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Jin X, Han Y, Yang M, Ye Q, Wang Q, Zheng D, Mei Z. Global trends in surgically based treatment of anal fistula in Crohn's disease: a bibliometric and visualization analysis. Int J Surg 2025; 111:2578-2589. [PMID: 39869383 DOI: 10.1097/js9.0000000000002238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 11/27/2024] [Indexed: 01/28/2025]
Abstract
BACKGROUND Crohn's disease (CD) is a chronic, recurrent gastrointestinal disorder characterized by a complex etiology. Among its perianal complications, anal fistulas represent a challenging comorbidity. With the increase of surgical options, a comprehensive bibliometric analysis was deemed necessary to consolidate the vast array of research in this field. METHODS We extracted 1608 articles spanning from 1 January 1994, to 1 May 2024, from the Web of Science Core Collection. Using VOSviewer, CiteSpace, and Scimago Graphica for visual analytics, we synthesized key trends across multiple bibliometric indicators, encompassing geographic and institutional contributions, individual authorship, journal prominence, citation metrics, and thematic prevalence. RESULTS From the delineated corpus, we identified publications from 325 countries and 5110 research institutions, with the US and UK at the forefront of publication volume and academic impact. The data indicated a leading role for institutions like the Cleveland Clinic and Imperial College London. "Diseases of the Colon and Rectum" emerged as a central journal due to its high publication and citation frequency. Distinctly, the analysis uncovered trending keywords, signifying the field's prioritization on surgical intervention, biologic therapy, imaging modalities, and emerging biological treatments. CONCLUSION Our findings elucidate a trajectory toward prominent advancements in CD fistula research. This analysis underscores the field's shift towards integrative treatment strategies, spotlighting the pressing need for comprehensive comparative studies of surgical approaches. It underscores the imperative for robust clinical trials to standardize treatments and extend care to a broader CD patient population.
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Affiliation(s)
- Xingtao Jin
- Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ye Han
- Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Min Yang
- Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qianqian Ye
- Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qingming Wang
- Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - De Zheng
- Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Anorectal Disease Institute of Shuguang Hospital, Shanghai, China
| | - Zubing Mei
- Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Anorectal Disease Institute of Shuguang Hospital, Shanghai, China
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McCurdy JD, Munir J, Parlow S, Reid J, Yanofsky R, Alenezi T, Meserve J, Becker B, Lahijanian Z, Eddin AH, Mallick R, Ramsay T, Rosenfeld G, Bessissow A, Bessissow T, Jairath V, Singh S, Bruining DH, Macdonald B. Development of an MRI-Based Prediction Model for Anti-TNF Treatment Failure in Perianal Crohn's Disease: A Multicenter Study. Clin Gastroenterol Hepatol 2024; 22:1058-1066.e2. [PMID: 38122958 DOI: 10.1016/j.cgh.2023.12.006] [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: 09/02/2023] [Revised: 11/10/2023] [Accepted: 12/05/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND & AIMS Clinical and radiologic variables associated with perianal fistula (PAF) outcomes are poorly understood. We developed prediction models for anti-tumor necrosis factor (TNF) treatment failure in patients with Crohn's disease-related PAF. METHODS In a multicenter retrospective study between 2005 and 2022 we included biologic-naive adults (>17 years) who initiated their first anti-TNF therapy for PAF after pelvic magnetic resonance imaging (MRI). Pretreatment MRI studies were prospectively reread centrally by blinded radiologists. We developed and internally validated a prediction model based on clinical and radiologic parameters to predict the likelihood of anti-TNF treatment failure, clinically, at 6 months. We compared our model and a simplified version of MRI parameters alone with existing imaging-based PAF activity indices (MAGNIFI-CD and modified Van Assche MRI scores) by De Long statistical test. RESULTS We included 221 patients: 32 ± 14 years, 60% males, 76% complex fistulas; 68% treated with infliximab and 32% treated with adalimumab. Treatment failure occurred in 102 (46%) patients. Our prediction model included age at PAF diagnosis, time to initiate anti-TNF treatment, and smoking and 8 MRI characteristics (supra/extrasphincteric anatomy, fistula length >4.3 cm, primary tracts >1, secondary tracts >1, external openings >1, tract hyperintensity on T1-weighted imaging, horseshoe anatomy, and collections >1.3 cm). Our full and simplified MRI models had fair discriminatory capacity for anti-TNF treatment failure (concordance statistic, 0.67 and 0.65, respectively) and outperformed MAGNIFI-CD (P = .002 and < .0005) and modified Van Assche MRI scores (P < .0001 and < .0001), respectively. CONCLUSIONS Our risk prediction models consisting of clinical and/or radiologic variables accurately predict treatment failure in patients with PAF.
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Affiliation(s)
- Jeffrey D McCurdy
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada.
| | - Javeria Munir
- Division of Diagnostic Imaging, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Simon Parlow
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Jacqueline Reid
- Department of Medicine, UBC, Vancouver, British Columbia, Canada
| | - Russell Yanofsky
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada
| | - Talal Alenezi
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada
| | - Joseph Meserve
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California
| | - Brenda Becker
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Zubin Lahijanian
- Division of Diagnostic Imaging, McGill University, Montreal, Quebec, Canada
| | - Anas Hussam Eddin
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada
| | - Ranjeeta Mallick
- Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Tim Ramsay
- Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Greg Rosenfeld
- Department of Medicine, UBC, Vancouver, British Columbia, Canada
| | - Ali Bessissow
- Division of Diagnostic Imaging, McGill University, Montreal, Quebec, Canada
| | - Talat Bessissow
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California
| | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Blair Macdonald
- Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada; Division of Diagnostic Imaging, The Ottawa Hospital, Ottawa, Ontario, Canada
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Khan SZ, Arline A, Williams KM, Lee MJ, Steinhagen E, Stein SL. The use of core descriptors from the ENiGMA code study in recent literature: a systematic review. Colorectal Dis 2024; 26:428-438. [PMID: 38296841 DOI: 10.1111/codi.16893] [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: 06/08/2023] [Accepted: 01/10/2024] [Indexed: 02/02/2024]
Abstract
AIM The heterogeneity in data quality presented in studies regarding Crohn's anal fistula (CAF) limit extrapolation into clinical practice. The ENiGMA collaborators established a core descriptor set to standardize reporting of CAF. The aim of this work was to quantify the use of these descriptors in recent literature. METHOD We completed a systematic review of PubMed and the Cochrane Library, extracting publications from the past 10 years specific to the clinical interventions and outcomes of CAF, and reported in line with PRISMA guidance. Each article was assessed for inclusion of ENiGMA descriptors. The median number of descriptors per publication was evaluated along with the overall frequency of each individual descriptor. Use of ENiGMA descriptors was compared between medical and procedural publications. RESULTS Ninety publications were included. The median number of descriptors was 15 of 37; 16 descriptors were used in over half of the publications while 17 were used in fewer than a third. Descriptors were more frequently used in procedural (n = 16) than medical publications (n = 14) (p = 0.031). In procedural publications, eight descriptors were more frequently used including Faecal incontinence, Number of previous fistula interventions, Presence and severity of anorectal stenosis and Current proctitis. Medical publications were more likely to include Previous response to biological therapy and Duration and type of current course of biological therapy. CONCLUSION With many descriptors being used infrequently and variations between medical and procedural literature, the colorectal community should assess the need for all 37 descriptors.
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Affiliation(s)
- Saher-Zahra Khan
- University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, USA
| | - Andrea Arline
- Case Western Reserve University School of Medicine, Cleveland, USA
| | | | - Matthew J Lee
- Academic Directorate of General Surgery, Sheffield Teaching Hospitals NHS FT, Sheffield, UK
- Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK
| | - Emily Steinhagen
- University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, USA
| | - Sharon L Stein
- University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, USA
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Rosevics L, Savio MC, Lima Júnior E, Ramos Júnior O. FISTULIZING PERIANAL CROHN'S DISEASE: IS THE PATIENT'S SEX A BURDEN? A SYSTEMATIC REVIEW. ARQUIVOS DE GASTROENTEROLOGIA 2023; 60:490-524. [PMID: 38018554 DOI: 10.1590/s0004-2803.230402023-28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 07/31/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome. OBJECTIVE Thus, the aim of this study was to assess whether sex influences the response to treatment for these patients. METHODS This systematic review (PROSPERO CRD42022319629) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. We selected articles published in English, Spanish, Portuguese, and Italian between 2010 and 2020 in the PubMed and Science Direct databases. According to the PICO acronym, prospective studies in patients older than 18 years with the objective of treating fistulizing perianal Crohn's disease were selected. Studies in pediatric populations, retrospective, without treatment objectives, and that included only rectovaginal fistulas or a single sex were excluded. Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale. RESULTS Of the 1887 articles found, 33 were included. Most studies used anti-TNF drugs as treatment (n=11). Ten studies had subgroup analyses; of them, the two studies reporting sex differences used infliximab and adalimumab as treatment and showed that women had a longer fistula closure time than men. CONCLUSION This systematic review showed that few data corroborate the difference between sexes in the treatment of fistulizing perianal Crohn's disease, possibly having a greater relationship with the phenotype. However, considering the lack of results, further studies with this objective and with standardization of fistulas and response assessment methods are needed.
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Laland M, François M, D'Amico F, Zallot C, Brochard C, Dewitte M, Siproudhis L, Peyrin-Biroulet L, Bouguen G. Identification of the optimal medical and surgical management for patients with perianal fistulising Crohn's disease. Colorectal Dis 2023; 25:75-82. [PMID: 36016511 DOI: 10.1111/codi.16314] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 06/28/2022] [Accepted: 08/08/2022] [Indexed: 02/02/2023]
Abstract
AIM The aim of our study was to assess the best medical and surgical approaches for perianal Crohn's disease (PCD) in order to identify an optimal combined medical and surgical treatment. METHODS Medical records of all patients with PCD treated with TNFα antagonists in two referral centres between 1998 and 2018 were reviewed. Predictors of long-term outcomes were identified using a Cox proportional hazard model. RESULTS A total of 200 patients were included. Fifty-three patients (26.5%) were treated with adalimumab and 147 (73.5%) with infliximab. A combination of TNFα antagonist with an immunosuppressant and the presence of proctitis were independently associated with fistula closure. Seton was placed in 127 patients (63.5%) before starting biological therapy. Eighty patients (40%) underwent additional perineal surgery. Prior PCD surgery, seton positioning, additional perineal surgery, and additional surgery within 52 weeks of anti-TNFα treatment were associated with an increased rate of fistula closure. Finally, medical combination therapy (anti-TNFα plus immunosuppressant) along with seton placement and additional surgery within 1 year was the best management for PCD patients (p = 0.02). CONCLUSION Combined medical and surgical management is required for the treatment of PCD patients. Medical combination therapy associated with seton placement and additional surgery within 1 year is the best management for PCD patients.
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Affiliation(s)
| | | | - Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Camille Zallot
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Charlène Brochard
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), Rennes, France
| | - Marie Dewitte
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Rennes, France
| | - Laurent Siproudhis
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), Rennes, France
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Guillaume Bouguen
- CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), Rennes, France
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Wetwittayakhlang P, Al Khoury A, Hahn GD, Lakatos PL. The Optimal Management of Fistulizing Crohn's Disease: Evidence beyond Randomized Clinical Trials. J Clin Med 2022; 11:3045. [PMID: 35683433 PMCID: PMC9181669 DOI: 10.3390/jcm11113045] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/21/2022] [Accepted: 05/25/2022] [Indexed: 02/04/2023] Open
Abstract
Fistulizing Crohn's disease (FCD) remains the most challenging aspect of treating patients with CD. FCD can occur in up to 30% of patients with CD and may lead to significant disability and impaired quality of life. The optimal treatment strategies for FCD require a multidisciplinary approach, including a combined medical and surgical approach. The therapeutic options for FCD are limited due to sparse evidence from randomized clinical trials (RCTs). The current recommendations are mainly based on post hoc analysis from RCTs, real-world clinical studies and expert opinion. There is variation in everyday clinical practice amongst gastroenterologists and surgeons. The evidence for anti-tumor necrosis factor therapy is the strongest in the treatment of FCD. However, long-term fistula healing can be achieved in only 30-50% of patients. In recent years, emerging data in the advent of therapeutic modalities, including the use of new biologic agents, therapeutic drug monitoring, novel surgical methods and mesenchymal stem cell therapy, have been shown to improve outcomes in achieving fistula healing. This review summarizes the existing literature on current and emerging therapies to provide guidance beyond RCTs in managing FCD.
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Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
| | - Alex Al Khoury
- Division of Gastroenterology, University of Florida, Jacksonville, FL 32209, USA;
| | - Gustavo Drügg Hahn
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- Graduate Course Sciences in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-002, Brazil
| | - Peter Laszlo Lakatos
- Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada or (P.W.); (G.D.H.)
- First Department of Medicine, Semmelweis University, 1085 Budapest, Hungary
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Iglay K, Bennett D, Kappelman MD, Thai S, Aldridge M, Karki C, Cook SF. A systematic review of the patient burden of Crohn’s disease-related rectovaginal and anovaginal fistulas. BMC Gastroenterol 2022; 22:36. [PMID: 35090384 PMCID: PMC8796404 DOI: 10.1186/s12876-021-02079-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 12/22/2021] [Indexed: 01/09/2023] Open
Abstract
Abstract
Background
Crohn’s disease (CD)-related rectovaginal fistulas (RVFs) and anovaginal fistulas (AVFs) are rare, debilitating conditions that present a substantial disease and treatment burden for women. This systematic literature review (SLR) assessed the burden of Crohn’s-related RVF and AVF, summarizing evidence from observational studies and highlighting knowledge gaps.
Methods
This SLR identified articles in PubMed and Embase that provide data and insight into the patient experience and disease burden of Crohn’s-related RVF and AVF. Two trained reviewers used pre-specified eligibility criteria to identify studies for inclusion and evaluate risk of bias using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies.
Results
Of the 582 records identified, 316 full-text articles were assessed, and 16 studies met a priori eligibility criteria and were included. Few epidemiology studies were identified, with one study estimating the prevalence of RVF to be 2.3% in females with Crohn’s disease. Seven of 12 treatment pattern studies reported that patients had or required additional procedures before and/or after the intervention of interest, demonstrating a substantial treatment burden. Seven of 11 studies assessing clinical outcomes reported fistula healing rates between 50 and 75%, with varying estimates based on population and intervention.
Conclusions
This SLR reports the high disease and treatment burden of Crohn’s-related RVF and AVF and identifies multiple evidence gaps in this field. The literature lacks robust, generalizable data, and demonstrates a compelling need for substantial, novel research into these rare and debilitating sequelae of CD.
Registration The PROSPERO registration number for the protocol for this systematic literature review is CRD42020177732.
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Angriman I, Tomassi M, Ruffolo C, Bordignon G, Saadeh L, Gruppo M, Pucciarelli S, Bardini R, Scarpa M. Impact on Quality of Life of Seton Placing in Perianal Crohn's Disease. Front Surg 2022; 8:806497. [PMID: 35141271 PMCID: PMC8818691 DOI: 10.3389/fsurg.2021.806497] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 12/20/2021] [Indexed: 11/13/2022] Open
Abstract
IntroductionOften, in perineal Crohn's disease (CD), a seton is placed to guarantee a constant drainage and prevent septic complication while biologic therapy is ongoing. This study aimed to assess the long-term quality of life after surgery for perineal CD in relation to seton placing.Patients and MethodsData of 65 consecutive patients with CD and non-CD operated on from 2014 to 2019 for perianal fistula or abscess were retrieved. Forty-three had CD and 14 of them had a seton placed during surgery and they kept it on while they had anti-TNF-alpha therapy. Patients were interviewed with the Cleveland Global Quality of Life (CGQL) and SF-12 quality of life questionnaires. Disease activity was defined as Harvey-Bradshaw Index (HBI) and Perianal Disease Activity Index (PDAI). Comparisons between groups were carried out with the nonparametric tests, and multiple regression models were used to assess predictors of quality of life.ResultsThe total CGQL score and SF-12 mental component score (MCS) were significantly higher (and thus better) in the seton group than in patients treated without seton. On the contrary, SF-12 physical component score (PCS) was not different between the two groups. HBI was significantly better in patients in the seton group. At multivariate analysis, seton placement and HBI were confirmed to be independent predictors of long-term SF-12 MCS whereas only HBI confirmed to be a predictor of total CGQL score.ConclusionsSeton placing during anti-TNF-alpha therapy is independently associated with a better MCS. Unexpectedly, this device, instead of to cause psychological distress, seems to assure patients during their biologic therapy providing psychological benefit beyond the mere medical effect.
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Affiliation(s)
- Imerio Angriman
- Chirurgia Generale III, Department of Surgical Oncological and Gastroenterological Sciences, Azienda Ospedale Università di Padova, Padua, Italy
- General Surgery Unit, Azienda Ospedale Università di Padova, Padua, Italy
- *Correspondence: Imerio Angriman
| | - Monica Tomassi
- Chirurgia Generale III, Department of Surgical Oncological and Gastroenterological Sciences, Azienda Ospedale Università di Padova, Padua, Italy
- General Surgery Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Cesare Ruffolo
- Chirurgia Generale III, Department of Surgical Oncological and Gastroenterological Sciences, Azienda Ospedale Università di Padova, Padua, Italy
- General Surgery Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Giovanni Bordignon
- General Surgery Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Luca Saadeh
- General Surgery Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Mario Gruppo
- General Surgery Unit, Azienda Ospedale Università di Padova, Padua, Italy
- Surgical Oncology Unit, Veneto Institute of Oncology IOV Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Castelfranco Veneto, Italy
| | - Salvatore Pucciarelli
- Chirurgia Generale III, Department of Surgical Oncological and Gastroenterological Sciences, Azienda Ospedale Università di Padova, Padua, Italy
| | - Romeo Bardini
- General Surgery Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Marco Scarpa
- Chirurgia Generale III, Department of Surgical Oncological and Gastroenterological Sciences, Azienda Ospedale Università di Padova, Padua, Italy
- General Surgery Unit, Azienda Ospedale Università di Padova, Padua, Italy
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Zhu P, Sun JF, Gu YF, Chen HJ, Xu MM, Li YR, Yang BL. Combined therapy with early initiation of infliximab following drainage of perianal fistulising Crohn's disease: a retrospective cohort study. BMC Gastroenterol 2022; 22:15. [PMID: 35012467 PMCID: PMC8751033 DOI: 10.1186/s12876-021-02078-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 12/21/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Recent studies have confirmed that combined surgery and anti-TNF therapy could improve outcomes in patients with perianal fistulising Crohn's disease (PFCD). However, the optimal timing for infliximab infusion after surgical intervention is uncertain. We aimed to determine the long-term efficacy of early initiation of infliximab following surgery among PFCD patients. METHODS We performed a retrospective cohort study of PFCD patients who received combined infliximab and surgical treatment between 2010 and 2018 at a tertiary referral hospital. Patients were grouped according to the time interval between surgery and infliximab infusion, with < 6 weeks into early infliximab induction group and > 6 weeks into delayed infliximab induction group. The primary outcome was to compare surgical re-intervention between early and delayed infliximab induction groups. The secondary outcomes were fistula healing and predictors associated with these outcomes of early infliximab induction approach. RESULTS One hundred and seventeen patients were included (73 in early infliximab induction, 44 in delayed infliximab induction). The median interval between surgery and infliximab initiation was 9.0 (IQR 5.5-17.0) days in early infliximab induction group and 188.0 (IQR 102.25-455.75) days in delayed infliximab induction group. After followed-up for a median of 36 months, 61.6% of patients in early infliximab induction group and 65.9% in delayed infliximab induction group attained fistula healing (p = 0.643). The cumulative re-intervention rate was 23%, 32%, 34% in early infliximab induction group and 16%, 25%, 25% in delayed infliximab induction group, at 1, 2, and 3 years respectively (p = 0.235). Presence of abscess at baseline (HR = 5.283; 95% CI, 1.61-17.335; p = 0.006) and infliximab maintenance therapy > 3 infusions (HR = 3.691; 95% CI, 1.233-11.051; p = 0.02) were associated with re-intervention in early infliximab induction group. Presence of abscess at baseline also negatively influenced fistula healing (HR = 3.429, 95% CI, 1.216-9.668; p = 0.02). CONCLUSION Although no clear benefit was shown compared with delayed infliximab induction group, early initiation of infliximab after surgery could achieve promising results for PFCD patients. Before infliximab infusion, durable drainage is required for patients with concomitant abscess or prolonged infliximab maintenance therapy.
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Affiliation(s)
- Ping Zhu
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China
| | - Jin-Fang Sun
- Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China
| | - Yun-Fei Gu
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China
| | - Hong-Jin Chen
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China
| | - Min-Min Xu
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China
| | - You-Ran Li
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China
| | - Bo-Lin Yang
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, China.
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Aloi M, Cucchiara S. Crohn’s Disease. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:379-391. [DOI: 10.1007/978-3-030-80068-0_28] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Alyami A, Hoad CL, Tench C, Bannur U, Clarke C, Latief K, Argyriou K, Lobo A, Lung P, Baldwin-Cleland R, Sahnan K, Hart A, Limdi JK, Mclaughlin J, Atkinson D, Parker GJM, O’Connor JPB, Little RA, Gowland PA, Moran GW. Quantitative Magnetic Resonance Imaging in Perianal Crohn's Disease at 1.5 and 3.0 T: A Feasibility Study. Diagnostics (Basel) 2021; 11:2135. [PMID: 34829482 PMCID: PMC8624877 DOI: 10.3390/diagnostics11112135] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/08/2021] [Accepted: 11/12/2021] [Indexed: 01/06/2023] Open
Abstract
Perianal Crohn's Disease (pCD) is a common manifestation of Crohn's Disease. Absence of reliable disease measures makes disease monitoring unreliable. Qualitative MRI has been increasingly used for diagnosing and monitoring pCD and has shown potential for assessing response to treatment. Quantitative MRI sequences, such as diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE) and magnetisation transfer (MT), along with T2 relaxometry, offer opportunities to improve diagnostic capability. Quantitative MRI sequences (DWI, DCE, MT and T2) were used in a cohort of 25 pCD patients before and 12 weeks after biological therapy at two different field strengths (1.5 and 3 T). Disease activity was measured with the Perianal Crohn's Disease Activity index (PDAI) and serum C-reactive protein (CRP). Diseased tissue areas on MRI were defined by a radiologist. A baseline model to predict outcome at 12 weeks was developed. No differences were seen in the quantitative MR measured in the diseased tissue regions from baseline to 12 weeks; however, PDAI and CRP decreased. Baseline PDAI, CRP, T2 relaxometry and surgical history were found to have a moderate ability to predict response after 12 weeks of biological treatment. Validation in larger cohorts with MRI and clinical measures are needed in order to further develop the model.
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Affiliation(s)
- Ali Alyami
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia;
- Translational Medical Sciences Academic Unit, School of Medicine, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2UH, UK;
- National Institute of Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK; (C.L.H.); (C.T.); (P.A.G.)
| | - Caroline L. Hoad
- National Institute of Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK; (C.L.H.); (C.T.); (P.A.G.)
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2QX, UK
| | - Christopher Tench
- National Institute of Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK; (C.L.H.); (C.T.); (P.A.G.)
- Division of Clinical Neurosciences, Clinical Neurology, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK
| | - Uday Bannur
- Department of Radiology, Queens Medical Centre Campus, Nottingham University Hospitals, Nottingham NG7 2UH, UK; (U.B.); (C.C.); (K.L.)
| | - Christopher Clarke
- Department of Radiology, Queens Medical Centre Campus, Nottingham University Hospitals, Nottingham NG7 2UH, UK; (U.B.); (C.C.); (K.L.)
| | - Khalid Latief
- Department of Radiology, Queens Medical Centre Campus, Nottingham University Hospitals, Nottingham NG7 2UH, UK; (U.B.); (C.C.); (K.L.)
| | - Konstantinos Argyriou
- Translational Medical Sciences Academic Unit, School of Medicine, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2UH, UK;
| | - Alan Lobo
- Department of Gastroenterology, Sheffield Teaching Hospitals NHS Trust, Sheffield S10 2JF, UK;
| | - Philip Lung
- Department of Radiology, St Mark’s Hospital and Academic Institute, London North West Healthcare NHS Trust, London HA1 3UJ, UK; (P.L.); (R.B.-C.)
| | - Rachel Baldwin-Cleland
- Department of Radiology, St Mark’s Hospital and Academic Institute, London North West Healthcare NHS Trust, London HA1 3UJ, UK; (P.L.); (R.B.-C.)
| | - Kapil Sahnan
- Fistula Research Unit, St Mark’s Hospital and Academic Institute, London North West Healthcare NHS Trust, London HA1 3UJ, UK; (K.S.); (A.H.)
| | - Ailsa Hart
- Fistula Research Unit, St Mark’s Hospital and Academic Institute, London North West Healthcare NHS Trust, London HA1 3UJ, UK; (K.S.); (A.H.)
| | - Jimmy K. Limdi
- Department of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Greater Manchester, Crumpsall M8 5RB, UK;
| | - John Mclaughlin
- Department of Gastroenterology, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre, Salford M6 8HD, UK;
| | - David Atkinson
- Centre for Medical Imaging, University College London, London W1W 7TS, UK;
| | - Geoffrey J. M. Parker
- Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London WC1V 6LJ, UK;
- Bioxydyn Limited, Manchester M15 6SZ, UK
| | - James P. B. O’Connor
- Quantitative Biomedical Imaging Laboratory, Division of Cancer Science, University of Manchester, Manchester M13 9PL, UK (R.A.L.)
| | - Ross A. Little
- Quantitative Biomedical Imaging Laboratory, Division of Cancer Science, University of Manchester, Manchester M13 9PL, UK (R.A.L.)
| | - Penny A. Gowland
- National Institute of Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK; (C.L.H.); (C.T.); (P.A.G.)
- Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2QX, UK
| | - Gordon W. Moran
- Translational Medical Sciences Academic Unit, School of Medicine, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2UH, UK;
- National Institute of Health Research Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK; (C.L.H.); (C.T.); (P.A.G.)
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12
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Merten J, Eichelmann AK, Mennigen R, Flammang I, Pascher A, Rijcken E. Minor Sphincter Sparing Surgery for Successful Closure of Perianal Fistulas in Patients with Crohn's Disease. J Clin Med 2021; 10:jcm10204721. [PMID: 34682844 PMCID: PMC8540669 DOI: 10.3390/jcm10204721] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 10/07/2021] [Accepted: 10/09/2021] [Indexed: 11/25/2022] Open
Abstract
The purpose of this study is to demonstrate that repetitive minor surgical procedures allow for a high rate of permanent closure of perianal fistulas in patients with Crohn’s disease (CD). Patients with perianal fistulizing CD (PFCD) who underwent perianal surgery at the University Hospital of Muenster between 2003 and 2018 were assessed for fistula characteristics and surgical procedures. We included 45 patients (m:f = 28:17) with a mean age of 27 years at first fistula appearance. Of these, 49% suffered from a complex fistula. An average of 4.2 (1–14) procedures were performed, abscess incisions and fistula seton drainages included. Draining setons were left in place for 5 (1–54) months, until fistula closure. Final surgical techniques were fistulotomy (31.1%), seton removal with sustained biological therapy (26.7%), Anal Fistula Plug (AFP) (17.8%), Over-The Scope-Clip proctology (OTSC) (11.1%), and mucosa advancement flap (4.4%). In 8.9% of cases, the seton was kept as permanent therapy. The time from first to last surgery was 18 (0–182) months and the median follow-up time after the last surgery was 90 (15–200) months. The recurrence rate was 15.5% after 45 (17–111) months. Recurrent fistulas healed after another 1.86 (1–2) surgical re-interventions. The final success rate was 80%. Despite biological treatment, PFCD management remains challenging. However, by repeating minor surgical interventions over a prolonged period of time, high permanent healing rates can be achieved.
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Affiliation(s)
- Jennifer Merten
- Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1, Building W1, 48149 Muenster, Germany; (A.-K.E.); (I.F.); (A.P.)
- Correspondence: (J.M.); (E.R.)
| | - Ann-Kathrin Eichelmann
- Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1, Building W1, 48149 Muenster, Germany; (A.-K.E.); (I.F.); (A.P.)
| | - Rudolf Mennigen
- MVZ Portal 10, Albersloher Weg 10, 48155 Muenster, Germany; (R.M.)
| | - Isabelle Flammang
- Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1, Building W1, 48149 Muenster, Germany; (A.-K.E.); (I.F.); (A.P.)
| | - Andreas Pascher
- Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1, Building W1, 48149 Muenster, Germany; (A.-K.E.); (I.F.); (A.P.)
| | - Emile Rijcken
- Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1, Building W1, 48149 Muenster, Germany; (A.-K.E.); (I.F.); (A.P.)
- Correspondence: (J.M.); (E.R.)
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13
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Buscail E, Le Cosquer G, Gross F, Lebrin M, Bugarel L, Deraison C, Vergnolle N, Bournet B, Gilletta C, Buscail L. Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn's Disease: Rationale, Clinical Results and Perspectives. Int J Mol Sci 2021; 22:ijms22189967. [PMID: 34576129 PMCID: PMC8470328 DOI: 10.3390/ijms22189967] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/07/2021] [Accepted: 09/12/2021] [Indexed: 12/16/2022] Open
Abstract
Between 20 to 25% of Crohn’s disease (CD) patients suffer from perianal fistulas, a marker of disease severity. Seton drainage combined with anti-TNFα can result in closure of the fistula in 70 to 75% of patients. For the remaining 25% of patients there is room for in situ injection of autologous or allogenic mesenchymal stem cells such as adipose-derived stem/stromal cells (ADSCs). ADSCs exert their effects on tissues and effector cells through paracrine phenomena, including the secretome and extracellular vesicles. They display anti-inflammatory, anti-apoptotic, pro-angiogenic, proliferative, and immunomodulatory properties, and a homing within the damaged tissue. They also have immuno-evasive properties allowing a clinical allogeneic approach. Numerous clinical trials have been conducted that demonstrate a complete cure rate of anoperineal fistulas in CD ranging from 46 to 90% of cases after in situ injection of autologous or allogenic ADSCs. A pivotal phase III-controlled trial using allogenic ADSCs (Alofisel®) demonstrated that prolonged clinical and radiological remission can be obtained in nearly 60% of cases with a good safety profile. Future studies should be conducted for a better knowledge of the local effect of ADSCs as well as for a standardization in terms of the number of injections and associated procedures.
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Affiliation(s)
- Etienne Buscail
- Department of Surgery, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France;
- IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Guillaume Le Cosquer
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
| | - Fabian Gross
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
| | - Marine Lebrin
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
| | - Laetitia Bugarel
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
| | - Céline Deraison
- IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Nathalie Vergnolle
- IRSD, University of Toulouse, INSERM 1022, INRAe, ENVT, UPS, 31300 Toulouse, France; (C.D.); (N.V.)
| | - Barbara Bournet
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
| | - Cyrielle Gilletta
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
| | - Louis Buscail
- Department of Gastroenterology and Pancreatology, CHU Toulouse-Rangueil and Toulouse University, UPS, 31059 Toulouse, France; (G.L.C.); (B.B.); (C.G.)
- Centre for Clinical Investigation in Biotherapy, CHU Toulouse-Rangueil and INSERM U1436, 31059 Toulouse, France; (F.G.); (M.L.); (L.B.)
- Correspondence: ; Tel.: +33-561323055
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14
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Ji L, Zhang Y, Xu L, Wei J, Weng L, Jiang J. Advances in the Treatment of Anal Fistula: A Mini-Review of Recent Five-Year Clinical Studies. Front Surg 2021; 7:586891. [PMID: 33644110 PMCID: PMC7905164 DOI: 10.3389/fsurg.2020.586891] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 12/15/2020] [Indexed: 12/16/2022] Open
Abstract
Anal fistula, with its complicated pathogenesis, has been considered as a clinical challenge for centuries. The risk of frequent recurrence and incontinence constitutes a considerable threat in the long-term treatment of anal fistula. In this work, we narratively reviewed the scientific literature of new techniques that have been used for anal fistula treatment over the recent 5 years, objectively evaluated the pros and cons of each technique on the basis of clinical outcomes, and tried to disclose the effective strategies for anal fistula treatment. Up to date, surgery is the main method used for treating anal fistula, but there is no simple technique that can completely heal complex anal fistula. In the course of surgery treatment, the healing outcome, and the protection of anal function should be weighed comprehensively. Among the innovative techniques that have emerged in recent years, combined techniques based on drainage Seton and LIFT-plug seem to be the relatively effective therapies, but their effectiveness requires more multi-center prospective randomized controlled trials with large sample size and long-term follow-up to be validated.
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Affiliation(s)
- Lijiang Ji
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
| | - Yang Zhang
- Colorectal Disease Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Liang Xu
- Department of General Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
| | - Jun Wei
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
| | - Liping Weng
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
| | - Jie Jiang
- Department of Anorectal Surgery, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
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15
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Lee JL, Yoon YS, Yu CS. Treatment Strategy for Perianal Fistulas in Crohn Disease Patients: The Surgeon's Point of View. Ann Coloproctol 2021; 37:5-15. [PMID: 33730796 PMCID: PMC7989558 DOI: 10.3393/ac.2021.02.08] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/08/2021] [Accepted: 02/08/2021] [Indexed: 12/12/2022] Open
Abstract
Perianal fistula is a frequent complication and one of the subclassifications of Crohn disease (CD). It is the most commonly observed symptomatic condition by colorectal surgeons. Accurately classifying a perianal fistula is the initial step in its management in CD patients. Surgical management is selected based on the type of perianal fistula and the presence of rectal inflammation; it includes fistulotomy, fistulectomy, seton procedure, fistula plug insertion, video-assisted ablation of the fistulous tract, stem cell therapy, and proctectomy with stoma creation. Perianal fistulas are also managed medically, such as antibiotics, immunomodulators, and biologics including anti-tumor necrosis factor-alpha agents. The current standard treatment of choice for perianal fistula in CD patients is the multidisciplinary approach combining surgical and medical management; however, the rate of long-term remission is low and is reported to be 50% at most. Therefore, the optimum management strategy for perianal fistulas associated with CD remains controversial. Currently, the goal of management for CD-related perianal fistulas are controlling symptoms and maintaining long-term anal function without proctectomy, while monitoring progression to anorectal carcinoma. This review evaluates perianal fistula in CD patients and determines the optimal surgical management strategy based on recent evidence.
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Affiliation(s)
- Jong Lyul Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Sik Yoon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Sik Yu
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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16
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Chapuis-Biron C, Kirchgesner J, Pariente B, Bouhnik Y, Amiot A, Viennot S, Serrero M, Fumery M, Allez M, Siproudhis L, Buisson A, Pineton de Chambrun G, Abitbol V, Nancey S, Caillo L, Plastaras L, Savoye G, Chanteloup E, Simon M, Dib N, Rajca S, Amil M, Parmentier AL, Peyrin-Biroulet L, Vuitton L. Ustekinumab for Perianal Crohn's Disease: The BioLAP Multicenter Study From the GETAID. Am J Gastroenterol 2020; 115:1812-1820. [PMID: 33156100 DOI: 10.14309/ajg.0000000000000810] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. METHODS We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. RESULTS Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. DISCUSSION Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.
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Affiliation(s)
- Constance Chapuis-Biron
- Department of Gastroenterology, University Hospital of Besançon, University Bourgogne Franche-Comté, Besançon, France
| | - Julien Kirchgesner
- Department of Gastroenterology, Saint-Antoine Hospital, Assitance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Benjamin Pariente
- Department of Hepatogastroenterology, University Hospital of Lille, Lille, France
| | - Yoram Bouhnik
- Department of Gastroenterology, AP-HP, Hôpital Beaujon, Paris, France
| | - Aurélien Amiot
- Department of Gastroenterology, AP-HP, Hôpital Henri-Mondor, Paris, France
| | - Stéphanie Viennot
- Department of Hepatogastroenterology, University Hospital of Caen, Caen, France
| | - Mélanie Serrero
- Department of Gastroenterology, AP-HM, Hôpital Nord, Marseille, France
| | - Mathurin Fumery
- Department of Hepatogastroenterology, Peritox, University Hospital of Amiens, Amiens, France
| | - Matthieu Allez
- Department of Gastroenterology, AP-HP, Hôpital Saint Louis, Paris, France
| | - Laurent Siproudhis
- Department of Hepatogastroenterology, CHU Pontchaillou, University Hospital of Rennes, Rennes, France
| | - Anthony Buisson
- Department of Hepatogastroenterology, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France
| | | | - Vered Abitbol
- Department of Gastroenterology, AP-HP, Hôpital Cochin, Paris, France
| | - Stéphane Nancey
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France
| | - Ludovic Caillo
- Department of Hepatogastroenterology, University Hospital of Nimes, Nimes, France
| | | | - Guillaume Savoye
- Department of Hepatogastroenterology, University Hospital of Rouen
| | - Elise Chanteloup
- Department of Gastroenterology, Hôpital Paris Saint Joseph, Paris, France
| | - Marion Simon
- Department of Gastroenterology, Institut Mutualiste Montsouris, Paris, France
| | - Nina Dib
- Department of Hepatogastroenterology, University Hospital of Angers, Angers, France
| | - Sylvie Rajca
- Department of Gastroenterology, AP-HP, Hôpital Louis-Mourier, Paris, France
| | - Morgane Amil
- Department of Hepatogastroenterology, Centre hospitalier La Roche-sur-Yon, La Roche-sur-Yon, France
| | | | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Inserm U954, University Hospital of Nancy, Lorraine University, Nancy, France
| | - Lucine Vuitton
- Department of Gastroenterology, University Hospital of Besançon, University Bourgogne Franche-Comté, Besançon, France
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17
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Chapuis-Biron C, Bourrier A, Nachury M, Nancey S, Bouhnik Y, Serrero M, Armengol-Debeir L, Buisson A, Tran-Minh ML, Zallot C, Fumery M, Bouguen G, Abitbol V, Viennot S, Chanteloup E, Rajca S, Dib N, Parmentier AL, Peyrin-Biroulet L, Vuitton L. Vedolizumab for perianal Crohn's disease: a multicentre cohort study in 151 patients. Aliment Pharmacol Ther 2020; 51:719-727. [PMID: 32080886 DOI: 10.1111/apt.15665] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 12/05/2019] [Accepted: 01/30/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND The management of Crohn's disease patients with perianal lesions and anti-TNF failure is challenging. AIMS To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real-life cohort. METHODS We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments. RESULTS One hundred and fifty-one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti-TNF. The median follow-up time was 52 weeks. Sixty-eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04-0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25-18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. CONCLUSIONS We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies.
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18
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Laureti S, Gionchetti P, Cappelli A, Vittori L, Contedini F, Rizzello F, Golfieri R, Campieri M, Poggioli G. Refractory Complex Crohn's Perianal Fistulas: A Role for Autologous Microfragmented Adipose Tissue Injection. Inflamm Bowel Dis 2020; 26:321-330. [PMID: 31220252 PMCID: PMC6943693 DOI: 10.1093/ibd/izz051] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Complex perianal fistulas represent one of the most challenging manifestations of Crohn's disease. Combined surgical and medical therapy with biologic drugs today represent the first-line treatment option, but its efficacy does not exceed 60%. Recently, new therapeutic approaches, such as the use of mesenchymal stromal cells, have shown promising results. The adipose tissue is an abundant and easy to access source. The effectiveness, safety, and feasibility of local injections of microfragmented adipose tissue in patients with refractory complex fistulizing perianal Crohn's disease (PCD) were evaluated. METHODS Fifteen patients with persistent complex fistulizing PCD after biosurgical approach and subsequent surgical "rescue" repair were treated in S. Orsola-Malpighi Hospital with a single-local administration of microfragmented adipose tissue prepared using a minimal manipulation technique (Lipogems) in a closed system. Clinical outcomes were determined at 24-week follow-ups assessing success rate, defined as combined clinical and radiological remission. RESULTS Upon clinical examination at 24 weeks, 10 patients had combined remission (clinical and radiographic), 4 patients showed improvements, and 1 patient failed. The results were confirmed in all patients by pelvic MRI. No relevant postoperative complications nor adverse events were reported. CONCLUSION These results suggest that the local injection of autologous microfragmented adipose tissue is a safe and promising "rescue therapy" for patients with multiresistant complex fistulizing PCD. This approach might be proposed as routine because it is affordable, is minimally invasive, has no risk of sphincteric damage, and can be carried out in a day-surgery setting.
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Affiliation(s)
- Silvio Laureti
- Surgery of the Alimentary Tract, S. Orsola-Malpighi Hospital and Department of Medical and Surgical Sciences University of Bologna, Bologna, Italy,Address correspondence to: Silvio Laureti, MD, PhD, Associate Professor of Surgery, University of Bologna, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Via Massarenti 9, Bologna, Italy. E-mail:
| | - Paolo Gionchetti
- IBD Unit, S. Orsola-Malpighi Hospital and Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Alberta Cappelli
- Radiology Unit, Department of Digestive Disease and Internal Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Laura Vittori
- Surgery of the Alimentary Tract, S. Orsola-Malpighi Hospital and Department of Medical and Surgical Sciences University of Bologna, Bologna, Italy
| | - Federico Contedini
- Plastic Surgery Unit, S. Orsola-Malpighi Hospital and Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Fernando Rizzello
- IBD Unit, S. Orsola-Malpighi Hospital and Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Rita Golfieri
- Radiology Unit, Department of Digestive Disease and Internal Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Massimo Campieri
- IBD Unit, S. Orsola-Malpighi Hospital and Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Gilberto Poggioli
- Surgery of the Alimentary Tract, S. Orsola-Malpighi Hospital and Department of Medical and Surgical Sciences University of Bologna, Bologna, Italy
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19
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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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20
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Wong DJ, Roth EM, Feuerstein JD, Poylin VY. Surgery in the age of biologics. Gastroenterol Rep (Oxf) 2019; 7:77-90. [PMID: 30976420 PMCID: PMC6454839 DOI: 10.1093/gastro/goz004] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 11/02/2018] [Indexed: 02/07/2023] Open
Abstract
Since the introduction of the first anti-tumor necrosis factor antibodies in the late 1990s, biologic therapy has revolutionized the medical treatment of patients with inflammatory bowel disease (IBD). Nevertheless, surgery continues to play a significant role in treating IBD patients. Rates of intestinal resection in patients with Crohn's disease or colectomy in ulcerative colitis are reducing but not substantially over the long term. An increasing variety of biologic medications are now available to treat IBD patients in various clinical situations. Consequently, a number of questions persist about how biologic medications affect the need for surgery and overall course in IBD patients. Given the trend for earlier and more frequent use of biologic medications in IBD patients, a working knowledge of the effects of these medications on surgical decision-making and outcomes is essential for the practicing colorectal surgeon and gastroenterologist. This review seeks to summarize the relevant literature surrounding biologic use and IBD surgery with a focus on the effect of biologics on the frequency, type and complications of surgery in this 'age of biologics'.
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Affiliation(s)
- Daniel J Wong
- Department of Surgery, Division of Colon & Rectum Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Eve M Roth
- Department of Surgery, Division of Colon & Rectum Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Joseph D Feuerstein
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Vitaliy Y Poylin
- Department of Surgery, Division of Colon & Rectum Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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21
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Bouchard D, Pigot F, Staumont G, Siproudhis L, Abramowitz L, Benfredj P, Brochard C, Fathallah N, Faucheron JL, Higuero T, Panis Y, de Parades V, Vinson-Bonnet B, Laharie D. Management of anoperineal lesions in Crohn's disease: a French National Society of Coloproctology national consensus. Tech Coloproctol 2019; 22:905-917. [PMID: 30604249 DOI: 10.1007/s10151-018-1906-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 12/07/2018] [Indexed: 12/11/2022]
Abstract
The French National Society of Coloproctology established national recommendations for the treatment of anoperineal lesions associated with Crohn's disease. Treatment strategies for acute abscesses, active fistulas (active denovo and still active under treatment), fistulas in remission, and rectovaginal fistulas are suggested. Recommendations have been graded following the international recommendations, and when absent, professional agreement has been established. For each situation, practical algorithms have been drawn.
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Affiliation(s)
- D Bouchard
- Hôpital Bagatelle, 203 Route de Toulouse, 33401, Talence Cedex, France.
| | - F Pigot
- Hôpital Bagatelle, 203 Route de Toulouse, 33401, Talence Cedex, France
| | - G Staumont
- Clinique Saint Jean du Languedoc, 20 Route de Revel, 31400, Toulouse, France
| | - L Siproudhis
- Centre Hospitalier Universitaire, 35033, Rennes Cedex 9, France
| | - L Abramowitz
- Centre Hospitalier Universitaire Bichat, 75877, Paris, France
| | - P Benfredj
- Hôpital Saint Joseph, 185 Rue Raymond Losserand, 75014, Paris, France
| | - C Brochard
- Centre Hospitalier Universitaire, 35033, Rennes Cedex 9, France
| | - N Fathallah
- Hôpital Saint Joseph, 185 Rue Raymond Losserand, 75014, Paris, France
| | - J-L Faucheron
- Centre Hospitalier Universitaire Grenoble-Alpes, Avenue Maquis du Grésivaudan, 38700, La Tronche, France
| | - T Higuero
- , 11 Boulevard du Général Leclerc, 06240, Beausoleil, France
| | - Y Panis
- Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - V de Parades
- Hôpital Saint Joseph, 185 Rue Raymond Losserand, 75014, Paris, France
| | - B Vinson-Bonnet
- Hôpital de Poissy-Saint Germain en Laye, 10 Rue Champ Gaillard, 78300, Poissy, France
| | - D Laharie
- Centre Hospitalier Universitaire Haut Lévêque, Avenue Magellan, 33604, Pessac Cedex, France
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22
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Brown SR, Fearnhead NS, Faiz OD, Abercrombie JF, Acheson AG, Arnott RG, Clark SK, Clifford S, Davies RJ, Davies MM, Douie WJP, Dunlop MG, Epstein JC, Evans MD, George BD, Guy RJ, Hargest R, Hawthorne AB, Hill J, Hughes GW, Limdi JK, Maxwell-Armstrong CA, O'Connell PR, Pinkney TD, Pipe J, Sagar PM, Singh B, Soop M, Terry H, Torkington J, Verjee A, Walsh CJ, Warusavitarne JH, Williams AB, Williams GL, Wilson RG. The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease. Colorectal Dis 2018; 20 Suppl 8:3-117. [PMID: 30508274 DOI: 10.1111/codi.14448] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 09/17/2018] [Indexed: 12/14/2022]
Abstract
AIM There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.
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Affiliation(s)
- S R Brown
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - N S Fearnhead
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - O D Faiz
- St Mark's Hospital, Middlesex, Harrow, UK
| | | | - A G Acheson
- Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - R G Arnott
- Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK
| | - S K Clark
- St Mark's Hospital, Middlesex, Harrow, UK
| | | | - R J Davies
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - M M Davies
- University Hospital of Wales, Cardiff, UK
| | - W J P Douie
- University Hospitals Plymouth NHS Trust, Plymouth, UK
| | | | - J C Epstein
- Salford Royal NHS Foundation Trust, Salford, UK
| | - M D Evans
- Morriston Hospital, Morriston, Swansea, UK
| | - B D George
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - R J Guy
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - R Hargest
- University Hospital of Wales, Cardiff, UK
| | | | - J Hill
- Manchester Foundation Trust, Manchester, UK
| | - G W Hughes
- University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - J K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
| | | | | | - T D Pinkney
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - J Pipe
- Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK
| | - P M Sagar
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - B Singh
- University Hospitals of Leicester NHS Trust, Leicester, UK
| | - M Soop
- Salford Royal NHS Foundation Trust, Salford, UK
| | - H Terry
- Crohn's and Colitis UK, St Albans, UK
| | | | - A Verjee
- Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK
| | - C J Walsh
- Wirral University Teaching Hospital NHS Foundation Trust, Arrowe Park Hospital, Upton, UK
| | | | - A B Williams
- Guy's and St Thomas' NHS Foundation Trust, London, UK
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23
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Panes J, Reinisch W, Rupniewska E, Khan S, Forns J, Khalid JM, Bojic D, Patel H. Burden and outcomes for complex perianal fistulas in Crohn's disease: Systematic review. World J Gastroenterol 2018; 24:4821-4834. [PMID: 30479468 PMCID: PMC6235801 DOI: 10.3748/wjg.v24.i42.4821] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 09/24/2018] [Accepted: 10/21/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To systematically review the literature on epidemiology, disease burden, and treatment outcomes for Crohn's disease (CD) patients with complex perianal fistulas. METHODS PubMed, Embase, and Cochrane were searched for relevant articles (published 2000-November 2016) and congress abstracts (published 2011-November 2016). RESULTS Of 535 records reviewed, 62 relevant sources were identified (mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14% (follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment (failure and relapse rates, respectively: medical, 12%-73% and 0%-41%; surgical: 0%-100% and 11%-20%; combined medical/surgical: 0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies (1 of infliximab; 3 of surgical interventions) have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD. CONCLUSION Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to anti-tumour necrosis factor-α agents, as evidenced by high failure and relapse rates.
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Affiliation(s)
- Julian Panes
- Department of Gastroenterology, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona 08036, Spain
| | | | - Ewa Rupniewska
- RTI Health Solutions, Manchester M20 2LS, United Kingdom
| | - Shahnaz Khan
- RTI Health Solutions, Research Triangle Park, NC 27709, United States
| | - Joan Forns
- RTI Health Solutions, Barcelona 08028, Spain
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24
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Sebastian S, Black C, Pugliese D, Armuzzi A, Sahnan K, Elkady SM, Katsanos KH, Christodoulou DK, Selinger C, Maconi G, Fearnhead NS, Kopylov U, Davidov Y, Bosca-Watts MM, Ellul P, Muscat M, Karmiris K, Hart AL, Danese S, Ben-Horin S, Fiorino G. The role of multimodal treatment in Crohn's disease patients with perianal fistula: a multicentre retrospective cohort study. Aliment Pharmacol Ther 2018; 48:941-950. [PMID: 30226271 DOI: 10.1111/apt.14969] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 06/18/2018] [Accepted: 08/08/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Treatment paradigms for Crohn's disease with perianal fistulae (CD-pAF) are evolving. AIMS To study the impact of multimodality treatment in CD-pAF on recurrence rates and the need for re-interventions and to identify predictive factors for these outcomes. METHODS This was a multinational multicentre retrospective cohort study. Multimodality approach was defined as using a combination of medical treatments (anti-TNFs ± immunomodulators ± antibiotics) along with surgical approach (examination under anaesthesia (EUA) ± seton drainage) at diagnosis of CD-pAF. Univariable and multivariable analyses were performed for variables indicative of the need for reintervention. RESULTS A total of 253 patients were included. 65% of patients received multimodality approach. Multimodality treatment resulted in complete fistula healing in 52% of patients. Re-intervention was needed in 27% of patients with simple and in 40.3% of those with complex fistula. On multivariable analysis multimodality treatment (OR: 0.35, 95% CI: 0.17-0.57, P = 0.001), seton removal (OR: 0.090, 95% CI: 0.027-0.30, P = 0.0001, therapy with infliximab (OR: 0.19, 95% CI: 0.06-0.64, P = 0.007), and therapy with adalimumab (OR: 0.12, "95% CI: 0.026-0.56, P = 0.007) were predictive of avoiding repeat surgery. Proctitis (OR: 3.76, 95% CI: 1.09-12.96, P = 0.03) was predictive of the need for radical surgery (proctectomy, diverting stoma) while multimodality treatment reduced the need for radical surgery (OR: 0.21, 95% CI: 0.05-0.81, P = 0.02). CONCLUSIONS Multimodality treatment, anti-TNFs use, and removal of setons after multimodality treatment can result in improved outcomes in CD patients with perianal fistulae and reduce the need for repeat surgery and radical surgery.
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Abstract
INTRODUCTION Misconceptions exist about the proper way to use draining setons in the management of anal fistulas. This technical note lays out the principles for their use. TECHNIQUE Insertion of draining setons is a prerequisite to successful management of anal fistulas. The correct technique involves identification of the correct track and internal opening and drainage of the track with a silastic seton. This sets the stage for definitive repair after the inflammation subsides. RESULTS Three cases are presented to illustrate common errors made during the insertion of draining setons. CONCLUSIONS Appropriate seton drainage of an anorectal fistula is an important part of the ultimate repair. Correct use of setons minimizes symptoms from the seton itself and optimizes its effectiveness.
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26
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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: 106] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [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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27
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Braithwaite GC, Lee MJ, Hind D, Brown SR. Prognostic factors affecting outcomes in fistulating perianal Crohn's disease: a systematic review. Tech Coloproctol 2017. [PMID: 28639073 PMCID: PMC5550543 DOI: 10.1007/s10151-017-1647-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND One in three patients with Crohn's disease will develop a perianal fistulae, and one third of these will achieve long-term healing or closure. A barrier to conducting well-designed clinical trials for these patients is a lack of understanding of prognostic factors. This systematic review sets out to identify factors associated with prognosis of perianal Crohn's fistulae. METHODS This review was registered on the PROSPERO database (CRD42016050316) and conducted in line with PRISMA guidelines along a predefined protocol. English-language studies assessing baseline factors related to outcomes of fistulae treatment in adult patients were included. Searches were performed on MEDLINE and Embase databases. Screening of abstracts and full texts for eligibility was performed prior to extraction of data into predesigned forms. Bias was assessed using the QUIPS tool. RESULTS Searches identified 997 papers. Following removal of duplicates and secondary searches, 923 were screened for inclusion. Forty-seven papers were reviewed at full-text level and 13, 2 of which were randomised trials, were included in the final qualitative review. Two studies reported distribution of Crohn's disease as a prognostic factor for healing. Two studies found that CARD15 mutations decreased response of fistulae to antibiotics. Complexity of fistulae anatomy was implicated in prognosis by 4 studies. CONCLUSIONS This systematic review has identified potential prognostic markers, including genetic factors and disease behaviour. We cannot, however, draw robust conclusions from this heterogeneous group of studies; therefore, we recommend that a prospective cohort study of well-characterised patients with Crohn's perianal fistulae is undertaken.
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Affiliation(s)
| | - M J Lee
- University of Sheffield Medical School, Sheffield, UK. .,Department of General Surgery, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK.
| | - D Hind
- Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
| | - S R Brown
- Department of General Surgery, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK.,Clinical Trials Research Unit, University of Sheffield, Sheffield, UK
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28
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Lee MJ, Heywood N, Sagar PM, Brown SR, Fearnhead NS. Association of Coloproctology of Great Britain and Ireland consensus exercise on surgical management of fistulating perianal Crohn's disease. Colorectal Dis 2017; 19:418-429. [PMID: 28387062 DOI: 10.1111/codi.13672] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Accepted: 01/04/2017] [Indexed: 02/08/2023]
Abstract
AIM Management of fistulating perianal Crohn's disease (fpCD) is a significant challenge for a colorectal surgeon. A recent survey of surgical practice in this condition showed variation in management approaches. As a result we set out to devise recommendations for practice for UK colorectal surgeons. METHOD Results from a national survey were used to devise a set of potential consensus statements. Consultant colorectal surgeons were invited to participate in the exercise via the previous survey and the mailing list of the professional society. Iterative voting was performed on each statement using a five-point Likert scale and electronic voting, with opportunity for discussion and refinement between each vote. Consensus was defined as > 80% agreement. RESULTS Seventeen surgeons and two patient representatives voted upon 51 statements. Consensus was achieved on 39 items. Participants advocated a patient-centred approach by a colorectal specialist, within strong multidisciplinary teamworking. The use of anti-TNFα therapy is advocated. Where definitive surgical techniques are considered they should be carefully selected to avoid adverse impact on function. Ano/rectovaginal fistulas should be managed by specialists in fistulating disease. Stoma or proctectomy could be discussed earlier in a patient's treatment pathway to improve choice, as they may improve quality of life. CONCLUSION This consensus provides principles and guidance for best practice in managing patients with fpCD.
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Affiliation(s)
- M J Lee
- Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.,Department of General Surgery, Sheffield Teaching Hospitals, Sheffield, UK
| | - N Heywood
- University Hospital South Manchester, Manchester, UK
| | - P M Sagar
- St James University Hospital, Leeds, UK
| | - S R Brown
- Department of General Surgery, Sheffield Teaching Hospitals, Sheffield, UK
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29
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Ferrari L, Krane MK, Fichera A. Inflammatory bowel disease surgery in the biologic era. World J Gastrointest Surg 2016; 8:363-370. [PMID: 27231514 PMCID: PMC4872064 DOI: 10.4240/wjgs.v8.i5.363] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 01/13/2016] [Accepted: 03/14/2016] [Indexed: 02/06/2023] Open
Abstract
Anti-tumour necrosis factor (TNF)-α therapy has revolutionized inflammatory bowel disease (IBD) treatment. Infliximab and adalimumab either as monotherapy or in combination with an immunomodulator are able to induce clinical and biological remission in patients with moderate and severe Crohn’s disease (CD) and ulcerative colitis (UC). These new therapies have led to a shift in the goals of IBD management from just controlling clinical symptoms to preventing disease progression. However, despite these advances in medical therapy, surgery is still required in 30%-40% of patients with CD and 20%-30% of patients with UC at some point during their lifetime. While biologics certainly play a major role in the medical treatment of IBD, there is concern about the effects of these anti-TNF-α agents on postoperative complications and morbidity. The purpose of this article is to review the role of surgery in the treatment of IBD in the age of biologics and the impact of these medications on per-operative outcomes. In this manuscript we review the relationship between biologic agents and surgery in the treatment of IBD. We also discuss in detail the periopetative risks and complications.
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