Are pANCA, ASCA, or cytokine gene polymorphisms associated with pouchitis? Long-term follow-up in 102 ulcerative colitis patients

OBJECTIVE: Pouchitis is the most frequent complication after ileal pouch-anal anastomosis for ulcerative colitis. This study aims to analyze the frequency and characteristics of pouchitis in long-term follow-up in a large population, and to determine whether a significant association exists between five immunogenetic markers and pouchitis. METHODS: From a population of over 500 ulcerative colitis patients who had undergone ileal pouch-anal anastamosis 5-12 yr earlier, 102 subjects participated in the study. Using clinical data obtained from interviews and chart reviews, patients were classified into three groups: no pouchitis; 1-2 episodes per year; and >2 episodes per year. Coded sera from the patients were analyzed for ulcerative colitis-associated perinuclear antineutrophil cytoplasmic antibodies and Crohn's disease-associated anti-saccharomyces cerevesiae antibodies. Interleukin-1 receptor antagonist, tumor necrosis factor (TNF), and lymphotoxin beta (lymphotoxin) polymorphisms were also analyzed. RESULTS: Pouchitis affected 49% of the study population. Antineutrophil cytoplasmic antibodies, anti-saccharomyces cerevesiae antibodies, and lymphotoxin-beta polymorphisms were not associated with pouchitis. Carriage of interleukin-1 receptor antagonist allele 2 was significantly greater among those without pouchitis than those with pouchitis. Patients without pouchitis had a significantly greater carriage rate of TNF allele 2. CONCLUSIONS: Perinuclear antineutrophil cytoplasmic antibodies and anti-saccharomyces cerevesiae antibodies are not correlated with pouchitis, but interleukin-1 receptor antagonist and TNF may play a role in its development. Further evaluation of these markers in pouchitis will require larger populations, long-term prospective observation, and studies that correlate polymorphisms with specific immunologic functions.     

Indeterminate colitis: the real story

PURPOSE: Up to one in five patients undergoing surgery for ulcerative colitis will have ambiguous histology, with features of both ulcerative colitis and Crohn's disease, and are categorized as having indeterminate colitis. We hypothesized that functional outcomes in indeterminate colitis patients undergoing ileal pouch-anal anastomosis are comparable with those of ulcerative colitis patients undergoing ileal pouch-anal anastomosis. METHODS: Physician-conducted interviews of 120 consecutive ileal pouch-anal anastomosis patients with a preoperative diagnosis of ulcerative colitis were reviewed, with a mean follow-up of 54 months. All colectomy specimens were reviewed by a single pathologist. Any changes in histologic diagnosis from ulcerative colitis to indeterminate colitis or Crohn's disease, frequency of postoperative complications, pouch function, and long-term postoperative medication usage were recorded. RESULTS: Although postoperative fistulas were more common in indeterminate colitis than ulcerative colitis (26 vs. 10 percent; P = 0.02, chi-squared), no indeterminate colitis patient required a permanent ileostomy as compared with six ulcerative colitis patients. Long-term functional results were similar. Overall, two-thirds of patients developed pouchitis. Ulcerative colitis and Crohn's disease patients were more likely to have had >3 episodes of pouchitis (58 and 72 percent) compared with indeterminate colitis patients (29 percent; P = 0.006, chi-squared). A greater number of Crohn's disease patients required maintenance oral antibiotic therapy (64 percent) to achieve satisfactory functional results compared with both indeterminate colitis and ulcerative colitis patients (20 and 28 percent; P = 0.014, chi-squared). CONCLUSIONS: Although ileal pouch-anal anastomosis patients with indeterminate colitis have more postoperative fistulas, long-term function is equal to that of ulcerative colitis patients and better than Crohn's disease patients. Ileal pouch-anal anastomosis should be offered to patients with indeterminate colitis and those with severe colitis in whom clear differentiation between indeterminate colitis and ulcerative colitis cannot be made.     

Association of the interleukin 1 receptor antagonist gene with ulcerative colitis in Northern European Caucasians

BACKGROUND AND AIMS: An association between the allele 2 of the interleukin 1 receptor antagonist gene variable number tandem repeats polymorphism in intron 2 and ulcerative colitis was first reported in 1994. Subsequent studies in Caucasian Northern European patients have not confirmed this, although trends towards an association were observed. The lack of statistical significance could reflect inadequate power. In this study the association was reassessed in a large independent set of well characterised Caucasian patients and a meta-analysis of reported patient series was performed. PATIENTS AND METHODS: A total of 320 patients with endoscopically and histologically confirmed ulcerative colitis (124 pancolitis, 196 left sided and distal disease) and 827 ethnically matched controls were genotyped at polymorphic sites in the interleukin 1 receptor antagonist gene. Carriage rates were compared using chi(2) statistics. A meta-analysis of this and seven previous studies in North European Caucasian patients was performed using the Mantel-Haenszel chi(2) test. RESULTS: Patients had a significantly increased carriage rate of allele 2 compared with controls (52% v 45%; odds ratio 1.3 (95% confidence interval (CI) 1.01-1.7); p=0.04). The allele 2 carriage rate was highest in extensive colitis (carriage rate 56%; odds ratio 1.5 (95% CI 1.1-2.3) p=0.02) and in individuals who had undergone colectomy (carriage rate 55%; odds ratio 1.5 (95% CI 0.95-2.4); p=0.08). Meta-analysis of all eight studies showed a significant association between carriage of allele 2 and ulcerative colitis (odds ratio 1.23 (95% CI 1.04-1.45); p=0.01). CONCLUSIONS: The association of the interleukin 1 receptor antagonist gene polymorphism with ulcerative colitis is confirmed. The association is minor and confers only a small risk to an individual but will contribute a high attributable risk in a population due to the high allelic frequency. Accurate phenotypic characterisation defines more homogeneous subsets of patients, such as those with extensive disease, in whom the association is greater.     

Pouchitis Disease Course after Orthotopic Liver Transplantation in Patients with Primary Sclerosing Cholangitis and an Heal Pouch-Anal Anastomosis

Objective: Primary sclerosing cholangitis is associated with the development of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis. This study determined the effect of liver transplantation for primary sclerosing cholangitis on the disease course of pouchitis.
Methods: Seven patients with an ileal pouch-anal anastomosis for ulcerative colitis underwent liver transplantation for primary sclerosing cholangitis. The medical record was reviewed to determine the pouchitis activity and pattern (no pouchitis, single acute, recurrent acute, chronic) before and after transplantation.
Results: Five of seven patients had pouchitis before transplant [recurrent acute (n = 3), chronic (n = 2)], and four of those five continued to have pouchitis after transplant (all chronic). Pretransplant sera were positive for antineutrophil cytoplasmic antibody in 6/6 patients, compared to 5/6 patients posttransplant. One patient with pouchitis pre-transplant became negative for antineutrophil cytoplasmic antibody posttransplant but continued to have pouchitis.
Conclusion: Pouchitis occurs frequently in patients with primary sclerosing cholangitis and an ileal pouch-anal anstomosis for ulcerative colitis. Liver transplantation does not alter the disease course of pouchitis for most of these patients.     

Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC), present in 5% of patients with ulcerative colitis, may be associated with pouchitis after ileal pouch-anal anastomosis. The cumulative frequency of pouchitis in patients with and without PSC who underwent ileal pouch-anal anastomosis for ulcerative colitis was determined. A total of 1097 patients who had an ileal pouch-anal anastomosis for ulcerative colitis, 54 with associated PSC, were studied. Pouchitis was defined by clinical criteria in all patients and by clinical, endoscopic, and histological criteria in 83% of PSC patients and 85% of their matched controls. PSC was defined by clinical, radiological, and pathological findings. One or more episodes of pouchitis occurred in 32% of patients without PSC and 63% of patients with PSC. The cumulative risk of pouchitis at one, two, five, and 10 years after ileal pouch-anal anastomosis was 15.5%, 22.5%, 36%, and 45.5% for the patients without PSC and 22%, 43%, 61%, and 79% for the patients with PSC. In the PSC group, the risk of pouchitis was not related to the severity of liver disease. In conclusion, the strong correlation between PSC and pouchitis suggest a common link in their pathogenesis.     

Secondary pouchitis in a post-operative patient with ulcerative colitis, successfully treated by salvage surgery

We report a case of secondary pouchitis, defined as a mucosal inflammatory lesion in the ileal reservoir provoked by pouch-related complication following total colectomy and pouch anal anastomosis, which was successfully treated by salvage surgery- A 20-year-old woman with ulcerative colitis developed acute severe bloody diarrhea following proctocolectomy, ileal pouch-anal anastomosis and diverting ileostomy. She was diagnosed as having a secondary pouchitis mainly caused by a peripouch abscess and partly concerned with the abnormal pouch formation. The remnant rectum and ileal pouch were excised and ileal pouch-anal anastomosis and diverting ileostomy were constructed. The postoperative course was uneventful with no sign of pouchitis. Salvage surgery may be indicated to treat secondary pouchitis when caused by surgery-related complications.     

Misdiagnosis of specific cytomegalovirus infection of the ileoanal pouch as refractory idiopathic chronic pouchitis

PURPOSE: Chronic nonspecific reservoir ileitis (pouchitis) occurs in 5 to 10 percent of patients who undergo ileal pouch-anal anastomosis for ulcerative colitis. Specific infection of the ileal pouch-anal anastomosis with cytomegalovirus has not been reported. AIM: We report two patients with specific cytomegalovirus infection of the ileal pouchanal anastomosis, initially misdiagnosed as idiopathic chronic pouchitis. CASE SERIES: Patient 1 had ileal pouchanal anastomosis for ulcerative colitis. Three years later she had diarrhea, fever, pelvic pain, and pouch inflammation at endoscopy consistent with pouchitis. She had no response to medical therapy. Repeat endoscopy showed persistent inflammation and biopsies showed cytomegalovirus. She had symptomatic improvement after treatment with intravenous ganciclovir, 10 mg/kg/day for ten days (stopped for rash). Repeat pouch biopsies were negative for cytomegalovirus. Patient 2 had ileal pouch-anal anastomosis for ulcerative colitis. Nine years later she had resection of obstructing stricture at previous loop ileostomy site. She underwent reoperation with ileostomy and pouch defunctionalization for peritonitis. Four weeks later she had fever and bloody discharge from the diverted pouch. Pouch endoscopy with biopsy showed inflammation consistent with pouchitis. She had no response to medical therapy. Re-examination of pouch biopsies with a specific monoclonal immunofluorescent stain showed cytomegalovirus. She had symptomatic improvement after treatment with intravenous ganciclovir, 10 mg/kg/day for 21 days. Repeat pouch biopsies were negative for cytomegalovirus. CONCLUSIONS: Specific cytomegalovirus infection of the ileal pouch-anal anastomosis may be misdiagnosed as idiopathic refractory chronic pouchitis. Cytomegalovirus must be excluded before immune modifier therapy or pouch excision in these patients.     

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 liters 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.     

Surgical Management of Ulcerative Colitis in the Presence of Primary Sclerosing Cholangitis

INTRODUCTION: The surgical management of ulcerative colitis in the patient with primary sclerosing cholangitis is controversial. METHODS: This study was designed as a retrospective chart review of all patients with primary sclerosing cholangitis who were surgically treated for ulcerative colitis. RESULTS: Sixteen patients with primary sclerosing cholangitis and ulcerative colitis were identified. The indication for ulcerative colitis surgery was dysplasia in 7 patients (44 percent), cancer in 2 (13 percent), intractability in 4 (25 percent), and unknown in 1. Final colon pathology demonstrated cancer in three patients and dysplasia in four. Two patients had biliary cancer discovered at the time of orthotopic liver transplantation. Thirteen patients were known to have primary sclerosing cholangitis when they underwent surgery for ulcerative colitis; two patients with severe primary sclerosing cholangitis underwent simultaneous orthotopic liver transplantation/total abdominal colectomy and did well with subsequent ileal pouch reconstruction. Two patients had orthotopic liver transplantation first and then ileal pouch-anal anastomosis (1 patient) or total abdominal colectomy (1 patient) and did well. Seven patients had well-controlled primary sclerosing cholangitis on medication and underwent ileal pouch-anal anastomosis or total abdominal proctocolectomy without significant hepatic compromise. One patient with moderate primary sclerosing cholangitis underwent ileorectal anastomosis and had severe liver failure postoperatively but survived. Another patient with worsening primary sclerosing cholangitis after total abdominal colectomy has since developed persistent bleeding from peristomal varices. CONCLUSIONS: The overall cancer/premalignant lesion rate was high (50 percent in this study) in patients with primary sclerosing cholangitis and ulcerative colitis. Complications associated with the surgical management of ulcerative colitis are largely dictated by the degree of liver disease present at the time of surgery. Patients with significant primary sclerosing cholangitis that requires colectomy can undergo simultaneous orthotopic liver transplantation/total abdominal colectomy and then be candidates for subsequent ileal pouch-anal anastomosis reconstruction once liver function has improved. Patients with well-controlled primary sclerosing cholangitis can undergo ileal pouch-anal anastomosis surgery safely.     

Is Ileal pouch-anal anastomosis really the procedure of choice for patients with ulcerative colitis?

PURPOSE: Ileal pouch-anal anastomosis is widely claimed to have replaced total proctocolectomy with ileostomy as the “procedure of choice” for ulcerative colitis, largely on the basis of a perceived improved quality of life. There exists relatively little support for this assertion in the literature. Our aim was to determine if educated patients choosing total proctocolectomy with ileostomy have a similar quality of life as with ileal pouch-anal anastomosis. METHODS: All patients with ulcerative colitis referred to a single surgeon and deemed an appropriate surgical candidate were educated and then offered ileal pouch-anal anastomosis or total proctocolectomy with ileostomy. Age, gender, and complications (including pouchitis) were recorded prospectively, and all patients were questioned regarding functional outcome and level of satisfaction. They were then asked to complete a slightly modified Inflammatory Bowel Disease Questionnaire, which was analyzed by categoric and overall scores. RESULTS: Sixty-seven patients underwent elective surgery for ulcerative colitis during the study period. Fifty-five patients chose ileal pouch-anal anastomosis, and 12 had total proctocolectomy with ileostomy. The groups were similar except for younger age and longer follow-up in the ileal pouch-anal anastomosis group. Patients undergoing ileal pouch-anal anastomosis had significantly more short-term or long-term complications (49vs. 8 percent), with pouchitis being the most frequent complication. There was no difference in level of satisfaction between the two groups, and no patient in either group wishes they had undergone the other procedure. There was no difference in the overall or any categoric Inflammatory Bowel Disease Questionnaire score. CONCLUSION: Patient satisfaction with both procedures was similarly high. Patients who undergo ileal pouch-anal anastomosis can expect a high level of satisfaction, with a good quality of life. However, educated patients choosing an ileostomy can achieve the same quality of life, without the higher complication rate associated with a pelvic pouch.     

Leukocytapheresis for the treatment of active pouchitis: a pilot study

BACKGROUND: Pouchitis is a major long-term complication of ileal pouch-anal anastomosis for ulcerative colitis. The aim of this study is to investigate the efficacy of leukocytapheresis for the treatment of active pouchitis. METHODS: Eight patients with active pouchitis received leukocytapheresis weekly for 5 weeks in an open-label treatment protocol together with baseline therapy. RESULTS: Patients showed significant improvement in their pouchitis disease activity index scores, from 9.5 (range, 8-10) to 4.0 (range, 2-8) (P < 0.05). Six (75%) of the 8 treated patients achieved remission. No adverse events were observed. CONCLUSIONS: Leukocytapheresis therapy could be a new therapeutic strategy for patients with pouchitis after ileal pouch-anal anastomosis for ulcerative colitis. These encouraging results lead us to propose a randomized controlled trial.     

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.Reprints are not available.Supported by USPHS Grant PO 1 DK46763 and the Feintech Family Foundation.     

Ileal pouch-anal anastomosis in patients with indeterminate colitis

PURPOSE: Patients with chronic ulcerative colitis who undergo proctocolectomy and are found intraoperatively to harbor histologic signs suggesting Crohn's disease have indeterminate colitis; nonetheless, ileal pouch-anal anastomosis is usually performed. The aim of this study was to determine the long-term outcome of ileal pouch-anal anastomosis in patients with indeterminate colitis compared with a cohort of patients with chronic ulcerative colitis. METHOD: Review of an ileal pouch-anal anastomosis registry identified 1,437 patients with chronic ulcerative colitis and 82 patients with indeterminate colitis who underwent an ileal pouch-anal anastomosis between 1981 and 1995. The median follow-up was 83 (range, 1–192) months. Demographic data and functional outcomes were compared by chi-squared and Wilcoxon's rank-sum tests. Probabilities of complications and pouch failure were analyzed using Kaplan-Meier and log-rank techniques. Finally, Bonferroni adjustments were used for multiple comparisons. RESULTS: Patients with indeterminate colitis and chronic ulcerative colitis were comparable in terms of gender and length of follow-up. The mean age of the chronic ulcerative colitis group was higher (34vs. 31; P<0.01). At ten years patients with indeterminate colitis had significantly more episodes of pelvic sepsis (17 percent indeterminate colitisvs. 7 percent chronic ulcerative colitis; P<0.001), pouch fistula (31vs. 9 percent; P<0.001), and pouch failure (27vs. 11 percent; P<0.001). Importantly, during follow-up fully 15 percent of patients with indeterminate colitis, but only 2 percent of patients with chronic ulcerative colitis, had their original diagnosis changed to Crohn's disease (P<0.001). When the outcomes of these patients newly diagnosed with Crohn's disease were considered separately, the rate of complications for the remaining patients with indeterminate colitis was identical to that of patients with chronic ulcerative colitis. Functional outcomes were comparable among all three groups. CONCLUSION: After ileal pouch-anal anastomosis patients with indeterminate colitis who did not develop Crohn's disease subsequently experienced long-term outcomes nearly identical to patients with chronic ulcerative colitis. Crohn's disease, whether it develops after surgery for chronic ulcerative colitis or indeterminate colitis, is associated with poor long-term outcomes.Presented at the meeting of the American College of Surgeons, San Francisco, California, October 10 to 15, 1999.     

Predictors of Pouchitis after Ileal Pouch-Anal Anastomosis: A Retrospective Review

Purpose The primary end point of this study was to determine the risk factors that predict chronic pouchitis in those patients having ileal pouch-anal anastomosis. Methods A total of 237 patients with ulcerative colitis and undergoing ileal pouch-anal anastomosis by one surgeon at Oregon Health & Science University from 1993 to 2003 were evaluated. Data were gathered via retrospective chart reviews and by a questionnaire administered by telephone in 2004. Patients were excluded if there was less than one-year follow-up documented in the chart or they could not be contacted by telephone (n = 62), postoperative diagnosis of Crohn’s disease (n = 3), failed ileoanal procedure (n = 1), and one-stage ileal pouch-anal anastomosis (n = 3), leaving 167 patients for evaluation. Patients were defined as having chronic pouchitis (>3 episodes of pouchitis) or no pouchitis (≤ 3 episodes of pouchitis). Potential risk factors included number of operations used to perform ileal pouch-anal anastomosis, fulminant ulcerative colitis with two-stage operation, duration of diverting ileostomy after pouch formation, primary sclerosing cholangitis, other extraintestinal manifestations of ulcerative colitis, preoperative liver function tests, duration of ulcerative colitis, and the occurrence of postoperative complications. Initial univariate analysis was performed on all risk factors. Multivariate analysis was performed on all univariate risk factors with P values < 0.2. Results The prevalence of chronic pouchitis in our population was 46 percent. The following variables were identified during univariate analysis and entered into a multivariate model: preoperative serum albumin (P = 0.07), PSC (P = 0.126), duration of diverting ileostomy (P = 0.111), fulminant ulcerative colitis with two-stage operation, (P = 0.051), the presence of postoperative complications (P = 0.031), and the type of postoperative complications (anastomotic complications, P = 0.013). Patients who did not undergo diverting ileostomy at the time of their ileal pouch-anal anastomosis trended toward a lower likelihood of developing chronic pouchitis (P = 0.06). Multivariate analysis showed that patients with postoperative complications (53 percent, P = 0.042), specifically anastomotic complications, were more likely to develop chronic pouchitis (P = 0.005). Eight percent of patients had primary sclerosing cholangitis and 11 percent of patients had at least one extraintestinal manifestation of ulcerative colitis. Patients with primary sclerosing cholangitis were not more likely to develop chronic pouchitis (P = 0.168). Patients with extraintestinal manifestations also were not more likely to develop chronic pouchitis (P = 0.273). Conclusions Chronic pouchitis is a frequent complication after ileal pouch-anal anastomosis. In this study patients with primary sclerosing cholangitis or other extraintestinal manifestations of ulcerative colitis were not more likely to develop chronic pouchitis. Patients with postoperative complications, specifically anastomotic complications after ileal pouch-anal anastomosis, were more likely to develop chronic pouchitis and may benefit from early strategies to prevent pouchitis. Poster presentation at the meeting of the American College of Gastroenterology, Honolulu, Hawaii, October 28 to November 2, 2005.     

Crohn's disease-associated genetic marker is seen in medically unresponsive ulcerative colitis patients and may be associated with pouch-specific complications

PURPOSE: Genetic markers have been used to define subgroups of patients within the broad categories of Crohn's disease and ulcerative colitis that may differ in clinical course and response to medical therapy. The tumor necrosis factor microsatellite haplotype a2b1c2d4e1 has been found previously to be present in 24 percent of patients with Crohn's disease and only 5 percent of patients with ulcerative colitis. This study examined associations between this microsatellite haplotype and the postoperative clinical course of patients with ulcerative colitis undergoing ileal pouch-anal anastomosis. METHODS: As part of a large, controlled, prospective study to correlate genetic markers with clinical phenotypes, tumor necrosis factor microsatellite alleles at five loci (a, b, c, d, and e) were determined from genomic DNA by polymerase chain reaction in 32 patients with a clinical and histopathologic diagnosis of ulcerative colitis who underwent ileal pouch-anal anastomosis for medically unresponsive disease. All patients with ileal pouch-anal anastomosis were also studied prospectively for pouch-specific complications. RESULTS: The tumor necrosis factor haplotype a2b1c2d4e1 was present in 11 patients. Median follow-up was 19 months. Thirteen patients had a pouch-specific complication (12 pouchitis and 1 pouch-perineal fistula). Six of 11 patients (55 percent) with the haplotype had a pouch-specific complication compared with 7 of the 21 patients (33 percent) who did not possess this haplotype (P=0.22). Median time from surgery to pouch-specific complication was eight months. Patients with the haplotype had a median time to pouch-specific complication of three months, whereas patients without the haplotype had a median time of 11 months (P=0.04). In addition, 36 percent of patients with the haplotype had chronic pouch complicationsvs. only 10 percent of patients without the haplotype (P=0.05). CONCLUSION: The Crohn's disease-associated tumor necrosis factor haplotype a2b1c2d4e1 may define a subgroup of medically unresponsive patients with ulcerative colitis who are predisposed to a higher incidence of pouch-specific complications after ileal pouch-anal anastomosis.Read at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997.     

Pregnancy and Delivery Before and After Ileal Pouch-Anal Anastomosis for Inflammatory Bowel Disease: Immediate and Long-Term Consequences and Outcomes

PURPOSE: This study was designed to evaluate pregnancy, delivery, and functional outcome in females before and after ileal pouch-anal anastomosis for chronic ulcerative colitis.METHODS: From a prospective database of 1,454 patients who underwent ileal pouch-anal anastomosis for chronic ulcerative colitis between 1981 and 1995, a standardized questionnaire was sent to all female patients aged 40 years or younger at the time of ileal pouch-anal anastomosis (n = 544).RESULTS: The response rate was 83 percent (450/544) with a mean follow-up after ileal pouch-anal anastomosis of 13 years. A total of 141 females were pregnant after the chronic ulcerative colitis diagnosis, but before ileal pouch-anal anastomosis (236 pregnancies; mean, 1.7) and 87 percent delivered vaginally. A mean of five (range, 1–16) years after ileal pouch-anal anastomosis, 135 females were pregnant (232 pregnancies; mean, 1.7). Comparison of pregnancy and delivery before and after ileal pouch-anal anastomosis in the same females (n = 37) showed no difference in birth weight, duration of labor, pregnancy/delivery complications, vaginal delivery rates (59 percent before vs. 54 percent after ileal pouch-anal anastomosis), and unplanned cesarean section (19 vs.14 percent). Planned cesareans occurred only after ileal pouch-anal anastomosis and were prompted by obstetrical concerns in only one of eight. Pouch function at first follow-up after delivery (mean, 7 months) was similar to pregravida function. After ileal pouch-anal anastomosis, daytime stool frequency was the same after delivery as pregravida (5.4 vs. 5.4, not significant) but was increased at the time of last follow-up (68 months after delivery; 5.4 vs. 6.4; P < 0.001). The rate of occasional fecal incontinence also was higher (20 percent after ileal pouch-anal anastomosis and 21 percent pregravida vs. 36 percent at last follow-up; P = 0.01). No difference in functional outcome was noted compared with females who were never pregnant after ileal pouch-anal anastomosis (n = 307). Age and becoming pregnant did not affect the probability of pouch-related complications, such as stricture, pouchitis, and obstruction.CONCLUSIONS: Successful pregnancy and vaginal delivery occur routinely in females with chronic ulcerative colitis before and after ileal pouch-anal anastomosis. The method of delivery should be dictated by obstetrical considerations. Pouch function and the incidence of complications in females with pregnancies seem largely unaffected long-term.Read at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 23 to 27, 2003.     

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 pouchanal 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.Presented at the XVIIth Biennial Congress of the International Society of University Colon and Rectal Surgeons, Malmö, Sweden, June 7 to 11, 1998.     

Quality of life after proctocolectomy and ileal pouch-anal anastomosis in patients with ulcerative colitis

Purpose

While ileal pouch-anal anastomosis is performed in many patients with ulcerative colitis, conflicting data exist about its effects on quality of life. We aimed to determine quality of life and to identify risk factors for impaired quality of life in these patients.

Methods

Forty-eight of 82 patients (59 %; median follow-up 57 months [range 21–93 months]) after ileal pouch-anal anastomosis for ulcerative colitis were compared to 48 matched healthy controls. Generic, health-, and disease-related, as well as symptom-specific quality of life was analyzed using five well-established quality of life instruments.

Results

Although generic quality of life was comparable between groups, health-related quality of life was impaired after ileal pouch-anal anastomosis. While high stool frequency was associated with impaired health-related and disease-specific quality of life, fecal incontinence and history of pouchitis also caused a deterioration of generic and symptom-related quality of life. Seventy-seven percent of patients reported their quality of life to be better compared to the situation before surgery and 88 % would undergo ileal pouch-anal anastomosis again.

Conclusions

Overall quality of life after ileal pouch-anal anastomosis is good. However, high stool frequency, fecal incontinence, and pouchitis are associated with impaired quality of life and should be prevented or treated to the best possible extent.     

Ileal pouch-anal anastomosis in patients with colorectal cancer

When colorectal cancer complicates chronic ulcerative colitis or familial adenomatous polyposis, the role of ileal pouch-anal anastomosis is uncertain because of concerns that the procedure may compromise oncologic therapy and that oncologic therapy may compromise ileal pouch-anal anastomosis function. AIM: This study was undertaken to investigate the impact both of ileal pouch-anal anastomosis on cancer outcomes and of cancer treatments on ileal pouch-anal anastomosis function. PATIENTS AND METHODS: Of 1,616 patients undergoing ileal pouch-anal anastomosis for chronic ulcerative colitis or familial adenomatous polyposis (1981–1994), 77 patients were identified with adenocarcinoma of the colon (56), rectum (17), or both (4). Data were obtained from an ileal pouch-anal anastomosis registry, case notes, and postal and telephone surveys. RESULTS: Mean age of the 77 index patients was 37 (range, 13–60) years. Stage distribution was as follows: Stage 0, 9; Stage I, 31; Stage II, 15; Stage III, 22 patients. Twelve patients died with systemic disease (6 with a local component) after a mean follow-up of 6 (range, 2–15) years. Twenty-two patients received adjuvant therapy (chemotherapy, 16; radiotherapy, 2; both, 4 patients). Chemotherapy complications requiring dose reduction or interruption occurred in three (15 percent) patients. One patient developed radiation enteritis (17 percent). Pouch failure occurred in 16 percent of cancer patients, compared with 7 percent for the overall registry. There were no differences between cancer and non-cancer groups in operative complications, median stool frequency, incontinence, pad usage, or pouchitis. CONCLUSIONS: Although pouch failure is more common, ileal pouch-anal anastomosis can be performed in the setting of colorectal cancer without significant impact on oncologic outcome or long-term ileal pouch-anal anastomosis function.     

Indeterminate colitis

Uncertainty persists concerning the long-term results of ileal pouch-anal anastomosis performed for indeterminate colitis. PURPOSE: This study was designed to compare functional outcomes of ileal pouch-anal anastomosis in patients with typical chronic ulcerative colitis and indeterminate colitis. METHOD: Seventy-one ileoanal pouch patients were identified with a diagnosis of indeterminate colitis. Mean follow-up was 56 months. Outcomes were compared with 1,232 chronic ulcerative colitis patients after ileal pouchanal anastomosis. Mean follow-up was 60 months. RESULTS: (mean±SD) There was no difference in the frequency of daily bowel movements (indeterminate colitis, 7±3,vs.chronic ulcerative colitis, 7±2). Daytime and nighttime incontinence rates were likewise similar. Prevalence of pouchitis was identical (33 percent). However, failure rate was higher in the indeterminate colitis group (indeterminate colitis, 19 percent,vs. chronic ulcerative colitis, 8 percent; (P =0.03)). CONCLUSIONS: At a mean of nearly five years after surgery, failure appears to occur more frequently in patients with indeterminate colitis than in patients with chronic ulcerative colitis. However, the great majority of indeterminate colitis patients (>80 percent) have long-term functional results identical to those of patients with chronic ulcerative colitis.