|
1
|
Goldenshluger M, Segev L. Ileocolic resection with temporary ileostomy for Crohn's disease: does it affect long-term disease recurrence compared with primary anastomosis? ANZ J Surg 2025; 95:143-150. [PMID: 39297737 DOI: 10.1111/ans.19237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 08/24/2024] [Accepted: 09/09/2024] [Indexed: 03/04/2025]
Abstract
BACKGROUND We aimed to assess whether the risk of disease recurrence in Crohn's disease (CD) patients that undergone ileocolic resection (ICR) with temporary ileostomy and a later stoma reversal is different compared to patients that underwent a one-stage operation. METHODS A single-center retrospective review of all patients that underwent elective primary ICR for CD between 2010 and 2022 divided into: 2S-ICR group-patients who underwent two-stage ICR. 1S-ICR group-patients who underwent one-stage ICR. RESULTS The cohort included 191 patients (mean age 33.4, range 15-70), with 40 and 151 patients in the 2S-ICR and 1S-ICR groups, respectively. The 2S-ICR were more comorbid, with a lower mean BMI (18 vs. 21.3, P < 0.001), higher median ASA score (3 vs. 2, P = 0.036), higher percentage on pre-operative total parenteral nutrition (TPN) (62.5% vs. 24.5%, P < 0.001), and lower levels of pre-operative albumin (3.3 g/dL vs. 3.8 g/dL, P < 0.001). There were no significant differences in the overall postoperative complication rate (47.5% vs. 47.7% respectively, P = 1), nor in the rate of severe complications (17.5% vs. 13.2%, P = 0.6), but, the 2S-ICR had a longer post-operative length-of-stay (14 vs. 6 days, P < 0.001) and higher rates of 30-day readmission (30% vs. 13.2%, P = 0.017). After an overall median follow-up of 63 months, the groups showed similar rates of endoscopic, clinical, and surgical recurrence. CONCLUSIONS Two-stage ICR with a temporary ileostomy does not change long-term CD recurrence rates compared with one-stage ICR.
Collapse
Affiliation(s)
- Michael Goldenshluger
- Department of General Surgery, The Chaim Sheba Medical Center, Ramat Gan, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Lior Segev
- Department of General Surgery, The Chaim Sheba Medical Center, Ramat Gan, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| |
Collapse
|
|
2
|
Adamina M, Minozzi S, Warusavitarne J, Buskens CJ, Chaparro M, Verstockt B, Kopylov U, Yanai H, Vavricka SR, Sigall-Boneh R, Sica GS, Reenaers C, Peros G, Papamichael K, Noor N, Moran GW, Maaser C, Luglio G, Kotze PG, Kobayashi T, Karmiris K, Kapizioni C, Iqbal N, Iacucci M, Holubar S, Hanzel J, Sabino JG, Gisbert JP, Fiorino G, Fidalgo C, Ellu P, El-Hussuna A, de Groof J, Czuber-Dochan W, Casanova MJ, Burisch J, Brown SR, Bislenghi G, Bettenworth D, Battat R, Atreya R, Allocca M, Agrawal M, Raine T, Gordon H, Myrelid P. ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment. J Crohns Colitis 2024; 18:1556-1582. [PMID: 38878002 DOI: 10.1093/ecco-jcc/jjae089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Indexed: 07/28/2024]
Abstract
This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines.
Collapse
Affiliation(s)
- Michel Adamina
- Department of Surgery, Cantonal Hospital of Fribourg & Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
| | - Silvia Minozzi
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | | | | | - Maria Chaparro
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Bram Verstockt
- Department Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Belgium
- Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Henit Yanai
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Rotem Sigall-Boneh
- Pediatric Gastroenterology and Nutrition Unit, The E. Wolfson Medical Center, Holon, Israel
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
| | - Giuseppe S Sica
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, Università Tor Vergata, Roma, Italy
| | | | - Georgios Peros
- Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
| | - Konstantinos Papamichael
- Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Nurulamin Noor
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - Gordon William Moran
- National Institute of Health Research Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals, Nottingham, UK
- Translational Medical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
| | - Christian Maaser
- Outpatients Department of Gastroenterology, University Teaching Hospital Lueneburg, Lueneburg, Germany
| | - Gaetano Luglio
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Paulo Gustavo Kotze
- Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná [PUCPR], Curitiba, Brazil
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | | | | | - Nusrat Iqbal
- Department of Surgery, Worcestershire Acute Hospitals NHS Trust, Worcester, UK
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
| | - Stefan Holubar
- Department of Colon & Rectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Jurij Hanzel
- Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Department of of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - João Guedelha Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Javier P Gisbert
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | | | - Catarina Fidalgo
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal
| | - Pierre Ellu
- Division of Gastroenterology, Mater Dei Hospital, l-Msida, Malta
| | - Alaa El-Hussuna
- OpenSourceResearch Organization [OSRC.Network], Aalborg, Denmark
| | - Joline de Groof
- Colorectal Surgery, Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Wladyslawa Czuber-Dochan
- Florence Nightingale Faculty of Nursing-Midwifery and Palliative Care, King's College London, London, UK
| | - María José Casanova
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | | | | | - Dominik Bettenworth
- CED Schwerpunktpraxis, Münster and Medical Faculty of the University of Münster, Münster, Germany
| | - Robert Battat
- Division of Gastroenterology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
| | - Raja Atreya
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Mariangela Allocca
- IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milan, Italy
| | - Manasi Agrawal
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Tim Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Hannah Gordon
- Translational Gastroenterology and Liver Unit, Gastroenterology Office, University of Oxford, Oxford, UK
| | - Pär Myrelid
- Department of Surgery and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| |
Collapse
|
|
3
|
Jew M, Meserve J, Eisenstein S, Jairath V, McCurdy J, Singh S. Temporary Faecal Diversion for Refractory Perianal and/or Distal Colonic Crohn's Disease in the Biologic Era: An Updated Systematic Review with Meta-analysis. J Crohns Colitis 2024; 18:375-391. [PMID: 37707480 PMCID: PMC10906955 DOI: 10.1093/ecco-jcc/jjad159] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 08/20/2023] [Accepted: 09/12/2023] [Indexed: 09/15/2023]
Abstract
BACKGROUND AND AIMS We evaluated short- and long-term outcomes of temporary faecal diversion [FD] for management of refractory Crohn's disease [CD], focusing on outcomes in the biologic era. METHODS Through a systematic literature review until March 15, 2023, we identified 33 studies [19 conducted in the biologic era] that evaluated 1578 patients with perianal and/or distal colonic CD who underwent temporary FD [with intent of restoring bowel continuity] and reported long-term outcomes [primary outcome: successful restoration of bowel continuity, defined as remaining ostomy-free after reconnection at a minimum of 6 months after diversion or at the end of follow-up]. We calculated pooled rates (with 95% confidence interval [CI]) using random effects meta-analysis, and examined factors associated with successful restoration of bowel continuity. RESULTS Overall, 61% patients [95% CI, 52-68%; 50% in biologic era] experienced clinical improvement after FD. Stoma takedown was attempted in 34% patients [28-41%; 37% in biologic era], 6-18 months after diversion. Among patients where bowel restoration was attempted, 63% patients [54-71%] had successful restoration of bowel continuity, and 26% [20-34%] required re-diversion. Overall, 21% patients [17-27%; 24% in biologic era] who underwent FD were successfully restored; 34% patients [30-39%; 31% in biologic era] required proctectomy with permanent ostomy. On meta-regression, post-diversion biologic use and absence of proctitis was associated with successful bowel restoration after temporary FD in contemporary studies. CONCLUSION In the biologic era, temporary FD for refractory perianal and/or distal colonic CD improves symptoms in half the patients, and bowel continuity can be successfully restored in a quarter of patients.
Collapse
Affiliation(s)
- Michael Jew
- Department of Internal Medicine, University of California San Diego, La Jolla, CA, USA
| | - Joseph Meserve
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Samuel Eisenstein
- Division of Colorectal Surgery, Department of Surgery, University of California San Diego, La Jolla, CA, USA
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
- Department of Epidemiology & Biostatistics, Western University, London, ON, Canada
| | - Jeffrey McCurdy
- Division of Gastroenterology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
- Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| |
Collapse
|
|
4
|
Halper-Stromberg A, Dalal SR. The Role of the Microbiome in the Etiology of Inflammatory Bowel Diseases. Clin Colon Rectal Surg 2023; 36:120-126. [PMID: 36844713 PMCID: PMC9946717 DOI: 10.1055/s-0042-1760680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Inflammatory bowel diseases (IBDs) result from dysregulated immune responses to environmental and microbial triggers in genetically susceptible hosts. Many clinical observations and animal studies support the role of the microbiome in the pathogenesis of IBD. Restoration of the fecal stream leads to postoperative Crohn's recurrence, while diversion can treat active inflammation. Antibiotics can be effective in prevention of postoperative Crohn's recurrence and in pouch inflammation. Several gene mutations associated with Crohn's risk lead to functional changes in microbial sensing and handling. However, the evidence linking the microbiome to the IBD is largely correlative, given the difficulty in studying the microbiome before disease occurs. Attempts to modify the microbial triggers of inflammation have had modest success to date. Exclusive enteral nutrition can treat Crohn's inflammation though no whole food diet to date has been shown to treat inflammation. Manipulation of the microbiome through fecal microbiota transplant and probiotics have had limited success. Further focus on early changes in the microbiome and functional consequences of microbial changes through the study of metabolomics are needed to help advance the field.
Collapse
Affiliation(s)
- Ariel Halper-Stromberg
- University of Chicago Medicine Inflammatory Bowel Disease Center, Dept of Medicine, Chicago, Illinois
| | - Sushila R. Dalal
- University of Chicago Medicine Inflammatory Bowel Disease Center, Dept of Medicine, Chicago, Illinois
| |
Collapse
|
|
5
|
Microbial Signature in Adipose Tissue of Crohn's Disease Patients. J Clin Med 2020; 9:jcm9082448. [PMID: 32751800 PMCID: PMC7465250 DOI: 10.3390/jcm9082448] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 07/28/2020] [Accepted: 07/29/2020] [Indexed: 02/08/2023] Open
Abstract
Crohn’s disease (CD) is characterized by compromised immune tolerance to the intestinal commensal microbiota, intestinal barrier inflammation, and hyperplasia of creeping fat (CF) and mesenteric adipose tissue (AT), which seems to be directly related to disease activity. Gut microbiota dysbiosis might be a determining factor in CD etiology, manifesting as a low microbial diversity and a high abundance of potentially pathogenic bacteria. We tested the hypothesis that CF is a reservoir of bacteria through 16S-rRNA sequencing of several AT depots of patients with active and inactive disease and controls. We found a microbiome signature within CF and mesenteric AT from patients, but not in subcutaneous fat. We failed to detect bacterial DNA in any fat depot of controls. Proteobacteria was the most abundant phylum in both CF and mesenteric AT, and positively correlated with fecal calprotectin/C-reactive protein. Notably, the clinical status of patients seemed to be related to the microbiome signature, as those with the inactive disease showed a reduction in the abundance of pathogenic bacteria. Predictive functional profiling revealed many metabolic pathways including lipopolysaccharide biosynthesis and sulfur metabolism overrepresented in active CD relative to that in inactive CD. Our findings demonstrate that microbiota dysbiosis associated with CD pathophysiology is reflected in AT and might contribute to disease severity.
Collapse
|
|
6
|
Bolckmans R, Singh S, Ratnatunga K, Wickramasinghe D, Sahnan K, Adegbola S, Kalman D, Jones H, Travis S, Warusavitarne J, Myrelid P, George B. Temporary faecal diversion in ileocolic resection for Crohn's disease: is there an impact on long-term surgical recurrence? Colorectal Dis 2020; 22:430-438. [PMID: 31715062 DOI: 10.1111/codi.14895] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 09/06/2019] [Indexed: 12/12/2022]
Abstract
AIM Temporary faecal diversion after ileocolic resection (ICR) for Crohn's disease reduces postoperative anastomotic complications in high-risk patients. The aim of this study was to assess if this approach also reduces long-term surgical recurrence. METHOD This was a multicentre retrospective review of prospectively maintained databases. Patient demographics, medical and surgical details were collected by three specialist centres. All patients had undergone an ICR between 2000 and 2012. The primary end-point was surgical recurrence. RESULTS Three hundred and twelve patients (80%) underwent an ICR without covering ileostomy (one stage). Seventy-seven (20%) had undergone an ICR with end ileostomy/double-barrel ileostomy/enterocolostomy followed by closure (two stage). The median follow-up was 105 months [interquartile range (IQR) 76-136 months]. The median time to ileostomy closure was 9 months (IQR 5-12 months). There was no significant difference in surgical recurrence between the one- and two-stage groups (18% vs 16%, P = 0.94). We noted that smokers (20% vs 34%, P = 0.01) and patients with penetrating disease (28% vs 52%, P < 0.01) were more likely to be defunctioned. A reduced recurrence rate was observed in the small high-risk group of patients who were smokers with penetrating disease behaviour treated with a two-stage strategy (0/10 vs 4/7, P = 0.12). CONCLUSION Despite having higher baseline risk factors, the results in terms of rate of surgical recurrence over 9 years are similar for patients having a two-stage compared with a one-stage procedure.
Collapse
Affiliation(s)
- R Bolckmans
- Department of Colorectal Surgery, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - S Singh
- Department of Colorectal Surgery, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - K Ratnatunga
- Department of Colorectal Surgery, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - D Wickramasinghe
- Department of Colorectal Surgery, St Mark's Hospital, London, UK
| | - K Sahnan
- Department of Colorectal Surgery, St Mark's Hospital, London, UK
| | - S Adegbola
- Department of Colorectal Surgery, St Mark's Hospital, London, UK
| | - D Kalman
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.,Department of Surgery, County Council of Östergötland, Linköping, Sweden
| | - H Jones
- Department of Colorectal Surgery, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - S Travis
- Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK
| | - J Warusavitarne
- Department of Colorectal Surgery, St Mark's Hospital, London, UK
| | - P Myrelid
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.,Department of Surgery, County Council of Östergötland, Linköping, Sweden
| | - B George
- Department of Colorectal Surgery, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| |
Collapse
|
|
7
|
Adamina M, Bonovas S, Raine T, Spinelli A, Warusavitarne J, Armuzzi A, Bachmann O, Bager P, Biancone L, Bokemeyer B, Bossuyt P, Burisch J, Collins P, Doherty G, El-Hussuna A, Ellul P, Fiorino G, Frei-Lanter C, Furfaro F, Gingert C, Gionchetti P, Gisbert JP, Gomollon F, González Lorenzo M, Gordon H, Hlavaty T, Juillerat P, Katsanos K, Kopylov U, Krustins E, Kucharzik T, Lytras T, Maaser C, Magro F, Marshall JK, Myrelid P, Pellino G, Rosa I, Sabino J, Savarino E, Stassen L, Torres J, Uzzan M, Vavricka S, Verstockt B, Zmora O. ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment. J Crohns Colitis 2020; 14:155-168. [PMID: 31742338 DOI: 10.1093/ecco-jcc/jjz187] [Citation(s) in RCA: 355] [Impact Index Per Article: 71.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This article is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of previous guidelines.
Collapse
Affiliation(s)
- Michel Adamina
- Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
- University of Basel, Basel, Switzerland
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Tim Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Antonino Spinelli
- Humanitas Clinical and Research Center, Division of Colon and Rectal Surgery, Humanitas University, Department of Biomedical Sciences, Milan, Italy
| | - Janindra Warusavitarne
- Imperial College London, Department of Surgery and Cancer, St Mark's Hospital, Department of Gastroenterology, London, UK
| | - Alessandro Armuzzi
- IBD Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita' Cattolica del Sacro Cuore, Rome, Italy
| | - Oliver Bachmann
- Department of Internal Medicine I, Siloah St Trudpert Hospital, Pforzheim, Germany
| | - Palle Bager
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Livia Biancone
- Department of Systems Medicine, University 'Tor Vergata' of Rome, Rome, Italy
| | | | - Peter Bossuyt
- Imelda GI Clinical Research Centre, Imelda General Hospital, Bonheiden, Belgium
| | - Johan Burisch
- Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Paul Collins
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Glen Doherty
- Department of Gastroenterology and Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
| | - Alaa El-Hussuna
- Department of Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | - Gionata Fiorino
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | | | - Federica Furfaro
- IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Christian Gingert
- Visceral Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland; Department of Human Medicine, Faculty of Health, University of Witten/Herdecke, Witten, Germany
| | | | - Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-IP], Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Fernando Gomollon
- IBD UNIT, Hospital Clíico Universitario 'Lozano Blesa', IIS Aragón, CIBEREHD, Zaragoza, Spain
| | | | - Hannah Gordon
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, UK
| | - Tibor Hlavaty
- Fifth Department of Internal Medicine, Sub-department of Gastroenterology and Hepatology, University Hospital Bratislava and Faculty of Medicine, Comenius University Bratislava, Slovakia
| | - Pascal Juillerat
- Clinic for Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Uri Kopylov
- Department of Gastroenterology, Tel-HaShomer Sheba Medical Center, Ramat Gan, Israel; and Sackler Medical School, Tel Aviv, Israel
| | - Eduards Krustins
- Department of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical University Hospital, Department of Internal Medicine, Riga Stradiņš University, Riga, Latvia
| | - Torsten Kucharzik
- Department of Internal Medicine and Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | | | - Christian Maaser
- Outpatients Department of Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Fernando Magro
- Department of Pharmacology and Therapeutics; Institute for Molecular and Cell Biology, University of Porto, Faculty of Medicine, Porto, Portugal
| | - John Kenneth Marshall
- Department of Medicine [Division of Gastroenterology] and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Pär Myrelid
- Department of Surgery, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Gianluca Pellino
- Department of Advanced Medical and Surgical Sciences, Universitá degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | - Isadora Rosa
- Department of Gastroenterology, IPOLFG, Lisbon, Portugal
| | - Joao Sabino
- Department of Gastroenterology and Hepatology, University Hospitals, KU Leuven, Leuven, Belgium
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Laurents Stassen
- Department of General Surgery, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Joana Torres
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Mathieu Uzzan
- Department of Gastroenterology, IBD unit, Beaujon Hospital, APHP, Clichy, France
| | - Stephan Vavricka
- Division of Gastroenterology and Hepatology, University Hospital, Zürich, Switzerland
| | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium, and Department of Chronic Diseases, Metabolism and Ageing, TARGID - IBD, KU Leuven, Leuven, Belgium
| | - Oded Zmora
- Department of Surgery, Shamir Medical Center [Assaf Harofe], Tel Aviv, Israel
| |
Collapse
|
|
8
|
Kiernan MG, Coffey JC, Sahebally SM, Tibbitts P, Lyons EM, O’leary E, Owolabi F, Dunne CP. Systemic Molecular Mediators of Inflammation Differentiate Between Crohn's Disease and Ulcerative Colitis, Implicating Threshold Levels of IL-10 and Relative Ratios of Pro-inflammatory Cytokines in Therapy. J Crohns Colitis 2020; 14:118-129. [PMID: 31241755 PMCID: PMC6930002 DOI: 10.1093/ecco-jcc/jjz117] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Faecal diversion is associated with improvements in Crohn's disease but not ulcerative colitis, indicating that differing mechanisms mediate the diseases. This study aimed to investigate levels of systemic mediators of inflammation, including fibrocytes and cytokines, [1] in patients with Crohn's disease and ulcerative colitis preoperatively compared with healthy controls and [2] in patients with Crohn's disease and ulcerative colitis prior to and following faecal diversion. METHODS Blood samples were obtained from healthy individuals and patients with Crohn's disease or ulcerative colitis. Levels of circulating fibrocytes were quantified using flow cytometric analysis and their potential relationship to risk factors of inflammatory bowel disease were determined. Levels of circulating cytokines involved in inflammation and fibrocyte recruitment and differentiation were investigated. RESULTS Circulating fibrocytes were elevated in Crohn's disease and ulcerative colitis patients when compared with healthy controls. Smoking, or a history of smoking, was associated with increases in circulating fibrocytes in Crohn's disease, but not ulcerative colitis. Cytokines involved in fibrocyte recruitment were increased in Crohn's disease patients, whereas patients with ulcerative colitis displayed increased levels of pro-inflammatory cytokines. Faecal diversion in Crohn's disease patients resulted in decreased circulating fibrocytes, pro-inflammatory cytokines, and TGF-β1, and increased IL-10, whereas the inverse was observed in ulcerative colitis patients. CONCLUSIONS The clinical effect of faecal diversion in Crohn's disease and ulcerative colitis may be explained by differing circulating fibrocyte and cytokine responses. Such differences aid in understanding the disease mechanisms and suggest a new therapeutic strategy for inflammatory bowel disease.
Collapse
Affiliation(s)
- Miranda G Kiernan
- Graduate Entry Medical School and Centre for Interventions in Infection, Inflammation & Immunity [4i], University of Limerick, Limerick, Ireland
| | - J Calvin Coffey
- Graduate Entry Medical School and Centre for Interventions in Infection, Inflammation & Immunity [4i], University of Limerick, Limerick, Ireland,Department of Surgery, University Hospital Limerick, Limerick, Ireland
| | - Shaheel M Sahebally
- Graduate Entry Medical School and Centre for Interventions in Infection, Inflammation & Immunity [4i], University of Limerick, Limerick, Ireland,Department of Surgery, University Hospital Limerick, Limerick, Ireland
| | - Paul Tibbitts
- Graduate Entry Medical School and Centre for Interventions in Infection, Inflammation & Immunity [4i], University of Limerick, Limerick, Ireland,Department of Surgery, University Hospital Limerick, Limerick, Ireland
| | - Emma M Lyons
- Department of Surgery, University Hospital Limerick, Limerick, Ireland
| | - Eimear O’leary
- Graduate Entry Medical School and Centre for Interventions in Infection, Inflammation & Immunity [4i], University of Limerick, Limerick, Ireland
| | - Funke Owolabi
- Graduate Entry Medical School and Centre for Interventions in Infection, Inflammation & Immunity [4i], University of Limerick, Limerick, Ireland
| | - Colum P Dunne
- Graduate Entry Medical School and Centre for Interventions in Infection, Inflammation & Immunity [4i], University of Limerick, Limerick, Ireland,Corresponding author: Professor Colum Dunne, Graduate Entry Medical School, University of Limerick, Limerick, Ireland. Tel.: 353-[0]61-234703;
| |
Collapse
|
|
9
|
Abstract
Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract resulting in progressive tissue damage, which can result in strictures, fistulae, and abscesses formation. The triggering mechanism is thought to be in the fecal stream, and diversion of this fecal stream is sometimes required to control disease when all other avenues of medical and surgical management have been exhausted. Fecal diversion can be temporary or permanent with the indications being defunctioning a high-risk anastomosis, as a result of a surgical complication, for disease control, or due to severe colonic, rectal, or perianal disease. The incidence of ostomy formation in CD has increased epidemiologically over time. The primary indication for ostomy formation is severe perianal fistulizing disease. However, while 64% of patients have an early clinical response after diversion for refractory perianal CD, restoration of bowel continuity is attempted in only 35% of patients, and is successful in only 17%. The current review discusses the indications for ostomy creation in complex CD, strategies for procedure selection, and patient outcomes.
Collapse
Affiliation(s)
- John P Burke
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.,Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland
| |
Collapse
|
|
10
|
Landerholm K, Wood C, Bloemendaal A, Buchs N, George B, Guy R. The rectal remnant after total colectomy for colitis - intra-operative,post-operative and longer-term considerations. Scand J Gastroenterol 2018; 53:1443-1452. [PMID: 30451043 DOI: 10.1080/00365521.2018.1529195] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Acute severe colitis requires surgery in around 30% of the cases. Total colectomy with ileostomy is the standard procedure with distinct advantages to a laparoscopic approach. Less agreement exists regarding the formation or configuration of the retained rectal stump and its short-term and long-term management. In this review, aspects of management of the rectal remnant, including perioperative considerations, potential complications, medical treatment, surveillance and implications for proctectomy and reconstructive surgery are explored. METHODS A thorough literature review exploring the PubMed and EMBASE databases was undertaken to clarify the evidence base surrounding areas of controversy in the surgical approach to acute severe colitis. In particular, focus was given to evidence surrounding management of the rectal remnant. RESULTS There is a paucity of high quality evidence for optimal management of the rectal stump following colectomy, and randomised trials are lacking. Establishment of laparoscopic colectomy has been associated with distinct advantages as well as the emergence of unique considerations, including those specific to rectal remnant management. CONCLUSIONS Early surgical involvement and a multidisciplinary approach to the management of acute severe colitis are advocated. Laparoscopic subtotal colectomy and ileostomy should be the operation of choice, with division of the rectum at the pelvic brim leaving a closed intraperitoneal remnant. If the rectum is severely inflamed, a mucus fistula may be useful, and an indwelling rectal catheter is probably advantageous to reduce the complications associated with stump dehiscence. Patients electing not to proceed to proctectomy should undergo surveillance for dysplasia of the rectum.
Collapse
Affiliation(s)
- Kalle Landerholm
- a Department of Colorectal Surgery , Oxford University Hospital NHS Foundation Trust , Oxford , UK
| | - Christopher Wood
- a Department of Colorectal Surgery , Oxford University Hospital NHS Foundation Trust , Oxford , UK
| | - Alexander Bloemendaal
- a Department of Colorectal Surgery , Oxford University Hospital NHS Foundation Trust , Oxford , UK
| | - Nicolas Buchs
- a Department of Colorectal Surgery , Oxford University Hospital NHS Foundation Trust , Oxford , UK
| | - Bruce George
- a Department of Colorectal Surgery , Oxford University Hospital NHS Foundation Trust , Oxford , UK
| | - Richard Guy
- a Department of Colorectal Surgery , Oxford University Hospital NHS Foundation Trust , Oxford , UK
| |
Collapse
|
|
11
|
Wang X, Shen B. Management of Crohn's Disease and Complications in Patients With Ostomies. Inflamm Bowel Dis 2018; 24:1167-1184. [PMID: 29722891 DOI: 10.1093/ibd/izy025] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Indexed: 12/13/2022]
Abstract
Fecal diversion with ostomy construction can be a temporary or definitive surgical measure for the treatment of refractory inflammatory bowel disease (IBD). However, the fecal diversion surgery is associated with various stoma, peristomal complications, and recurrence or occurrence of de novo small bowel Crohn's disease (CD). Stoma complications often need enterostomal therapy or surgical revision. Peristomal cutaneous lesions, such as pyoderma gangrenosum, usually require immunomodulator or biological therapy. Routine monitoring for occurrence or recurrence of CD with endoscopy or imaging should be performed, and prophylaxis with mesalamines, antibiotics, immunomodulators, or anti-TNFα or anti-integrin agents is needed for patients at risk. Those agents, along with corticosteroids, may also be used for the treatment of CD of the neo-small intestine, particularly inflammatory and fistulizing phenotypes. Endoscopic balloon dilation or endoscopic stricturotomy via stoma is safe and feasible to treat short (<4-5 cm), straight strictures in the neo-small intestine. Medically or endoscopically refractory fibrostenotic disease usually requires surgical intervention, with bowel-sparing stricturoplasty being the surgical treatment of choice.
Collapse
Affiliation(s)
- Xinying Wang
- Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Bo Shen
- Center for Inflammatory Bowel Diseases, Digestive Disease and Surgery Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
| |
Collapse
|
|
12
|
Amil-Dias J, Kolacek S, Turner D, Pærregaard A, Rintala R, Afzal NA, Karolewska-Bochenek K, Bronsky J, Chong S, Fell J, Hojsak I, Hugot JP, Koletzko S, Kumar D, Lazowska-Przeorek I, Lillehei C, Lionetti P, Martin-de-Carpi J, Pakarinen M, Ruemmele FM, Shaoul R, Spray C, Staiano A, Sugarman I, Wilson DC, Winter H, Kolho KL. Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr 2017; 64:818-835. [PMID: 28267075 DOI: 10.1097/mpg.0000000000001562] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.
Collapse
Affiliation(s)
- Jorge Amil-Dias
- *Department of Pediatrics, Centro Hospitalar, S. João, Porto, Portugal †Children's Hospital Zagreb, Faculty of Medicine, Zagreb, Croatia ‡The Juliet Keidan Institute of Pediatric Gastroenterology & Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel §Department of Pediatrics, Hvidovre University Hospital, Hvidovre, Denmark ||Pediatric Surgery, Children's Hospital, University of Helsinki, Helsinki, Finland ¶Department of Pediatric Gastroenterology, University Hospital Southampton, Southampton, UK #Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland **Department of Pediatrics, University Hospital Motol, Prague, Czech Republic ††Queen Mary's Hospital for Children, Epsom and St Helier NHS Trust, Surrey ‡‡Chelsea and Westminster Hospital, London, UK §§Paris-Diderot Sorbonne-Paris-Cité University and Robert Debré Hospital, Paris, France ||||Pediatric Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, Ludwig Maximilians-University, Munich, Germany ¶¶St George's, University of London, London, UK ##Boston Children's Hospital and Harvard Medical School, Boston, MA ***Department NEUROFARBA, University of Florence - Meyer Hospital, Florence, Italy †††Unit for the Comprehensive Care of Pediatric Inflammatory Bowel Disease, Hospital Sant Joan de Déu, Barcelona, Spain ‡‡‡Department of Pediatric Gastroenterology, Necker Enfants Malades University Hospital, Sorbonne Paris Cité University, Paris Descartes University, Institut IMAGINE - INSERM U1163, Paris, France §§§Pediatric Gastroenterology Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel ||||||Department of Pediatric Gastroenterology, Bristol Royal Hospital for Children, Bristol, UK ¶¶¶Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy ###Department of Pediatric Surgery, Leeds Children's Hospital, Leeds General Infirmary, Leeds, UK ****Child Life and Health, University of Edinburgh, Scotland, UK ††††MassGeneral Hospital for Children, Harvard Medical School, Boston, MA ‡‡‡‡Children's Hospital, University of Helsinki, Helsinki, Finland
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Abstract
Perianal Crohn’s disease affects a significant number of patients with Crohn’s disease and is associated with poor quality of life. The nature of the disease, compounded by presentation of various disease severities, has made the treatment of perianal Crohn’s disease difficult. The field continues to evolve with the use of both historical and contemporary solutions to address the challenges associated with it. The goal of this article is to review current literature regarding medical and surgical treatment, as well as the future directions of therapy.
Collapse
Affiliation(s)
- Katherine A Kelley
- Department of General Surgery, Division of Gastrointestinal and General Surgery, Oregon Health and Sciences University, Portland, OR, USA
| | - Taranjeet Kaur
- Department of General Surgery, Division of Gastrointestinal and General Surgery, Oregon Health and Sciences University, Portland, OR, USA
| | - Vassiliki L Tsikitis
- Department of General Surgery, Division of Gastrointestinal and General Surgery, Oregon Health and Sciences University, Portland, OR, USA
| |
Collapse
|
|
14
|
Subramanian S, Ekbom A, Rhodes JM. Recent advances in clinical practice: a systematic review of isolated colonic Crohn's disease: the third IBD? Gut 2017; 66:362-381. [PMID: 27802156 DOI: 10.1136/gutjnl-2016-312673] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 09/05/2016] [Accepted: 09/06/2016] [Indexed: 12/13/2022]
Abstract
The genetics of isolated colonic Crohn's disease place it approximately midway between Crohn's disease with small intestinal involvement and UC, making a case for considering it as a separate condition. We have therefore systematically reviewed its epidemiology, pathophysiology and treatment. Key findings include a higher incidence in females (65%) and older average age at presentation than Crohn's disease at other sites, a mucosa-associated microbiota between that found in ileal Crohn's disease and UC, no response to mesalazine, but possibly better response to antitumour necrosis factor than Crohn's disease at other sites. Diagnostic distinction from UC is often difficult and also needs to exclude other conditions including ischaemic colitis, segmental colitis associated with diverticular disease and tuberculosis. Future studies, particularly clinical trials, but also historical cohorts, should assess isolated colonic Crohn's disease separately.
Collapse
Affiliation(s)
- Sreedhar Subramanian
- Institute of Translational Medicine, University of Liverpool, The Henry Wellcome Laboratory, Liverpool, UK
| | - Anders Ekbom
- Department of Medicine, Karolinska Institute, Stockholm, Sweden
| | - Jonathan M Rhodes
- Institute of Translational Medicine, University of Liverpool, The Henry Wellcome Laboratory, Liverpool, UK
| |
Collapse
|
|
15
|
Neovaginal Sparing in a Transgender Woman With Ulcerative Colitis. Clin Gastroenterol Hepatol 2016; 14:e73-4. [PMID: 26780535 DOI: 10.1016/j.cgh.2016.01.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Revised: 12/30/2015] [Accepted: 01/05/2016] [Indexed: 02/07/2023]
|
|
16
|
Abstract
The gut microbiota influences essential human functions including digestion, energy metabolism, and inflammation by modulating multiple endocrine, neural, and immune pathways of the host. Its composition and complexity varies markedly across individuals and across different sites of the gut, but provides a certain level of resilience against external perturbation. Short-term antibiotic treatment is able to shift the gut microbiota to long-term alternative dysbiotic states, which may promote the development and aggravation of disease. Common features of post-antibiotic dysbiosis include a loss of taxonomic and functional diversity combined with reduced colonization resistance against invading pathogens, which harbors the danger of antimicrobial resistance. This review summarizes the antibiotic-related changes of the gut microbiota and potential consequences in health and disease.
Collapse
Affiliation(s)
- Kathleen Lange
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
| | | | | | | |
Collapse
|
|
17
|
Reshef L, Kovacs A, Ofer A, Yahav L, Maharshak N, Keren N, Konikoff FM, Tulchinsky H, Gophna U, Dotan I. Pouch Inflammation Is Associated With a Decrease in Specific Bacterial Taxa. Gastroenterology 2015; 149:718-27. [PMID: 26026389 DOI: 10.1053/j.gastro.2015.05.041] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Revised: 05/13/2015] [Accepted: 05/20/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Pouchitis is a common long-term complication in patients with ulcerative colitis (UC) undergoing proctocolectomy with ileal pouch-anal anastomosis. Because the inflammation occurs in a previously normal small bowel, studies of this process might provide information about the development of Crohn's disease. Little is known about the intestinal microbiome of patients with pouchitis. We investigated whether specific bacterial populations correlate with the pouch disease phenotype and inflammatory activity. METHODS We performed a prospective study of patients with UC who underwent pouch surgery (N = 131) from 1981 through 2012 and were followed at Tel Aviv Medical Center. Patients were assigned to groups based on their degree and type of pouch inflammation. Patients with familial adenomatous polyposis after pouch surgery (n = 9), individuals with intact colons undergoing surveillance colonoscopy (n = 10), and patients with UC who did not undergo surgery (n = 9) served as controls. We collected demographic and disease activity data (based on the Pouchitis Disease Activity Index) and measured levels of C-reactive protein. Fecal samples were collected, levels of calprotectin were measured, and microbiota were analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. RESULTS Increased proportions of the Fusobacteriaceae family correlated with increased disease activity and levels of C-reactive protein in patients with UC who underwent pouch surgery. In contrast, proportions of Faecalibacterium were reduced in patients with pouchitis vs controls; there was a negative correlation between proportion of Faecalibacterium and level of C-reactive protein. There was an association between antibiotic treatment, but not biologic or immunomodulatory therapy, with reduced proportions of 11 genera and with increased proportions of Enterococcus and Enterobacteriaceae. CONCLUSIONS Reductions in protective bacteria and increases in inflammatory bacteria are associated with pouch inflammation in patients with UC who underwent pouch surgery. The finding that antibiotics exacerbate dysbiosis indicates that these drugs might not provide long-term benefit for patients with pouchitis. Additional studies of this form of dysbiosis could provide information about the pathogenesis of Crohn's disease.
Collapse
Affiliation(s)
- Leah Reshef
- Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Amir Kovacs
- Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Amos Ofer
- IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Lior Yahav
- IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Nitsan Maharshak
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Nirit Keren
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology and Hepatology, Meir Medical Center, Kfar Saba, Israel
| | - Fred M Konikoff
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology and Hepatology, Meir Medical Center, Kfar Saba, Israel
| | - Hagit Tulchinsky
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Colorectal Unit, Department of Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Uri Gophna
- Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
| | - Iris Dotan
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel.
| |
Collapse
|
|
18
|
|
|
19
|
Mege D, Bege T, Beyer-Berjot L, Loundou A, Grimaud JC, Brunet C, Berdah S. Does faecal diversion prevent morbidity after ileocecal resection for Crohn's disease? Retrospective series of 80 cases. ANZ J Surg 2015; 87:E74-E79. [PMID: 25780907 DOI: 10.1111/ans.13034] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND After ileocecal resection for Crohn's disease, a temporary faecal diversion is indicated in high-risk patients. The impact of a temporary stoma on post-operative morbidity has been poorly assessed so far. The aim was to analyse post-operative morbidity of temporary faecal diversion after ileocecal resection for Crohn's disease. METHODS Patients undergoing temporary faecal diversion combined with ileocecal resection were retrospectively included. Patients presenting with complications were compared with patients with an uneventful post-operative course, to identify any predictive factor for morbidity. RESULTS Eighty faecal diversions were performed (43 males, 33.5 (18-75) years), including 63 split stoma (79%) and 17 covering loop ileostomies (21%). Fifty-two patients (65%) presented with a perforating disease. Post-operative complications occurred in 15 patients (19%), 15 days after surgery (1-30). The main complications were intra-abdominal abscess (n = 6), functional renal failure (n = 6), fistula (n = 2) and stomal prolapse (n = 2). Two patients required surgery. Previous bowel resections (60% versus 28%, P = 0.01) were significantly associated with post-operative morbidity. CONCLUSIONS Temporary faecal diversion is useful in high-risk patients after ileocecal resection for Crohn's disease. Patients' information about post-operative risks remains an important issue. Risk factors for post-operative morbidity despite faecal diversion are previous bowel resections.
Collapse
Affiliation(s)
- Diane Mege
- Department of Digestive Surgery, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Université de la Méditerranée, Marseille, France
| | - Thierry Bege
- Department of Digestive Surgery, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Université de la Méditerranée, Marseille, France.,Laboratory of Biomechanics and Applications UMRT24, Marseille, France
| | - Laura Beyer-Berjot
- Department of Digestive Surgery, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Université de la Méditerranée, Marseille, France
| | - Anderson Loundou
- Department of Public Health, Medicine University, Marseille, France
| | - Jean-Charles Grimaud
- Department of Gastroenterology, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Université de la Méditerranée, Marseille, France
| | - Christian Brunet
- Department of Digestive Surgery, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Université de la Méditerranée, Marseille, France.,Laboratory of Biomechanics and Applications UMRT24, Marseille, France
| | - Stéphane Berdah
- Department of Digestive Surgery, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Université de la Méditerranée, Marseille, France.,Laboratory of Biomechanics and Applications UMRT24, Marseille, France
| |
Collapse
|
|
20
|
Temporary fecal diversion in the management of colorectal and perianal Crohn's disease. Gastroenterol Res Pract 2015; 2015:286315. [PMID: 25649893 PMCID: PMC4305613 DOI: 10.1155/2015/286315] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Revised: 12/20/2014] [Accepted: 12/20/2014] [Indexed: 11/26/2022] Open
Abstract
Aim. To evaluate the results of temporary fecal diversion in colorectal and perianal Crohn's disease. Method. We retrospectively identified 29 consecutive patients (14 females, 15 males; median age: 30.0 years, range: 18–76) undergoing temporary fecal diversion for colorectal (n = 14), ileal (n = 4), and/or perianal Crohn's disease (n = 22). Follow-up was in median 33.0 (3–103) months. Response to fecal diversion, rate of stoma reversal, and relapse rate after stoma reversal were recorded. Results. The response to temporary fecal diversion was complete remission in 4/29 (13.8%), partial remission in 12/29 (41.4%), no change in 7/29 (24.1%), and progress in 6/29 (20.7%). Stoma reversal was performed in 19 out of 25 patients (76%) available for follow-up. Of these, the majority (15/19, 78.9%) needed further surgical therapies for a relapse of the same pathology previously leading to temporary fecal diversion, including colorectal resections (10/19, 52.6%) and creation of a definitive stoma (7/19, 36.8%). At the end of follow-up, only 4/25 patients (16%) had a stable course without the need for further definitive surgery. Conclusion. Temporary fecal diversion can induce remission in otherwise refractory colorectal or perianal Crohn's disease, but the chance of enduring remission after stoma reversal is low.
Collapse
|
|
21
|
Reprint of: Musculoskeletal system in the old age and the demand for healthy ageing biomarkers. Mech Ageing Dev 2014; 136-137:94-100. [PMID: 24662191 DOI: 10.1016/j.mad.2014.03.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Population ageing has emerged as a major demographic trend worldwide due to improved health and longevity. This global ageing phenomenon will have a major impact on health-care systems worldwide due to increased morbidity and greater needs for hospitalization/institutionalization. As the ageing population increases worldwide, there is an increasing awareness not only of increased longevity but also of the importance of "healthy ageing" and "quality of life". Yet, the age related chronic inflammation is believed to be pathogenic with regards to its contribution to frailty and degenerative disorders. In particular, the frailty syndrome is increasingly being considered as a key risk indicator of adverse health outcomes. In addition, elderly may be also prone to be resistant to anabolic stimuli which is likely a key factor in the loss of skeletal muscle mass with ageing. Vital to understand these key biological processes is the development of biological markers, through system biology approaches, aiding at strategies for tailored therapeutic and personalized nutritional program. Overall aim is to prevent or attenuate decline of key physiological functions required to live an active, independent life. This review focus on core indicators of health and functions in older adults, where nutrition and tailored personalized programs could exhibit preventive roles, and where the aid of metabolomics technologies are increasingly displaying potential in revealing key molecular mechanisms/targets linked to specific ageing and/or healthy ageing processes.
Collapse
|
|
22
|
Musculoskeletal system in the old age and the demand for healthy ageing biomarkers. Mech Ageing Dev 2013; 134:541-7. [DOI: 10.1016/j.mad.2013.11.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Revised: 10/24/2013] [Accepted: 11/11/2013] [Indexed: 12/19/2022]
|
|
23
|
Flanagan PK, Campbell BJ, Rhodes JM. Lessons from diversion studies and antibacterial interventions. Dig Dis 2012; 30:347-50. [PMID: 22796795 DOI: 10.1159/000338122] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
If bacteria cause IBD, then it should be possible to target the bacteria with therapies and cure or at least treat the disease. Discovery of a successful intervention, unless found by chance, will depend on knowing more about which bacteria are involved, where they are and how to remove them. Some evidence for the possible role of bacteria has come from in vivo studies of the effects of diverting the faecal stream away from sites of IBD. Alternative hypotheses arise from the diversion studies that could incriminate other components of the faecal stream that include bile acids and dietary components. Antibiotics will only really be adequately tested when we know what the target bacteria are and where they are, e.g. whether in the lumen or mucosa and whether intracellular or extracellular. Some encouraging responses have been observed, however, with empirical antibiotic therapy.
Collapse
|
|
24
|
Martin FPJ, Collino S, Rezzi S, Kochhar S. Metabolomic applications to decipher gut microbial metabolic influence in health and disease. Front Physiol 2012; 3:113. [PMID: 22557976 PMCID: PMC3337463 DOI: 10.3389/fphys.2012.00113] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2011] [Accepted: 04/05/2012] [Indexed: 12/22/2022] Open
Abstract
Dietary preferences and nutrients composition have been shown to influence human and gut microbial metabolism, which ultimately has specific effects on health and diseases’ risk. Increasingly, results from molecular biology and microbiology demonstrate the key role of the gut microbiota metabolic interface to the overall mammalian host’s health status. There is therefore raising interest in nutrition research to characterize the molecular foundations of the gut microbial–mammalian cross talk at both physiological and biochemical pathway levels. Tackling these challenges can be achieved through systems biology approaches, such as metabolomics, to underpin the highly complex metabolic exchanges between diverse biological compartments, including organs, systemic biofluids, and microbial symbionts. By the development of specific biomarkers for prediction of health and disease, metabolomics is increasingly used in clinical applications as regard to disease etiology, diagnostic stratification, and potentially mechanism of action of therapeutical and nutraceutical solutions. Surprisingly, an increasing number of metabolomics investigations in pre-clinical and clinical studies based on proton nuclear magnetic resonance (1H NMR) spectroscopy and mass spectrometry provided compelling evidence that system wide and organ-specific biochemical processes are under the influence of gut microbial metabolism. This review aims at describing recent applications of metabolomics in clinical fields where main objective is to discern the biochemical mechanisms under the influence of the gut microbiota, with insight into gastrointestinal health and diseases diagnostics and improvement of homeostasis metabolic regulation.
Collapse
Affiliation(s)
- François-Pierre J Martin
- Metabolomics and Biomarkers, Department of BioAnalytical Science, Nestlé Research Center, Nestec Ltd. Lausanne, Switzerland
| | | | | | | |
Collapse
|
|
25
|
Myrelid P, Söderholm JD, Olaison G, Sjödahl R, Andersson P. Split stoma in resectional surgery of high-risk patients with ileocolonic Crohn's disease. Colorectal Dis 2012; 14:188-93. [PMID: 21689286 DOI: 10.1111/j.1463-1318.2011.02578.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIM The aim of this retrospective study of ileocolonic resection in patients with Crohn's disease was to compare the outcome of primary anastomosis with that of split stoma and delayed anastomosis in a high-risk setting. METHOD From 1995 to 2006, 132 patients had 146 operations for ileocolonic Crohn's disease. Preoperative data, including risk factors for complications, were obtained from a prospectively registered database. Operations on patients who had two or more preoperative risk factors (n = 76) were considered to be high-risk operations and formed the main study. Primary outcome variables were postoperative anastomotic complications and the alteration in the number of preoperative risk factors achieved by a delayed anastomosis. Secondary outcome was time in hospital and the number of operations performed. RESULTS Early anastomotic complications were diagnosed in 19% (11/57) of patients receiving a primary anastomosis compared with 0% (0/19) of patients after a delayed anastomosis (P = 0.038). The mean number of risk factors in the split stoma group was 3.5 at the time of resection and 0.2 when the split stoma was reversed (P < 0.0001). The total number of operations was 1.9 ± 1.5 (mean ± SD) after a primary anastomosis and 2.0 ± 0.2 after a split stoma (P = 0.70). Total in-hospital time for all operations was 20.9 ± 35.6 days after a primary anastomosis and 17.8 ± 10.4 days after a delayed anastomosis (P = 0.74). CONCLUSION Delayed anastomosis after ileocolonic resection in high-risk Crohn's disease patients was associated with a reduction in the number of preoperative risk factors and fewer anastomotic complications. Hospital stay and number of operations were similar after delayed and primary anastomosis in high-risk patients.
Collapse
Affiliation(s)
- P Myrelid
- Division of Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
| | | | | | | | | |
Collapse
|
|
26
|
Free colonic perforation in a patient with Crohn's disease and loop ileostomy: report of a case. Int Surg 2011; 96:159-61. [PMID: 22026309 DOI: 10.9738/1388.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Free bowel perforation in Crohn's disease is a relatively rare complication. In this report, we present a case of free colonic perforation in a Crohn's disease patient with loop ileostomy previously constructed for intractable perianal abscess. Normally, fecal diversion by ileostomy results in an improvement in Crohn's colitis. However, in some cases, fecal diversion is reported to adversely affect the inflammation of the diverted bowel, and it is this unusual complication of Crohn's disease that we discuss here.
Collapse
|
|
27
|
Martin FPJ, Rezzi S, Philippe D, Tornier L, Messlik A, Hölzlwimmer G, Baur P, Quintanilla-Fend L, Loh G, Blaut M, Blum S, Kochhar S, Haller D. Metabolic assessment of gradual development of moderate experimental colitis in IL-10 deficient mice. J Proteome Res 2009; 8:2376-87. [PMID: 19323467 DOI: 10.1021/pr801006e] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Evidence has linked genetic predisposition and environmental exposures to the worldwide pandemic of inflammatory bowel diseases (IBD), but underlying biochemical events remain largely undefined. Here, we studied the gradual development of colitis in Interleukin 10 deficient mice using a combination of (i) histopathological analysis of intestinal sections, (ii) metabolic profiling of blood plasma, and (iii) measurement of plasma inflammatory biomarkers. Data integration using chemometric tools, including Independent Component Analysis, provided a new strategy for measuring and mapping the metabolic effects associated with the development of intestinal inflammation at the age of 1, 8, 16, and 24 weeks. Chronic inflammation appeared at 8 weeks and onward, and was associated with altered cecum and colon morphologies and increased inflammatory cell infiltration into the mucosa and the submucosa. Blood plasma profiles provided additional evidence of loss of energy homeostasis, impaired metabolism of lipoproteins and glycosylated proteins. In particular, IL-10-/-mice were characterized by decreased levels of VLDL and increased concentrations of LDL and polyunsaturated fatty acids, which are related to the etiology of IBD. Moreover, higher levels of lactate, pyruvate, citrate and lowered glucose suggested increased fatty acid oxidation and glycolysis, while higher levels of free amino acids reflected muscle atrophy, breakdown of proteins and interconversions of amino acids to produce energy. These integrated system investigations demonstrate the potential of metabonomics for investigating the mechanistic basis of IBD, and it will provide novel avenues for management of IBD.
Collapse
|
|
28
|
Salzman NH, Bevins CL. Negative interactions with the microbiota: IBD. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2009; 635:67-78. [PMID: 18841704 DOI: 10.1007/978-0-387-09550-9_6] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Mucosal surfaces are colonized by a complex microbiota that provides beneficial functions under normal physiological conditions, but is capable of contributing to chronic inflammatory disease in susceptible individuals. Of the mucosal tissues, the mammalian intestine harbors an especially high number of microbes with a remarkable diversity. Inflammatory bowel disease (IBD) is a group of chronic relapsinginflammatory disorders of the intestinal mucosa. Evidence from human studies and animal models provides compelling support that intestinal microbes play a key role in disease pathogenesis. While the existence a specific causative pathogen is possible, it appears more likely that intestinal microbes normally present as commensal microbiota may trigger inflammation and perpetuate disease in genetically susceptible individuals. There may be also a shift in the makeup of the commensal flora to a nonphysiologic composition that is more prone to disease (termed dysbiosis). Evidence supports that genetic susceptibility stems from one or more defects in mucosal immune functions, including microbe recognition, barrier function, intercellular communication and antimicrobial effector mechanisms. It is quite plausible to imagine that the chronic inflammation of IBD may in some cases be a normal immune response to an abnormal adherent invasive microbiota and in other cases an over exuberant immune response to an otherwise normal commensal microbiota.
Collapse
Affiliation(s)
- Nita H Salzman
- Department of Pediatrics, Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, WI, USA
| | | |
Collapse
|
|
29
|
Olbe L. Concept of Crohn's disease being conditioned by four main components, and irritable bowel syndrome being an incomplete Crohn's disease. Scand J Gastroenterol 2008; 43:234-41. [PMID: 17918000 DOI: 10.1080/00365520701676971] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Several mechanisms have been proposed for the development of Crohn's disease. Evidence in favour of a unifying 4-component concept to explain the development of Crohn's disease is presented. The four components are a genetic predisposition to an increased intestinal permeability, the key and initial triggering factor being an oral-pharyngeal bacterium that increases the mucosal permeability of the small intestine with only a minimal inflammatory reaction, an adherent-invasive strain of Escherichia coli that penetrates the mucosa and causes an acute inflammatory reaction in the intestinal wall, and finally a secondary invasion of bacteria causing the chronic inflammatory characteristics. Irritable bowel syndrome (IBS) is a functional bowel disorder with intermittent symptoms of varying intensity. Clinically, there is evidence to suggest a link between IBS patients with diarrhoea and patients with Crohn's disease. The common denominator and initial trigger for IBS with diarrhoea and Crohn's disease seems to be an increased small intestinal permeability, probably caused by an oral-pharyngeal bacterial strain. The important missing factor in IBS patients seems to be the adherent-invasive strain of E. coli in the proximal colon, causing the acute inflammatory process in patients with Crohn's disease. IBS with diarrhoea can then be looked upon as an incomplete Crohn's disease.
Collapse
Affiliation(s)
- Lars Olbe
- Department of Gastrosurgical Research, Sahlgrenska University Hospital, Gothenburg, Sweden.
| |
Collapse
|
|
30
|
Abstract
Ulcerative colitis (UC) is a relapsing and remitting disease characterised by chronic mucosal and submucosal inflammation of the colon and rectum. Treatment may vary depending upon the extent and severity of inflammation. Broadly speaking medical treatments aim to induce and then maintain remission. Surgery is indicated for inflammatory disease that is refractory to medical treatment or in cases of neoplastic transformation. Approximately 25% of patients with UC ultimately require colectomy. Ileal pouch-anal anastomosis (IPAA) has become the standard of care for patients with ulcerative colitis who ultimately require colectomy. This review will examine indications for IPAA, patient selection, technical aspects of surgery, management of complications and long term outcome following this procedure.
Collapse
Affiliation(s)
- Simon P Bach
- Nuffield Department of Surgery, University of Oxford, United Kingdom.
| | | |
Collapse
|
|
31
|
Salzman NH, Underwood MA, Bevins CL. Paneth cells, defensins, and the commensal microbiota: A hypothesis on intimate interplay at the intestinal mucosa. Semin Immunol 2007; 19:70-83. [PMID: 17485224 DOI: 10.1016/j.smim.2007.04.002] [Citation(s) in RCA: 272] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2007] [Accepted: 04/16/2007] [Indexed: 02/06/2023]
Abstract
Mucosal surfaces are colonized by a diverse and dynamic microbiota. Much investigation has focused on bacterial colonization of the intestine, home to the vast majority of this microbiota. Experimental evidence has highlighted that these colonizing microbes are essential to host development and homeostasis, but less is known about host factors that may regulate the composition of this ecosystem. While evidence shows that IgA has a role in shaping this microbiota, it is likely that effector molecules of the innate immune system are also involved. One hypothesis is that gene-encoded antimicrobial peptides, key elements of innate immunity throughout nature, have an essential role in this regulation. These effector molecules characteristically have activity against a broad spectrum of bacteria and other microbes. At mucosal surfaces, antimicrobial peptides may affect the numbers and/or composition of the colonizing microbiota. In humans and other mammals, defensins are a predominant class of antimicrobial peptides. In the small intestine, Paneth cells (specialized secretory epithelial cells) produce high quantities of defensins and several other antibiotic peptides and proteins. Data from murine models indicate that Paneth cell defensins play a pivotal role in defense from food and water-borne pathogens in the intestinal lumen. Recent studies in humans provide evidence that reduced Paneth cell defensin expression may be a key pathogenic factor in ileal Crohn's disease, a subgroup of inflammatory bowel disease (IBD), and changes in the colonizing microbiota may mediate this pathogenic mechanism. It is also possible that low levels of Paneth cell defensins, characteristic of normal intestinal development, may predispose premature neonates to necrotizing enterocolitis (NEC) through similar close links with the composition of the intestinal microbiota. Future studies to further define mechanisms by which defensins and other host factors regulate the composition of the intestinal microbiota will likely provide new insights into intestinal homeostasis and new therapeutic strategies for inflammatory and infectious diseases of the bowel.
Collapse
Affiliation(s)
- Nita H Salzman
- Department of Pediatrics, Division of Gastroenterology, The Medical College of Wisconsin, 8701 Watertown Plank Rd. Milwaukee, WI 53226, USA
| | | | | |
Collapse
|
|
32
|
Spivak J, Landers CJ, Vasiliauskas EA, Abreu MT, Dubinsky MC, Papadakis KA, Ippoliti A, Targan SR, Fleshner PR. Antibodies to I2 predict clinical response to fecal diversion in Crohn's disease. Inflamm Bowel Dis 2006; 12:1122-30. [PMID: 17119386 DOI: 10.1097/01.mib.0000235833.47423.d7] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES Fecal diversion is occasionally indicated in patients with advanced perianal or colorectal Crohn's disease (CD). Because CD may result from an aberrant immunologic response to bacteria within the gut lumen, fecal diversion should be effective in managing these complications. However, not all patients achieve a clinical response after fecal diversion. CD patients can be characterized by their antibody responses against Pseudomonas fluorescens (I2), E.coli outer membrane porin C (OmpC), oligomannan (anti-Saccharomyces cerevisiae antibodies [ASCA]), and antinuclear antigens (perinuclear antineutrophil cytoplasmic antibodies [pANCA]). This study examines the association between clinical features and seroreactivity to these microbial and auto-antigens in predicting a clinical response to fecal diversion. METHODS Twenty-seven consecutive CD patients undergoing fecal diversion were included. Sera were drawn and tested for anti-I2, anti-OmpC, ASCA, and pANCA in a blinded fashion. Response was assessed using clinical parameters. RESULTS Seventeen (63%) patients underwent fecal diversion for medically resistant proctocolitis and 10 (37%) for severe perianal disease. Median follow-up was 41 months. Seventeen (63%) patients achieved a clinical response. No preoperative clinical or surgical factor predicted response to diversion. Clinical response after fecal diversion was seen in 15 of 16 (94%) patients who were I2 positive compared with only 2 of 11 (18%) patients who were I2 negative (P = 0.0001). Seroreactivity to OmpC, ASCA, or pANCA was not associated with a clinical response to diversion. CONCLUSION Expression of I2 antibodies against a bacterial antigen of Pseudomonas fluorescens was highly associated with clinical response to fecal diversion in CD patients.
Collapse
Affiliation(s)
- Jacob Spivak
- Division of Colon and Rectal Surgery, Department of Surgery, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Kucharzik T, Maaser C, Lügering A, Kagnoff M, Mayer L, Targan S, Domschke W. Recent understanding of IBD pathogenesis: implications for future therapies. Inflamm Bowel Dis 2006; 12:1068-83. [PMID: 17075348 DOI: 10.1097/01.mib.0000235827.21778.d5] [Citation(s) in RCA: 162] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The inflammatory bowel diseases (IBD) are comprised of two major phenotypes, Crohn's disease (CD) and ulcerative colitis (UC). Research over the last couple of years has led to great advances in understanding the inflammatory bowel diseases and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses to a subset of luminal bacteria. Susceptibility to disease is thereby determined by genes encoding immune responses which are triggered by environmental stimuli. Based on extensive research over the last decade, there are several new and novel pathways and specific targets on which to focus new therapeutics. The following review summarizes the current view on the four basic tenets of the pathophysiological basis of IBD and its implications for therapies of IBD: genetics, immune dysregulation, barrier dysfunction and the role of the microbial flora.
Collapse
|
|
34
|
Fukuda Y, Tao Y, Tomita T, Hori K, Fukunaga K, Noguchi T, Hayashi T, Shimoyama T, Tahahashi R. A traditional Japanese medicine mitigates TNBS-induced colitis in rats. Scand J Gastroenterol 2006; 41:1183-9. [PMID: 16990203 DOI: 10.1080/00365520600575704] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Differences in dietary habits may be one of the reasons that the incidence of inflammatory bowel disease has remained lower in Japan than in Western countries. We investigated whether a traditional Japanese medicine (Strong Wakamto), based on Aspergillus oryzae koji, would exert any effect on experimental colitis in rats. MATERIAL AND METHODS Colitis was induced using an enema of trinitrobenzene sulfonic acid (TNBS) and ethanol. Strong Wakamto was administered for 28 days before induction of colitis and for 7 days thereafter, and the effect of this medicine was evaluated. RESULTS Treatment with 5% Strong Wakamto improved loss of body-weight, increased colon weight and significantly decreased the histological damage score for colon mucosa. Decreases in faecal Lactobacillus sp., superoxide dismutase activity and zinc concentrations, and the increased IL-1beta expression in colonic tissue after TNBS enema were improved when Strong Wakamto was given. The present in vitro studies indicate that administration of Strong Wakamto prevents lipopolysaccharide-induced TNF-alpha production in human macrophages. CONCLUSIONS Oral administration of Strong Wakamto mitigates experimental inflammatory bowel disease induced by TNBS enema in rats. The beneficial effects seem attributable to a combination of balancing microflora, immunomodulatory effects on gut macrophages, and enhancement of anti-superoxide activity in colonic tissues.
Collapse
Affiliation(s)
- Yoshihiro Fukuda
- Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Larson DW, Wolff BG. Colectomy for Crohn’s Disease, What Operation? SEMINARS IN COLON AND RECTAL SURGERY 2006. [DOI: 10.1053/j.scrs.2006.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
|
|
36
|
Abstract
Ileal pouch-anal anastomosis (IPAA) has become the standard of care for the 25% of patients with ulcerative colitis who ultimately require colectomy. IPAA is favored by patients because it avoids the necessity for a long-term stoma. This review examines how 3 decades of experience with IPAA has molded current practice, highlighting 5- and 10-year follow-up of large series to determine durability and functional performance, in addition to causes of failure and the management of complications.
Collapse
Affiliation(s)
- Simon P Bach
- Nuffield Department of Surgery, University of Oxford and the Department of Colorectal Surgery, John Radcliffe Hospital, Oxford, United Kingdom.
| | | |
Collapse
|
|
37
|
Magee EA, Edmond LM, Tasker SM, Kong SC, Curno R, Cummings JH. Associations between diet and disease activity in ulcerative colitis patients using a novel method of data analysis. Nutr J 2005; 4:7. [PMID: 15705205 PMCID: PMC549081 DOI: 10.1186/1475-2891-4-7] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2004] [Accepted: 02/10/2005] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The relapsing nature and varying geographical prevalence of ulcerative colitis (UC) implicates environmental factors such as diet in its aetiology. METHODS In order to determine which foods might be related to disease activity in UC a new method of dietary analysis was developed and applied. Eighty-one UC patients were recruited at all stages of the disease process. Following completion of a 7 d diet diary, clinical assessment including a sigmoidoscopic examination (scale 0 (normal mucosa) to 6 (very active disease)) was conducted. Food weights for each person were adjusted (divided) by the person's calorific intake for the week. Each food consumed was given a food sigmoidoscopy score (FSS) calculated by summing the products of the (adjusted) weight of food consumed and sigmoidoscopy score for each patient and occurrence of food and dividing by the total (adjusted) weight of the food consumed by all 81 patients. Thus, foods eaten in large quantities by patients with very active disease have high FSSs and vice versa. Foods consumed by <10 people or weighing <1 kg for the whole group were excluded, leaving 75 foods. RESULTS High FSS foods were characterized by high levels of the anti-thiamin additive sulfite (Mann-Whitney, p < 0.001), i.e. bitter, white wine, burgers, soft drinks from concentrates, sausages, lager and red wine. Caffeine also has anti-thiamin properties and decaffeinated coffee was associated with a better clinical state than the caffeine containing version. Beneficial foods (average intake per week) included pork (210 g), breakfast cereals (200 g), lettuce (110 g), apples and pears (390 g), milk (1250 ml), melon (350 g), bananas (350 g), bacon (120 g), beef and beef products (500 g), tomatoes (240 g), soup (700 g), citrus fruits (300 g), fish (290 g), yogurt (410 g), cheese (110 g), potatoes (710 g) and legumes (120 g). CONCLUSIONS The dietary analysis method described provides a new tool for establishing relationships between diet and disease and indicates a potentially therapeutic diet for UC.
Collapse
Affiliation(s)
- Elizabeth A Magee
- Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK
| | - Laurie M Edmond
- Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK
| | - Shiona M Tasker
- Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK
| | - San Choon Kong
- Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK
| | - Richard Curno
- Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK
| | - John H Cummings
- Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK
| |
Collapse
|
|
38
|
Champault A, Benoist S, Alvès A, Panis Y. [Surgical therapy for Crohn's disease of the colon and rectum]. GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE 2004; 28:882-92. [PMID: 15523226 DOI: 10.1016/s0399-8320(04)95153-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/01/2023]
Affiliation(s)
- Axèle Champault
- Service de Chirurgie Digestive, Hôpital Lariboisière, 2, Rue Ambroise Paré, 75475 Paris Cedex 10, France
| | | | | | | |
Collapse
|
|
39
|
Endoscopic evaluation of postoperative recurrence in the patient with Crohn’s disease. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2004. [DOI: 10.1016/j.tgie.2004.09.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
|
|
40
|
Murillo LS, Morré SA, Peña AS. Role of the CARD15 gene in the pathogenesis of Crohn disease: phenotypic classification and prognostic implications. Scand J Gastroenterol 2003; 38:1107-14. [PMID: 14686713 DOI: 10.1080/00365520310005703] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- L S Murillo
- VU University Medical Centre, Department of Gastroenterology, Laboratory of Immunogenetics, Amsterdam, The Netherlands
| | | | | |
Collapse
|
|
41
|
Ogawa H, Fukushima K, Naito H, Funayama Y, Unno M, Takahashi KI, Kitayama T, Matsuno S, Ohtani H, Takasawa S, Okamoto H, Sasaki I. Increased expression of HIP/PAP and regenerating gene III in human inflammatory bowel disease and a murine bacterial reconstitution model. Inflamm Bowel Dis 2003; 9:162-70. [PMID: 12792221 DOI: 10.1097/00054725-200305000-00003] [Citation(s) in RCA: 126] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Although microorganisms play a role in gut inflammation, it remains uncertain which epithelial genes are expressed in response to luminal flora and whether these molecules are also involved in pathologic mucosal inflammation. Germ-free mice were orally challenged with a bacterial suspension prepared from conventionally housed mice (bacterial reconstitution). Thereafter, the differential gene expression in gut epithelial cells was identified by differential display. The expression of the identified genes was also examined in dextran sulfate sodium (DSS)-induced colitis and human inflammatory bowel disease (IBD) epithelial cells. Regenerating gene III (Reg III) was strongly induced in gut epithelial cells following bacterial reconstitution, as well as in the colitis initiated by DSS. The mRNA expression of hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP), a human counterpart of Reg III, was enhanced in colonic epithelial cells of patients with IBD. Reg III mRNA expression was localized in the epithelial cells including goblet cells and columnar cells in mice; on the other hand, HIP/PAP-expressing cells were correlated with Paneth cell metaplasia in human colon. Epithelial expression of Reg III or HIP/PAP was induced under mucosal inflammation initiated by exposure to commensal bacteria or DSS as well as inflamed IBD colon.
Collapse
Affiliation(s)
- Hitoshi Ogawa
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Abstract
The normal intestinal flora and the mucosal immune system exist in close spatial proximity. A normal structure and function of both very complex systems is required for health and develops in a constant and interactive process. An abnormal host response to the normal intestinal flora leads to chronic intestinal inflammation. Probiotic bacteria may modulate the intestinal flora and the mucosal immune response and are an effective therapy for remission maintenance of ulcerative colitis and pouchitis.
Collapse
Affiliation(s)
- Frank Heller
- Medizinische Klinik I, Universitätsklinikum Benjamin Franklin, FU-Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany
| | | |
Collapse
|
|
43
|
Wehkamp J, Fellermann K, Herrlinger KR, Baxmann S, Schmidt K, Schwind B, Duchrow M, Wohlschläger C, Feller AC, Stange EF. Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease. Eur J Gastroenterol Hepatol 2002; 14:745-52. [PMID: 12169983 DOI: 10.1097/00042737-200207000-00006] [Citation(s) in RCA: 148] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE Various antimicrobial peptides such as defensins are part of innate immunity and contribute to the intestinal barrier that may be defective in inflammatory bowel disease (IBD). This study investigated beta-defensin mRNA and peptide expression in the colon from controls and patients with Crohn's disease, ulcerative colitis or unspecific colitis as inflammatory controls. METHODS Mucosal mRNA expression was measured by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) with primers for human beta-defensin 1 (HBD-1) and human beta-defensin 2 (HBD-2) in CaCo-2 cells and in biopsies from 103 patients (33 controls, 24 Crohn's disease patients, 36 ulcerative colitis patients, 10 unspecific colitis patients). Paraffin-embedded tissue from colonic resections was tested for HBD-1 and HBD-2 peptides by immunohistochemistry. RESULTS HBD-1 mRNA was expressed constitutively whereas HBD-2 was induced by pro-inflammatory cytokines in CaCo-2 cells. HBD-1 mRNA was detectable in 61% of control and Crohn's disease biopsies and 53% of ulcerative colitis biopsies. HBD-2 transcript was expressed differentially, with 18% of control biopsies positive as opposed to 34% in Crohn's disease and 53% in ulcerative colitis. HBD-2 mRNA but not HBD-1 mRNA was expressed preferentially in inflamed areas. Immunohistochemical investigation demonstrated the presence of defensin peptides in colonic epithelium as well as the differential induction in IBD. CONCLUSIONS HBD-1 is expressed constitutively in colonic tissue irrespective of inflammation. HBD-2 is barely present in uninflamed colon but it is induced in inflammation. The lower expression of HBD-2 in Crohn's disease compared with ulcerative colitis indicates different responses of the mucosal innate defence. Defensins may play a crucial role in controlling pathogen invasion in IBD, although the functional significance remains to be established.
Collapse
Affiliation(s)
- Jan Wehkamp
- Department of Internal Medicine I, Division of Gastroenterology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Wehkamp J, Schwind B, Herrlinger KR, Baxmann S, Schmidt K, Duchrow M, Wohlschläger C, Feller AC, Stange EF, Fellermann K. Innate immunity and colonic inflammation: enhanced expression of epithelial alpha-defensins. Dig Dis Sci 2002; 47:1349-55. [PMID: 12064812 DOI: 10.1023/a:1015334917273] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Human alpha-defensins contribute to local intestinal host defense as part of innate immunity and may be of major relevance in microbial infection and chronic inflammatory bowel disease. The objective was to investigate human defensin 5 and 6 (HD-5, HD-6) mRNA expression by RT-PCR from colonic biopsies and peptide expression by immunohistochemistry from colonic resections under basal and inflammatory conditions. Both alpha-defensins were induced by proinflammatory cytokines in cell culture. HD-5 mRNA expression was enhanced in both idiopathic and nonidiopathic inflammatory states of the large bowel [32% of control vs 73% of unspecific colitis, 69% of Crohn's disease (CD) and 73% of ulcerative colitis (UC)], whereas HD-6 was specifically related to CD and UC (14% in controls vs 20% in unspecific coltis, 49% in CD and 42% in UC). Immunohistochemistry confirmed the presence of HD-5 in colonic epithelium. Antimicrobial peptides in the colon may be of importance in maintaining the mucosal barrier and controlling microbial invasion in inflammatory bowel diseases.
Collapse
Affiliation(s)
- J Wehkamp
- Department of Internal Medicine I, University of Lübeck, Germany
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Abstract
The surgical treatment of Crohn's disease of the colon is distinct from that used in treating ulcerative colitis. Crohn's disease often involves the small bowel and is not "cured" by colorectal resection. The popular ileo-anal pouch procedures used in the management of ulcerative colitis generally are not used for the treatment of Crohn's colitis, because of higher complication rates. Commonly performed operations include ileostomy, segmental colon resection, subtotal colectomy, and proctocolectomy. The general surgeon, therefore, is provided with many options when faced with complications of Crohn's colitis. This article examines the attributes of and results reported for each of these options.
Collapse
Affiliation(s)
- T S Guy
- Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, USA
| | | | | |
Collapse
|
|
46
|
Edwards CM, George BD, Jewell DP, Warren BF, Mortensen NJ, Kettlewell MG. Role of a defunctioning stoma in the management of large bowel Crohn's disease. Br J Surg 2000; 87:1063-6. [PMID: 10931051 DOI: 10.1046/j.1365-2168.2000.01467.x] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The faecal stream plays a significant role in the pathogenesis of Crohn's disease. This retrospective study aimed to assess the effect of faecal diversion on the natural history of refractory Crohn's colitis (RCC) and severe perianal disease (PAD). METHODS All patients undergoing a defunctioning stoma without resection for RCC or PAD between 1970 and 1997 were studied. Indications for surgery, acute clinical response, subsequent outcome and stoma rates were recorded. RESULTS Some 73 patients underwent a defunctioning stoma (55 RCC and 18 PAD). Acute remission was achieved in 63 patients (48 RCC, 15 PAD). Twenty-nine patients had subsequent closure of the defunctioning stoma (25 of 48 acute responders with RCC and four of 15 acute responders with PAD). Eleven patients with RCC and two with PAD achieved good long-term function without disease relapse (median follow-up 36 months). Overall 52 patients have undergone proctocolectomy or remain with a defunctioning stoma (37 with RCC and 15 with PAD). CONCLUSION Faecal diversion is associated with acute clinical remission in the majority of patients with RCC and PAD, but sustained benefit occurs less often. For selected patients, diversionary surgery alone offers a realistic alternative to major bowel resection.
Collapse
Affiliation(s)
- C M Edwards
- Departments of Gastroenterology, Colorectal Surgery and Cellular Pathology, John Radcliffe Hospital, Oxford OX3 9DU, UK
| | | | | | | | | | | |
Collapse
|
|
47
|
Abstract
This review concentrates on the clinical evaluation, imaging, therapy, and prognostic factors in acute severe colitis of idiopathic as well as infectious origin. Older concepts as well as more recent are critically scrutinized.
Collapse
Affiliation(s)
- B Blomberg
- Department of Medicine, Orebro Medical Centre Hospital, Sweden
| | | |
Collapse
|
|
48
|
Kennedy RJ, Kirk SJ, Gardiner KR. Promotion of a favorable gut flora in inflammatory bowel disease. JPEN J Parenter Enteral Nutr 2000; 24:189-95. [PMID: 10850949 DOI: 10.1177/0148607100024003189] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Recent evidence suggests that the composition of colonic flora plays a role in intestinal inflammation in inflammatory bowel disease (IBO). This review examines the evidence that altering the concentrations of colonic bacteria might benefit patients with this condition.
Collapse
Affiliation(s)
- R J Kennedy
- Department of Surgery, The Queen's University of Belfast, Institute of Clinical Science, Northern Ireland
| | | | | |
Collapse
|
|
49
|
Abstract
Clinical recurrence of Crohn's disease after surgical resection is a significant problem, with reported rates as high as 55% at 5 yr and 76% at 15 yr. Specific factors that predispose to postoperative recurrence of Crohn's disease have not been well defined. In addition, the underlying pathophysiology of recurrent disease and the reason for its localization to the neoterminal ileum are not well understood. Various operative techniques have been evaluated but none, aside from formation of an ostomy, has been shown to reduce the risk of recurrence. In contrast, there is increasing evidence that postoperative medical therapy has the potential to decrease the risk of postoperative recurrence. Historically, sulfasalazine may have a modest effect on reducing postoperative recurrence of ileal or ileocolonic disease. However, 5-ASA preparations that can selectively deliver mesalamine to the small bowel or anastomotic margin should be more effective. Indeed, in several studies and as confirmed by a meta-analysis, mesalamine has been demonstrated to reduce significantly postoperative recurrence of Crohn's disease. Metronidazole and 6-mercaptopurine or azathioprine also seem to be of benefit in postoperative prophylaxis of disease recurrence, but additional controlled studies are required to define better the efficacy and dose-response of these agents. Corticosteroids are ineffective at reducing postoperative recurrence.
Collapse
Affiliation(s)
- J P Achkar
- Department of Gastroenterology, The Cleveland Clinic Foundation, Ohio 44195, USA
| | | |
Collapse
|
|
50
|
Schmit A, Van Gossum A, Carol M, Houben JJ, Mascart F. Diversion of intestinal flow decreases the numbers of interleukin 4 secreting and interferon gamma secreting T lymphocytes in small bowel mucosa. Gut 2000; 46:40-5. [PMID: 10601053 PMCID: PMC1727786 DOI: 10.1136/gut.46.1.40] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
BACKGROUND/AIMS The intestinal immune system faces large amounts of antigens, and its regulation is tightly balanced by cytokines. In this study, the effect of intestinal flow diversion on spontaneous secretion of interleukin (IL)-4 and interferon (IFN)- gamma was analysed. METHODS Eight patients (two with Crohn's disease, four with ulcerative colitis, and two with previous colon cancer) carrying a double lumen small bowel stoma after a total colectomy procedure were included in the study. For each patient, eight biopsy samples were taken endoscopically from both the diverted and non-diverted part of the small bowel. Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) were isolated separately and assayed for numbers of cells spontaneously secreting IL-4 and/or IFN-gamma by an ELISPOT technique. RESULTS Compared with the non-diverted mucosa, a significant decrease in the number of spontaneously IFN-gamma secreting CD3 lymphocytes was observed in the diverted small bowel mucosa among both IELs (p = 0.008) and LPLs (p = 0.007). The same results, although less significant, were obtained for IL-4, especially in LPLs (p = 0.01). CONCLUSION The intestinal content influences the spontaneous secretion of IFN-gamma and IL-4 by intestinal lymphocytes. These results could help to elucidate the anti-inflammatory role of split ileostomy in patients suffering from inflammatory bowel diseases.
Collapse
Affiliation(s)
- A Schmit
- Department of Immunology, Erasme University Hospital, Free University of Brussels, Route de Lennik, 808, B-1070 Belgium
| | | | | | | | | |
Collapse
|