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PubMed1994

Pouchitis--recurrence of the inflammatory bowel disease?

The incidence and characteristics of reservoir inflammation after restorative proctocolectomy for ulcerative colitis were studied in a series of 179 patients. The median follow up time was 27 months (range 6-80). Pouchitis occurred in 36 patients (20%) and nine of these (5%) developed a chronic, persisting pouchitis. There were no pouch failures as a result of pouchitis and no significant adverse effect on longterm functional outcome. The overall cumulative risk to develop pouchitis four years after surgery was 23%. The risk of pouchitis is unpredictable on clinical grounds except that there were significantly less patients with left sided colitis in the group who subsequently developed pouchitis. Morphological and histochemical studies showed a greater degree of colonic metaplasia in the pouch mucosa in patients with pouchitis and patients with a chronic pouchitis had the highest degree of changes. The results support the view that pouchitis is a novel manifestation of inflammatory bowel disease in ileal mucosa that has changed slowly to a colon like mucosa.

Adolescent↗
PubMed2001

Association of decreased perfusion of the ileoanal pouch mucosa with early postoperative pouchitis and local septic complications.

BACKGROUND: After ileoanal pouch operation, 5% to 40% of patients with ulcerative colitis and 2% to 8% of patients with familial adenomatous polyposis develop pouchitis. Seven percent to 32% of all patients have local septic complications. Pouch ischemia is discussed as a pathophysiologic factor. Tonometry is a minimally invasive method for estimating intramucosal pH (pHi), with a decreased pHi showing intramucosal acidosis characteristic of hypoperfusion. HYPOTHESIS: Decreased perfusion of the iloanal pouch measured by pHi is associated with local septic complications and the development of pouchitis. DESIGN: Prospective cohort study. SETTING: Surgical department of a university hospital. PATIENTS AND METHODS: The pHi in the ileoanal pouch of 98 patients was measured directly after the pouch procedure and correlated to the clinical course. Endoscopic examination of the pouch with biopsy and blinded histologic assessment, including calculation of a histologic pouchitis score, were routinely performed 3 months postoperatively. MAIN OUTCOME MEASURES: Development of pouchitis and local septic complications in correlation to pHi. RESULTS: A decreased pHi was statistically significantly associated with the development of pouchitis and the rate of local septic complications. All 3 patients with anastomotic stenosis had a pHi less than 7.00. The diagnosis of ulcerative colitis just failed in statistical significance as a risk factor for pouchitis. An increased body mass index just failed as a statistically significant risk factor for complications but was a risk factor for the development of acute pouchitis. CONCLUSION: Pouch hypoperfusion is a risk factor for the development of pouchitis and local septic complications.

Adenomatous Polyposis Coli↗
PubMed2006

Anatomic extent of colitis and disease severity are not predictors of pouchitis after restorative proctocolectomy for mucosal ulcerative colitis.

BACKGROUND: Pouchitis is a common complication following restorative proctocolectomy with ileal pouch anal anastomosis (RPC-IPAA) for mucosal ulcerative colitis (MUC). The aim of this study was to determine if perioperative anatomic extent and severity of disease are predictors of pouchitis. METHODS: All consecutive patients who underwent RPC-IPAA for MUC between 1988 and 2002 were retrospectively studied. Pouchitis was classified as acute, recurrent or refractory. Colectomy specimen slides were histopathologically evaluated by a single blinded pathologist (MB), who assessed extent and severity of disease. RESULTS: Of 112 patients assessed, 70 (62.5%) had some form of pouchitis at a median follow-up of 38 months (range, 1-204 months). No association was found between the extent or severity of disease and subsequent development of acute or chronic pouchitis. A positive correlation was found between the histopathologic score and the occurrence of clinical pouchitis (p=0.014). The presence of colonic metaplasia in the pouch biopsy was significantly correlated with a histopathologic diagnosis of pouchitis (p<0.0001, r=-0.449). CONCLUSIONS: Following RPC for MUC, the extent and severity of disease do not predict the subsequent development of pouchitis.

Adolescent↗
PubMed2001

Activation of signal-transducer and activator of transcription 1 (STAT1) in pouchitis.

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.

Adult↗
PubMed2004

Factors associated with disease activity of pouchitis after surgery for ulcerative colitis.

BACKGROUND: Pouchitis occurs in 20% to 59% of patients operated on for ulcerative colitis. Several risk factors have been identified for the development of pouchitis. This study was undertaken to assess the incidence of pouchitis at least 5 years after ileal pouch-anal anastomosis for ulcerative colitis, and to evaluate possible predictive factors for inflammation activity. METHODS: A total of 107 subjects were enrolled (54 M, 53 F, mean age 45 years, range 23-69) with a J-pouch created between 1985 and 1994. Preoperative medical history was determined, an endoscopy performed, and biopsies taken from the pouch and neoterminal ileum above the pouch. Sera from all patients were tested for perinuclear antineutrophil cytoplasmic antibodies (pANCAs). RESULTS: After a mean 7.5-years' follow-up time, the cumulative incidence of pouchitis was 58%. Risk for development of active inflammation (PDAI > or = 7) was significantly higher in patients with preoperative extraintestinal manifestations (OR 2.7, 95% CI 1.1-6.4, P=0.03). Patients who had had ankylosing spondylitis (AS) (OR 11.7, P=0.006) or iritis (OR 9.8, P=0.013) were especially at risk. Positive titres of pANCAs were associated with inflammation in the neoterminal ileum; 80% of patients with high pANCA levels (>100) had pouchitis. Current smokers tended to have a more benign disease course. CONCLUSIONS: A correlation existed between the prevalence and titre of pANCAs and extent and disease activity of pouchitis. Chronic pouchitis may continuously stimulate the immunological process, keeping pANCAs at detectable levels. A strong correlation between AS, iritis and pouchitis suggests a common link in their pathogenesis.

Adult↗
PubMed1996

Genetic and immunological markers in pouchitis.

OBJECTIVES: Previous studies of the interleukin-1 receptor antagonist (IL-1RN) have found an increased frequency of the associated variable number tandem repeat (VNTR) allele 2 for ulcerative colitis (UC) and further evidence has been reported that this allele is associated with increased severity of several other inflammatory conditions. The HLA type of UC patients has also been implicated in the extent of disease as has the presence of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA). We therefore decided to test the hypothesis that the p-ANCA, HLA type or the presence of the IL-1RN allele 2 in patients who received a restorative proctocolectomy for UC had an effect on the risk of developing pouchitis. PATIENTS: We determined the genotypes of the IL-1RN and HLA DR beta and DQ beta loci for 28 subjects with previous UC and a pouch with no evidence of pouchitis for a minimum of 2 years after formation of an ileo-anal reservoir (mean 6.3 years; range 2-17 years) and 25 subjects with previous UC and pouchitis confirmed by strict histological examination of pouch mucosal biopsy. The IL-1RN genotypes were also determined for 86 healthy controls and 61 unrelated patients with familial adenomatous polyposis (FAP). The p-ANCA status was determined for all 25 pouchitis subjects but only 23/28 non-pouchitis subjects, with 15 unaffected subjects as a negative control. METHODS: The HLA haplotypes of the UC groups were determined by polymerase chain reaction sequence-specific primer (PCR-SSP) typing and the IL-1RN genotypes were determined by PCR and agarose gel electrophoresis. The p-ANCA status was determined by indirect immunofluorescence. RESULTS: A chi 2 of 5.686 with 1 degree of freedom and a P value of 0.0171 using Yates' correction was obtained by comparing the IL-1RN allele frequencies of the combined UC groups to the FAP controls, and a chi 2 of 6.801 with 1 degree of freedom and a P value of 0.0091 comparing the pouchitis group to the FAP controls. The HLA haplotype frequencies did not vary significantly between groups nor did they correlate with p-ANCA status. There were also no significant associations of the p-ANCA status and pouchitis. CONCLUSION: There is an increased frequency of IL-1RN allele 2 in UC, with the majority of the association arising from the pouchitis group, suggesting that the presence of allele 2 in patients with UC affects the disease outcome. However, the HLA frequencies and p-ANCA status do not have any significant associations.

Adult↗
PubMed2000

Pouchitis is associated with mucosal imbalance between interleukin-8 and interleukin-10.

BACKGROUND: Mucosal lesions of pouchitis are characterized by a neutrophil infiltrate. Interleukin (IL)-8 is the main mediator involved in neutrophil recruitment and is down-regulated by IL-10. AIM: To look for an imbalance between IL-8 and IL-10 in patients with pouchitis. PATIENTS/METHODS: 18 patients having an ileoanal pouch for ulcerative colitis were studied. Eleven had pouchitis defined by the pouchitis disease activity index of > or =7 points and 7 had no history of pouchitis. Biopsies taken at the site of inflammation or in the normal mucosa were scored for the histologic lesions, the intensity of neutrophil infiltration, and the presence of crypt abscesses. Mucosal IL-8 and IL-10 mRNA were quantified by competitive polymerase chain reaction. RESULTS: IL-8, IL-10, and IL-10/IL-8 mRNA were similar in patients with or without pouchitis. IL-8 mRNA levels were significantly higher in patients with a histologic score >2 (p = 0.01) and in patients with crypt abscesses (p = 0.01). IL-10/IL-8 mRNA was significantly lower in patients having a histologic score >2 (p = 0.019), a neutrophil infiltration > or =10% (p = 0.013), and crypt abscesses (p = 0.01). CONCLUSION: Histologic lesions of pouchitis are associated with a mucosal imbalance between IL-8 and IL-10. IL-10 could be proposed as a new treatment for pouchitis.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2007

Iron-deficiency anemia as presentation of pouchitis.

GOALS: This study sought to describe the percentage and cause of anemia in patients who underwent ileal pouch with anal anastomosis (IPAA) for ulcerative colitis (UC), and to compare the distribution of complications in patients with and without anemia, especially pouchitis, after IPAA. BACKGROUND: IPAA is the surgical procedure of choice for UC. Complications include pouchitis (40%), strictures (30%), small bowel obstruction (10%), pelvic sepsis (<5%), and urinary and sexual dysfunctions (<5%). Few studies have described the prevalence of anemia after IPAA, but no conclusive findings have been reported. STUDY: Patients who had undergone IPAA for UC were recruited from the UPR Inflammatory Bowel Disease Clinic and the Gastroenterology Research Unit. Demographic and medical data were obtained. Anemia was diagnosed using standard hematologic criteria. Serum iron, ferritin, transferrin, folate, vitamin B12, erythropoietin, total iron-binding capacity, reticulocyte count, peripheral smear, and bone marrow aspirate were evaluated in patients with anemia. Data analysis was performed with EPI Info version 6.4d. RESULTS: Iron-deficiency anemia was identified in 55.5% (10/18) of patients and pouchitis was found in 77% (14/18). All 10 patients with anemia had pouchitis, whereas only 4 of the 8 without anemia had pouchitis. In half of the anemic patients, pouchitis was asymptomatic. CONCLUSIONS: Iron-deficiency anemia may be a clinical presenting sign of pouchitis. Hemoglobin levels may be considered as surveillance tools for pouchitis in patients with IPAA.

Adult↗
PubMed2004

Incidence and therapeutic outcome of pouchitis for ulcerative colitis in Japanese patients.

AIM: The aim of this study was to examine the cumulative risk of pouchitis following restorative proctocolectomy for UC and FAP in Japanese patients, and to assess the response to medical treatment and its outcome. PATIENTS AND METHODS: 521 patients with UC and 117 FAP patients underwent proctocolectomy and received a J-shaped IPAA at our department of surgery. We investigated these patients using PDAI for the diagnostic criteria of pouchitis. RESULTS: Pouchitis occurred in only 32 UC patients (6.1%). The cumulative risk of developing pouchitis for a UC patient was 7% at 5 years after and 12% at 10 years after surgery. The medical treatment of acute pouchitis was usually oral metronidazole (250 mg twice daily) for 2 weeks or oral ciprofloxacin (200 mg thrice daily) in patients who could not tolerate metronidazole. Single episodes of pouchitis occurred in 21 patients (65.6%) and chronic or frequent relapses of pouchitis in 11 patients (34.4%). Three patients (9.4%) required re-ileostomy. Two patients (6.3%) required pouch excision. There were no patients with complicated dysplasia. CONCLUSION: The cumulative risk of pouchitis in Japanese UC patients is lower than that of western countries.

Adenomatous Polyposis Coli↗
PubMed2003

Diagnosis and treatment of patients with pouchitis.

Pouchitis is the most common long-term complication of ileal pouch-anal anastomosis in patients with underlying ulcerative colitis. Clinical symptoms of pouchitis are not specific, and they can be caused by other conditions such as rectal cuff inflammation and irritable pouch syndrome. Therefore, to make an accurate diagnosis, endoscopic evaluation together with symptom assessment is necessary. Among five available treat-first and test-first strategies, the initial approach with pouch endoscopy without histology was the most cost-effective strategy for the diagnosis of pouchitis. On the basis of clinical course, pouchitis can be classified into acute, relapsing and chronic forms. Pouchitis can also be classified into three categories based on the response to antibacterial therapy: antibacterial-responsive; antibacterial-dependent; and antibacterial-resistant. Metronidazole and ciprofloxacin are both effective in treating acute pouchitis. Although antibacterial therapy can induce and maintain remission, probiotics such as VSL#3 can also be used as to maintain clinical remission and prevent relapse in patients with relapsing or chronic pouchitis. For patients with chronic pouchitis that is resistant to antibacterials, therapy with anti-inflammatory agents and immunomodulators is often required.

Acute Disease↗
PubMed2004

Diagnostic difficulties in pouchitis--experience from a single institution.

The aim of the study was to analyze the clinical, endoscopic and histological signs of pouchitis in patients operated on because of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Between 1984 and 2002, the Department of Surgery carried out 218 restorative proctocolectomies in patients with UC and 120 in FAP patients. The follow-up to assess the intensity of inflammatory changes included 110 patients: 72 UC and 38 FAP. During the endoscopic examination, samples were taken for routine histological examinations. The histological assessment was based on the so-called Moskwitz's Histological System. Acute pouchitis is diagnosed if the score is > or =4, and chronic condition--if the score is > or =4. We used a modified PDAI scale to analyze the symptoms, taking into account the microscopically detectable histological features of chronic pouchitis. The clinical symptoms of pouchitis were revealed in 28 patients (25.5%), endoscopic symptoms in 36 patients (32.7%), and histological parameters in 48 patients (28-58.3% with > or =4 score of acute pouchitis and 20-41.7% with > or =4 score of chronic pouchitis). The signs of acute and chronic pouchitis were evident in endoscopy and histology, with no clinical features observed in many cases. Patients with symptoms of chronic pouchitis require a continuous follow-up.

Adenomatous Polyposis Coli↗
PubMed1995

Acute pouchitis and deficiencies of fuel.

PURPOSE: Acute pouchitis is a troublesome complication after restorative proctocolectomy. Deficiency of fuel, especially short chain fatty acids (SCFA), produced by anaerobic bacterial fermentation of saccharides, is implicated in ulcerative and diversion colitis. Our hypothesis was that SCFA deficiency occurs in acute pouchitis, and correction of the deficiency is associated with resolution of pouchitis. METHODS: Thirty-two patients were studied, 10 with histologically confirmed acute pouchitis and 22 with healthy pouches. Stool concentrations of SCFA (acetic, propionic, butyric, and valeric acids) were determined by gas-liquid chromatography. Quantitative bacteriologic studies of stool were carried out, and four-quadrant pouch biopsies were assessed by a pathologist who was unaware of the clinical state. Patients with pouchitis were treated for six weeks with metronidazole and given dietary advice to increase their intake of fermentable saccharides. RESULTS: Stool concentrations of SCFA were significantly less in pouchitis patients compared with patients with healthy pouches (340 mumol/g (range, 124-492) vs. 93 (range, 44-136) P < 0.01). No differences in anaerobic or aerobic counts were seen. Resolution of pouchitis was associated with a significant increase in SCFA, but anaerobic counts fell. CONCLUSION: Deficiency of SCFA is implicated in acute pouchitis.

Acetates↗
PubMed1995

Fecal bile acids, short-chain fatty acids, and bacteria after ileal pouch-anal anastomosis do not differ in patients with pouchitis.

Construction of an ileal reservoir changes the fecal bacterial flora and the fecal composition of bile acids and short-chain fatty acids. We examined the relationships between pouch inflammation (pouchitis) and pouch content, as assessed by analysis of fecal bacteria, bile acids, and short chain fatty acids. Four groups were studied: ileal pouch-anal anastomosis (IPAA) for ulcerative colitis with pouchitis (N = 10), IPAA without pouchitis (N =5), IPAA for familial adenomatous polyposis without pouchitis (N = 5); and Brooke ileostomy for ulcerative colitis, which served as controls (N = 5). Pouchitis was defined as > or = 7 points on an 18-point pouchitis disease activity index. Aerobic and anaerobic bacteria were quantitatively cultured. Total aqueous-phase bile acids were measured by thin-layer chromatography and an enzymatic 3 alpha-OH hydroxysteroid dehydrogenase method. Fecal short chain fatty acids were measured by gas liquid chromatography. All patients with an IPAA had higher ratios of anaerobes/aerobes and concentrations of anaerobic gram-negative rods than did patients with an ileostomy. There were no other differences between patient groups with respect to bacteria, aqueous-phase total bile acids, or fecal short-chain fatty acids. Fecal concentrations of bacteria, bile acids, and short-chain fatty acids were similar in patients with and without pouchitis, indicating that these factors can not be the sole cause of pouchitis.

Adenomatous Polyposis Coli↗
PubMed1992

Short-chain fatty acids in pouch contents from patients with and without pouchitis after ileal pouch-anal anastomosis.

Fecal concentrations of short-chain fatty acids were markedly reduced in 6 patients with pouchitis (mean +/- SE, 56.2 +/- 13.3 mmol/L) compared with 28 patients without pouchitis (139.0 +/- 8.5 mmol/L; P less than 10(-3)). The ratios of acetate to propionate to butyrate were not changed (pouchitis, 75:12:11%; normal pouches, 76:12:11%), i.e., all acids were equally reduced. The 24-hour production of total short-chain fatty acids in 16.6% fecal homogenates from patients with pouchitis was decreased (17.5 +/- 5.3 mmol/L) compared with patients without pouchitis (33.3 +/- 3.4 mmol/L; P less than 0.05), which could be overcome by the addition of saccharides to the homogenates. Pouch excretions of saccharides were similar in the two groups, but dilution occurred during pouchitis because of the increased outputs. Concentrations and productions of short-chain fatty acids correlated with pouch concentrations and excretions of sodium and saccharides. L-Lactate was elevated in pouchitis outputs, but differences in stool culture counts, mucosal histology, fecal concentration, assimilation or production of ammonia, nitrogen excretion, pH, and osmolality were not found. Pouchitis is characterized by decreased fecal concentrations and productions of short-chain fatty acids possibly caused by low pouch concentrations of fermentable saccharides.

Adult↗
PubMed1993

Chronic pouchitis after ileal pouch-anal anastomosis: responses to butyrate and glutamine suppositories in a pilot study.

Nonspecific, idiopathic inflammation of ileal pouch mucosa ("pouchitis") after ileal pouch-anal anastomosis is a common complication of this surgical approach. The epithelium of the pouch is ileal, but variable degrees of colonic metaplasia are natural sequelae of construction of such a pouch. One hypothesis is that pouchitis is caused by a deficiency of epithelial nutrition. Thus, a lack of butyric acid (the principal metabolic fuel of colonocytes) or of glutamine (the main fuel of enterocytes) may develop. In this study, our aims were to determine the concentration of total short-chain fatty acids in random stool samples obtained from patients with an ileal pouch-anal anastomosis with and without pouchitis and to test the therapeutic effects of butyrate and glutamine suppositories on pouchitis. During the study, all conventional therapy for pouchitis was discontinued. For 21 days, 9 patients participated in a butyrate trial, and 10 patients were treated with glutamine. Total concentrations of fecal short-chain fatty acids were significantly less in patients with pouchitis than in those without pouchitis. During treatment, 6 of the 10 patients who received glutamine had no recurrence of symptoms, but only 3 of the 9 patients who received butyrate responded similarly. Hence, further studies of glutamine in the treatment of pouchitis seem warranted.

Adolescent↗
PubMed1995

Antineutrophil cytoplasmic antibody correlates with chronic pouchitis after ileal pouch-anal anastomosis.

BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies, present in 60% of patients with ulcerative colitis, may be a marker for a genetically distinct subset of patients who develop chronic pouchitis after undergoing ileal pouch-anal anastomosis. The frequency of these antibodies in chronic pouchitis was determined. METHODS: Four groups were studied: patients who underwent ileal pouch-anal anastomosis for colitis with and without chronic pouchitis, familial polyposis without pouchitis and ileostomy for colitis. Antineutrophil cytoplasmic antibody levels and titers were detected by ELISA, and positive results were confirmed by perinuclear staining with indirect immunofluorescence. RESULTS: The frequency of perinuclear antineutrophil cytoplasmic antibodies in chronic pouchitis (100%) was significantly greater than in colitis (50%) or familial polyposis (0%) without pouchitis and colitis with an ileostomy (70%); p = 0.00, 0.00, and 0.01, respectively. CONCLUSIONS: The finding that perinuclear antineutrophil cytoplasmic antibodies occur more frequently in patients with chronic pouchitis raises the possibility that this antibody may mark a genetically distinct subset of ulcerative colitis patients. Further studies are needed to determine whether the presence of this antibody before ileal pouch-anal anastomosis is predictive for later development of chronic pouchitis.

Adenomatous Polyposis Coli↗
PubMed1993

["Pouchitis": new routes of research and signification].

"Pouchitis" is clearly disease-related, in that patients with ulcerative colitis are more likely to get the condition after the ileal pouch-anal canal operation than are patients with familial adenomatous polyposis. Moreover, extraintestinal manifestations of colitis may flare up with the onset of pouchitis in colitis patients, and RFD9+ macrophages characteristics of colitis patients are more common in the pouch mucosa of patients with pouchitis than in those without pouchitis. Nonetheless, luminal factors have a role. Some, like bacteria and their products and nonsulfated bile acids, likely aggravate pouchitis, while others, like glutamine, short-chain fatty acids and perhaps calcium, seem to improve symptoms and suppress pouchitis. The inflammatory response may also be suppressed by corticoids, 5-aminosalicylic acid, allopurinol, and the immunosuppressive agents, cyclosporine and FK 506. Nonetheless, the prevention of pouchitis is empiric and imperfect, and the response to treatment of often temporary. The exact cause and the specific cure of pouchitis are still unknown.

Bacterial Infections↗
PubMed2001

Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of increased epithelial apoptosis in the etiology of pouchitis. METHODS: Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. RESULTS: A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05) were significantly increased in pouches with previous pouchitis when compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. CONCLUSIONS: Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.

Adolescent↗