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1
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Rodríguez-Lago I, Casas-Deza D, Rimola J, Calafat M, Ferreiro-Iglesias R, Pellino G, Avellaneda N, Iborra M, Barreiro-de Acosta M, Gutiérrez Casbas A, Menchén L, Ordás I, Rodríguez-Moranta F, Zabana Y. Spanish Working Group in Crohn's Disease and Ulcerative Colitis (GETECCU) position paper for the management of non-perianal fistulizing Crohn's disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2025:502450. [PMID: 40250758 DOI: 10.1016/j.gastrohep.2025.502450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2025] [Accepted: 04/11/2025] [Indexed: 04/20/2025]
Abstract
Crohn's disease consists on a complex condition where, despite most patients initially present with an inflammatory behavior, a significant proportion develop complicated lesions such as strictures, fistulas, abscesses, or even perforations. These lesions progressively increase over time and are associated with a higher risk of surgery and hospitalization. Despite significant advances in their management after the introduction of biological therapies, particularly anti-TNF agents, these complications continue to pose challenges for the multiple professionals involved in their care. Fistulas that do not involve the perianal region (entero-enteric, entero-urinary, or entero-cutaneous) require a multidisciplinary strategy that combines medical, interventional, and surgical approaches. Their treatment ranges from general supportive measures to the use of antibiotics or, frequently, advanced therapies. Nevertheless, in cases of certain septic complications or those refractory to medical treatment, percutaneous drainage or surgical intervention remains essential. Although these lesions have a significant impact, evidence regarding the best strategies in this context, as well as the efficacy and safety of different therapies in these patients, remains limited. This is highlighted by the absence of specific recommendations in current guidelines. The objective of this document is to provide a comprehensive overview of non-perianal fistulizing Crohn's disease, addressing its epidemiological, clinical, and therapeutic aspects from a multidisciplinary perspective.
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Affiliation(s)
- Iago Rodríguez-Lago
- Servicio de Aparato Digestivo, Hospital Universitario de Galdakao; Instituto de Investigación Sanitaria Biobizkaia, Galdakao, Bizkaia, España.
| | - Diego Casas-Deza
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet; Instituto de Investigación Sanitaria de Aragón (IISA), Zaragoza, España
| | - Jordi Rimola
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, España
| | - Margalida Calafat
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol; Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Barcelona, España
| | - Rocío Ferreiro-Iglesias
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela; Fundación Galega de Investigación Sanitaria (IDIS), Santiago de Compostela, A Coruña, España
| | - Gianluca Pellino
- Servicio de Cirugía Colorrectal, Hospital Universitari Vall d'Hebron; Universitat Autònoma de Barcelona (UAB), Barcelona, España
| | - Nicolás Avellaneda
- Unidad de Investigación, Hospital Universitario CEMIC, Buenos Aires, Argentina
| | - Marisa Iborra
- Gastroenterología, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - Manuel Barreiro-de Acosta
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela; Fundación Galega de Investigación Sanitaria (IDIS), Santiago de Compostela, A Coruña, España
| | - Ana Gutiérrez Casbas
- Servicio de Aparato Digestivo, Hospital General Universitario Dr. Balmis; Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL); Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Alicante, España
| | - Luis Menchén
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón; Instituto de Investigación Sanitaria Gregorio Marañón; Universidad Complutense, Madrid, España
| | - Ingrid Ordás
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Hospital Clínic, Barcelona; Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS); Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), España
| | - Francisco Rodríguez-Moranta
- Servicio de Aparato Digestivo, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, España
| | - Yamile Zabana
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitari Mútua Terrassa; Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Terrassa, Barcelona, España
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Rinebold E, Huang AL, Hahn SJ. How to Approach the Difficult Perineum in Crohn's Disease. Clin Colon Rectal Surg 2025; 38:148-159. [PMID: 39944307 PMCID: PMC11813606 DOI: 10.1055/s-0044-1786377] [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: 05/09/2025]
Abstract
Crohn's disease (CD) is a chronic, inflammatory bowel disease with a wide range of presentations, including perianal disease. Presentation is variable, ranging from skin tags to complex fistulas, strictures, and nonhealing wounds. Symptoms of perianal CD can be devastating and may impact quality of life. Optimal management requires coordinated medical and surgical therapy. When possible, conservative treatment of perianal disease should be attempted. However, surgical treatment is often required, and some patients may ultimately require total proctocolectomy with permanent diversion due to the severity of disease. Even with close attention and treatment, disease can be recurrent, and complications of treatment are sometimes worse than the initial presentation. Novel treatments, including use of mesenchymal stem cells and autologous fat grafting, hold some promise, but are not yet widely available. Thorough knowledge of treatment options, careful patient selection, coordination between medical and surgical providers, and setting realistic expectations are important in the successful treatment of difficult perineal CD.
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Affiliation(s)
- Emily Rinebold
- Division of Colon and Rectal Surgery, Department of Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, New York
| | - Alex L. Huang
- Division of Colon and Rectal Surgery, Department of Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, New York
| | - Sue J. Hahn
- Division of Colon and Rectal Surgery, Department of Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, New York
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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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Singh A, Midha V, Kochhar GS, Shen B, Sood A. Management of Perianal Fistulizing Crohn's Disease. Inflamm Bowel Dis 2024; 30:1579-1603. [PMID: 37672347 DOI: 10.1093/ibd/izad195] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Indexed: 09/08/2023]
Abstract
Perianal fistulizing Crohn's disease (CD) represents a severe phenotype of CD that is associated with significant morbidity and reduction in quality of life. Perianal fistulizing CD is caused by a complex interplay of genetic predisposition, immune dysregulation, gut dysbiosis, and various unknown physiological and mechanical factors. A multidisciplinary approach is hence required for optimal management . A detailed anatomical description and classification of perianal fistula, including comprehensive clinical, endoscopic, and radiological diagnostic workup, is an important prerequisite to treatment. For simple perianal fistulas, use of antibiotics and immunomodulators, with or without fistulotomy, are appropriate measures. The medical management of complex perianal fistula, on the other hand, requires adequate control of infection before initiation of therapy with immunomodulators. In active complex perianal fistula, anti-tumor necrosis factors remain the most accepted therapy, with concomitant use of antibiotics or immunomodulators enhancing the efficacy. For patients refractory to anti-tumor necrosis factors, treatment with anti-integrins, anti-interleukins, and small molecules is being evaluated. Mesenchymal stem cells, hyperbaric oxygen therapy, and exclusive enteral nutrition have also been investigated as adjunct therapies. Despite the expansion of the medical armamentarium, a large proportion of the patients require surgical interventions. In this review, we provide an up-to-date overview of the pathophysiology, clinical presentation, diagnosis, and medical management of perianal fistulizing CD. A brief overview of the surgical management of perianal fistulizing CD is also provided.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College, Ludhiana, India
| | - Gursimran Singh Kochhar
- Division of Gastroenterology, Hepatology and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
| | - Bo Shen
- Center for Interventional Inflammatory Bowel Disease, NewYork-Presbyterian Hospital, Columbia University Irving Medical Center, New York, NY, USA
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College, Ludhiana, India
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Katsube S, Matsumoto S, Misawa M, Kakizawa N, Hashimoto R, Mizutani T, Matsumoto K, Yoshikawa S, Mashima H. Successful Fistula Closure After Treatment with Colostomy and Infliximab in a Patient with Ulcerative Colitis Complicated by Rectovaginal Fistula. Biologics 2024; 18:107-113. [PMID: 38736705 PMCID: PMC11086393 DOI: 10.2147/btt.s457300] [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: 12/30/2023] [Accepted: 04/23/2024] [Indexed: 05/14/2024]
Abstract
The patient was a 50-year-old Japanese woman who was diagnosed with total-colitis-type ulcerative colitis (UC) at the age of 26 years. She was treated with mesalazine and azathioprine, and her disease activity was well controlled. At the age of 50 years, the patient was experiencing fever, abdominal pain, diarrhea, bloody stool, and anal pain, which led to a diagnosis of a relapse of UC. Although steroid therapy was administered and tended to improve her symptoms, fecaloid vaginal discharge occurred, and rectovaginal fistula (RVF) was confirmed. Colostomy was performed, and infliximab was initiated as maintenance therapy for UC. All symptoms improved, and RVF closure was confirmed 6 months after the initiation of infliximab. To date, she has been free from relapse of UC. There have been only a few reports of UC complicated by RVF, and this condition is often difficult to treat. To the best of our knowledge, no other case of UC complicated by RVF in which the fistula was closed after treatment with colostomy and infliximab has been previously reported; thus, our report of the present case is valuable to the literature.
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Affiliation(s)
- Sota Katsube
- Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Satohiro Matsumoto
- Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Masahiro Misawa
- Department of Obstetrics and Gynecology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Nao Kakizawa
- Department of General and Gastrointestinal Surgery, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Ryo Hashimoto
- Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Taku Mizutani
- Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Keita Matsumoto
- Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Shuhei Yoshikawa
- Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Hirosato Mashima
- Department of Gastroenterology, Jichi Medical University Saitama Medical Center, Saitama, Japan
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7
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Sohrabi M, Bahrami S, Mosalli M, Khaleghian M, Obaidinia M. Perianal Fistula; from Etiology to Treatment - A Review. Middle East J Dig Dis 2024; 16:76-85. [PMID: 39131109 PMCID: PMC11316198 DOI: 10.34172/mejdd.2024.373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 01/18/2024] [Indexed: 08/13/2024] Open
Abstract
Anal fistula has been a challenging clinical issue for years due to its complex pathogenesis. The risk of frequent recurrence and incontinence complicates long-term treatment. Recent scientific literature has reviewed new techniques used for anal fistula treatment in recent years, assessing the advantages and disadvantages of each based on clinical outcomes. Although surgery is the main method used to treat anal fistula, there is no simple technique that can completely heal complex anal fistula. The surgical treatment should consider the healing outcome and the protection of anal function comprehensively. Several innovative techniques have emerged in recent years, such as combined techniques based on drainage seton and LIFT-plug, which appear to be relatively effective therapies. However, more multi-center prospective trials with long-term follow-up are needed to validate their effectiveness. In some situations, medical treatment may also be considered.
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Affiliation(s)
- Masoudreza Sohrabi
- Gastrointestinal and liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Somayeh Bahrami
- Gastrointestinal and liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mozhdeh Mosalli
- Gastrointestinal and liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Khaleghian
- Gastrointestinal and liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of General Surgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mobin Obaidinia
- Gastrointestinal and liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
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8
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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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9
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Parian AM, Obi M, Fleshner P, Schwartz DA. Management of Perianal Crohn's Disease. Am J Gastroenterol 2023; 118:1323-1331. [PMID: 37207318 DOI: 10.14309/ajg.0000000000002326] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 05/10/2023] [Indexed: 05/21/2023]
Abstract
Perianal Crohn's disease affects 25%-35% of patients with Crohn's disease and has proven to be one of the most difficult complications of the disease to treat. Patients with perianal Crohn's disease have lower health-related quality of life scores typically related to pain and fecal incontinence. In addition, patients with perianal Crohn's disease have higher rates of hospitalizations, surgeries, and overall healthcare costs. A multidisciplinary approach is necessary for the successful management of Crohn's disease with perianal fistula. Medical management is required to treat the underlying immune dysregulation to heal the luminal inflammation and the inflammation within the fistula tracts. Current options for medical therapy include biologics, dual therapy with thiopurines, therapeutic drug monitoring, and a close follow-up. Surgical management is critical to drain abscesses before immunosuppressive therapy and place setons when appropriate. Once the patient's inflammatory burden is well managed, definitive surgical therapies including fistulotomies, advancement flaps, and ligation of intersphincteric fistula tract procedures can be considered. Most recently, the use of stem cell therapy in the treatment of perianal fistula has given new hope to the cure of perianal fistula in Crohn's disease. This review will outline the most current data in the medical and surgical management of perianal Crohn's disease.
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Affiliation(s)
- Alyssa M Parian
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Megan Obi
- Department of General Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Phillip Fleshner
- Division of Colorectal Surgery, Cedars Sinai Medical Center, Los Angeles, California, USA
| | - David A Schwartz
- Inflammatory Bowel Disease Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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10
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The Intersection of Human and Veterinary Medicine-A Possible Direction towards the Improvement of Cell Therapy Protocols in the Treatment of Perianal Fistulas. Int J Mol Sci 2022; 23:ijms232213917. [PMID: 36430390 PMCID: PMC9696944 DOI: 10.3390/ijms232213917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/31/2022] [Accepted: 11/08/2022] [Indexed: 11/16/2022] Open
Abstract
The effective treatment of perianal fistulizing Crohn's disease is still a challenge. Local administration of mesenchymal stromal cells (MSCs) is becoming a part of accepted treatment options. However, as a fledgling technique, it still can be optimized. A new trend in translational research, which is in line with "One Health" approach, bases on exploiting parallels between naturally occurring diseases affecting humans and companion animals. Canine anal furunculosis (AF) has been indicated as condition analogous to human perianal Crohn's disease (pCD). This narrative review provides the first comprehensive comparative analysis of these two diseases based on the published data. The paper also outlines the molecular mechanisms of action of MSCs which are likely to have a role in modulating the perianal fistula niche in humans, and refers them to the current knowledge on the immunomodulatory properties of canine MSCs. Generally, the pathogenesis of both diseases shares main determinants such as the presence of genetic predispositions, dysregulation of immune response and the relation to intestine microbiota. However, we also identified many aspects which should be further specified, such as determining the frequency of true fistulas formation in AF patients, elucidating the role of TNF and Th17 pathway in the pathogenesis of AF, or clarifying the role of epithelial-to-mesenchymal transition phenomenon in the formation of canine fistulae. Nevertheless, the available data support the hypothesis that the results from testing cell therapies in dogs with anal furunculosis have a significant translational value in optimizing MSC transplants procedures in pCD patients.
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Gaertner WB, Burgess PL, Davids JS, Lightner AL, Shogan BD, Sun MY, Steele SR, Paquette IM, Feingold DL. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Anorectal Abscess, Fistula-in-Ano, and Rectovaginal Fistula. Dis Colon Rectum 2022; 65:964-985. [PMID: 35732009 DOI: 10.1097/dcr.0000000000002473] [Citation(s) in RCA: 76] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Wolfgang B Gaertner
- Division of Colon and Rectal Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Pamela L Burgess
- Department of Surgery, Uniformed Services University of the Health Sciences, Eisenhower Army Medical Center, Fort Gordon, Georgia
| | - Jennifer S Davids
- Department of Surgery, University of Massachusetts, Worcester, Massachusetts
| | - Amy L Lightner
- Department of Colon and Rectal Surgery, Cleveland Clinic, Cleveland, Ohio
| | | | - Mark Y Sun
- Department of Surgery, University of Cincinnati, Cincinnati, Ohio
| | - Scott R Steele
- Department of Colon and Rectal Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Ian M Paquette
- Department of Surgery, University of Cincinnati, Cincinnati, Ohio
| | - Daniel L Feingold
- Division of Colorectal Surgery, Rutgers University, New Brunswick, New Jersey
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12
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Park MY, Yoon YS, Lee JL, Park SH, Ye BD, Yang SK, Yu CS. Comparative perianal fistula closure rates following autologous adipose tissue-derived stem cell transplantation or treatment with anti-tumor necrosis factor agents after seton placement in patients with Crohn's disease: a retrospective observational study. Stem Cell Res Ther 2021; 12:401. [PMID: 34256838 PMCID: PMC8278611 DOI: 10.1186/s13287-021-02484-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 06/23/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Perianal fistula is one of the most common complications in Crohn's disease, and various medical and surgical treatments are being tried. The aim of this study was to compare the perianal fistula closure rates following treatment with anti-tumor necrosis factor (TNF) agents or autologous adipose tissue-derived stem cell (auto-ASC) transplantation with Crohn's disease (CD). METHODS CD patients who underwent seton placement for perianal fistula from January 2015 to December 2019 at a tertiary referral center were retrospectively reviewed. Patients were divided into two groups, one that received sequential treatments with anti-TNF agents (anti-TNF group) and the other that underwent auto-ASC transplantation (stem cell group). Clinical variables and fistula closure rates were compared in the two groups. RESULTS Of the 69 patients analyzed, 39 were treated with anti-TNF agents and 30 underwent auto-ASC transplantation. Compared with the stem cell group, patients in the anti-TNF group were older (p=0.028), were more frequently male (p=0.019), had fistulas with more penetrating behavior (p=0.002), had undergone surgery more frequently (p=0.010), and had a shorter interval from seton placement to intended treatment (p<0.001). During a median follow-up of 46 months (range, 30-52.5 months), fistula closure rates were significantly faster (83.3% vs. 23.1%, p<0.001), and the mean interval from seton placement to fistula closure significantly shorter (14 vs. 37 months, p<0.001) in the stem cell than in the anti-TNF group. Three patients experienced fistula recurrence, all in the stem cell group. CONCLUSIONS Medical treatment using anti-TNF agents and auto-ASC transplantation are feasible treatment options after seton placement for Crohn's perianal fistula. However, the closure rate was significantly faster and the time to closure significantly shorter in patients who underwent auto-ASC transplantation than medical treatment. TRIAL REGISTRATION This study was retrospectively registered and approved by the Institutional Review Board of Asan Medical Center, number 2020-1059 .
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Affiliation(s)
- Min Young Park
- Department of Colon and Rectal Surgery, Asan Medical Center, University of College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Yong Sik Yoon
- Department of Colon and Rectal Surgery, Asan Medical Center, University of College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
| | - Jong Lyul Lee
- Department of Colon and Rectal Surgery, Asan Medical Center, University of College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chang Sik Yu
- Department of Colon and Rectal Surgery, Asan Medical Center, University of College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
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13
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Yang Y, Hu N, Gao XJ, Li T, Yan ZX, Wang PP, Wei B, Li S, Zhang ZJ, Li SL, Yan R. Dextran sulfate sodium-induced colitis and ginseng intervention altered oral pharmacokinetics of cyclosporine A in rats. JOURNAL OF ETHNOPHARMACOLOGY 2021; 265:113251. [PMID: 32810615 DOI: 10.1016/j.jep.2020.113251] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 07/04/2020] [Accepted: 08/04/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Application of cyclosporine A (CsA) as a rescue treatment in acute severe ulcerative colitis (UC) is limited by its narrow therapeutic window and great interpatient variability. As a substrate of cytochrome P450 3A enzyme (CYP3A) and P-glycoprotein (P-gp), the oral pharmacokinetics of CsA is susceptible to disease status and concomitant medications. Combined treatment with ginseng, a famous medicinal herb frequently prescribed for ameliorating abnormal immune response in many diseases including UC, showed immunologic safety in CsA-based immunosuppression. AIM OF THE STUDY Since the therapeutic levels of CsA can be achieved within 24 h, this study first assessed the impact of acute colitis and ginseng intervention on the single oral dose pharmacokinetics of CsA and explored the underlying mechanisms in dextran sulfate sodium (DSS)-induced colitis rats and Caco-2 cells. MATERIALS AND METHODS Rats received drinking water (normal group), 5% DSS (UC group), or 5% DSS plus daily oral ginseng extract (GS+UC group). On day 7, GS+UC group only received an oral dose of CsA (5 mg/kg), while animals of normal or UC group received an oral, intravenous (1.25 mg/kg), or intraperitoneal dose of CsA (1.25 mg/kg), respectively. Blood, liver/intestine tissues and fecal samples were collected for determining CsA and main hydroxylated metabolite HO-CsA or measuring hepatic/intestinal CYP3A activity. Caco-2 cells were incubated with gut microbial culture supernatant (CS) of different groups or ginseng (decoction or polysaccharides), and then CYP3A, P-gp and tight junction (TJ) proteins were determined. RESULTS Oral CsA exhibited enhanced absorption, systemic exposure and tissue accumulation, and lower fecal excretion, while intravenous or intraperitoneal CsA showed lower systemic exposure and enhanced distribution, in colitis rats. Diminished intestinal and hepatic P-gp expression well explained the changes with DSS-induced colitis. Moreover, blood exposures of HO-CsA in both normal and colitis after oral dosing were significantly higher than intravenous/intraperitoneal dosing, supporting the dominant role of intestinal first-pass metabolism. Interestingly, colitis reduced CYP3A expression in intestine and liver but only potentiated intestinal CYP3A activity, causing higher oral systemic exposure of HO-CsA. Oral ginseng mitigated colitis-induced down-regulation of CYP3A and P-gp expression, facilitated HO-CsA production, biliary excretion and colonic sequestration of CsA, while not affected CsA oral systemic exposure. In Caco-2 cells, gut microbial CS from both colitis and GS+UC group diminished P-gp function, while ginseng polysaccharides directly affected ZO-1 distribution and suppressed TJ proteins expression, explaining unaltered oral CsA systemic exposure. CONCLUSIONS DSS-induced colitis significantly altered oral CsA disposition through regulating intestinal and hepatic P-gp and CYP3A. One-week ginseng treatment enhanced colonic accumulation while not altered the systemic exposure of CsA after single oral dosing, indicating pharmacokinetic compatibility between the two medications.
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Affiliation(s)
- Ying Yang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, 519080, China
| | - Nan Hu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, 519080, China
| | - Xue-Jiao Gao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, 519080, China
| | - Ting Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, 519080, China
| | - Zhi-Xiang Yan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, 519080, China
| | - Pan-Pan Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, 519080, China
| | - Bin Wei
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, 519080, China
| | - Sai Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, 519080, China
| | - Zai-Jun Zhang
- Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou, 510632, China
| | - Song-Lin Li
- Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, China
| | - Ru Yan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China; Zhuhai UM Science & Technology Research Institute, Zhuhai, 519080, China.
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Abstract
Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract from the mouth to the anus, sparing the rectum. The goal of medical therapy is to induce remission with medications, followed by the administration of maintenance medications to prevent a relapse of the disease. The concept of induction of remission and maintenance of remission is very important, as there is an overlap of medications used to induce and maintain remission. Physicians first direct treatment to induce a remission that involves relief of symptoms and mucosal healing of the lining of the colon and then provide long-term treatment to maintain the remission. Standard treatment for CD depends on the extent of involvement and disease severity, for example, mild, moderate, severe, and fulminant.
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Affiliation(s)
- Ajay K Gade
- Internal Medicine, Brookwood Baptist Medical Center, Birmingham, USA
| | - Nathan T Douthit
- Medical Education Internal Medicine, Brookwood Baptist Health, Birmingham, USA
| | - Erin Townsley
- Medical Education Internal Medicine, Brookwood Baptist Medical Center, Birmingham, USA
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15
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Weissman S, Chris-Olaiya A, Mehta TI, Aziz M, Alshati A, Berry R, Fatima R, Kolli S, Hassan A, Sciarra MA. A novel player: cyclosporine therapy in the management of inflammatory bowel disease. Transl Gastroenterol Hepatol 2019; 4:67. [PMID: 31620649 DOI: 10.21037/tgh.2019.08.08] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 08/15/2019] [Indexed: 11/06/2022] Open
Abstract
Amongst other indications, cyclosporine therapy has emerged as a novel agent for the management of severe refractory ulcerative colitis (UC). In the historic population of patients receiving cyclosporine therapy-namely solid organ transplant patients-renal toxicity has proven to be a significant mitigating side effect limiting the therapeutic window. However, dose-limiting sequelae amongst patients receiving cyclosporine for inflammatory bowel disease (IBD) have not been as significant. As a result, the fear of renal toxicity as an adverse effect is less of a concern in IBD patients. The goal of this manuscript is to emphasize the need for future research to explore optimal drug dosing and extended use of cyclosporine therapy in the treatment of IBD-given its pathophysiology, efficacy, and safety profile in patients with IBD.
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Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack University-Palisades Medical Center, North Bergen, NJ, USA
| | | | - Tej I Mehta
- Department of Medicine, University of South Dakota Sanford school of Medicine, Sioux falls, SD, USA
| | - Muhammad Aziz
- Department of Medicine, University of Kansas Medical Center, Kansas City, MO, USA
| | - Ali Alshati
- Department of Medicine, Maricopa Integrated Health System, Creighton University, Phoenix, AZ, USA
| | - Rani Berry
- Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA
| | - Rawish Fatima
- Department of Medicine, University of Toledo Medical Center, Toledo, OH, USA
| | - Sindhura Kolli
- Department of Medicine, The Brooklyn Hospital Center, Brooklyn, NY, USA
| | - Ammar Hassan
- Division of Gastroenterology and Hepatology, Hackensack University-Palisades Medical Center, North Bergen, NJ, USA
| | - Michael A Sciarra
- Division of Gastroenterology and Hepatology, Hackensack University-Palisades Medical Center, North Bergen, NJ, USA
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16
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DeLeon MF, Hull TL. Treatment Strategies in Crohn's-Associated Rectovaginal Fistula. Clin Colon Rectal Surg 2019; 32:261-267. [PMID: 31275072 DOI: 10.1055/s-0039-1683908] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Rectovaginal fistula (RVF) is a rare, but dreaded complication of Crohn's disease (CD) that is exceedingly difficult to manage. Treatment algorithms range from observation and medical therapy to local surgical repair and proctectomy. The multitude of surgical options and lack of consensus between experts speak to the complexity and shortcomings encountered to correct this disease process surgically. The key to successful management of these fistulae therefore rests on a multidisciplinary approach between the patient, gastroenterologists, and surgeons, with open communication about expectations and goals of care. In this article, we review the management of CD-associated RVF with an emphasis on surgical technique.
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Affiliation(s)
| | - Tracy L Hull
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio
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17
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Bislenghi G, Wolthuis A, Van Assche G, Vermeire S, Ferrante M, D'Hoore A. Cx601 (darvadstrocel) for the treatment of perianal fistulizing Crohn's disease. Expert Opin Biol Ther 2019; 19:607-616. [PMID: 31121104 DOI: 10.1080/14712598.2019.1623876] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Introduction: Given the well-documented difficulty to treat perianal fistulizing Crohn's disease (pCD), with 40% of patients experiencing recurrence even after reiterative surgery and advanced medical therapy, research in this field has focused on the role of mesenchymal stem cells (MSC). Areas covered: The aim of this article is to furnish an overview of the pathogenetic mechanisms, clinical applications and evidences for the use of MSC for pCD with particular focus on adipose-derived allogenic MSC including darvadstrocel. Expert Opinion: The effect of MSC on fistula healing is probably mediated by their anti-inflammatory properties more than by their ability to engraft and trans-differentiate in the healthy tissue. A holistic treatment of pCD, addressing different pathophysiological factors, may represent the key for an improvement in the healing rate. In this setting, MSC might play a role as 'augmentation' therapy in combination with more conventional treatments. Whether MSC have benefit in non-complex fistula in biological naïve patients, in complex fistula with many tracts and/or in rectovaginal fistulas, are unexplored fields that need further investigation. A central registry of pCD patients undergoing treatment with MSC should be created in order to elucidate the efficacy, safety and costs of stem cells treatment on long term follow up.
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Affiliation(s)
- G Bislenghi
- a Department of Abdominal Surgery , University Hospitals Leuven, KU Leuven , Leuven , Belgium
| | - A Wolthuis
- a Department of Abdominal Surgery , University Hospitals Leuven, KU Leuven , Leuven , Belgium
| | - G Van Assche
- b Department of Gastroenterology and Hepatology , University Hospitals Leuven, KU Leuven , Leuven , Belgium
| | - S Vermeire
- b Department of Gastroenterology and Hepatology , University Hospitals Leuven, KU Leuven , Leuven , Belgium
| | - M Ferrante
- b Department of Gastroenterology and Hepatology , University Hospitals Leuven, KU Leuven , Leuven , Belgium
| | - A D'Hoore
- a Department of Abdominal Surgery , University Hospitals Leuven, KU Leuven , Leuven , Belgium
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18
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Lopez N, Ramamoorthy S, Sandborn WJ. Recent advances in the management of perianal fistulizing Crohn's disease: lessons for the clinic. Expert Rev Gastroenterol Hepatol 2019; 13:563-577. [PMID: 31023087 PMCID: PMC6545251 DOI: 10.1080/17474124.2019.1608818] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Managing fistulizing perianal disease is among the most challenging aspects of treating patients with Crohn's disease. Perianal fistulas are indicative of poor long-term prognosis. They are commonly associated with significant morbidities and can have detrimental effects on quality of life. While durable fistula closure is ideal, it is uncommon. In optimal circumstances, reported long-term fistula healing rates are only slightly higher than 50% and recurrence is common. Achieving these results requires a combined medical and surgical approach, highlighting the importance of a highly skilled and collaborative multidisciplinary team. In recent years, advances in imaging, biologic therapies and surgical techniques have lent to growing enthusiasm amongst treatment teams, however the most advantageous approach is yet to be determined. Areas covered: Here we review current management approaches, incorporating recent guidelines and novel therapies. Additionally, we discuss recently published and ongoing studies that will likely impact practice in the coming years. Expert opinion: Investing in concerted collaborative multi-institutional efforts will be necessary to better define optimal timing and dosing of medical therapy, as well as to identify ideal timing and approach of surgical interventions. Standardizing outcome measures can facilitate these efforts. Clearly, experienced multidisciplinary teams will be paramount in this process.
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Affiliation(s)
- Nicole Lopez
- Division of Colon and Rectal Surgery, University of California San Diego, California, USA
| | - Sonia Ramamoorthy
- Division of Colon and Rectal Surgery, University of California San Diego, California, USA
| | - Willam J. Sandborn
- Inflammatory Bowel Disease Center, University of California San Diego, California, USA,Division of Gastroenterology, University of California San Diego, California, USA
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19
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Consider using biological agents or stem cell therapy when managing perianal Crohn’s disease. DRUGS & THERAPY PERSPECTIVES 2018. [DOI: 10.1007/s40267-018-0549-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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20
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Abstract
Crohn's disease (CD) leads to the development of complications through progressive uncontrolled inflammation and the transmural involvement of the bowel wall. Most of the available literature on penetrating CD focuses on the perianal phenotype. The management of nonperianal penetrating complications poses its own set of challenges and can result in significant morbidity and an increased risk of mortality. Few controlled trials have been published evaluating this subgroup of patients for clinicians to use for guidance. Utilizing the available evidence, we review the epidemiology, presentation, and modalities used to diagnosis and assess intestinal fistulas, phlegmons, and abscesses. The literature regarding the medical, endoscopic, and surgical management options are reviewed providing physicians with a therapeutic framework to comprehensively treat these nonperianal penetrating complications. Through a multidisciplinary evidence-based approach to the complex sequela of CD outcomes can be improved and patient's quality of life enhanced.10.1093/ibd/izx108_video1izx108_Video5754037501001.
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Affiliation(s)
- Robert P Hirten
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Shailja Shah
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - David B Sachar
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Jean-Frederic Colombel
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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21
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Bermejo F, Guerra I, Algaba A, López-Sanromán A. Pharmacological Approach to the Management of Crohn's Disease Patients with Perianal Disease. Drugs 2018; 78:1-18. [PMID: 29139091 DOI: 10.1007/s40265-017-0842-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Perianal localization of Crohn's disease involves significant morbidity, affects quality of life and results in an increased use of healthcare resources. Medical and surgical therapies contribute to its management. The objective of this review is to address the current understanding in the management of perianal Crohn's disease, with the main focus in reviewing pharmacological therapies, including stem cells. In complex fistulas, once local sepsis has been controlled by surgical drainage and/or antibiotics, anti-TNF drugs (infliximab, adalimumab) are the first-line therapy, with or without associated immunomodulators. Combining surgery and anti-TNF therapy has additional benefits for healing. However, response is inadequate in up to half of cases. A possible role of new biological drugs in this context (vedolizumab, ustekinumab) is an area of ongoing investigation, as is the local application of autologous or allogeneic mesenchymal stem cells. These are non-hematopoietic multipotent cells with anti-inflammatory and immunomodulatory properties, the use of which may successfully treat refractory patients, and seem to be a promising and safe alternative to achieving fistula healing in Crohn's disease, without known systemic effects.
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Affiliation(s)
- Fernando Bermejo
- Department of Gastroenterology, University Hospital of Fuenlabrada, Madrid, Spain.
- Department of Medicine and Surgery, Universidad Rey Juan Carlos, Madrid, Spain.
| | - Iván Guerra
- Department of Gastroenterology, University Hospital of Fuenlabrada, Madrid, Spain
| | - Alicia Algaba
- Department of Gastroenterology, University Hospital of Fuenlabrada, Madrid, Spain
| | - Antonio López-Sanromán
- Department of Gastroenterology and Hepatology, University Hospital Ramón y Cajal, Madrid, Spain
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22
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Abstract
Perianal Crohn's is a common manifestation of Crohn's disease. Primary manifestations of perianal disease mirror common anorectal conditions, however treatment is less successful than in those patients without Crohn's related perianal disease. A multimodal approach to therapy including medical and surgical modalities is often necessary. The goal of treatment is to manage symptoms while maintaining continence.
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Affiliation(s)
- Jill M Zalieckas
- Department of Surgery, Boston Children's Hospital, Harvard Medical School, Fegan 3, 300 Longwood Ave, Boston, MA.
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23
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Abstract
Perianal fistulizing Crohn's disease has a major negative effect on patient quality of life and is a predictor of poor long-term outcomes. Factors involved in the pathogenesis of perianal fistulizing Crohn's disease include an increased production of transforming growth factor β, TNF and IL-13 in the inflammatory infiltrate that induce epithelial-to-mesenchymal transition and upregulation of matrix metalloproteinases, leading to tissue remodelling and fistula formation. Care of patients with perianal Crohn's disease requires a multidisciplinary approach. A complete assessment of fistula characteristics is the basis for optimal management and must include the clinical evaluation of fistula openings, endoscopic assessment of the presence of proctitis, and MRI to determine the anatomy of fistula tracts and presence of abscesses. Local injection of mesenchymal stem cells can induce remission in patients not responding to medical therapies, or to avoid the exposure to systemic immunosuppression in patients naive to biologics in the absence of active luminal disease. Surgery is still required in a high proportion of patients and should not be delayed when criteria for drug failure is met. In this Review, we provide an up-to-date overview on the pathogenesis and diagnosis of fistulizing Crohn's disease, as well as therapeutic strategies.
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24
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Abstract
Fistulas still represent one of the most important complications in patients with Crohn’s disease (CD). At least one third of CD patients suffer from fistulas during their disease course and amongst them longstanding remission of complex fistulas occurs only in about one third. So far, fistula pathogenesis is only partially understood. From a histopathological view, a fistula is a tube covered by flat epithelial cells. Current research suggests that the driving force for fistula development is epithelial-to-mesenchymal transition (EMT). Around the fistula, high levels of tumor necrosis factor (TNF), IL-13, and TGFβ can be detected and recent studies indicated an involvement of the intestinal microbiota. Fistula diagnosis requires clinical and surgical assessment, radiologic investigations, e.g., magnet resonance imaging and endoscopy. Routine medical treatment of fistulas includes antibiotics, immunosuppressives, and anti-TNF antibodies. There is no well-established role for calcineurin inhibitors in fistula treatment, corticosteroids appear to be even contra-productive. A promising novel approach might be the application of adipose tissue-derived or bone marrow-derived mesenchymal stem cells that have been studied recently. Due to insufficient efficacy of medical treatment and recurrence of fistulas, surgical interventions are frequently necessary. Further research is needed to better understand fistula pathogenesis aiming to develop novel treatment option for our patients.
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25
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Park JJ, Yang SK, Ye BD, Kim JW, Park DI, Yoon H, Im JP, Lee KM, Yoon SN, Lee H. [Second Korean Guidelines for the Management of Crohn's Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 69:29-54. [PMID: 28135790 DOI: 10.4166/kjg.2017.69.1.29] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Crohn's disease (CD) is a chronic, progressive, and disabling inflammatory bowel disease (IBD) with an uncertain etiopathogenesis. CD can involve any site of the gastrointestinal tract from the mouth to the anus, and is associated with serious complications, such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower compared with those in Western countries, but they have been rapidly increasing during the recent decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies have been applied for the treatment of this disease. Concerning CD management, there have been substantial discrepancies among clinicians according to their personal experience and preference. To suggest recommendable approaches to the diverse problems of CD and to minimize the variations in treatment among physicians, guidelines for the management of CD were first published in 2012 by the IBD Study Group of the Korean Association for the Study of the Intestinal Diseases. These are the revised guidelines based on updated evidence, accumulated since 2012. These guidelines were developed by using mainly adaptation methods, and encompass induction and maintenance treatment of CD, treatment based on disease location, treatment of CD complications, including stricture and fistula, surgical treatment, and prevention of postoperative recurrence. These are the second Korean guidelines for the management of CD and will be continuously revised as new evidence is collected.
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Affiliation(s)
- Jae Jun Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Suk Kyun Yang
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong Wook Kim
- Department of Internal Medicine, Inje University College of Medicine Ilsan Paik Hospital, Goyang, Korea
| | - Dong Il Park
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jong Pil Im
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Kang Moon Lee
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Suwon, Korea
| | - Sang Nam Yoon
- Department of Surgery, Hallym University College of Medicine, Chuncheon, Korea
| | - Heeyoung Lee
- Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea
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Mahmoud NN, Halwani Y, Montbrun SD, Shah PM, Hedrick TL, Rashid F, Schwartz DA, Dalal RL, Kamiński JP, Zaghiyan K, Fleshner PR, Weissler JM, Fischer JP. Current management of perianal Crohn’s disease. Curr Probl Surg 2017; 54:262-298. [DOI: 10.1067/j.cpsurg.2017.02.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 02/04/2017] [Indexed: 12/11/2022]
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27
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Park JJ, Yang SK, Ye BD, Kim JW, Park DI, Yoon H, Im JP, Lee KM, Yoon SN, Lee H. Second Korean guidelines for the management of Crohn's disease. Intest Res 2017; 15:38-67. [PMID: 28239314 PMCID: PMC5323307 DOI: 10.5217/ir.2017.15.1.38] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 01/15/2017] [Accepted: 01/16/2017] [Indexed: 02/07/2023] Open
Abstract
Crohn's disease (CD) is a chronic, progressive, and disabling inflammatory bowel disease (IBD) with an uncertain etiopathogenesis. CD can involve any site of the gastrointestinal tract from the mouth to the anus, and is associated with serious complications, such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower compared with those in Western countries, but they have been rapidly increasing during the recent decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies have been applied for the treatment of this disease. Concerning CD management, there have been substantial discrepancies among clinicians according to their personal experience and preference. To suggest recommendable approaches to the diverse problems of CD and to minimize the variations in treatment among physicians, guidelines for the management of CD were first published in 2012 by the IBD Study Group of the Korean Association for the Study of Intestinal Diseases. These are the revised guidelines based on updated evidence, accumulated since 2012. These guidelines were developed by using mainly adaptation methods, and encompass induction and maintenance treatment of CD, treatment based on disease location, treatment of CD complications, including stricture and fistula, surgical treatment, and prevention of postoperative recurrence. These are the second Korean guidelines for the management of CD and will be continuously revised as new evidence is collected.
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Affiliation(s)
- Jae Jun Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong Wook Kim
- Department of Internal Medicine, Inje University College of Medicine Ilsan Paik Hospital, Goyang, Korea
| | - Dong Il Park
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jong Pil Im
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Kang Moon Lee
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Suwon, Korea
| | - Sang Nam Yoon
- Department of Surgery, Hallym University College of Medicine, Chuncheon, Korea
| | - Heeyoung Lee
- Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea
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Clinical Practice Guideline for the Management of Anorectal Abscess, Fistula-in-Ano, and Rectovaginal Fistula. Dis Colon Rectum 2016; 59:1117-1133. [PMID: 27824697 DOI: 10.1097/dcr.0000000000000733] [Citation(s) in RCA: 215] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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A Systematic Review Assessing Medical Treatment for Rectovaginal and Enterovesical Fistulae in Crohn's Disease. J Clin Gastroenterol 2016; 50:714-21. [PMID: 27466166 DOI: 10.1097/mcg.0000000000000607] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Rectovaginal and enterovesical fistulae are difficult to treat in patients with Crohn's disease. Currently, there is no consensus regarding their appropriate management. AIM OF THE STUDY The aim of the study was to review the literature on the medical management of rectovaginal and enterovesical fistulae in Crohn's disease and to assess their response to treatment. METHOD A literature search of MEDLINE, EMBASE, Science Citation Index Expanded, and Cochrane was performed. RESULTS Twenty-three studies were identified, reporting on 137 rectovaginal and 44 enterovesical fistulae. The overall response rates of rectovaginal fistulae to medical therapy were: 38.3% complete response (fistula closure), 22.3% partial response, and 39.4% no response. For enterovesical fistulae the response rates to medical therapy were: 65.9% complete response, 20.5% partial response, and 13.6% no response. Specifically, response to anti-tumor necrosis factor therapy of 78 rectovaginal fistulae was: 41.0% complete response, 21.8% partial response, and 37.2% no response. Response of 14 enterovesical fistulae to anti-tumor necrosis factor therapy was: 57.1% complete response, 35.7% partial response, and 7.1% no response. The response to a combination of medical and surgical therapy in 43 rectovaginal fistulae was: 44.2% complete response, 20.9% partial response, and 34.9% no response. CONCLUSIONS Medical therapy, alone or in combination with surgery, appears to benefit some patients with rectovaginal or enterovesical fistula. However, given the small size and low quality of the published studies, it is still difficult to draw conclusions regarding treatment. Larger, better quality studies are required to assess response to medical treatment and evaluate indications for surgery.
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de Groof EJ, Cabral VN, Buskens CJ, Morton DG, Hahnloser D, Bemelman WA. Systematic review of evidence and consensus on perianal fistula: an analysis of national and international guidelines. Colorectal Dis 2016; 18:O119-34. [PMID: 26847796 DOI: 10.1111/codi.13286] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Accepted: 01/04/2016] [Indexed: 12/29/2022]
Abstract
AIM Treatment of perianal fistula has evolved with the introduction of new techniques and biologicals in Crohn's disease (CD). Several guidelines are available worldwide, but many recommendations are controversial or lack high-quality evidence. The aim of this work was to provide an overview of the current available national and international guidelines for perianal fistula and to analyse areas of consensus and areas of conflicting recommendations, thereby identifying topics and questions for future research. METHOD MEDLINE, EMBASE and PubMed were systematically searched for guidelines on perianal fistula. Inclusion was limited to papers in English less than 10 years old. The included topics were classified as having consensus (unanimous recommendations in at least two-thirds of the guidelines) or controversy (fewer than three guidelines commenting on the topic or no consensus) between guidelines. The highest level of evidence was scored as sufficient (level 3a or higher of the Oxford Centre for Evidence-based Medicine Levels of Evidence 2009, http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/) or insufficient. RESULTS Twelve guidelines were included and topics with recommendations were compared. Overall, consensus was present in 15 topics, whereas six topics were rated as controversial. Evidence levels varied from strong to lack of evidence. CONCLUSION Evidence on the diagnosis and treatment of perianal fistulae (cryptoglandular or related to CD) ranged from nonexistent to strong, regardless of consensus. The most relevant research questions were identified and proposed as topics for future research.
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Affiliation(s)
- E J de Groof
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - V N Cabral
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - C J Buskens
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - D G Morton
- Academic Department of Surgery, University of Birmingham, Birmingham, UK
| | - D Hahnloser
- Department of Visceral Surgery, University Hospital CHUV, Lausanne, Switzerland
| | - W A Bemelman
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
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Klag T, Goetz M, Stange EF, Wehkamp J. Medical Therapy of Perianal Crohn's Disease. VISZERALMEDIZIN 2015; 31:265-72. [PMID: 26557835 PMCID: PMC4608613 DOI: 10.1159/000434664] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background Development of perianal fistulas are a common feature of Crohn's disease (CD). Consequences are severe impairment of quality of life as well as potentially life-threatening complications like abscess formation or bacterial sepsis. Therefore, appropriate treatment is an important task in the management of CD. Methods This review describes the epidemiology, pathogenesis, diagnosis, and conservative medical treatment of perianal CD with regard to the available literature. In February 2015, a PubMed search was performed with the following terms (combined and separate): ‘Crohn's disease management’, ‘Crohn's disease complications’, ‘perianal Crohn's disease’, ‘fistulizing Crohn's disease’, ‘perianal fistulas’, ‘fistula healing’, ‘fistula closure’. From the search results, 36 articles were chosen as core elements of this review. Results Pelvic magnetic resonance imaging and rectal endosonography are established diagnostic approaches to evaluate perianal fistulas in conjunction with endoscopy. Antibiotics, thiopurines, and calcineurin inhibitors are useful agents in the management of perianal CD. The availability of anti-TNF-alpha therapies has substantially changed the prospects and goals of medical treatment, and fistula healing seems to be possible in a substantial proportion of patients. Conclusion Antibiotics and several immunosuppressive drugs have improved the treatment of fistulizing CD and should be combined with surgical measures.
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Affiliation(s)
- Thomas Klag
- Department of Internal Medicine I, University of Tübingen, Tübingen, Germany
| | - Martin Goetz
- Department of Internal Medicine I, University of Tübingen, Tübingen, Germany
| | - Eduard F Stange
- Department of Internal Medicine I, Robert-Bosch-Hospital, Stuttgart, Germany
| | - Jan Wehkamp
- Department of Internal Medicine I, University of Tübingen, Tübingen, Germany
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Review article: The pharmacokinetics and pharmacodynamics of drugs used in inflammatory bowel disease treatment. Eur J Clin Pharmacol 2015; 71:773-99. [PMID: 26008212 DOI: 10.1007/s00228-015-1862-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 05/04/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND The following review is a compilation of the recent advances and knowledge on the behaviour of the most frequently used compounds to treat inflammatory bowel disease in an organism. RESULTS It considers clinical aspects of each entity and the pharmacokinetic/pharmacodynamic relationship supported by the use of plasma monitoring, tissue concentrations, and certain aspects derived from pharmacogenetics.
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Valente MA, Hull TL. Contemporary surgical management of rectovaginal fistula in Crohn's disease. World J Gastrointest Pathophysiol 2014; 5:487-495. [PMID: 25400993 PMCID: PMC4231514 DOI: 10.4291/wjgp.v5.i4.487] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2014] [Revised: 03/27/2014] [Accepted: 07/17/2014] [Indexed: 02/07/2023] Open
Abstract
Rectovaginal fistula is a disastrous complication of Crohn’s disease (CD) that is exceedingly difficult to treat. It is a disabling condition that negatively impacts a women’s quality of life. Successful management is possible only after accurate and complete assessment of the entire gastrointestinal tract has been performed. Current treatment algorithms range from observation to medical management to the need for surgical intervention. A wide variety of success rates have been reported for all management options. The choice of surgical repair methods depends on various fistula and patient characteristics. Before treatment is undertaken, establishing reasonable goals and expectations of therapy is essential for both the patient and surgeon. This article aims to highlight the various surgical techniques and their outcomes for repair of CD associated rectovaginal fistula.
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Gecse KB, Bemelman W, Kamm MA, Stoker J, Khanna R, Ng SC, Panés J, van Assche G, Liu Z, Hart A, Levesque BG, D'Haens G. A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease. Gut 2014; 63:1381-92. [PMID: 24951257 DOI: 10.1136/gutjnl-2013-306709] [Citation(s) in RCA: 272] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To develop a consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease (pCD), based on best available evidence. METHODS Based on a systematic literature review, statements were formed, discussed and approved in multiple rounds by the 20 working group participants. Consensus was defined as at least 80% agreement among voters. Evidence was assessed using the modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. RESULTS Highest diagnostic accuracy can only be established if a combination of modalities is used. Drainage of sepsis is always first line therapy before initiating immunosuppressive treatment. Mucosal healing is the goal in the presence of proctitis. Whereas antibiotics and thiopurines have a role as adjunctive treatments in pCD, anti-tumour necrosis factor (anti-TNF) is the current gold standard. The efficacy of infliximab is best documented although adalimumab and certolizumab pegol are moderately effective. Oral tacrolimus could be used in patients failing anti-TNF therapy. Definite surgical repair is only of consideration in the absence of luminal inflammation. CONCLUSIONS Based on a multidisciplinary approach, items relevant for fistula management were identified and algorithms on diagnosis and treatment of pCD were developed.
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Affiliation(s)
- Krisztina B Gecse
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Robarts Research Institute, Amsterdam, The Netherlands
| | - Willem Bemelman
- Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Michael A Kamm
- St. Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Jaap Stoker
- Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Reena Khanna
- Robarts Research Institute, London, Ontario, Canada University of Western Ontario, London, Ontario, Canada
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Julián Panés
- Department of Gastroenterology, Hospital Clinic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Gert van Assche
- Department of Gastroenterology, University of Leuven, Leuven, Belgium
| | - Zhanju Liu
- Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Ailsa Hart
- APRG, Imperial College, London, UK IBD Unit, St. Mark's Hospital, London, UK
| | - Barrett G Levesque
- Robarts Research Institute, San Diego, CA, USA Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | - Geert D'Haens
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Robarts Research Institute, Amsterdam, The Netherlands
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Sordo-Mejia R, Gaertner WB. Multidisciplinary and evidence-based management of fistulizing perianal Crohn's disease. World J Gastrointest Pathophysiol 2014; 5:239-51. [PMID: 25133026 PMCID: PMC4133523 DOI: 10.4291/wjgp.v5.i3.239] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 05/07/2014] [Accepted: 05/28/2014] [Indexed: 02/06/2023] Open
Abstract
Perianal symptoms are common in patients with Crohn's disease and cause considerable morbidity. The etiology of these symptoms include skin tags, ulcers, fissures, abscesses, fistulas or stenoses. Fistula is the most common perianal manifestation. Multiple treatment options exist although very few are evidence-based. The phases of treatment include: drainage of infection, assessment of Crohn's disease status and fistula tracts, medical therapy, and selective operative management. The impact of biological therapy on perianal Crohn's disease is uncertain given that outcomes are conflicting. Operative treatment to eradicate the fistula tract can be attempted once infection has resolved and Crohn's disease activity is controlled. The operative approach should be tailored according to the anatomy of the fistula tract. Definitive treatment is challenging with medical and operative treatment rarely leading to true healing with frequent complications and recurrence. Treatment success must be weighed against the risk of complications, specially anal sphincter injury. A full understanding of the etiology and all potential therapeutic options is critical for success. Multidisciplinary management of fistulizing perianal Crohn's disease is crucial to improve outcomes.
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36
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Improving the outcome of fistulising Crohn's disease. Best Pract Res Clin Gastroenterol 2014; 28:505-18. [PMID: 24913389 DOI: 10.1016/j.bpg.2014.04.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2014] [Revised: 03/13/2014] [Accepted: 04/13/2014] [Indexed: 01/31/2023]
Abstract
Fistulas are a frequent manifestation of Crohn's disease (CD) and can result in considerable morbidity. Approximately 35% of all patients with CD will experience one fistula episode during their disease course of which 54% is perianal. The major symptoms of patients with perianal fistulas are constant anal pain, the formation of painful swellings around the anus and continuous discharge of pus and/or blood from the external fistula opening. The exact aetiology of perianal fistulas in CD patients remains unclear, but it is thought that a penetrating ulcer in the rectal mucosa caused by active CD forms an abnormal passage between the epithelial lining of the rectum and the perianal skin. Genetic, microbiological and immunological factors seem to play important roles in this process. Although the incidence of perianal fistulas in patients with CD is quite high, an effective treatment is not yet discovered. In this review all available medical and surgical therapies are discussed and new treatment options and research targets will be highlighted.
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Cox JH, Hussell S, Søndergaard H, Roepstorff K, Bui JV, Deer JR, Zhang J, Li ZG, Lamberth K, Kvist PH, Padkjær S, Haase C, Zahn S, Odegard VH. Antibody-mediated targeting of the Orai1 calcium channel inhibits T cell function. PLoS One 2013; 8:e82944. [PMID: 24376610 PMCID: PMC3871607 DOI: 10.1371/journal.pone.0082944] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Accepted: 11/08/2013] [Indexed: 01/03/2023] Open
Abstract
Despite the attractiveness of ion channels as therapeutic targets, there are no examples of monoclonal antibodies directed against ion channels in clinical development. Antibody-mediated inhibition of ion channels could offer a directed, specific therapeutic approach. To investigate the potential of inhibiting ion channel function with an antibody, we focused on Orai1, the pore subunit of the calcium channel responsible for store-operated calcium entry (SOCE) in T cells. Effector T cells are key drivers of autoimmune disease pathogenesis and calcium signaling is essential for T cell activation, proliferation, and cytokine production. We show here the generation of a specific anti-human Orai1 monoclonal antibody (mAb) against an extracellular loop of the plasma membrane-spanning protein. The anti-Orai1 mAb binds native Orai1 on lymphocytes and leads to cellular internalization of the channel. As a result, T cell proliferation, and cytokine production is inhibited in vitro. In vivo, anti-Orai1 mAb is efficacious in a human T cell-mediated graft-versus host disease (GvHD) mouse model. This study demonstrates the feasibility of antibody-mediated inhibition of Orai1 function and, more broadly, reveals the possibility of targeting ion channels with biologics for the treatment of autoimmunity and other diseases.
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Affiliation(s)
- Jennifer H. Cox
- Department of Cellular Immunology, Novo Nordisk Research Center, Seattle, Washington, United States of America
| | - Scott Hussell
- Department of Cellular Immunology, Novo Nordisk Research Center, Seattle, Washington, United States of America
| | | | | | - John-Vu Bui
- Department of Cellular Immunology, Novo Nordisk Research Center, Seattle, Washington, United States of America
| | - Jen Running Deer
- Department of Molecular Immunology, Novo Nordisk Research Center, Seattle, Washington, United States of America
| | - Jun Zhang
- Department of Cell Biology, Beijing Novo Nordisk Pharmaceuticals Science & Technology Co., Beijing, China
| | - Zhan-Guo Li
- Department of Rheumatology & Immunology, Beijing University People’s Hospital, Beijing, China
| | - Kasper Lamberth
- Department of Screening and Cell Technology, Novo Nordisk A/S, Maløv, Denmark
| | | | - Søren Padkjær
- Department of Protein Structure and Biophysics, Novo Nordisk A/S, Maløv, Denmark
| | - Claus Haase
- Department of Immunopharmacology, Novo Nordisk A/S, Maløv, Denmark
| | - Stefan Zahn
- Department of Antibody Technology, Novo Nordisk A/S, Maløv, Denmark
| | - Valerie H. Odegard
- Department of Cellular Immunology, Novo Nordisk Research Center, Seattle, Washington, United States of America
- * E-mail:
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Diagnosis and treatment of perianal Crohn disease: NASPGHAN clinical report and consensus statement. J Pediatr Gastroenterol Nutr 2013; 57:401-12. [PMID: 23974063 DOI: 10.1097/mpg.0b013e3182a025ee] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes both Crohn disease (CD) and ulcerative colitis. Abdominal pain, rectal bleeding, diarrhea, and weight loss characterize both CD and ulcerative colitis. The incidence of IBD in the United States is 70 to 150 cases per 100,000 individuals and, as with other autoimmune diseases, is on the rise. CD can affect any part of the gastrointestinal tract from the mouth to the anus and frequently will include perianal disease. The first description connecting regional enteritis with perianal disease was by Bissell et al in 1934, and since that time perianal disease has become a recognized entity and an important consideration in the diagnosis and treatment of CD. Perianal Crohn disease (PCD) is defined as inflammation at or near the anus, including tags, fissures, fistulae, abscesses, or stenosis. The symptoms of PCD include pain, itching, bleeding, purulent discharge, and incontinence of stool. In this report, we review and discuss the etiology, diagnosis, evaluation, and treatment of PCD.
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Tozer PJ, Balmforth D, Kayani B, Rahbour G, Hart AL, Phillips RKS. Surgical management of rectovaginal fistula in a tertiary referral centre: many techniques are needed. Colorectal Dis 2013; 15:871-7. [PMID: 23331635 DOI: 10.1111/codi.12114] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Accepted: 08/17/2012] [Indexed: 12/15/2022]
Abstract
AIM Surgery is the mainstay of treatment for rectovaginal fistula (RVF). Published success rates vary with initial success being around 50% rising to 80% with repeated surgery. Fistulae in Crohn's disease are more likely to recur. METHOD A retrospective study was performed of RVF repair carried out between 2003 and 2008 in a tertiary referral centre. Patients undergoing surgery for an RVF under the senior author during the study period were identified and their clinical notes were reviewed. RESULTS Thirty-five patients underwent 50 operations. The median age was 42 years and 83% were tertiary referrals. Two patients were lost to follow-up. Healing occurred in 19 (58%) of 33 patients after a mean of 1.4 operations. The median time to success was 11 (2.5-48) months. The 'curative' group had an overall success of 73% (19 of 26). Seventy-five per cent of non-inflammatory bowel disease patients and 67% of those with Crohn's disease had successful treatment of the RVF. Twenty-four of 35 patients (67%) underwent creation of a stoma. Sixteen of 24 (67%) were deemed fit for restoration of continuity. No demographic or disease related factors were found to influence healing. CONCLUSION Cure of RVF can be achieved by a range of surgical approaches including abdominal and anal. A variety of different anal techniques are necessary, depending on the integrity of the anal sphincter and the presence or absence of perineal descent/internal intussusception.
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Affiliation(s)
- P J Tozer
- Imperial College London and St Mark's Hospital, London, UK
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The effect of intravenous cyclosporine on rates of colonic surgery in hospitalized patients with severe Crohn's colitis. J Clin Gastroenterol 2012; 46:764-7. [PMID: 22751334 DOI: 10.1097/mcg.0b013e31824e14a8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND The role of intravenous (IV) cyclosporine in severe Crohn's colitis (CC) is poorly studied. AIM Our primary aim was to determine the in-hospital colonic resection rate in patients with severe CC who received IV cyclosporine, and the potential predictors of resection among these patients. METHODS An inpatient pharmacy query of all patients who received IV cyclosporine at Mount Sinai Medical Center for 12.5 years after January 1, 1996 was reviewed. Patients with CC or indeterminate colitis favoring Crohn's were included and their medical records were reviewed. Subsequent need for colonic surgery was assessed. A Kaplan-Meier plot with log-rank testing was performed to determine the rate of colonic surgery avoidance. Forward stepwise logistic regression was performed to determine independent predictors of surgery. RESULTS Forty-eight patients met our inclusion criteria. Prior thiopurine and anti-tumor necrosis factor (anti-TNF) use was 85% and 69%, respectively. The median follow-up time was 12 months (range, 1 to 60 mo). 12.5% of patients required colonic resection during their admission for IV cyclosporine. Anti-TNF use in the 4 weeks preceding IV cyclosporine was the only predictor of surgery in this setting (P=0.05). The cumulative colonic surgery avoidance rate was 72±13% at 6 months and 59±15% at 12 months. CONCLUSIONS The use of IV cyclosporine resulted in a low rate of in-hospitalization colonic surgery among CC patients with severe disease, the majority of whom previously failed anti-TNFs and thiopurines.
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Cyclosporine: does it matter if it is given for Crohn's colitis or ulcerative colitis? J Clin Gastroenterol 2012; 46:721-2. [PMID: 22955259 DOI: 10.1097/mcg.0b013e31826aafd2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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El-Gazzaz G, Hull T, Church JM. Biological immunomodulators improve the healing rate in surgically treated perianal Crohn's fistulas. Colorectal Dis 2012; 14:1217-23. [PMID: 22251452 DOI: 10.1111/j.1463-1318.2012.02944.x] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
AIM The role of biological therapy in perianal fistulas associated with Crohn's disease (CD) is uncertain as available data are confused and conflicting. In order to provide some clarity to the issue we have examined a large cohort of patients with perianal fistulas and CD and stratified them according to use of biological agents. METHOD Patients with perianal Crohn's fistulas treated between June 1999 and June 2009 were stratified according to use of biological agents and outcome was examined. Healing was defined as absence of fistula or drainage. Prior to surgery perianal sepsis was eradicated with drains or setons. Endpoints were defined as either complete healing, improvement (minimal symptoms and drainage) or unhealed, as noted at subsequent outpatient follow-up. Variables assessed were age, body mass index, smoking, perineal involvement with Crohn's granuloma and type of procedure. Fisher's exact test and χ(2) test were used for analysis. RESULTS Two hundred and eighteen patients had anal fistulas and CD. Mean follow-up was 3.2±3 years with mean age 38.8±12.2years and body mass index of 25.3±6. One hundred and seventeen patients (53.7%) underwent surgery alone (Group A) and 101 patients (46.3%) underwent surgery and biological immunomodulator treatments (Group B). Demographic data and CD history were similar between groups. Surgeries included seton drainge (n=90), fistulotomy (n=22), rectal advancement flap (n=39), fistulotomy plus seton (n=47) and others (n=20). Overall improvement in Group A was in 42 patients (35.9%) vs 72 patients (71.3%) in Group B (P=0.001). There was no significant difference in other studied variables between both groups. CONCLUSIONS There is a definite role for biological therapy as an adjuvant to surgery in patients with perianal fistulas and CD.
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Affiliation(s)
- G El-Gazzaz
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
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de la Poza G, López-Sanroman A, Taxonera C, Marín-Jimenez I, Gisbert JP, Bermejo F, Opio V, Muriel A. Genital fistulas in female Crohn's disease patients.: clinical characteristics and response to therapy. J Crohns Colitis 2012; 6:276-80. [PMID: 22405162 DOI: 10.1016/j.crohns.2011.08.015] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2011] [Revised: 08/16/2011] [Accepted: 08/17/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Genital fistulas (GF) can arise in the course of Crohn's disease (CD), are difficult to manage and determine a significant alteration of the quality of life. AIMS To review the joint experience of the Inflammatory Bowel Disease Units in six University Hospitals in the management of GF in Crohn's disease on female patients. RESULTS A total of 47 patients with GF were identified, affecting 3.8% of women with CD treated in our centers. A 47.5% of patients were smokers. The median of time from the diagnosis of CD reached 102 months. According to anatomical type, GF were classified as rectovaginal (74.5%), anovaginal/anovulvar (21.3%) and enterovaginal (4.3%). Main symptoms were vaginal discharge of fecal material (55.3%), vaginal passage of gas (40.4%), or both. Fistulas were treated with antibiotics in 59.6% of patients, without any lasting success. Thiopurines were used in 80.9% of cases, with 13.2% of complete and 23.7% of partial responses. Anti TNF-alpha therapy was applied in 63.8%, with a 16.7% of complete and a 30% of partial responses (all responding patients received infliximab). Surgery was indicated in 38.3% of patients, with a 22% of complete responses after a first operation and 38.8% after reintervention. In all, definitive closure after one or more of these therapies was achieved in only 31.9% of cases. CONCLUSION Genital fistulas are a significant problem in female Crohn's disease patients. Therapy is not well defined and only partially effective (one in three cases). Surgical therapy stands out as the most effective treatment.
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Gaertner WB, Madoff RD, Spencer MP, Mellgren A, Goldberg SM, Lowry AC. Results of combined medical and surgical treatment of recto-vaginal fistula in Crohn's disease. Colorectal Dis 2011; 13:678-83. [PMID: 20163426 DOI: 10.1111/j.1463-1318.2010.02234.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
AIM Surgical repair of recto-vaginal fistula (RVF) in Crohn's disease (CD) has been associated with high rates of failure. The aim of this study was to compare the outcome in patients with CD who underwent RVF surgery with or without infliximab infusion. METHOD A retrospective review was carried out of 51 consecutive patients with CD treated for a symptomatic RVF between March 1998 and December 2004. RESULTS Fifty-one patients (mean age 39 years) underwent 65 procedures, including seton drainage (n = 35), advancement flap (n = 8), fibrin glue injection (n = 8), transperineal repair (n = 6), collagen plug placement (n = 4) and bulbocavernosus flap (n = 4). All patients were on medical treatment at the time of surgery and 26 patients had received preoperative infliximab treatment (minimum of three infusions, 5 mg/kg). Ten patients underwent preoperative diversion. At a mean follow up of 38.6 months, 27 fistulas (53%) had healed and 24 (47%) had recurred. Fistula healing occurred in 60% of patients treated with preoperative diversion, whereas 51% of nondiverted repairs were successful. Neither active proctitis nor infliximab therapy significantly affected fistula healing. Fourteen (27%) patients eventually required proctectomy. CONCLUSION RVF in CD is difficult to treat. Failure rates are significant despite repeated surgical interventions and concomitant medical treatment.
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Affiliation(s)
- W B Gaertner
- Division of Colon and Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
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Samimi R, Flasar MH, Kavic S, Tracy K, Cross RK. Outcome of medical treatment of stricturing and penetrating Crohn's disease: a retrospective study. Inflamm Bowel Dis 2010; 16:1187-94. [PMID: 19902541 DOI: 10.1002/ibd.21160] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Outcomes of medical treatment in patients with stricturing and penetrating Crohn's disease (CD) are not well characterized. METHODS Adults with stricturing and penetrating CD who underwent medical treatment from 2004 to 2008 were evaluated. We assessed response rates to medical treatment, time to relapse or surgery, and postoperative complications. RESULTS In all, 53 patients underwent medical therapy. 60% had stricturing disease, 11% had penetrating, and 28% had both. Disease location was ileal in 38%, colonic in 2%, and ileocolonic in 60%. At 30, 60, and 90 days, 54%, 60%, and 64% experienced a response to medical therapy, respectively. At 30 days, 75% of patients with ileal CD responded to therapy compared to 38% of patients with ileocolonic CD (P = 0.026). Overall, 64% of patients required surgery. Patients with ileocolonic disease required surgery at 0.55 years versus 1.07 years in patients with ileal disease (P = 0.023). 24% of patients experienced an anastomotic leak, fistula, or abscess (IASC). 29% of patients with penetrating disease developed IASC compared to 6% of patients with stricturing disease (P = 0.047). 32% of patients on biologic therapy had IASC compared to 0% of those not on biologics (P = 0.059). CONCLUSIONS The outcomes of medical treatment of stricturing or penetrating CD are poor, as 64% ultimately require surgery. Important factors that seem to be associated with either failed therapy include ileocolonic or colonic disease location. We report a high rate of IASC, especially in patients with penetrating disease and those treated with biologic therapy. This should be considered prior to attempted medical therapy.
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Affiliation(s)
- Roxana Samimi
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Keshaw H, Foong KS, Forbes A, Day RM. Perianal fistulae in Crohn's Disease: current and future approaches to treatment. Inflamm Bowel Dis 2010; 16:870-80. [PMID: 19834976 DOI: 10.1002/ibd.21137] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
: affecting sphincter integrity and continence. Traditional surgical and medical approaches are not without their limitations and may result in either comorbidity, such as fecal incontinence, or incomplete healing of the fistulae. Over the last 2 decades these limitations have led to a paradigm shift toward the use of biomaterials, and more recently cell-based therapies, which have met with variable degrees of success. This review discusses the traditional and current methods of treatment, as well as emerging and possible alternative approaches that may improve fistula healing.
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Affiliation(s)
- Hussila Keshaw
- Biomaterials and Tissue Engineering Group, Centre for Gastroenterology & Nutrition, University College London, UK
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Abstract
Gut inflammation occurring in patients with IBDs (inflammatory bowel diseases) is associated with exaggerated and poorly controlled T-cell-mediated immune responses, which are directed against normal components of the gut flora. T-cells accumulate in the inflamed gut of IBD patients as a result of multiple mechanisms, including enhanced recruitment of cells from the bloodstream, sustained cell cycling and diminished susceptibility of cells to undergo apoptosis. Activated T-cells produce huge amounts of cytokines, which contribute to amplify and sustain the ongoing mucosal inflammation. Strategies aimed at interfering with T-cell accumulation and/or function in the gut have been employed with clinical success in patients with IBDs. In the present article, we review the available results showing that T-cell-directed therapies are useful to dampen the tissue-damaging immune response in IBDs.
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Abstract
Despite the prevalence and severe implications of rectovaginal fistula, there is no universally accepted evidence-based approach to surgical management. This article offers a disease-based review of traditional management strategies and highlights the variety of technical approaches that are currently effective for the eradication of this socially disabling condition.
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Affiliation(s)
- Bradley J Champagne
- Division of Colorectal Surgery, University Hospitals Case Medical Center, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5047, USA.
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Aronoff JS, Korelitz BI, Sohn N, Ky A, Rajapakse R, Weinstein MA, Cohen FS. Anorectal Crohn's disease: surgical and medical management. BioDrugs 2009; 13:95-105. [PMID: 18034516 DOI: 10.2165/00063030-200013020-00003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
In some patients with Crohn's disease the anorectal complications are the major cause of symptoms and morbidity. Anorectal Crohn's disease may be present in patients with intestinal Crohn's disease, may be the initial manifestation of the disease, or rarely occurs without involvement of Crohn's disease elsewhere in the intestinal tract. The pathogenesis of these anorectal complications remains to be clarified. The anorectal examination is very important in the assessment of patients with suspected or documented inflammatory bowel disease. Meticulous physical examination, examination under anaesthesia and radiological imaging modalities may be utilised to specifically identify the location of abscesses and fistulae. Treatment strategy should be directed toward symptomatic relief; the most important symptom is pain. In most patients this pain will be attributable to an incompletely drained rectal abscess. Simple incision and drainage procedures are often all that is required as initial treatment of anorectal abscesses. Treatment of the anorectal fistulae that occur secondary to Crohn's disease requires combined medical and surgical therapy. Drug therapy is more often initiated for Crohn's disease that involves other areas of the gastrointestinal tract. The anorectal manifestations often respond to these same medications. Lay-open procedures (fistulotomies) are often all that is required surgically for simple (low) anorectal fistulae. High (complex) fistulae that involve large portions of the anorectal muscular ring are more difficult to treat. Patients with these fistulae must be treated on an individual basis, usually local surgical therapy combined with a medical regimen. Many surgical procedures are performed and many classes of medications are utilised on patients with these complex anorectal fistulae. Choosing the appropriate surgical and medical interventions is often quite difficult. Although sulfasalazine, mesalazine and corticosteroids have no lasting or maintenance value for fistulae, the immunosuppressive agents mercaptopurine, azathioprine and cyclosporin, the antibacterial metronidazole and the anti-tumour necrosis factor-alpha monoclonal antibody infliximab have varying degrees of effect. The goal of the combined regimen is to cure the fistula, or at least make it minimally symptomatic, without altering the patient's continence.
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Affiliation(s)
- J S Aronoff
- Department of Surgery, Lenox Hill Hospital and New York University School of Medicine, New York, New York, USA
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