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1
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Pelly T, Anand E, Hanna L, Shakweh E, Joshi S, Lung P, Hart A, Tozer P. Time to classify: a narrative and scoping review of the old and the new classifications of perianal Crohn's disease. Tech Coloproctol 2025; 29:123. [PMID: 40419817 DOI: 10.1007/s10151-025-03161-z] [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: 12/09/2024] [Accepted: 04/13/2025] [Indexed: 05/28/2025]
Abstract
Perianal Crohn's disease (pCD) is a complex manifestation of Crohn's disease. Classifying this patient cohort for both clinical purposes and for inclusion into research trials is challenging but crucial in order to improve outcomes. This review provides an overview of historical classifications of both fistulising and non-fistulising pCD, including the Park's, Cardiff-Hughes and American Gastroenterological Association (AGA) classifications, as well as recent advances including the Treatment Optimisation and CLASSification of perianal Crohn's disease (TOpClass) classification of fistulising pCD. Secondly, this article provides a scoping review of recent trials in pCD and describes how the cohorts in these trials relate to the TOpClass classification. Of the 19 studies relating to pCD that were identified, four could be confidently classified as class 2a. Seven could be classified as class 2a or 2b, but it was not possible to subdivide further, and seven to class 2a, 2b or 2c, but it was not possible to subdivide further. One study population was classified as class 2a or 2c. In eight studies, it was not specified whether patients with a defunctioning stoma were included or excluded. This review demonstrates the heterogeneous nature of some patient cohorts in previous clinical trials, and how the TOpClass classification may be used to group patients more accurately for clinical use and inclusion in research trials.
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Affiliation(s)
- T Pelly
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
| | - E Anand
- Imperial College London, London, UK.
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK.
| | - L Hanna
- Imperial College London, London, UK
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
| | - E Shakweh
- Imperial College London, London, UK
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
| | - S Joshi
- Imperial College London, London, UK
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
| | - P Lung
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
| | - A Hart
- Imperial College London, London, UK
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
| | - P Tozer
- Imperial College London, London, UK
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
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2
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Dawes AJ, Lightner AL. Perianal Fistulizing Crohn's Disease: Outcomes of Surgical Repairs and Current State of Stem Cell-Based Therapies. Clin Colon Rectal Surg 2025; 38:126-140. [PMID: 39944301 PMCID: PMC11813615 DOI: 10.1055/s-0044-1786543] [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: 05/17/2025]
Abstract
Perianal fistulizing Crohn's disease is one of the most disabling phenotypes of Crohn's disease, due to the severe impairment in quality of life including social and personal wellbeing. A multimodal approach with patient-tailored care is the key to optimal management of this condition. Medical therapy is needed to optimize the luminal disease, and surgical intervention is required to control any associated perianal sepsis and attempt palliative or definitive fistula repair. While several medical and surgical options are available, the majority of patients continue to have symptomatic disease. Fortunately, this continues to drive novel innovations which are revolutionizing the treatment and outcomes of perianal fistulizing Crohn's disease. However, there continues to be a need for randomized trials and consistent metrics utilized for classification and treatment outcomes in order to accurately describe optimal treatment outcomes.
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Affiliation(s)
- Aaron J. Dawes
- Section of Colon & Rectal Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California
- Stanford-Surgery Policy Improvement Research and Education Center, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Amy L. Lightner
- Department of General Surgery, Scripps Clinic, La Jolla, California
- Department of Molecular Medicine, Scripps Research Institute, La Jolla, California
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3
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Laharie D, Vuitton L, Bourreille A, Bouhnik Y, Colombel JF, Louis E, Fumery M, Mailhat C, Mary JY, Peyrin-Biroulet L. The Groupe d'Etude sur les Affections Inflammatoires Digestives (GETAID): 40 Years of a Family Story in Inflammatory Bowel Disease. J Crohns Colitis 2025; 19:jjae122. [PMID: 39207018 DOI: 10.1093/ecco-jcc/jjae122] [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: 04/16/2024] [Indexed: 09/04/2024]
Abstract
The Groupe d'Etude sur les Affections Inflammatoires Digestives (GETAID) was founded in Paris in 1983 by Professor Robert Modigliani and colleagues. From the beginning, the aim of this international (France, Belgium, and Switzerland), multicenter, French-speaking group was to address clinical questions raised by patients or physicians in their daily practice or the inflammatory bowel disease community, by focusing on clinical research on treatments through randomized controlled trials, prospective cohorts, and cross-sectional studies, quantifying the severity of various facets of the disease when necessary for these studies. This very innovative approach has contributed to the advancement of knowledge in inflammatory bowel diseases by publishing more than 120 original articles in peer-reviewed journals throughout the GETAID's 40-year history, most of them in top publications in gastroenterology and hepatology journals. In this paper, we will see what GETAID's contribution has been over the last 4 decades and review the reasons for its success and forthcoming challenges.
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Affiliation(s)
- David Laharie
- CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Lucine Vuitton
- CHU de Besançon, Service de Gastroentérologie, UMR Inserm Right, Université de Franche-Comté, Besançon, France
| | - Arnaud Bourreille
- Nantes Université, CHU de Nantes, Hôtel-Dieu, Hépato-Gastroentérologie, Institut des Maladies de l'Appareil Digestif, CIC Inserm 1413, Nantes, France
| | - Yoram Bouhnik
- Paris IBD Center, Groupe Hospitalier Privé Ambroise Paré - Hartmann, Neuilly sur Seine, France
| | - Jean-Frédéric Colombel
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Edouard Louis
- Department of Gastroenterology, University Hospital CHU of Liège, Liège, Belgium
| | - Mathurin Fumery
- Department of Gastroenterology, Amiens University Hospital, Amiens, France
- PeriTox, Université de Picardie, Amiens, France
| | | | - Jean-Yves Mary
- UMR-S-1153 Inserm, Equipe ECSTRRA, Denis Diderot - Paris 7 University, Hôpital Saint-Louis, Paris, France
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Brabois Hospital, Nancy University, Nancy les Vandoeuvre-lès-Nancy, France
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4
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Takano S, Nakamura Y, Tamaoka K, Yoshimoto T, Irei Y, Tsuji Y. Management of Anal Fistula with Crohn's Disease. J Anus Rectum Colon 2025; 9:10-19. [PMID: 39882221 PMCID: PMC11772789 DOI: 10.23922/jarc.2024-067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 07/31/2024] [Indexed: 01/31/2025] Open
Abstract
Crohn's disease (CD) causes gastrointestinal symptoms (i.e., diarrhea and abdominal pain), systemic symptoms (i.e., fatigue, anemia, weight loss, and fever), and perianal fistulas that produce anal pain. Because of the frequent occurrence of diarrhea and ulcers in the rectum, CD is often exacerbated by perianal abscesses and/or fistulas. Perianal fistulizing CD (PFCD) has an unknown etiology and recurring symptoms such as pain and discharge, which seriously affects the patient's quality of life (QOL). In the past, radical surgery was performed for PFCD, but due to the risk of anal sphincter impairment, conservative therapy using antibiotics and immunosuppressive medications is currently the first treatment option. PFCD management has greatly improved with the use of biologics such as the antitumor necrosis factor alpha (TNF-α) antibodies infliximab and adalimumab. In this review, the results of the administration of anti-TNF-α (certolizumab pegol), anti-interleukin-12/23 (ustekinumab), and anti-α4β7 integrin antibodies (vedolizumab) were evaluated. Our investigation showed that these medications may be effective for maintenance therapy to prevent the recurrence of anal fistulas. In addition to biologics, molecular target drugs and even regenerative medicine using mesenchymal stem cells have been introduced to further expand the treatment options for consideration by medical personnel. We herein discuss the management of PFCD by focusing on studies conducted in the United States and Europe where researchers used recommended guidelines and consensus statements to evaluate the efficacy of each medication and published their findings in peer-reviewed journals.
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Affiliation(s)
- Shota Takano
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Yasushi Nakamura
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Kohei Tamaoka
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Takafumi Yoshimoto
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Yasue Irei
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
| | - Yoriyuki Tsuji
- Inflammatory Bowel Disease Center, Coloproctology Center Takano Hospital, Kumamoto, Japan
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Singh JP, Aleissa M, Drelichman ER, Mittal VK, Bhullar JS. Navigating the complexities of perianal Crohn's disease: Diagnostic strategies, treatment approaches, and future perspectives. World J Gastroenterol 2024; 30:4745-4753. [PMID: 39610776 PMCID: PMC11580605 DOI: 10.3748/wjg.v30.i44.4745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/25/2024] [Accepted: 10/24/2024] [Indexed: 11/12/2024] Open
Abstract
This article discusses the literature review article by Pacheco et al published in July 2024; the authors provided good reviews of perianal Crohn's disease (CD), and challenges faced by clinicians in the management. CD, characterized by its chronic and relapsing nature, is an idiopathic condition that can involve any segment of the gastrointestinal tract. Perianal disease impacts up to 40% of patients with CD, with perianal fistulas constituting up to 80% of perianal lesions. Perianal CD can be highly incapacitating and profoundly diminish the overall well-being of patients. The management focuses on controlling the perianal sepsis and treating luminal CD. Biologics are crucial to the treatment approach, and results have been encouraging. The surgery focuses on controlling the sepsis, with more definitive treatments being fistula surgery, fecal diversion, and proctectomy as the last resort. This manuscript briefly describes the burden of CD, the challenges posed by perianal CD, and the role of different treatment modalities from colorectal surgeon's perspective.
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Affiliation(s)
- Jai P Singh
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Southfield, MI 48075, United States
| | - Maryam Aleissa
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Ernesto R Drelichman
- Department of Surgery-Colon and Rectal Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Vijay K Mittal
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
| | - Jasneet S Bhullar
- Department of Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, Southfield, MI 48075, United States
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6
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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.
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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
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Shehab M, De Marco D, Lakatos PL, Bessissow T. The potential for medical therapies to address fistulizing Crohn's disease: a state-of-the-art review. Expert Opin Biol Ther 2024; 24:733-746. [PMID: 39045643 DOI: 10.1080/14712598.2024.2383882] [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: 02/27/2024] [Revised: 06/25/2024] [Accepted: 07/20/2024] [Indexed: 07/25/2024]
Abstract
INTRODUCTION Crohn's disease (CD) is a chronic, relapsing immune mediated disease, which is one of the two major types of inflammatory bowel disease (IBD). Fistulizing CD poses a significant clinical challenge for physicians. Effective management of CD requires a multidisciplinary approach, involving a gastroenterologist and a GI surgeon while tailoring treatment to each patient's unique risk factors, clinical representations, and preferences. AREAS COVERED This comprehensive review explores the intricacies of fistulizing CD including its manifestations, types, impact on quality of life, management strategies, and novel therapies under investigation. EXPERT OPINION Antibiotics are often used as first-line therapy to treat symptoms. Biologics that selectively target TNF-α, such infliximab (IFX), have shown high efficacy in randomized controlled trials. However, more than 50% of patients lose response to IFX, prompting them to explore alternative strategies. Current options include adalimumab and certolizumab pegol combination therapies, as well as small-molecule drugs targeting Janus kinases such as Upadacitinib. Furthermore, a promising treatment for complex fistulas is mesenchymal stem cells such as Darvadstrocel (Alofisel), an allogeneic stem cell-based therapy. However, surgical interventions are necessary for complex cases or intra-abdominal complications. Setons and LIFT procedures are the most common surgical options.
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Affiliation(s)
- Mohammad Shehab
- Division of Gastroenterology, Department of Internal Medicine, Mubarak Al-Kabeer University Hospital, Kuwait University, Kuwait City, Kuwait
| | - Davide De Marco
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Center, Montreal, Canada
| | - Peter L Lakatos
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Center, Montreal, Canada
- 1st Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Talat Bessissow
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Center, Montreal, Canada
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Gordon SR, Eichenwald LS, Systrom HK. Endoscopic techniques for management of large colorectal polyps, strictures and leaks. Surg Open Sci 2024; 20:156-168. [PMID: 39100384 PMCID: PMC11296069 DOI: 10.1016/j.sopen.2024.06.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 06/17/2024] [Accepted: 06/29/2024] [Indexed: 08/06/2024] Open
Abstract
The implementation of screening colonoscopy with polyp removal has significantly decreased mortality rates associated with colorectal cancer (CRC), although it remains a major cause of cancer-related deaths globally. CRC typically originates from adenomatous polyps, and increased removal of these growths has led to reduced CRC incidence and mortality. Endoscopic polypectomy techniques, including hot and cold snare polypectomy, play a pivotal role in this process. While both methods are effective for small polyps (<10 mm), recent evidence favors cold snare polypectomy due to its superior safety profile and comparable complete resection rates. Large polyps (>10 mm), particularly those with advanced features, pose increased cancer risks and often require meticulous assessment and advanced endoscopic techniques, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), for resection. This chapter also provides a practical overview of endoscopic techniques for managing colonic obstructions and pericolonic fluid collections, detailing their indications, advantages, disadvantages, and complications. The goal is to improve understanding and application in clinical practice. Additionally, we provide a summary of endoscopic closure techniques that have revolutionized the management of perforations and fistulas, offering safe and effective alternatives to surgery.
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Affiliation(s)
- Stuart R. Gordon
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, NH, Lebanon
| | - Lauren S. Eichenwald
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, NH, Lebanon
| | - Hannah K. Systrom
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, NH, Lebanon
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9
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Pacheco T, Monteiro S, Barros L, Silva J. Perianal disease in inflammatory bowel disease: Broadening treatment and surveillance strategies for anal cancer. World J Gastroenterol 2024; 30:3373-3385. [PMID: 39091713 PMCID: PMC11290399 DOI: 10.3748/wjg.v30.i28.3373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 06/17/2024] [Accepted: 07/08/2024] [Indexed: 07/24/2024] Open
Abstract
The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.
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Affiliation(s)
- Tatiana Pacheco
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
| | - Sara Monteiro
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
| | - Luísa Barros
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
| | - Jorge Silva
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
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10
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Pal P, Reddy DN. Interventional endoscopy in inflammatory bowel disease: a comprehensive review. Gastroenterol Rep (Oxf) 2024; 12:goae075. [PMID: 39055373 PMCID: PMC11272179 DOI: 10.1093/gastro/goae075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 07/03/2024] [Accepted: 07/11/2024] [Indexed: 07/27/2024] Open
Abstract
Interventional endoscopy can play a key role in the multidisciplinary management of complex inflammatory bowel disease (IBD) as an adjunct to medical and surgical therapy. The primary role of interventional IBD (IIBD) includes the treatment of Crohn's disease-related stricture, fistula, and abscess. Endoscopic balloon dilation (EBD), endoscopic stricturotomy, and placement of endoscopic stents are different forms of endoscopic stricture therapy. EBD is the most widely used therapy whereas endoscopic stricturotomy has higher long-term efficacy than EBD. Fully covered and partially covered self-expanding metal stents are useful in long and refractory strictures whereas lumen-apposing metal stents can be used in short, and anastomotic strictures. Endoscopic fistula/abscess therapy includes endoscopic fistulotomy, seton placement, endoscopic ultrasound-guided drainage of rectal/pelvic abscess, and endoscopic injection of filling agents (fistula plug/glue/stem cell). Endoscopic seton placement and fistulotomy are mainly feasible in short, superficial, single tract fistula and in those with prior surgical seton placement. Similarly, endoscopic fistulotomy is usually feasible in short, superficial, single-tract fistula. Endoscopic closure therapies like over-the-scope clips, suturing, and self-expanding metal stent should be avoided for de novo/bowel to hollow organ fistulas. Other indications include management of postoperative complications in IBD such as management of surgical leaks and complications of pouchitis in ulcerative colitis. Additional indications include endoscopic resection of ulcerative colitis-associated neoplasia (by endoscopic mucosal resection, endoscopic submucosal dissection, and endoscopic full-thickness resection), retrieval of retained capsule endoscope, and control of bleeding. IIBD therapies can potentially act as a bridge between medical and surgical therapy for properly selected IBD patients.
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Affiliation(s)
- Partha Pal
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - D Nageshwar Reddy
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
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Yamamoto-Furusho J, López-Gómez J, Bosques-Padilla F, Martínez-Vázquez M, De-León-Rendón J. Primer consenso mexicano de la enfermedad de Crohn. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2024; 89:280-311. [DOI: 10.1016/j.rgmx.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2024]
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12
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Yamamoto-Furusho JK, López-Gómez JG, Bosques-Padilla FJ, Martínez-Vázquez MA, De-León-Rendón JL. First Mexican Consensus on Crohn's disease. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:280-311. [PMID: 38762431 DOI: 10.1016/j.rgmxen.2024.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 03/19/2024] [Indexed: 05/20/2024]
Abstract
INTRODUCTION Crohn's disease (CD) is a subtype of chronic and incurable inflammatory bowel disease. It can affect the entire gastrointestinal tract and its etiology is unknown. OBJECTIVE The aim of this consensus was to establish the most relevant aspects related to definitions, diagnosis, follow-up, medical treatment, and surgical treatment of Crohn's disease in Mexico. MATERIAL AND METHODS Mexican specialists in the areas of gastroenterology and inflammatory bowel disease were summoned. The consensus was divided into five modules, with 69 statements. Applying the Delphi panel method, the pre-meeting questions were sent to the participants, to be edited and weighted. At the face-to-face meeting, all the selected articles were shown, underlining their level of clinical evidence; all the statements were discussed, and a final vote was carried out, determining the percentage of agreement for each statement. RESULTS The first Mexican consensus on Crohn's disease was produced, in which recommendations for definitions, classifications, diagnostic aspects, follow-up, medical treatment, and surgical treatment were established. CONCLUSIONS Updated recommendations are provided that focus on definitions, classifications, diagnostic criteria, follow-up, and guidelines for conventional medical treatment, biologic therapy, and small molecule treatment, as well as surgical management.
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Affiliation(s)
- J K Yamamoto-Furusho
- Clínica de Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
| | - J G López-Gómez
- Clínica de Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Mexico City, Mexico
| | - F J Bosques-Padilla
- Departamento de Gastroenterología, Hospital Universitario de la Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | | | - J L De-León-Rendón
- Clínica de Enfermedad Inflamatoria Intestinal, Servicio de Coloproctología, Hospital General de México, Mexico City, Mexico
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Esposito C, Autorino G, Cerulo M, Del Conte F, Coppola V, Esposito G, Chiodi A, Di Mento C, Bagnara V, Escolino M. Video-assisted anal fistula treatment (VAAFT) combined with ozonide oil dressing: standardization of technique in pediatric patients. Surg Endosc 2024; 38:2273-2279. [PMID: 38443498 PMCID: PMC10978665 DOI: 10.1007/s00464-024-10759-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 02/16/2024] [Indexed: 03/07/2024]
Abstract
BACKGROUND Anal fistula and perianal abscess are commonly acquired anorectal pathologies in children. Surgical treatment options commonly adopted are fistulotomy, fistulectomy, cutting seton placement, and more recently video-assisted anal fistula treatment (VAAFT). Optimal postoperative wound dressing remains debated. This study aimed to report our series of pediatric patients, who received VAAFT and postoperative wound dressing using ozonide oil. METHODS All patients who underwent VAAFT between August 2018 and May 2023 were included in the study. Demographics, clinical features, pre-operative imaging, surgical details, outcome, and mid-term outcome data were retrospectively reviewed for each patient. All VAAFT procedures were performed under general anesthesia and using a 10-Ch fistuloscope. RESULTS Thirty-three VAAFT procedures were performed in 30 patients over the study period. The median patient age was 5.7 years (range 1.75-14). Anal fistula was idiopathic in 26/30 (86.6%), iatrogenic in 2/30 (6.7%), and secondary to Crohn's disease in 2/30 (6.7%). The median duration of surgery was 23 min (range 18-40). All patients received ozonide oil dressing twice a day for 5 weeks postoperatively. The median hospital stay was 24 h (range 9-36). The median healing time was 28 days (range 17-39). With a median follow-up of 2 years (range 0.5-5), disease recurrence occurred in 3/30 (10%) patients with idiopathic fistula, who were re-operated using the same technique, with no further recurrence. No fecal incontinence or soiling was observed. CONCLUSION Our series confirmed that VAAFT is a safe and effective technique to treat children with perianal fistula. The technique is versatile, allowing to treat fistulae of different etiologies. Postoperative course was painless and fast. Future comparative prospective studies are needed to better establish these conclusions.
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Affiliation(s)
- Ciro Esposito
- Division of Pediatric Surgery, Federico II University Hospital, Via Pansini 5, 80131, Naples, Italy
| | - Giuseppe Autorino
- Division of Pediatric Surgery, Federico II University Hospital, Via Pansini 5, 80131, Naples, Italy
| | - Mariapina Cerulo
- Division of Pediatric Surgery, Federico II University Hospital, Via Pansini 5, 80131, Naples, Italy
| | - Fulvia Del Conte
- Division of Pediatric Surgery, Federico II University Hospital, Via Pansini 5, 80131, Naples, Italy
| | - Vincenzo Coppola
- Division of Pediatric Surgery, Federico II University Hospital, Via Pansini 5, 80131, Naples, Italy
| | | | - Annalisa Chiodi
- Division of Pediatric Surgery, Federico II University Hospital, Via Pansini 5, 80131, Naples, Italy
| | - Claudia Di Mento
- Division of Pediatric Surgery, Federico II University Hospital, Via Pansini 5, 80131, Naples, Italy
| | - Vincenzo Bagnara
- Department of Pediatric Surgery, Policlinico G.B. Morgagni, Catania, Italy
| | - Maria Escolino
- Division of Pediatric Surgery, Federico II University Hospital, Via Pansini 5, 80131, Naples, Italy.
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Fathallah N, Akaffou M, Haouari MA, Spindler L, Alam A, Barré A, Pommaret E, Fels A, de Parades V. Deep remission improves the quality of life of patients with Crohn's disease and anoperineal fistula treated with darvadstrocel: results of a French pilot study. Tech Coloproctol 2023; 27:1201-1210. [PMID: 36811811 DOI: 10.1007/s10151-023-02765-7] [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: 11/05/2022] [Accepted: 01/31/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND The injection of allogeneic adipose tissue-derived mesenchymal stem cells (MSC) into anal fistulas in patients with Crohn's disease has never been evaluated in "real-life" conditions in France. METHODS We prospectively studied the first patients receiving MSC injections at our center and undergoing 12 months of follow-up. The primary endpoint was the clinical and radiological response rate. The secondary endpoints were symptomatic efficacy, safety, anal continence, quality of life (Crohn's anal fistula-quality of life scale, CAF-QoL), and predictive factors of success. RESULTS We included 27 consecutive patients. The complete clinical and radiological response rates at M12 were 51.9% and 50%, respectively. The combined complete clinical-radiological response (deep remission) rate was 34.6%. No major adverse effects or changes in anal continence were reported. The perianal disease activity index decreased from 6.4 to 1.6 (p < 0.001) for all patients. The CAF-QoL score also decreased from 54.0 to 25.5 (p < 0.001). At the end of the study, M12, the CAF-QoL score was significantly lower only in patients with a complete combined clinical-radiological response relative to those without a complete clinical-radiological response (15.0 versus 32.8, p = 0.01). Having a multibranching fistula and infliximab treatment were associated with a combined complete clinical-radiological response. CONCLUSIONS This study confirms reported efficacy data for the injection of MSC for complex anal fistulas in Crohn's disease. It also shows a positive impact on the quality of life of patients, particularly those for whom a combined clinical-radiological response was achieved.
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Affiliation(s)
- N Fathallah
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France.
| | - M Akaffou
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - M A Haouari
- Radiology Department, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - L Spindler
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - A Alam
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - A Barré
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - E Pommaret
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - A Fels
- Clinical Research Centre, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - V de Parades
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
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Anandabaskaran S, Hanna L, Iqbal N, Constable L, Tozer P, Hart A. Where Are We and Where to Next?-The Future of Perianal Crohn's Disease Management. J Clin Med 2023; 12:6379. [PMID: 37835022 PMCID: PMC10573672 DOI: 10.3390/jcm12196379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/26/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Perianal fistulizing Crohn's Disease (pCD) affects about 25% of patients with Crohn's Disease (CD). It remains a difficult entity to manage with a therapeutic ceiling of treatment success despite improving medical and surgical management. The refractory nature of the disease calls for an imminent need to better understand its immunopathogenesis and classification to better streamline our treatment options. In this article, we overview the current state of pCD management and discuss where the future of its management may lie.
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Affiliation(s)
- Sulak Anandabaskaran
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London W12 0NN, UK
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Faculty of Medicine, St Vincent’s Clinical School, University of New South Wales, 390 Victoria Street, Darlinghurst, NSW 2010, Australia
| | - Luke Hanna
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London W12 0NN, UK
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
| | - Nusrat Iqbal
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2BX, UK
| | - Laura Constable
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London W12 0NN, UK
| | - Phil Tozer
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2BX, UK
| | - Ailsa Hart
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2BX, UK
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Rosevics L, Savio MC, Lima Júnior E, Ramos Júnior O. FISTULIZING PERIANAL CROHN'S DISEASE: IS THE PATIENT'S SEX A BURDEN? A SYSTEMATIC REVIEW. ARQUIVOS DE GASTROENTEROLOGIA 2023; 60:490-524. [PMID: 38018554 DOI: 10.1590/s0004-2803.230402023-28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 07/31/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome. OBJECTIVE Thus, the aim of this study was to assess whether sex influences the response to treatment for these patients. METHODS This systematic review (PROSPERO CRD42022319629) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. We selected articles published in English, Spanish, Portuguese, and Italian between 2010 and 2020 in the PubMed and Science Direct databases. According to the PICO acronym, prospective studies in patients older than 18 years with the objective of treating fistulizing perianal Crohn's disease were selected. Studies in pediatric populations, retrospective, without treatment objectives, and that included only rectovaginal fistulas or a single sex were excluded. Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale. RESULTS Of the 1887 articles found, 33 were included. Most studies used anti-TNF drugs as treatment (n=11). Ten studies had subgroup analyses; of them, the two studies reporting sex differences used infliximab and adalimumab as treatment and showed that women had a longer fistula closure time than men. CONCLUSION This systematic review showed that few data corroborate the difference between sexes in the treatment of fistulizing perianal Crohn's disease, possibly having a greater relationship with the phenotype. However, considering the lack of results, further studies with this objective and with standardization of fistulas and response assessment methods are needed.
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Bhat S, Xu W, Varghese C, Dubey N, Wells CI, Harmston C, O'Grady G, Bissett IP, Lin AY. Efficacy of different surgical treatments for management of anal fistula: a network meta-analysis. Tech Coloproctol 2023; 27:827-845. [PMID: 37460830 PMCID: PMC10485107 DOI: 10.1007/s10151-023-02845-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 07/06/2023] [Indexed: 09/09/2023]
Abstract
PURPOSE Currently, the anal fistula treatment which optimises healing and preserves bowel continence remains unclear. The aim of our study was to compare the relative efficacy of different surgical treatments for AF through a network meta-analysis. METHODS Systematic searches of MEDLINE, EMBASE and CENTRAL databases up to October 2022 identified randomised controlled trials (RCTs) comparing surgical treatments for anal fistulae. Fistulae were classified as simple (inter-sphincteric or low trans-sphincteric fistulae crossing less than 30% of the external anal sphincter (EAS)) and complex (high trans-sphincteric fistulae involving more than 30% of the EAS). Treatments evaluated in only one trial were excluded from the primary analyses to minimise bias. The primary outcomes were rates of success in achieving AF healing and bowel incontinence. RESULTS Fifty-two RCTs were included. Of the 14 treatments considered, there were no significant differences regarding short-term (6 months or less postoperatively) and long-term (more than 6 months postoperatively) success rates between any of the treatments in patients with both simple and complex anal fistula. Ligation of the inter-sphincteric fistula tract (LIFT) ranked best for minimising bowel incontinence in simple (99.1% of comparisons; 3 trials, n = 70 patients) and complex anal fistula (86.2% of comparisons; 3 trials, n = 102 patients). CONCLUSIONS There is insufficient evidence in existing RCTs to recommend one treatment over another regarding their short and long-term efficacy in successfully facilitating healing of both simple and complex anal fistulae. However, LIFT appears to be associated with the least impairment of bowel continence, irrespective of AF classification.
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Affiliation(s)
- S Bhat
- Surgical and Translational Research Centre, Department of Surgery, The University of Auckland, Auckland, New Zealand
- Department of Surgery, Te Whatu Ora MidCentral, Palmerston North, New Zealand
| | - W Xu
- Surgical and Translational Research Centre, Department of Surgery, The University of Auckland, Auckland, New Zealand
- Department of Surgery, Te Whatu Ora Te Toka Tumai, Whangārei, New Zealand
| | - C Varghese
- Surgical and Translational Research Centre, Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - N Dubey
- Department of General Medicine, Tauranga Hospital, Te Whatu Ora, Tauranga, New Zealand
| | - C I Wells
- Surgical and Translational Research Centre, Department of Surgery, The University of Auckland, Auckland, New Zealand
- Department of Surgery, Te Whatu Ora Te Toka Tumai, Auckland, New Zealand
| | - C Harmston
- Surgical and Translational Research Centre, Department of Surgery, The University of Auckland, Auckland, New Zealand
- Department of Surgery, Te Whatu Ora Te Toka Tumai, Whangārei, New Zealand
| | - G O'Grady
- Surgical and Translational Research Centre, Department of Surgery, The University of Auckland, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - I P Bissett
- Surgical and Translational Research Centre, Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - A Y Lin
- Department of Surgery and Anaesthesia, University of Otago, Wellington, New Zealand.
- Department of Surgery, Wellington Regional Hospital, Te Whatu Ora, Wellington, New Zealand.
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Dimova A, Erceg Ivkošić I, Brlek P, Dimov S, Pavlović T, Bokun T, Primorac D. Novel Approach in Rectovaginal Fistula Treatment: Combination of Modified Martius Flap and Autologous Micro-Fragmented Adipose Tissue. Biomedicines 2023; 11:2509. [PMID: 37760949 PMCID: PMC10525900 DOI: 10.3390/biomedicines11092509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 09/01/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open
Abstract
In this paper, we introduce an innovative therapeutic approach for managing rectovaginal fistulas (RVF), by combining the modified Martius flap and micro-fragmented adipose tissue (MFAT) enriched with mesenchymal stem cells (MSC). This novel approach aims to deal with the difficulties associated with RVF, a medically complex condition with a lack of effective treatment options. We present the case of a 45-year-old female patient with a 15-year history of Crohn's disease (CD). During the preceding eight years, she had encountered substantial difficulties resulting from a rectovaginal fistula (RVF) that was active and considerable in size (measuring 3.5 cm in length and 1 cm in width). Her condition was accompanied by tissue alterations at both the vaginal and rectal openings. Following her admission to our hospital, the patient's case was discussed during both surgical and multidisciplinary hospital team (IRB) meetings. The team decided to combine a modified Martius flap with autologous MFAT containing MSCs. The results were remarkable, leading to comprehensive anatomical and clinical resolution of the RVF. Equally significant was the improvement in the patient's overall quality of life and sexual satisfaction during the one-year follow-up period. The integration of the modified Martius flap with MFAT emerges as a highly promising approach for addressing CD-related RVFs that had historically been, and still are, difficult to treat, given their often refractory nature and low healing success rates.
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Affiliation(s)
- Ana Dimova
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
| | - Ivana Erceg Ivkošić
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Petar Brlek
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
- School of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
| | - Stefan Dimov
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
| | - Tomislav Pavlović
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
- School of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
| | | | - Dragan Primorac
- St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
- School of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
- Medical School, University of Split, 21000 Split, Croatia
- Department of Biochemistry & Molecular Biology, The Pennsylvania State University, State College, PA 16802, USA
- The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, West Haven, CT 06516, USA
- Medical School REGIOMED, 96450 Coburg, Germany
- Medical School, University of Rijeka, 51000 Rijeka, Croatia
- National Forensic Sciences University, Gandhinagar 382007, India
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Cheng F, Zhong H, Huang Z, Li Z. Up-to-date meta-analysis of long-term evaluations of mesenchymal stem cell therapy for complex perianal fistula. World J Stem Cells 2023; 15:866-875. [PMID: 37700821 PMCID: PMC10494567 DOI: 10.4252/wjsc.v15.i8.866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 06/21/2023] [Accepted: 07/19/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Local mesenchymal stem cell (MSC) therapy for complex perianal fistulas (PFs) has shown considerable promise. But, the long-term safety and efficacy of MSC therapy in complex PFs remain unknown. AIM To explore the long-term effectiveness and safety of local MSC therapy for complex PFs. METHODS Sources included the PubMed, EMBASE, and Cochrane Library databases. A standard meta-analysis was performed using RevMan 5.3. RESULTS After screening, 6 studies met the inclusion criteria. MSC therapy was associated with an improved long-term healing rate (HR) compared with the control condition [odds ratio (OR) = 2.13; 95% confidence interval (95%CI): 1.34 to 3.38; P = 0.001]. Compared with fibrin glue (FG) therapy alone, MSC plus FG therapy was associated with an improved long-term HR (OR = 2.30; 95%CI: 1.21 to 4.36; P = 0.01). When magnetic resonance imaging was used to evaluate fistula healing, MSC therapy was found to achieve a higher long-term HR than the control treatment (OR = 2.79; 95%CI: 1.37 to 5.67; P = 0.005). There were no significant differences in long-term safety (OR = 0.77; 95%CI: 0.27 to 2.24; P = 0.64). CONCLUSION Our study indicated that local MSC therapy promotes long-term and sustained healing of complex PFs and that this method is safe.
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Affiliation(s)
- Fang Cheng
- Division of Gastroenterology, Zigong First People's Hospital, Zigong 643000, Sichuan Province, China
- Department of Gastroenterology, Zigong First People's Hospital, Zigong 643000, Sichuan Province, China.
| | - Huang Zhong
- Department of Gastroenterology, Zigong First People's Hospital, Zigong 643000, Sichuan Province, China
| | - Zhong Huang
- Department of Gastroenterology, Zigong First People's Hospital, Zigong 643000, Sichuan Province, China
| | - Zhi Li
- Department of Gastroenterology, Zigong First People's Hospital, Zigong 643000, Sichuan Province, China
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20
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Chahal JK, Sriranganathan D, Poo S, Lo SW, Kashkooli S, Garg M, Segal JP. Network meta-analysis: efficacy and safety of treatments for fistulising Crohn's disease. Eur J Gastroenterol Hepatol 2023; 35:702-710. [PMID: 37115969 DOI: 10.1097/meg.0000000000002552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Abstract
INTRODUCTION Fistulas are a debilitating complication of Crohn's disease and treatment options remain limited. There is a lack of head-to-head comparisons between treatments. To our knowledge, this is the first network meta-analysis on the efficacy of medical therapies in achieving fistula remission and maintenance of fistula closure in Crohn's disease. METHODS Biomedical databases and the Cochrane Central Registry were searched between 1978 and 2022 for randomized controlled trials (RCTs) reporting on treatments. A network meta-analysis was performed using the frequentist model with pooled relative risks (RRs) and P -scores used to rank treatments. RESULTS Twenty-five RCTs were included for analysis with 2239 patients included. At the 16-24 week time point, infliximab produced the only statistically significant result with the 5 mg/kg dose proving the most effective [RR, 2.30; 95% confidence interval (CI), 1.40-3.77]. At 44 weeks, ustekinumab was found to be most superior with it being 2.38 times (RR, 2.38; 95% CI, 1.24-4.56) more superior to placebo, with adalimumab (RR, 2.06; 95% CI, 1.06-3.99) and infliximab 5 mg/kg (RR, 1.68; 95% CI, 1.03-2.75) also producing a statistically significant result. CONCLUSION Despite infliximab being favoured in international guidelines for the treatment of perianal fistulising Crohn's disease, biologics such as ustekinumab, vedolizumab and adalimumab show promising results.
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Affiliation(s)
- Jacinder K Chahal
- Department of Surgery, Queen Elizabeth Hospital, Lewisham and Greenwich NHS Trust
| | - Danujan Sriranganathan
- Department of Gastroenterology, Whipps Cross University Hospital, Barts Health NHS Trust, London
| | - Stephanie Poo
- Department of Gastroenterology, The Hillingdon Hospitals NHS Foundation Trust, Middlesex, UK
| | - Sheng Wei Lo
- Department of Gastroenterology, Northern Hospital, Epping
| | - Soleiman Kashkooli
- Department of Gastroenterology, Northern Hospital, Epping
- Department of Medicine, University of Melbourne, Parkville, Melbourne, Australia
| | - Mayur Garg
- Department of Gastroenterology, Northern Hospital, Epping
- Department of Medicine, University of Melbourne, Parkville, Melbourne, Australia
| | - Jonathan P Segal
- Department of Gastroenterology, Northern Hospital, Epping
- Department of Medicine, University of Melbourne, Parkville, Melbourne, Australia
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21
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Scheurlen KM, MacLeod A, Kavalukas SL, Galandiuk S. State-of-the-art surgery for Crohn's disease: part III-perianal Crohn's disease. Langenbecks Arch Surg 2023; 408:132. [PMID: 36995518 DOI: 10.1007/s00423-023-02856-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 03/04/2023] [Indexed: 03/31/2023]
Abstract
PURPOSE Diagnosis and treatment of perianal Crohn's disease is challenging and requires its own domain of therapy. Different types of perianal disease require a spectrum of treatment strategies. Treatment options range from conservative therapy, including immunosuppressives, biologics, or stem cell therapy, to surgical treatment with specific indications depending on the underlying lesion. This is part III of the series "state-of-the-art surgery for Crohn's disease," focusing on the management of perianal disease. We discuss the definition and diagnosis of perianal Crohn's disease, the treatment of perianal lesions, and specific surgical indications and techniques. RESULTS AND CONCLUSION Pitfalls and complications play a substantial role in the treatment of perianal Crohn's disease, and surgical therapy may fail. Realistic treatment goals and an individual patient-oriented treatment approach are crucial in the treatment of perianal Crohn's disease.
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Affiliation(s)
- Katharina M Scheurlen
- Price Institute of Surgical Research, Hiram C. Polk Jr MD Department of Surgery, University of Louisville, Louisville, KY, 40202, USA
| | - Anne MacLeod
- Price Institute of Surgical Research, Hiram C. Polk Jr MD Department of Surgery, University of Louisville, Louisville, KY, 40202, USA
| | - Sandra L Kavalukas
- Price Institute of Surgical Research, Hiram C. Polk Jr MD Department of Surgery, University of Louisville, Louisville, KY, 40202, USA
- Division of Colon & Rectal Surgery, Hiram C Polk Jr MD Department of Surgery, University of Louisville, Louisville, KY, 40202, USA
| | - Susan Galandiuk
- Price Institute of Surgical Research, Hiram C. Polk Jr MD Department of Surgery, University of Louisville, Louisville, KY, 40202, USA.
- Division of Colon & Rectal Surgery, Hiram C Polk Jr MD Department of Surgery, University of Louisville, Louisville, KY, 40202, USA.
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22
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Cheng F, Huang Z, Wei W, Li Z. Efficacy and safety of mesenchymal stem cells in the treatment of perianal fistulas in Crohn's disease: a meta-analysis of randomized controlled trials. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023. [PMID: 36896932 DOI: 10.17235/reed.2023.9213/2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/09/2023]
Abstract
OBJECTIVES Local mesenchymal stem cell (MSC) therapy for perianal fistulas in Crohn's disease (CD) has yielded promising results, but it still remains controversial. In this study, we aimed to conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of MSC therapy for perianal CD (pCD). METHODS RCTs reporting MSC therapy for perianal fistulas in CD were searched and included. The effectiveness and safety data were analyzed using RevMan 5.3. RESULTS A total of 7 RCTs were included in this meta-analysis. The analysis showed that patients receiving MSC therapy presented a higher healing rate (HR) of pCD than those in the control group (odds ratio (OR)=1.42; 95% confidence interval (CI) 1.18, 1.71; P=0.0002). Compared with placebo (saline solution), MSC therapy improved the HR of pCD (OR=1.85; 95% CI 1.32, 2.60; P=0.0004). MSC therapy showed significant long-term efficacy (OR=1.36; P=0.009; 95% CI 1.08, 1.71). When MRI was used to evaluate fistula healing, a pooled analysis showed that the MSC group achieved a higher HR than the control group (OR=1.95; 95% CI 1.33, 2.87; P=0.0007). Allogeneic MSC therapy was superior to the control treatment in improving HR (OR = 1.97; 95% CI 1.40, 2.75; P<0.001). Furthermore, no significant differences were observed between MSC therapy and placebo in terms of adverse events (AEs) (OR = 1.16; 95% CI 0.76, 1.76; P = 0.48). None of the AEs were judged to be related to MSC treatment. CONCLUSIONS This meta-analysis of RCTs provided evidence that local MSC injection is safe and efficacious for perianal fistulas in CD. In addition, this treatment has favorable long-term efficacy and safety profiles.
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Affiliation(s)
- Fang Cheng
- Gastroenterology, Zigong First People's Hospital, China
| | - Zhong Huang
- Gastroenterology, Zigong First People's Hospital
| | - Wei Wei
- Gastroenterology, Zigong First People's Hospital
| | - Zhi Li
- Gastroenterology, Zigong First People's Hospital
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23
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Systematic Review of Endoscopic Management of Stricture, Fistula and Abscess in Inflammatory Bowel Disease. GASTROENTEROLOGY INSIGHTS 2023. [DOI: 10.3390/gastroent14010006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/16/2023] Open
Abstract
Background: Interventional inflammatory bowel disease (IIBD) therapies can play a key role in inflammatory bowel disease (IBD) related stricture/fistula/abscess deferring or avoiding invasive surgery. Methods: A total of 112 studies pertaining to IIBD therapy for strictures/fistula/abscess between 2002 and December 2022 were included by searching Pubmed, Medline and Embase with a focus on technical/clinical success, recurrence, re-intervention and complications. Results: IIBD therapy for strictures include endoscopic balloon dilation (EBD), endoscopic stricturotomy (ES) and self-expanding metal stent (SEMS) placement. EBD is the primary therapy for short strictures while ES and SEMS can be used for refractory strictures. ES has higher long-term efficacy than EBD. SEMS is inferior to EBD although it can be useful in long, refractory strictures. Fistula therapy includes endoscopic incision and drainage (perianal fistula)/endoscopic seton (simple, low fistula) and endoscopic ultrasound-guided drainage (pelvic abscess). Fistulotomy can be done for short, superficial, single tract, bowel-bowel fistula. Endoscopic injection of filling agents (fistula plug/glue/stem cell) is feasible although durability is unknown. Endoscopic closure therapies like over-the-scope clips (OTSC), suturing and SEMS should be avoided for de-novo/bowel to hollow organ fistulas. Conclusion: IIBD therapies have the potential to act as a bridge between medical and surgical therapy for properly selected IBD-related stricture/fistula/abscess although future controlled studies are warranted.
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24
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Dozois EJ, Lightner AL, Dietz AB, Fletcher JG, Lee YS, Friton JJ, Faubion WA. Durable Response in Patients With Refractory Fistulizing Perianal Crohn's Disease Using Autologous Mesenchymal Stem Cells on a Dissolvable Matrix: Results from the Phase I Stem Cell on Matrix Plug Trial. Dis Colon Rectum 2023; 66:243-252. [PMID: 36538706 DOI: 10.1097/dcr.0000000000002579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Refractory perianal Crohn's disease remains notoriously difficult to treat. We developed a novel technology using a commercially available bioabsorbable fistula plug to deliver autologous adipose-derived mesenchymal stem cells. OBJECTIVE This study aimed to assess therapeutic safety and feasibility in the completed STOMP (stem cells on matrix plugs) phase 1 clinical trial. DESIGN Prospective single-arm phase I clinical trial. SETTING Tertiary academic medical center. PATIENTS Adults (aged 18-65 y) with complex single-tract Crohn's disease perianal fistula who have failed conventional therapy were included in this study. INTERVENTION Autologous adipose-derived mesenchymal stem cells were isolated, ex vivo culture expanded, and seeded onto a commercially available bioabsorbable fistula plug. Six weeks later, patients returned to the operating room for removal of the seton and placement of the stem cell-loaded plug. MAIN OUTCOME MEASURES Patients were followed up for a total of 8 visits through 12 months. Safety was the primary end point; clinical healing and MRI response were secondary end points. RESULTS Twenty patients (12 females; mean age 36 y) were treated with the stem cell-loaded plug. Of the 20 patients enrolled, 3 were not included in the 12-month analysis because of study withdrawal. Through 12 months, no patient experienced a serious adverse event related to the stem cell-loaded plug. Four patients experienced 7 serious adverse events and 12 patients experienced 22 adverse events. Complete clinical healing occurred in 14 of 18 patients at 6 months and 13 of 17 patients at 12 months. MRI response was observed in 12 of 18 patients at 6 months. LIMITATIONS The main limitations were the small sample size and restrictive inclusion criteria. CONCLUSIONS A stem cell-loaded plug can safely and effectively deliver cell-based therapy for patients with single-tract fistulizing perianal Crohn's disease. See Video Abstract at http://links.lww.com/DCR/C70 . RESPUESTA DURADERA OBSERVADA EN PACIENTES CON ENFERMEDAD DE CROHN PERIANAL FISTULIZANTE REFRACTARIA MEDIANTE EL USO DE CLULAS MADRE MESENQUIMALES AUTLOGAS EN UNA MATRIZ DISOLUBLE RESULTADOS DEL ENSAYO DE FASE I STEM CELL ON MATRIX PLUG ANTECEDENTES:La enfermedad de Crohn perianal refractaria sigue siendo notoriamente difícil de tratar. Desarrollamos una tecnología novedosa utilizando un tapón de fístula bioabsorbible disponible comercialmente para administrar células madre mesenquimales derivadas de tejido adiposo autólogo.OBJETIVO:Evaluar la seguridad y viabilidad terapéutica en el ensayo finalizado STOMP.DISEÑO:Ensayo clínico prospectivo de fase I de un solo brazo.AJUSTE:Centro médico académico terciario.PACIENTES:Adultos (18-65) con fístula perianal compleja de la enfermedad de Crohn de un solo tracto que han fracasado con la terapia convencional.INTERVENCIÓN:Se aislaron células madre mesenquimales derivadas de tejido adiposo autólogo, se expandieron en cultivo ex vivo y se sembraron en un tapón de fístula bioabsorbible disponible comercialmente. Seis semanas después, los pacientes regresaron al quirófano para retirar el setón y colocar el tapón cargado de células madre.PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes fueron seguidos durante un total de 8 visitas durante 12 meses. La seguridad fue el criterio principal de valoración; la curación clínica y la respuesta a la resonancia magnética fueron criterios de valoración secundarios.RESULTADOS:Veinte pacientes (12 mujeres, edad media 36 años) fueron tratados con el tapón cargado de células madre. De los 20 pacientes inscritos, tres no se incluyeron en el análisis de 12 meses porque se retiraron del estudio. A lo largo de 12 meses, ningún paciente experimentó un evento adverso grave relacionado con el tapón cargado de células madre. Cuatro pacientes experimentaron 7 eventos adversos graves y 12 pacientes experimentaron 22 eventos adversos. La curación clínica completa ocurrió en 14 de 18 pacientes a los 6 meses y en 13 de 17 pacientes a los 12 meses. La respuesta a la resonancia magnética se observó en 12 de 18 pacientes a los 6 meses.LIMITACIONES:Las principales limitaciones son el tamaño pequeño de la muestra y los criterios de inclusión restrictivos.CONCLUSIONES:Un tapón cargado de células madre se puede administrar de manera segura y efectiva, una terapia basada en células para pacientes con enfermedad de Crohn perianal fistulizante de un solo tracto. Consule Video Resumen en http://links.lww.com/DCR/C70 . (Traducción- Dr. Yesenia Rojas-Khalil ).
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Affiliation(s)
- Eric J Dozois
- Department of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Amy L Lightner
- Department of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Allan B Dietz
- Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota
| | | | - Yong S Lee
- Department of Radiology, Mayo Clinic, Rochester, Minnesota
| | - Jessica J Friton
- Department of Gastroenterology, Mayo Clinic, Rochester Minnesota
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25
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Lin C, Lin H, Chen H, Chen N, Shih I, Hung J, Yueh T, Chiang F, Lin P, Tsai Y, Wei S. Perioperative optimization of Crohn's disease. Ann Gastroenterol Surg 2023; 7:10-26. [PMID: 36643355 PMCID: PMC9831910 DOI: 10.1002/ags3.12621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 09/07/2022] [Indexed: 01/18/2023] Open
Abstract
Crohn's disease (CD) is a chronic inflammatory disease mainly affecting the gastrointestinal tract. With the increased availability of modalities in the last two decades, the treatment of CD has advanced remarkably. Although medical treatment is the mainstay of therapy, most patients require surgery during the course of their illness, especially those who experience complications. Nutritional optimization and ERAS implementation are crucial for patients with CD who require surgical intervention to reduce postoperative complications. The increased surgical risk was found to be associated with the use of corticosteroids, but the association of surgical risk with immunomodulators, biologic therapy, such as anti-TNF mediations, anti-integrin medications, and anti-IL 12/23 was low in certainty. Decisions about preoperative medication must be made on an individual case-dependent basis. Preoperative imaging studies can assist in the planning of appropriate surgical strategies and approaches. However, patients must be informed of any alterations to their treatment. In summary, the management of perioperative medications and surgery-related decision-making should be individualized and patient-centered based on a multidisciplinary approach.
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Affiliation(s)
- Chun‐Chi Lin
- Division of Colon & Rectal Surgery, Department of SurgeryTaipei Veterans General HospitalTaipeiTaiwan
- Department of Surgery, Faculty of Medicine, School of MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Hung‐Hsin Lin
- Division of Colon & Rectal Surgery, Department of SurgeryTaipei Veterans General HospitalTaipeiTaiwan
- Department of Surgery, Faculty of Medicine, School of MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Hui‐Chuen Chen
- National Taiwan University Hospital, Dietetics DepartmentTaipeiTaiwan
| | - Nai‐Chia Chen
- National Taiwan University Hospital, Dietetics DepartmentTaipeiTaiwan
| | - I‐Lun Shih
- Department of Medical ImagingNational Taiwan University HospitalTaipeiTaiwan
- Department of Radiology, College of MedicineNational Taiwan UniversityTaipeiTaiwan
| | - Ji‐Shiang Hung
- Division of Colorectal Surgery, Department of SurgeryNational Taiwan University Hospital and College of MedicineTaipeiTaiwan
| | - Te‐Cheng Yueh
- Division of Colon and Rectal SurgeryTaichung Armed Forces General HospitalTaichungTaiwan
- National Defense Medical CenterTaipeiTaiwan
| | - Feng‐Fan Chiang
- Division of Colorectal Surgery, Department of SurgeryTaichung Veterans General HospitalTaichungTaiwan
- Department of Food and NutritionProvidence UniversityTaichungTaiwan
| | - Ping‐Wei Lin
- Division of colorectal surgery, Department of SurgeryMackay Memorial HospitalTaipeiTaiwan
| | - Yuan‐Yao Tsai
- Department of Colorectal SurgeryChina Medical University HospitalTaichungTaiwan
| | - Shu‐Chen Wei
- Division of Hepatology and Gastroenterology, Department of Internal MedicineNational Taiwan University Hospital and College of MedicineTaipeiTaiwan
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26
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Pokala A, Shen B. Endoscopic Treatment of Acute and Chronic Anastomotic Leaks from Inflammatory Bowel Disease Surgery. Gastrointest Endosc Clin N Am 2022; 32:801-815. [PMID: 36202517 DOI: 10.1016/j.giec.2022.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Acute or chronic anastomotic leak is a common complication after any gastrointestinal surgery in inflammatory bowel disease (IBD). The underlying disease of the bowel, comorbidities, malnutrition, anemia, and concurrent use of corticosteroids increase the risk for the development of anastomotic leaks. Anastomotic leak is traditionally managed with surgery. However, recent innovation has allowed the use of endoscopic methods in the management of some anastomotic leaks and their consequences. This article discusses a variety of endoscopic techniques that have either been established or are under current evaluation, for the management of anastomotic leaks in patients with IBD.
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Affiliation(s)
- Aditya Pokala
- Center for Inflammatory Bowel Disease, Columbia University Irving Medical Center/NewYork Presbyterian Hospital, Herbert Irving Pavilion Suite 843, 161 Ft Washington Avenue, New York, NY 10032, USA
| | - Bo Shen
- Center for Inflammatory Bowel Disease, Columbia University Irving Medical Center/NewYork Presbyterian Hospital, Herbert Irving Pavilion Suite 843, 161 Ft Washington Avenue, New York, NY 10032, USA.
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27
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Lan N, Shen B. Endoscopic Therapy for Fistulas and Abscesses in Crohn's Disease. Gastrointest Endosc Clin N Am 2022; 32:733-746. [PMID: 36202513 DOI: 10.1016/j.giec.2022.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Crohn disease (CD) patients can develop fistula or abscess from persistent active disease or postsurgical complications. Penetrating CD is traditionally treated with medication and surgery. The role of medication alone in the treatment of fistula is limited, except perianal fistulas or enterocutaneous fistula. Surgery is the standard treatment in those with hollow-organ to hollow-organ fistula, like ileovesicular fistula. Surgery is invasive with a higher risk of postoperative complications. Endoscopic therapy has evolved as a valid option. Fistulotomy, surgical or endoscopic, should be considered first-line therapy when feasible. Incision and drainage of perianal abscesses with an endoscopic device may be attempted.
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Affiliation(s)
- Nan Lan
- Center for Inflammatory Bowel Disease, Columbia University Irving Medical Center-NewYork Presbyterian Hospital, 161 Fort Washington Avenue, HIP Floor 8-843, New York, NY 10032, USA
| | - Bo Shen
- Center for Inflammatory Bowel Disease, Columbia University Irving Medical Center-NewYork Presbyterian Hospital, 161 Fort Washington Avenue, HIP Floor 8-843, New York, NY 10032, USA.
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28
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Wetwittayakhlang P, Al Khoury A, Hahn GD, Lakatos PL. The Optimal Management of Fistulizing Crohn's Disease: Evidence beyond Randomized Clinical Trials. J Clin Med 2022; 11:3045. [PMID: 35683433 PMCID: PMC9181669 DOI: 10.3390/jcm11113045] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/21/2022] [Accepted: 05/25/2022] [Indexed: 02/04/2023] Open
Abstract
Fistulizing Crohn's disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require a multidisciplinary approach, including a combined medical and surgical approach. The therapeutic options for FCD are limited due to sparse evidence from randomized clinical trials (RCTs). The current recommendations are mainly based on post hoc analysis from RCTs, real-world clinical studies and expert opinion. There is variation in everyday clinical practice amongst gastroenterologists and surgeons. The evidence for anti-tumor necrosis factor therapy is the strongest in the treatment of FCD. However, long-term fistula healing can be achieved in only 30-50% of patients. In recent years, emerging data in the advent of therapeutic modalities, including the use of new biologic agents, therapeutic drug monitoring, novel surgical methods and mesenchymal stem cell therapy, have been shown to improve outcomes in achieving fistula healing. This review summarizes the existing literature on current and emerging therapies to provide guidance beyond RCTs in managing FCD.
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Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Alex Al Khoury
- Division of Gastroenterology, University of Florida, Jacksonville, FL 32209, USA;
| | - Gustavo Drügg Hahn
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- Graduate Course Sciences in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil
| | - Peter Laszlo Lakatos
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- First Department of Medicine, Semmelweis University, 1085 Budapest, Hungary
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29
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Choshen S, Turner D, Pratt LT, Precel R, Greer ML, Castro DA, Assa A, Martínez-León MI, Herman-Sucharska I, Coppenrath E, Konen O, Davila J, Bekhit E, Alsabban Z, Focht G, Gavish M, Griffiths A, Cytter-Kuint R. Development and Validation of a Pediatric MRI-Based Perianal Crohn Disease (PEMPAC) Index-A Report from the ImageKids Study. Inflamm Bowel Dis 2022; 28:700-709. [PMID: 34151950 DOI: 10.1093/ibd/izab147] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND As part of the prospective multicenter ImageKids study, we aimed to develop and validate the pediatric MRI-based perianal Crohn disease (PEMPAC) index. METHODS Children with Crohn disease with any clinical perianal findings underwent pelvic magnetic resonance imaging at 21 sites globally. The site radiologist and 2 central radiologists provided a radiologist global assessment (RGA) on a 100 mm visual analog scale and scored the items selected by a Delphi group of 35 international radiologists and a review of the literature. Two weighted multivariable statistical models were constructed against the RGA. RESULTS Eighty children underwent 95 pelvic magnetic resonance imaging scans; 64 were used for derivation and 31 for validation. The following items were included: fistula number, location, length and T2 hyperintensity; abscesses; rectal wall involvement; and fistula branching. The last 2 items had negative beta scores and thus were excluded in a contending basic model. In the validation cohort, the full and the basic models had the same strong correlation with the RGA (r = 0.75; P < 0.01) and with the adult Van Assche index (VAI; r = 0.93 and 0.92; P < 0.001). The correlation of the VAI with the RGA was similar (r = 0.77; P < 0.01). The 2 models and the VAI had a similar ability to differentiate remission from active disease (area under the receiver operating characteristic curve, 0.91-0.94). The PEMPAC index had good responsiveness to change (area under the receiver operating characteristic curve, 0.89; 95% confidence interval, 0.69-1.00). CONCLUSIONS Using a blended judgmental and mathematical approach, we developed and validated an index for quantifying the severity of perianal disease in children with CD. The adult VAI may also be used with confidence in children.
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Affiliation(s)
- Sapir Choshen
- Pediatric Department, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Dan Turner
- The Juliet Keidan Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel.,Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Li-Tal Pratt
- Pediatric Imaging Unit, Imaging Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ronit Precel
- Pediatric Imaging Unit, Imaging Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Mary-Louise Greer
- Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada.,Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Denise A Castro
- Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada.,Department of Diagnostic Radiology, Kingston Health Science Centre, Queen's University, Kingston, Canada
| | - Amit Assa
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Diagnostic Imaging, Schneider Children's Hospital, Petach-Tikva, Israel
| | | | | | | | - Osnat Konen
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Diagnostic Imaging, Schneider Children's Hospital, Petach-Tikva, Israel
| | - Jorge Davila
- Department of Medical Imaging, Children's Hospital of Eastern Ontario, Ottawa, Canada
| | - Elhamy Bekhit
- Department of Medicine and Radiology, The Royal Children's Hospital, Melbourne, Australia
| | - Zehour Alsabban
- Department of Radiology, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Gili Focht
- The Juliet Keidan Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Matan Gavish
- School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel
| | - Anne Griffiths
- Department of Gastroenterology, Hospital for Sick Children, University of Toronto, Canada
| | - Ruth Cytter-Kuint
- Radiology Department, Shaare Zedek Medical Center, Jerusalem, Israel
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30
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Vieujean S, Caron B, Jairath V, Benetos A, Danese S, Louis E, Peyrin-Biroulet L. Is it time to include older adults in inflammatory bowel disease trials? A call for action. THE LANCET. HEALTHY LONGEVITY 2022; 3:e356-e366. [PMID: 36098310 DOI: 10.1016/s2666-7568(22)00060-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 03/04/2022] [Accepted: 03/09/2022] [Indexed: 02/07/2023] Open
Abstract
The therapeutic management of older patients with inflammatory bowel disease (IBD) is challenging, particularly because of the absence of evidence-based guidelines for these patients, who seem to frequently be excluded from clinical trials. In this systematic review we investigated the exclusion of older patients with IBD from phase 3 studies registered on PubMed and ClinicalTrials.gov, by assessing the upper limit of age exclusion criteria and the percentage of patients older than 65 years included in the trials. Exclusion criteria other than age were also recorded, and comorbidities were analysed separately. Our review of 222 phase 3 studies shows that older patients are frequently excluded from IBD clinical trials because of their age, which was used as an exclusion criterion in 129 (58%) of the 222 assessed trials. Of the 32 trials that detailed the percentage of included patients who were 65 years or older, only 763 (5·4%) patients of the 14 124 patients included were older than 65 years. In addition to age, patients were also excluded because of comorbidities (mainly renal, hepatic, and cardiovascular, and used as an exclusion criterion in 76% of trials), a history of dysplasia (45% of trials), and previous treatment for IBD (19% of trials). We propose a three-step process that should enable the inclusion of all older patients in IBD clinical trials, regardless of their age, comorbidities, and frailty.
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Affiliation(s)
- Sophie Vieujean
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
| | - Bénédicte Caron
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Vipul Jairath
- Department of Medicine, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada; Alimentiv, London, ON, Canada
| | - Athanase Benetos
- Inserm, DCAC, University of Lorraine, Vandoeuvre-lès-Nancy, France; CHRU-Nancy Brabois, Department of Clinical Geriatrics, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Edouard Louis
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France.
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Queiroz NSF, Garcia KS, Miranda EF, Kotze PG. Patient-Reported Outcomes Measures in Perianal Fistulizing Crohn's Disease. Rev Recent Clin Trials 2022; 17:RRCT-EPUB-122860. [PMID: 35469573 DOI: 10.2174/1574887117666220425125424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 01/06/2022] [Accepted: 01/10/2022] [Indexed: 06/14/2023]
Abstract
Perianal fistulizing Crohn's disease (PFCD) is a disabling complication of Crohn's disease (CD) that can significantly impact on patients' quality of life (QoL) and often requires multidisciplinary care. Clinical trials assessing the efficacy of medical and surgical interventions for fistulas usually evaluate outcomes such as closure of fistula tracts or radiologic healing. However, these traditional outcome assessments fail in capturing the impact of the disease from patients' perspectives. In this context, regulatory authorities have increasingly encouraged the inclusion of validated patient-reported outcomes (PRO) that assess disease activity and reveal how a patient functions and feels. This recent trend towards patient-centered care aims to ensure that improvements in efficacy outcomes are accompanied by meaningful benefits to patients. The aim of this review is to discuss currently available PRO measures (PROMS) for the assessment of PFCD to provide to physicians appropriate tools aiming to optimize patient care and disseminate the use of these instruments in clinical practice.
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Affiliation(s)
| | - Karoline Soares Garcia
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Eron Fabio Miranda
- Colorectal Surgery Unit, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
| | - Paulo Gustavo Kotze
- Colorectal Surgery Unit, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
- Health Sciences Postgraduate Program, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil
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Huang H, Ji L, Gu Y, Li Y, Xu S. Efficacy and Safety of Sphincter-Preserving Surgery in the Treatment of Complex Anal Fistula: A Network Meta-Analysis. Front Surg 2022; 9:825166. [PMID: 35211503 PMCID: PMC8861434 DOI: 10.3389/fsurg.2022.825166] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 01/07/2022] [Indexed: 12/23/2022] Open
Abstract
Background There are many surgical methods of sphincter preservation in treating complex anal fistula, but the therapeutic effects of each operation are different. Therefore, this study aimed to compare the impact of other treatment methods through a network meta-analysis to evaluate the best sphincter preservation method for treating complex anal fistula. Methods We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Journal Database, and the Wanfang Database to collate randomized controlled trials on sphincter-preserving surgery for complex anal fistula. Results A total of 29 articles were included in this meta-analysis. The cure rates showed no statistically significant differences between any two interventions (P > 0.05). The recurrence rate results showed that the rate of patients after Fistulectomy was higher than others (P < 0.05). The incidence rate of complications showed that the incidence rate after fistulectomy treatment was higher than that of others (P < 0.05). The surface under the cumulative ranking (SUCRA) was used to arrange their advantages and disadvantages, and a larger SUCRA value indicates that the intervention may be more effective. The results showed that TROPIS may have the highest cure rate (SUCRA = 78.6%), stem cell transplantation (SCT) may have the lowest recurrence rate (SUCRA = 85.5%), and imLIFT may have the least complications (SUCRA = 88.2%). Conclusion According to the existing literature data, for patients with complex anal fistula, TROPIS may be the surgical method with the highest cure rate, SCT may be the treatment method with the lowest recurrence rate, and imLIFT may be the surgical method with the lowest incidence of postoperative complications. Systematic Review Registration PROSPERO, identifier: CRD42020221907.
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Affiliation(s)
- Hua Huang
- Department of Anorectal, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
| | - Lijiang Ji
- Department of Anorectal, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
- *Correspondence: Lijiang Ji
| | - Yunfei Gu
- Department of Anorectal, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Youran Li
- Department of Anorectal, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Shanshan Xu
- Nanjing University of Chinese Medicine, Nanjing, China
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Wood T, Truong A, Mujukian A, Zaghiyan K, Fleshner P. Increasing experience with the LIFT procedure in Crohn's disease patients with complex anal fistula. Tech Coloproctol 2022; 26:205-212. [PMID: 35103901 DOI: 10.1007/s10151-022-02582-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 01/21/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Surgical management of anal fistulas in Crohn's disease (CD) is associated with high failure rates, and treatment options are limited due to ongoing proctitis, multiple tracts, and concern for incontinence and non-healing wounds. The aim of this study was to investigate the healing rate of ligation of the inters-sphincteric fistula tract (LIFT) for anal fistulas in Crohn's disease and identify prognostic factors for healing. METHODS This prospective analysis compared long-term healing rates of CD patients undergoing LIFT for anal fistulas. Consecutive patients with CD who underwent LIFT procedure at our institution, in the period from March 2012 to September 2019 were included. The main outcome was anal fistula healing rate. RESULTS The study cohort of 46 patients (mean age of 34.2 ± 13.0 years, 18 (40%) males). After a mean follow-up time of 33 ± 28 months, fistula healing was seen in 30 (65%) patients. A total of 8 patients were noted to have inter-sphincteric recurrence and 8 patients had trans-sphincteric recurrence. Smoking at the time of surgery was significantly associated with LIFT failure (HR 3.18, 95% CI 1.18-8.61, p = 0.02). Other factors, such as age, sex, race, disease duration and location, type of fistula history of proctitis, preoperatively use of biologics or a seton, and previous repair attempts, did not appear to influence LIFT healing. Although not statistically significant, there was a trend toward increase in failure among patients with active proctitis at the time of surgery (HR 1.97, 95% CI 0.71-5.42, p = 0.19). CONCLUSION Our increasing experience with LIFT for anal fistula in CD demonstrates a higher rate of healing (65%) than previously reported (48%). Smoking appears to negatively influence healing of LIFT in CD.
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Affiliation(s)
- T Wood
- Department of Surgery, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 101, Los Angeles, CA, 90048, USA
| | - A Truong
- Department of Surgery, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 101, Los Angeles, CA, 90048, USA
| | - A Mujukian
- Department of Surgery, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 101, Los Angeles, CA, 90048, USA
| | - K Zaghiyan
- Department of Surgery, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 101, Los Angeles, CA, 90048, USA
| | - P Fleshner
- Department of Surgery, Cedars-Sinai Medical Center, 8737 Beverly Blvd, Suite 101, Los Angeles, CA, 90048, USA.
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Geldof J, Iqbal N, Warusavitarne J, Hart A. The Essential Role of a Multidisciplinary Approach in Inflammatory Bowel Diseases: Combined Medical-Surgical Treatment in Complex Perianal Fistulas in CD. Clin Colon Rectal Surg 2022; 35:21-31. [PMID: 35069027 PMCID: PMC8763455 DOI: 10.1055/s-0041-1740035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Perianal fistulizing Crohn's disease (PFCD) represents a challenging and complex disease phenotype. Patients typically suffer a more severe disease course than those without perianal complications and are often managing debilitating symptoms. Etiology is understood to be multifactorial, with genetic predisposition, microbiological insult, aberrant immunity, and mechanical factors all implicated. As a result, multimodal treatment strategies must be employed to achieve disease control and fistula closure. This requires the complimentary involvement of medical and surgical disciplines in order to ensure thorough assessment and treatment tailored to the individual scenario and patient goals. The aim of this article is to describe an overview of the various treatment strategies available for PFCD, focusing on how a synergistic approach is required to ensure maximal chances of success.
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Affiliation(s)
- Jeroen Geldof
- IBD Unit, St. Mark's Hospital, Harrow, United Kingdom,Gastroenterology Department, University Hospital Ghent, Ghent, Belgium,Address for correspondence Jeroen Geldof, MD IBD Unit, St. Mark's HospitalWatford Road, Harrow HA1 3UJUnited Kingdom
| | - Nusrat Iqbal
- Robin Phillips Fistula Research Unit, St. Mark's Hospital, Harrow, United Kingdom
| | | | - Ailsa Hart
- IBD Unit, St. Mark's Hospital, Harrow, United Kingdom,Robin Phillips Fistula Research Unit, St. Mark's Hospital, Harrow, United Kingdom
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Yzet C, Brazier F, Sabbagh C, Fumery M. Managing complex perianal disease after anti-TNF failure: Where to go next? CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2022; 3:100081. [PMID: 35106477 PMCID: PMC8784625 DOI: 10.1016/j.crphar.2022.100081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 01/10/2022] [Accepted: 01/10/2022] [Indexed: 12/05/2022] Open
Abstract
Crohn's disease is a chronic inflammatory bowel disease that affects various intestinal segments and can involve the perianal region. Although anti-tumor necrosis factor (TNF) agents have revolutionized the management of Crohn's disease and improved the prognosis for patients with perianal Crohn's disease (pCD), their long-term effectiveness is limited: over 60% of patients relapse after one year of maintenance therapy. In recent years, significant advances have been made in the treatment of complex perianal fistulas after anti-TNF failure. Concomitant treatment with antibiotics and immunosuppressants improves the effectiveness of anti-TNF agents. Therapeutic drug monitoring and dose adjustment of anti-TNF therapy (targeting a higher trough level) might also improve treatment response. Novel therapeutic strategies might provide new opportunities for pCD management; for example, ustekinumab might be effective after anti-TNF treatment failure, although more studies are needed. As suggested in recent international guidelines, mesenchymal stem cell injection might be an effective, safe treatment for complex pCD.
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Affiliation(s)
- Clare Yzet
- Gastroenterology Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| | - Franck Brazier
- Gastroenterology Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| | - Charles Sabbagh
- Digestive Surgery Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens University Medical Center and Jules Verne University of Picardie, Amiens, France
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An Affordable Approach of Mesenchymal Stem Cell Therapy in Treating Perianal Fistula Treatment. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1401:73-95. [DOI: 10.1007/5584_2022_716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Meyer J, Ris F, Parkes M, Davies J. Rectovaginal Fistula in Crohn's Disease: When and How to Operate? Clin Colon Rectal Surg 2022; 35:10-20. [PMID: 35069026 PMCID: PMC8763467 DOI: 10.1055/s-0041-1740029] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Rectovaginal fistula (RVF) occurring during the course of Crohn's disease (CD) constitutes a therapeutic challenge and is characterized by a high rate of recurrence. To optimize the outcome of CD-related RVF repair, the best conditions for correct healing should be obtained. Remission of CD should be achieved with no active proctitis, the perianal CD activity should be minimized, and local septic complications should be controlled. The objective of surgical repair is to close the fistula tract with minimal recurrence and functional disturbance. Several therapeutic strategies exist and the approach should be tailored to the anatomy of the RVF and the quality of the local supporting tissues. Herein, we review the medical and surgical management of CD-related RVF.
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Affiliation(s)
- Jeremy Meyer
- Division of Digestive Surgery, University Hospitals of Geneva, Geneva, Switzerland
- Medical School, University of Geneva, Genève, Switzerland
| | - Frédéric Ris
- Division of Digestive Surgery, University Hospitals of Geneva, Geneva, Switzerland
- Medical School, University of Geneva, Genève, Switzerland
| | - Miles Parkes
- Division of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Justin Davies
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
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Buscail E, Le Cosquer G, Gross F, Lebrin M, Bugarel L, Deraison C, Vergnolle N, Bournet B, Gilletta C, Buscail L. Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn's Disease: Rationale, Clinical Results and Perspectives. Int J Mol Sci 2021; 22:ijms22189967. [PMID: 34576129 PMCID: PMC8470328 DOI: 10.3390/ijms22189967] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/07/2021] [Accepted: 09/12/2021] [Indexed: 12/16/2022] Open
Abstract
Between 20 to 25% of Crohn’s disease (CD) patients suffer from perianal fistulas, a marker of disease severity. Seton drainage combined with anti-TNFα can result in closure of the fistula in 70 to 75% of patients. For the remaining 25% of patients there is room for in situ injection of autologous or allogenic mesenchymal stem cells such as adipose-derived stem/stromal cells (ADSCs). ADSCs exert their effects on tissues and effector cells through paracrine phenomena, including the secretome and extracellular vesicles. They display anti-inflammatory, anti-apoptotic, pro-angiogenic, proliferative, and immunomodulatory properties, and a homing within the damaged tissue. They also have immuno-evasive properties allowing a clinical allogeneic approach. Numerous clinical trials have been conducted that demonstrate a complete cure rate of anoperineal fistulas in CD ranging from 46 to 90% of cases after in situ injection of autologous or allogenic ADSCs. A pivotal phase III-controlled trial using allogenic ADSCs (Alofisel®) demonstrated that prolonged clinical and radiological remission can be obtained in nearly 60% of cases with a good safety profile. Future studies should be conducted for a better knowledge of the local effect of ADSCs as well as for a standardization in terms of the number of injections and associated procedures.
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Affiliation(s)
- Etienne Buscail
- Department of Surgery, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France;
- IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Guillaume Le Cosquer
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
| | - Fabian Gross
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
| | - Marine Lebrin
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
| | - Laetitia Bugarel
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
| | - Céline Deraison
- IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Nathalie Vergnolle
- IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Barbara Bournet
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
| | - Cyrielle Gilletta
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
| | - Louis Buscail
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
- Correspondence: ; Tel.: +33-561323055
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El-Nakeep S. Stem Cell Therapy For The Treatment Of Crohn's Disease; Current Obstacles And Future Hopes. (Mini-Review). Curr Stem Cell Res Ther 2021; 17:727-733. [PMID: 34514993 DOI: 10.2174/1574888x16666210910112403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/14/2021] [Accepted: 07/19/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Crohn's disease (CD) is an autoimmune disease of the gastrointestinal tract, characterized by relapsing and remitting courses. The disease is debilitating in nature with three prominent phenotypic clinical presentations; fistulizing, stenosing, and inflammatory. Stem cells offer a new hope for CD patients with modifying the immune response and progression of the healing process. AIM This mini-review discusses the role of stem cells in treating CD, their effectiveness as a new therapy and their current limitations faced. METHODS The author conducted a literature review on recent randomized controlled trials and cohort studies concerned with the topic in question using the following keywords (Crohn's Disease, perianal fistula, Stem cell therapy, mesenchymal stem cells, remission). RESULTS Clinical trials show that the stem cells are more effective in the CD associated complex perianal fistula than the CD enteritis. Till the time being, there are no standardized guidelines regarding; dose of stem cells used, number of doses administered, route of administration, type of stem cells used. Only one group of researchers proposed a standardized procedure for injecting mesenchymal stem cells in complex perianal fistula, according to their own experience in clinical trials. Moreover, mesenchymal stem cells and their related types (placental, adipose tissue, umbilical tissue, etc.) are the most safe and effective in clinical trials. Currently; the commercially available mesenchymal stem cells preparation (Darvadstrocel (Cx601)) is the only one approved by The United States Food and Drug Administration (FDA) for clinical use in refractory CD associated complex perianal fistula. CONCLUSIONS Stem cell therapy (SCT) shows promise in; inducing remission in refractory Crohn's colitis, and perianal fistula, but further research is required before SCT could be applied to clinical practice guidelines.
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Affiliation(s)
- Sarah El-Nakeep
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo. Egypt
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Rectovaginal fistula in Crohn's disease treatment: a low long-term success rate and a high definitive stoma risk after a conservative surgical approach. Tech Coloproctol 2021; 25:1143-1149. [PMID: 34436729 DOI: 10.1007/s10151-021-02506-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 08/11/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND Management of rectovaginal fistula (RVF) in Crohn's disease (CD) is challenging. Available studies are heterogeneous and retrospective, with short-term follow-up. The aim of this study was to assess the overall long-term medico-surgical treatment results in women with RVF due to CD. METHODS A retrospective study was conducted on consecutive patients operated on for RVF in CD from September 1996 to November 2019 at a tertiary teaching hospital. All surgeries were classified as preliminary, closure, or salvage procedures. Primary outcome was fistula remission defined as the combination of fistula closure and no stoma, at least 6 months since last procedure. RESULTS Thirty-two patients (median age 34 [range 21-55] years), with a median follow-up of 11.3 years (0-23.7) after first surgery, were included. Altogether, 138 procedures were performed; 36 (26%) preliminary, 80 (58%) closure, and 13 (9%) salvage procedures. RVF remission was obtained in 7/32 patients (22%). At the end of follow-up, a stoma was present in 13/32 patients (41%). The percentage of time on biologics was 86% for patients in remission, versus 36% for the others (p = 0.0057). After univariate analysis, only anti-TNF-α was significantly related to successful closure techniques (p = 0.007). CONCLUSIONS The RVF remission rate in CD was low in the long term. However, patients underwent a succession of interventions, and the stoma rate was high. Combination of biologics with surgical management was crucial.
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Caron B, D'Amico F, Danese S, Peyrin-Biroulet L. Endpoints for Perianal Crohn's Disease Trials: Past, Present and Future. J Crohns Colitis 2021; 15:1387-1398. [PMID: 33550374 DOI: 10.1093/ecco-jcc/jjab026] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Since the 1980s, many studies have evaluated the efficacy of therapies to improve the outcomes of patients with perianal Crohn's disease. We performed a systematic review to describe the evolution of endpoints in perianal fistulizing Crohn's disease. Efficacy outcomes, definitions and measurement tools were assessed. METHODS Electronic databases were searched up to November 1, 2020. All published randomized placebo-controlled trials enrolling patients with perianal fistula and Crohn's disease were eligible for inclusion. Ongoing randomized clinical trials were also described. RESULTS Nineteen randomized controlled trials were included. Clinical efficacy endpoints were reported in all trials. Clinical response was the most frequent primary endpoint [6/19 studies, 31.6%], followed by clinical remission in four studies [21%]. Clinical response was defined as closure of at least 50% of fistulas, while remission was defined as closure of all fistulas. A combined clinical and radiological primary endpoint was used to assess fistula healing in four studies [21%]. The Perianal Disease Activity Index was a primary endpoint in only one study [5.5%]. In addition, eight ongoing controlled trials were identified. Combined clinical and radiological remission was the most frequent primary endpoint in these studies [4/8, 50%]. CONCLUSION In this systematic review, significant changes in outcomes used in randomized clinical trials of perianal Crohn's disease were observed. Radiological endpoints are increasingly used in perianal fistulizing Crohn's disease trials.
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Affiliation(s)
- Bénédicte Caron
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Department of Gastroenterology, IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Department of Gastroenterology, IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
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Shi G, Wang Y, Wang Z, Thoreson AR, Jacobson DS, Amadio PC, Behfar A, Moran SL, Zhao C. A novel engineered purified exosome product patch for tendon healing: An explant in an ex vivo model. J Orthop Res 2021; 39:1825-1837. [PMID: 32936480 PMCID: PMC9235100 DOI: 10.1002/jor.24859] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 09/04/2020] [Accepted: 09/14/2020] [Indexed: 02/04/2023]
Abstract
Reducing tendon failure after repair remains a challenge due to its poor intrinsic healing ability. The purpose of this study is to investigate the effect of a novel tissue-engineered purified exosome product (PEP) patch on tendon healing in a canine ex vivo model. Lacerated flexor digitorum profundus (FDP) tendons from three canines' paws underwent simulated repair with Tisseel patch alone or biopotentiated with PEP. For the ex vivo model, FDP tendons were randomly divided into three groups: FDP tendon repair alone group (Control), Tisseel patch alone group, and the Tisseel plus PEP (TEPEP) patch group. Following 4 weeks of tissue culture, the failure load, stiffness, histology, and gene expression of the healing tendon were evaluated. Transmission electron microscopy revealed that in exosomes of PEP the diameters ranged from 93.70 to 124.65 nm, and the patch release test showed this TEPEP patch could stably release the extracellular vesicle over 2 weeks. The failure strength of the tendon in the TEPEP patch group was significantly higher than that of the Control group and Tisseel alone group. The results of histology showed that the TEPEP patch group had the smallest healing gap and the largest number of fibroblasts on the surface of the injured tendon. Quantitative reverse transcription polymerase chain reaction showed that TEPEP patch increased the expression of collagen type III, matrix metallopeptidase 2 (MMP2), MMP3, MMP14, and reduced the expression of transforming growth factor β1, interleukin 6. This study shows that the TEPEP patch could promote tendon repair by reducing gap formation and inflammatory response, increasing the activity of endogenous cells, and formation of type III collagen.
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Affiliation(s)
- Guidong Shi
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
- Tianjin Medical University, Tianjin, China
| | - Yicun Wang
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Zhanwen Wang
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | | | | | - Peter C. Amadio
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Atta Behfar
- Van Cleve Cardiac Regenerative Medicine Program, Center for Regenerative Medicine, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
| | - Steven L. Moran
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Chunfeng Zhao
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
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Pedersen KE, Lightner AL. Managing Complex Perianal Fistulizing Disease. J Laparoendosc Adv Surg Tech A 2021; 31:890-897. [PMID: 34314631 DOI: 10.1089/lap.2021.0285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Perianal disease is a particularly morbid phenotype of Crohn's disease, affecting up to one third of patients, with a significantly diminished quality of life. Conventional medical therapy and surgical interventions have limited efficacy. Medical treatment options achieve long-term durable remission in only a third of patients. Therefore, most patients undergo an operation, leaving them with a chronic seton or at risk of incontinence with multiple interventions. Mesenchymal stem cell therapy is an emerging therapy without risk of incontinence and improved efficacy as compared with conventional therapy. Laser therapy is another new intervention. Unfortunately, up to 40% of patients still require a stoma related to perianal fistulizing disease.
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Affiliation(s)
- Karina E Pedersen
- College of Medicine, Northeast Ohio Medical University, Rootstown, Ohio, USA
| | - Amy L Lightner
- Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, Ohio, USA
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Studniarek A, Abcarian A, Pan J, Wang H, Gantt G, Abcarian H. What is the best method of rectovaginal fistula repair? A 25-year single-center experience. Tech Coloproctol 2021; 25:1037-1044. [PMID: 34101044 DOI: 10.1007/s10151-021-02475-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 05/30/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND The surgical treatment of rectovaginal fistula (RVF) remains challenging and there is a lack of data to demonstrate the best, single procedure. The aim of this study was to assess the results of different surgical operations for rectovaginal fistula. METHODS Patients with RVF who underwent surgical repair between 1992 and 2017 at a single, tertiary care center were included. Twenty different procedures were performed including: primary closure, closure with sphincter repair, flap repairs, plug/fibrin/mesh repair, examination under anesthesia (EUA) ± seton placement, abdominal resections with and without diversion and ileostomy takedown, gracilis muscle transposition, fistulotomy/ligation of intersphincteric fistula tract. All patients with RVF due to diverticulitis and patients without complete data from paper charting were excluded. Success was defined based on the absence of symptoms related to RVF and absence of diverting stoma at 6 months. RESULTS One hundred twenty-four women were analyzed. The median age was 45 (range 18-84) years. Median follow-up time from the last procedure was 6 months (range 0-203 months). The total number of patients considered successfully treated at the end of their treatment was 91 (91/124, 73.4%). When considering all procedures (n = 255), the success rate for flap procedures was 57.9% (22/38), followed by abdominal resections with and without proximal diversion and ileostomy takedown (16/29, 55.2%) and primary closure with sphincter repair (17/32, 53.1%) while fistula plug, and fibrin glue had among the lowest success rates (4/22, 18.2%). The highest success rate was observed among patients whose RVF etiology was due to malignancy (11/16, 68.8%) followed by unknown (8/14, 57%) and iatrogenic (21/48, 43.8%) causes. CONCLUSIONS Local procedures such as mucosal flap or primary closure and sphincteroplasty are associated with a high success rate should be considered in patients with low-lying, simple RVF. Abdominal resections with and without proximal diversions and ileostomy takedown have a relatively high success rate in selected patients. The low success rate of fibrin glue and fistula plugs demonstrates their low efficacy in RVF; thus, these procedures should be avoided in the treatment algorithm.
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Affiliation(s)
- A Studniarek
- Division of Colon and Rectal Surgery, University of Illinois at Chicago, 840 S. Wood St., Suite 518E CSB (MC 958), Chicago, USA.
| | - A Abcarian
- Cook County Health and Hospitals Systems, Chicago, IL, USA
| | - J Pan
- Division of Colon and Rectal Surgery, University of Illinois at Chicago, 840 S. Wood St., Suite 518E CSB (MC 958), Chicago, USA
| | - H Wang
- Division of Epidemiology and Biostatistics, and Center for Clinical and Translational Science, University of Illinois at Chicago, Chicago, IL, USA
| | - G Gantt
- Division of Colon and Rectal Surgery, University of Illinois at Chicago, 840 S. Wood St., Suite 518E CSB (MC 958), Chicago, USA
| | - H Abcarian
- Division of Colon and Rectal Surgery, University of Illinois at Chicago, 840 S. Wood St., Suite 518E CSB (MC 958), Chicago, USA.,Cook County Health and Hospitals Systems, Chicago, IL, USA
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Vidon M, Munoz-Bongrand N, Lambert J, Maggiori L, Zeitoun JD, Corte H, Panis Y, Seksik P, Treton X, Abramowitz L, Allez M, Gornet JM. Long-term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease. Colorectal Dis 2021; 23:894-900. [PMID: 33278859 DOI: 10.1111/codi.15477] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 11/16/2020] [Accepted: 11/26/2020] [Indexed: 12/13/2022]
Abstract
AIM The treatment of perianal fistulas in Crohn's disease remains challenging. Fibrin glue injection has previously shown short-term efficacy in a randomized controlled trial. No long-term data are available to assess the benefit of this treatment. METHODS This retrospective multicentre study included all patients with drained fistulas treated by at least one fibrin glue injection between January 2004 and June 2015 in three tertiary French centres. The primary end-point was the rate of complete clinical remission at 1 year after injection defined by the closure of all fistula tracts with no need for iterative anal surgery or for optimization of immunosuppressants and/or biologics. RESULTS In all, 119 patients (median age 33 years, complex fistulas 65%, median previous anal surgery two, median Harvey Bradshaw score 3, immunosuppressants exposure 50%, anti-tumor necrosis factor exposure 60% with median time of administration of 1.1 year) were analysed with a median follow-up of 18.3 months. The complete clinical remission rate at 1 year was 45.4%. The primary end-point was achieved in 63% of the cases in the combination therapy group and 37% in other patients. The only predictor of complete clinical remission at 1 year was combination therapy at the time of injection (P = 0.01). The rate of early reintervention after glue injection was 2.5%. The cumulative incidence of iterative anal surgery and ostomy in the whole population was 54% and 5.6% respectively at 5 years. CONCLUSION An adjunct of fibrin glue to conventional medical therapy may be an effective and safe treatment for perianal fistulas in patients with Crohn's disease.
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Affiliation(s)
- Mathias Vidon
- Service de Gastroentérologie, Hôpital Saint-Louis, Paris, France
| | | | - Jérôme Lambert
- Université Paris-Denis Diderot, Paris, France.,Service de Biostatistiques, Hôpital Saint-Louis, Paris, France
| | - Léon Maggiori
- Université Paris-Denis Diderot, Paris, France.,Service de Chirurgie Digestive, Hôpital Beaujon, Clichy, France
| | - Jean-David Zeitoun
- Service de Proctologie, Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France
| | - Hélène Corte
- Service de Chirurgie Digestive, Hôpital Saint-Louis, Paris, France
| | - Yves Panis
- Université Paris-Denis Diderot, Paris, France.,Service de Chirurgie Digestive, Hôpital Beaujon, Clichy, France
| | - Philippe Seksik
- Service de Gastroentérologie et Nutrition, APHP, Hôpital Saint-Antoine, Sorbonne Université, Paris, France.,Université Sorbonne-UPMC Paris VI, Paris, France
| | - Xavier Treton
- Université Paris-Denis Diderot, Paris, France.,Service de Gastroentérologie, Hôpital Beaujon, Clichy, France
| | - Laurent Abramowitz
- Proctologie du service de Gastroentérologie, Hôpital Bichat, Clinique Blomet, Groupe Ramsay générale de santé, Paris, France
| | - Matthieu Allez
- Service de Gastroentérologie, Hôpital Saint-Louis, Paris, France.,Université Paris-Denis Diderot, Paris, France
| | - Jean-Marc Gornet
- Service de Gastroentérologie, Hôpital Saint-Louis, Paris, France
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Villiger R, Cabalzar-Wondberg D, Zeller D, Frei P, Biedermann L, Schneider C, Scharl M, Rogler G, Turina M, Rickenbacher A, Misselwitz B. Perianal fistulodesis – A pilot study of a novel minimally invasive surgical and medical approach for closure of perianal fistulae. World J Gastrointest Surg 2021; 13:187-197. [PMID: 33643538 PMCID: PMC7898183 DOI: 10.4240/wjgs.v13.i2.187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/20/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Perianal fistulae strongly impact on quality of life of affected patients.
AIM To challenge and novel minimally invasive treatment options are needed.
METHODS Patients with Crohn’s disease (CD) in remission and patients without inflammatory bowel disease (non-IBD patients) were treated with fistulodesis, a method including curettage of fistula tract, flushing with acetylcysteine and doxycycline, Z-suture of the inner fistula opening, fibrin glue instillation, and Z-suture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks. Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included. The primary end point was fistula healing, defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk.
RESULTS Fistulodesis was performed in 17 non-IBD and 3 CD patients, with a total of 22 fistulae. After 24 wk, all fistulae were healed in 4 non-IBD and 2 CD patients (overall 30%) and fistula remained closed until the end of follow-up at 10-25 mo. In a secondary per-fistula analysis, 7 out of 22 fistulae (32%) were closed. Perianal disease activity index (PDAI) improved in patients with fistula healing. Low PDAI was associated with favorable outcome (P = 0.0013). No serious adverse events were observed.
CONCLUSION Fistulodesis is feasible and safe for perianal fistula closure. Overall success rates is at 30% comparable to other similar techniques. A trend for better outcomes in patients with low PDAI needs to be confirmed.
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Affiliation(s)
- Roxanne Villiger
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
| | | | - Daniela Zeller
- Department of Surgery, Zeller Surgery, Zurich 8008, Switzerland
| | - Pascal Frei
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Christian Schneider
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Michael Scharl
- Department of Gastroenterology, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Matthias Turina
- Visceral- and Transplant Surgery, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Andreas Rickenbacher
- Visceral- and Transplant Surgery, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Benjamin Misselwitz
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
- Visceral Surgery and Medicine, University Hospital of Bern, Bern 3010, Switzerland
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Lee JL, Yoon YS, Yu CS. Treatment Strategy for Perianal Fistulas in Crohn Disease Patients: The Surgeon's Point of View. Ann Coloproctol 2021; 37:5-15. [PMID: 33730796 PMCID: PMC7989558 DOI: 10.3393/ac.2021.02.08] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/08/2021] [Accepted: 02/08/2021] [Indexed: 12/12/2022] Open
Abstract
Perianal fistula is a frequent complication and one of the subclassifications of Crohn disease (CD). It is the most commonly observed symptomatic condition by colorectal surgeons. Accurately classifying a perianal fistula is the initial step in its management in CD patients. Surgical management is selected based on the type of perianal fistula and the presence of rectal inflammation; it includes fistulotomy, fistulectomy, seton procedure, fistula plug insertion, video-assisted ablation of the fistulous tract, stem cell therapy, and proctectomy with stoma creation. Perianal fistulas are also managed medically, such as antibiotics, immunomodulators, and biologics including anti-tumor necrosis factor-alpha agents. The current standard treatment of choice for perianal fistula in CD patients is the multidisciplinary approach combining surgical and medical management; however, the rate of long-term remission is low and is reported to be 50% at most. Therefore, the optimum management strategy for perianal fistulas associated with CD remains controversial. Currently, the goal of management for CD-related perianal fistulas are controlling symptoms and maintaining long-term anal function without proctectomy, while monitoring progression to anorectal carcinoma. This review evaluates perianal fistula in CD patients and determines the optimal surgical management strategy based on recent evidence.
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Affiliation(s)
- Jong Lyul Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Sik Yoon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Sik Yu
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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48
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Zabot GP, Cassol O, Saad-Hossne R, Bemelman W. Modern surgical strategies for perianal Crohn's disease. World J Gastroenterol 2020; 26:6572-6581. [PMID: 33268947 PMCID: PMC7673971 DOI: 10.3748/wjg.v26.i42.6572] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 09/05/2020] [Accepted: 09/28/2020] [Indexed: 02/06/2023] Open
Abstract
One of the most challenging phenotypes of Crohn’s disease is perianal fistulizing disease (PFCD). It occurs in up to 50% of the patients who also have symptoms in other parts of the gastrointestinal tract, and in 5% of the cases it occurs as the first manifestation. It is associated with severe symptoms, such as pain, fecal incontinence, and a significant reduction in quality of life. The presence of perianal disease in conjunction with Crohn’s disease portends a significantly worse disease course. These patients require close monitoring to identify those at risk of worsening disease, suboptimal biological drug levels, and signs of developing neoplasm. The last 2 decades have seen significant advancements in the management of PFCD. More recently, newer biologics, cell-based therapies, and novel surgical techniques have been introduced in the hope of improved outcomes. However, in refractory cases, many patients face the decision of having a stoma made and/or a proctectomy performed. In this review, we describe modern surgical management and the most recent advances in the management of complex PFCD, which will likely impact clinical practice.
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Affiliation(s)
- Gilmara Pandolfo Zabot
- Department of Coloproctology, Hospital Moinhos de Vento, Porto Alegre 90035-902, RS, Brazil
| | - Ornella Cassol
- Department of Surgery, Hospital de Clínicas de Passo Fundo, Passo Fundo 99010-260, RS, Brazil
| | - Rogerio Saad-Hossne
- Department of Internal Medicine, São Paulo State University (Unesp), Medical School, Botucatu 18618687, São Paulo, Brazil
| | - Willem Bemelman
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 19268, Netherlands
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49
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Lightner AL, Ashburn JH, Brar MS, Carvello M, Chandrasinghe P, van Overstraeten ADB, Fleshner PR, Gallo G, Kotze PG, Holubar SD, Reza LM, Spinelli A, Strong SA, Tozer PJ, Truong A, Warusavitarne J, Yamamoto T, Zaghiyan K. Fistulizing Crohn's disease. Curr Probl Surg 2020; 57:100808. [PMID: 33187597 DOI: 10.1016/j.cpsurg.2020.100808] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 04/22/2020] [Indexed: 02/06/2023]
Affiliation(s)
- Amy L Lightner
- Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, OH.
| | - Jean H Ashburn
- Department of Surgery, Wake Forest University Baptist Medical Center, Winston-Salem, NC
| | - Mantaj S Brar
- Department of Surgery, Mount Sinai Hospital, Toronto, ON; Zane Cohen Center for Digestive Diseases, Toronto, ON; Department of Surgery, University of Toronto, ON
| | - Michele Carvello
- Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy
| | | | - Anthony de Buck van Overstraeten
- Department of Surgery, Mount Sinai Hospital, Toronto, ON; Zane Cohen Center for Digestive Diseases, Toronto, ON; Department of Surgery, University of Toronto, ON
| | | | - Gaetano Gallo
- Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy
| | - Paulo Gustavo Kotze
- IBD Outpatient Clinics, Colorectal Surgery Unit, Catholic University of Parana (PUCPR), Curitiba, Brazil
| | - Stefan D Holubar
- Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, OH
| | - Lillian M Reza
- Fistula research Unit, St Mark's Hospital and academic institute, London, UK
| | - Antonino Spinelli
- Humanitas Clinical and Research Center, Colon and Rectal Surgery Unit, Italy; Humanitas University, Department of Biomedical Sciences, Italy
| | - Scott A Strong
- Department of Gastrointestinal Surgery, Northwestern University, Chicago, IL
| | - Philip J Tozer
- Fistula research Unit, St Mark's Hospital and academic institute, London, UK
| | - Adam Truong
- Department of Surgery, Cedars Sinai, Los Angeles, CA
| | | | - Takayuki Yamamoto
- Inflammatory Bowel Disease Center & Department of Surgery, Yokkaichi Hazu Medical Center, Yokkaichi, Japan
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50
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Gallo G, Tiesi V, Fulginiti S, De Paola G, Vescio G, Sammarco G. Mesenchymal Stromal Cell Therapy in the Management of Perianal Fistulas in Crohn's Disease: An Up-To-Date Review. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:563. [PMID: 33121049 PMCID: PMC7692376 DOI: 10.3390/medicina56110563] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 10/19/2020] [Accepted: 10/26/2020] [Indexed: 12/12/2022]
Abstract
Crohn's Disease (CD) is a chronic inflammatory disorder that potentially involves the entire gastrointestinal tract. Perianal fistulizing CD (pCD) is a serious and frequent complication associated with significant morbidities and a heavy negative impact on quality of life. The aim of CD treatment is to induce and maintain disease remission and to promote mucosal repair. Unfortunately, even the best therapeutic regimens in pCD do not have long-term efficacy and cause a significant number of side effects. Therefore, it is mandatory to study new therapeutical options such as the use of mesenchymal stromal cells (MSCs). These cells promote tissue repair via the induction of immunomodulation. The present review aims to analyze the existing updated scientific literature on MSCs adoption in the treatment of pCD to evaluate its efficacy and safety and to compare the use of bone marrow and adipose tissue derived MSCs, type of administration, and dose required for recovery.
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Affiliation(s)
- Gaetano Gallo
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (V.T.); (S.F.); (G.D.P.); (G.V.)
| | - Vincenzo Tiesi
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (V.T.); (S.F.); (G.D.P.); (G.V.)
| | - Serena Fulginiti
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (V.T.); (S.F.); (G.D.P.); (G.V.)
| | - Gilda De Paola
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (V.T.); (S.F.); (G.D.P.); (G.V.)
| | - Giuseppina Vescio
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (V.T.); (S.F.); (G.D.P.); (G.V.)
| | - Giuseppe Sammarco
- Department of Health Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy;
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