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Bertin L, Nasrallah M, Redavid C, Bonazzi E, Maniero D, Lorenzon G, De Barba C, Facchin S, Scarpa M, Ruffolo C, Angriman I, Buda A, Fassan M, Lacognata C, Barberio B, Zingone F, Savarino EV. Risk Factors and Postoperative Outcomes in Pouchitis Following Restorative Proctocolectomy: An 18-Year Single-Center Study. GASTROENTEROLOGY INSIGHTS 2024; 15:1075-1092. [DOI: 10.3390/gastroent15040074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/11/2025] Open
Abstract
Background/Objectives: Restorative proctocolectomy with ileo-anal pouch anastomosis (IPAA) remains the preferred surgical treatment for ulcerative colitis (UC). However, complications like pouchitis can occur. This study aimed to describe patients who underwent IPAA for inflammatory bowel disease (IBD) at Padua Hospital from 2005 to 2023 and identify risk factors for pouchitis. Secondary objectives included evaluating the effectiveness of biological therapy in chronic antibiotic-refractory pouchitis (CARP), Crohn’s disease of the pouch (CDP), and Crohn’s-like inflammation of the pouch (CDLPI), and assessing risk factors for pouch failure. Methods: This retrospective, observational study included 109 patients whose data were collected from medical records. Univariate logistic regression was used to analyze associations between preoperative and postoperative factors and outcomes such as acute pouchitis and pouch failure. The effectiveness of biological therapy was assessed by measuring changes in the Pouchitis Disease Activity Index (PDAI) and the Modified Pouchitis Disease Activity Index (mPDAI) over a 12-month treatment period. Results: Univariate logistic regression revealed significant associations between preoperative extraintestinal manifestations (OR 3.569, 95% CI 1.240–10.720), previous diagnosis of Crohn’s disease (OR 10.675, 95% CI 1.265–90.089), and transmural inflammation at cross-sectional imaging before surgery (OR 3.453, 95% CI 1.193–9.991) with an acute pouchitis risk. Pouch failure was significantly associated with a previous diagnosis of Crohn’s disease (OR 9.500, 95% CI 1.821–49.571) and post-surgical fistulas (OR 41.597, 95% CI 4.022–430.172). Biological therapy led to a significant reduction in the PDAI score in patients with CARP, decreasing from a median of 10 to 4 (p = 0.006). Similarly, in patients with CDP or CDLPI, the mPDAI score was significantly reduced from a median of 9 to 1 (p = 0.034), with remission achieved in 5/6 (83.3%) of these patients. Conclusions: This study provides valuable insights into the management of IPAA patients and highlights the importance of early identification and treatment of risk factors for pouchitis and failure. Biological therapy demonstrated significant effectiveness in reducing disease activity in patients with CARP, CDP, and CDLPI, suggesting its role as a crucial component in managing these complications.
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Affiliation(s)
- Luisa Bertin
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
- Gastroenterology Unit, Azienda Ospedale—Università Padova, 35128 Padua, Italy
| | - Mohamad Nasrallah
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
| | - Carlo Redavid
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
| | - Erica Bonazzi
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
| | - Daria Maniero
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
| | - Greta Lorenzon
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
| | - Caterina De Barba
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
| | - Sonia Facchin
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
| | - Marco Scarpa
- Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Via Giustiniani 2, 35128 Padua, Italy
| | - Cesare Ruffolo
- Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Via Giustiniani 2, 35128 Padua, Italy
| | - Imerio Angriman
- Chirurgia Generale 3 Unit, Azienda Ospedale Università di Padova, Via Giustiniani 2, 35128 Padua, Italy
| | - Andrea Buda
- Gastroenterology Unit, Department of Oncological Gastrointestinal Surgery, S. Maria del Prato Hospital, 32032 Feltre, Italy
| | - Matteo Fassan
- Veneto Institute of Oncology IOV—Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), 35128 Padova, Italy
- Department of Medicine, University of Padova, 35122 Padova, Italy
| | | | - Brigida Barberio
- Gastroenterology Unit, Azienda Ospedale—Università Padova, 35128 Padua, Italy
| | - Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
- Gastroenterology Unit, Azienda Ospedale—Università Padova, 35128 Padua, Italy
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
- Gastroenterology Unit, Azienda Ospedale—Università Padova, 35128 Padua, Italy
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Gionchetti P, Calabrese C, Laureti S, Poggioli G, Rizzello F. Pouchitis: Clinical Features, Diagnosis, and Treatment. Int J Gen Med 2021; 14:3871-3879. [PMID: 34335051 PMCID: PMC8318718 DOI: 10.2147/ijgm.s306039] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 04/20/2021] [Indexed: 12/18/2022] Open
Abstract
Procto-colectomy with an ileal pouch anal anastomosis is the procedure of choice for ulcerative colitis patients that require colectomy. Pouchitis is a non-specific inflammation of the ileal reservoir, and the most common, inflammatory and long-term, complication after pouch surgery for ulcerative colitis. The aetiology is still unknown, but many risk factors have been individuated. Pouchitis can be classified based on aetiology, duration, clinical course, and response to antibiotic therapy. Accurate diagnosis and classification is the key factor for an adequate management, and exclusion of secondary causes of pouchitis is pivotal. Most of the patients consistently respond to antibiotic therapy, but management of the subgroup of patients with chronic-antibiotic-resistant-pouchitis is still challenging, being this entity one of the major causes of pouch failure.
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Affiliation(s)
- Paolo Gionchetti
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Bologna, Italia
| | - Carlo Calabrese
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Bologna, Italia
| | - Silvio Laureti
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Bologna, Italia
| | - Gilberto Poggioli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Bologna, Italia
| | - Fernando Rizzello
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Bologna, Italia
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Rabbenou W, Chang S. Medical treatment of pouchitis: a guide for the clinician. Therap Adv Gastroenterol 2021; 14:17562848211023376. [PMID: 34249146 PMCID: PMC8239975 DOI: 10.1177/17562848211023376] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 05/18/2021] [Indexed: 02/04/2023] Open
Abstract
Pouchitis is the most common complication in patients who have undergone restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Up to 81% of IPAA patients experience pouchitis, with 40% of patients presenting within the first year of surgery. Common risk factors include genetic mutations, extensive colitis, rheumatologic disorders, and primary sclerosing cholangitis. Currently, there are no medications with approved indications for pouchitis. As such, the conventional treatment of pouchitis is entirely off-label. This paper is intended to be a practical and up-to-date review of available therapies used for the management of pouchitis. The mainstay of treatment for acute pouchitis remains antibiotics, but newer therapeutics have also shown promise in the treatment of chronic pouchitis. Common lifestyle considerations that may play a role in pouchitis are also reviewed. PLAIN LANGUAGE SUMMARY Medical treatment of pouchitis: a guide for the clinician The ileal pouch-anal anastomosis ("pouch") is the most common way patients who require surgery to remove their colon are able to avoid a permanent ileostomy ("ostomy"). This pouch, created from the small intestines, serves as a reservoir to hold stool. The most common complication after pouch surgery is pouchitis. Pouchitis symptoms include more frequent bowel movements, urgency to defecate, blood in the stool, incontinence, and abdominal pain. This paper is intended to be a practical review of available therapies including medications and lifestyle changes that can be considered for the management of acute pouchitis, chronic pouchitis, and cuffitis.
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Affiliation(s)
- Wendy Rabbenou
- Division of Gastroenterology and Hepatology, New York University Langone Medical Center, New York, NY, USA
| | - Shannon Chang
- Division of Gastroenterology and Hepatology, New York University Langone Medical Center, 305 E 33rd Street, New York, NY 10016, USA
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Li H, Chen J, Ren X, Yang C, Liu S, Bai X, Shan S, Dong X. Gut Microbiota Composition Changes in Constipated Women of Reproductive Age. Front Cell Infect Microbiol 2021; 10:557515. [PMID: 33552996 PMCID: PMC7859112 DOI: 10.3389/fcimb.2020.557515] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 12/03/2020] [Indexed: 12/12/2022] Open
Abstract
Background Chronic constipation is one of the most prevalent functional gastrointestinal disorders, yet its etiology is multifactorial, and the pathophysiological mechanism is still unclear. Previous studies have shown that the gut microbiota of constipated patients differs from healthy controls; however, many discrepancies exist in the findings, and no clear link has been confirmed between chronic constipation and changes in the gut microbiota. Growing evidence indicates that age, gender, and hormone levels can affect the composition of gut microbiota. The aim of this study is to examine the overall changes in gut microbiota within a specific sub-population of patients, namely, constipated women of reproductive age. Methods We carried out a cross-sectional study comparing the fecal microbial composition of 30 healthy women and 29 constipated women using 16S rRNA gene sequencing. Only women of reproductive age were recruited to reduce the effects of age, gender, and hormone levels on the microbiome, and to prevent conflating the impact of these factors with the effects of constipation. Results There were obvious differences in the gut microbiota in constipated women of reproductive age compared with the healthy controls, manifesting mainly as a significant increase in the abundance of Bacteroides (p < 0.05) and a significant decrease in the abundance of Proteobacteria (p < 0.01). The overall composition of the gut microbiota in each group was different, which was reflected in the ratios of Firmicutes to Bacteroidetes (F/B), which was 1.52 in the constipated group vs. 2.21 in the healthy group. Additionally, there was a significant decrease in butyrate-producing bacteria, like Roseburia and Fusicatenibacter (p < 0.01). Conclusion The overall composition of the gut microbiota changed in constipated women of reproductive age, characterized by a loss in Proteobacteria and an increase in Bacteroidetes. Furthermore, the abundance of some butyrate-producing bacteria also reduced. These changes may reflect the unique interactions between host and some bacteria, or some bacterial metabolic products, which may be important targets for future studies to explore the pathogenesis of constipation.
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Affiliation(s)
- Hongxia Li
- Department of General Surgery, Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Jianwei Chen
- Department of General Surgery, Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Xiaojing Ren
- Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, China
| | - Chuanli Yang
- Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, China
| | - Shuai Liu
- Department of General Surgery, Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Xinshu Bai
- Department of General Surgery, Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Shuhua Shan
- Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, China
| | - Xiushan Dong
- Department of General Surgery, Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, China
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Yanagi M, Komura T, Kagaya T, Yoshio T, Nishino M, Orita N, Nishikawa M, Kawashima A, Kaneko S, Unoura M. A case of refractory pouchitis complicated by cytomegalovirus infection requiring administration of ganciclovir and infliximab. Clin J Gastroenterol 2021; 14:181-186. [PMID: 33475967 DOI: 10.1007/s12328-020-01289-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 10/28/2020] [Indexed: 11/29/2022]
Abstract
Pouchitis is a frequent complication of surgical treatment of ulcerative colitis (UC), and is typically treated using antimicrobials. If pouchitis is refractory to antimicrobials, screening for complications, such as cytomegalovirus (CMV) infection, is necessary. However, the optimal approach to management of pouchitis complicated by CMV infection is unclear. We report the case of a 41-year-old female patient with UC presenting with pouchitis associated with CMV infection; she had received subtotal colectomy/ileal pouch anal anastomosis (IPAA). She was admitted to hospital with persistent fever, epigastric discomfort, and watery diarrhea despite receiving antibiotics. Laboratory findings showed inflammation and reactivation of CMV infection accompanied by liver injury. The endoscopic findings showed inflammation of the pouch and ileal mucosa on the oral side with extensive and deep punched-out ulcers. Immunohistological staining of biopsy specimens from an ulcerated lesion demonstrated CMV infection. Therefore, we diagnosed the patient with pouchitis complicated by CMV infection. The patient was treated with ganciclovir and infliximab, which resolved her symptoms and led to the disappearance of CMV-positive cells. There has been no recurrence of pouchitis. CMV infection should be considered in patients with UC who develop refractory pouchitis.
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Affiliation(s)
- Masahiro Yanagi
- Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, 1-1 Shimoishibikicho, Kanazawa, Ishikawa, 920-8650, Japan.
| | - Takuya Komura
- Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, 1-1 Shimoishibikicho, Kanazawa, Ishikawa, 920-8650, Japan
| | - Takashi Kagaya
- Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, 1-1 Shimoishibikicho, Kanazawa, Ishikawa, 920-8650, Japan
| | - Takatoshi Yoshio
- Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, 1-1 Shimoishibikicho, Kanazawa, Ishikawa, 920-8650, Japan
| | - Michiko Nishino
- Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, 1-1 Shimoishibikicho, Kanazawa, Ishikawa, 920-8650, Japan
| | - Noriaki Orita
- Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, 1-1 Shimoishibikicho, Kanazawa, Ishikawa, 920-8650, Japan
| | - Masashi Nishikawa
- Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, 1-1 Shimoishibikicho, Kanazawa, Ishikawa, 920-8650, Japan
| | - Atsuhiro Kawashima
- Department of Clinical Laboratory, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan
| | - Shuichi Kaneko
- System Biology, Graduate School of Advanced Preventive Medical Science, Kanazawa University, Kanazawa, Japan
| | - Masashi Unoura
- Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, 1-1 Shimoishibikicho, Kanazawa, Ishikawa, 920-8650, Japan
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Nguyen N, Zhang B, Holubar SD, Pardi DS, Singh S. Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev 2019; 11:CD001176. [PMID: 31785173 PMCID: PMC6885001 DOI: 10.1002/14651858.cd001176.pub5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC). OBJECTIVES The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis. SEARCH METHODS We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings. SELECTION CRITERIA Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion. DATA COLLECTION AND ANALYSIS Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. MAIN RESULTS Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear. Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty-three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty-seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty-five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty-eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy-five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence). Chronic pouchitis: Eighty-five per cent (34/40) of De Simone Formulation (a probiotic formulation) participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty-five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty-five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain. PREVENTION At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty-six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty-six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty-one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence). AUTHORS' CONCLUSIONS The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.
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Affiliation(s)
- Nghia Nguyen
- University of California San DiegoDivision of GastroenterologyLa JollaCaliforniaUSA
| | - Bing Zhang
- University of California San FranciscoDivision of GastroenterologySan FranciscoCaliforniaUSA
| | - Stefan D Holubar
- Cleveland ClinicDepartment of Colon and Rectal SurgeryClevelandOHUSA
| | - Darrell S Pardi
- Mayo ClinicDivision of Gastroenterology and Hepatology200 First Street SWRochesterMNUSA55905
| | - Siddharth Singh
- University of California San DiegoDivision of GastroenterologyLa JollaCaliforniaUSA
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Nguyen N, Zhang B, Holubar SD, Pardi DS, Singh S. Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev 2019; 5:CD001176. [PMID: 31136680 PMCID: PMC6538309 DOI: 10.1002/14651858.cd001176.pub4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC). OBJECTIVES The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis. SEARCH METHODS We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings. SELECTION CRITERIA Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion. DATA COLLECTION AND ANALYSIS Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. MAIN RESULTS Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear.Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty-three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty-seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty-five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty-eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy-five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence).Chronic pouchitis: Eighty-five per cent (34/40) of De Simone Formulation participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty-five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty-five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain. PREVENTION At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty-six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty-six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty-one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence). AUTHORS' CONCLUSIONS The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.
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Affiliation(s)
- Nghia Nguyen
- University of California San DiegoDivision of GastroenterologyLa JollaUSA
| | - Bing Zhang
- University of California San FranciscoDivision of GastroenterologySan FranciscoUSA
| | - Stefan D Holubar
- Cleveland ClinicDepartment of Colon and Rectal SurgeryClevelandUSA
| | - Darrell S Pardi
- Mayo ClinicDivision of Gastroenterology and Hepatology200 First Street SWRochesterUSA55905
| | - Siddharth Singh
- University of California San DiegoDivision of GastroenterologyLa JollaUSA
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Kjær MD, Qvist N, Nordgaard-Lassen I, Christensen LA, Kjeldsen J. Adalimumab in the treatment of chronic pouchitis. A randomized double-blind, placebo-controlled trial. Scand J Gastroenterol 2019; 54:188-193. [PMID: 30739519 DOI: 10.1080/00365521.2019.1569718] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Pouchitis is a complication of ileal pouch-anal anastomosis and occurs in up to 50% of patients 10 years after IPAA with 10% developing refractory pouchitis. OBJECTIVE To evaluate the effect of a TNF-α inhibitor (Adalimumab) in the treatment of refractory pouchitis. MATERIALS AND METHODS A multicenter, randomized double-blind, placebo-controlled trial includes patients with refractory pouchitis for more than 4 weeks despite antibiotic treatment. Patients were randomized to Adalimumab or placebo for 12 weeks. Primary outcome was reduction in clinical pouchitis disease activity index (PDAI) of ≥2 at any time. Secondary endpoints were remission of pouchitis, endoscopic and histologic effect and quality of life. RESULTS Thirteen patients were included; six patients received active treatment and seven patients received placebo. Nine patients (5/4, Adalimumab/placebo) completed the 12-week program. Reduction in clinical PDAI ≥ 2 was achieved in three patients in each group (50%/43%, Adalimumab/placebo, p > .5). Total PDAI improved in six patients treated with Adalimumab and two patients on placebo (100%/29%, p = .13). There were no differences in secondary endpoints between the groups. CONCLUSIONS In this randomized controlled trial of treatment with Adalimumab in patients with refractory pouchitis, we were not able to identify any clinical benefit in the primary or secondary endpoints.
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Affiliation(s)
- Mie Dilling Kjær
- a Department of Surgery , Odense University Hospital , Odense C , Denmark
| | - Niels Qvist
- a Department of Surgery , Odense University Hospital , Odense C , Denmark
| | | | | | - Jens Kjeldsen
- d Department of Medical Gastroenterology , Odense University Hospital , Odense , Denmark
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9
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Brown SR, Fearnhead NS, Faiz OD, Abercrombie JF, Acheson AG, Arnott RG, Clark SK, Clifford S, Davies RJ, Davies MM, Douie WJP, Dunlop MG, Epstein JC, Evans MD, George BD, Guy RJ, Hargest R, Hawthorne AB, Hill J, Hughes GW, Limdi JK, Maxwell-Armstrong CA, O'Connell PR, Pinkney TD, Pipe J, Sagar PM, Singh B, Soop M, Terry H, Torkington J, Verjee A, Walsh CJ, Warusavitarne JH, Williams AB, Williams GL, Wilson RG. The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease. Colorectal Dis 2018; 20 Suppl 8:3-117. [PMID: 30508274 DOI: 10.1111/codi.14448] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 09/17/2018] [Indexed: 12/14/2022]
Abstract
AIM There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.
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Affiliation(s)
- S R Brown
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - N S Fearnhead
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - O D Faiz
- St Mark's Hospital, Middlesex, Harrow, UK
| | | | - A G Acheson
- Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - R G Arnott
- Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK
| | - S K Clark
- St Mark's Hospital, Middlesex, Harrow, UK
| | | | - R J Davies
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - M M Davies
- University Hospital of Wales, Cardiff, UK
| | - W J P Douie
- University Hospitals Plymouth NHS Trust, Plymouth, UK
| | | | - J C Epstein
- Salford Royal NHS Foundation Trust, Salford, UK
| | - M D Evans
- Morriston Hospital, Morriston, Swansea, UK
| | - B D George
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - R J Guy
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - R Hargest
- University Hospital of Wales, Cardiff, UK
| | | | - J Hill
- Manchester Foundation Trust, Manchester, UK
| | - G W Hughes
- University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - J K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
| | | | | | - T D Pinkney
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - J Pipe
- Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK
| | - P M Sagar
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - B Singh
- University Hospitals of Leicester NHS Trust, Leicester, UK
| | - M Soop
- Salford Royal NHS Foundation Trust, Salford, UK
| | - H Terry
- Crohn's and Colitis UK, St Albans, UK
| | | | - A Verjee
- Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK
| | - C J Walsh
- Wirral University Teaching Hospital NHS Foundation Trust, Arrowe Park Hospital, Upton, UK
| | | | - A B Williams
- Guy's and St Thomas' NHS Foundation Trust, London, UK
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10
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Uchino M, Ikeuchi H, Bando T, Hirata A, Chohno T, Sasaki H, Horio Y, Nakamura S. Association between serum tumor necrosis factor-alpha level and the efficacy of infliximab for refractory pouchitis after restorative proctocolectomy in patients with ulcerative colitis. JOURNAL OF THE ANUS RECTUM AND COLON 2018; 1:106-111. [PMID: 31583309 PMCID: PMC6768686 DOI: 10.23922/jarc.2016-008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 05/08/2017] [Indexed: 12/03/2022]
Abstract
Objectives: Although the aetiology of pouchitis after restorative proctocolectomy in ulcerative colitis (UC) remains unknown, infliximab (IFX) is often effective for this condition. However, indicators and predictors of treatment efficacy remain unclear. In this study, the association between serum tumor necrosis factor-alpha (TNF-α) levels and refractory pouchitis was evaluated. Methods: We conducted a prospective study between January 2014 and April 2016. Patients with antibiotic-refractory pouchitis were treated with IFX. Serum TNF-α levels were measured before IFX induction. Diagnoses were confirmed using the modified Pouchitis Disease Activity Index (m-PDAI). Responders were defined as patients with an m-PDAI score lower than 5. Recurrence was defined as an m-PDAI score exceeding 5 during maintenance treatment or a need for additional treatments. Associations between serum TNF-α level and efficacy of IFX during 52 weeks of maintenance therapy were evaluated. Results: Thirteen patients were eligible for this study. The short-term efficacy was 8/13 (61.5%). Four patients could not be maintained with IFX alone. The cumulative maintenance ratio was 30.8%/52 weeks, and the cut-off value for serum TNF-α was 1.93 pg/mL for short-term response. Although there was no significant association between serum TNF-α and treatment response, IFX treatment was unsuccessful for all five patients with TNF-α levels below 1.93 pg/mL, including four short-term non-responders and one long-term non-responder. Conclusion: Serum TNF-α level was not an independent predictor of IFX efficacy for refractory pouchitis. However, IFX may be effective for patients with elevated serum TNF-α. Future studies should assess this possibility.
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Affiliation(s)
- Motoi Uchino
- Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan
| | - Hiroki Ikeuchi
- Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan
| | - Toshihiro Bando
- Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan
| | - Akihiro Hirata
- Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan
| | - Teruhiro Chohno
- Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan
| | - Hirofumi Sasaki
- Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan
| | - Yuki Horio
- Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan
| | - Shiro Nakamura
- Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan
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11
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Dalal RL, Shen B, Schwartz DA. Management of Pouchitis and Other Common Complications of the Pouch. Inflamm Bowel Dis 2018; 24:989-996. [PMID: 29688472 DOI: 10.1093/ibd/izy020] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the preferred surgical treatment for refractory or complicated ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Pouchitis is the most common complication of this procedure and can occur in about 50% of patients. Treatment of pouchitis depends on the phenotype of disease. Pouchitis can be classified as acute, chronic/refractory, or secondary pouchitis, which includes pouchitis occurring due to Crohn's disease (CD). CD of the pouch is becoming an increasingly recognized problem, and management is challenging. This article reviews the literature and offers treatment recommendations regarding management of pouchitis and CD of the pouch.
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Affiliation(s)
- Robin L Dalal
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Bo Shen
- Department of Gastroenterology/Hepatology, the Cleveland Clinic, Foundation, Cleveland, Ohio
| | - David A Schwartz
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
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12
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Abstract
Alicaforsen is a 20-base antisense oligonucleotide inhibiting ICAM-1 production, which is an important adhesion molecule involved in leukocyte migration and trafficking to the site of inflammation. Hitherto, alicaforsen has been granted orphan drug designation and is prescribed as an unlicensed medicine in accordance with international regulation for the treatment of pouchitis and left-sided ulcerative colitis. Given the positive results evolving from one open-label trial and one case series in patients with chronic refractory pouchitis, US FDA has agreed to a rolling submission for a license application for the treatment of pouchitis, which has been recently initiated. Whether alicaforsen leads to higher endoscopic and clinical remission rates as placebo and whether the response can be maintained in the long-term in larger studies is yet unknown. An ongoing multicenter international Phase III trial will definitely address these unanswered questions.
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Affiliation(s)
- Thomas Greuter
- Department of Gastroenterology & Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology & Hepatology, University Hospital Zurich, Zurich, Switzerland
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13
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Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis 2017; 11:649-670. [PMID: 28158501 DOI: 10.1093/ecco-jcc/jjx008] [Citation(s) in RCA: 1250] [Impact Index Per Article: 156.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 02/01/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Fernando Magro
- Department of Pharmacology and Therapeutics, University of Porto; MedInUP, Centre for Drug Discovery and Innovative Medicines; Centro Hospitalar São João, Porto, Portugal
| | | | - Rami Eliakim
- Department of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Sandro Ardizzone
- Gastrointestinal Unit ASST Fatebenefratelli Sacco-University of Milan-Milan, Italy
| | - Alessandro Armuzzi
- IBD Unit Complesso Integrato Columbus, Gastroenterological and Endocrino-Metabolical Sciences Department, Fondazione Policlinico Universitario Gemelli Universita' Cattolica del Sacro Cuore, Rome, Italy
| | - Manuel Barreiro-de Acosta
- Department of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), A Coruña, Spain
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Krisztina B Gecse
- First Department of Medicine, Semmelweis University, Budapest,Hungary
| | | | - Pieter Hindryckx
- Department of Gastroenterology, University Hospital of Ghent, Ghent, Belgium
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust; Institute of Inflammation and Repair, University of Manchester, Manchester, UK
| | - Gianluca Pellino
- Unit of General Surgery, Second University of Naples,Napoli, Italy
| | - Edyta Zagórowicz
- Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Oncological Gastroenterology Warsaw; Medical Centre for Postgraduate Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, Poland
| | - Tim Raine
- Department of Medicine, University of Cambridge, Cambridge,UK
| | - Marcus Harbord
- Imperial College London; Chelsea and Westminster Hospital, London,UK
| | - Florian Rieder
- Department of Pathobiology /NC22, Lerner Research Institute; Department of Gastroenterology, Hepatology and Nutrition/A3, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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14
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Lightner AL, Pemberton JH, Dozois EJ, Larson DW, Cima RR, Mathis KL, Pardi DS, Andrew RE, Koltun WA, Sagar P, Hahnloser D. The surgical management of inflammatory bowel disease. Curr Probl Surg 2017; 54:172-250. [PMID: 28576304 DOI: 10.1067/j.cpsurg.2017.02.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Amy L Lightner
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN.
| | - John H Pemberton
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN
| | - Eric J Dozois
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN
| | - David W Larson
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN
| | - Robert R Cima
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN
| | - Kellie L Mathis
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Rachel E Andrew
- Division of Colorectal Surgery, Penn State Health Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, PA
| | - Walter A Koltun
- Division of Colorectal Surgery, Penn State Health Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, PA
| | - Peter Sagar
- Division of Colorecal surgery, St. James University Hospital, Leeds, England
| | - Dieter Hahnloser
- Division of Colorecal surgery, Lausanne University Hospital, Lausanne, Switzerland
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15
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Singh S, Stroud AM, Holubar SD, Sandborn WJ, Pardi DS. Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev 2015:CD001176. [PMID: 26593456 PMCID: PMC4917283 DOI: 10.1002/14651858.cd001176.pub3] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis. OBJECTIVES The primary objective was to determine the efficacy and safety of medical therapies (including antibiotics, probiotics, and other agents) for prevention or treatment of acute or chronic pouchitis. SEARCH METHODS We searched MEDLINE, EMBASE and the Cochrane Library from inception to October 2014. SELECTION CRITERIA Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for ulcerative colitis were considered for inclusion. DATA COLLECTION AND ANALYSIS Two authors independently screened studies for eligibility, extracted data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome was the proportion of patients with clinical improvement or remission of pouchitis in patients with acute or chronic pouchitis, or the proportion of patients with no episodes of pouchitis after IPAA. The proportion of patients who developed at least one adverse event was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. MAIN RESULTS Thirteen studies (517 participants) were included in the review. Four studies assessed treatment of acute pouchitis. One study (16 participants) compared ciprofloxacin and metronidazole; another (26 participants) compared metronidazole to budesonide enemas; another (18 participants) compared rifaximin to placebo; and the fourth study (20 participants) compared Lactobacillus GG to placebo. Four studies assessed treatment of chronic pouchitis. One study (19 participants) compared glutamine to butyrate suppositories; another (40 participants) compared bismuth enemas to placebo; and two studies (76 participants) compared VSL#3 to placebo. Five studies assessed prevention of pouchitis. One study (40 participants) compared VSL#3 to placebo; another (28 participants) compared VLS#3 to no treatment; one study (184 participants) compared allopurinol to placebo; another (12 participants) compared the probiotic Bifidobacterium longum to placebo; and one study (38 participants) compared tinidazole to placebo. Three studies were judged to be of high quality. Two studies were judged to be low quality and the quality of the other studies was unclear. Treatment of acute pouchitis: The results of one small study (16 participants) suggest that ciprofloxacin may be more effective than metronidazole for the treatment of acute pouchitis. One hundred per cent (7/7) of ciprofloxacin patients achieved remission at two weeks compared to 33% (3/9) of metronidazole patients. A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to high risk of bias (no blinding) and very sparse data (10 events). There was no difference in the proportion of patients who had at least one adverse event (RR 0.18, 95% CI 0.01 to 2.98). Adverse events included vomiting, dysgeusia or transient peripheral neuropathy. There were no differences between metronidazole and budesonide enemas in terms of clinical remission, clinical improvement or adverse events. Adverse events included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. There were no differences between rifaximin and placebo in terms of clinical remission, clinical improvement, or adverse events. Adverse events included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. There was no difference in clinical improvement between Lactobacillus GG and placebo. The results of these studies are uncertain due to very low quality evidence. Treatment of chronic pouchitis: A pooled analysis of two studies (76 participants) suggests that VSL#3 may be more effective than placebo for maintenance of remission. Eighty-five per cent (34/40) of VLS#3 patients maintained remission at 9 to 12 months compared to 3% (1/36) of placebo patients (RR 20.24, 95% CI 4.28 to 95.81). A GRADE analysis indicated that the quality of evidence supporting this outcome was low due to very sparse data (35 events). Adverse events included abdominal cramps, vomiting and diarrhea. There was no difference in effectiveness between glutamine and butyrate suppositories for maintenance of remission. There was no difference in clinical improvement or adverse event rates between bismuth carbomer foam enemas and placebo. Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain. The results of these studies are uncertain due to very low quality evidence. Prevention of pouchitis: The results of one small study (40 participants) suggest that VSL#3 may be more effective than placebo for prevention of pouchitis. Ninety per cent (18/20) of VSL#3 patients had no episodes of acute pouchitis during the 12 month study compared to 60% (12/20) of placebo patients (RR 1.50, 95% CI 1.02 to 2.21). A GRADE analysis indicated that the quality of evidence supporting this outcome was low due to very sparse data (30 events). Another small study (28 participants) found that VLS#3 was not more effective than no treatment for prevention of pouchitis. Bifidobacterium longum, allopurinol and tinidazole were not more effective than placebo for prevention of pouchitis. The results of these studies are uncertain due to very low quality evidence. AUTHORS' CONCLUSIONS For acute pouchitis, very low quality evidence suggests that ciprofloxacin may be more effective than metronidazole. For chronic pouchitis, low quality evidence suggests that VSL#3 may be more effective than placebo for maintenance of remission. For the prevention of pouchitis, low quality evidence suggests that VSL#3 may be more effective than placebo. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | - Andrea M Stroud
- Section of General Surgery, Dartmouth-Hitchcock Medical Cente, Lebanon, NH, USA
| | - Stefan D Holubar
- Division of Colon and Rectal Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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16
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van Assche G, Dignass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, Beaugerie L, Gomollón F, Häuser W, Herrlinger K, Oldenburg B, Panes J, Portela F, Rogler G, Stein J, Tilg H, Travis S, Lindsay JO. [Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 3: Special situations (Spanish version)]. REVISTA DE GASTROENTEROLOGIA DE MEXICO 2015; 80:74-106. [PMID: 25769216 DOI: 10.1016/j.rgmx.2014.10.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 10/23/2014] [Indexed: 12/12/2022]
Affiliation(s)
- G van Assche
- En nombre de la ECCO; G.V.A. y A.D. actúan como coordinadores del consenso y han contribuido igualmente para este trabajo.
| | - A Dignass
- G.V.A. y A.D. actúan como coordinadores del consenso y han contribuido igualmente para este trabajo.
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Reduced neurons in the ileum of proctocolectomized rat models. Med Mol Morphol 2014; 48:155-63. [PMID: 25432768 DOI: 10.1007/s00795-014-0093-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Accepted: 10/31/2014] [Indexed: 10/24/2022]
Abstract
Ileal pouch-anal anastomosis (IPAA) is the operation of choice following proctocolectomy for patients who suffer from ulcerative colitis and familial adenomatous polyposis. The aim of this study was to morphologically examine the neurons, endocrine cells and mast cells in the ileum of rats subjected to proctocolectomy followed by three different types of ileoanal anastomosis. Rats were subjected to either sham operation or proctocolectomy followed by ileoanal anastomosis end-to-end, side-to-end or IPAA (J-pouch). In comparison to sham-operated rats, the body weight was reduced in rats that underwent proctocolectomy with end-to-end or side-to-end, but not IPAA procedure. In all three models of ileoanal anastomosis, the ileum displayed crypt hyperplasia with a chronic inflammatory infiltrate located in the interstitium, hyperplasia of goblet cells, but reduced protein gene product 9.5 (PGP 9.5)-immunoreactive neurons in the mucosa as well as submucosa. Numbers of endocrine cells in the mucosa (chromogranin A immunostaining) and mast cells in the mucosa and submucosa (Astra blue staining) were unchanged after proctocolectomy. In conclusion, neurons, but neither endocrine cells nor mast cells, were reduced in the ileum of proctocolectomized rats followed by either of three different types of ileoanal anastomosis.
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Mukewar S, Wu X, Lopez R, Shen B. Comparison of long-term outcomes of S and J pouches and continent ileostomies in ulcerative colitis patients with restorative proctocolectomy-experience in subspecialty pouch center. J Crohns Colitis 2014; 8:1227-36. [PMID: 24657364 DOI: 10.1016/j.crohns.2014.02.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Revised: 02/20/2014] [Accepted: 02/20/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND There are no published studies comparing pouch configurations and long-term adverse outcomes. AIM To evaluate outcomes of ulcerative colitis (UC) patients undergoing restorative proctocolectomy with S-, J- pouches or continent ileostomy (CI). METHODS We conducted a historical cohort study from the prospectively maintained Pouch Registry. Demographic and clinical variables were evaluated with univariate and multivariable analyses. RESULTS Fourty-five patients with S pouches and 36 with CI (33 K pouches and 3 Barnett continent ileal reservoirs) were compared with 215 J pouches serving as controls (ratio 1:2.5). In multivariable analysis, patients with S pouches were 93% less likely to develop chronic antibiotic-refractory pouchitis (CARP) than subjects with J pouches (odds ratio [OR]=0.07; 95% confidence interval: <0.001, 0.54; p<0.001). However, no significant difference in the frequency of CARP was found between the CI and J pouch groups (OR=0.68; 95% confidence interval: 0.17, 2.00, p=0.40). Patients with S pouches were 8 times more likely (95% confidence interval: 3.7, 17.5; p<0.001) and patients with CI 5.6 had times more likely (95% confidence interval: 2.4, 13.3; p<0.001) to have pouch surgery-related complications than those with J pouches. There was no difference in the rate of CD of the pouch, pouch-associated hospitalization and pouch failure between the S- pouch, CI and J- pouch groups. CONCLUSIONS Patients with J pouches appeared to have a greater risk for chronic pouchitis than those with S-pouches and but had a lower risk for developing pouch surgery-related complications than those with S pouches or CI.
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Affiliation(s)
- Saurabh Mukewar
- Departments of Gastroenterology/Hepatology, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Xianrui Wu
- Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Rocio Lopez
- Department of Quantitative Health Sciences, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Bo Shen
- Departments of Gastroenterology/Hepatology, The Cleveland Clinic Foundation, Cleveland, OH, USA.
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Angriman I, Scarpa M, Castagliuolo I. Relationship between pouch microbiota and pouchitis following restorative proctocolectomy for ulcerative colitis. World J Gastroenterol 2014; 20:9665-9674. [PMID: 25110406 PMCID: PMC4123357 DOI: 10.3748/wjg.v20.i29.9665] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Revised: 12/23/2013] [Accepted: 05/05/2014] [Indexed: 02/06/2023] Open
Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for many patients with medically refractory ulcerative colitis (UC) and familial adenomatous polyposis (FAP). UC patients with IPAA (UC-IPAA) are, nevertheless, susceptible to inflammatory and noninflammatory sequelae such as pouchitis, which is only rarely noted in FAP patients with IPAA. Pouchitis is the most frequent long-term complication of UC-IPAA patients, with a cumulative prevalence of up to 50%. Although the aetiology of pouchitis remains unclear, accumulating evidence suggests that a dysbiosis of the pouch microbiota and an abnormal mucosal immune response are implicated in its pathogenesis. Studies using culture and molecular techniques have detected a dysbiosis of the pouch microbiota in patients with pouchitis. Risk factors, genetic associations, and serological markers suggest that interactions between the host immune response and the pouch microbiota underlie the aetiology of this idiopathic inflammatory condition. This systematic review focuses on the dysbiosis of the microbiota that inhabit the pouch in UC and FAP patients and its interaction with the mucosal immune system. A meta-analysis was not attempted due to the highly heterogeneous microbiota composition and the different detection methods used by the various studies. Although no specific bacterial species, genus, or family has as yet been identified as pathogenic, there is evidence that a dysbiosis characterized by decreased gut microbiota diversity in UC-IPAA patients may, in genetically predisposed subjects, lead to aberrant mucosal immune regulation triggering an inflammatory process.
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Van Assche G, Dignass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, Beaugerie L, Gomollón F, Häuser W, Herrlinger K, Oldenburg B, Panes J, Portela F, Rogler G, Stein J, Tilg H, Travis S, Lindsay JO. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. J Crohns Colitis 2013; 7:1-33. [PMID: 23040453 DOI: 10.1016/j.crohns.2012.09.005] [Citation(s) in RCA: 334] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Accepted: 09/03/2012] [Indexed: 02/07/2023]
Affiliation(s)
- Gert Van Assche
- Division of Gastroenterology, Department of Medicine, Mt. Sinai Hospital and University Health Network,University of Toronto and University of Leuven, 600 University Avenue, Toronto, ON, Canada M5G 1X5.
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Abstract
Although restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for patients with refractory ulcerative colitis (UC) or UC with dysplasia, surgical, inflammatory, and noninflammatory adverse sequelae are common. Pouchitis, representing a spectrum of disease phenotypes, is the most common long-term complication of IPAA. De novo Crohn disease (CD) of the pouch can occur in patients with a preoperative diagnosis of UC. Differential diagnosis between fibrostenotic or fistulizing CD and surgery-associated strictures, sinuses, and fistulas often requires a combined assessment of symptom, endoscopy, histology, radiography, and examination under anesthesia. There is a role for endoscopic therapy for stricturing complications of IPAA. Chronic antibiotic-refractory pouchitis, refractory cuffitis, as well as fibrostenotic or fistulizing CD of the pouch are the leading late-onset causes for pouch failure.
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Affiliation(s)
- Bo Shen
- Department of Gastroenterology/Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio. USA.
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Shen B, Bennett AE, Navaneethan U, Lian L, Shao Z, Kiran RP, Fazio VW, Remzi FH. Primary sclerosing cholangitis is associated with endoscopic and histologic inflammation of the distal afferent limb in patients with ileal pouch-anal anastomosis. Inflamm Bowel Dis 2011; 17:1890-900. [PMID: 21830267 DOI: 10.1002/ibd.21594] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2010] [Accepted: 11/03/2010] [Indexed: 12/16/2022]
Abstract
BACKGROUND We hypothesized that patients with primary sclerosing cholangitis (PSC) may have a higher risk for prepouch ileitis in the setting of ileal pouch-anal anastomosis (IPAA). The aim of this study was to compare endoscopic and histologic inflammation in the afferent limb (prepouch ileum) and pouch between IPAA patients with and without PSC. METHODS In all, 39 consecutive inflammatory bowel disease (IBD) and IPAA patients with PSC (study group) were identified and 91 IBD and IPAA patients without PSC (control group) were randomly selected with a 1:2 ratio. Demographic, clinical, endoscopic, and histologic variables were analyzed. RESULTS There were no significant differences in age, gender, and nonsteroidal antiinflammatory drug use between the study and control groups. Twelve (30.8%) patients in the IPAA-PSC group had coexisting autoimmune disorders, in contrast to five (5.5%) patients in the IPAA control group (P < 0.001). More patients in the study group had endoscopic inflammation as demonstrated by the higher Pouchitis Disease Activity Index (PDAI) endoscopic scores of the afferent limb and pouch body than those in the control group (P = 0.02 and P < 0.001, respectively). In addition, more patients with PSC had higher PDAI histologic scores of the afferent limb than those without PSC (P < 0.001). Multivariate analysis showed higher PDAI endoscopy and histology subscores were associated with risk for PSC, with odds ratio 1.34 (95% confidence interval [CI]: 1.34, 3.79) and 1.61 (95% CI: 1.00, 2.58), respectively. CONCLUSIONS Concurrent PSC appears to be associated with a significant prepouch ileitis on endoscopy and histology in patients with IPAA. Pouch patients with long segment of ileitis should be evaluated for PSC.
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Affiliation(s)
- Bo Shen
- Department of Gastroenterology, the Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
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Navaneethan U, Shen B. Diagnosis and management of pouchitis and ileoanal pouch dysfunction. Curr Gastroenterol Rep 2010; 12:485-94. [PMID: 20890738 DOI: 10.1007/s11894-010-0143-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC with dysplasia and for the majority of patients with familial adenomatous polyposis. However, UC patients with IPAA are susceptible to inflammatory and noninflammatory sequelae, such as pouchitis, Crohn's disease of the pouch, cuffitis, and irritable pouch syndrome, in addition to common surgery-associated complications, which adversely affect the surgical outcome and compromise health-related quality of life. Pouchitis is the most frequent long-term complication of IPAA in patients with UC, with a cumulative prevalence of up to 50%. Pouchitis may be classified based on the etiology into idiopathic and secondary types, and the management is often different. Pouchoscopy is the most important tool for the diagnosis and differential diagnosis in patients with pouch dysfunction. Antibiotic therapy is the mainstay of treatment for active pouchitis. Some patients may develop dependency on antibiotics, requiring long-term maintenance therapy. Although management of antibiotic-dependent or antibiotic-refractory pouchitis has been challenging, secondary etiology for pouchitis should be evaluated and modified, if possible.
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Affiliation(s)
- Udayakumar Navaneethan
- The Pouchitis Clinic, Digestive Disease Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
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Holubar SD, Cima RR, Sandborn WJ, Pardi DS. Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev 2010:CD001176. [PMID: 20556748 DOI: 10.1002/14651858.cd001176.pub2] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Pouchitis may occur following ileal pouch-anal anastomosis for chronic ulcerative colitis in approximately 30% of patients. OBJECTIVES The primary objective was to determine the efficacy of medical therapies for pouchitis (including antibiotic, probiotic, and other agents) as substantiated by data from randomized controlled trials (RCTs). SEARCH STRATEGY A search for RCTs from 1966 to October 2009 was performed using the MEDLINE, Cochrane Library, EMBASE, Web of Science, and Scopus databases. SELECTION CRITERIA Randomized controlled treatment or prevention trials of adult patients who underwent ileal pouch-anal anastomosis for ulcerative colitis who subsequently developed pouchitis or were at risk for pouchitis were considered for inclusion. DATA COLLECTION AND ANALYSIS Extracted data were converted to 2X2 tables and then synthesized in to a summary statistic using the Peto odds ratio (OR) and [95% confidence intervals], or weighted mean difference (WMD), using RevMan-5 for Mac OS 10.6. MAIN RESULTS Eleven RCTs fulfilled the inclusion criteria and were included in the review. The efficacy of 10 different pharmacologic agents was assessed. For the treatment of acute pouchitis (4 RCTS, 5 agents), ciprofloxacin was more effective at inducing remission than metronidazole. Neither rifaximin nor lactobacillus GG were more effective than placebo, while budesonide enemas and metronidazole were similarly effective, for inducing remission of acute pouchitis. For the treatment and maintenance of remission of chronic pouchitis (4 RCTs, 4 agents), glutamine suppositories were not more effective than butyrate suppositories, and bismuth carbomer foam enemas were not more effective than placebo, while VSL#3 was more effective than placebo in maintaining remission of chronic pouchitis in patients with chronic pouchitis who achieved remission with antibiotics. For the prevention of pouchitis (3 RCTs, 2 agents), in one study VSL#3 was more effective than placebo while in another study VSL#3 was not more effective than no treatment. Allopurinol was not more effective than placebo, while inulin was more effective than placebo but the results were not clinically significant. AUTHORS' CONCLUSIONS For acute pouchitis, ciprofloxacin was more effective than metronidazole, while budesonide enemas and metronidazole were similarly effective. For chronic pouchitis, VSL#3 was more effective than placebo. For the prevention of pouchitis, VSL#3 was more effective than placebo. Larger RCTs are needed to determine the optimal agent(s) for the treatment and prevention of pouchitis.
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Affiliation(s)
- Stefan D Holubar
- Division of Colon and Rectal Surgery, Department of Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, USA, 55905
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26
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Johnson MW, Rogers GB, Bruce KD, Lilley AK, von Herbay A, Forbes A, Ciclitira PJ, Nicholls RJ. Bacterial community diversity in cultures derived from healthy and inflamed ileal pouches after restorative proctocolectomy. Inflamm Bowel Dis 2009; 15:1803-11. [PMID: 19637361 DOI: 10.1002/ibd.21022] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2009] [Accepted: 05/11/2009] [Indexed: 12/16/2022]
Abstract
BACKGROUND Pouchitis is believed to occur as a reaction to dysbiosis. In this study we assessed differences between mucosal bacterial communities cultured from noninflamed and inflamed ileal pouches. METHODS Thirty-two ileal pouch patients, 22 with ulcerative colitis (UC) and 10 with familial adenomatous polyposis (FAP), underwent symptomatic, endoscopic, and histological assessment. The Objective Pouchitis Score (OPS) and the Pouch Disease Activity Index (PDAI) were used to diagnose pouchitis. Seven UC patients had pouchitis (UC+), 15 had a noninflamed pouch (UC-), 9 had a noninflamed pouch (FAP-), and 1 FAP patient had pouchitis (FAP+). Biopsies taken from the ileal mucosa of the pouch were cultured under aerobic and anaerobic conditions. Following standardized DNA extraction a polymerase chain reaction (PCR) was performed to generate 16S rRNA gene products. A "fingerprint" of the bacterial community within each sample was created using terminal-restriction fragment length polymorphism (T-RFLP) profiling. Species richness and evenness were determined using T-RF band lengths and relative band intensities. RESULTS From the 64 DNA samples, 834 bands were detected, of which 179 represented different species (operational taxonomic units [OTUs]). The average species richness for the FAP-, FAP+, UC-, and UC+ groups was 26, 35, 23.9, and 29.6 per patient, with the average species diversity within the groups of 10.6, 29, 8.3, and 11.4, respectively. Similar trends were observed when the anaerobic and aerobic-derived bacterial groups were analyzed separately. CONCLUSIONS No significant differences were found between the bacterial cultures derived from any of the clinical groups or between pouchitis and nonpouchitis patients.
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Affiliation(s)
- Matt W Johnson
- Gastroenterology Surgical Department, St. Mark's Hospital, Harrow, Middlesex, UK
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Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for patients with medically refractory ulcerative colitis or ulcerative colitis with dysplasia and for the majority of patients with familial adenomatous polyposis. However, pouchitis and other pouch-associated complications frequently occur following surgery. Pouchitis is the most common long-term complication of ileal pouch-anal anastomosis in patients with ulcerative colitis, with a cumulative prevalence of up to 50%. The pathogenesis of pouchitis is probably associated with alterations in commensal bacterial flora, and most patients with pouchitis respond favorably to antibiotic therapy. Antibiotic therapy is the mainstay of treatment for active pouchitis, with ciprofloxacin or metronidazole traditionally being first-line agents. Some patients may develop dependency on antibiotics, thus requiring long-term maintenance therapy. In a subset of patients, the disease course may be refractory to antibiotic therapy, which is one of the common causes of pouch failure, requiring permanent ileostomy or pouch excision. On the other hand, long-term antibiotic use is expensive and can be associated with adverse effects and bacterial resistance. There may also be the risk of secondary infections, such as Clostridium difficile and fungal infections. The risks and benefits should be carefully balanced in patients who require long-term antibiotic therapy, and safe, efficacious, non-antibiotic-based agents are needed.
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Affiliation(s)
- Udayakumar Navaneethan
- The Pouchitis Clinic, Digestive Disease Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
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Wasmuth HH, Tranø G, Endreseth B, Rydning A, Wibe A, Myrvold HE. Long-term surgical load in patients with ileal pouch-anal anastomosis. Colorectal Dis 2009; 11:711-8. [PMID: 19708089 DOI: 10.1111/j.1463-1318.2008.01671.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM To evaluate surgical workload and complications in patients who had undergone restorative proctocolectomy, through long-term follow-up in one single institution. METHOD From 1984 to 2006, 304 consecutive patients underwent Ileal Pouch-Anal Anastomosis (IPAA). There were 182 stapled and 122 hand-sewn anastomoses. A protective loop ileostomy was established in 256 patients (84%), whereas 48 patients (16%) were without a covering stoma. RESULTS Twenty-nine patients (10%) suffered from early anastomotic leakage. A protective stoma did not prevent early anastomotic dehiscence (P = 0.11) or the number of pelvic abscesses (P = 0.09). Early complications required 20 laparotomies with creation of a diverting stoma in nine patients. There were 16 (6%) complications related to closure of the loop ileostomy. Sixty-six patients needed an additional re-operation related to the IPAA procedure. There were 20 removals of pouches and three permanent diverting stomas. The estimated removal rate at 20 years of a functioning pouch was 11% (CI +/- 6). Altogether 100 (33%) patients had one or more surgical procedures, excluding dilations of anastomotic strictures and closing of a loop ileostomy. These 100 patients underwent 187 surgical procedures. The estimated rate of a first re-operation due to complications was 52% (CI +/- 16) in 20 years. Hand-sewn anastomoses had similar complications and failure rates as stapled anastomoses. CONCLUSIONS More than half of patients operated with restorative proctocolectomy will need surgical intervention within 20 years and the failure rate is more than 10%. The high risk of complications and failure inherent in the procedure should not be ignored.
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Affiliation(s)
- H H Wasmuth
- Department of Gastrointestinal Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
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Pardi DS, D'Haens G, Shen B, Campbell S, Gionchetti P. Clinical guidelines for the management of pouchitis. Inflamm Bowel Dis 2009; 15:1424-31. [PMID: 19685489 DOI: 10.1002/ibd.21039] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
When surgery is necessary in patients with ulcerative colitis, total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the procedure of choice. Several inflammatory and noninflammatory complications can occur after IPAA. Pouchitis is the most common, occurring in approximately 50% of patients. Whereas "acute" pouchitis can be treated rapidly and successfully in the majority of patients, "refractory" and "chronic pouchitis" remain therapeutic challenges to patients and physicians. This article reviews the literature and offers consensus guidelines on issues related to the epidemiology, diagnosis, pathogenesis, risk factors, and treatment of pouchitis.
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Affiliation(s)
- Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
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Abstract
PURPOSE OF REVIEW One of the significant limitations to the investigation of inflammatory bowel disease (IBD) in humans is the impossibility of studying this condition from the beginning of the disease process to understand the individual contribution of the various microbiological and immunological components to its pathogenesis. Pouchitis can serve as a human model for IBD, as the time of the pouch creation is known, which allows to prospectively study the events that might eventually lead to the development of a form of intestinal inflammation (i.e., pouchitis) that mimics IBD. RECENT FINDINGS A considerable amount of progress has been made in the last few years on the mechanisms underlying the pathogenesis of pouchitis. Recent literature suggests that pouchitis may present a spectrum of disease processes, with a wide range of causes, risk factors, clinical phenotypes, disease courses, and prognoses. Genetic, microbiological, and immunological profiles in pouchitis were evaluated. SUMMARY Ileal pouch and pouchitis represent a valuable human model to study the evolution of bacterial communities and host-bacteria interactions in IBD by sequentially monitoring microbiological and immunological profile before, during, and after pouch construction and before and after development and treatment of pouchitis.
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Abstract
Ileal pouch-anal anastomosis is the procedure of choice in the surgical management of refractory ulcerative colitis. Pouchitis affects up to 60% of patients following ileal pouch-anal anastomosis for ulcerative colitis. It overlaps significantly with ulcerative colitis such that improvements in our understanding of one will impact considerably on the other. The symptoms are distressing and impinge significantly on patients' quality of life. Despite 30 years of scientific and clinical investigation, the pathogenesis of pouchitis is unknown; however, recent advances in molecular and cell biology make a synergistic hypothesis possible. This hypothesis links interaction between epithelial metaplasia, changes in luminal bacteria (in particular sulfate-reducing bacteria), and altered mucosal immunity. Specifically, colonic metaplasia supports colonization by sulfate-reducing bacteria that produce hydrogen sulfide. This causes mucosal depletion and subsequent inflammation. Although in most cases antibiotics lead to bacterial clearance and symptom resolution, immunogenetic subpopulations can develop a chronic refractory variant of pouchitis. The aims of this paper are to discuss proposed pathogenic mechanisms and to describe a novel mechanism that combines many hypotheses and explains several aspects of pouchitis. The implications for the management of both pouchitis and ulcerative colitis are discussed.
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Shen B, Remzi FH, Nutter B, Bennett AE, Lashner BA, Lavery IC, Brzezinski A, Bambrick ML, Queener E, Fazio VW. Association between immune-associated disorders and adverse outcomes of ileal pouch-anal anastomosis. Am J Gastroenterol 2009; 104:655-64. [PMID: 19262522 DOI: 10.1038/ajg.2008.76] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Autoimmune disorders (ADs) frequently coexist with inflammatory bowel disease. The aim of the study was to determine whether coexisting AD in patients with ileal pouches increases the risk for chronic antibiotic-refractory pouchitis (CARP) and other inflammatory conditions of the pouch. METHODS A total of 622 patients seen in our Pouchitis Clinic were enrolled. We compared the prevalence of adverse outcomes of the pouch (including CARP, Crohn's disease of the pouch, and pouch failure) in patients with or without concurrent AD and assessed the factors for these adverse outcomes. RESULTS There were seven pouch disease categories: normal (N=60), irritable pouch syndrome (N=112), active pouchitis (N=131), CARP (N=67), Crohn's disease (N=131), cuffitis (N=83), surgical complications (N=36), and anismus (N=2). The prevalence of AD in these pouch disease categories was 4.5%, 12.5%, 9.2%, 13.4%, 10.7%, 3.8%, 1.5%, and 0%, respectively. The presence of at least one AD at time of pouch surgery was shown to be associated with a twofold increase in the risk for CARP (hazard ratio=2.29; 95% CI: 1.52, 3.46; P<0.001) and for pouch-associated hospitalization (hazard ratio=2.39; 95% CI: 1.59, 3.58; P<0.001). The presence of AD was not associated with increased risk for irritable pouch syndrome, active pouchitis, Crohn's disease, cuffitis, surgical complications, or pouch failure. Patients with Crohn's disease of the pouch had a 2.42 times higher risk for pouch failure (P=0.042) than these without. Active smoking or a history of smoking was shown to be associated with an increased risk for pouch-associated hospitalization and pouch failure. CONCLUSIONS AD appears to be associated with an increased risk for CARP, and the presence of the association between these AD and pouch disorders may stimulate further research on the link of these organ systems on an immunological basis.
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Affiliation(s)
- Bo Shen
- Pouchitis Clinic, Digestive Disease Institute, Cleveland Clinic, Ohio 44195, USA.
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Abstract
While the overall incidence of pouchitis is low, extensive research continues at clinical and experimental levels in attempts to unravel its etiology. The ileal pouch and pouchitis together represent a unique in vivo opportunity to study mucosal adaptation and inflammation in depth. In the recent past, molecular data relating to pouchitis has significantly expanded. These data provide invaluable insight into intracellular and extracellular events that underpin mucosal adaptation and inflammation. Advances in classification, risk factor evaluation, and prevention have meant that a review of this data, as well as its relationship to our current understanding of pouchitis, is both timely and warranted. Therefore, the aim of this review is to summarize recent data in the context of the established literature.
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Affiliation(s)
- John Calvin Coffey
- Department of Academic Surgery, Cork University Hospital, Cork, Ireland.
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ROBERT MARIEE. Inflammatory Disorders of the Small Intestine. SURGICAL PATHOLOGY OF THE GI TRACT, LIVER, BILIARY TRACT, AND PANCREAS 2009:321-354. [DOI: 10.1016/b978-141604059-0.50016-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Calabrese C, Gionchetti P, Rizzello F, Liguori G, Gabusi V, Tambasco R, Poggioli G, Pierangeli F, Campieri M, Di Febo G. Short-term treatment with infliximab in chronic refractory pouchitis and ileitis. Aliment Pharmacol Ther 2008; 27:759-64. [PMID: 18298639 DOI: 10.1111/j.1365-2036.2008.03656.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Chronic refractory pouchitis is a long-term complication after ileal pouch-anal anastomosis and it may be associated with ileal inflammation. AIM To determine the efficacy of infliximab in treatment of chronic refractory pouchitis complicated by ileitis, using a wireless capsule endoscopy. METHODS Sixteen patients with chronic refractory pouchitis complicated by ileitis were enrolled. Pouchitis was diagnosed by clinical, endoscopic and histological criteria. Ileitis was documented using wireless capsule endoscopy. Duodenum-jejunum and proximal-middle ileum were evaluated and the presence of small lesions and large lesions were noted. Crohn's disease, intestinal infections were excluded in all patients. Patients were treated with infliximab and clinical response was recorded. Wireless capsule endoscopy was repeated at week 10 and Pouchitis Disease Activity Index score was determined. RESULTS Ten patients were enrolled and completed the study. Clinical remission was achieved in nine patients. At wireless capsule endoscopy and pouch endoscopy, a complete recovery of lesions was observed in eight patients. One patient presented four small lesions of the ileum at the 6 weeks of treatment and one patient did not show any modification. Clinical and endoscopic remission was maintained in these eight patients at least 6 months. CONCLUSION These preliminary results indicate that infliximab may be recommended for the treatment of chronic refractory pouchitis complicated by ileitis.
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Affiliation(s)
- C Calabrese
- Dipartimento di Medicina Interna e Gastroenterologia, Università di Bologna, Bologna, Italy.
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Fleshner P, Ippoliti A, Dubinsky M, Vasiliauskas E, Mei L, Papadakis KA, Rotter J, Landers C, Targan S. Both preoperative perinuclear antineutrophil cytoplasmic antibody and anti-CBir1 expression in ulcerative colitis patients influence pouchitis development after ileal pouch-anal anastomosis. Clin Gastroenterol Hepatol 2008; 6:561-8. [PMID: 18378498 PMCID: PMC2742560 DOI: 10.1016/j.cgh.2008.01.002] [Citation(s) in RCA: 93] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Acute pouchitis (AP) and chronic pouchitis (CP) are common after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. The aim of this study was to assess associations of preoperative perinuclear antineutrophil cytoplasmic antibody (pANCA) and anti-CBir1 flagellin on AP or CP development. METHODS Patients were assessed prospectively for clinically and endoscopically proven AP (antibiotic responsive) or CP (antibiotic-dependent or refractory to antibiotic therapy). Sera from 238 patients were analyzed for ANCA and anti-CBir1 using an enzyme-linked immunosorbent assay. pANCA(+) patients were substratified into high-level (>100 EU/mL) and low-level (<100 EU/mL) groups. RESULTS After a median follow-up period of 47 months, 72 patients (30%) developed pouchitis. Pouchitis developed in 36% of pANCA(+) patients versus 16% of pANCA(-) patients (P = .005), 46% of anti-CBir1(+) patients versus 26% of anti-CBir1(-) patients (P = .02), and 54% of 35 pANCA(+)/anti-CBir1(+) patients versus 31% of 136 pANCA(+)/anti-CBir1(-) patients (P = .02). AP developed in 37 pANCA(+) patients (22%) versus 6 pANCA(-) patients (9%) (P = .02), and 12 anti-CBir1(+) patients (26%) versus 31 anti-CBir1(-) patients (16%) (P = .1). Although AP was not influenced by pANCA level, AP was seen in 38% of low-level pANCA(+)/anti-CBir1(+) patients versus 18% low-level pANCA(+)/anti-CBir1(-) patients (P = .03). CP was seen in 29% of high-level pANCA(+) patients versus 11% of low-level pANCA(+) patients (P = .03). CONCLUSIONS Both pANCA and anti-CBir1 expression are associated with pouchitis after IPAA. Anti-CBir1 increases the incidence of AP only in patients who have low-level pANCA expression, and increases the incidence of CP only in patients who have high-level pANCA expression. Diverse patterns of reactivity to microbial antigens may manifest as different forms of pouchitis after IPAA.
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Affiliation(s)
- Phillip Fleshner
- Division of Colon and Rectal Surgery, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
| | - Andrew Ippoliti
- Division of Gastroenterology, Departments of Surgery, Medicine and Pediatrics, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Marla Dubinsky
- Division of Pediatric Gastroenterology, Departments of Surgery, Medicine and Pediatrics, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Eric Vasiliauskas
- Division of Gastroenterology, Departments of Surgery, Medicine and Pediatrics, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Ling Mei
- Division of Medical Genetics, Departments of Surgery, Medicine and Pediatrics, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Konstantinos A. Papadakis
- Division of Gastroenterology, Departments of Surgery, Medicine and Pediatrics, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Jerome Rotter
- Division of Medical Genetics, Departments of Surgery, Medicine and Pediatrics, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Carol Landers
- Division of Gastroenterology, Departments of Surgery, Medicine and Pediatrics, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Stephan Targan
- Division of Gastroenterology, Departments of Surgery, Medicine and Pediatrics, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048
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Biancone L, Michetti P, Travis S, Escher JC, Moser G, Forbes A, Hoffmann JC, Dignass A, Gionchetti P, Jantschek G, Kiesslich R, Kolacek S, Mitchell R, Panes J, Soderholm J, Vucelic B, Stange E. European evidence-based Consensus on the management of ulcerative colitis: Special situations. J Crohns Colitis 2008; 2:63-92. [PMID: 21172196 DOI: 10.1016/j.crohns.2007.12.001] [Citation(s) in RCA: 148] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2007] [Accepted: 12/30/2007] [Indexed: 02/08/2023]
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Shen B, Remzi FH, Lavery IC, Lashner BA, Fazio VW. A proposed classification of ileal pouch disorders and associated complications after restorative proctocolectomy. Clin Gastroenterol Hepatol 2008; 6:145-58; quiz 124. [PMID: 18237865 DOI: 10.1016/j.cgh.2007.11.006] [Citation(s) in RCA: 152] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Both medical and surgical therapies for ulcerative colitis have inherent advantages and disadvantages that must be balanced for patients with moderate to severe disease. Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for the majority of patients with ulcerative colitis who require proctocolectomy. However, adverse sequelae of mechanical, inflammatory, functional, neoplastic, and metabolic conditions related to the pouch can occur postoperatively. Recognition and familiarization of the disease conditions related to the ileal pouch can be challenging for practicing gastroenterologists. Accurate diagnosis and classification of the disease conditions are imperative for proper management and prognosis.
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Affiliation(s)
- Bo Shen
- Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
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Freeman K, Shao Z, Remzi FH, Lopez R, Fazio VW, Shen B. Impact of orthotopic liver transplant for primary sclerosing cholangitis on chronic antibiotic refractory pouchitis. Clin Gastroenterol Hepatol 2008; 6:62-8. [PMID: 18065274 DOI: 10.1016/j.cgh.2007.09.018] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The effect of orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) and post-OLT immunosuppression on the disease course of pouchitis is not clear. The aims of this study were to compare the frequency of chronic antibiotic-refractory pouchitis (CARP) in PSC patients with or without OLT and to assess potential risk factors for CARP in these patients. METHODS Ulcerative colitis patients with PSC and ileal pouch-anal anastomosis (IPAA) with or without OLT identified from our prospectively maintained pouch database were analyzed. CARP was diagnosed based on persistent symptomatic pouchitis after a 4-week single- or dual-antibiotic therapy. RESULTS A total of 63 PSC/IPAA patients were studied, including 19 patients with OLT and 44 patients without OLT. Fifty patients (79.4%) had CARP. In both univariable and multivariable analyses (adjusting for OLT status), none of the variables studied was associated significantly with CARP (P > .20). All 7 patients (100%) with IPAA-then-OLT were diagnosed as having CARP, of whom 4 developed CARP before OLT, which persisted after OLT, and 3 had CARP after OLT. Of 12 patients with OLT-then-IPAA, 7 (58.3%) developed CARP. The frequency of CARP in OLT-then-IPAA was statistically significantly lower than that in IPAA-then-OLT (58.3% vs 100%; P = .047). CONCLUSIONS CARP is common in patients with ulcerative colitis and PSC. OLT in these patients may not affect the frequency of CARP in general and appears not to alter the disease course of pre-existing CARP. However, in a subset of patients, OLT might reduce the risk for the development of de novo CARP.
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Affiliation(s)
- Katherine Freeman
- Digestive Disease Center, Cleveland Clinic, Cleveland, Ohio 44195, USA
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Shen B, Fazio VW, Remzi FH, Bennett AE, Lopez R, Lavery IC, Brzezinski A, Sherman KK, Lashner BA. Effect of withdrawal of nonsteroidal anti-inflammatory drug use on ileal pouch disorders. Dig Dis Sci 2007; 52:3321-8. [PMID: 17410449 DOI: 10.1007/s10620-006-9710-3] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2006] [Accepted: 11/27/2006] [Indexed: 12/15/2022]
Abstract
NSAID use has been shown to exacerbate disease activity of inflammatory bowel disease. The detrimental effect of NSAIDs on the ileal pouch has not been characterized. To study the effect of withdrawal of NSAID use on ileal pouch disorders. The study consisted of a cohort of 17 symptomatic patients seen in the Pouchitis Clinic who had ulcerative colitis and ileal pouch-anal anastomosis with chronic (>6 months) daily use of NSAIDs. The patients were treated by withdrawing NSAID use. The Pouchitis Disease Activity Index (PDAI) consisting of symptom, endoscopy and histology scores, and Cleveland Global Quality of Life, Irritable Bowel Disease Quality of Life, and Short Inflammatory Bowel Disease Questionnaire scores were measured before and after a 4-week intervention. The cohort consisted of 11 patients with chronic refractory pouchitis (65%), 2 with acute pouchitis (12%), 1 with cuffitis (6%), 1 with cuffitis and chronic refractory pouchitis (6%), and 2 with irritable pouch syndrome (12%). The withdrawal of NSAID use alone resulted in a significant reduction in the mean PDAI scores of -3.6 +/- -3.0 (p<0.02) and a significant improvement in mean quality-of-life scores (p<0.05). Patients with pouch disorders who regularly used NSAIDs appeared to benefit from the complete cessation of such agents, suggesting an association between NSAID use and pouch disorders.
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Affiliation(s)
- Bo Shen
- Center for Inflammatory Bowel Disease, Department of Gastroenterology/Hepatology-Desk A30, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA.
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Abstract
While restorative proctocolectomy with ileal pouch-anal anastomosis has significantly improved the quality of life in patients with underlying ulcerative colitis who require surgery, complications can occur. Pouchitis as the most common long-term complication represents a spectrum of disease processes ranging from acute, antibiotic-responsive type to chronic antibiotic-refractory entity. Accurate diagnosis using a combined assessment of symptoms, endoscopy and histology and the stratification of clinical phenotypes is important for treatment and prognosis the disease. The majority of patients respond favorably to antibiotic therapy. However, management of chronic antibiotic-refractory pouchitis remains a challenge.
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Fleshner P, Ippoliti A, Dubinsky M, Ognibene S, Vasiliauskas E, Chelly M, Mei L, Papadakis KA, Landers C, Targan S. A prospective multivariate analysis of clinical factors associated with pouchitis after ileal pouch-anal anastomosis. Clin Gastroenterol Hepatol 2007; 5:952-8; quiz 887. [PMID: 17544871 DOI: 10.1016/j.cgh.2007.03.020] [Citation(s) in RCA: 87] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Although acute pouchitis (AP) after ileal pouch-anal anastomosis (IPAA) for UC is common and easily treated, chronic pouchitis (CP) remains a difficult management issue. The aim of this study was to identify important clinical risk factors associated with AP or CP. METHODS AP and CP were prospectively assessed, and demographic, disease, and treatment characteristics were tabulated. Univariate and multivariate analyses were performed to evaluate associations between AP or CP and potential risk factors. RESULTS Two hundred IPAA patients were followed for a median of 24 months (range, 3-117 months). Thirty-six patients (18%) developed AP, and 23 patients (12%) developed CP. On univariate analysis, the use of steroids before colectomy and smoking were associated with the development of AP. CP was associated with male gender, smoking, length of follow-up, extraintestinal manifestations, backwash ileitis, and elevated (450x10(9)/L) platelet count. On multivariate analysis, the following risk factors were found to be independently associated with AP: use of steroids before colectomy (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5-8.9; P = .004) and smoking (OR, 2.3; 95% CI, 1.1-5.3; P = .04). CP was directly associated with extraintestinal manifestations (OR, 3.5; 95% CI, 1.1-11.1; P = .03), elevated platelet count (OR, 3.1; 95% CI, 1.1-8.9; P = .03), and increased length of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P = .002). Smoking reduced the incidence of CP (OR, 0.2; 95% CI, 0.05-0.74; P = .04). CONCLUSIONS Clinical factors associated with AP included use of steroids before colectomy and smoking. Factors directly related to CP were extraintestinal manifestations, elevated platelet count, and length of follow-up after IPAA. Smoking appears to protect against the development of CP.
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Affiliation(s)
- Phillip Fleshner
- Division of Colon and Rectal Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
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Abstract
Ulcerative colitis (UC) is a relapsing and remitting disease characterised by chronic mucosal and submucosal inflammation of the colon and rectum. Treatment may vary depending upon the extent and severity of inflammation. Broadly speaking medical treatments aim to induce and then maintain remission. Surgery is indicated for inflammatory disease that is refractory to medical treatment or in cases of neoplastic transformation. Approximately 25% of patients with UC ultimately require colectomy. Ileal pouch-anal anastomosis (IPAA) has become the standard of care for patients with ulcerative colitis who ultimately require colectomy. This review will examine indications for IPAA, patient selection, technical aspects of surgery, management of complications and long term outcome following this procedure.
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Affiliation(s)
- Simon P Bach
- Nuffield Department of Surgery, University of Oxford, United Kingdom.
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Calabrese C, Fabbri A, Gionchetti P, Rizzello F, Morselli C, Liguori G, Poggioli G, Campieri M, Di Febo G. Controlled study using wireless capsule endoscopy for the evaluation of the small intestine in chronic refractory pouchitis. Aliment Pharmacol Ther 2007; 25:1311-6. [PMID: 17509099 DOI: 10.1111/j.1365-2036.2007.03323.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Pouchitis is a common long-term complication after ileal pouch anal anastomosis for ulcerative colitis. Chronic refractory pouchitis is a treatment-resistant condition that affects 5-15% of patients. AIM To test the hypothesis of a small bowel involvement using wireless capsule endoscopy. MATERIAL AND METHODS This is a single-blind, prospective, cohort study. Twenty-four patients: 16 were patients with chronic refractory pouchitis and eight, with a macroscopically and histologically normal ileal pouch, were considered as control subjects. Diagnosis of pouchitis was confirmed using the pouchitis disease activity index. All subjects were submitted to wireless capsule endoscopy procedure. Within 2 weeks before wireless capsule endoscopy, patients underwent a pouch endoscopy and a small bowel follow-through. Re-examination of the colonic surgical and histological specimens was also performed. RESULTS One patient with chronic pouchitis was excluded because of incomplete bowel cleaning. At small bowel follow-through of 16 patients, two subjects (13%) showed only a focal ectasia of the middle ileum and a substenosis of the pouch. At wireless capsule endoscopy all the 15 evaluable patients with chronic pouchitis (100%) showed diffuse lesions from duodenum to ileum consisting of aphthae, erosions, erythema, atrophy, cobblestone, deep/fissural ulcers. CONCLUSIONS This enteropathy needs further research, and wireless capsule endoscopy could be useful to show involvement of small bowel in patients with chronic pouchitis.
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Affiliation(s)
- C Calabrese
- Department of Internal Medicine and Gastroenterology, University of Bologna, Policlinico Sant'Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy.
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Gionchetti P, Rizzello F, Poggioli G, Pierangeli F, Laureti S, Morselli C, Tambasco R, Calabrese C, Campieri M. Oral budesonide in the treatment of chronic refractory pouchitis. Aliment Pharmacol Ther 2007; 25:1231-6. [PMID: 17451569 DOI: 10.1111/j.1365-2036.2007.03306.x] [Citation(s) in RCA: 94] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pouchitis is the major long-term complication after ileal-pouch nal anastomosis for ulcerative colitis. Ten to 15% of patients develop a chronic pouchitis, either treatment responsive or treatment refractory. AIM To evaluate the efficacy of oral budesonide in inducing remission and improving quality of life in patients with chronic refractory pouchitis. METHODS Twenty consecutive patients with active pouchitis, not responding after 1 month of antibiotic treatment were treated with budesonide controlled ileal release 9 mg/day for 8 weeks. Symptomatic, endoscopic and histological evaluations were undertaken before and after treatment according to Pouchitis Disease Activity Index. Remission was defined as a combination of Pouchitis Disease Activity Index clinical score of < or = 2, endoscopic score of < or = 1 and total Pouchitis Disease Activity Index score of < or = 4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire. RESULTS Fifteen of 20 patients (75%) achieved remission. The median total Pouchitis Disease Activity Index scores before and after therapy were, respectively, 14 (range 9-16) and 3 (range 2-10) (P < 0.001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 105 (range 77-175) to 180 (range 85-220) (P < 0.001). CONCLUSION Eight-week treatment with oral budesonide appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment in this open-label study.
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Affiliation(s)
- P Gionchetti
- Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy.
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Das P, Johnson MW, Tekkis PP, Nicholls RJ. Risk of dysplasia and adenocarcinoma following restorative proctocolectomy for ulcerative colitis. Colorectal Dis 2007; 9:15-27. [PMID: 17181842 DOI: 10.1111/j.1463-1318.2006.01148.x] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Restorative proctocolectomy (RPC) with or without mucosectomy is the treatment of choice for most patients with ulcerative colitis (UC) requiring surgery. The ileal mucosa in the reservoir and the anorectal columnar epithelium below the ileo-anal anastomosis are at risk of neoplastic transformation. METHOD The literature has been reviewed to identify patients developing this complication and an attempt has been made to develop a rational follow-up policy based on the data available. RESULTS Dysplasia in the ileal reservoir is rare. It is associated with histological type C changes, sclerosing cholangitis and unremitting pouchitis in the ileal mucosa and to the presence of sclerosing cholangitis. Nine patients who have developed adenocarcinoma in the residual anorectal mucosa and seven in the reservoir have been reported in the literature. A further hitherto unreported patient treated by the authors brings the total to 17 patients. Twelve of these had histopathological data on either dysplasia or carcinoma in the original operative specimen. The time intervals from the onset of UC and from the RPC to the development of cancer were 120-528 (median 246) and 16-216 (median 60) months respectively. Cancer appeared to be related to the duration of disease rather than to the interval from RPC. In all the reported patients the interval from the onset of UC was 10 years. CONCLUSION Based on these data a surveillance programme should begin at 10 years from the onset of disease. Patients with dysplasia or carcinoma in the original specimen, those with type C ileal mucosal changes and patients with sclerosing cholangitis should be selected for surveillance. This will involve multiple biopsies of the ileal reservoir and the anorectal mucosa below the ileo-anal anastomosis.
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Affiliation(s)
- P Das
- Department of Surgery, St Mark's Hospital, Harrow, Middlesex, UK
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Abstract
BACKGROUND AND METHODS The exact aetiology of pouchitis is unknown, but an association with dysbiosis has been suggested. This is a retrospective review of 17 studies published between 1985 and 2005, identified by a search of the Medline, Pubmed and Embase databases. RESULTS The methodology of the studies varied widely. Many were performed at a time when the distinction between a healthy and an inflamed pouch was vague; misclassification of patients makes the analysis of data difficult and conclusions uncertain. CONCLUSION The evidence that dysbiosis is a cause of pouchitis is poor. Nevertheless, available data allow the construction of an algorithm to aid management and suggest a structured approach for future research.
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Affiliation(s)
- M Lim
- Department of Colorectal Surgery, Leeds General Infirmary, Leeds, UK.
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Villanacci V, Bassotti G. Histological aspects of the terminal ileum: a windows on coeliac disease too? Dig Liver Dis 2006; 38:820-2. [PMID: 16979962 DOI: 10.1016/j.dld.2006.07.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2006] [Accepted: 07/04/2006] [Indexed: 12/11/2022]
Affiliation(s)
- V Villanacci
- Second Department of Pathology, Spedali Civili, University of Brescia, Piazzale Spedali Civili 1, 25100 Brescia, Italy.
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Abstract
Pouchitis is the most common complication following proctocolectomy and ileal pouch-anal anastomosis in patients with ulcerative colitis. We aim at discussing relevant information on epidemiology, clinical features, risk factors, diagnostic testing, differential diagnosis and treatment of this idiopathic inflammatory condition. A computerized search of PubMed was performed with the search term 'pouchitis', limited to English papers on humans. This strategy identified 514 references. Relevant articles were selected from this list. In addition, the reference list for each of the selected articles was reviewed to identify any additional references. Pouchitis occurs in up to 60% of patients after ileal pouch-anal anastomosis for ulcerative colitis, and has characteristic clinical, endoscopic and histological features. The most important test for diagnosis is pouch endoscopy with biopsy. Antibiotics remain the mainstay of treatment, and other options are discussed for those patients who are refractory to antibiotic therapy.
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Affiliation(s)
- D S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
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Shen B, Lashner B. Diagnosis and treatment of ileal pouch diseases in patients with underlying ulcerative colitis. ACTA ACUST UNITED AC 2006; 9:3-12. [PMID: 16423309 DOI: 10.1007/s11938-006-0019-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Ileal pouch-anal anastomosis (IPAA) after total proctocolectomy is the surgical treatment of choice for ulcerative colitis (UC) patients with medically refractory disease or dysplasia. IPAA significantly improves quality of life in UC patients who require surgery. However, certain inflammatory and noninflammatory diseases can develop after the surgery, including pouchitis, Crohn's disease (CD) of the pouch, cuffitis, and irritable pouch syndrome. The cause and pathogenesis of these disease conditions of IPAA are largely unknown. Accurate diagnosis and classification are important for appropriate management.
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Affiliation(s)
- Bo Shen
- Department of Gastroenterology/Hepatology-Desk A30, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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