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Akiyama S, Barnes EL, Onoda T, Ishikawa N, Shiroyama M, Ito Y, Rubin DT, Tsuchiya K. Endoscopic assessment of the J pouch in ulcerative colitis: A narrative review. DEN OPEN 2025; 5:e373. [PMID: 38694540 PMCID: PMC11058686 DOI: 10.1002/deo2.373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 04/08/2024] [Indexed: 05/04/2024]
Abstract
Patients with ulcerative colitis sometimes need a total colectomy with ileal pouch-anal anastomosis due to medically refractory disease or colitis-associated neoplasia. Up to 50% of patients with ulcerative colitis postoperatively develop pouchitis and the rate of chronic inflammatory pouch conditions requiring pouch excision or diverting ileostomy is reported to be 10%. In order to diagnose and monitor pouchitis, pouchoscopy is essential to assess endoscopic inflammatory findings of the J pouch and to survey neoplasia development, particularly in the remnant distal rectum. However, endoscopic protocols for the evaluation of the pouch may not be standardized worldwide and the reliability of existing disease activity indices for pouchitis has been questioned due to the lack of validation. Recently, reliable endoscopic scoring systems based on an observation of the anatomical location of the J pouch were reported and a significant association between the distribution pattern of endoscopic inflammation (i.e., endoscopic phenotype) and pouch outcomes was also uncovered. In this review, we discuss how to survey the J pouch using pouchoscopy, endoscopic indices for pouchitis disease activity, endoscopic phenotypes and classification, and the pathological mechanisms of pouchitis phenotype in patients with ulcerative colitis.
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Affiliation(s)
- Shintaro Akiyama
- Department of GastroenterologyInstitute of MedicineUniversity of TsukubaTsukubaIbarakiJapan
| | - Edward L Barnes
- Division of Gastroenterology and HepatologyUniversity of North Carolina at Chapel HillChapel HillUSA
| | - Tsubasa Onoda
- Department of GastroenterologyNHO Mito Medical CenterIbarakiJapan
- Doctoral Program in Medical SciencesGraduate School of Comprehensive Human SciencesUniversity of TsukubaTsukubaIbarakiJapan
| | - Naoki Ishikawa
- Department of GastroenterologyInstitute of MedicineUniversity of TsukubaTsukubaIbarakiJapan
- Doctoral Program in Medical SciencesGraduate School of Comprehensive Human SciencesUniversity of TsukubaTsukubaIbarakiJapan
| | - Mamiko Shiroyama
- Department of GastroenterologyInstitute of MedicineUniversity of TsukubaTsukubaIbarakiJapan
- Doctoral Program in Medical SciencesGraduate School of Comprehensive Human SciencesUniversity of TsukubaTsukubaIbarakiJapan
| | - Yuka Ito
- Department of GastroenterologyNHO Mito Medical CenterIbarakiJapan
| | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease CenterChicagoUSA
| | - Kiichiro Tsuchiya
- Department of GastroenterologyInstitute of MedicineUniversity of TsukubaTsukubaIbarakiJapan
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Abstract
BACKGROUND Pouchitis is the most common inflammatory complication in ulcerative colitis patients undergoing postoperative construction of an IPAA. Pouchitis refers to a spectrum of diseases, and as such, it lacks a universally accepted definition as well as validated instruments to measure disease activity and treatment response. Assessing pouchitis activity is challenging, and methods for diagnosis and classification of severity of pouchitis are not universally agreed upon. CLINICAL FEATURES Pouchitis is characterized by a constellation of clinical symptoms, including increased stool frequency, urgency, incontinence, bleeding, and rarely constitutional symptoms such as malaise and low-grade fever. However, these symptoms are subjective, and similar symptoms can be caused by noninflammatory conditions including anal sphincter dysfunction, anastomotic strictures, occult leaks, pouch inlet obstruction, and cuffitis. Objective scores that include endoscopic and histologic criteria have been developed for subjects with an IPAA. However, these instruments are not validated for measuring pouchitis disease activity and are associated with a number of challenges. In addition, the clinical components of the scores correlate poorly with endoscopic and histologic findings. CONCLUSION AND FUTURE DIRECTIONS There is a need for prospective studies to facilitate the development and validation of novel instruments that are valid, reliable, and responsive to change that would facilitate the development of therapeutic agents for the treatment of pouchitis.
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Le Cosquer G, Buscail E, Gilletta C, Deraison C, Duffas JP, Bournet B, Tuyeras G, Vergnolle N, Buscail L. Incidence and Risk Factors of Cancer in the Anal Transitional Zone and Ileal Pouch following Surgery for Ulcerative Colitis and Familial Adenomatous Polyposis. Cancers (Basel) 2022; 14:530. [PMID: 35158797 PMCID: PMC8833833 DOI: 10.3390/cancers14030530] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 01/17/2022] [Accepted: 01/18/2022] [Indexed: 12/29/2022] Open
Abstract
Proctocolectomy with ileal pouch-anal anastomosis is the intervention of choice for ulcerative colitis and familial adenomatous polyposis requiring surgery. One of the long-term complications is pouch cancer, having a poor prognosis. The risk of high-grade dysplasia and cancer in the anal transitional zone and ileal pouch after 20 years is estimated to be 2 to 4.5% and 3 to 10% in ulcerative colitis and familial polyposis, respectively. The risk factors for ulcerative colitis are the presence of pre-operative dysplasia or cancer, disease duration > 10 years and severe villous atrophy. For familial polyposis, the risk factors are the number of pre-operative polyps > 1000, surgery with stapled anastomosis and the duration of follow-up. In the case of ulcerative colitis, a pouchoscopy should be performed annually if one of the following is present: dysplasia and cancer at surgery, primary sclerosing cholangitis, villous atrophy and active pouchitis (every 5 years without any of these factors). In the case of familial polyposis, endoscopy is recommended every year including chromoendoscopy. Even if anal transitional zone and ileal pouch cancers seldom occur following proctectomy for ulcerative colitis and familial adenomatous polyposis, the high mortality rate associated with this complication warrants endoscopic monitoring.
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Affiliation(s)
- Guillaume Le Cosquer
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil (University Hospital Centre) and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (C.G.); (B.B.)
| | - Etienne Buscail
- Department of Surgery, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (E.B.); (J.-P.D.); (G.T.)
- IRSD, Toulouse University, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Cyrielle Gilletta
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil (University Hospital Centre) and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (C.G.); (B.B.)
| | - Céline Deraison
- IRSD, Toulouse University, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Jean-Pierre Duffas
- Department of Surgery, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (E.B.); (J.-P.D.); (G.T.)
| | - Barbara Bournet
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil (University Hospital Centre) and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (C.G.); (B.B.)
| | - Géraud Tuyeras
- Department of Surgery, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (E.B.); (J.-P.D.); (G.T.)
| | - Nathalie Vergnolle
- IRSD, Toulouse University, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Louis Buscail
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil (University Hospital Centre) and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (C.G.); (B.B.)
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France
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4
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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: 13] [Impact Index Per Article: 3.3] [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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Chande N, Singh S, Narula N, Gordon M, Kuenzig ME, Nguyen TM, MacDonald JK, Feagan BG. Medical Management Following Surgical Therapy in Inflammatory Bowel Disease: Evidence from Cochrane Reviews. Inflamm Bowel Dis 2021; 27:1513-1524. [PMID: 33452527 PMCID: PMC8376125 DOI: 10.1093/ibd/izaa350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Nilesh Chande
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada
| | - Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | - Neeraj Narula
- Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
| | - Morris Gordon
- School of Medicine, University of Central Lancashire, Preston, United Kingdom
| | - M Ellen Kuenzig
- Children’s Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre, Division of Gastroenterology & Hepatology, Ottawa, Ontario, Canada,CHEO Research Institute, Ottawa, Ontario, Canada
| | | | | | - Brian G Feagan
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada,Alimentiv Inc, London, Ontario, Canada,Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada,Address correspondence to: Brian G Feagan, MD, Alimentiv (formerly Robarts Clinical Trials), 100 Dundas Street, Suite 200, London, Ontario, Canada N6A 5B6. E-mail:
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Magro F, Doherty G, Peyrin-Biroulet L, Svrcek M, Borralho P, Walsh A, Carneiro F, Rosini F, de Hertogh G, Biedermann L, Pouillon L, Scharl M, Tripathi M, Danese S, Villanacci V, Feakins R. ECCO Position Paper: Harmonization of the Approach to Ulcerative Colitis Histopathology. J Crohns Colitis 2020; 14:1503-1511. [PMID: 32504534 DOI: 10.1093/ecco-jcc/jjaa110] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Currently, the main targets of drug therapy for ulcerative colitis [UC] are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia. Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible. We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index [RHI] or the Nancy index [NI]. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores.
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Affiliation(s)
- Fernando Magro
- Department of Gastroenterology, Centro Hospitalar Universitário São João, Porto, Portugal.,Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.,Department of Clinical Pharmacology, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Glen Doherty
- School of Medicine & Medical Science, University College Dublin, Dublin, Ireland
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandoeuvre-Les-Nancy, France.,Inserm U1256 NGERE, Lorraine University, Vandoeuvre-Les-Nancy, France
| | - Magali Svrcek
- Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Department of Pathology, 184 rue du Faubourg Saint-Antoine, Paris, France
| | - Paula Borralho
- Department of Pathology, Hospital Cuf Descobertas, Lisboa and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Alissa Walsh
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
| | - Fatima Carneiro
- Department of Pathology, Faculty of Medicine of the University of Porto (FMUP) & Centro Hospitalar Universitário de São João (CHUSJ), Porto, Portugal.,Instituto de Investigação e Inovação em Saúde (i3S) & Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal
| | - Francesca Rosini
- Department of Cellular Pathology, North West London Pathology, Imperial College Healthcare NHS Trust, London, UK
| | - Gert de Hertogh
- Pathology Lab, UZ Gasthuisberg and KULeuven, Leuven, Belgium
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Lieven Pouillon
- Imelda GI Clinical Research Center, Imeldaziekenhuis Bonheiden, Bonheiden, Belgium
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Monika Tripathi
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD center, Department of Gastroenterology, Humanitas Clinical and Research Center, IRCCS, Milan, Italy
| | - Vincenzo Villanacci
- Department of Histopathology, Spedali Civili and University of Brescia, Brescia, Italy
| | - Roger Feakins
- Department of Cellular Pathology, Royal Free Hospital, London, UK
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Abstract
PURPOSE OF REVIEW Pouchitis is the most common complication in patients who undergo ileal pouch-anal anastomosis (IPAA), occurring more frequently in patients with ulcerative colitis. Pouchitis - the inflammation of the pouch - can be due to idiopathic or secondary causes. Chronic antibiotic-dependent pouchitis (CADP) and chronic antibiotic-resistant pouchitis (CARP) are the most difficult forms of chronic idiopathic pouchitis to treat. Crohn's disease of the pouch may develop de novo in ulcerative colitis patients following colectomy with IPAA. It carries a high risk for pouch failure, and its diagnosis and management are challenging. The purpose of this review is to illustrate the present trends in the diagnosis and treatment of idiopathic pouchitis and Crohn's disease of the pouch. RECENT FINDINGS The use of the newer biologic agents, vedolizumab and ustekinumab, has shown promising results in patients with CADP, CARP, and Crohn's disease of the pouch. Fecal microbiota transplantation has also been reported to have encouraging preliminary results in small studies and case series for the treatment of chronic pouchitis. SUMMARY Promising new treatments are emerging for difficult-to-treat forms of pouchitis. Larger prospective and head-to-head comparative studies among the various treatments are needed to evaluate the efficacy and safety of these agents across the pouchitis subgroups, and to identify predictors of response.
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Affiliation(s)
- Hyder Shah
- Department of Internal Medicine Division of Gastroenterology, Department of Internal Medicine, Thunder Bay Regional Health Sciences Centre, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada
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Nguyen N, Zhang B, Holubar SD, Pardi DS, Singh S, Cochrane IBD Group. 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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9
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Ng KS, Gonsalves SJ, Sagar PM. Ileal-anal pouches: A review of its history, indications, and complications. World J Gastroenterol 2019; 25:4320-4342. [PMID: 31496616 PMCID: PMC6710180 DOI: 10.3748/wjg.v25.i31.4320] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 03/12/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
Abstract
The ileal pouch anal anastomosis (IPAA) has revolutionised the surgical management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Despite refinement in surgical technique(s) and patient selection, IPAA can be associated with significant morbidity. As the IPAA celebrated its 40th anniversary in 2018, this review provides a timely outline of its history, indications, and complications. IPAA has undergone significant modification since 1978. For both UC and FAP, IPAA surgery aims to definitively cure disease and prevent malignant degeneration, while providing adequate continence and avoiding a permanent stoma. The majority of patients experience long-term success, but “early” and “late” complications are recognised. Pelvic sepsis is a common early complication with far-reaching consequences of long-term pouch dysfunction, but prompt intervention (either radiological or surgical) reduces the risk of pouch failure. Even in the absence of sepsis, pouch dysfunction is a long-term complication that may have a myriad of causes. Pouchitis is a common cause that remains incompletely understood and difficult to manage at times. 10% of patients succumb to the diagnosis of pouch failure, which is traditionally associated with the need for pouch excision. This review provides a timely outline of the history, indications, and complications associated with IPAA. Patient selection remains key, and contraindications exist for this surgery. A structured management plan is vital to the successful management of complications following pouch surgery.
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Affiliation(s)
- Kheng-Seong Ng
- John Goligher Colorectal Unit, St. James’s University Hospital, Leeds LS9 7TF, United Kingdom
- Institute of Academic Surgery, University of Sydney, Camperdown, New South Wales 2050, Australia
| | - Simon Joseph Gonsalves
- Department of Colorectal Surgery, Huddersfield Royal Infirmary, Calderdale and Huddersfield NHS Foundation Trust, Huddersfield HD3 3EA, United Kingdom
| | - Peter Michael Sagar
- John Goligher Colorectal Unit, St. James’s University Hospital, Leeds LS9 7TF, United Kingdom
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10
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Bhattacharya A, Shen B, Regueiro M. Endoscopy in Postoperative Patients with Crohn's Disease or Ulcerative Colitis. Does It Translate to Better Outcomes? Gastrointest Endosc Clin N Am 2019; 29:487-514. [PMID: 31078249 DOI: 10.1016/j.giec.2019.02.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
This article discusses the use of endoscopy in patients with Crohn disease and ulcerative colitis in the postoperative setting. Endoscopy is the most sensitive and validated tool available in the diagnosis of recurrence of Crohn disease in the postoperative setting. It is also the most effective diagnostic modality available for evaluating complications of pouch anatomy in patients with ulcerative colitis. In addition to diagnosis, management postoperatively can be determined through endoscopy.
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Affiliation(s)
- Abhik Bhattacharya
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Avenue, A30, Cleveland, OH 44195, USA
| | - Bo Shen
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Avenue, A30, Cleveland, OH 44195, USA
| | - Miguel Regueiro
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, 9500 Euclid Avenue, A30, Cleveland, OH 44195, USA.
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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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12
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Maaser C, Sturm A, Vavricka SR, Kucharzik T, Fiorino G, Annese V, Calabrese E, Baumgart DC, Bettenworth D, Borralho Nunes P, Burisch J, Castiglione F, Eliakim R, Ellul P, González-Lama Y, Gordon H, Halligan S, Katsanos K, Kopylov U, Kotze PG, Krustinš E, Laghi A, Limdi JK, Rieder F, Rimola J, Taylor SA, Tolan D, van Rheenen P, Verstockt B, Stoker J. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis 2019; 13:144-164. [PMID: 30137275 DOI: 10.1093/ecco-jcc/jjy113] [Citation(s) in RCA: 1130] [Impact Index Per Article: 188.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Christian Maaser
- Outpatients Department of Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Andreas Sturm
- Department of Gastroenterology, DRK Kliniken Berlin I Westend, Berlin, Germany
| | | | - Torsten Kucharzik
- Department of Internal Medicine and Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Gionata Fiorino
- Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Vito Annese
- Department of Gastroenterology, Valiant Clinic & American Hospital, Dubai, UAE
| | - Emma Calabrese
- Department of Systems Medicine, University of Rome, Tor Vergata, Italy
| | - Daniel C Baumgart
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Dominik Bettenworth
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Paula Borralho Nunes
- Department of Anatomic Pathology, Hospital Cuf Descobertas; Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark
| | - Fabiana Castiglione
- Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Rami Eliakim
- Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel Aviv, Israel
| | - Pierre Ellul
- Department of Medicine, Mater Dei Hospital, Msida, Malta
| | - Yago González-Lama
- Department of Gastroenterology, University Hospital Puerta De Hierro, Majadahonda [Madrid], Spain
| | - Hannah Gordon
- Department of Gastroenterology, Royal London Hospital, London, UK
| | - Steve Halligan
- Centre for Medical Imaging, University College London, London, UK
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel Aviv, Israel
| | - Paulo G Kotze
- Colorectal Surgery Unit, Catholic University of Paraná [PUCPR], Curitiba, Brazil
| | - Eduards Krustinš
- Department of of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical University Hospital, Riga, Latvia
| | - Andrea Laghi
- Department of Clinical and Surgical Translational Medicine, Sapienza University of Rome, Rome, Italy
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust, Manchester; Manchester Academic Health Sciences Centre, University of Manchester, UK
| | - Florian Rieder
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Jordi Rimola
- Department of Radiology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Stuart A Taylor
- Centre for Medical Imaging, University College London, London, UK
| | - Damian Tolan
- Clinical Radiology, St James's University Hospital, Leeds, UK
| | - Patrick van Rheenen
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, University Medical Center Groningen, Groningen, The Netherlands
| | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven and CHROMETA - Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Academic Medical Center [AMC], University of Amsterdam, Amsterdam, The Netherlands
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13
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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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14
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Increase in chromogranin A- and serotonin-positive cells in pouch mucosa of patients with ulcerative colitis undergoing proctocolectomy. Dig Liver Dis 2018; 50:1205-1213. [PMID: 29803758 DOI: 10.1016/j.dld.2018.04.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 04/15/2018] [Accepted: 04/15/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is associated with neuroendocrine cell hyperplasia. AIMS We investigated neuroendocrine cells in J-pouches of patients with ulcerative colitis undergoing restorative proctocolectomy and ileal pouch-anal anastomosis. METHODS Sections from pouch biopsies of 17 patients and ileal biopsies of 17 active IBD patients and 16 controls were processed by immunohistochemistry for chromogranin A (CgA) and serotonin. Mucosal tryptophan hydroxylase (TpH)-1 and serotonin-selective reuptake transporter (SERT) transcripts were measured by quantitative RT-PCR. TpH-1 and SERT transcripts were detected in pouch biopsies cultured with infliximab or its isotype control, while interleukin (IL)-6 and IL-8 were measured in biopsy supernatants. RESULTS A significant increase in CgA-positive cells and serotonin-positive cells was observed in both pouch and IBD ileum compared to control ileum. Significantly raised transcripts of TpH-1, but not SERT, were found in IBD ileum in comparison to control ileum, with no significant difference between pouch and IBD ileum. Infliximab had no influence on ex vivo pouch expression of TpH-1 and SERT, nor on the production of IL-6 and IL-8. CONCLUSION We here demonstrated neuroendocrine cell hyperplasia in pouch mucosa. Further studies are needed to clarify the pathophysiological implication of this finding.
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15
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Reliability among central readers in the evaluation of endoscopic disease activity in pouchitis. Gastrointest Endosc 2018; 88:360-369.e2. [PMID: 29660321 DOI: 10.1016/j.gie.2018.04.2330] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 04/04/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Pouchitis is a common adverse event after proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis. Evaluation of pouchitis disease activity and response to treatment requires use of validated indices. We assessed the reliability of items evaluating endoscopic pouchitis disease activity. METHODS Twelve panelists used a modified RAND appropriateness methodology to rate the appropriateness of items evaluating endoscopic pouchitis disease activity derived from a systematic review and also identified additional potential endoscopic items based on expert opinion. Four central readers then evaluated 50 pouchoscopy videos in triplicate, in random order. Intra- and inter-rater reliability for each item was assessed by calculating and comparing intraclass correlation coefficients (ICCs). A Delphi process identified common sources of disagreement among the readers. RESULTS Ten existing endoscopic items were identified from the systematic review and an additional 7 exploratory items from the panelists. ICCs for inter-rater reliability were highest for the existing item of pouch ulceration (.72; 95% confidence interval [CI], .60-.82) and for the exploratory item of ulcerated surface in the pouch body (.67; 95% CI, .53-.75). Inter-rater reliability for all other existing and exploratory items was "moderate" (ICC < .60). The item "ulcerated surface in the pouch body" demonstrated the best correlation with a global evaluation of lesion severity (r = .80; 95% CI, .73-.85). CONCLUSION Substantial reliability was observed only for the endoscopic items of ulceration and ulcerated surface in the pouch body. Future studies should assess responsiveness to treatment in the next stage toward development of an endoscopic pouchitis disease activity index.
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16
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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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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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18
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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: 1267] [Impact Index Per Article: 158.4] [Reference Citation Analysis] [MESH Headings] [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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19
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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: 4] [Impact Index Per Article: 0.5] [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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20
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Lee H, Westerhoff M, Shen B, Liu X. Clinical Aspects of Idiopathic Inflammatory Bowel Disease: A Review for Pathologists. Arch Pathol Lab Med 2017; 140:413-28. [PMID: 27128299 DOI: 10.5858/arpa.2015-0305-ra] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
CONTEXT -Idiopathic inflammatory bowel disease manifests with different clinical phenotypes showing varying behavior and risk for neoplasia. The clinical questions that are posed to pathologists differ depending on phase of the disease and the clinical circumstances. Understanding the clinical aspects of the dynamic disease process will enhance the role of pathology in optimizing the care of patients with inflammatory bowel disease. OBJECTIVE -To review clinical and surgical aspects of inflammatory bowel disease that are relevant to practicing pathologists. DATA SOURCES -The literature was reviewed. CONCLUSIONS -Diagnosis and management of inflammatory bowel disease require an integrated evaluation of clinical, endoscopic, radiologic, and pathologic features. Therefore, close interaction between clinicians and pathologists is crucial. Having this team approach improves understanding of the pertinent clinical and surgical aspects of the disease and assists in the recognition of unusual presentation of variants, as well as mimics of idiopathic inflammatory bowel disease, by pathologists.
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Affiliation(s)
| | | | | | - Xiuli Liu
- From the Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York (Dr Lee); the Department of Anatomic Pathology, University of Washington Medical Center, Seattle (Dr Westerhoff); and the Department of Gastroenterology/Hepatology, Digestive Disease Institute (Dr Shen), and the Department of Pathology, Immunology, and Laboratory Medicine (Dr Liu), University of Florida, Gainesville
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Bengtsson J, Adlerberth I, Östblom A, Saksena P, Öresland T, Börjesson L. Effect of probiotics (Lactobacillus plantarum 299 plus Bifidobacterium Cure21) in patients with poor ileal pouch function: a randomised controlled trial. Scand J Gastroenterol 2016; 51:1087-92. [PMID: 27150635 DOI: 10.3109/00365521.2016.1161067] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Poor pouch function after restorative proctocolectomy for ulcerative colitis is a considerable problem. Pouchitis and functional disorders are the most common reasons. Probiotics seem to have a beneficial effect in pouchitis but have not been assessed in functional pouch disorders. The aim was to analyse the effects of probiotics in patients with poor pouch function. METHODS Thirty-three patients were randomized to probiotics (Lactobacillus plantarum 299 and Bifidobacterium infantis Cure 21) or placebo in a double blinded, 1:1 fashion. The treatment effect was assessed by the pouch functional score (PFS; 0-15, 15 worst), pouchitis disease activity index (PDAI; 0-18, 18 worst), and levels of four faecal biomarkers of inflammation (calprotectin, lactoferrin, myeloperoxidase [MPO] and eosinophilic cationic protein [ECP]). RESULTS Thirty-two patients were included (probiotics = 17, placebo = 16). There was no difference in change in the PFS from before to after treatment between the groups (median difference: -1.00, 95% C.I. -3.00 to 0.00, p = 0.119). Furthermore, probiotics had no effect on PDAI (median difference: 0.00, 95% C.I. 0.00-1.00, p = 0.786), or on faecal biomarkers. Significant correlations were observed between PDAI and each of the faecal biomarkers at study start. There were no correlations between PFS or PDAI symptom subscore and the biomarkers. PDAI endoscopic and histologic subscores correlated significantly to each of the biomarkers. CONCLUSION The hypothesis that probiotics improves pouch-related dysfunction was not confirmed. Faecal biomarkers could play a future role in the management of pouch patients.
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Affiliation(s)
- J Bengtsson
- a Department of Surgery , Sahlgrenska University Hospital , Gothenburg , Sweden
| | - I Adlerberth
- b Department of Infectious Diseases , Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - A Östblom
- b Department of Infectious Diseases , Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - P Saksena
- c Department of Pathology , Sahlgrenska University Hospital , Gothenburg , Sweden
| | - T Öresland
- d Akershus University Hospital, University of Oslo , Oslo , Norway
| | - L Börjesson
- a Department of Surgery , Sahlgrenska University Hospital , Gothenburg , Sweden
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Gonzalo DH, Collinsworth AL, Liu X. Common Inflammatory Disorders and Neoplasia of the Ileal Pouch: A Review of Histopathology. Gastroenterology Res 2016; 9:29-38. [PMID: 27785322 PMCID: PMC5040541 DOI: 10.14740/gr706e] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2016] [Indexed: 12/24/2022] Open
Abstract
Ileal pouch-anal anastomosis (IPAA) is the standard restorative procedure after proctocolectomy in patients with ulcerative colitis (UC) who require colectomy. The ileal pouch is susceptible to a variety of insults including mechanical injury, ischemia, fecal stasis, and infectious agents. In addition, the development of recurrent and idiopathic inflammatory bowel disease and neoplasia may occur in the ileal pouch. Although clinical, endoscopic, and radiographic examination can diagnose many ileal pouch diseases, histologic examination plays an essential role in diagnosis and management, particularly in cases with antibiotic refractory chronic pouchitis and pouch neoplasia.
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Affiliation(s)
- David Hernandez Gonzalo
- Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Amy L. Collinsworth
- Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Xiuli Liu
- Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
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Value of histopathology for predicting the post-operative complications of ileo-anal anastomosis (J-pouch) procedure in children with refractory ulcerative colitis. Pathology 2016; 48:330-5. [DOI: 10.1016/j.pathol.2016.01.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 12/26/2015] [Accepted: 01/03/2016] [Indexed: 01/27/2023]
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Gionchetti P, Calabrese C, Lauri A, Rizzello F. The therapeutic potential of antibiotics and probiotics in the treatment of pouchitis. Expert Rev Gastroenterol Hepatol 2016. [PMID: 26202437 DOI: 10.1586/17474124.2015.1072046] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Pouchitis is the most frequent long-term complication of pouch surgery for ulcerative colitis. There is consistent evidence on the implication of bacterial flora in the pathogenesis of pouchitis, and there is evidence for a therapeutic role of antibiotics and probiotics in therapy of this disease. Antibiotics, particularly ciprofloxacin and metronidazole, are the mainstay of treatment for acute pouchitis. In chronic refractory pouchitis, after having excluded other diagnoses (infections, Crohn's disease of the pouch, ischemia and irritable pouch), antibiotic combination therapy is the treatment of choice. The highly concentrated probiotic mixture VSL#3 has been shown to be effective in prevention of pouchitis onset and in maintaining antibiotic-induced remission.
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Affiliation(s)
- Paolo Gionchetti
- a Department of Medical and Surgical Sciences (DIMEC), University of Bologna-Italy, Bologna, Italy
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25
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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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Greuter T, Biedermann L, Rogler G, Sauter B, Seibold F. Alicaforsen, an antisense inhibitor of ICAM-1, as treatment for chronic refractory pouchitis after proctocolectomy: A case series. United European Gastroenterol J 2015; 4:97-104. [PMID: 26966529 DOI: 10.1177/2050640615593681] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 06/02/2015] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND AND AIMS The published data about the efficacy of the intercellular adhesion molecule-1 (ICAM-1) antisense oligonucleotide termed alicaforsen in inflammatory bowel disease (IBD) is rather inconsistent. This case series analyzes its efficacy in chronic refractory pouchitis, after proctocolectomy. METHODS We performed a retrospective analysis on all patients who had received at least one dose of alicaforsen for IBD at three referral centers in Switzerland. We assessed the drug's efficacy in patients treated for chronic refractory pouchitis, by comparing the clinical and/or endoscopic disease activity at baseline with a 2-3-month follow-up visit. RESULTS We identified 22 patients who had received at least one dose. Among them, 13 patients were being treated for chronic refractory pouchitis. These patients had a median age of 38.0 years (95% CI 21.0-69.0) and five were female (38.5%). The median time since pouch surgery was 102.5 months (95% CI 16.0-288.0), with a median pouchitis duration of 16.0 months (95% CI 4.0-216.0). At 2-3 months after therapy, clinical and endoscopic disease activity was significantly reduced (stool frequency 9.0 versus 6.0, the Pouchitis Disease Activity Index (PDAI) clinical subscore was 4.0 versus 1.0, and the endoscopic disease activity was 4.0 versus 2.0). Clinical improvement was achieved in 11 out of 13 pouchitis patients (84.6%); however, a relapse was observed in nine of these patients (81.8%). The median time from clinical improvement to relapse was 16 weeks (95% CI 9.0-23.0). CONCLUSIONS Alicaforsen seemed to be efficacious in inducing clinical and/or endoscopic improvement in chronic refractory pouchitis and may be a promising treatment alternative in those patients; however, given the high proportion of relapse, one 6-week course of alicaforsen may not be sufficient.
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Affiliation(s)
- Thomas Greuter
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Luc Biedermann
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Gerhard Rogler
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Bernhard Sauter
- Gastrozentrum Hirslanden, Hirslanden Private Clinic Group, Zurich, Switzerland
| | - Frank Seibold
- Division of Gastroenterology and Hepatology, Tiefenauspital Bern, Bern, Switzerland
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27
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Block M, Börjesson L, Willén R, Bengtson J, Lindholm E, Brevinge H, Saksena P. Neoplasia in the colorectal specimens of patients with ulcerative colitis and ileal pouch-anal anastomosis - need for routine surveillance? Scand J Gastroenterol 2015; 50:528-35. [PMID: 25648657 DOI: 10.3109/00365521.2015.1004364] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Patients who undergo ileal pouch-anal anastomosis (IPAA) after colectomy for ulcerative colitis (UC) occasionally have neoplasia in the IPAA. Patients with evidence of dysplasia or carcinoma in the colorectal specimen may have an increased risk of such neoplasia. A surveillance program has been suggested. The aims of this study were to evaluate the outcomes of surveillance of a large patient cohort, and to investigate the prevalences of neoplasia in the ileal pouch mucosa and in the anal transitional zone (ATZ). MATERIAL AND METHODS A total of 629 patients underwent IPAA for UC at Sahlgrenska University Hospital, Gothenburg, Sweden. Identified from a register, 73 patients with neoplasia in their specimen considered eligible for the trial were prospectively enrolled, and underwent clinical examination, endoscopy with macroscopic evaluation, and mucosal biopsies from the ileal pouch and the ATZ. The biopsies were independently evaluated by two experienced gastro-pathologists. RESULTS In all, 56 patients (39 males) with a median follow-up time of 18 (range, 1-29) years were evaluated. One patient (1.8%; 95% CI 0%-5.3%) showed low-grade dysplasia in the pouch, as recorded by one of the two pathologists. The individual pathologists recorded indefinite for dysplasia (IFD) in the pouch for 19 and 20 patients, respectively, and IFD in the ATZ for 2 and 4 patients, respectively. None of the biopsies showed evidence of high-grade dysplasia (HGD) or carcinoma. CONCLUSIONS Neoplasia in the ileal pouch or ATZ after IPAA for UC is rare in the proposed risk group. The necessity for and value of a routine surveillance program should be prospectively evaluated.
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Affiliation(s)
- Mattias Block
- Department of Surgery, Sahlgrenska University Hospital, Institution for Clinical Sciences, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden
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28
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Abstract
Given the number of inflammatory disorders affecting the gastrointestinal tract directly and indirectly, coupled with the considerable overlap with functional disorders, it is evident that more useful noninvasive diagnostic tests are required to aid with diagnosis. If these tests can also have some utility for individual patient follow-up in terms of disease activity and response to treatment, as well as providing forewarning of disease relapse, it would be extremely useful information for the clinician. One recently described test that may fulfill several of these attributes is based on leakage of a mononuclear cell cytoplasmic protein, calprotectin, along the intestinal tract, which can then be quantified in feces. This has been used to distinguish patients exhibiting symptoms of irritable bowel syndrome from patients with inflammatory bowel disease, with a measure of success greater than with currently used techniques. The present article summarizes the experience with this test used in inflammatory bowel disease, as well as a variety of gastrointestinal disorders.
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29
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Cockrell RC, Christley S, Chang E, An G. Towards anatomic scale agent-based modeling with a massively parallel spatially explicit general-purpose model of enteric tissue (SEGMEnT_HPC). PLoS One 2015; 10:e0122192. [PMID: 25806784 PMCID: PMC4373890 DOI: 10.1371/journal.pone.0122192] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
Perhaps the greatest challenge currently facing the biomedical research community is the ability to integrate highly detailed cellular and molecular mechanisms to represent clinical disease states as a pathway to engineer effective therapeutics. This is particularly evident in the representation of organ-level pathophysiology in terms of abnormal tissue structure, which, through histology, remains a mainstay in disease diagnosis and staging. As such, being able to generate anatomic scale simulations is a highly desirable goal. While computational limitations have previously constrained the size and scope of multi-scale computational models, advances in the capacity and availability of high-performance computing (HPC) resources have greatly expanded the ability of computational models of biological systems to achieve anatomic, clinically relevant scale. Diseases of the intestinal tract are exemplary examples of pathophysiological processes that manifest at multiple scales of spatial resolution, with structural abnormalities present at the microscopic, macroscopic and organ-levels. In this paper, we describe a novel, massively parallel computational model of the gut, the Spatially Explicitly General-purpose Model of Enteric Tissue_HPC (SEGMEnT_HPC), which extends an existing model of the gut epithelium, SEGMEnT, in order to create cell-for-cell anatomic scale simulations. We present an example implementation of SEGMEnT_HPC that simulates the pathogenesis of ileal pouchitis, and important clinical entity that affects patients following remedial surgery for ulcerative colitis.
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Affiliation(s)
| | - Scott Christley
- Department of Surgery, University of Chicago, Chicago, IL, United States of America
| | - Eugene Chang
- Department of Medicine, University of Chicago, Chicago, IL, United States of America
| | - Gary An
- Department of Surgery, University of Chicago, Chicago, IL, United States of America
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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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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: 21] [Impact Index Per Article: 1.9] [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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Pavlides M, Cleland J, Rahman M, Christian A, Doyle J, Gaunt R, Travis S, Mortensen N, Chapman R. Outcomes after ileal pouch anal anastomosis in patients with primary sclerosing cholangitis. J Crohns Colitis 2014; 8:662-70. [PMID: 24418660 DOI: 10.1016/j.crohns.2013.12.007] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Revised: 12/11/2013] [Accepted: 12/11/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Outcomes after ileal pouch anal anastomosis (IPAA) are not well established in patients with primary sclerosing cholangitis (PSC). We conducted a comprehensive outcomes assessment in these patients. METHODS A retrospective case note review of complications in all PSC-IPAA (n=21) and matched ulcerative colitis patients with IPAA (UC-IPAA; n=79) after surgery in Oxford (1983-2012) was conducted, and functional outcomes (Öresland score) were evaluated (2012). Quality of life [Cleveland Global Quality of Life Questionnaire, Short Form-36 (SF-36)], and sexual function were also assessed (2012) including patients with PSC-associated UC without IPAA (PSC-UC; n=19). Sub-group analysis of patients with large duct (ld) PSC-IPAA (n=17) was also performed. RESULTS The 1-, 5-, 10- and 20-year risk of acute pouchitis for PSC-IPAA was 10%, 19%, 31% and 65% respectively, compared to 3%, 10%, 14% and 28% in UC-IPAA (p=0.03). More PSC-IPAA (36%) had poor nocturnal pouch function (vs 2% in UC-IPAA; p=0.0016). There were no differences in surgical complications, quality of life or sexual function between the 3 main groups. LdPSC-IPAA had poorer pouch function (Öresland score: 7.7 vs 5.4 in UC-IPAA; p=0.02), and worse quality of life [SF-36 Physical: 42 vs 50.5 in UC-IPAA; 47.7 in PSC-UC; p=0.03 and Mental Health summary scores: 41.6 vs 51.2 in UC-IPAA; 42.3 in PSC-UC; p=0.04]. CONCLUSIONS PSC-IPAA suffer more acute pouchitis and have worse functional outcomes than UC-IPAA. LdPSC-IPAA also have poorer quality of life.
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Affiliation(s)
- Michael Pavlides
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Jon Cleland
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Monira Rahman
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | | | - Jennifer Doyle
- Division of Medical Sciences, University of Oxford, Oxford, UK
| | - Robert Gaunt
- Department of Statistics, University of Oxford, Oxford, UK
| | - Simon Travis
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Neil Mortensen
- Nuffield Department of Surgery, University of Oxford, Oxford, UK
| | - Roger Chapman
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
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Downregulation of expression of xenobiotic efflux genes is associated with pelvic pouch inflammation in ulcerative colitis. Inflamm Bowel Dis 2014; 20:1157-64. [PMID: 24874456 DOI: 10.1097/mib.0000000000000078] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND As many as 50% of patients with ulcerative colitis who have undergone ileal pouch-anal anastomosis develop de novo inflammation in the ileal pouch after surgery. With the use of microarray technology, we investigated what gene expression changes occur in the pelvic pouch after surgery for ulcerative colitis and how these changes vary by pouch outcome. METHODS Patients who had undergone ileal pouch-anal anastomosis and closure of ileostomy had biopsy specimens from the pouch and pre-pouch ileum prospectively collected. The subjects were allocated into 4 outcome groups: no pouchitis, pouchitis, Crohn's disease-like phenotype, and familial adenomatous polyposis controls. RNA was extracted and transcriptomes were analyzed using a genome-wide approach. The statistical significance of each gene was assessed, and raw P values were corrected for multiple comparisons. RESULTS The expression levels of 2733 transcripts in the pouch were significantly associated with outcome. These genes could be classified into 3 categories: regulation of the immune system, modification of the extracellular matrix, and xenobiotic activity. Contrary to the first 2 categories, genes involved in xenobiotic activity, such as ABCB1, had lower expression in the pouchitis and Crohn's disease-like groups compared with the no pouchitis and familial adenomatous polyposis groups. CONCLUSIONS Transporters of compounds including xenobiotics are downregulated in recurrent disease after ileal pouch-anal anastomosis, whereas inflammatory pathways are upregulated. These findings corroborate the hypothesis that changes in barrier function could contribute to development of intestinal inflammation.
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Abstract
Proctitis accounts for a significant proportion of cases of ulcerative colitis (UC), and some patients subsequently develop more extensive disease. However, most patients continue to have limited inflammation, although the changes in the distal colon and rectum can occasionally be severe, and symptoms of increased frequency, rectal bleeding and urgency can be as disabling as they are for patients with more extensive colitis. Furthermore, although symptoms are typically well controlled with standard medications, medically refractory proctitis poses particular problems. Patients generally are not systemically unwell, and there is no added fear of cancer. Therefore, the prospect of colectomy for such limited disease is resisted by patients, physicians and surgeons alike. Unusual therapies, often delivered locally by enema or suppository, have been tested in small case series without definitive outcomes. The pathogenesis of such limited, yet intractable inflammation remains unclear, and the differential diagnosis should be carefully reviewed to ensure that local disease, whether it is infectious, vascular, or a result of injury or degeneration, is not overlooked. Ileo-anal pouch formation is the surgery of choice for about 20% of patients with UC who undergo colectomy. In the majority of cases, this surgery results in an acceptable quality of life and freedom from a stoma. However, in a sizeable minority of cases, pouch dysfunction can cause intractable problems. The causes of pouch dysfunction are varied and must all be considered carefully, particularly in refractory cases. Pouchitis is a common issue and is usually transient and easily treated. However, refractory and chronic pouchitis can be challenging. Ischaemia, injury, infection and Crohn's disease can all cause refractory pouch dysfunction. In a minority of cases, there appears to be no apparent organic pathology, and the presumptive diagnosis is that of a functional pouch disorder. Although it is much rarer, neoplastic changes in the pouch must also be considered, and the risk managed appropriately. The management of both intractable proctitis and the problematic pouch is made more challenging by the wide differential diagnosis that must be considered and by the paucity of high-quality clinical trials to support any one therapy. Key strategies to overcoming these limitations include methodical and systematic investigation and review, and a willingness to tailor therapy to the individual patient. Clinical trials of new treatments should be supported, and data from the experience with small cohorts of patients should be meticulously collected, critically analysed and widely disseminated.
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Affiliation(s)
- Alex Kent
- Translational Gastroenterology Unit, John Radcliffe Hospital and the University of Oxford, Oxford, UK
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Ileal pouch symptoms do not correlate with inflammation of the pouch. Clin Gastroenterol Hepatol 2014; 12:831-837.e2. [PMID: 24075890 DOI: 10.1016/j.cgh.2013.09.027] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Revised: 09/04/2013] [Accepted: 09/06/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA). However, symptoms are not specific. The Pouchitis Disease Activity Index (PDAI) and the Pouchitis Activity Score (PAS) have been used to diagnose pouchitis. We evaluated the correlation between the clinical components of these scores and endoscopic and histologic findings. METHODS We performed a cross-sectional study, analyzing data from 278 patients from Mount Sinai Hospital (Toronto, Canada) who had an IPAA. Patients underwent pouchoscopy with a biopsy, and data were collected on patients' clinical status. The PDAI and PAS were calculated for each subject. The Spearman rank correlation (ρ) statistical test was used to evaluate correlations between the PDAI scores and PAS, and between total scores and subscores. RESULTS The total PDAI scores and PAS scores were correlated; the clinical components of each correlated with the total score (ρ = 0.59 and ρ = 0.71, respectively). However, we observed a low level of correlation between clinical and endoscopic or histologic subscores, with ρ of 0.20 and 0.10, respectively, by PDAI, and ρ of 0.19 and 0.04, respectively, by PAS. CONCLUSIONS There is a low level of correlation between clinical and endoscopic and histologic subscores of patients with IPAA; clinical symptoms therefore might not reflect objective evidence of inflammation. These findings, along with evidence of correlation between total scores and clinical symptoms, indicate that these indices do not accurately identify patients with pouch inflammation. Further research is required to understand additional factors that contribute to clinical symptoms in the absence of objective signs of pouch inflammation.
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Colectomy for patients with ulcerative colitis and primary sclerosing cholangitis - what next? J Crohns Colitis 2014; 8:421-30. [PMID: 24239402 DOI: 10.1016/j.crohns.2013.10.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2013] [Revised: 09/24/2013] [Accepted: 10/24/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Primary sclerosing cholangitis (PSC) occurs in 2%-8% of patients who suffer from ulcerative colitis (UC). For patients who require colectomy, ileal pouch-anal anastomosis (IPAA) or ileorectal anastomosis (IRA) is employed to preserve continence.We evaluated the outcomes after IPAA and IRA for patients with UC-PSC, using patients with UC but without PSC as controls (UC-only group). PATIENTS In a case-control study conducted at Sahlgrenska University Hospital, Sweden, patients with UC-PSC (N=48; 31 IPAA and 17 IRA) were compared to patients with UC only (N=113; 62 IPAA and 51 IRA). Functional outcomes (Öresland score), pouchitis, surgical complications, and failure were evaluated. RESULTS For patients with IPAA, the median Öresland scores were similar for the two groups: 5 (range, 0-13) for the UC-PSC group and 5 for the UC-only group (range, 0-12; p>0.05). However, the IRA scores were significantly different at 7 (range, 2-11) and 3 (range, 0-11) for the respective groups (p=0.005). Pouchitis was more frequent in patients with UC-PSC. Complication rates did not differ. For patients with IPAA, the failure rate was 16% for those in the UC-PSC group versus 6% for those in the UC-only group (p>0.05); the corresponding results for IRA were 53% versus 22% (p=0.03). CONCLUSIONS For cases of IPAA, pouchitis seems to be more common in patients with UC-PSC. However, the functional outcomes and failure rates are unaffected by concurrent PSC. For patients with UC-PSC, functional outcome is poor and the failure rate is high after IRA.
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Nisar PJ, Turina M, Lavery IC, Kiran RP. Perineal wound healing following ileoanal pouch excision. J Gastrointest Surg 2014; 18:200-7. [PMID: 24146336 DOI: 10.1007/s11605-013-2340-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Accepted: 08/20/2013] [Indexed: 01/31/2023]
Abstract
INTRODUCTION There is paucity of information relating to perineal wound healing when pouch failure after ileal pouch anal anastomosis necessitates pouch excision (PE). The aim of this study is to evaluate perineal healing and factors associated with the development of persistent perineal sinus (PPS) after PE. METHODS Perineal wound-related outcomes for patients who underwent PE from 1985-2009 were evaluated by type of closure (extrasphincteric, intersphincteric, and sphincter-preserving (SP)) and other factors (presence of Crohn's disease (CD) and/or perineal fistulae). Primary outcomes were PPS and delayed healing (healing after PPS development). RESULTS One hundred ten patients (CD 48 %) underwent PE. PPS occurred in 39.8 % patients, 51 % had delayed perineal healing with further procedures, with an overall healing rate of 80.7 %. Closure technique was not associated with PPS (p = 0.37) or eventual healing (p = 0.94). For CD patients, risk of PPS (41 vs. 39 %, p = 0.83) and delayed healing (44 vs. 59 %, p = 0.61) was similar to non-CD patients, but uncomplicated healing took longer (p = 0.04). Four of 15 (26.7 %) patients who underwent SP closure developed PPS; all eventually healed with secondary sphincter excision. CONCLUSIONS Perineal healing may be prolonged after pouch excision. Since eventual healing can be achieved in most patients, perineal dissection and closure can be tailored to the individual circumstance. Sphincter preservation may be used in non-CD patients if future reconstruction is possible. Extrasphincteric closure is preferable with cancer or perineal sepsis. Sphincter resection allows for complete healing in patients who undergo SP dissection and develop PPS.
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Affiliation(s)
- Pasha J Nisar
- Department of Colorectal Surgery, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH, USA
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Annese V, Daperno M, Rutter MD, Amiot A, Bossuyt P, East J, Ferrante M, Götz M, Katsanos KH, Kießlich R, Ordás I, Repici A, Rosa B, Sebastian S, Kucharzik T, Eliakim R. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis 2013; 7:982-1018. [PMID: 24184171 DOI: 10.1016/j.crohns.2013.09.016] [Citation(s) in RCA: 582] [Impact Index Per Article: 48.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Accepted: 09/20/2013] [Indexed: 02/08/2023]
Affiliation(s)
- Vito Annese
- Dept. Gastroenterology, University Hospital Careggi, Largo Brambilla 3, 50139 Florence, Italy.
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Pouchitis: what every gastroenterologist needs to know. Clin Gastroenterol Hepatol 2013; 11:1538-49. [PMID: 23602818 DOI: 10.1016/j.cgh.2013.03.033] [Citation(s) in RCA: 111] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2013] [Revised: 03/12/2013] [Accepted: 03/28/2013] [Indexed: 02/07/2023]
Abstract
Pouchitis is the most common complication among patients with ulcerative colitis who have undergone restorative proctocolectomy with ileal pouch-anal anastomosis. Pouchitis is actually a spectrum of diseases that vary in etiology, pathogenesis, phenotype, and clinical course. Although initial acute episodes typically respond to antibiotic therapy, patients can become dependent on antibiotics or develop refractory disease. Many factors contribute to the course of refractory pouchitis, such as the use of nonsteroidal anti-inflammatory drugs, infection with Clostridium difficile, pouch ischemia, or concurrent immune-mediated disorders. Identification of these secondary factors can help direct therapy.
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Zippi M, Cassieri C, Avallone EV, Pica R. Infliximab for the treatment of pouchitis. World J Clin Cases 2013; 1:191-196. [PMID: 24303499 PMCID: PMC3845959 DOI: 10.12998/wjcc.v1.i6.191] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Revised: 07/30/2013] [Accepted: 08/06/2013] [Indexed: 02/05/2023] Open
Abstract
Pouchitis is not a rare complication that develops after an ileal-pouch anastomosis, performed after colectomy in patients refractory to treatment or with complicated ulcerative colitis. This condition may become chronic and unresponsive to medical therapies, including corticosteroids, antibiotics and probiotics. The advent of biological therapies (tumor necrosis factor-α inhibitors) has changed the course of these complications. In particular, in these cases, infliximab (IFX) may represent a safe and effective therapy in order to avoid the subsequent operation for a permanent ileostomy. This article reviews the therapeutic effects of one of the most widely used anti-tumor necrosis factor-α molecules, IFX, for the treatment of complicated pouchitis (refractory to conventional treatment and/or fistulizing).
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Kabakchiev B, Silverberg MS. Expression quantitative trait loci analysis identifies associations between genotype and gene expression in human intestine. Gastroenterology 2013; 144:1488-96, 1496.e1-3. [PMID: 23474282 PMCID: PMC3775712 DOI: 10.1053/j.gastro.2013.03.001] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2012] [Revised: 01/30/2013] [Accepted: 03/01/2013] [Indexed: 01/05/2023]
Abstract
BACKGROUND & AIMS Genome-wide association studies have greatly increased our understanding of intestinal disease. However, little is known about how genetic variations result in phenotypic changes. Some polymorphisms have been shown to modulate quantifiable phenotypic traits; these are called quantitative trait loci. Quantitative trait loci that affect levels of gene expression are called expression quantitative trait loci (eQTL), which can provide insight into the biological relevance of data from genome-wide association studies. We performed a comprehensive eQTL scan of intestinal tissue. METHODS Total RNA was extracted from ileal biopsy specimens and genomic DNA was obtained from whole-blood samples from the same cohort of individuals. Cis- and trans-eQTL analyses were performed using a custom software pipeline for samples from 173 subjects. The analyses determined the expression levels of 19,047 unique autosomal genes listed in the US National Center for Biotechnology Information database and more than 580,000 variants from the Single Nucleotide Polymorphism database. RESULTS The presence of more than 15,000 cis- and trans-eQTL was detected with statistical significance. eQTL associated with the same expression trait were in high linkage disequilibrium. Comparative analysis with previous eQTL studies showed that 30% to 40% of genes identified as eQTL in monocytes, liver tissue, lymphoblastoid cell lines, T cells, and fibroblasts are also eQTL in ileal tissue. Conversely, most of the significant eQTL have not been previously identified and could be tissue specific. These are involved in many cell functions, including division and antigen processing and presentation. Our analysis confirmed that previously published cis-eQTL are single nucleotide polymorphisms associated with inflammatory bowel disease: rs2298428/UBE2L3, rs1050152/SLC22A4, and SLC22A5. We identified many new associations between inflammatory bowel disease susceptibility loci and gene expression. CONCLUSIONS eQTL analysis of intestinal tissue supports findings that some eQTL remain stable across cell types, whereas others are specific to the sampled location. Our findings confirm and expand the number of known genotypes associated with expression and could help elucidate mechanisms of intestinal disease.
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Affiliation(s)
- Boyko Kabakchiev
- Zane Cohen Centre for Digestive Diseases, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
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Banasiewicz T, Walkowiak J, Drzymała-Czyż S, Borejsza-Wysocki M, Majewski P, Biczysko M, Stojcev Z, Herzig KH, Drews M. Stricture of ileo-anal J pouch anastomosis increased the intensity of pouchitis in an experimental rat model. Med Sci Monit 2013; 18:BR409-13. [PMID: 23018348 PMCID: PMC3560548 DOI: 10.12659/msm.883481] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Pouchitis appears to be the most common complication after restorative proctocolectomy. Material/Methods In experimental models we investigated the correlation between the width of anastomosis and the frequency of pouchitis. Twenty-three Wistar rats underwent restorative proctocolectomy under pentobarbital anesthesia. Normal width anastomosis was performed in 11 animals (Group I). In the remaining 12 animals (Group II) the diameter of anastomosis was reduced by 50%. All animals were sacrificed and the pouch mucosa was histologically (Moskowitz score) and immunohistochemically (IL-1, IL-6, IL-10, IL-12 expression) examined. Results Morphological assessment of pouchitis symptoms based on Moskowitz scale revealed considerably more severe inflammation (p=0.0079) in the animals from Group II than in the rats from Group I. The expressions of investigated cytokines, assessed qualitatively in histopathological examination, were higher in rats with narrow anastomosis in comparison with animals with normal anastomosis. Conclusions The stricture of anastomosis increases the intensity of pouchitis and stimulates the production of interleukins. It seems that anastomotic stricture plays an important role in the development of pouchitis.
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Affiliation(s)
- Tomasz Banasiewicz
- Department of General Surgery, Gastroenterological Oncological Surgery and Plastic Surgery, K. Marcinkowski University of Medical Sciences, Poznan, Poland.
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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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Characteristics of extremely early-onset pouchitis after proctocolectomy with ileal pouch-anal anastomosis. J Gastrointest Surg 2013; 17:533-9. [PMID: 23254315 PMCID: PMC3568199 DOI: 10.1007/s11605-012-2120-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2012] [Accepted: 12/03/2012] [Indexed: 02/06/2023]
Abstract
OBJECTIVE This study aims to evaluate the clinical characteristics of patients with postoperative ulcerative colitis developing extremely early-onset pouchitis within 4 weeks of restoration of gastrointestinal continuity. MATERIAL AND METHODS This retrospective study involved 225 consecutive patients from January 2000 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis with a minimum follow-up of 12 months. Extremely early-onset pouchitis was defined as pouchitis developing within 4 weeks of restoration of gastrointestinal continuity. Patients with pouchitis were divided into extremely early-onset pouchitis and non-extremely early-onset pouchitis groups for comparison. RESULTS Of 212 patients who met the inclusion criteria, 62 had pouchitis (29.2 %). Eight (3.8 %) patients developed extremely early-onset pouchitis. There was a significant difference in the dosage of steroid per month just before colectomy between the two groups (P = 0.039). The modified Pouchitis Disease Activity Index score for patients with extremely early-onset pouchitis was higher than in patients with non-extremely early-onset pouchitis (P = 0.0009). The occurrence of extremely early-onset pouchitis was associated with the development of chronic pouchitis (P = 0.0056). CONCLUSION Extremely early-onset pouchitis may be related to high steroid dosages before colectomy and may be more severe than pouchitis that occurs >4 weeks after restoration of gastrointestinal continuity.
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Rameshshanker R, Arebi N. Endoscopy in inflammatory bowel disease when and why. World J Gastrointest Endosc 2012; 4:201-11. [PMID: 22720120 PMCID: PMC3377861 DOI: 10.4253/wjge.v4.i6.201] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2011] [Revised: 11/21/2011] [Accepted: 05/27/2012] [Indexed: 02/05/2023] Open
Abstract
Endoscopy plays an important role in the diagnosis and management of inflammatory bowel disease (IBD). It is useful to exclude other aetiologies, differentiate between ulcerative colitis (UC) and Crohn’s disease (CD), and define the extent and activity of inflammation. Ileocolonoscopy is used for monitoring of the disease, which in turn helps to optimize the management. It plays a key role in the surveillance of UC for dysplasia or neoplasia and assessment of post operative CD. Capsule endoscopy and double balloon enteroscopy are increasingly used in patients with CD. Therapeutic applications relate to stricture dilatation and dysplasia resection. The endoscopist’s role is vital in the overall management of IBD.
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Affiliation(s)
- Rajaratnam Rameshshanker
- Rajaratnam Rameshshanker, Naila Arebi, Department of Gastroenterology, St Mark's Hospital, Watford Road, London, HA1 3UJ, United Kingdom
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Landy J, Al-Hassi HO, McLaughlin SD, Knight SC, Ciclitira PJ, Nicholls RJ, Clark SK, Hart AL. Etiology of pouchitis. Inflamm Bowel Dis 2012; 18:1146-55. [PMID: 22021180 DOI: 10.1002/ibd.21911] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Accepted: 09/06/2011] [Indexed: 12/16/2022]
Abstract
Restorative proctocolectomy with ileal-pouch anal anastomosis (RPC) is the operation of choice for ulcerative colitis (UC) patients requiring surgery. It is also used for patients with familial adenomatous polyposis (FAP). Pouchitis accounts for 10% of pouch failures. It is an idiopathic inflammatory condition that may occur in up to 50% of patients after RPC for UC. It is rarely seen in FAP patients after RPC. The etiology of pouchitis remains unclear. An overlap with UC is suggested by the frequency with which pouchitis affects patients with UC compared with FAP patients. There is significant clinical evidence implicating bacteria in the pathogenesis of pouchitis. Studies using culture and molecular methods demonstrate a dysbiosis of the pouch microbiota in pouchitis. Risk factors, genetic associations, and serological markers of pouchitis suggest that the interactions between the host immune responses and the pouch microbiota underlie the etiology of this idiopathic inflammatory condition. Here we present a detailed review of the data focusing on the pouch microbiota and the immune responses that support this hypothesis. We also discuss the contribution of luminal metabolic factors and the epithelial membrane in the etiology of this inflammatory process. The ileoanal pouch offers a unique opportunity to study the inter-relationships between the gut microbiota and host immune responses from before the onset of disease. For this reason the study of pouchitis could serve as a human model that significantly enhances our understanding of inflammatory bowel diseases in general.
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Affiliation(s)
- J Landy
- Department of Gastroenterology St Mark's Hospital, Harrow, London, UK
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Tannock GW, Lawley B, Munro K, Lay C, Taylor C, Daynes C, Baladjay L, Mcleod R, Thompson-Fawcett M. Comprehensive analysis of the bacterial content of stool from patients with chronic pouchitis, normal pouches, or familial adenomatous polyposis pouches. Inflamm Bowel Dis 2012; 18:925-34. [PMID: 22114001 DOI: 10.1002/ibd.21936] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2011] [Accepted: 10/04/2011] [Indexed: 12/26/2022]
Abstract
BACKGROUND Chronic pouchitis is an important long-term complication following ileal pouch-anal anastomosis for ulcerative colitis. Antibiotic administration reduces symptoms of pouchitis, indicating that bacteria have a role in pathogenesis. The aim of the research was to investigate the bacterial content of pouches using nucleic acid-based methods. METHODS Stool microbiota of 17 patients with normal pouches (NP), 17 patients with pouchitis (CP) utilizing samples collected from each patient when antibiotic-treated (CP-on, asymptomatic) and when untreated (CP-off, symptomatic), and 14 familial adenomatous polyposis (FAP) patients were analyzed by high-throughput sequencing, fluorescence in situ hybridization technologies, and quantitative polymerase chain reaction (qPCR). RESULTS Fluorescence in situ hybridization analysis revealed an expanded phylogenetic gap in NP and CP-off patients relative to FAP. Antibiotic treatment reduced the gap in CP stool. The phylogenetic gap of CP-off patients was due to members of the bacterial families Caulobacteriaceae, Sphingomonadaceae, Comamonadaceae, Peptostreptococcaceae, and Clostridiaceae. There was a greater diversity of phylotypes of Clostridiaceae in CP-off subjects. The phylogenetic gap of NP stool was enriched by Ruminococcaceae and Bifidobacteriaceae. CP stool microbiota had reduced diversity relative to NP and FAP stool due largely to a reduction in Lachnospiraceae/Insertae Sedis XIV/clostridial cluster IV groups. CONCLUSIONS Bacterial groups within the expanded phylogenetic gap of pouch patients may have roles in the pathogenesis of pouchitis. Further research concerning the physiology of cultured members of these groups will be necessary to explain their specific roles. Members of the Lachnospiraceae, Incertae Sedis XIV, and clostridial cluster IV could be useful biomarkers of pouch health.
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Affiliation(s)
- Gerald W Tannock
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
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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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Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis has become the procedure of choice for the majority of patients with ulcerative colitis who require surgical treatment. Pouchitis, the most common long-term complication of the procedure, involves a spectrum of disease processes with heterogeneous risk factors, clinical features, disease courses and prognoses. In addition, clinical symptoms of pouchitis are not specific and often overlap with those of other inflammatory and functional pouch disorders, such as Crohn's disease of the pouch and irritable pouch syndrome. Pouchoscopy and biopsy, along with laboratory and radiographic evaluations, are often required for accurate diagnosis in patients with symptoms indicative of pouchitis. Dysbiosis has been implicated as a triggering factor for pouchitis, and concurrent infection with pathogens, such as Clostridium difficile, might contribute to disease relapse and exacerbation. Antibiotic therapy is the main treatment modality. However, the management of antibiotic-dependent and antibiotic-refractory pouchitis remains challenging. Secondary causes of pouchitis, such as ischaemia, NSAID use, the presence of concurrent primary sclerosing cholangitis and other systemic immune-mediated disorders, should be evaluated and properly managed.
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Banasiewicz T, Marciniak R, Paszkowski J, Krokowicz P, Kaczmarek E, Walkowiak J, Szmeja J, Majewski P, Drews M. Pouchitis may increase the risk of dysplasia after restorative proctocolectomy in patients with ulcerative colitis. Colorectal Dis 2012; 14:92-7. [PMID: 21689264 DOI: 10.1111/j.1463-1318.2011.02547.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
AIM Dysplasia of the pouch mucosa after restorative proctocolectomy is rare. The aim of this study was to establish whether there is a correlation between pouchitis and dysplasia. METHOD A group of 276 patients treated for ulcerative colitis by restorative proctocolectomy between 1984 and 2009 was analysed. The presence or absence of pouchitis and dysplasia within the pouch was evaluated. RESULTS Inflammation was diagnosed in 66 (23.9%) patients, low-grade dysplasia in five (1.8%), high-grade dysplasia in three (1.1%), and cancer in one patient (0.4%). The prevalence of low-grade dysplasia was significantly higher in patients with inflammation than in those without (P < 0.04). High-grade dysplasia was significantly more frequent in pouchitis than in non-inflamed pouches (P < 0.01). Logistic regression analysis suggested that the occurrence of mucosal inflammation increased the risk of low grade dysplasia. CONCLUSION Patients with chronic pouchitis are at risk of dysplasia and require surveillance of the pouch.
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Affiliation(s)
- T Banasiewicz
- Department of General, Gastroenterological and Endocrinological Surgery, Poznan University of Medical Sciences, Poznań, Poland.
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