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Chronic pouchitis is associated with pouch polyp formation in patients with underlying ulcerative colitis
Journal of Crohn's and Colitis (2014) 8, 363–369
Available online at www.sciencedirect.com
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Chronic pouchitis is associated with pouch polyp formation in patients with underlying ulcerative colitis Zhao-Xiu Liu a,b,1 , Ming-Bing Xiao a,1 , Xian-Rui Wu c , Elaine Queener b , Run-Zhou Ni a , Bo Shen b,⁎ a
Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, China Department of Gastroenterology/Hepatology, The Cleveland Clinic Foundation, Cleveland, OH, USA c Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH, USA b
Received 27 August 2012; received in revised form 21 September 2013; accepted 21 September 2013 KEYWORDS Inflammatory bowel disease; Ileal pouch-anal anastomosis; Pouch polyp; Restorative proctocolectomy; Ulcerative colitis
Abstract Background: Polypoid lesions can develop in ileal pouches. The risk factors associated with the development of pouch polyps have not been studied. Aim: To characterize clinical features, risk factors, and disease course of pouch polyp in a cohort of patients with underlying inflammatory bowel disease (IBD) from a subspecialty clinic. Method: A total of 1094 patients with restorative proctocolectomy and IPAA for IBD presenting to our Pouchitis Clinic from 2002 to 2010 were included. Demographic, clinical, and endoscopic variables were analyzed. Results: The median durations from UC diagnosis to colectomy and from pouch creation to the last follow-up for the whole cohort were 6 (interquartile range [IQR]: 3–13) and 9 years (IQR: 5–14), respectively. A total of 2472 surveillance and/or diagnostic pouchoscopies were performed for the cohort with a median follow-up of 5 (IQR: 2–6) years in the Pouchitis Clinic. The median number of pouchoscopies per patient was 2 (IQR: 1–3). Of the 1094 patients, 96 (8.8%) were found to have pouch polyps. The median size of the polyps was 1.2 (IQR: 1.0–2.0) cm. On histology, 93 patients (96.9%) had inflammatory-type polyps and 3 (3.1%) had polyps with low-grade dysplasia or indefinite for dysplasia. Multivariate logistic regression analysis demonstrated that chronic pouch
Abbreviations: ATZ, anal transitional zone; CARP, chronic antbiotic-refractory pouchitis; CD, Crohn's disease; CI, confidence interval; CRC, colorectal cancer; DALM, dysplasia-associated lesion or mass; FAP, familial adenomatous polyposis; HR, hazard ratio; IBD, inflammatory bowel disease; IC, indeterminate colitis; IPS, irritable pouch syndrome; IQR, interquartile range; NSAID, non-steroidal anti-inflammatory drug; OR, odds ratio; PDAI, Pouchitis Disease Activity Index; PGM, pyloric gland metaplasia; PSC, primary sclerosing cholangitis; UC, ulcerative colitis. ⁎ Corresponding author at: Digestive Disease Institute/A31, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA. Tel.: + 1 216 444 9252; fax: + 1 216 444 6305. E-mail address: [email protected] (B. Shen). 1 The authors contributed equally to the study. 1873-9946/$ - see front matter © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.crohns.2013.09.020
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Z.-X. Liu et al. inflammatory change was a risk factor for the development of pouch polyp with an odds ratio of 2.26 (95% confidence interval: 1.35–3.79; P = 0.002). Conclusion: The majority of pouch polyps in patients with underlying UC were benign. Patients with concomitant chronic pouch inflammatory changes had an increased risk for developing pouch polyps. © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
1. Introduction Restorative proctocolectomy with an ileal pouch-anal anastomosis (IPAA) has become the most accepted surgical treatment for patients with refractory ulcerative colitis (UC), UC-associated neoplasia as well as familial adenomatous polyposis (FAP) who require colectomy. Although this procedure provides an attractive way to avoid permanent ileostomy and improves health-related quality of life, post-operative complications are common.1 The most frequent complication is pouchitis, with a reported cumulative probability of 20% at 1 year, 32% at 5 years, and 40% at 10 years.2 While reducing the risk for colorectal cancer (CRC) in UC patients, colectomy with IPAA, even with mucosectomy, does not eliminate the subsequent risk for developing pouch neoplasia. Dysplastic and neoplastic transformation within the ileal pouch mucosa in patients undergoing IPAA for UC is rare even after a long follow-up.3 Patients with type C villous atrophy may harbor a higher risk for developing malignant transformation than those with A or B mucosa.4 Previous studies have confirmed that the most significant risk factor for pouch dysplasia and neoplasia was the presence of UC-associated dysplasia or cancer before or at the time of colectomy.5–9 Reported cumulative risk for pouch polyps or malignancy in the patients with underlying FAP was 8% at 3.5 years and 18% at 7 years.10 In contrast, pouch polyps in patients with UC occurred less frequently. The etiology, natural history, malignant potential, and treatment and prognosis of pouch polyp in these patients have not been well defined. Our previous non-controlled cohort study of 23 cases showed that pouch polyps were typically seen in the background of pouchitis, cuffitis, or CD of pouch and the polyps with the size N 1 cm may bear malignant potential.11 However, the risk factors and management of pouch polyps have not been studied. We hypothesized that chronic inflammatory conditions of the pouch may increase the risk for the development of inflammatory polyps. This study was designed to assess the frequency of pouch polyps in UC patients with IPAA, to investigate the associated risk factors.
2. Patients and methods 2.1. Patients The Cleveland Clinic Institutional Review Board approved this historical cohort study, and routine informed consent for diagnostic, surveillance, and therapeutic endoscopy was obtained from all patients. All 1094 cases seen at our Pouchitis Clinic from 2002 to 2010 after a previous restorative proctocolectomy
and IPAA for IBD were included in the study. The subspecialty Pouchitis Clinic has been a national and international referral center, covering virtually all aspects of healthy and known diseased pouch conditions. The patients were divided into those with polyps (the study group) and those without (the control group).
2.2. Inclusion and exclusion criteria To be qualified for the study, patients needed to meet all the following inclusion criteria: 1) had a preoperative diagnosis of UC, indeterminate colitis (IC), or Crohn's colitis; 2) had ileal pouches; and 3) underwent evaluation and had regular follow-up at our Pouchitis Clinic. Exclusion criteria were IPAA patients with an underlying diagnosis of FAP or other underlying diseases of the colon.
2.3. Study variables The preoperative diagnosis of UC, IC, or Crohn's colitis was determined by a combined assessment of colonoscopic features and histopathological evaluation of the colectomy specimen. Chronic pouch inflammatory changes were defined as chronic antibiotic-refractory pouchitis, Crohn's disease of the pouch or cuffitis. Chronic antibiotic-refractory pouchitis (CARP) was defined by a modified Pouchitis Disease Activity Index ≥ 5 points and symptoms lasting 4 weeks or more and failed to respond to a 4-week course of single antibiotic therapy (ciprofloxacin, metronidazole, or tinidazole).12 Crohn's disease (CD) of the pouch was diagnosed based on our previously published criteria,13 i.e., the presence of nonsurgery-related perianal fistula or inflammation or ulcerations at the pre-pouch neo-terminal ileum or small bowel in the absence of non-steroidal anti-inflammatory drug (NSAID) use, or granulomas on histology. Cuffitis was defined as inflammation of the rectal cuff or ATZ. Pouch failure was defined to have occurred if the pouch was either excised or permanently diverted with an ileostomy. Late-onset surgical complications (occurring N 12 months after ileostomy closure) were defined as conditions which were attributed directly to surgical techniques. These conditions included pouch sinuses, non-CD severe anastomotic or small bowel strictures, pouch ischemia, and pouch prolapse. Irritable pouch syndrome (IPS) was diagnosed based on the presence of active symptoms in the absence of endoscopic and histologic inflammation of the pouch. The variables considered in the univariate analysis were as follows: age at the time of IBD diagnosis, age at pouch construction, duration from IBD diagnosis to pouch construction, duration from pouch construction to last follow-up, gender, ethnicity, smoking status, NSAID use, family history of IBD,
Ileal pouch and polyp
365
preoperative diagnosis, indication for colectomy, preoperative biologic use, pouch type, stage of pouch surgery, presence of chronic pouch inflammatory changes, post-operative immunomodulator use, post-operative biologic use, PSC, phenotype of CD of pouch, and final pouch diagnosis. Of primary interest was the association between chronic pouch inflammatory changes and the development of pouch polyp.
2.4. Clinical practice pattern Diagnostic pouch endoscopy was routinely performed in patients with symptoms, such as diarrhea, bleeding, and abdominal cramps. In addition, patients underwent surveillance endoscopy every 1 to 3 years by the treating IBD specialist (B.S.) after a UC diagnosis of more than 10 years. Patients were given 1 Fleets® enema before the procedure. Outpatient sedated or unsedated pouch endoscopy was performed with careful inspection of the cuff or anal transitional zone (ATZ), pouch body, and afferent limb. During a typical diagnostic and/or surveillance pouchoscopy, 2 to 6 pieces of biopsy were taken from the ATZ; 2 to 6 pieces of biopsy were taken from the pouch body; and 2 to 6 pieces of biopsy were taken from the afferent limb. The area with the most marked inflammation was biopsied. Biopsy of suture ulcers was intentionally avoided. The biopsy specimens were separately labeled and submitted for pathological evaluation. Whether endoscopic polypectomy (see Fig. 1) was performed was the discretion of the treating IBD specialist (B.S.), depending on the size and location of the polyps, the presence of preoperative diagnosis of colon dysplasia or cancer, and patients' symptoms. Treatment strategy and outcome were documented. For patients who underwent endoscopic polypectomy, the PDAI symptom subscores (range, 0–6, with 6 being the most severe) were calculated before and after the procedure to quantify the clinical response to the treatment.
2.5. Histopathological evaluation Endoscopic features of polyps were carefully reviewed for polyp size, shape, number, and location. Histopathology of polypectomy specimens and mucosal biopsy specimens of the afferent limb, pouch, and cuff was reviewed and reported by
Figure 1
gastrointestinal pathologists. H&E slides were evaluated for the presence of acute and chronic inflammation, the presence of pyloric gland metaplasia (PGM), granulomas, features of ischemia, prolapse, or dysplasia.
2.6. Outcome measures The primary outcomes of this study were the prevalence and risk factors associated with the development of pouch polyps.
2.7. Statistical analysis Descriptive statistics were computed for all variables. These included means and standard deviations (SD) or medians and interquartile ranges (IQR) for continuous factors, and frequencies for categorical factors. Comparisons between two groups were made by using the 2-tail t test (or Wilcoxon rank sum test as appropriate) for continuous variables and chi-square test (or the Fisher exact test as appropriate) for categorical variables. All variables which showed statistical significance in the univariate analysis were considered as the potential candidates for the multivariate analysis. The multivariate logistic regression analysis was constructed using the forward stepwise method with an entry criterion of P b 0.05 and a removal criterion of P N 0.10, with the variable “active pouchitis” being forced into the final model. All statistical analyses were performed with SPSS software version 16 (SPSS, Chicago, IL). P value less than 0.05 was considered statistically significant.
3. Results A total of 2472 surveillance, diagnostic, and/or therapeutic pouchoscopies were performed for the 1094-case cohort during a median follow-up of 5.0 (interquartile range [IQR]: 2.0–6.0) years in Pouchitis Clinic, with a median number of pouchoscopies per patient of 2.0 (IQR: 1.0–3.0). A total of 96 (8.8%) patients were diagnosed with pouch polyps and served as the study group. The remaining patients served as controls.
Endoscopic polypectomy of a large obstructing, inflammatory polyp at the pouch inlet.
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Z.-X. Liu et al.
3.1. Prevalence of pouch dysplasia and/or neoplasia Of the 1094 patients included in this study, 5 (0.46%) had pouch dysplasia and/or cancer, with 3 (3.1%) being from the pouch polyp group and 2 (0.2%) being from the control group. The pathological diagnosis for the 2 patients (0.2%) in the control group were high grade dysplasia (n = 1, 0.1%) and cancer (n = 1, 0.1%), both of which were located at the anal transitional zone (ATZ). Of the 3 patients in the study group, 1 (1.0%) was pathologically diagnosed as being indefinite for dysplasia which was contained in the polyp from the pouch body, 1 (1.0%) with inflammatory polyp in
Table 1
the pouch body was found to be indefinite for dysplasia after an 18 month follow-up, and 1 (1.0%) with inflammatory polyp in the cuff developed LGD five years later. The incidence rate of definite dysplasia or cancer in ileal pouches was low (3/1094, 0.3%), with it being comparable between patients with and without pouch polyps (1.0% vs. 0.2%, P = 0.24). None of the patients had a history of IBD-associated dysplasia or cancer on preoperative endoscopy and/or histopathological examination of colectomy specimens. Sixteen patients (16.7%) in the study group underwent colectomy for IBD-associated neoplasia versus 117 controls (11.7%) (P = 0.16) (Table 1). Particularly for the
Patient characteristics.
Characteristics
All cases
Patients without pouch polyps
Patients with pouch polyps
P value
Number of patients Age at the time of IBD diagnosis, yrs Age at pouch construction, yrs Duration from IBD diagnosis to pouch construction, yrs Duration from pouch construction to last follow-up, yrs Male, n (%) Race, n (%) Caucasian African American Others Ex or current smoker, n (%) Chronic NSAID use, n (%) Family history of UC, n (%) Family history of CD, n (%) Indication for colectomy, n (%) Refractory disease Neoplasia Preoperative diagnosis, n (%) Ulcerative colitis Crohn's colitis/indeterminate colitis Extensive colitis, n (%) Toxic megacolon, n (%) Preoperative use of anti-TNF biologics, n (%) Pouch configuration, n (%) J pouch S pouch Others Stage of pouch, n (%) 1 2 3 4 or redo Concurrent autoimmune disorders, n (%) Significant comorbidity, n (%) xtra-intestinal manifestations, n (%) Primary sclerosing cholangitis, n (%) History of liver transplant, n (%) Postoperative use of immunomodulators, n (%) Postoperative use of anti-TNF biologics, n (%)
1094 26.3 ± 12.2 35.4 ± 13.8 6.0 (3.0–13.0)
998 26.4 ± 12.2 35.4 ± 13.7 6.0 (3.0–13.0)
96 25.6 ± 12.8 35.3 ± 15.0 7.5 (4.0–11.8)
0.53 0.93 0.18
9.0(5.0–14.0)
9.0(4.0–14.0)
12.0(7.0–16.0)
b 0.001
604
548 (54.9%)
56 (58.3%)
1057 16 20 230 87 166 65
965 (96.7%) 15 (1.5%) 18 (1.8%) 208 (20.9%) 75 (7.5%) 151 (15.1%) 53 (5.3%)
92 (96.8%) 1 (1.1%) 2 (2.1%) 22 (22.9%) 12 (12.5%) 15 (15.6%) 12 (12.5%)
961 133
881 (88.3%) 117 (11.7%)
80 (83.3%) 16 (16.7%)
1005 89 1037 120 149
915 (91.7%) 83 (8.3%) 948 (95.0%) 111 (11.1%) 139 (13.9%)
90 (93.8%) 6 (6.2%) 89 (92.7%) 9 (9.4%) 10 (10.4%)
1016 34 43
927 (93.0%) 31 (3.1%) 39 (3.9%)
89 (92.7%) 3 (3.1%) 4 (4.2%)
31 806 187 70 137 85 399 57 13 106 87
26 (2.6%) 730 (73.1%) 179 (17.9%) 63 (6.3%) 125 (12.5%) 77 (7.8%) 358 (36.5%) 51 (5.1%) 12 (1.2%) 94 (9.4%) 77 (7.7%)
5 (5.2%) 76 (79.2%) 8 (8.3%) 7 (7.3%) 12 (12.5%) 8 (8.5%) 41 (44.1%) 6 (6.2%) 1 (1.0%) 12 (12.5%) 10 (10.4%)
0.52 0.89
0.64 0.085 0.9 0.004 0.16
0.48
0.34 0.6 0.34 0.95
0.061
0.99 0.8 0.15 0.63 1.0 0.33 0.35
Ileal pouch and polyp Table 2
367
Associations between pouch polyps and pouch complications.
Characteristics
All cases
Patients without pouch polyps
Patients with pouch polyps
P value
Active pouchitis, n (%) Chronic pouch inflammatory changes, n (%) Chronic antibiotic-refractory pouchitis Cuffitis Crohn's disease of the pouch Pouch procedure-related complications, n (%)
189 489 158 103 228 143
173 431 141 92 198 128
16 (16.7%) 58 (60.4%) 17 (17.7%) 11 (11.5%) 30 (31.2%) 15 (15.6%)
0.87 0.001
patient with pouch polyp who developed LGD in the cuff, no dysplasia or cancer was later on found either on preoperative endoscopy or histopathological examination of colectomy specimens.
3.2. Demographic, clinical, and endoscopic features The distributions of patient characteristics between patients with and without pouch polyps are shown in Table 1. Associations between pouch polyps and pouch complications are listed in Table 2. The majority of the 96 patients (60.4%, n = 58) had concomitant chronic antibiotic-refractory pouchitis, cuffitis, or Crohn's disease. Of the 96 patients, 43.8% (n = 42) of patients had polyps in the pouch, 20.8% (n = 20) in the ATZ, and 21.9% (n = 21) in the afferent limb. The median size of pouch polyps was 1.2 (IQR: 1.0–2.0) cm. On histology, 93 patients (96.9%) had inflammatory-type polyps, 2 (2.1%) were indefinite for dysplasia, and 1 (1.0%) had low-grade dysplasia (LGD) in subsequent biopsy (Table 3).
3.3. Multivariate analysis of risk factors for pouch polyps To assess the risk factors for pouch polyps, we conducted multivariate logistic regression analysis. Candidate variables derived from the univariate analysis included duration from pouch construction to last follow-up, the presence of chronic pouch inflammatory changes, active pouchitis, and a family history of CD. Multivariate-adjusted OR of pouch polyps between patients with concurrent chronic pouch inflammatory changes and those who didn't was 2.26 (95% CI: 1.35– 3.79; P = 0.002) (Table 4).
3.4. Outcomes of pouch polyps Forty-one patients (42.7%) had endoscopic snare polypectomy along with concurrent medical therapy. There were no procedure-associated major complications, such as transfusionrequiring bleeding or hospitalization, bowel perforation, or mortality.
4. Discussion This large series of 1094 cases showed that pouch polyps can occur in patients with UC who underwent restorative proctocolectomy with IPAA. The estimated cumulative probability of pouch polyps was 8.8% in our study, a rate which was consistent with those reported in the literature.10
(17.3%) (43.2%) (14.1%) (9.2%) (19.8%) (12.8%)
0.44
Up to 43.8% of pouch polyps were detected at the pouch body. The frequency for dysplastic lesion was lower than that previously reported and only 5 patients (0.46%) were found to have pre- or neoplastic lesions. As anticipated in our hypothesis, both the univariate and multivariate analysis revealed that patients with concomitant chronic pouch inflammatory changes were predisposed to the development of pouch polyps. Clinical manifestations of pouch polyps (together with underlying pouch inflammation) ranged from diarrhea to bleeding, cramps, or dyschezia. We previously reported a case in which a 7-cm pedunculated inflammatory cap polyp at the distal pouch caused patient's dyschezia which was resolved immediately after polypectomy.14 Tysk et al. described a case with a large inflammatory fibroid polyp within the pouch that developed symptoms of obstruction defecation following restorative proctocolectomy with IPAA.15 In another case from Switzerland, the patient with UC suffered severe anemia 2.5 years after the construction of a J pouch. A larger submucosal inflammatory polyp occupying the entire pouch was discovered.16 In our present study, the majority of patients were symptomatic. Although patients with pouch polyps did not present with specific symptoms, they usually had diarrhea, abdominal pain, urgency or bleeding. In our clinical practice, endoscopic polypectomy was routinely performed for the polyps in patients with symptoms of partial small bowel obstruction (assumed caused by the polyps at the pouch inlet or outlet), dyschezia, or persistent bleeding or with a
Table 3
Endoscopic and histologic features of polyps (N = 96).
Features
Number
No. of polyps per patient Anatomic location of polyps Pouch body Afferent limb Cuff/anal transitional zone Pouch and afferent limb Pouch, afferent limb and cuff/anal transitional zone Pouch and cuff Size of the largest polyps per patient, cm
1.0 (1.0–2.0)
Histology pathology Inflammatory polyp Indefinite for dysplasia Low-grade dysplasia High-grade dysplasia/cancer
42 (43.8%) 21 (21.9%) 20 (20.8%) 10 (10.4%) 1 (1.0%) 2 (2.1%) 1.2 (1.0–2.0%)
93 (96.9%) 2 (2.1%) 1 (1.0%) 0 (0.0%)
368 Table 4
Z.-X. Liu et al. Multivariate analysis of the risk factors for the development of pouch polyps.
Characteristics
Odds ratio
5% confidence interval
P value
Duration from pouch construction to last follow-up, every 5-yrs increase Family history of CD (yes vs. no) Chronic pouch inflammatory changes (chronic antibioticrefractory pouchitis, Crohn's disease of the pouch or cuffitis) (yes vs. no) Active pouchitis (yes vs. no)
1.10
1.03–1.17
0.003
2.02 2.26
1.02–3.99 1.35–3.79
0.043 0.002
1.62
0.83–3.17
0.16
preoperative diagnosis of CRC, and for the polyps N 1 cm. On the other hand, the majority of the patients were on concurrent medical therapy at the time of endoscopic polypectomy. Risk factors for the development of ileal pouch polyps have not been studied till now. Our present study demonstrated that chronic pouchitis posed a 2-fold increased risk for developing pouch polyps in patients with underlying UC. The association may explain that a large number (43.8%) of pouch polyps were detected in the pouch body in the present study. Whether the severity of the chronic pouch inflammatory change is correlated with the risk for the development of pouch polyps is another interesting scientific question; however it is not pursued in the current study due to difficulties with the technique. Analogous to inflammatory or pseudopolyps in UC, pouch polyps can be speculated to be from chronic mucosal inflammation. The natural history of pouch polyps in patients with underlying UC is not well known, as there are only a few published case reports or case series. A case report by Freeman et al. 17 showed that a polypoid lesion was detected in the pelvic pouch after IPAA in a patient with UC. Although the lesion had the macroscopic appearance of an inflammatory polyp, pathological examination eventually revealed dysplastic change. In another study by Thompson-Fawcett et al.,18 10 pouch patients with underlying UC developed polyps and none of them were malignant. In this study, two patient had pouch polyps indefinite for dysplasia on histology. Another patient with inflammatory polyps eventually progressed to dysplastic polyps. Our current study further confirmed that a vast majority of pouch polyps are benign, bearing no malignant potential. The present study has several clinical implications. First of all, a vast majority of pouch polyps were of inflammatory type and dysplastic lesion or malignant progression was rare. Our finding that pouch polyps in the patients who underwent IPAA for UC almost certainly did not transform to dysplasia or pouch cancer may lead to controversy on the need and time interval of routine endoscopic surveillance. Since there are no published guidelines for pouch polyp surveillance, the need for surveillance endoscopies may need to be determined on a case-by-case basis. However, close pouch surveillance with biopsy was routinely offered to our patients in the clinical practice at our Pouchitis Clinic, especially for those with risk factors for the development of pouch dysplasia or cancer, for the following reasons: 1) The natural history of pouch polyps and pouch neoplasia in patients with underlying UC is yet to be elaborated. Pouch dysplasia may even escape from routine surveillance pouchoscopy; 2) Prognosis of pouch cancer is poor, once it is diagnosed; 3) Surveillance pouchoscopy is
easier to perform than surveillance colonoscopy for colitisassociated dysplasia; and 4) Surveillance pouchoscopy may provide additional benefits by the detection of endoscopically treatable lesions, such as strictures and polyps, in asymptomatic patients.19 Secondly, patients with concurrent chronic pouchitis may represent a subgroup of pouch patients at a higher risk for pouch polyps, while those patients typically had an antibiotic-dependent or antibiotic-refractory disease course. Our study has limitations. Firstly, there might have been a referral bias since we analyzed cases from the subspecialty Pouchitis Clinic. The prevalence of pouch polyps in our study may thus not be applicable to the general pouch population. However, the main finding of the current study supported that a polyp detected in a pouch of a patient having IPAA for UC was almost certainly not going to contain dysplasia rather than representing true incidence of polyps in pouches. Secondly, the duration of follow-up for the patients with pouch polyps might not be long enough to delineate the natural history. To conclude, dysplasia or malignant progression is rare in pouch polyps. The patients with concomitant chronic pouchitis had an increased risk for developing pouch polyps.
Conflict of interest The authors declare no financial conflict of interest.
References 1. Navaneethan U, Shen B. Diagnosis and management of pouchitis and ileoanal pouch dysfunction. Curr Gastroenterol Rep Dec 2010;12(6):485–94. 2. Lepisto A, Luukkonen P, Jarvinen HJ. Cumulative failure rate of ileal pouch-anal anastomosis and quality of life after failure. Dis Colon Rectum 2002;45:1289–94. 3. Börjesson L, Willén R, Haboubi N, et al. The risk of dysplasia and cancer in the ileal pouch mucosa after restorative proctocolectomy for ulcerative proctocolitis is low: a long-term term follow-up study. Colorectal Dis Nov 2004;6(6):494–8. 4. Veress B, Reinholt FP, Lindquist K, et al. Long-term histomorphological surveillance of the pelvic ileal pouch: dysplasia develops in a subgroup of patients. Gastroenterology Oct 1995;109(4):1090–7. 5. Thompson-Fawcett MW, Rust NA, Warren BF, et al. Aneuploidy and columnar cuff surveillance after stapled ileal pouchanal anastomosis in ulcerative colitis. Dis Colon Rectum Mar 2000;43(3):408–13. 6. Kariv R, Remzi FH, Lian L, et al. Preoperative colorectal neoplasia increases risk for pouch neoplasia in patients with restorative
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proctocolectomy. Gastroenterology Sep 2010;139(3):806–12 [812.e1-2]. Sandborn WJ, Pardi DS. Clinical management of pouchitis. Gastroenterology Dec 2004;127(6):1809–14. Sandborn WJ. Pouchitis: risk factors, frequency, natural history, classification and public health prospective. In: McLeod RS, Martin F, Sutherland LR, Wallace JL, Williams CN, editors. Trends in Inflammatory Bowel Disease 1996. Lancaster, UK: Kluwer Academic Publishers; 1997. p. 51–63. Das P, Johnson MW, Tekkis PP, et al. Risk of dysplasia and adenocarcinoma following restorative proctocolectomy for ulcerative colitis. Colorectal Dis Jan 2007;9(1):15–27 [Review]. van Duijvendijk P, Vasen HF, Bertario L, et al. Cumulative risk of developing polyps at the ileal pouch-anal anastomosis in patients with familial adenomatous polyposis. J Gastrointest Surg May–Jun 1999;3(3):325–30. Schaus BJ, Fazio VW, Remzi FH, et al. Clinical features of ileal pouch polyps in patients with underlying ulcerative colitis. Dis Colon Rectum Jun 2007;50(6):832–8. Shen B, Achkar JP, Connor JT, et al. Modified pouchitis disease activity index: a simplified approach to the diagnosis of pouchitis. Dis Colon Rectum Jun 2003;46(6):748–53.
369 13. Shen B, Fazio VW, Remzi FH, et al. Risk factors for clinical phenotypes of Crohn's disease of the pouch. Am J Gastroenterol 2006;101:2760–8. 14. Obusez EC, Liu X, Shen B. Large pedunculated inflammatory cap polyp in an ileal pouch causing intermittent dyschezia. Colorectal Dis Sep 2011;13(9):e308–9. 15. Tysk C, Schnürer LB, Wickbom G. Obstructing inflammatory fibroid polyp in pelvic ileal reservoir after restorative proctocolectomy in ulcerative colitis. Report of a case. Dis Colon Rectum Oct 1994;37(10):1034–7. 16. Widgren S, Cox JN. Inflammatory fibroid polyp in a continent ileo-anal pouch after colectomy for ulcerative colitis—case report. Pathol Res Pract 1997;193(9):643–7. 17. Freeman H. Dysplasia-associated polypoid mucosal lesion in a pelvic pouch after restorative proctocolectomy for ulcerative colitis. Can J Gastroenterol Jul 2001;15(7):485–8. 18. Thompson-Fawcett MW, Marcus V, Redston M, et al. Risk of dysplasia in long-term ileal pouches and pouches with chronic pouchitis. Gastroenterology Aug 2001;121(2):275–81. 19. Zhu H, Wu XR, Queener E, et al. Clinical value of surveillance pouchoscopy in asymptomatic ileal pouch patients with underlying inflammatory bowel disease. Surg Endosc Nov 2013;27(11):4325–32.
Available online at www.sciencedirect.com
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Chronic pouchitis is associated with pouch polyp formation in patients with underlying ulcerative colitis Zhao-Xiu Liu a,b,1 , Ming-Bing Xiao a,1 , Xian-Rui Wu c , Elaine Queener b , Run-Zhou Ni a , Bo Shen b,⁎ a
Department of Gastroenterology, Affiliated Hospital of Nantong University, Jiangsu, China Department of Gastroenterology/Hepatology, The Cleveland Clinic Foundation, Cleveland, OH, USA c Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH, USA b
Received 27 August 2012; received in revised form 21 September 2013; accepted 21 September 2013 KEYWORDS Inflammatory bowel disease; Ileal pouch-anal anastomosis; Pouch polyp; Restorative proctocolectomy; Ulcerative colitis
Abstract Background: Polypoid lesions can develop in ileal pouches. The risk factors associated with the development of pouch polyps have not been studied. Aim: To characterize clinical features, risk factors, and disease course of pouch polyp in a cohort of patients with underlying inflammatory bowel disease (IBD) from a subspecialty clinic. Method: A total of 1094 patients with restorative proctocolectomy and IPAA for IBD presenting to our Pouchitis Clinic from 2002 to 2010 were included. Demographic, clinical, and endoscopic variables were analyzed. Results: The median durations from UC diagnosis to colectomy and from pouch creation to the last follow-up for the whole cohort were 6 (interquartile range [IQR]: 3–13) and 9 years (IQR: 5–14), respectively. A total of 2472 surveillance and/or diagnostic pouchoscopies were performed for the cohort with a median follow-up of 5 (IQR: 2–6) years in the Pouchitis Clinic. The median number of pouchoscopies per patient was 2 (IQR: 1–3). Of the 1094 patients, 96 (8.8%) were found to have pouch polyps. The median size of the polyps was 1.2 (IQR: 1.0–2.0) cm. On histology, 93 patients (96.9%) had inflammatory-type polyps and 3 (3.1%) had polyps with low-grade dysplasia or indefinite for dysplasia. Multivariate logistic regression analysis demonstrated that chronic pouch
Abbreviations: ATZ, anal transitional zone; CARP, chronic antbiotic-refractory pouchitis; CD, Crohn's disease; CI, confidence interval; CRC, colorectal cancer; DALM, dysplasia-associated lesion or mass; FAP, familial adenomatous polyposis; HR, hazard ratio; IBD, inflammatory bowel disease; IC, indeterminate colitis; IPS, irritable pouch syndrome; IQR, interquartile range; NSAID, non-steroidal anti-inflammatory drug; OR, odds ratio; PDAI, Pouchitis Disease Activity Index; PGM, pyloric gland metaplasia; PSC, primary sclerosing cholangitis; UC, ulcerative colitis. ⁎ Corresponding author at: Digestive Disease Institute/A31, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA. Tel.: + 1 216 444 9252; fax: + 1 216 444 6305. E-mail address: [email protected] (B. Shen). 1 The authors contributed equally to the study. 1873-9946/$ - see front matter © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.crohns.2013.09.020
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Z.-X. Liu et al. inflammatory change was a risk factor for the development of pouch polyp with an odds ratio of 2.26 (95% confidence interval: 1.35–3.79; P = 0.002). Conclusion: The majority of pouch polyps in patients with underlying UC were benign. Patients with concomitant chronic pouch inflammatory changes had an increased risk for developing pouch polyps. © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
1. Introduction Restorative proctocolectomy with an ileal pouch-anal anastomosis (IPAA) has become the most accepted surgical treatment for patients with refractory ulcerative colitis (UC), UC-associated neoplasia as well as familial adenomatous polyposis (FAP) who require colectomy. Although this procedure provides an attractive way to avoid permanent ileostomy and improves health-related quality of life, post-operative complications are common.1 The most frequent complication is pouchitis, with a reported cumulative probability of 20% at 1 year, 32% at 5 years, and 40% at 10 years.2 While reducing the risk for colorectal cancer (CRC) in UC patients, colectomy with IPAA, even with mucosectomy, does not eliminate the subsequent risk for developing pouch neoplasia. Dysplastic and neoplastic transformation within the ileal pouch mucosa in patients undergoing IPAA for UC is rare even after a long follow-up.3 Patients with type C villous atrophy may harbor a higher risk for developing malignant transformation than those with A or B mucosa.4 Previous studies have confirmed that the most significant risk factor for pouch dysplasia and neoplasia was the presence of UC-associated dysplasia or cancer before or at the time of colectomy.5–9 Reported cumulative risk for pouch polyps or malignancy in the patients with underlying FAP was 8% at 3.5 years and 18% at 7 years.10 In contrast, pouch polyps in patients with UC occurred less frequently. The etiology, natural history, malignant potential, and treatment and prognosis of pouch polyp in these patients have not been well defined. Our previous non-controlled cohort study of 23 cases showed that pouch polyps were typically seen in the background of pouchitis, cuffitis, or CD of pouch and the polyps with the size N 1 cm may bear malignant potential.11 However, the risk factors and management of pouch polyps have not been studied. We hypothesized that chronic inflammatory conditions of the pouch may increase the risk for the development of inflammatory polyps. This study was designed to assess the frequency of pouch polyps in UC patients with IPAA, to investigate the associated risk factors.
2. Patients and methods 2.1. Patients The Cleveland Clinic Institutional Review Board approved this historical cohort study, and routine informed consent for diagnostic, surveillance, and therapeutic endoscopy was obtained from all patients. All 1094 cases seen at our Pouchitis Clinic from 2002 to 2010 after a previous restorative proctocolectomy
and IPAA for IBD were included in the study. The subspecialty Pouchitis Clinic has been a national and international referral center, covering virtually all aspects of healthy and known diseased pouch conditions. The patients were divided into those with polyps (the study group) and those without (the control group).
2.2. Inclusion and exclusion criteria To be qualified for the study, patients needed to meet all the following inclusion criteria: 1) had a preoperative diagnosis of UC, indeterminate colitis (IC), or Crohn's colitis; 2) had ileal pouches; and 3) underwent evaluation and had regular follow-up at our Pouchitis Clinic. Exclusion criteria were IPAA patients with an underlying diagnosis of FAP or other underlying diseases of the colon.
2.3. Study variables The preoperative diagnosis of UC, IC, or Crohn's colitis was determined by a combined assessment of colonoscopic features and histopathological evaluation of the colectomy specimen. Chronic pouch inflammatory changes were defined as chronic antibiotic-refractory pouchitis, Crohn's disease of the pouch or cuffitis. Chronic antibiotic-refractory pouchitis (CARP) was defined by a modified Pouchitis Disease Activity Index ≥ 5 points and symptoms lasting 4 weeks or more and failed to respond to a 4-week course of single antibiotic therapy (ciprofloxacin, metronidazole, or tinidazole).12 Crohn's disease (CD) of the pouch was diagnosed based on our previously published criteria,13 i.e., the presence of nonsurgery-related perianal fistula or inflammation or ulcerations at the pre-pouch neo-terminal ileum or small bowel in the absence of non-steroidal anti-inflammatory drug (NSAID) use, or granulomas on histology. Cuffitis was defined as inflammation of the rectal cuff or ATZ. Pouch failure was defined to have occurred if the pouch was either excised or permanently diverted with an ileostomy. Late-onset surgical complications (occurring N 12 months after ileostomy closure) were defined as conditions which were attributed directly to surgical techniques. These conditions included pouch sinuses, non-CD severe anastomotic or small bowel strictures, pouch ischemia, and pouch prolapse. Irritable pouch syndrome (IPS) was diagnosed based on the presence of active symptoms in the absence of endoscopic and histologic inflammation of the pouch. The variables considered in the univariate analysis were as follows: age at the time of IBD diagnosis, age at pouch construction, duration from IBD diagnosis to pouch construction, duration from pouch construction to last follow-up, gender, ethnicity, smoking status, NSAID use, family history of IBD,
Ileal pouch and polyp
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preoperative diagnosis, indication for colectomy, preoperative biologic use, pouch type, stage of pouch surgery, presence of chronic pouch inflammatory changes, post-operative immunomodulator use, post-operative biologic use, PSC, phenotype of CD of pouch, and final pouch diagnosis. Of primary interest was the association between chronic pouch inflammatory changes and the development of pouch polyp.
2.4. Clinical practice pattern Diagnostic pouch endoscopy was routinely performed in patients with symptoms, such as diarrhea, bleeding, and abdominal cramps. In addition, patients underwent surveillance endoscopy every 1 to 3 years by the treating IBD specialist (B.S.) after a UC diagnosis of more than 10 years. Patients were given 1 Fleets® enema before the procedure. Outpatient sedated or unsedated pouch endoscopy was performed with careful inspection of the cuff or anal transitional zone (ATZ), pouch body, and afferent limb. During a typical diagnostic and/or surveillance pouchoscopy, 2 to 6 pieces of biopsy were taken from the ATZ; 2 to 6 pieces of biopsy were taken from the pouch body; and 2 to 6 pieces of biopsy were taken from the afferent limb. The area with the most marked inflammation was biopsied. Biopsy of suture ulcers was intentionally avoided. The biopsy specimens were separately labeled and submitted for pathological evaluation. Whether endoscopic polypectomy (see Fig. 1) was performed was the discretion of the treating IBD specialist (B.S.), depending on the size and location of the polyps, the presence of preoperative diagnosis of colon dysplasia or cancer, and patients' symptoms. Treatment strategy and outcome were documented. For patients who underwent endoscopic polypectomy, the PDAI symptom subscores (range, 0–6, with 6 being the most severe) were calculated before and after the procedure to quantify the clinical response to the treatment.
2.5. Histopathological evaluation Endoscopic features of polyps were carefully reviewed for polyp size, shape, number, and location. Histopathology of polypectomy specimens and mucosal biopsy specimens of the afferent limb, pouch, and cuff was reviewed and reported by
Figure 1
gastrointestinal pathologists. H&E slides were evaluated for the presence of acute and chronic inflammation, the presence of pyloric gland metaplasia (PGM), granulomas, features of ischemia, prolapse, or dysplasia.
2.6. Outcome measures The primary outcomes of this study were the prevalence and risk factors associated with the development of pouch polyps.
2.7. Statistical analysis Descriptive statistics were computed for all variables. These included means and standard deviations (SD) or medians and interquartile ranges (IQR) for continuous factors, and frequencies for categorical factors. Comparisons between two groups were made by using the 2-tail t test (or Wilcoxon rank sum test as appropriate) for continuous variables and chi-square test (or the Fisher exact test as appropriate) for categorical variables. All variables which showed statistical significance in the univariate analysis were considered as the potential candidates for the multivariate analysis. The multivariate logistic regression analysis was constructed using the forward stepwise method with an entry criterion of P b 0.05 and a removal criterion of P N 0.10, with the variable “active pouchitis” being forced into the final model. All statistical analyses were performed with SPSS software version 16 (SPSS, Chicago, IL). P value less than 0.05 was considered statistically significant.
3. Results A total of 2472 surveillance, diagnostic, and/or therapeutic pouchoscopies were performed for the 1094-case cohort during a median follow-up of 5.0 (interquartile range [IQR]: 2.0–6.0) years in Pouchitis Clinic, with a median number of pouchoscopies per patient of 2.0 (IQR: 1.0–3.0). A total of 96 (8.8%) patients were diagnosed with pouch polyps and served as the study group. The remaining patients served as controls.
Endoscopic polypectomy of a large obstructing, inflammatory polyp at the pouch inlet.
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Z.-X. Liu et al.
3.1. Prevalence of pouch dysplasia and/or neoplasia Of the 1094 patients included in this study, 5 (0.46%) had pouch dysplasia and/or cancer, with 3 (3.1%) being from the pouch polyp group and 2 (0.2%) being from the control group. The pathological diagnosis for the 2 patients (0.2%) in the control group were high grade dysplasia (n = 1, 0.1%) and cancer (n = 1, 0.1%), both of which were located at the anal transitional zone (ATZ). Of the 3 patients in the study group, 1 (1.0%) was pathologically diagnosed as being indefinite for dysplasia which was contained in the polyp from the pouch body, 1 (1.0%) with inflammatory polyp in
Table 1
the pouch body was found to be indefinite for dysplasia after an 18 month follow-up, and 1 (1.0%) with inflammatory polyp in the cuff developed LGD five years later. The incidence rate of definite dysplasia or cancer in ileal pouches was low (3/1094, 0.3%), with it being comparable between patients with and without pouch polyps (1.0% vs. 0.2%, P = 0.24). None of the patients had a history of IBD-associated dysplasia or cancer on preoperative endoscopy and/or histopathological examination of colectomy specimens. Sixteen patients (16.7%) in the study group underwent colectomy for IBD-associated neoplasia versus 117 controls (11.7%) (P = 0.16) (Table 1). Particularly for the
Patient characteristics.
Characteristics
All cases
Patients without pouch polyps
Patients with pouch polyps
P value
Number of patients Age at the time of IBD diagnosis, yrs Age at pouch construction, yrs Duration from IBD diagnosis to pouch construction, yrs Duration from pouch construction to last follow-up, yrs Male, n (%) Race, n (%) Caucasian African American Others Ex or current smoker, n (%) Chronic NSAID use, n (%) Family history of UC, n (%) Family history of CD, n (%) Indication for colectomy, n (%) Refractory disease Neoplasia Preoperative diagnosis, n (%) Ulcerative colitis Crohn's colitis/indeterminate colitis Extensive colitis, n (%) Toxic megacolon, n (%) Preoperative use of anti-TNF biologics, n (%) Pouch configuration, n (%) J pouch S pouch Others Stage of pouch, n (%) 1 2 3 4 or redo Concurrent autoimmune disorders, n (%) Significant comorbidity, n (%) xtra-intestinal manifestations, n (%) Primary sclerosing cholangitis, n (%) History of liver transplant, n (%) Postoperative use of immunomodulators, n (%) Postoperative use of anti-TNF biologics, n (%)
1094 26.3 ± 12.2 35.4 ± 13.8 6.0 (3.0–13.0)
998 26.4 ± 12.2 35.4 ± 13.7 6.0 (3.0–13.0)
96 25.6 ± 12.8 35.3 ± 15.0 7.5 (4.0–11.8)
0.53 0.93 0.18
9.0(5.0–14.0)
9.0(4.0–14.0)
12.0(7.0–16.0)
b 0.001
604
548 (54.9%)
56 (58.3%)
1057 16 20 230 87 166 65
965 (96.7%) 15 (1.5%) 18 (1.8%) 208 (20.9%) 75 (7.5%) 151 (15.1%) 53 (5.3%)
92 (96.8%) 1 (1.1%) 2 (2.1%) 22 (22.9%) 12 (12.5%) 15 (15.6%) 12 (12.5%)
961 133
881 (88.3%) 117 (11.7%)
80 (83.3%) 16 (16.7%)
1005 89 1037 120 149
915 (91.7%) 83 (8.3%) 948 (95.0%) 111 (11.1%) 139 (13.9%)
90 (93.8%) 6 (6.2%) 89 (92.7%) 9 (9.4%) 10 (10.4%)
1016 34 43
927 (93.0%) 31 (3.1%) 39 (3.9%)
89 (92.7%) 3 (3.1%) 4 (4.2%)
31 806 187 70 137 85 399 57 13 106 87
26 (2.6%) 730 (73.1%) 179 (17.9%) 63 (6.3%) 125 (12.5%) 77 (7.8%) 358 (36.5%) 51 (5.1%) 12 (1.2%) 94 (9.4%) 77 (7.7%)
5 (5.2%) 76 (79.2%) 8 (8.3%) 7 (7.3%) 12 (12.5%) 8 (8.5%) 41 (44.1%) 6 (6.2%) 1 (1.0%) 12 (12.5%) 10 (10.4%)
0.52 0.89
0.64 0.085 0.9 0.004 0.16
0.48
0.34 0.6 0.34 0.95
0.061
0.99 0.8 0.15 0.63 1.0 0.33 0.35
Ileal pouch and polyp Table 2
367
Associations between pouch polyps and pouch complications.
Characteristics
All cases
Patients without pouch polyps
Patients with pouch polyps
P value
Active pouchitis, n (%) Chronic pouch inflammatory changes, n (%) Chronic antibiotic-refractory pouchitis Cuffitis Crohn's disease of the pouch Pouch procedure-related complications, n (%)
189 489 158 103 228 143
173 431 141 92 198 128
16 (16.7%) 58 (60.4%) 17 (17.7%) 11 (11.5%) 30 (31.2%) 15 (15.6%)
0.87 0.001
patient with pouch polyp who developed LGD in the cuff, no dysplasia or cancer was later on found either on preoperative endoscopy or histopathological examination of colectomy specimens.
3.2. Demographic, clinical, and endoscopic features The distributions of patient characteristics between patients with and without pouch polyps are shown in Table 1. Associations between pouch polyps and pouch complications are listed in Table 2. The majority of the 96 patients (60.4%, n = 58) had concomitant chronic antibiotic-refractory pouchitis, cuffitis, or Crohn's disease. Of the 96 patients, 43.8% (n = 42) of patients had polyps in the pouch, 20.8% (n = 20) in the ATZ, and 21.9% (n = 21) in the afferent limb. The median size of pouch polyps was 1.2 (IQR: 1.0–2.0) cm. On histology, 93 patients (96.9%) had inflammatory-type polyps, 2 (2.1%) were indefinite for dysplasia, and 1 (1.0%) had low-grade dysplasia (LGD) in subsequent biopsy (Table 3).
3.3. Multivariate analysis of risk factors for pouch polyps To assess the risk factors for pouch polyps, we conducted multivariate logistic regression analysis. Candidate variables derived from the univariate analysis included duration from pouch construction to last follow-up, the presence of chronic pouch inflammatory changes, active pouchitis, and a family history of CD. Multivariate-adjusted OR of pouch polyps between patients with concurrent chronic pouch inflammatory changes and those who didn't was 2.26 (95% CI: 1.35– 3.79; P = 0.002) (Table 4).
3.4. Outcomes of pouch polyps Forty-one patients (42.7%) had endoscopic snare polypectomy along with concurrent medical therapy. There were no procedure-associated major complications, such as transfusionrequiring bleeding or hospitalization, bowel perforation, or mortality.
4. Discussion This large series of 1094 cases showed that pouch polyps can occur in patients with UC who underwent restorative proctocolectomy with IPAA. The estimated cumulative probability of pouch polyps was 8.8% in our study, a rate which was consistent with those reported in the literature.10
(17.3%) (43.2%) (14.1%) (9.2%) (19.8%) (12.8%)
0.44
Up to 43.8% of pouch polyps were detected at the pouch body. The frequency for dysplastic lesion was lower than that previously reported and only 5 patients (0.46%) were found to have pre- or neoplastic lesions. As anticipated in our hypothesis, both the univariate and multivariate analysis revealed that patients with concomitant chronic pouch inflammatory changes were predisposed to the development of pouch polyps. Clinical manifestations of pouch polyps (together with underlying pouch inflammation) ranged from diarrhea to bleeding, cramps, or dyschezia. We previously reported a case in which a 7-cm pedunculated inflammatory cap polyp at the distal pouch caused patient's dyschezia which was resolved immediately after polypectomy.14 Tysk et al. described a case with a large inflammatory fibroid polyp within the pouch that developed symptoms of obstruction defecation following restorative proctocolectomy with IPAA.15 In another case from Switzerland, the patient with UC suffered severe anemia 2.5 years after the construction of a J pouch. A larger submucosal inflammatory polyp occupying the entire pouch was discovered.16 In our present study, the majority of patients were symptomatic. Although patients with pouch polyps did not present with specific symptoms, they usually had diarrhea, abdominal pain, urgency or bleeding. In our clinical practice, endoscopic polypectomy was routinely performed for the polyps in patients with symptoms of partial small bowel obstruction (assumed caused by the polyps at the pouch inlet or outlet), dyschezia, or persistent bleeding or with a
Table 3
Endoscopic and histologic features of polyps (N = 96).
Features
Number
No. of polyps per patient Anatomic location of polyps Pouch body Afferent limb Cuff/anal transitional zone Pouch and afferent limb Pouch, afferent limb and cuff/anal transitional zone Pouch and cuff Size of the largest polyps per patient, cm
1.0 (1.0–2.0)
Histology pathology Inflammatory polyp Indefinite for dysplasia Low-grade dysplasia High-grade dysplasia/cancer
42 (43.8%) 21 (21.9%) 20 (20.8%) 10 (10.4%) 1 (1.0%) 2 (2.1%) 1.2 (1.0–2.0%)
93 (96.9%) 2 (2.1%) 1 (1.0%) 0 (0.0%)
368 Table 4
Z.-X. Liu et al. Multivariate analysis of the risk factors for the development of pouch polyps.
Characteristics
Odds ratio
5% confidence interval
P value
Duration from pouch construction to last follow-up, every 5-yrs increase Family history of CD (yes vs. no) Chronic pouch inflammatory changes (chronic antibioticrefractory pouchitis, Crohn's disease of the pouch or cuffitis) (yes vs. no) Active pouchitis (yes vs. no)
1.10
1.03–1.17
0.003
2.02 2.26
1.02–3.99 1.35–3.79
0.043 0.002
1.62
0.83–3.17
0.16
preoperative diagnosis of CRC, and for the polyps N 1 cm. On the other hand, the majority of the patients were on concurrent medical therapy at the time of endoscopic polypectomy. Risk factors for the development of ileal pouch polyps have not been studied till now. Our present study demonstrated that chronic pouchitis posed a 2-fold increased risk for developing pouch polyps in patients with underlying UC. The association may explain that a large number (43.8%) of pouch polyps were detected in the pouch body in the present study. Whether the severity of the chronic pouch inflammatory change is correlated with the risk for the development of pouch polyps is another interesting scientific question; however it is not pursued in the current study due to difficulties with the technique. Analogous to inflammatory or pseudopolyps in UC, pouch polyps can be speculated to be from chronic mucosal inflammation. The natural history of pouch polyps in patients with underlying UC is not well known, as there are only a few published case reports or case series. A case report by Freeman et al. 17 showed that a polypoid lesion was detected in the pelvic pouch after IPAA in a patient with UC. Although the lesion had the macroscopic appearance of an inflammatory polyp, pathological examination eventually revealed dysplastic change. In another study by Thompson-Fawcett et al.,18 10 pouch patients with underlying UC developed polyps and none of them were malignant. In this study, two patient had pouch polyps indefinite for dysplasia on histology. Another patient with inflammatory polyps eventually progressed to dysplastic polyps. Our current study further confirmed that a vast majority of pouch polyps are benign, bearing no malignant potential. The present study has several clinical implications. First of all, a vast majority of pouch polyps were of inflammatory type and dysplastic lesion or malignant progression was rare. Our finding that pouch polyps in the patients who underwent IPAA for UC almost certainly did not transform to dysplasia or pouch cancer may lead to controversy on the need and time interval of routine endoscopic surveillance. Since there are no published guidelines for pouch polyp surveillance, the need for surveillance endoscopies may need to be determined on a case-by-case basis. However, close pouch surveillance with biopsy was routinely offered to our patients in the clinical practice at our Pouchitis Clinic, especially for those with risk factors for the development of pouch dysplasia or cancer, for the following reasons: 1) The natural history of pouch polyps and pouch neoplasia in patients with underlying UC is yet to be elaborated. Pouch dysplasia may even escape from routine surveillance pouchoscopy; 2) Prognosis of pouch cancer is poor, once it is diagnosed; 3) Surveillance pouchoscopy is
easier to perform than surveillance colonoscopy for colitisassociated dysplasia; and 4) Surveillance pouchoscopy may provide additional benefits by the detection of endoscopically treatable lesions, such as strictures and polyps, in asymptomatic patients.19 Secondly, patients with concurrent chronic pouchitis may represent a subgroup of pouch patients at a higher risk for pouch polyps, while those patients typically had an antibiotic-dependent or antibiotic-refractory disease course. Our study has limitations. Firstly, there might have been a referral bias since we analyzed cases from the subspecialty Pouchitis Clinic. The prevalence of pouch polyps in our study may thus not be applicable to the general pouch population. However, the main finding of the current study supported that a polyp detected in a pouch of a patient having IPAA for UC was almost certainly not going to contain dysplasia rather than representing true incidence of polyps in pouches. Secondly, the duration of follow-up for the patients with pouch polyps might not be long enough to delineate the natural history. To conclude, dysplasia or malignant progression is rare in pouch polyps. The patients with concomitant chronic pouchitis had an increased risk for developing pouch polyps.
Conflict of interest The authors declare no financial conflict of interest.
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