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PubMed2003

Colonic metaplasia in the ileal pouch is associated with inflammation and is not the result of long-term adaptation.

Ileal pouch-anal anastomosis (IPAA) is the preferred surgical therapy for chronic ulcerative colitis (CUC) and familial adenomatous polyposis (FAP). Previous studies have demonstrated morphologic changes in pouch mucosa such as villous atrophy and crypt hyperplasia. These changes have been labeled "colonic metaplasia." The aims of this study were to determine whether these changes represent "normal" long-term adaptation of the nondiseased pouch or instead are present only in the setting of inflammation. Twenty-four patients were identified, greater than 5 years status post-IPAA for CUC, who underwent pouchoscopy for surveillance and had no history of pouchitis. Thirty-one patients were identified greater than 5 years status post-IPAA for CUC, who had a history of pouchitis and had undergone pouchoscopy at least 5 years status post-IPAA. Eight patients status post-IPAA for FAP were also identified. Biopsy specimens were reevaluated by a single, blinded pathologist for degree of inflammation, the presence of villous atrophy and crypt hyperplasia, and evidence of dysplasia. Among the patients with CUC, the inflammation score was greater in the pouchitis group, 13.2 +/- 1.2, compared to the nonpouchitis group, 4.0 +/- 0.5 (P < 0.0001). Median colonic metaplasia score was greater in the pouchitis group (4 [range 2 to 6]) vs. 2 (9 [range 0 to 6]; P < 0.0001). The colonic metaplasia score correlated with the inflammation score (Spearman coefficient r = 0.83; P < 0.0001). In the eight patients with FAP, the inflammation score was 5.1 +/- 0.9 and the median colonic metaplasia score was 1 (range 0 to 4). There was no evidence of dysplasia in any of the biopsy specimens. Patients without a history of pouchitis or symptoms of pouchitis have only a minimal degree of villous atrophy and crypt hyperplasia. These morphologic changes in the ileal pouch are found primarily in the setting of inflammation, and likely represent a reparative response.

Adaptation, Physiological↗
PubMed2004

Assessment of mucosal inflammation and blood flow in response to four weeks' intervention with probiotics in patients operated with a J-configurated ileal-pouch-anal-anastomosis (IPAA).

BACKGROUND: Pouchitis is a common and troublesome condition in patients operated on with ileal-pouch-anal-anastomosis (IPAA). A disturbed mucosal perfusion in the pouch has been suggested as a possible cause. Laser Doppler flowmetry (LDF) has been used successfully to measure gastric and colonic mucosal perfusion in humans. In a previous study, we demonstrated a reduced mucosal perfusion in the distal part of the pouch, during probiotic intervention, examined by LDF measurement. The aim of the present study was to confirm our previous results in a much larger material, and to compare the results of LDF measurements and inflammatory activity in ulcerative colitis (UC) patients with those in familial adenomatous polyposis (FAP) patients. METHODS: Five hundred millilitres of a fermented milk product (Cultura), containing live lactobacilli (La-5) and bifidobacteria (Bb-12), was given daily for 4 weeks to 41 UC and 10 patients with FAP, operated on with IPAA. Mucosal perfusion was measured with LDF and the degree of inflammation was examined at predefined levels of the distal bowel by histology and faecal calprotectin measurements both before and after intervention. We also evaluated the applicability of a Pouchitis Disease Activity Index (PDAI). RESULTS: The LDF measurements were reproducible in the pelvic pouch at each of the predefined levels, but did not change during intervention. Mucosal perfusion was significantly reduced in the distal compared to the proximal part of the pouch in the UC group (P < 0.05). The perfusion levels were higher in the FAP patients compared to the UC patientsat all predefined levels (P < 0.05). Calprotectin levels and histological score did not change significantlyafter intervention in any of the groups. The calprotectin level was significantly lower in the FAP compared to the UC group both before and after intervention. The PDAI decreased in both groups from alevel considered diagnostic for pouchitis to a level considered as not active pouchitis. The decreasewas significant for the UC patients. CONCLUSIONS: The results did not demonstrate an effect of probiotics on histology, although a significant effect on the PDAI was achieved, which concurs with the previously reported effect on symptoms and endoscopic score. The significantly reduced blood flow in the UC group compared to the FAP group, operated on with the same procedure, and the significantly increased calprotectin levels in the UC group, are original findings. Both findings may be related to an increased risk for pouchitis among UC patients. The lack of effect of intervention on mucosal perfusion does not exclude a role for reduced circulation as a cause of pouchitis based on the reduced LDF measurements in the distal part of the pouch.

Adult↗
PubMed1998

Chronic inflammatory changes in the pouch mucosa are associated with cholangitis found on peroperative liver biopsy specimens at restorative proctocolectomy for ulcerative colitis.

BACKGROUND: The clinical syndrome of primary sclerosing cholangitis (PSC), diagnosed in about 5% of patients with ulcerative colitis (UC), has been shown to be associated with pouchitis after ileal pouch-anal anastomosis. The aim of this study was to ascertain whether UC patients with cholangitis on liver biopsy at proctocolectomy, with or without the clinical syndrome of PSC, have an increased risk of inflammatory changes in the ileal reservoir mucosa and clinical pouchitis. METHODS: Of the consecutive 81 UC patients treated with restorative proctocolectomy with ileal J reservoir at Tampere University Hospital between 1985 and 1991, 73 with peroperative liver biopsy were included. A peroperative liver biopsy was obtained during proctocolectomy. After a median follow up of 64 months, pouch biopsy specimens were obtained. Periods of clinical pouchitis were diagnosed by means of clinical criteria alone or by clinical criteria combined with the results of previous pouch endoscopies in all patients. RESULTS: Ten patients (14%) showed histologic features consistent with small-duct PSC on liver biopsy. Endoscopic retrograde cholangiography had previously been performed on four of these patients, and all four had large-duct PSC. Patients with cholangitis had significantly more severe chronic, but not acute, inflammation in the pouch mucosa than patients without cholangitis. At least one episode of pouchitis occurred in 30% of the patients without cholangitis as compared with 90% of the patients with cholangitis. Chronic pouchitis was more frequent in the group with cholangitis than in the group without it (70% versus 11%). CONCLUSIONS: The only means of detecting all UC patients with cholangitis is a liver biopsy. Cholangitis, either with the clinical syndrome of PSC or found on liver biopsy, seems to be a risk factor for chronic-type inflammatory changes in the pouch mucosa and for the development of pouchitis.

Adult↗
PubMed1997

Crohn's-like complications in patients with ulcerative colitis after total proctocolectomy and ileal pouch-anal anastomosis.

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become an established surgical procedure for ulcerative colitis. Occasional patients who have undergone IPAA develop persistent or recurrent episodes of pouchitis (chronic pouchitis), from which a subset also develop gastrointestinal and systemic complications that are identical to those seen in Crohn's disease. These complications include enteric stenoses or fistulas in the pouch or pouch inlet segment, perianal fistulas or abscesses, pouch fistulas, arthritis, iridocyclitis, and pyoderma gangrenosum. The development of Crohn's-like gastrointestinal complications in a patient with chronic pouchitis frequently engenders concern that the pathologist misinterpreted the proctocolectomy specimen as ulcerative colitis instead of Crohn's disease. We describe eight patients who developed chronic pouchitis and Crohn's-like complications after IPAA and total proctocolectomy. In each case, concern was voiced about misinterpretation of the proctocolectomy specimen as ulcerative colitis instead of Crohn's disease after the development of the Crohn's-like complications. Preoperatively, all eight patients had characteristic clinical, radiographic, and pathologic features of ulcerative colitis. Review of the pathology specimens indicated that all eight had ulcerative colitis. Crohn's-like complications are most likely related to chronic pouchitis, which probably is a form of recrudescent ulcerative colitis within the novel environment of the pouch. A diagnosis of Crohn's disease after IPAA surgery should only be made when reexamination of the original proctocolectomy specimen shows typical pathologic features of Crohn's disease, Crohn's disease arises in parts of the gastrointestinal tract distant from the pouch, pouch biopsies contain active enteritis with granulomas, or excised pouches show the characteristic features of Crohn's disease, including granulomas. There were no histologic differences in the total colectomy specimens between the eight ulcerative colitis study patients and 16 control ulcerative colitis patients who had a favorable clinical outcome after IPAA surgery groups. Crohn's-like complications and chronic pouchitis does not necessarily imply an incorrect original interpretation of ulcerative colitis by the pathologist.

Adolescent↗
PubMed2003

A cost-effectiveness analysis of diagnostic strategies for symptomatic patients with ileal pouch-anal anastomosis.

OBJECTIVE: Pouchitis is often diagnosed based on symptoms and empirically treated with antibiotics (treat-first strategy). However, symptom assessment alone is not reliable for diagnosis, and an initial evaluation with pouch endoscopy (test-first strategy) has been shown to be more accurate. Cost-effectiveness of these strategies has not been compared. The aim of this study was to compare cost-effectiveness of different clinical approaches for patients with symptoms suggestive of pouchitis. METHODS: Pouchitis was defined as pouchitis disease activity index scores > or =7. The frequency of pouchitis in symptomatic patients with ileal pouch was estimated to be 51%; the efficacy for initial therapy with metronidazole (MTZ) and ciprofloxacin (CIP) was 75% and 85%, respectively. Cost estimates were obtained from Medicare reimbursement data. RESULTS: Six competing strategies (MTZ trial, CIP trial, MTZ-then-CIP trial, CIP-then-MTZ trial, pouch endoscopy with biopsy, and pouch endoscopy without biopsy) were modeled in a decision tree. Costs per correct diagnosis with appropriate treatment were $194 for MTZ trial, $279 for CIP trial, $208 for MTZ-then-CIP trial, $261 for CIP-then-MTZ trial, $352 for pouch endoscopy with biopsy, and $243 for pouch endoscopy without biopsy. Of the two strategies with the lowest cost, the pouch endoscopy without biopsy strategy costs $50 more per patient than the MTZ trial strategy but results in an additional 15 days for early diagnosis and thus initiation of appropriate treatment (incremental cost-effectiveness ratio $3 per additional day gained). The results of base-case analysis were robust in sensitivity analyses. CONCLUSIONS: Although the MTZ-trial strategy had the lowest cost, the pouch endoscopy without biopsy strategy was most cost-effective. Therefore, based on its relatively low cost and the avoidance of both diagnostic delay and adverse effects associated with unnecessary antibiotics, pouch endoscopy without biopsy is the recommended strategy among those tested for the diagnosis of pouchitis.

Aged↗
PubMed2005

Comprehensive evaluation of inflammatory and noninflammatory sequelae of ileal pouch-anal anastomoses.

BACKGROUND AND AIMS: Ileal pouch-anal anastomosis (IPAA) improves quality of life (QOL) for ulcerative colitis patients who require surgery. Crohn's disease (CD) of the pouch, pouchitis, cuffitis, and irritable pouch syndrome (IPS) have an adverse impact on physical and psychological well-being, which can compromise the gain in QOL after the surgery. Their clinical, endoscopic, and histologic features have not been fully characterized. The aim of this study was to compare demographic, clinical, endoscopic, and histologic features between CD of the pouch, pouchitis, cuffitis, IPS, and normal pouches. METHODS We enrolled 124 patients: normal pouches (N = 26), CD of the pouch (N = 23), pouchitis (N = 22), cuffitis (N = 21), and IPS (N = 32). Symptomatology, endoscopy, histology, and the Cleveland Global QOL and the Irritable Bowel Syndrome-QOL scores were compared among the groups. RESULTS: Univariate analysis of demographic and clinical data showed a possible association between NSAID use and pouchitis, extraintestinal manifestation and cuffitis, and antidepressant use and IPS. There were no differences in the Pouchitis Disease Activity Index symptom scores between the disease groups, with an exception of bleeding, which occurred almost exclusively in cuffitis. Endoscopy was useful in discriminating between CD of the pouch, pouchitis, cuffitis, and normal pouches or IPS. Patients with diseased IPAA had worse QOL scores. CONCLUSIONS: Symptoms largely overlapped among the disease groups of IPAA. Endoscopy is valuable for diagnosis. Inflammatory or noninflammatory sequelae of IPAA adversely affected patients' QOL.

Adult↗
PubMed2003

A neurokinin 1 receptor antagonist reduces an ongoing ileal pouch inflammation and the response to a subsequent inflammatory stimulus.

Ileal pouch-anal anastomosis (IPAA) is an excellent surgical option for patients with chronic ulcerative colitis (CUC) requiring colectomy; however, persistent episodes of ileal pouch inflammation, or pouchitis, may result in debilitating postoperative complications. Because considerable evidence implicates substance P (SP) as an inflammatory mediator of CUC, we investigated whether SP participates in the pathophysiology of pouchitis. With the use of a rat model of IPAA that we developed, we showed that ileal pouch MPO levels and neurokinin 1 receptor (NK-1R) protein expression by Western blot analysis were significantly elevated 28 days after IPAA surgery. In situ hybridization and immunohistochemistry showed that the increase in NK-1R protein expression was localized to the lamina propria and epithelia of pouch ileum. The intraperitoneal administration of the NK-1R antagonist (NK-1RA) CJ-12,255 for 4 days, starting on day 28, was effective in reducing MPO levels. Starting on day 28, animals with IPAA were given 5% dextran sulfate sodium (DSS) in their drinking water for 4 days, which caused histological and physical signs of clinical pouchitis concomitant with significant increases in ileal pouch MPO concentrations as well as NK-1R protein expression by Western blot analysis. In situ hybridization and immunohistochemistry showed that the increase in NK-1R protein expression was especially evident in crypt epithelia of pouch ileum. When the NK-1RA was administered 1 day before starting DSS and continued for the duration of DSS administration, the physical signs of clinical pouchitis and the rise in MPO were prevented. These data implicate SP in the pathophysiology of pouchitis and suggest that NK-1RA may be of therapeutic value in the management of clinical pouchitis.

Animals↗
PubMed1994

Histologic and microbiologic features of biopsy samples from patients with normal and inflamed pouches.

PURPOSE: This study was undertaken to assess the electron microscopic and microbiologic findings in tissue biopsy samples from patients with pouchitis and to compare them with findings in patients with normal pouches, conventional ileostomies, and normal ileum. METHODS: Tissue samples were obtained from 78 patients: 23 patients with normal pouches endoscopically and histologically (Group 1), 12 patients with endoscopic and histologic evidence of inflammation (pouchitis) (Group 2), 14 patients who had either endoscopic or histologic evidence of inflammation but not both (Group 3), 20 patients with conventional ileostomies (Group 4), and 9 patients without ileostomies from whom biopsy samples of normal ileum were obtained (Group 5). RESULTS: The mean total aerobic facultative counts in the biopsy samples from the pouchitis patients were significantly higher when compared with biopsy samples from Groups 4 and 5 (P < 0.05). There were no significant differences in the mean anaerobic counts among the five groups. Positive cultures were obtained in 90 percent of patients with pouches compared with 69 percent of patients with conventional ileostomies or normal ileum (P < 0.05). Intramural bacteria were observed on electron microscopy in biopsy specimens of 47 percent patients with pouches compared with 14 percent of patients with conventional ileostomies or normal ileum (P < 0.05). However, the proportion of patients with positive cultures or intramural bacteria was not increased in the pouchitis group compared with the normal pouch group. CONCLUSION: These data suggest that intramural aerobic facultative bacterial counts are elevated in patients with pouchitis and may play a role in the pathogenesis of pouchitis.

Adult↗
PubMed2001

Gut transit time after ileal pouch-anal anastomosis using a radiopaque marker.

PURPOSE: The aim of this study was to determine the contribution of gastrointestinal motility to bowel function and the pathogenesis of pouchitis after ileal pouch-anal anastomosis. METHODS: Gastrointestinal transit time was assessed by a radiopaque marker technique in 32 patients with ulcerative colitis. RESULTS: Small intestinal transit time and pouch emptying time were 4.1 +/- 2 hours and 4.1 +/- 2.5 hours, respectively. There was no significant difference in pouch emptying time between patients with and without pouchitis. When only patients with acute pouchitis that responded to metronidazole were analyzed, there was a trend toward a prolonged pouch emptying time compared with those without pouchitis (P = 0.095). Whole gut transit time was inversely correlated with 24-hour stool frequency in patients without pouchitis (r = -0.63, P < 0.005). In the analysis of regional transit time, only small intestinal transit time was inversely correlated with 24-hour stool frequency (r = -0.472, P < 0.05). Significant prolongation of small intestinal transit time was demonstrated in patients over a period of 41 months (the median time) after ileostomy closure compared with those whose pouches had been functioning for 6 to 41 months (5.4 +/- 1.7 hours vs. 3.1 +/- 1.3 hours, P < 0.005). CONCLUSIONS: There was an association between small intestinal motility and bowel frequency. Further investigation is necessary in the pathogenesis of acute pouchitis regarding the relationship between delayed pouch emptying and subsequent development of mucosal inflammation.

Adolescent↗
PubMed2007

Pouch outcomes among children with ulcerative colitis treated with calcineurin inhibitors before ileal pouch anal anastomosis surgery.

PURPOSE: The purpose of this article is to describe the outcomes of the pouches of 14 children with ulcerative colitis (UC) who were pretreated with calcineurin inhibitors before they underwent their ileal pouch anal anastomosis (IPAA) surgery. METHODS: An institutional review board-approved retrospective review of the charts of consecutive patients with UC treated with calcineurin inhibitors before undergoing IPAA surgery at a tertiary pediatric center between 1998 and 2003 was performed. The primary endpoint was pouch outcome after at least 2 years of follow-up (healthy pouch, acute pouchitis, chronic refractory pouchitis, or pouch failure); the secondary endpoints were early postoperative complications, number of stages, and time between stages. RESULTS: Fourteen of 53 consecutive patients who underwent IPAA for UC were treated with calcineurin inhibitors before their surgery (26%; 6 with cyclosporine and 8 with tacrolimus). All 14 patients were concomitantly treated with systemic steroids. Ten patients (71%) were also taking 6-mercaptopurine or azathioprine, and 9 (64%) were also taking mesalamine. Three patients (21%) had healthy pouches with no clinical evidence of pouchitis, 6 (43%) had at least one episode of acute pouchitis (average of 2 episodes per year), 3 (21%) had chronic relapsing pouchitis, and 2 (14%) were later determined to have Crohn's disease. There was no pouch failure. Two patients (14%) had an early postoperative complication (intraabdominal abscess, anastomotic stricture). Five patients (36%) had a 2-staged procedure, and 8 (64%) had a 3-staged procedure. For the 2-staged procedures, the mean time between the first and second stages was 3.14 months (range, 3-4 months). For the 3-staged procedures, the mean time between the first and second stages was 4.25 months (range, 2-6 months) and that between the second and third stages was 4 months (range, 2.5-6 months). CONCLUSIONS: In this series, chronic pouchitis was an infrequent complication among children who were pretreated with calcineurin inhibitors. Calcineurin inhibitor use did not lead to or portend increased early postoperative complications or affect the number or duration of surgical stages. Further studies are required to determine if preoperative calcineurin inhibitors improve pouch outcomes or facilitate the performance of 2-staged procedures.

Adolescent↗
PubMed2000

Long-term clinical outcome and anemia after restorative proctocolectomy for ulcerative colitis.

BACKGROUND: The purpose of this study was to evaluate long-term outcome and hematologic data after restorative proctocolectomy (RPC) and mucosectomy with hand-sewn J-pouch-anal anastomosis for ulcerative colitis (UC). METHODS: Forty-eight (75%) out of 64 consecutive patients operated on during the period 1985-1990 participated in a long-term follow-up in 1998. Study visits involved an interview according to a 23-item functional questionnaire, pouch endoscopy and blood samples. Pre- and postoperative data on these patients were reviewed at our own database covering all operations performed for UC at our institute. RESULTS: Functional disturbances were common and unchanged during long-term follow-up. Minor incontinence occurred in 37.5% and outlet difficulties in 10.5% of patients. Bowel obstruction occurred in 16.7% and usually needed operative treatment. Twenty-four (50.0%) patients had had at least one episode of pouchitis and chronic or severe pouchitis occurred in 18 (37.5%) cases. Males seem to have chronic pouchitis more often. Ten (20.8%) patients had anemia during follow-up. Recurrent bleeding from the pelvic pouch and chronic pouchitis exposed to the anemia. CONCLUSIONS: Minor morbidity is common after RPC. Pouchitis occurred in half of our patients during long-term follow-up. There may be a risk of anemia with chronic pouchitis and bleeding from the pelvic pouch mucosa.

Adult↗
PubMed1999

Arthritis and the gut.

Mild arthritis/arthralgia is the most frequent extraintestinal manifestation in inflammatory bowel disease (IBD) and has been reported to occur in 10-35% of patients in different studies. A classification of peripheral arthropathy in relation to inflammatory bowel disease has recently been proposed. Type 1: pauciarticular, asymmetrical, preferably large joints, and related to IBD activity. Type 2: polyarticular, symmetrical, preferably small joints, and occurring independently of IBD activity. While this classification requires the presence of synovitis, arthralgia without swelling or other objective signs are of equal frequency but are not covered by this system. In this issue of the journal, Thomas et al. report a prospective study, incorporating strict endoscopic and histological criteria for pouchitis, which elucidates the correlation to arthropathy. Both pouchitis and symptoms of the joints occurred more frequently in ulcerative colitis patients than in patients with familial polyposis. Surprisingly, arthropathy was not more frequent among patients with pouchitis than among patients without pouchitis in this study. Extraintestinal manifestations of the joints are thus not likely to be a reactive arthritis secondary to pouchitis, which would have been an obvious explanation. Preoperative occurrence of extraintestinal manifestations from the joints does not seem to be predictive for the outcome of an ileo-anal pouch anastomosis and especially development of pouchitis. The arthritic symptoms were generally mild and not disabling.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1990

Crypt cell proliferation and HLA-DR expression in pelvic ileal pouches.

To investigate the nature of the morphological changes that occur in ileal pouches, 26 biopsy specimens from patients with functioning ileo-anal pouches (eight with pouchitis) were studied. Normal ileum (n = 10) was used as a control. Mucosal morphometry (using linear measurements), crypt cell proliferation (CCP) (using the monoclonal antibody Ki67), and epithelial HLA-DR expression (monoclonal antibody CR3/43) were assessed. CCP (expressed as the percentage of Ki67 positive nuclei for each crypt) was significantly higher in pouches with pouchitis, compared with those without, and in pouches without pouchitis compared with normal ileum. CCP values in some pouches without pouchitis approached values found in those with pouchitis. CCP was related inversely to villous height and an index of villous atrophy (VH/TMT), and directly to crypt depth. In the presence of pouchitis there was intense epithelial HLA-DR expression that extended into the crypts. In some pouches with high CCP values, but without clinically important inflammation, surface epithelial HLA-DR expression was weak and patchy. It is concluded that villous atrophy and crypt hyperplasia in ileal pouches are associated with high CCP values. These may be increased even in the absence of active inflammation, and this increase may occur as a response to the new luminal environment.

Adenomatous Polyposis Coli↗
PubMed2002

Assessment of ileoanal pouch inflammation by interleukin 1beta and interleukin 8 concentrations in the gut lumen.

PURPOSE: The cytokines interleukin 1beta and interleukin 8 have previously been shown to be present in mucosal biopsy specimens from inflamed ileoanal pouches. Our aim was to use the method of whole gut lavage fluid to measure cytokine concentrations and relate these to disease activity. METHODS: Forty-two patients with ulcerative colitis were recruited (23 males). Their ages ranged from 20 to 73 years (median 39). A questionnaire was completed and whole gut lavage, pouchoscopy, and biopsy were performed. RESULTS: Both interleukin 1beta and interleukin 8 were present in the whole gut lavage fluid of ileoanal pouches, with concentrations ranging from 4 to 143 pg/ml (median 6.3 pg/ml) for whole gut lavage fluid interleukin 1beta and from 18 to 1000 pg/ml (median 53.7 pg/ml) for whole gut lavage fluid interleukin 8. Whole gut lavage fluid interleukin 1beta and interleukin 8 were simultaneously detectable in 24 patients. These included the five patients with pouchitis, who had higher levels of interleukin 1beta (75 pg/ml vs. 8 pg/ml, P < 0.005) and interleukin 8 (668 pg/ml vs. 106 pg/ml, P < 0.005) compared with the rest of the patients with detectable cytokines (n = 19). The sensitivity of whole gut lavage fluid interleukin 8 (>200 pg/ml) in the diagnosis of pouchitis was 1, and the specificity was 0.86. There was a significant positive correlation of both whole gut lavage fluid interleukin 1beta and interleukin 8 with all the gut protein loss markers (immunoglobulin G, albumin, alpha1-antitrypsin). CONCLUSION: Cytokine interleukin 1beta and interleukin 8 concentrations, along with other parameters of inflammation, are raised in pouchitis in the whole gut lavage. The results also suggest a spectrum of severity of "pouchitis," with clinical pouchitis fulfilling Moskowitz criteria at the severe end of the spectrum.

Adult↗
PubMed2003

Factors associated with ileal mucosal morphology and inflammation in patients with ileal pouch-anal anastomosis for ulcerative colitis.

PURPOSE: Pouchitis has been associated with abnormal bacterial flora responding to antibiotics. Dietary factors may play a role in modifying the qualitative and quantitative components of the microflora. We evaluated interactions between nutritional factors, fecal and mucosal bacterial flora, and mucosal morphology in patients with a history of pouchitis compared with patients with optimal outcome at least five years after ileal pouch-anal anastomosis for ulcerative colitis. METHODS: Thirty-two patients were enrolled in the study: 11 (7 males; mean age, 49.8 years) with optimal outcome and 21 (11 males; mean age, 47.3 years) with pouchitis history. A seven-day food diary was recorded, endoscopy performed, and biopsies taken from the pouch for histology, mucin staining, and bacterial culture. Fresh fecal samples were quantitatively cultured, and fecal bile acids analyzed by gas-liquid chromatography. RESULTS: No differences existed in mean nutrient intake, composition of fecal bile acids, or microbial tissue biopsy cultures between the groups with and without pouchitis. Those with optimal outcome tended to have more benign disease course of ulcerative colitis than patients with pouchitis. In those patients, fecal concentrations (log10 colony-forming unit/g) of anaerobes and aerobes were significantly higher (P = 0.007). Degree of villous atrophy and colonic metaplasia were both associated with fecal anaerobic flora. Low intake of lactose was associated with sulfomucin predominance. A negative correlation existed between fecal aerobes and dietary lactose consumption. CONCLUSIONS: A higher total load of fecal anaerobic bacterial flora is strongly associated with degree of colonic metaplasia, villous atrophy, and inflammation activity after surgery for ulcerative colitis. An association existed between dietary lactose, fecal bacteria, and pouch morphology. Lactose may have prebiotic properties.

Adult↗
PubMed2005

Serologic responses in indeterminate colitis patients before ileal pouch-anal anastomosis may determine those at risk for continuous pouch inflammation.

PURPOSE: Although acute pouchitis after ileal pouch-anal anastomosis is common and easily treated, continuous pouch inflammation seen clinically as chronic, antibiotic-dependent pouchitis, and/or Crohn's disease remains a difficult management problem. Compared with ulcerative colitis, indeterminate colitis patients undergoing ileal pouch-anal anastomosis have a higher incidence of continuous pouch inflammation, which may represent persistent immune reactivity to microbial antigens. Antibody responses to three microbial antigens (oligomannan anti-Saccharomyces cerevisiae, outer membrane porin C of Escherichia coli, and an antigen (I2) from Pseudomonas flourescens) are more commonly seen in Crohn's disease, whereas antibodies to a cross-reactive antigen (perinuclear antineutrophil cytoplasmic antibodies) is more suggestive of ulcerative colitis. We examined whether preoperative serologic responses to these antigens were associated with Crohn's disease in indeterminate colitis patients after ileal pouch-anal anastomosis. METHODS: Twenty-eight indeterminate colitis patients undergoing ileal pouch-anal anastomosis were prospectively assessed for the development of pouchitis or Crohn's disease. Serologic responses were determined by enzyme-linked immunosorbent assay and immunofluorescence. Patients were classified based on four predominant profiles of antibody expression. Antibody profiles were determined before knowledge of clinical outcome. RESULTS: Median follow-up was 38 (range, 3-75) months. Of 16 patients (61 percent) who developed pouch inflammation, 4 (25 percent) had acute pouchitis and 12 (75 percent) had continuous pouch inflammation (9 had chronic pouchitis, 3 had Crohn's disease). No preoperative clinical factor predicted the development of these pouch complications. Overall, 16 patients (57 percent) had a positive antibody reactivity profile. Serologic expression of any marker alone did not predict the development of continuous pouch inflammation. However, continuous pouch inflammation developed in 10 of 16 patients (63 percent) who had a positive antibody reactivity profile compared with only 2 of 12 patients (17 percent) who had a negative antibody reactivity profile (P = 0.015). CONCLUSIONS: Indeterminate colitis patients who have a positive antibody reactivity profile before ileal pouch-anal anastomosis have a significantly higher incidence of continuous pouch inflammation after surgery than those with a negative profile.

Adolescent↗
PubMed2006

Risk factors for diseases of ileal pouch-anal anastomosis after restorative proctocolectomy for ulcerative colitis.

BACKGROUND & AIMS: Although pouchitis is considered the most common adverse sequela of ileal pouch-anal anastomosis (IPAA), inflammatory and noninflammatory conditions other than pouchitis are increasingly being recognized. The risk factors for these non-pouchitis conditions, including Crohn's disease (CD) of the pouch, cuffitis, and irritable pouch syndrome (IPS), have not been studied. The aim of this study was to assess risk factors for inflammatory and noninflammatory diseases of IPAA in a tertiary care setting. METHODS: The study consisted of 240 consecutive patients who were classified as having healthy pouches (N = 49), pouchitis (N = 61), CD of the pouch (N = 39), cuffitis (N = 41), or IPS (N =50). Demographic and clinical features were assessed to determine risk factors for each of these conditions by using logistic regression analysis. RESULTS: Risk factors remaining in the final logistic regression models were for pouchitis: IPAA indication for dysplasia (odds ratio [OR], 3.89; 95% confidence interval [CI], 1.69-8.98), never having smoked (OR, 5.09; 95% CI, 1.01-25.69), no use of anti-anxiety agents (OR, 5.19; 95% CI, 1.45-18.59), or use of NSAIDs (OR, 3.24; 95% CI, 1.71-6.13); for CD of the pouch: a long duration of IPAA (OR, 1.20; 95% CI, 1.12-1.30) and current smoking (OR, 4.77; 95% CI, 1.39-16.25); for cuffitis: arthralgias (OR, 4.13; 95% CI, 1.91-8.94) and younger age (OR, 1.16; 95% CI, 1.01-1.33); and for IPS: use of antidepressants (OR, 4.17, 95% CI, 1.95-8.92) or anti-anxiety agents (OR, 3.21; 95% CI, 1.34-7.47). CONCLUSIONS: The majority of risk factors for the 4 inflammatory and noninflammatory conditions of IPAA are different, suggesting that each of these diseases has a different etiology and pathogenesis. The identification and modification of these risk factors might help patients and clinicians to make a preoperative decision for IPAA, reduce IPAA-related morbidity, and improve response to treatment.

Adult↗
PubMed2003

Fate of the pouch in 151 pediatric patients after ileal pouch anal anastomosis.

BACKGROUND/PURPOSE: Ileal pouch anal anastomosis (IPAA) offers many pediatric patients a surgical cure for mucosal ulcerative colitis (MUC) with preservation of anal continence. However, some patients incur serious problems after surgery including chronic pouchitis and pouch failure. The goal of this study is to identify clinical and pathologic factors that are associated with an adverse outcome of IPAA. METHODS: A retrospective analysis of outcome was performed in 151 consecutive patients < or = 21 years of age who underwent IPAA with a mean follow-up of 7.24 years (range, 2 to 15 years). Patients were categorized into 4 outcome groups: A, no pouchitis; B, mild, acute pouchitis; C, chronic refractory pouchitis; and D, pouch failure. Pairwise comparisons were used to test the association between the groups and clinical and pathologic variables including age, sex, duration of symptoms, perianal disease, colonoscopic histology, terminal ileitis, operation type, staged versus unstaged IPAA, colonic specimen histology, early postoperative complications defined as less than 31 days postsurgery, late postoperative complications defined as 31 or more days postsurgery, and pouch fistulae. Crohn's disease as a definitive diagnosis and indeterminant colitis, a histologic diagnosis, also were tested for association with the above variables and outcome groups. RESULTS: One hundred and fifty-one pediatric patients underwent IPAA utilizing mucosectomy and hand-sewn S or J (n = 44) and stapled J or S-W anastomosis (n = 107) with 0% mortality rate and outcome as follows: group A, n = 54; group B, n = 73; group C, n = 11; group D, n = 13. Variables strongly associated with poor outcome, groups C and D, were duration of symptoms (P =.03), perianal disease (P =.03), late complications (P <.001), pouch fistulae (P <.001), and Crohn's disease (P <.0001). Furthermore, Crohn's disease was associated strongly with female gender (P =.01), perianal disease (P =.004), early (P =.006) and late (P <.001) complications, and pouch fistula (P <.001). The findings of indeterminant colitis, terminal ileitis, and early postoperative complications did not show significant differences between the 4 outcome groups. CONCLUSIONS: Crohn's disease appears to be an important determinant of postoperative complications, chronic pouchitis, and pouch failure and occurred in 15% of the authors' patients after IPAA. Indeterminant colitis and the intraoperative findings of terminal ileitis are not associated with Crohn's disease or adverse outcome after IPAA in pediatric patients. Operation type and stage do not alter the clinical course after IPAA in pediatric patients.

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