Background

When patients with ulcerative colitis or familial adenomatous polyposis syndromes have a colectomy to manage their disease, the surgeon may create a continent ileostomy or an ileal pouch-anal anastomosis. Patients present with increased frequency and decreased viscosity of stools. Pain, fever, malaise and overall discomfort may accompany the disorder. Rarely there are extra-gastrointestinal manifestations including arthrtis and erythema nodosum. Endoscopic appearance of the pouch reveals a hemorrhagic friable appearance with ulcers, sometimes of the aphthous type, and edema. Pseudomembrane formation may occur.

OUTLINE

Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

PATHOGENESIS

CHARACTERIZATION

Altered expression of the lymphocyte activation markers CD30 and CD27 in patients with pouchitis. Thomas PD, Forbes A, Nicholls RJ, Ciclitira PJ. Gastroenterology Dept, St. Mark's Hospital, Harrow, Middlesex, UK.

Scand J Gastroenterol 2001 Mar;36(3):258-64 Abstract quote BACKGROUND: The mechanism underlying the development of ileal pouch inflammation in ulcerative colitis patients (pouchitis) after restorative proctocolectomy is unclear. Persistent systemic T cell activation or expansion of specific memory cell populations could predispose certain patients to develop local inflammation within the neo-rectum. Therefore, the aim was to study the expression of the lymphocyte activation markers CD27, CD30, CD25 and CD69 on the CD45RO+ memory cell subset of isolated peripheral blood mononuclear cells (PBMC), soluble CD30 levels and mucosal CD30 expression in patients with pouchitis and in controls. METHODS: Flow cytometry was performed on PBMC isolated from patients with pouchitis (n = 9), without pouchitis (n = 10) and normal controls (n = 9). Serum CD30 was measured in patients with pouchitis (n = 25), without pouchitis (n = 26) and normal controls (n = 20) by ELISA. CD30 expression was quantified in pouchitis (n = 15) and normal pouch (n = 15) mucosa using a three-stage immunoperoxidase method. RESULTS: Naive CD45RO-CD27+ PBMC were significantly decreased in pouchitis (25.6%) compared to normal controls (34.4%), (P = 0.03). CD30, CD25 and CD69 subsets did not differ between the groups. Serum CD30 was increased in pouchitis patients 58 (1-380) U/ml compared to non-pouchitis 16.5 (1-290) U/ml, P=0.007, and normal controls 11 (2-80) U/ml, P = 0.0005. In the mucosa, the numbers of CD30+ cells were increased in pouchitis compared to non-inflamed pouches (P = 0.02). CONCLUSIONS: Increased sCD30 in pouchitis is associated with elevated mucosal expression. Of the activation markers studied, only the circulating naive CD27+ population differed in pouchitis patients compared with controls. The observed decrease in this cell type may reflect antigen priming and subsequent loss of CD27 implying that antigen driven activation of specific T cell subsets may occur in pouchitis.

 

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
MRI of pouch-related fistulas in ulcerative colitis after restorative proctocolectomy. Libicher M, Scharf J, Wunsch A, Stern J, Dux M, Kauffmann GW. Department of Diagnostic Radiology, University of Heidelberg, Germany.	J Comput Assist Tomogr 1998 Jul-Aug;22(4):664-8 Abstract quote PURPOSE: Our purpose was to determine the value of MRI in diagnosing pouch-related fistulas in patients with ulcerative colitis and to compare pulse sequences with and without contrast enhancement in their performance of visualization. METHOD: Forty-four patients with pelvic symptoms after restorative proctocolectomy underwent MRI. All 26 patients with pouch-related fistulas were treated surgically; 18 patients with pouchitis were treated conservatively. MRI was performed at 1.0 T with T1-weighted FLASH sequences before and after administration of Gd-DTPA, T2-weighted and proton density-weighted turbo SE sequences, and a T2-weighted fat saturation sequence. Images were analyzed for the presence of fistula; pulse sequences were additionally compared for best visualization on a four point scale of diagnostic confidence. RESULTS: MRI detected 23 of 26 cases of fistulas; there were no false-positive diagnoses. Surgery revealed fistulas in three cases in which no pathology was found on MRI. Two patients had a short sinus tract at the pouch-anal anastomosis, and a third patient had a pouch-vaginal fistula. The Gd-enhanced FLASH sequence obtained the highest score, and second best was the T2-weighted fat saturation technique. CONCLUSION: MRI is a valuable technique for diagnosing pouch-related fistulas, However, there are limitations in detection of short sinus tracts and pouch-vaginal fistulas. Highest diagnostic confidence is obtained with a Gd-enhanced FLASH sequence, which might be helpful after pelvic surgery or if the fact saturation technique is equivocal.
LABORATORY MARKERS
High level perinuclear antineutrophil cytoplasmic antibody (pANCA) in ulcerative colitis patients before colectomy predicts the development of chronic pouchitis after ileal pouch-anal anastomosis. Fleshner PR, Vasiliauskas EA, Kam LY, Fleshner NE, Gaiennie J, Abreu-Martin MT, Targan SR. Division of Colon and Rectal Surgery, Department of Surgery, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.	Gut 2001 Nov;49(5):671-7 Abstract quote BACKGROUND: The reported cumulative risk of developing pouchitis in ulcerative colitis (UC) patients undergoing ileal pouch-anal anastomosis (IPAA) approaches 50% after 10 years. To date, no preoperative serological predictor of pouchitis has been found. AIMS: To assess whether preoperative perinuclear antineutrophil cytoplasmic antibody (pANCA) expression was associated with acute and/or chronic pouchitis after IPAA. METHODS: Patients were prospectively assessed for the development of clinically and endoscopically proved pouchitis. Serum obtained at the time of colectomy in 95 UC patients undergoing IPAA was analysed for pANCA by ELISA and indirect immunofluorescence. pANCA+ patients were stratified into high level (>100 ELISA units (EU)/ml) (n=9), moderate level (40-100 EU/ml) (n=32), and low level (<40 EU/ml) (n=19) subgroups. RESULTS: Sixty of the 95 patients (63%) expressed pANCA. After a median follow up of 32 months (range 1-89), 32 patients (34%) developed either acute (n=14) or chronic (n=18) pouchitis. Pouchitis was seen in 42% of pANCA+ patients compared with 20% of pANCA- patients (p=0.09). There was no significant difference in the incidence of acute pouchitis between the three pANCA+ patient subgroups. The cumulative risk of developing chronic pouchitis among patients with high level pANCA (56%) before colectomy was significantly higher than in patients with medium level (22%), low level (16%), and those who were pANCA- (20%) (p=0.005). Multivariate analysis revealed that the sole parameter significantly associated with the development of chronic pouchitis after IPAA was the presence of high level pANCA before colectomy (p=0.005). CONCLUSION: High level pANCA before colectomy is significantly associated with the development of chronic pouchitis after IPAA.

 

GROSS APPEARANCE/ CLINICAL VARIANTS

CHARACTERIZATION

Patterns of distribution of endoscopic and histological changes in the ileal reservoir after restorative proctocolectomy for ulcerative colitis. A long-term follow-up study. Setti Carraro PG, Talbot IC, Nicholls JR. Ospedale Maggiore, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.

Int J Colorectal Dis 1998;13(2):103-7 Abstract quote OBJECTIVE: This study was undertaken to assess the long-term macroscopic appearance of the ileal reservoir after restorative proctocolectomy for ulcerative colitis, to determine whether there is any correlation between macroscopic and histological changes and whether the distribution of these is homogeneous, focal or patchy. BACKGROUND: No study has examined the macroscopic appearance of the ileal reservoir over a long period and it is still unknown to what degree histological changes are diffuse or patchy. Moreover, the relationship between macroscopic and histological changes is poorly understood. METHOD: Fifty-nine patients were examined by one clinician (PSC) 5.3-14.5 years (median 8.2 years) postoperatively. A rigid sigmoidoscopy of the reservoir was performed. Four zones in the posterior midline at 5-cm intervals from the ileoanal anastomosis were inspected. At each level a macroscopic score of severity of inflammation was given and a biopsy taken. The degree of acute and chronic inflammation was assessed using a histopathological scoring system. RESULTS: All reservoirs showed macroscopic abnormalities, which were more marked distally in 14 (24%). There was no case in which severity of inflammation was greater in proximal than in distal zones. Endoscopy overall correlated with both acute and chronic histological changes. On histological examination the patients could be divided into three groups as follows: (1) all four biopsies were normal (group 1, n = 8, 14%), (2) the score of acute and chronic inflammation decreased from distal to proximal zones (group 2, n = 25, 42%) and (3) all four biopsies were abnormal with the same score (group 3, n = 26, 44%). The latter group significantly correlated with a present or past history of pouchitis. CONCLUSION: The study has shown that when there is a gradation of inflammation within the ileal reservoir this is more severe in distal than in proximal zones.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
Crohn's-like complications in patients with ulcerative colitis after total proctocolectomy and ileal pouch-anal anastomosis. Goldstein NS, Sanford WW, Bodzin JH. Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Michigan 48324, USA.	Am J Surg Pathol 1997 Nov;21(11):1343-53 Abstract quote 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.
Restorative proctocolectomy: histological assessment and cytometric DNA analysis of ileal pouch biopsies. Pronio A, Montesani C, Vecchione A, Giovagnoli MG, Giarnieri E, Nardi F, Nigri G, Ribotta G. University of Rome La Sapienza VI Department of Surgery, Italy.	Hepatogastroenterology 1997 May-Jun;44(15):691-7 Abstract quote BACKGROUND/AIMS: The pathological changes and the risk of developing cancer in the ileal pouch mucosa of patients who received restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) were studied. The presence or absence of remaining rectal mucosa below the IPAA in both patients with stapled and handsewn IPAA was also examined. MATERIALS AND METHODS: Endoscopy of the ileal pouch was performed on 38 patients at 4, 12, 18 and 36 months after restorative proctocolectomy with ileal pouch. Mucosal biopsy specimens were taken from the ileal reservoir in order to assess the histological incidence of inflammation. In 23 patients, biopsies were taken to perform cytometric DNA analysis. Clinical symptoms of pouchitis (over six evacuations in 24 hours, night-time evacuations, leakage of feces, bloody diarrhea, abdominal pain and fever) were recorded and correlated with the histological findings. Biopsies were also sampled below the ileo-anal anastomosis (IPAA) in order to identify residual rectal mucosa. RESULTS: Results of histological assessment showed various degrees of chronic inflammation increasing over time (from 42 to 60%) while the presence of both acute and chronic inflammation of the reservoir was less frequent (from 18 to 30%). Villous atrophy was present in 39-68% of patients and the grade of villous atrophy was correlated to the grade of inflammation. Clinical pouchitis was present in 3 to 8% of cases at the different controls and it was always associated with the highest grade of histological inflammation and severe villous atrophy. No significant alteration of the DNA cellular content was observed. Very low incidence of aneuploidy (0.7-1% Ex.R.) has been reported in three cases. However, we found dysplasia in only one patient who underwent surgical treatment for familial polyposis coli. IPAA evaluation showed no residual rectal mucosa in 40% of cases with stapled IPAA; in the remaining 60%, we found a small amount of rectal mucosa (maximum 1 cm). We did not find rectal mucosa after handsewn IPAA with mucosectomy. CONCLUSIONS: Patients treated with restorative proctocolectomy with IPAA showed a higher and increased incidence of inflammation during follow-up. No significant alteration of DNA cellular content nor dysplasia of the pouch mucosa were observed. In this study the chance of leaving rectal mucosa after stapled IPAA was about 60%.
Prospective study of morphologic and functional changes with time in the mucosa of the ileoanal pouch: functional appraisal using transmucosal potential differences. Garcia-Armengol J, Hinojosa J, Lledo S, Roig JV, Garcia-Granero E, Martinez B. Department of General Surgery, University Clinic Hospital, University of Valencia, Spain.	Dis Colon Rectum 1998 Jul;41(7):846-53 Abstract quote PURPOSE: This study was undertaken to investigate the morphologic and functional changes with time in the mucosa of the ileoanal pouch. METHODS: A morphologic study by histopathologic analysis, mucosal morphometry, and mucin histochemistry and a functional study by analysis of transmucosal potential difference were performed in 27 patients with an ileoanal J-pouch after restorative proctocolectomy for ulcerative colitis. In 19 patients with a normal ileoanal pouch, two prospective follow-up analyses were performed after median functional pouch times of 14 and 39 months. We also evaluated eight patients with the diagnosis of pouchitis (median follow-up, 52.5 months). RESULTS: In the normal ileoanal pouch group, some degree of chronic and acute inflammatory infiltration was identified in 100 percent and 63.2 percent of cases, respectively, with no significant differences being observed between the two follow-up analyses. The mean villous atrophy index at the first and second follow-up was 0.54 and 0.52, respectively, significantly lower (P < 0.001; an indication of a greater degree of villous atrophy) than the value obtained from the control group with a healthy terminal ileum (0.77). The group of patients with pouchitis exhibited statistically significant differences in the degree of acute and chronic inflammatory infiltration, the extent of ulceration, the crypt depth, and the villous atrophy index, compared with patients without pouchitis. In the normal ileoanal pouch group, the median percentage of sulfomucin with each degree of atrophy (1=mild; 2=moderate; and 3=severe) was 2.6, 4.5, and 20.9 percent, respectively. In patients with pouchitis, the median percentage of sulfomucin was 5.9 percent. The mean transmucosal potential difference at the first follow-up (-25.3 mV) was significantly lower (P=0.001) than at the second (-30.4 mV). Significant differences were apparent with respect to both the normal ileum (-8.9 mV) and the normal rectum (-40.2 mV). CONCLUSION: These results suggest that the ileal pouch behaves as a neorectum, with different degrees of colonic metaplasia from a morphologic and a functional perspective.
Endoscopic and histologic evaluation together with symptom assessment are required to diagnose pouchitis. Shen B, Achkar JP, Lashner BA, Ormsby AH, Remzi FH, Bevins CL, Brzezinski A, Petras RE, Fazio VW. Department of Gastroenterology, Center for Inflammatory Bowel Disease, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.	Gastroenterology 2001 Aug;121(2):261-7 Abstract quote BACKGROUND & AIMS: Pouchitis often is diagnosed based on symptoms alone. In this study, we evaluate whether symptoms correlate with endoscopic and histologic findings in patients with ulcerative colitis and an ileal pouch-anal anastomosis. METHODS: Symptoms, endoscopy, and histology were assessed in 46 patients using Pouchitis Disease Activity Index (PDAI). Patients were classified as either having pouchitis (PDAI score > or =7; N = 22) or as not having pouchitis (PDAI score <7; N = 24). RESULTS: Patients with pouchitis had significantly higher mean total PDAI scores, symptom scores, endoscopy scores, and histology scores. There was a similar magnitude of contribution of each component score to the total PDAI for the pouchitis group. Of note, 25% of patients with symptoms suggestive of pouchitis did not meet the PDAI diagnostic criteria for pouchitis. In both groups, the correlation coefficients between symptom, endoscopy, and histology scores were near zero (range, -0.26 to 0.20; P > 0.05). CONCLUSIONS: The symptom, endoscopy, and histology scores each contribute to the PDAI and appear to be independent of each other. Symptoms alone do not reliably diagnose pouchitis.

 

DIFFERENTIAL DIAGNOSIS

KEY DIFFERENTIATING FEATURES

Misdiagnosis of specific cytomegalovirus infection of the ileoanal pouch as refractory idiopathic chronic pouchitis: report of two cases. Munoz-Juarez M, Pemberton JH, Sandborn WJ, Tremaine WJ, Dozois RR. Division of Colon and Rectal Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.

Dis Colon Rectum 1999 Jan;42(1):117-20 Abstract quote 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 pouch-anal anastomosis, initially misdiagnosed as idiopathic chronic pouchitis. CASE SERIES: Patient 1 had ileal pouch-anal 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.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
Histologic Predictors of Pouchitis in Patients with Chronic Ulcerative Colitis. Yantiss RK, Sapp HL, Farraye FA, El-Zammar O, O'Brien MJ, Fruin AB, Stucchi AF, Brien TP, Becker JM, Odze RD. *Departments of Pathology of the University of Massachusetts Medical School/UMass Memorial Health Care, Worcester, MA; and the daggerBrigham & Women's Hospital, and the Departments of double daggerGastroenterology, section signPathology, and paragraph signSurgery, of the Boston University Medical Center, Boston, MA.	Am J Surg Pathol. 2004 Aug;28(8):999-1006. Abstract quote   Inflammation of ileal reservoir mucosa ("pouchitis") is a common sequelae in ulcerative colitis (UC) patients who have had a colectomy with ileal pouch anal-anastomosis (IPAA). Although several clinical, genetic, and laboratory parameters have been evaluated, reliable pathologic predictors for the development of pouchitis are lacking. The purpose of this case-control study was to determine whether there are any pathologic features in UC colectomy specimens that may help predict the subsequent development of pouchitis after an IPAA procedure. The study group consisted of 39 UC patients (male/female ratio: 21/18, mean age: 35 years), who had at least 1 episode of pouchitis after an IPAA procedure during the follow-up period (mean: 57 months, range: 12-121 months). There were 26 control patients (male/female ratio: 11/15, mean age: 37 years), all of whom also underwent a total colectomy and IPAA procedure for UC, but did not develop pouchitis during the follow-up period (mean: 78 months, range: 14-223 months). Routinely processed tissues from each colectomy specimen were evaluated for a variety of histologic features, such as extent of colitis, severity of colitis, extent of severe colitis, type and extent of ulceration, presence and severity of appendiceal inflammation, and the presence of active ileitis, and compared between the study and control patients. Pathologic features that were associated with the subsequent development of pouchitis included the presence of severe colitis that extended into the cecum (severe pancolitis), which was present in 7/39 (18%) pouchitis patients, but in none (0%) of the control patients (P = 0.03), early fissuring ulcers [9/39 (23%) pouchitis cases versus 1/26 (4%) controls (P = 0.04)], active inflammation of the appendix [20/32 (63%) pouchitis patients versus 7/19 (31%) controls (P = 0.03)], and appendiceal ulceration [13/32 (41%) pouchitis patients versus none (0%) of the controls (P = 0.002)]. No significant differences in patient gender or age, depth or extent of ulceration, or the presence or absence of "backwash ileitis" were identified between the 2 groups. In conclusion, there are several histologic features in colectomy specimens from UC patients who have undergone an IPAA procedure that may help predict the subsequent development of pouchitis. Of these features, appendiceal ulceration is highly associated with pouchitis.
The implications of acute pouchitis on the long-term functional results after restorative proctocolectomy. Hurst RD, Chung TP, Rubin M, Michelassi F. Department of Surgery, University of Chicago, Pritzker School of Medicine, Illinois, USA.	Inflamm Bowel Dis 1998 Nov;4(4):280-4 Abstract quote A prospective study was conducted to determine the implications of acute pouchitis on the long-term functional results of restorative proctocolectomy with J-pouch ileoanal anastomosis (IPAA). Between July 1988 and June 1996, 137 consecutive patients underwent IPAA for treatment of ulcerative colitis. 127 patients (93%) have been available for follow-up. All patients completed diaries detailing bowel habits over a 7-day period at 3, 6, 9, 12, 18, 24 months, and yearly after reestablishment of intestinal continuity. Diaries were completed only during time periods in which patients were not suffering from acute symptomatic pouchitis. Patients with chronic pouchitis (n = 7) were excluded from this study leaving 120 patients for analysis. Fifty patients suffered at least one episode of pouchitis (Pouchitis Group). Seventy patients never had pouchitis (No Pouchitis Group). Patients with a history of pouchitis having significantly more bowel movements per day were more likely to ever have minor incontinence (75% vs. 45%, p < 0.005) or major incontinence (37% vs. 17%, p < 0.02). The stools of Pouchitis Group were less likely to be formed (24% vs. 31%, p < 0.001). Pouchitis Group patients also were more likely to wear a protective pad during the day (21% vs. 7% p < 0.04) or during the night (40% vs. 13%, p < 0.001). Even in the absence of clinically active pouchitis, patients who have suffered at least one episode of pouchitis have a poorer long-term functional result after IPAA. The results of this study suggest that ileal pouchitis may represent a chronic condition that displays episodic symptomatic exacerbations
J ileal pouch-anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients. Meagher AP, Farouk R, Dozois RR, Kelly KA, Pemberton JH. Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota 55905, USA.	Br J Surg 1998 Jun;85(6):800-3 Abstract quote AIM: The purpose of the study was to determine the risk of postoperative complications and the functional outcome after a hand-sewn ileal pouch-anal anastomosis (IPAA) for ulcerative colitis using a single J-shaped pouch design. METHODS: Preoperative function, operative morbidity and long-term functional outcome were assessed prospectively in 1310 patients who underwent IPAA between 1981 and 1994 for ulcerative colitis. RESULTS: Three patients died after operation. Postoperative pelvic sepsis rates decreased from 7 per cent in 1981-1985 to 3 per cent in 1991-1994 (P = 0.02). After mean follow-up of 6.5 (range 2-15) years, the mean number of stools was 5 per day and 1 per night. Frequent daytime and nighttime incontinence occurred in 7 and 12 per cent of patients respectively, and did not change over a 10-year period. The cumulative probability of suffering at least one episode of 'clinical' pouchitis was 18 and 48 per cent at 1 and 10 years and the cumulative probability of pouch failure at 1 and 10 years was 2 and 9 per cent respectively. CONCLUSION: These results indicate that increased experience decreases the risk of pouch-related complications and that with time the functional results remain stable, but the failure rate increases.
Preoperative terminal ileal and colonic resection histopathology predicts risk of pouchitis in patients after ileoanal pull-through procedure. Schmidt CM, Lazenby AJ, Hendrickson RJ, Sitzmann JV. Department of Surgery, Georgetown University Medical Center, Washington, DC 20007, USA.	Ann Surg 1998 May;227(5):654-62; discussion 663-5 Abstract quote OBJECTIVE: This study seeks to compare the histopathology of preoperative terminal ileal and colonic resection specimens with pouch biopsies after the ileoanal pull-through (IAPT) procedure. SUMMARY BACKGROUND DATA: Pouchitis is the most frequent complication of transanal continent reservoirs in patients after IAPT. METHODS: The authors conducted 751 consecutive pouch biopsies on 73 patients with inflammatory bowel disease or familial adenomatous polyposis who underwent IAPT by a single surgeon over a 10-year period. In this preliminary report, a pathologist, in blinded fashion, has graded 468 of the IAPT pouch biopsies and 67 of the patients' preoperative terminal ileal and colonic resection histopathology to date. Colonic histopathology was graded by the extent and severity of disease, terminal ileal and pouch histopathology by active inflammation, chronic inflammation, lymphocyte aggregates, intraepithelial lymphocytes, eosinophils, and villous blunting. RESULTS: Extent of colonic disease (gross and microscopic) was a significant predictor of active inflammation in subsequent IAPT pouch biopsy specimens. Also, the gross extent of colonic disease exhibited a significant linear association with pouch inflammation. However, the severity of colonic disease was not significantly predictive of active inflammation in subsequent IAPT pouch biopsies. Terminal ileal active and chronic inflammation were significant predictors of subsequent IAPT pouch inflammation. Although lymphocyte aggregates and intraepithelial lymphocytes were not predictive, terminal ileum eosinophils and villous blunting were significant predictors of active inflammation in subsequent IAPT pouch biopsy specimens. CONCLUSIONS: Preoperative terminal ileal and colonic histopathology predicts active inflammation of pouches after IAPT. Patients who are preoperatively assessed to have extensive disease of the colon, ileal disease ("backwash ileitis"), or both appear to be at greater risk for the development of pouchitis after IAPT.
Risk of dysplasia in long-term ileal pouches and pouches with chronic pouchitis. Thompson-Fawcett MW, Marcus V, Redston M, Cohen Z, McLeod RS. Department of Surgery, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Toronto M5G 1X5 Canada.	Gastroenterology 2001 Aug;121(2):275-81 Abstract quote BACKGROUND & AIMS: Recent reports have suggested the mucosa of an ileal reservoir could be at risk of neoplasia. Risk factors may include the age of the pouch, chronic pouchitis, and previous colonic neoplasia. This study examined a group of such patients to determine the risk of dysplasia. METHODS: From a cohort of 1221 patients with ileal pouches, 171 patients with possible risk factors were selected. Successful contact was made with 138 patients who were invited for endoscopy and multiple biopsies. Biopsy specimens were stained with H&E and p53, scored for inflammatory changes including villous atrophy, and analyzed by flow cytometry. RESULTS: One hundred six patients took part and fell into 1 or more of the following clinical categories: chronic pouchitis (n = 34), pelvic pouch for > or =12 years (n = 42); Kock pouch for > or =14 years (n = 29), and neoplasia in colectomy specimen (n = 11). Thirty-three patients had severe villous atrophy. One patient of 106 (95% confidence interval, 0.9% +/- 1.6%) with a long-standing pouch had low-grade dysplasia that was multifocal. DNA analysis by flow cytometry showed aneuploidy in this patient and 2 others. CONCLUSIONS: These data suggest that the development of dysplasia in ileal pouches performed for ulcerative colitis is probably a rare event within 15-20 years of pouch surgery.
Long-term result of ileal pouch-anal anastomosis for colorectal Crohn's disease. Regimbeau JM, Panis Y, Pocard M, Bouhnik Y, Lavergne-Slove A, Rufat P, Matuchansky C, Valleur P. Department of Surgery, Lariboisiere Hospital, Paris, France.	Dis Colon Rectum 2001 Jun;44(6):769-78 Abstract quote INTRODUCTION: The aim of this study is to report ten-year results of ileal pouch-anal anastomosis in selected patients with colorectal Crohn's disease for whom coloproctectomy and definitive end ileostomy was the only alternative. METHODS: 41 patients (22 females/19 males) with a mean age of 36 +/- 13 (range, 16-72) years underwent ileal pouch-anal anastomosis for colorectal Crohn's disease between 1985 to 1998. None had past or present history of anal manifestations or evidence of small-bowel involvement. Diagnosis of Crohn's disease was established preoperatively in 26 patients, on the resected specimen after ileal pouch-anal anastomosis, or after occurrence of Crohn's disease-related complication in 15 patients. RESULTS: Follow-up was 113 +/- 37 months, (18-174) 20 patients having been followed for more than 10 years. There was no postoperative death. Eleven (27 percent) patients experienced Crohn's disease-related complications, 47 +/- 34 months (8-101) after ileal pouch-anal anastomosis: 2 had persistent anal ulcerations with pouchitis and granulomas on pouch biopsy and were treated medically; 2 experienced extrasphincteric abscesses and 7 presented pouch-perineal fistulas which were treated surgically. Among them, 3 patients with persistent perineal fistula despite surgery required definitive end-ileostomy. Of the 20 patients followed for more than 10 years, 7 (35 percent) experienced Crohn's disease-related complications which required pouch excision in 2 (10 percent). CONCLUSIONS: Ten years after ileal pouch-anal anastomosis for colorectal Crohn's disease, rates of Crohn's disease-related complications and pouch excision were 35 and 10 percent, respectively. These good long-term results justify for us to propose ileal pouch-anal anastomosis in selected patients with colorectal Crohn's disease (i.e., no past or present history of anal manifestations and no evidence of small-bowel involvement) for whom the only alternative is definitive end ileostomy.
Long term metabolic consequences of ileal pouch-anal anastomosis for ulcerative colitis. Kuisma J, Nuutinen H, Luukkonen P, Jarvinen H, Kahri A, Farkkila M. Department of Gastroenterology, Helsinki University Central Hospital, Finland.	Am J Gastroenterol 2001 Nov;96(11):3110-6 Abstract quote OBJECTIVES: Chronic inflammation in the ileal pouch is the most significant late complication after ileal pouch-anal anastomosis (IPAA). It leads to changes in mucosal morphology, with consequent decreased vitamin B12, bile acid and cholesterol absorption documented. The aims of this study were to evaluate long term metabolic consequences at least 5 yr after IPAA and the influence of pouchitis on pouch histology and on bile acid, lipid, and vitamin B12, A, E, and D metabolism. METHODS: A total of 104 patients with a J-pouch who were operated on between 1985 and 1994, as well as 21 ulcerative colitis patients with a conventional ileostomy were enrolled for the study. Routine blood tests, vitamin status, vitamin B12 levels, and bile acid absorption were determined, as well as endoscopy with biopsies. The pouchitis disease activity index (PDAI) was calculated. On the basis of histology, IPAA patients were divided into three subgroups: 1) those with no villous atrophy, 2) those with partial villous atrophy, and 3) those with subtotal or total villous atrophy. RESULTS: Incidence of pouchitis was 42.3%, and was strongly associated with villous atrophy. In IPAA patients with subtotal or total villous atrophy (32.7%), serum levels of albumin, calcium, total cholesterol, triglycerides, and vitamin E were significantly reduced (p < 0.05). The lowest bile acid and vitamin B12 absorption rates were seen in patients with inflammation in the proximal limb. Vitamin D deficiency was seen in 10.6%, and vitamin A and B12 deficiency in approximately 5% of IPAA patients. CONCLUSIONS: Metabolic consequences after IPAA are associated with pouchitis, grade of villous atrophy, and extent of inflammation in the remaining ileum. Patients with active chronic inflammation need long term follow-up.
Adenocarcinoma in the ileal pouch: late risk of cancer after restorative proctocolectomy. Heuschen UA, Heuschen G, Autschbach F, Allemeyer EH, Herfarth C. Department of Surgery, University of Heidelberg, Kirschnerstrasse 1, 69120 Heidelberg, Germany.	Int J Colorectal Dis 2001 Apr;16(2):126-30 Abstract quote Restorative proctocolectomy and ileal pouch-anal anastomosis is the surgical treatment of choice for patients with ulcerative colitis. As a long-term complication of this procedure, chronic pouchitis impairs the outcome in a number of patients. Aneuploidia and dysplasia have been observed after long-lasting inflammation of ileal mucosa. The question arises whether chronic inflammation of ileal mucosa predisposes to malignant transformation similar to the situation in the chronically inflamed colon. Cancer of the ileal mucosa has been reported in patients with Brooke's ileostomy and in patients with Kock pouch but not as yet in those with an ileoanal pouch. We report a patient with carcinoma in an ileoanal pouch originating from terminal ileal mucosa who had been suffering from pancolitis with long-term backwash ileitis before, and from chronic pouchitis after, restorative proctocolectomy. This case demonstrates the importance of regular follow-up with pouchoscopy and random biopsies in all patients with long-standing inflammation of the ileal mucosa.
Long-term follow-up after ileoanal pouch procedure: algorithm for diagnosis, classification, and management of pouchitis. Heuschen UA, Autschbach F, Allemeyer EH, Zollinger AM, Heuschen G, Uehlein T, Herfarth C, Stern J. Department of Surgery, University of Heidelberg, Germany.	Dis Colon Rectum 2001 Apr;44(4):487-99 Abstract quote PURPOSE: Inflammation of the ileoanal pouch (pouchitis) is one of the main complications after restorative proctocolectomy, yet its cause remains poorly understood. A standardized definition and diagnostic procedures in pouchitis are lacking. METHOD: We analyzed all cases of pouchitis occurring in a group of 308 patients (210 with ulcerative colitis, 98 with familial adenomatous polyposis) who took part in a prospective long-term follow-up program. The severity of pouchitis was measured using a pouchitis activity score (Heidelberg Pouchitis Activity Score). An algorithm for the classification and management of pouchitis was established which enables the clinician: 1) to determine the severity of pouchitis, 2) to differentiate between primary pouchitis and pouchitis caused by surgical complications (secondary pouchitis), and 3) to evaluate the course (acute vs. chronic (> 3 months)). \RESULTS: The median duration of follow-up was 48 (range, 13-119) months. At least one episode of pouchitis was diagnosed in 29 percent of patients with ulcerative colitis and in 2 percent of familial adenomatous polyposis patients. Secondary pouchitis occurred in 6 percent of ulcerative colitis patients and was cured by surgical treatment in 13 (87 percent) of 15 cases. Primary pouchitis was diagnosed in 23 percent of ulcerative colitis patients, including 6 percent of all ulcerative colitis patients with chronic primary pouchitis. The latter showed poor response to medical treatment. In one case multifocal high-grade dysplasia occurred. Histologic examination of the excised pouch identified a carcinoma originating from the ileal mucosa. CONCLUSIONS: Ulcerative colitis patients after restorative proctocolectomy face a high risk of developing pouchitis. The algorithm used in this study was highly efficient in identifying patients with a secondary pouchitis who require surgical treatment and patients with chronic primary pouchitis. For the latter, long-term surveillance seems mandatory because of the risk of malignant transformation of the pouch mucosa.
Mucosal assessment for dysplasia and cancer in the ileal pouch mucosa in patients operated on for ulcerative colitis-a 30-year follow-up study. Hulten L, Willen R, Nilsson O, Safarani N, Haboubi N. Institute of Surgical Science and Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden, and Department of Pathology, Withington Hospital, Manchester, United Kingdom.	Dis Colon Rectum 2002 Apr;45(4):448-52 Abstract quote PURPOSE: Sporadic reports of epithelial dysplasia and the occasional development of adenocarcinoma in the ileal pouch mucosa have recently appeared in the literature, pointing toward yet another long-term complication of the continent ileostomy and the pelvic pouch. The incidence of dysplasia and the risk for developing cancer has not been critically evaluated, however, and the reports are contradictory, with most having short observation times. The purpose of this study was to report long-term mucosal adaptation patterns and the incidence of dysplasia in Kock pouches after a mean follow-up of 30 years for patients previously operated on for ulcerative proctocolitis. METHODS: Two sets of two pathologists each (in Gothenburg, Sweden, and Manchester, United Kingdom) examined sequential, small-intestinal biopsy specimens from 40 patients with Kock pouch to observe long-term epithelial changes, with particular reference to the presence of dysplasia. RESULTS: There was full agreement between the two groups regarding the absence of high-grade dysplasia and invasive carcinoma (Categories 4 and 5 of the Vienna classification). There was, however, significant disagreement in reporting the frequency of low-grade and indefinite categories of dysplasia (Categories 2 and 3, of the Vienna classification). No attempt was made to report the differences within each set of pathologists. CONCLUSION: Because no case of high-grade dysplasia or invasive carcinoma was found in this study after a mean follow-up of 30 years, we conclude that it is very unlikely for invasive carcinoma to be a complication in ileal pouch mucosa. .
TREATMENT
A randomized clinical trial of ciprofloxacin and metronidazole to treat acute pouchitis. Shen B, Achkar JP, Lashner BA, Ormsby AH, Remzi FH, Brzezinski A, Bevins CL, Bambrick ML, Seidner DL, Fazio VW. Center for Inflammatory Bowel Disease, Department of Gastroenterology, The Cleveland Clinic Foundation, Ohio 44195, USA.	Inflamm Bowel Dis 2001 Nov;7(4):301-5 Abstract quote Metronidazole is effective for the treatment of acute pouchitis after ileal pouch-anal anastomosis, but it has not been directly compared with other antibiotics. This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis. Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less. Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9). Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy. Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores. Ciprofloxacin lowered the PDAI score from 10.1+/-2.3 to 3.3+/-1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7+/-2.3 to 5.8+/-1.7 (p = 0.0002). There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9+/-1.2 versus 3.8+/-1.7; p = 0.002), symptom score (2.4+/-0.9 versus 1.3+/-0.9; p = 0.03), and endoscopic score (3.6+/-1.3 versus 1.9+/-1.5; p = 0.03). None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy. Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores. Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole. Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis.
Allopurinol as prophylaxis against pouchitis following ileal pouch-anal anastomosis for ulcerative colitis. A randomized placebo-controlled double-blind study. Joelsson M, Andersson M, Bark T, Gullberg K, Hallgren T, Jiborn H, Magnusson I, Raab Y, Sjodahl R, Ojerskog B, Oresland T; Swedish Organization for the Study of Inflammatory Bowel Diseases.	Scand J Gastroenterol 2001 Nov;36(11):1179-84 Abstract quote BACKGROUND: Pouchitis is the major long-term complication of restorative proctocolectomy for ulcerative colitis (UC). Allopurinol is a scavenger of oxygen-derived free radicals, which it is suggested play a role in the development of UC and pouchitis. The first aim was to test the hypothesis that the incidence of pouchitis can be reduced by prophylactic Allopurinol, and secondly to evaluate if Allopurinol influences the overall pouch function. METHODS: 273 patients with UC who were planned for proctocolectomy and ileal pouch-anal anastomosis at 12 centres in Sweden between October 1994 and June 1997 were offered the opportunity to participate. 184 patients (67%) were randomized to receive postoperative prophylactic Allopurinol 100 mg twice daily or placebo. All 273 patients had clinical and endoscopic follow-up at 1, 3, 6, 12, 18, 24 months after surgery. RESULTS: Of the 184 randomized patients, 94 were randomized to Allopurinol and 90 to placebo; 116 patients (63%) completed follow-up and the crude incidence of pouchitis among those patients fullfilling the protocol was 31% in the Allopurinol group and 28% in the placebo group (ns). The cumulative risk for a first attack of pouchitis was 30% and 26% after 24 months (ns). The overall pouch function improved over time and did not differ significantly between the two groups. CONCLUSIONS: Prophylactic Allopurinol did not reduce the risk of a first attack of pouchitis.

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