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Greveson K, Haj O, Hart A, Geransar P, Zmora O. Management of Perianal Fistulas Associated with Crohn Disease: A Nurse's Perspective. Gastroenterol Nurs 2024; 47:428-446. [PMID: 39186387 DOI: 10.1097/sga.0000000000000833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 05/01/2024] [Indexed: 08/28/2024] Open
Abstract
Crohn disease perianal fistulas are associated with considerable morbidity and impaired quality of life. Nurses who specialize in inflammatory bowel disease (IBD) play a vital role in the management of Crohn disease perianal fistulas from diagnosis to long-term care; however, there is little evidence available to inform Crohn associated perianal fistula management strategies for nurses. This narrative review aims to provide IBD nurses with an up-to-date overview of Crohn perianal fistulas. It discusses the vital role IBD nurses play within the multidisciplinary team; the physical, social, and psychological impacts of Crohn perianal fistulas on patients; available treatment options; and how IBD nurses can support patients in their perianal fistula journey to enable optimum outcomes for patients. It also reviews diagnostic techniques and IBD nurses' involvement in Crohn perianal fistula diagnosis. While this article is aimed at IBD nurses, it is relevant to all nurses irrespective of their role (unit, clinic, community, and stoma) who interact with patients with Crohn perianal fistulas because awareness of the signs and symptoms of this condition will enable timely referrals and diagnosis.
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Affiliation(s)
- Kay Greveson
- About the authors: Kay Greveson, RN, is at The London IBD Clinic, London, United Kingdom; Ola Haj, RN, MPH, is at the IBD Clinic, Gastroenterology Department, Sheba Medical Center, Derech Sheba 2, Ramat Gan, Israel; Ailsa Hart, MD, PhD, is a Professor at the IBD Department, St Mark's Hospital, Harrow, London, United Kingdom; Parnia Geransar, BPharm, PhD, was a Senior Global Medical Director, Global Medical Affairs - Rare GI at Takeda Pharmaceuticals International AG, Glattpark-Opfikon, Zurich, Switzerland at the time of manuscript development; and Oded Zmora, MD, is a Professor at the Department of Surgery, Shamir Medical Center, Be'er Ya'akov, Tel Aviv, Israel
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White I, Karki C, Geransar P, Leisle L, Junker S, Fleshner P. Impact of Seton Use on Clinical, Patient-Reported, and Healthcare Resource Utilization Outcomes in Complex Crohn's Perianal Fistulas: A Systematic Literature Review. Inflamm Bowel Dis 2024:izae186. [PMID: 39298676 DOI: 10.1093/ibd/izae186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Optimal treatment strategies for seton use in patients with Crohn's perianal fistulas (CPF) remain elusive. This systematic literature review aimed to summarize clinical, patient-reported, and healthcare resource utilization (HCRU) outcomes associated with seton use for symptomatic relief and treatment of complex CPF. METHODS Electronic databases (MEDLINE, Embase, EBM Reviews, EconLit) were searched. Titles, abstracts, and relevant full texts were screened by 2 reviewers for inclusion using prespecified PICOS-T criteria. Articles published in English between January 1, 1980 and September 6, 2021 were included; animal/in vitro studies and case reports with <5 patients were excluded. Outcomes of interest included rates of complete response/remission and fistula recurrence in patients receiving seton with/without infliximab or biologics. Data were summarized using descriptive statistics. RESULTS Overall, 56 studies were included (full texts: n = 43; congress abstracts: n = 13). CPF and clinical outcome definitions were heterogeneous. Rates (range) of complete response/remission varied widely (seton: 13%-75%; seton + infliximab: 23%-100%; seton + biologics: 23%-59%) as did rates for fistula recurrence (seton: 4%-68%; seton + infliximab: 0%-50%; seton + biologics: 0%-17%). Rates of fistula-related reintervention, new fistula or abscess formation, and abscess recurrence were also varied; more consistency was observed regarding the use of patient-reported outcomes. Few studies reported outcomes from pediatric/adolescent patients or HCRU. CONCLUSIONS Optimal use of seton in patients with CPF remains unclear. International standardization of definitions for CPF and related clinical outcomes are required to permit data comparability and identify the most effective treatment strategies involving seton use in CPF.
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Affiliation(s)
- Ian White
- Department of Surgery, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Chitra Karki
- Takeda Pharmaceuticals USA, Inc., Cambridge, MA, USA
| | - Parnia Geransar
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
| | - Lilia Leisle
- Ingress-Health HWM GmbH, an affiliate of Cytel, Inc., Real World & Advanced Analytics, Berlin, Germany
| | - Sophia Junker
- Ingress-Health HWM GmbH, an affiliate of Cytel, Inc., Real World & Advanced Analytics, Berlin, Germany
| | - Phillip Fleshner
- Cedars-Sinai Medical Center, Division of Colon and Rectal Surgery, Los Angeles, CA, USA
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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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Boarini LR, Sobrado CW, Mota GR, Villa LL, de Albuquerque IC, Queiroz NSF, Facanali CBG, Nadal SR, Cecconello I. Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV in the anorectal fistula tract. A comparative study. Clinics (Sao Paulo) 2023; 78:100219. [PMID: 37257365 PMCID: PMC10244904 DOI: 10.1016/j.clinsp.2023.100219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 05/03/2023] [Accepted: 05/12/2023] [Indexed: 06/02/2023] Open
Abstract
BACKGROUND & AIMS Perianal fistulizing Crohn's disease is the main risk factor for anal cancer in patients with inflammatory bowel disease. Whether this occurs due to a higher frequency of human papillomavirus remains unclear. The authors aimed to evaluate the prevalence of HPV and high-risk HPV in patients with perianal Crohn's disease, compared with a control group. METHODS The authors conducted a two-center cross-sectional study in which perianal fistulizing Crohn's disease patients were matched for age and sex with patients with anorectal fistula without Crohn's disease. Biopsy specimens were obtained from fistulous tracts during examination under anesthesia for both groups. The samples were sent for HPV detection and genotyping using the INNO-LiPA test. RESULTS A total of 108 subjects (54 in each group) were recruited. The perianal fistulizing Crohn's disease group showed a statistically higher frequency of HPV in the fistulous tract than the control group (33.3% vs. 16.7%; p = 0.046). Separate analyses on high-risk types demonstrated that there was a numerically higher frequency of HPV in the perianal fistulizing Crohn's disease group. In multiple logistic regression, patients with perianal fistulizing Crohn's disease were found to have a chance of HPV 3.29 times higher than patients without Crohn's disease (OR = 3.29; 95% CI 1.20‒9.01), regardless of other variables. The types most frequently identified in the perianal fistulizing Crohn's disease group were HPV 11 (12.96%) and HPV 16 (9.26%). CONCLUSION Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV than in patients with anorectal fistula without Crohn's disease.
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Affiliation(s)
- Lucas Rodrigues Boarini
- Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
| | - Carlos Walter Sobrado
- Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Giana Rabello Mota
- Centro de Investigação Translacional em Oncologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Luisa Lina Villa
- Centro de Investigação Translacional em Oncologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | | | - Natalia Sousa Freitas Queiroz
- Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | | | | | - Ivan Cecconello
- Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
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Wetwittayakhlang P, Al Khoury A, Hahn GD, Lakatos PL. The Optimal Management of Fistulizing Crohn's Disease: Evidence beyond Randomized Clinical Trials. J Clin Med 2022; 11:3045. [PMID: 35683433 PMCID: PMC9181669 DOI: 10.3390/jcm11113045] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/21/2022] [Accepted: 05/25/2022] [Indexed: 02/04/2023] Open
Abstract
Fistulizing Crohn's disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require a multidisciplinary approach, including a combined medical and surgical approach. The therapeutic options for FCD are limited due to sparse evidence from randomized clinical trials (RCTs). The current recommendations are mainly based on post hoc analysis from RCTs, real-world clinical studies and expert opinion. There is variation in everyday clinical practice amongst gastroenterologists and surgeons. The evidence for anti-tumor necrosis factor therapy is the strongest in the treatment of FCD. However, long-term fistula healing can be achieved in only 30-50% of patients. In recent years, emerging data in the advent of therapeutic modalities, including the use of new biologic agents, therapeutic drug monitoring, novel surgical methods and mesenchymal stem cell therapy, have been shown to improve outcomes in achieving fistula healing. This review summarizes the existing literature on current and emerging therapies to provide guidance beyond RCTs in managing FCD.
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Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Alex Al Khoury
- Division of Gastroenterology, University of Florida, Jacksonville, FL 32209, USA;
| | - Gustavo Drügg Hahn
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- Graduate Course Sciences in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil
| | - Peter Laszlo Lakatos
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- First Department of Medicine, Semmelweis University, 1085 Budapest, Hungary
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Motamedi MAK, Serahati S, Rajendran L, Brown CJ, Raval MJ, Karimuddin A, Ghuman A, Phang PT. Long-term outcomes after seton placement for perianal fistulas with and without Crohn's disease. Colorectal Dis 2021; 23:2407-2415. [PMID: 34157210 DOI: 10.1111/codi.15771] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/07/2021] [Accepted: 05/19/2021] [Indexed: 02/08/2023]
Abstract
AIM Perianal sepsis in Crohn's disease (CD) fistulas is managed with antibiotics and surgical drainage; a noncutting seton is used for an identified transsphincteric fistula tract. The optimal management following seton placement for initial control of perianal sepsis remains to be determined. Our main aim was to assess the success rates of curative surgery, seton removal or long-term indwelling seton in patients with and without CD. METHOD This was a retrospective cohort of consecutive patients with a perianal fistula treated with a noncutting seton between 2010 and 2019, including 83 CD patients and 94 patients without CD. Initial control of symptomatic perianal infection with a seton and subsequent healing and reintervention rates were compared between the three postseton management strategies. RESULTS A total of 177 patients, 61% male and 83.1% with complex fistulas, were followed for a median of 23 months (interquartile range 11-40 months). Immunomodulatory treatment was used in 90.4% of CD patients after seton placement. Good initial control of perianal infection was achieved with a seton in CD and non-CD patients, at 92.9% and 96.7%, respectively (p = 0.11). Overall fistula healing or control for CD and non-CD patients was, respectively, 64% and 86% (p = 0.1) after curative surgery, 49% and 71% after seton removal (p = 0.21) and 58% and 50% with long-term seton placement (p = 0.72). Overall reintervention for recurrence was 83% in CD versus 53.1% in non-CD patients during the follow-up period (p = 0.002). CONCLUSION Definitive surgery was possible in only a minority of CD patients. Long-term seton management was an effective option in patients with CD with acceptable improvement and recurrence rates.
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Affiliation(s)
- Mohammad Ali K Motamedi
- Colorectal Surgery Division, Department of Surgery, St Paul's Hospital, Vancouver, BC, Canada
| | - Sara Serahati
- Department of Public Health, University of Saskatchewan, Saskatoon, SK, Canada
| | - Luckshi Rajendran
- Division of General Surgery, University of Toronto, Toronto, ON, Canada
| | - Carl J Brown
- Colorectal Surgery Division, Department of Surgery, St Paul's Hospital, Vancouver, BC, Canada
| | - Manoj J Raval
- Colorectal Surgery Division, Department of Surgery, St Paul's Hospital, Vancouver, BC, Canada
| | - Ahmer Karimuddin
- Colorectal Surgery Division, Department of Surgery, St Paul's Hospital, Vancouver, BC, Canada
| | - Amandeep Ghuman
- Colorectal Surgery Division, Department of Surgery, St Paul's Hospital, Vancouver, BC, Canada
| | - Paul T Phang
- Colorectal Surgery Division, Department of Surgery, St Paul's Hospital, Vancouver, BC, Canada
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Zabot GP, Cassol O, Saad-Hossne R, Bemelman W. Modern surgical strategies for perianal Crohn's disease. World J Gastroenterol 2020; 26:6572-6581. [PMID: 33268947 PMCID: PMC7673971 DOI: 10.3748/wjg.v26.i42.6572] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 09/05/2020] [Accepted: 09/28/2020] [Indexed: 02/06/2023] Open
Abstract
One of the most challenging phenotypes of Crohn’s disease is perianal fistulizing disease (PFCD). It occurs in up to 50% of the patients who also have symptoms in other parts of the gastrointestinal tract, and in 5% of the cases it occurs as the first manifestation. It is associated with severe symptoms, such as pain, fecal incontinence, and a significant reduction in quality of life. The presence of perianal disease in conjunction with Crohn’s disease portends a significantly worse disease course. These patients require close monitoring to identify those at risk of worsening disease, suboptimal biological drug levels, and signs of developing neoplasm. The last 2 decades have seen significant advancements in the management of PFCD. More recently, newer biologics, cell-based therapies, and novel surgical techniques have been introduced in the hope of improved outcomes. However, in refractory cases, many patients face the decision of having a stoma made and/or a proctectomy performed. In this review, we describe modern surgical management and the most recent advances in the management of complex PFCD, which will likely impact clinical practice.
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Affiliation(s)
- Gilmara Pandolfo Zabot
- Department of Coloproctology, Hospital Moinhos de Vento, Porto Alegre 90035-902, RS, Brazil
| | - Ornella Cassol
- Department of Surgery, Hospital de Clínicas de Passo Fundo, Passo Fundo 99010-260, RS, Brazil
| | - Rogerio Saad-Hossne
- Department of Internal Medicine, São Paulo State University (Unesp), Medical School, Botucatu 18618687, São Paulo, Brazil
| | - Willem Bemelman
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam 19268, Netherlands
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Lightner AL, Ashburn JH, Brar MS, Carvello M, Chandrasinghe P, van Overstraeten ADB, Fleshner PR, Gallo G, Kotze PG, Holubar SD, Reza LM, Spinelli A, Strong SA, Tozer PJ, Truong A, Warusavitarne J, Yamamoto T, Zaghiyan K. Fistulizing Crohn's disease. Curr Probl Surg 2020; 57:100808. [PMID: 33187597 DOI: 10.1016/j.cpsurg.2020.100808] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 04/22/2020] [Indexed: 02/06/2023]
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Spinelli A, Armuzzi A, Ciccocioppo R, Danese S, Gionchetti P, Luglio G, Orlando A, Rispo A, Rizzello F, Sofo L, Solina G, Poggioli G. Management of patients with complex perianal fistulas in Crohn's disease: Optimal patient flow in the Italian clinical reality. Dig Liver Dis 2020; 52:506-515. [PMID: 31901310 DOI: 10.1016/j.dld.2019.11.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 11/07/2019] [Accepted: 11/18/2019] [Indexed: 12/11/2022]
Abstract
Perianal fistulizing Crohn's disease (PFCD) is a common, disabling and aggressive phenotype that negatively impacts on the quality of life of affected patients. Its successful treatment is still a struggle for both physicians and patients. Significant advances in the management of this condition have occurred in the last two decades holding promise for a better future. This culminated into the concept of a collaborative multidisciplinary approach using the latest medical therapies combined with modern surgical and endoscopic techniques. Despite this, PFCD management and treatment have not been standardized yet. Thus the gastroenterologist and surgeon have to be familiar with several approaches and/or techniques. The positioning of each therapeutic option will certainly evolve with new data, but for the time being it should be driven by patient's characteristics, physician's preference and/or experience, costs and availability in local practice. Additionally, patient's perception of benefits and risks of treatment may differ from those of physicians and recognition of this difference is a starting point for difficult clinical decision-making. In this paper, a multidisciplinary group of Italian IBD experts explore and discuss current medical and surgical therapeutic options, highlighting areas of unmet needs in PFCD, with particular focus on the optimal patient flow within the Italian clinical reality.
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Affiliation(s)
- Antonino Spinelli
- Division of Colon and Rectal Surgery, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy.
| | | | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, G.B. Rossi University Hospital, Verona, Italy
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy; IBD Center, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy
| | - Paolo Gionchetti
- Emilia-Romagna IBD Regional Referral Center, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Gaetano Luglio
- Surgery Unit, Department of Public Health, Federico II University Hospital, Naples, Italy
| | | | - Antonio Rispo
- Gastroenterology Unit, Federico II University Hospital, Naples, Italy
| | - Fernando Rizzello
- Emilia-Romagna IBD Regional Referral Center, Department of Medical and Surgical Sciences, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Luigi Sofo
- Abdominal SUrgery Unit, Department of Gastroenterology, Endocrine-metabolic and Nephrourological Science, A. Gemelli Hospital, Cattolica University, Rome, Italy
| | - Gaspare Solina
- Unit of General and Oncological Surgery, Department of Surgery, "Villa Sofia-Cervello" Hospital, Palermo, Italy
| | - Gilberto Poggioli
- Digestive Surgery Department, S. Orsola-Malpighi University Hospital, Bologna, Italy
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Kotze PG, Spinelli A, Lightner AL. Cell-based Therapy for Perianal Fistulising Crohn's Disease. Curr Pharm Des 2020; 25:41-46. [PMID: 31092172 DOI: 10.2174/1381612825666190308095651] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 03/01/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND The management of complex perianal fistulas in Crohn's disease (CD) represents a challenge for patients, gastroenterologists and colorectal surgeons. There are clear limitations with current medical and surgical options, and healing rates remain far from what is expected. A multidisciplinary approach with optimized medical therapy, usually anti-TNF agents, associated with setons and additional surgical techniques is currently the best strategy to aim fistula healing. METHODS A comprehensive review of the literature was conducted on the use of mesenchymal stem cells (MSCs). RESULTS The use of mesenchymal stem cells (MSCs) has recently emerged as a promising new therapeutic strategy for complex fistulas in CD patients. This review summarizes the evidence of the use of MSCs in complex CD fistulas, by exploring in detail the types of cells that can be used and their modes of delivery. Additionally, the results of the most recent phase III randomized trial with local MSCs injection are described, and future challenges of this therapeutic option are discussed. CONCLUSION The use of MSCs represents hope for better outcomes in patients with CD-related perianal fistulas. More research in the field will help to position this specific therapy in treatment algorithms.
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Affiliation(s)
- Paulo Gustavo Kotze
- Colorectal Surgery Unit, IBD outpatient clinics, Catholic University of Parana, Curitiba, Brazil
| | - Antonino Spinelli
- Division of Colon and Rectal Surgery, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Amy Lee Lightner
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, United States
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Jeon M, Song K, Koo J, Kim S. Evaluation of a Seton Procedure Combined With Infliximab Therapy (Early vs. Late) in Perianal Fistula With Crohn Disease. Ann Coloproctol 2019; 35:249-253. [PMID: 31726000 PMCID: PMC6863002 DOI: 10.3393/ac.2018.11.23.1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 11/23/2018] [Indexed: 02/07/2023] Open
Abstract
PURPOSE We assessed the clinical outcomes of a seton procedure combined with early versus late institution of infliximab (IFX) therapy. METHODS This retrospective study comprised 76 patients who underwent surgery for perianal fistula associated with Crohn disease between January 2014 and November 2017. All patients underwent loose seton drainage combined with IFX therapy. Patients categorized as the early group (EG, 49 patients) received IFX therapy within 30 days of completion of the seton procedure. Patients categorized as the late group (LG, 27 patients) received IFX therapy >30 days after the seton procedure. IFX therapy was administered as induction and maintenance therapy. RESULTS There were no statistically significant intergroup differences in clinical characteristics of the patients. The mean follow-up was 21.0 ± 11.6 months in the EG and 34.5 ± 18.4 months in the LG (P = 0.001). The mean interval between seton procedure and IFX induction therapy was 12.2 days in the EG and 250.2 days in the LG (P = 0.002). Complete remission was observed in 32 patients (65.3%) in the EG and 17 patients (63.0%) in the LG (P = 0.844). Fistula recurrence was observed in 6 patients (7.9%). All recurrences occurred in a previous perianal fistula tract. CONCLUSION Patients showed a good response to a seton procedure combined with IFX therapy regardless of the time of initiation of IFX therapy.
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Affiliation(s)
| | - Kihwan Song
- Department of Surgery, Goo Hospital, Daegu, Korea
| | - Jail Koo
- Department of Surgery, Goo Hospital, Daegu, Korea
| | - Sohyun Kim
- Department of Surgery, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Korea
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12
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Saigusa N, Saigusa JI, Shinozaki M, Yokoyama T, Yokoi Y, Takami H, Miyahara R, Yokoyama Y. A series of seton techniques involving "top-down therapy" for patients with Crohn's disease who initially presented with perianal fistulas. J Anus Rectum Colon 2018; 2:122-129. [PMID: 31559354 PMCID: PMC6752135 DOI: 10.23922/jarc.2017-044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Accepted: 03/06/2018] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVES We determined the outcomes of seton treatment through a series of techniques using biological agents (BIOs) in 18 patients with Crohn's disease (CD) who initially presented with perianal fistulas. METHODS The patients underwent seton drainage using three seton types: a Penrose tube for fistulas with massive purulent discharge, a vessel loop for a small amount of discharge, and a rubber band for unproductive fistulas. If the distal end of the fistula extended more than 4 cm from the anal orifice, the skin and subcutaneous tissue were dissected along the outer edge of the anal sphincter to divide the fistulous tract into two portions. One seton encircled the sphincter from the primary opening throughout the anal canal (medial seton), and the other was inserted through the distal tract outside the sphincter (lateral seton). A BIO was then introduced immediately. When discharge ceased, the Penrose tube or vessel loop was replaced sequentially with a rubber band, which was tied fittingly and subsequently removed in medial to lateral order. RESULTS The mean interval between fistula onset and CD diagnosis was 2.1 years, and that between CD diagnosis and introduction of BIOs was 0.5 years. The mean follow-up duration was 4 years. The BIOs currently used were infliximab in 10 patients, adalimumab in 7, and ustekinumab in 1. The overall success rate was 94.4%, including unproductive fistulas in 10 (55.6%) patients and fistula disappearance in 7 (38.9%). CONCLUSIONS Our seton drainage techniques via the "top-down" approach represent a promising avenue for treating perianal fistulas in patients with CD.
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Affiliation(s)
- Naoto Saigusa
- Department of Surgery, Yokoyama Memorial Hospital, Nagoya City, Japan
- Saigusa Coloproctological Clinic, Shizuoka City, Japan
| | | | - Masaru Shinozaki
- Department of Surgery, Research Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | | | - Yoshihiro Yokoi
- Department of Surgery, Shinshiro Municipal Hospital, Shinshiro City, Japan
| | - Hideki Takami
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya City, Japan
| | - Ryoji Miyahara
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya City, Japan
| | - Yasuhisa Yokoyama
- Department of Surgery, Yokoyama Memorial Hospital, Nagoya City, Japan
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13
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Kotze PG, Shen B, Lightner A, Yamamoto T, Spinelli A, Ghosh S, Panaccione R. Modern management of perianal fistulas in Crohn's disease: future directions. Gut 2018; 67:1181-1194. [PMID: 29331943 DOI: 10.1136/gutjnl-2017-314918] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Revised: 11/20/2017] [Accepted: 12/15/2017] [Indexed: 12/12/2022]
Abstract
Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.
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Affiliation(s)
- Paulo Gustavo Kotze
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Unit, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Bo Shen
- Interventional IBD Unit, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Amy Lightner
- Division of Colorectal Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Antonino Spinelli
- Division of Colon and Rectal Surgery, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Subrata Ghosh
- Institute of Translational Medicine, University of Birmingham, Birmingham, UK
| | - Remo Panaccione
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Unit, Cumming School of Medicine, University of Calgary, Calgary, Canada
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14
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Lee MJ, Heywood N, Adegbola S, Tozer P, Sahnan K, Fearnhead NS, Brown SR. Systematic review of surgical interventions for Crohn's anal fistula. BJS Open 2017; 1:55-66. [PMID: 29951607 PMCID: PMC5989984 DOI: 10.1002/bjs5.13] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Accepted: 07/06/2017] [Indexed: 12/14/2022] Open
Abstract
Background Anal fistula occurs in approximately one in three patients with Crohn's disease and is typically managed through a multimodal approach. The optimal surgical therapy is not yet clear. The aim of this systematic review was to identify and assess the literature on surgical treatments of Crohn's anal fistula. Methods A systematic review was conducted that analysed studies relating to surgical treatment of Crohn's anal fistula published on MEDLINE, Embase and Cochrane databases between January 1995 and March 2016. Studies reporting specific outcomes of patients treated for Crohn's anal fistula were included. The primary outcome was fistula healing rate. Bias was assessed using the Cochrane ROBINS‐I and ROB tool as appropriate. Results A total of 1628 citations were reviewed. Sixty‐three studies comprising 1584 patients were ultimately selected in the analyses. There was extensive reporting on the use of setons, advancement flaps and fistula plugs. Randomized trials were available only for stem cells and fistula plugs. There was inconsistency in outcome measures across studies, and a high degree of bias was noted. Conclusion Data describing surgical intervention for Crohn's anal fistula are heterogeneous with a high degree of bias. There is a clear need for standardization of outcomes and description of study cohorts for better understanding of treatment options.
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Affiliation(s)
- M J Lee
- Sheffield Teaching Hospitals NHS Foundation Trust Sheffield UK
| | - N Heywood
- University Hospital South Manchester Manchester UK
| | | | - P Tozer
- St Mark's Hospital Harrow UK
| | | | | | - S R Brown
- Sheffield Teaching Hospitals NHS Foundation Trust Sheffield UK
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15
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Papamichael K, Cheifetz AS. Defining and predicting deep remission in patients with perianal fistulizing Crohn’s disease on anti-tumor necrosis factor therapy. World J Gastroenterol 2017; 23:6197-6200. [PMID: 28974885 PMCID: PMC5603485 DOI: 10.3748/wjg.v23.i34.6197] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 08/16/2017] [Accepted: 09/05/2017] [Indexed: 02/06/2023] Open
Abstract
Perianal fistulas can occur to up to one-third of patients with Crohn’s disease (CD) leading to significant disabling disease and morbidity. Fistulising perianal CD treatment often necessitates a combined pharmacological and surgical approach. Anti-tumor necrosis factor (anti-TNF) therapy, particularly infliximab, has been shown to be very effective for both perianal and internal fistulising CD. Nevertheless, current data suggest that sustained remission and long-term complete fistula healing can be achieved in only 30% to 50% of patients. Moreover, these percentages refer mostly to clinical rather than deep remission, defined as endoscopic and radiologic remission, which is quickly emerging as the preferred goal of therapy. Unfortunately, the therapeutic options for perianal fistulising CD are still limited. As such, it would be of great value to be able to predict, and more importantly, prevent treatment failure in these patients by early and continued optimization of anti-TNF therapy. Similar to ulcerative colitis and luminal CD, recent data demonstrate that higher infliximab concentrations are associated with better clinical outcomes in patients with perianal fistulising CD. This suggests that therapeutic drug monitoring and a treat-to-trough therapeutic approach may emerge as the new standard of care for optimizing anti-TNF therapy in patients with perianal fistulising CD.
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Affiliation(s)
- Konstantinos Papamichael
- Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Adam S Cheifetz
- Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
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16
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Feitosa MR, Féres Filho O, Tamaki CM, Perazzoli C, Bernardes MVAA, Parra RS, Rocha JJRD, Féres O. Adjunctive Hyperbaric Oxygen Therapy promotes successful healing in patients with refractory Crohn's disease. Acta Cir Bras 2017; 31 Suppl 1:19-23. [PMID: 27142900 DOI: 10.1590/s0102-86502016001300005] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
PURPOSE To investigate de adjunctive effect of Hyperbaric Oxygen Therapy in a group of patients with refractory Crohn's disease. METHODS A total of 29 subjects with refractory Crohn's disease were submitted to daily sessions of Hyperbaric Oxygen Therapy, in a 2800 Sechrist Monoplace Hyperbaric Chamber (Sechrist, USA) pressurized to 2.4 ATA. Each session lasted 2 hours. The endpoint was closure of enterocutaneous fistulas and complete healing of Pyoderma Gangrenosum and perineal Crohn's disease. RESULTS A total of 829 HBOT sessions were performed and no complications were noted. Overall success rate was 76% (22 cases). Pyoderma Gangrenosum and enterocutaneous fistulas had the highest successful healing rates (100% and 91%, respectively). Perineal Crohn's disease healing rate was 65%. CONCLUSION Adjunctive Hyperbaric Oxygen Therapy promoted satisfactory healing in a group of patients with refractory Crohn's disease.
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Affiliation(s)
- Marley Ribeiro Feitosa
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Brazil
| | | | | | - Camila Perazzoli
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Brazil
| | | | - Rogério Serafim Parra
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Brazil
| | | | - Omar Féres
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Brazil
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17
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Kantor N, Wayne C, Nasr A. What is the optimal surgical strategy for complex perianal fistulous disease in pediatric Crohn's disease? A systematic review. Pediatr Surg Int 2017; 33:551-557. [PMID: 28138950 DOI: 10.1007/s00383-017-4067-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/11/2017] [Indexed: 01/06/2023]
Abstract
PURPOSE Perianal fistulous disease is present in 10-15% of children with Crohn's disease (CD) and is frequently complex and refractory to treatment, with one-third of patients having recurrent lesions. We conducted a systematic review of the literature to examine the best surgical strategy or strategies for pediatric complex perianal fistulous disease (CPFD) in CD. METHODS We searched CENTRAL, MEDLINE, EMBASE, and CINAHL for studies discussing at least one surgical strategy for the treatment of pediatric CPFD in CD. Reference lists of included studies were hand-searched. Two researchers screened all studies for inclusion, quality assessed each relevant study, and extracted data. RESULTS One non-randomized prospective and two retrospective studies met our inclusion criteria. Combined use of setons and infliximab therapy shows promise as a first-line treatment. A specific form of fistulectomy, "cone-like resection," also shows promise when combined with biologics. Endoscopic ultrasound to guide medical and surgical management is feasible in the pediatric population, though it is unclear if it improves outcomes. CONCLUSION There is a paucity of evidence regarding the treatment of CPFD in the pediatric population, and further research is required before recommendations can be made as to what, if any, surgical management is optimal.
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Affiliation(s)
- Navot Kantor
- Department of Surgery, Children's Hospital of Eastern Ontario, 401 Smyth Rd, Ottawa, ON, K1H 8L1, Canada.,Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON, K1H 8L1, Canada
| | - Carolyn Wayne
- Department of Surgery, Children's Hospital of Eastern Ontario, 401 Smyth Rd, Ottawa, ON, K1H 8L1, Canada
| | - Ahmed Nasr
- Department of Surgery, Children's Hospital of Eastern Ontario, 401 Smyth Rd, Ottawa, ON, K1H 8L1, Canada. .,Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON, K1H 8L1, Canada.
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18
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de Groof EJ, Sahami S, Lucas C, Ponsioen CY, Bemelman WA, Buskens CJ. Treatment of perianal fistula in Crohn's disease: a systematic review and meta-analysis comparing seton drainage and anti-tumour necrosis factor treatment. Colorectal Dis 2016; 18:667-75. [PMID: 26921847 DOI: 10.1111/codi.13311] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 11/18/2015] [Indexed: 12/13/2022]
Abstract
AIM The introduction of anti-tumour necrosis factor (anti-TNF; infliximab and adalimumab) has changed the management of Crohn's perianal fistula from almost exclusively surgical treatment to one with a much larger emphasis on medical therapy. The aim of this systematic review was to provide an overview of the success rates of setons and anti-TNF for Crohn's perianal fistula. METHOD Studies evaluating the effect of setons and anti-TNF on Crohn's perianal fistula were included. Studies assessing perianal fistula in children, rectovaginal and rectourinary fistulae were excluded. The primary end-point was the fistula closure rate. Partial closure and recurrence rates were secondary end-points. RESULTS Ten studies on seton drainage were included (n = 305). Complete closure varied from 13.6% to 100% and recurrence from 0% to 83.3%. In 34 anti-TNF studies (n = 1449), complete closure varied from 16.7% and 93% (partial closure 8.0-91.2%) and recurrence from 8.0% to 40.9%. Four randomized controlled trials (n = 1028) comparing anti-TNF with placebo showed no significant difference in complete or partial closure in meta-analysis (risk difference 0.12, 95% CI -0.06 to 0.30 and 0.09, 95% CI -0.23 to 0.41, respectively). Subgroup analysis (n = 241) showed a significant advantage for complete fistula closure with anti-TNF in two trials with follow-up > 4 weeks (46% vs 13%, P = 0.003 and 30% vs 13%, P = 0.03). Of four included cohort studies, two revealed a significant difference in response in favour of combined treatment (P = 0.001 and P = 0.014). CONCLUSION Closure and recurrence rates after seton drainage as well as anti-TNF vary widely. Despite a large number of studies, no conclusions can be drawn regarding the preferred strategy. However, combination therapy with (temporary) seton drainage, immunomodulators and anti-TNF may be beneficial in achieving perianal fistula closure.
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Affiliation(s)
- E J de Groof
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - S Sahami
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - C Lucas
- Department of Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands
| | - C Y Ponsioen
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - W A Bemelman
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - C J Buskens
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
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19
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Dillman JR, Trout AT, Smith EA. MR enterography: how to deliver added value. Pediatr Radiol 2016; 46:829-37. [PMID: 26939974 DOI: 10.1007/s00247-016-3555-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 11/28/2015] [Accepted: 01/21/2016] [Indexed: 02/07/2023]
Abstract
MR enterography (MRE) is increasingly vital to the diagnosis and follow-up of children with Crohn disease. This diagnostic test, which can provide valuable information regarding the presence of intestinal inflammation, intestinal and intra-abdominal complications, and extra-intestinal disease-related manifestations, has the potential to directly impact both medical and surgical decision-making. Consequently, it is imperative that the interpretation and reporting of these examinations provide as much clinical information as possible. This article reviews specific ways radiologists can provide added value when interpreting MRE examinations in the setting of pediatric Crohn disease by (1) establishing the true extent of disease involvement, (2) subjectively and objectively assessing response to medical treatment and (3) accurately characterizing disease-related complications.
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Affiliation(s)
- Jonathan R Dillman
- Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229-3039, USA.
| | - Andrew T Trout
- Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229-3039, USA
| | - Ethan A Smith
- Department of Radiology, University of Michigan Health System, Section of Pediatric Radiology, C.S. Mott Children's Hospital, Ann Arbor, MI, USA
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20
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Abstract
Pediatric inflammatory bowel disease is a chronic gastrointestinal disease consisting of Crohn's disease (CD) and ulcerative colitis (UC). Both disease processes can share similar clinical symptoms including abdominal pain, diarrhea, hematochezia, and weight loss; CD can also be complicated by penetrating and fistulizing disease. Perianal skin tags, perianal abscesses, recto-cutaneous fistulae, and rectal stenosis are among the phenotypic characteristics of perianal CD. Current treatment strategies are focused on the surgical drainage of abscesses and the closure of fistulous tracts as well as controlling intestinal inflammation with the use of immunomodulators (6-mercaptopurine and methotrexate) and biologics (infliximab and adalimumab). Current guidelines by the American Gastroenterology Association and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommend a combination of surgical intervention and medical management for the treatment of perianal CD.
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