and the risk of dysplasia within the pouch after ileal pouch-anal anastomosis. METHODS: Thirty-seven patients with ileal pouch-anal anastomosis underwent endoscopies and biopsies of the pouch: 21 patients were affected by ulcerative colitis and 16 by Crohn's colitis. The mucosal biopsy specimens were studied to investigate the degree of acute and chronic inflammation and the occurrence of dysplasia. A score system was calculated for each patient and correlated with the histologic diagnosis of ulcerative colitis or Crohn's colitis. RESULTS: After a median follow-up of 85 (range, 7-198) months, the inflammation histologic score evaluated was 3.8 (95 percent confidence interval, 2.4-5.1) and 3.5 (95 percent confidence interval, 2.6-4.3), respectively, in patients with Crohn's colitis and ulcerative colitis (mean and 95 percent confidence interval; P = 0.74, not significant), and no patient developed mucosal dysplasia. Fifteen patients (40.5 percent) developed clinical pouchitis that occurred in Crohn's colitis (9/16 patients or 56 percent) and in ulcerative colitis (6/21 patients or 28 percent; P not significant). The score was 4.1 (95 percent confidence interval, 3.2-5) in patients with pouchitis and 3.2 (95 percent confidence interval, 2.1-4.3) in patients without clinical pouchitis (P = 0.012) and was 4.1 (95 percent confidence interval, 2.6-5.5) and 4 (95 percent confidence interval, 2.9-5.3), respectively, in pouchitis patients with Crohn's colitis and ulcerative colitis. CONCLUSION: No difference in the inflammation histologic score was observed in ileal pouches after restorative proctocolectomy for ulcerative and Crohn's colitis. In our series, which includes those patients with longer follow-up (>5 years) or with chronic unremitting pouchitis, no case of dysplasia was found. The occurrence of pouchitis was higher in the case of ileal pouch-anal anastomosis for Crohn's disease than for ulcerative colitis, but no difference in the severity of the histologic score was noted.

Adult↗
PubMed1999

[Ileoanal pouch as rectal substitute].

The ileoanal pouch procedure (IAPP) was the most remarkable breakthrough in the surgical therapy of ulcerative colitis (UC) and familial adenomatous polyposis (FAP) in the last 20 years. The underlying disease is under control, the function preserved and the quality of life markedly improved. Alternative procedures (terminal ileostomy, ileorectal anastomosis) are only indicated in special cases. In the last 16 years we have operated on 662 patients (n = 493 UC; n = 169 FAP) with an ileoanal J-pouch, short rectal cuff, complete mucosectomy and hand-sewn anastomosis. Normally there is a good function for UC and FAP patients after IAPP. Surgical experience, technical modifications concerning the pouch design and the pouch-anal anastomosis, and a differentiated indication lead to a further improvement of these complex procedures with consecutive reduction of complications. Specific complications concerned mainly the pouch-anal anastomosis (fistulas, abscesses, consecutive stenosis) and inflammation of the pouch mucosa (pouchitis). A multivariate analysis showed, that increasing experience of the specialized center is a significant factor reducing inflammatory problems at the anastomosis. The cumulative incidence of pouchitis was 29%. In general there is no problem in successful treatment. But patients with chronic pouchitis are a problematic group (6.2%). Chronic pouchitis is difficult to treat. It is likely that there exists an inflammation dysplasia carcinoma sequence for the ileal pouch mucosa, analogous to the colorectum. Recently we diagnosed the first case of a real ileum pouch carcinoma with associated epithelial dysplasias following chronic pouchitis. Therefore patients with chronic pouchitis must be followed up by endoscopy and random biopsies in a surveillance program. Patients with UC and FAP can gain the life quality of healthy controls, if postoperative complications can be avoided or treated successfully. For the further development of the procedure and the individual long-term success a qualified follow-up and therapy of complications is essential. Both can be carried out only by a specialized center.

Adenomatous Polyposis Coli↗