|
1
|
Everhov ÅH, Eberhardson M, Söderling J, Nordenvall C, Halfvarson J, Ludvigsson JF, Olén O, Myrelid P, Strid H, Hjortswang H, Olsson M, Bengtsson JL, Andersson MA, Karling P, Rejler M, Jäghult S, Fagerberg UL, Mårild K, Hreinsson J, Hedin C. Cumulative incidence and prevalence of perianal diseases in patients with inflammatory bowel disease and in the population: a nationwide Swedish study. Scand J Gastroenterol 2025; 60:349-354. [PMID: 40094394 DOI: 10.1080/00365521.2025.2476669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 03/01/2025] [Accepted: 03/03/2025] [Indexed: 03/19/2025]
Abstract
BACKGROUND Perianal diseases are more common in patients with Crohn's disease (CD) than in the general population, but data are scarce in other inflammatory bowel disease (IBD) subtypes. METHOD Using data from the Swedish National Patient Register (NPR) and SWIBREG, the national quality register for IBD, we estimated the cumulative incidence of perianal fistula/abscess and perianal diseases (fistula, abscess, stenosis, fissure or procedure code for perianal surgery) in relation to diagnosis, and the prevalence in 2023, in individuals with CD, ulcerative colitis (UC) and IBD-unclassified (IBD-U), and in a matched (age, sex, calendar year and region of residence) IBD-free cohort from the general population. RESULTS We identified 38,364 patients with incident IBD 2007-2017, and 98,229 patients with prevalent IBD as of 31 December 2022. The cumulative incidence of fistula/abscess was 6.7% at diagnosis, 8.3% at 1 year and 10.4% at 5 years in CD. The corresponding percentages in UC were 0.9%, 1.3% and 2.1%, and in IBD-U 2.4%, 3.1% and 4.5%, respectively. In 2023, 12.8%, 3.1% and 4.1% of patients with prevalent CD, UC and IBD-U had a history of fistula/abscess, compared to 0.8% in the general population. The corresponding numbers for perianal diseases were 19.7%, 7.4%, 8.6% and 2.2%. CONCLUSIONS The cumulative incidence and prevalence of perianal diseases in Swedish patients with CD was in parity with reports from other countries, and in patients with UC and IBD-U, it was 3-4 times higher than in the population.
Collapse
Affiliation(s)
- Åsa H Everhov
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
- Department of Medicine Solna, Division of Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden
| | - Michael Eberhardson
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Jonas Söderling
- Department of Medicine Solna, Division of Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden
| | - Caroline Nordenvall
- Department of Pelvic Cancer, IBD-Surgery Unit, Karolinska University Hospital, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, SE, Sweden
| | - Jonas F Ludvigsson
- Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden
| | - Ola Olén
- Department of Medicine Solna, Division of Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatric Gastroenterology and Nutrition, Sachs' Children and Youth Hospital, Stockholm, Sweden
| | - Pär Myrelid
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- Department of Surgery, Linköping University, Linköping, Sweden
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
2
|
Munster LJ, Meriba GR, Schuitema J, van Dieren S, de Groof EJ, Mundt MW, D'Haens GR, Bemelman WA, Buskens CJ, van der Bilt JDW. Early diagnosis of Crohn's disease in patients presenting with a perianal fistula: systematic review and development of a perianal red flags index. Tech Coloproctol 2025; 29:89. [PMID: 40155532 PMCID: PMC11953225 DOI: 10.1007/s10151-024-03106-y] [Citation(s) in RCA: 1] [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: 09/17/2024] [Accepted: 12/23/2024] [Indexed: 04/01/2025]
Abstract
BACKGROUND Delay in diagnosing Crohn's disease (CD) in patients presenting with perianal abscess (PAA) and/or fistula (PAF) is common. The aim of this study was to identify red flags suggestive of CD. METHODS A systematic literature review was conducted to identify symptoms associated with CD in patients presenting with PAA/PAF. A questionnaire including those symptoms, supplemented with items from the International Organization for the Study of Inflammatory Bowel Diseases (IO-IBD) red flags index for luminal CD, was administered to all adult patients presenting with a PAF and eventually diagnosed with CD and matched patients (1:3) from the same study period with a cryptoglandular PAF (2012-2023) at a single non-academic teaching hospital. All patients were asked to recall symptoms/signs experienced during their first PAF. RESULTS The systematic review identified 8 articles reporting on 15 clinical characteristics in patients presenting with PAA (n = 2)/PAF (n = 6), supplemented with 13 items from the IO-IBD red flags index (28 items in total). A total of 25 patients with CD and 75 patients with PAF without CD answered the questionnaire. Univariate analysis identified seven items associated with CD (age, family history, > 2 perianal interventions, weight loss, abdominal pain, diarrhoea and fatigue), and four items remained significant in multivariate analysis: age (OR 3.4 [1.0-11.5]), > 2 previous perianal interventions (OR 3.4 [1.0-10.1]), weight loss (OR 14.4 [3.7-55.6]) and abdominal pain (OR 9.8 [1.9-49.8]). Receiver-operating characteristic curve (ROC) analysis showed that a combination of these red flags was associated with good discrimination of CD versus non-CD (AUC 0.83 [0.72-0.94]). CONCLUSIONS The perianal red flags index has a good predictive value for early identification of patients with PAF at risk for underlying CD.
Collapse
Affiliation(s)
- L J Munster
- Department of Surgery, Flevoziekenhuis, Almere, The Netherlands.
- Department of Surgery, Amsterdam UMC (Location VUmc), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - G R Meriba
- Department of Surgery, Flevoziekenhuis, Almere, The Netherlands
- Department of Surgery, Amsterdam UMC (Location VUmc), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - J Schuitema
- Department of Surgery, Flevoziekenhuis, Almere, The Netherlands
- Department of Surgery, Amsterdam UMC (Location VUmc), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - S van Dieren
- Department of Surgery, Amsterdam UMC (Location VUmc), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - E J de Groof
- Department of Surgery, Flevoziekenhuis, Almere, The Netherlands
- Department of Surgery, Amsterdam UMC (Location VUmc), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - M W Mundt
- Department of Gastroenterology and Hepatology, Flevoziekenhuis, Almere, The Netherlands
| | - G R D'Haens
- Department of Gastroenterology and Hepatology, Amsterdam UMC (Location VUmc), Amsterdam, The Netherlands
| | - W A Bemelman
- Department of Surgery, Amsterdam UMC (Location VUmc), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - C J Buskens
- Department of Surgery, Amsterdam UMC (Location VUmc), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
| | - J D W van der Bilt
- Department of Surgery, Flevoziekenhuis, Almere, The Netherlands
- Department of Surgery, Amsterdam UMC (Location VUmc), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| |
Collapse
|
|
3
|
Munster LJ, Pronk AJM, Mundt MW, Hompes R, Bemelman WA, van der Bilt JDW, Buskens CJ. Prolonged Time to Diagnosis of Crohn's Disease in Patients With Perianal Fistulas Negatively Affects Long-Term Outcomes. J Crohns Colitis 2025; 19:jjae146. [PMID: 39297524 PMCID: PMC11945302 DOI: 10.1093/ecco-jcc/jjae146] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/28/2025]
Abstract
BACKGROUND AND AIM This study aims to evaluate the effect of time to Crohn's disease (CD) diagnosis on perianal fistula (PAF) outcomes in patients with a fistula as the first manifesting sign. METHODS In this multicenter, retrospective study, CD patients with a PAF preceding CD diagnosis between November 2015 and June 2022 were included. The primary outcome parameter was the time to CD diagnosis and its correlation with long-term outcomes. RESULTS In total, 126 patients with a PAF prior to CD diagnosis were identified. The median time to CD diagnosis was 15.0 months (IQR 3.8-47.3). A total of 49 patients (38.9%) had a clinically closed fistula of which 21 patients (42.9%) achieved radiological healing. Twenty-five patients (19.8%) underwent defunctioning, of which 9 patients (36.0%) needed proctectomy. Median time to CD diagnosis was shortest in patients with radiological healing (4.0 months, IQR 2.0-16.5) or clinical closure without radiological healing (11.0 months, IQR 3.0-47.8). In patients without fistula closure (n = 51), the median time to CD diagnosis was significantly longer compared to patients with fistula closure, 18.0 months vs 8.0 months (p = 0.031). In patients who needed defunctioning, the median time to diagnosis was more than twice as long compared to patients without defunctioning, 30.0 months vs 12.0 months (p = 0.054). CONCLUSION A prolonged time to CD diagnosis in patients with a PAF as a manifesting sign is associated with worse long-term outcomes. Patients in whom radiological healing could be achieved had the shortest time to CD diagnosis, emphasizing the relevance of increased clinical awareness of underlying CD in fistula patients.
Collapse
Affiliation(s)
- Liesbeth Jozefien Munster
- Department of Surgery, Flevoziekenhuis, Almere, The Netherlands
- Department of Surgery, Amsterdam UMC, Amsterdam, The Netherlands
| | | | - Marco William Mundt
- Department of Gastroenterology and Hepatology, Flevoziekenhuis, Almere, The Netherlands
| | - Roel Hompes
- Department of Surgery, Amsterdam UMC, Amsterdam, The Netherlands
| | | | | | | |
Collapse
|
|
4
|
Jiang J, Goodwin B, Athavale A, Cazzetta SE, Chen L, Edelblut J, Fan T, Hadker N, Nazarey PP. Patient and Healthcare Professional Perspectives on Crohn's Perianal Fistula Treatment: Results From a Discrete Choice Experiment. CROHN'S & COLITIS 360 2025; 7:otae076. [PMID: 39790994 PMCID: PMC11711682 DOI: 10.1093/crocol/otae076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Indexed: 01/12/2025] Open
Abstract
Background Crohn's perianal fistulas (CPF) are difficult to manage and often require multiple interventions. This study aimed to assess the preferences of patients and healthcare professionals (HCPs) for attributes of CPF-related procedures/surgeries to better inform CPF management. Methods This US cross-sectional, observational study was conducted via a web-enabled questionnaire (October 2021-January 2022) among patients aged 21-89 years with a self-reported physician diagnosis of CPF (with or without CPF-related surgery experience) and HCPs (gastroenterologists and colorectal surgeons who managed ≥3 patients with CPF in the past 12 months). Patient and HCP preferences for CPF-related procedure/surgery attributes were assessed using a discrete choice experiment and stated preference methodology. Results In total, 100 patients and 137 HCPs were recruited. Benefits of therapy (symptom control and/or fistula closure) were rated as the most important CPF treatment attribute by both patients and HCPs influencing treatment decisions (mean relative importance 23.9 and 36.3, respectively). The mean relative importance of procedure invasiveness and postoperative discomfort was higher for patients (19.3 and 20.2, respectively) than for HCPs (14.3 and 11.0, respectively), whereas the mean relative importance of fecal incontinence was greater for HCPs than patients (25.0 vs. 19.3, respectively). Conclusions Patients and HCPs have different perspectives on the importance of specific CPF-related procedure/surgery attributes. The attributes identified as important to patients and HCPs in this study should be considered when managing patients with CPF and making treatment decisions.
Collapse
Affiliation(s)
- Jeanne Jiang
- GI Medical, Takeda Pharmaceuticals USA, Inc., Lexington, MA, USA
| | - Bridgett Goodwin
- GI Medical, Takeda Pharmaceuticals USA, Inc., Lexington, MA, USA
| | - Amod Athavale
- Evidence Strategy, Trinity Life Sciences, Waltham, MA, USA
| | - Susan E Cazzetta
- GI Medical, Takeda Pharmaceuticals USA, Inc., Lexington, MA, USA
| | - Lily Chen
- GI Medical, Takeda Pharmaceuticals USA, Inc., Lexington, MA, USA
| | | | - Tao Fan
- GI Medical, Takeda Pharmaceuticals USA, Inc., Lexington, MA, USA
| | - Nandini Hadker
- Evidence Strategy, Trinity Life Sciences, Waltham, MA, USA
| | | |
Collapse
|
|
5
|
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.
Collapse
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
| | | | | | | | | |
Collapse
|
|
6
|
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.
Collapse
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
| |
Collapse
|
|
7
|
Fathallah N, Haouari MA, Alam A, Barré A, Roland D, Spindler L, Far ES, de Parades V. Closing the internal opening with a rectal advancement flap increases the efficacy of mesenchymal stem cell injection for complex Crohn's disease anal fistulas. Tech Coloproctol 2024; 28:118. [PMID: 39222151 DOI: 10.1007/s10151-024-02990-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 07/29/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND The efficacy of injections of mesenchymal stem cells (MSC) for anal fistula treatment may be impaired by the persistence of stools passing into the fistula, causing bacterial contamination and a local inflammatory reaction. We aimed to compare remission rates between patients treated by MSC injection with simple sutures and those treated with a rectal advancement flap. METHODS This single-center prospective study compared the first patients who underwent internal opening closure with sutures with the subsequent patients treated with a flap. Complete clinical remission was defined as complete closure of the external opening(s) without pain or discharge, and complete radiological remission was defined as a Magnifi-CD score of 0. RESULTS We compared the first 42 patients who had sutures with the 20 subsequent patients who had an advancement flap. The median follow-up was 15.5 [8.8-24.9] months. The cumulative incidence of complete clinical response at M12 was 53.8% [38.1-69.6%] in the suture group versus 93.3% [77.4-100.0] in the flap group (p < 0.001). The Magnifi-CD score was 0 for 41.7% [25.5-59.2%]) of patients treated with sutures versus 72.7% [39.0-63.9%]) of patients treated with a flap (p = 0.093). Anal incontinence score did not differ between the two groups. Practicing an advancement flap was the only significant factor associated with complete clinical remission over time (adjusted HR [95% CI] of 2.6 [1.4-4.9], p = 0.003). CONCLUSIONS Complete clinical remission rates following MSC injection are significantly higher after closure of the internal opening with a rectal flap than after closure with sutures, without consequences on anal continence.
Collapse
Affiliation(s)
- N Fathallah
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France.
| | - M A Haouari
- Radiology Department, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - A Alam
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - A Barré
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - D Roland
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - L Spindler
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - E Safa Far
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - V de Parades
- Department of MedicoSurgical Proctology, Institut Léopold Bellan, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| |
Collapse
|
|
8
|
Munster LJ, Mönnink GLE, van Dieren S, Mundt MW, D’Haens GRAM, Bemelman WA, Buskens CJ, van der Bilt JDW. Fistulizing Perianal Disease as a First Manifestation of Crohn's Disease: A Systematic Review and Meta-Analysis. J Clin Med 2024; 13:4734. [PMID: 39200879 PMCID: PMC11355404 DOI: 10.3390/jcm13164734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/16/2024] [Accepted: 07/17/2024] [Indexed: 09/02/2024] Open
Abstract
Background: Incidences of perianal fistulas (PAFs) as a first manifestation of Crohn's disease (CD) vary widely in the literature. Aim: To analyse the percentage of patients with a PAF preceding CD diagnosis and assess the time to diagnosis. Methods: A systematic literature search was conducted. Studies reporting on patients with a PAF preceding CD diagnosis were identified. Primary outcomes were the (weighted) percentage of patients with CD with a PAF preceding CD and their time to CD diagnosis. Secondary outcomes were the (weighted) percentage of patients with CD with a PAF preceding CD diagnosis in predefined patient subgroups, including (1) sex (men vs. women), (2) ethnicity (Asian vs. non-Asian), and (3) age (paediatric (0-18 y) and patients with elderly onset CD (>60 y) vs. adult patients (18-60 y)). Results: Seventeen studies were included (34,030 patients with CD). In the overall CD population, a PAF preceded CD in 8.6% [95%CI; 5.72; 12.71] with a weighted mean time to CD diagnosis of 45.9 (31.3) months. No studies reported details on sex differences in patients with a PAF as a manifesting sign of CD. In Asian populations, a PAF preceded CD in 17.66% [95%CI; 11.45; 26.25], which was significantly higher when compared with non-Asians (4.99% [95%CI; 3.75; 6.60], OR:3.99, p < 0.0001). In adolescents, an incidence of 9.17% [95%CI; 5.92; 13.93] was found with significantly lower incidences in paediatric patients (6.38% [95%CI; 1.84; 19.85], OR:0.53, p < 0.0001), and elderly-onset patients (3.77% [95%CI; 1.68; 8.25], OR:0.44, p = 0.0035). Conclusions: This systematic review shows that in the literature, almost 10% of patients present with a PAF as a first manifestation of CD, with a mean time to diagnosis of almost four years. These results emphasise that increased clinical awareness is needed.
Collapse
Affiliation(s)
- Liesbeth Jozefien Munster
- Department of Surgery, Flevoziekenhuis, 1315 RA Almere, The Netherlands
- Department of Surgery, Amsterdam UMC (Location VUMC), 1081 HV Amsterdam, The Netherlands (C.J.B.)
| | - Giulia Louise Emilia Mönnink
- Department of Surgery, Flevoziekenhuis, 1315 RA Almere, The Netherlands
- Department of Surgery, Amsterdam UMC (Location VUMC), 1081 HV Amsterdam, The Netherlands (C.J.B.)
| | - Susan van Dieren
- Department of Surgery, Amsterdam UMC (Location VUMC), 1081 HV Amsterdam, The Netherlands (C.J.B.)
| | - Marco William Mundt
- Department of Gastroenterology and Hepatology, Flevoziekenhuis, 1315 RA Almere, The Netherlands
| | | | - Willem Adrianus Bemelman
- Department of Surgery, Amsterdam UMC (Location VUMC), 1081 HV Amsterdam, The Netherlands (C.J.B.)
| | | | - Jarmila Dagmara Wendelien van der Bilt
- Department of Surgery, Flevoziekenhuis, 1315 RA Almere, The Netherlands
- Department of Surgery, Amsterdam UMC (Location VUMC), 1081 HV Amsterdam, The Netherlands (C.J.B.)
| |
Collapse
|
|
9
|
Pacheco T, Monteiro S, Barros L, Silva J. Perianal disease in inflammatory bowel disease: Broadening treatment and surveillance strategies for anal cancer. World J Gastroenterol 2024; 30:3373-3385. [PMID: 39091713 PMCID: PMC11290399 DOI: 10.3748/wjg.v30.i28.3373] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 06/17/2024] [Accepted: 07/08/2024] [Indexed: 07/24/2024] Open
Abstract
The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.
Collapse
Affiliation(s)
- Tatiana Pacheco
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
| | - Sara Monteiro
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
| | - Luísa Barros
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
| | - Jorge Silva
- Department of Gastroenterology, Centro Hospitalar do Tâmega e Sousa, Penafiel 4560-136, Portugal
| |
Collapse
|
|
10
|
Schaad M, Schoepfer A, Rossel JB, Barry MP, Rogler G, Hahnloser D. Long-Term Outcome of Surgery for Perianal Crohn's Fistula. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1035. [PMID: 39064464 PMCID: PMC11279190 DOI: 10.3390/medicina60071035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/18/2024] [Accepted: 06/21/2024] [Indexed: 07/28/2024]
Abstract
Background and Objectives: Patients with perianal Crohn's (CD) fistula often need repetitive surgeries and none of the established techniques was shown to be superior or preferable. Furthermore, the long-term outcome of fistula Seton drainage is not well described. The aims of this study were to analyze the long-term healing and recurrence rate of CD perianal fistulas in a large patient cohort. Materials and Methods: Database analysis of the Swiss IBD (Inflammatory Bowel Disease) cohort study. Results: 365 perianal fistula patients with 576 surgical interventions and a median follow-up of 7.5 years (0-12.6) were analyzed. 39.7% of patients required more than one procedure. The first surgical interventions were fistulectomies ± mucosal sliding flap (59.2%), Seton drainage (29.6%), fistula plugs or fibrin glue installations (2.5%) and combined procedures (8.8%). Fistulectomy patients required no more surgery in 69%, one additional surgery in 25% and more than one additional surgery in 6%, with closure rates at 7.5 years follow-up of 77.1%, 74.1% and 66.7%, respectively. In patients with Seton drainage as index surgery, 52% required no more surgery, and over 75% achieved fistula closure after 10 years. Conclusions: First-line fistulectomies, when feasible, achieved the highest healing rates, but one-third of patients required additional surgeries, and one-fourth of patients will remain with a fistula at 10 years. Initial Seton drainage and concurrent medical therapy can achieve fistula closure in 75%. However, in 50% of patients, more surgeries are needed, and fistula closure is achieved in only two-thirds of patients.
Collapse
Affiliation(s)
- Marie Schaad
- Service of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Bugnon 46, 1005 Lausanne, Switzerland
| | - Alain Schoepfer
- Service of Gastroenterology, Lausanne University Hospital (CHUV), University of Lausanne, Bugnon 46, 1005 Lausanne, Switzerland
| | - Jean-Benoît Rossel
- Unisanté, University Center for Primary Care and Public Health, University of Lausanne, 1011 Lausanne, Switzerland
| | - Mamadou Pathé Barry
- Unisanté, University Center for Primary Care and Public Health, University of Lausanne, 1011 Lausanne, Switzerland
| | - Gerhard Rogler
- Service of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, 8091 Zurich, Switzerland
| | - Dieter Hahnloser
- Service of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Bugnon 46, 1005 Lausanne, Switzerland
| |
Collapse
|
|
11
|
Kweon OS, Kang B, Lee YJ, Kim ES, Kim SK, Lee HS, Chung YJ, Kim KO, Jang BI. Self-screening questionnaire for perianal fistulizing disease in patients with Crohn's disease. Korean J Intern Med 2024; 39:430-438. [PMID: 38576234 PMCID: PMC11076884 DOI: 10.3904/kjim.2023.410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/02/2023] [Accepted: 12/19/2023] [Indexed: 04/06/2024] Open
Abstract
BACKGROUND/AIMS A poor prognostic factor for Crohn's disease (CD) includes perianal fistulizing disease, including perianal fistula and/or perianal abscess. Currently, a tool to assess perianal symptoms in patients with CD remains nonexistent. This study aimed to develop a perianal fistulizing disease self-screening questionnaire for patients with CD. METHODS This prospective pilot study was conducted at three tertiary referral centers between January 2019 and May 2020. We formulated questions on perianal symptoms, including tenesmus, anal discharge, bleeding, pain, and heat. A 4-point Likert scale was used to rate each question. Patients with CD completed a questionnaire and underwent pelvic magnetic resonance imaging (MRI). RESULTS Overall, 93 patients were enrolled, with 51 (54.8%) diagnosed with perianal fistulizing disease, as determined by pelvic MRI. The Spearman correlation findings demonstrated that anal pain (p = 0.450, p < 0.001) and anal discharge (p = 0.556, p < 0.001) were the symptoms that most significantly correlated with perianal disease. For anal pain and discharge, the area under the receiver operating characteristic curve of the scores was significantly higher than that of the combined score for all five symptoms (0.855 vs. 0.794, DeLong's test p = 0.04). For the two symptoms combined, the sensitivity, specificity, and positive predictive and negative predictive values were 88.2, 73.8, 80.4, and 83.8%, respectively, with 81.7% accuracy for detecting perianal fistulizing disease. CONCLUSION This study indicates that simple questions regarding anal pain and discharge can help accurately identify the presence of perianal fistulizing disease in patients with CD.
Collapse
Affiliation(s)
- O Seong Kweon
- Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea
| | - Ben Kang
- Department of Pediatrics, Kyungpook National University, School of Medicine, Daegu, Korea
| | - Yoo Jin Lee
- Division of Gastroenterology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Eun Soo Kim
- Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea
| | - Sung Kook Kim
- Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea
| | - Hyun Seok Lee
- Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea
| | - Yun Jin Chung
- Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea
| | - Kyeong Ok Kim
- Division of Gastroenterology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Byung Ik Jang
- Division of Gastroenterology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - on behalf of Crohn’s Colitis Association in Daegu-Gyeongbuk (CCAiD)
- Division of Gastroenterology, Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea
- Department of Pediatrics, Kyungpook National University, School of Medicine, Daegu, Korea
- Division of Gastroenterology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
- Division of Gastroenterology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| |
Collapse
|
|
12
|
White I, Yanai H, Avni I, Slavin M, Naftali T, Tovi S, Dotan I, Wasserberg N. Mesenchymal stem cell therapy for Crohn's perianal fistula-a real-world experience. Colorectal Dis 2024; 26:102-109. [PMID: 38095303 DOI: 10.1111/codi.16830] [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: 10/14/2022] [Revised: 04/11/2023] [Accepted: 09/05/2023] [Indexed: 01/28/2024]
Abstract
AIM Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long-term remission with local injection of allogeneic adipose-derived mesenchymal stem cells (darvadstrocel). Our aim was to analyse outcomes from our real-world experience with this new treatment. METHODS All patients with Crohn's disease suffering complex perianal fistulas who consecutively underwent administration of darvadstrocel at two centres were followed up and evaluated. Patients were assessed for clinical remission, response, failure, and any complications during follow-up. The results of all patients with a minimum of 3 months' follow-up are presented. RESULTS Thirty-three patients with Crohn's disease and complex perianal fistulas were included. Of these, 20 (61%) experienced clinical remission that was maintained for a mean follow-up of 14 (3-32) months. A total of 24 of 33 (73%) experienced at least 3 months of clinical remission, with four later having recurrence (3-12 months). Among the remaining nine patients who did not experience clinical remission, two (6%) had partial remission (such as one of two fistulas closing), two (6%) showed signs of response but not remission, and five (15%) showed no signs of healing. The mean time to maintained clinical remission was 6 weeks (range 2 weeks to 6 months), and there were no severe adverse events. CONCLUSION In this real-world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.
Collapse
Affiliation(s)
- Ian White
- Colorectal Unit, Division of Surgery, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Henit Yanai
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Irit Avni
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Moran Slavin
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Surgery B Department, Meir Medical Center, Kfar Saba, Israel
| | - Timna Naftali
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Gastroenterology Department, Meir Medical Center, Kfar Saba, Israel
| | - Shifra Tovi
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Iris Dotan
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Nir Wasserberg
- Colorectal Unit, Division of Surgery, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| |
Collapse
|
|
13
|
Anandabaskaran S, Hanna L, Iqbal N, Constable L, Tozer P, Hart A. Where Are We and Where to Next?-The Future of Perianal Crohn's Disease Management. J Clin Med 2023; 12:6379. [PMID: 37835022 PMCID: PMC10573672 DOI: 10.3390/jcm12196379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/26/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Perianal fistulizing Crohn's Disease (pCD) affects about 25% of patients with Crohn's Disease (CD). It remains a difficult entity to manage with a therapeutic ceiling of treatment success despite improving medical and surgical management. The refractory nature of the disease calls for an imminent need to better understand its immunopathogenesis and classification to better streamline our treatment options. In this article, we overview the current state of pCD management and discuss where the future of its management may lie.
Collapse
Affiliation(s)
- Sulak Anandabaskaran
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London W12 0NN, UK
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Faculty of Medicine, St Vincent’s Clinical School, University of New South Wales, 390 Victoria Street, Darlinghurst, NSW 2010, Australia
| | - Luke Hanna
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London W12 0NN, UK
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
| | - Nusrat Iqbal
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2BX, UK
| | - Laura Constable
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London W12 0NN, UK
| | - Phil Tozer
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2BX, UK
| | - Ailsa Hart
- Robin Phillip’s Fistula Research Unit, St Mark’s Hospital and Academic Institute, London HA1 3UJ, UK
- Department of Surgery and Cancer, South Kensington Campus, Imperial College London, London SW7 2BX, UK
| |
Collapse
|
|
14
|
Geldof J, Iqbal N, LeBlanc JF, Anandabaskaran S, Sawyer R, Buskens C, Bemelman W, Gecse K, Lundby L, Lightner AL, Danese S, Spinelli A, Carvello M, Faiz O, Warusavitarne J, Lung P, De Looze D, D'Hoore A, Vermeire S, Hart A, Tozer P. Classifying perianal fistulising Crohn's disease: an expert consensus to guide decision-making in daily practice and clinical trials. Lancet Gastroenterol Hepatol 2022; 7:576-584. [DOI: 10.1016/s2468-1253(22)00007-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 01/14/2022] [Accepted: 01/17/2022] [Indexed: 12/14/2022]
|
|
15
|
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.
Collapse
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
| |
Collapse
|
|
16
|
Kucharzik T, Tielbeek J, Carter D, Taylor SA, Tolan D, Wilkens R, Bryant RV, Hoeffel C, De Kock I, Maaser C, Maconi G, Novak K, Rafaelsen SR, Scharitzer M, Spinelli A, Rimola J. ECCO-ESGAR Topical Review on Optimizing Reporting for Cross-Sectional Imaging in Inflammatory Bowel Disease. J Crohns Colitis 2022; 16:523-543. [PMID: 34628504 DOI: 10.1093/ecco-jcc/jjab180] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS The diagnosis and follow up of patients with inflammatory bowel disease [IBD] requires cross-sectional imaging modalities, such as intestinal ultrasound [IUS], magnetic resonance imaging [MRI] and computed tomography [CT]. The quality and homogeneity of medical reporting are crucial to ensure effective communication between specialists and to improve patient care. The current topical review addresses optimized reporting requirements for cross-sectional imaging in IBD. METHODS An expert consensus panel consisting of gastroenterologists, radiologists and surgeons convened by the ECCO in collaboration with ESGAR performed a systematic literature review covering the reporting aspects of MRI, CT, IUS, endoanal ultrasonography and transperineal ultrasonography in IBD. Practice position statements were developed utilizing a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when ≥80% of the participants agreed on a recommendation. RESULTS Twenty-five practice positions were developed, establishing standard terminology for optimal reporting in cross-sectional imaging. Assessment of inflammation, complications and imaging of perianal CD are outlined. The minimum requirements of a standardized report, including a list of essential reporting items, have been defined. CONCLUSIONS This topical review offers practice recommendations to optimize and homogenize reporting in cross-sectional imaging in IBD.
Collapse
Affiliation(s)
- Torsten Kucharzik
- Department of Gastroenterology, Klinikum Lüneburg, University of Hamburg, Bögelstr. 1, 21339 Lüneburg, Germany
| | - Jeroen Tielbeek
- Department of Radiology, Spaarne Gasthuis, Boerhaavelaan 22, Haarlem, the Netherlands; Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
| | - Dan Carter
- Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hasomher, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Stuart A Taylor
- Centre for Medical Imaging, University College London, London, UK
| | - Damian Tolan
- Radiology Department, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Beckett Street, Leeds, UK
| | - Rune Wilkens
- Gastrounit, Division of Medicine, Hvidovre University Hospital, Copenhagen, Denmark; Copenhagen Centre for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Copenhagen, Denmark
| | - Robert V Bryant
- Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, South Australia
| | - Christine Hoeffel
- Department of Abdominal Radiology, CHU Reims and CRESTIC, URCA, 51100 Reims, France
| | - Isabelle De Kock
- Department of Radiology, Ghent University Hospital, Ghent, Belgium
| | - Christian Maaser
- Outpatient Department of Gastroenterology, Department of Geriatrics, Klinikum Lüneburg, University of Hamburg, Bögelstr. 1, 21339 Lüneburg, Germany
| | - Giovanni Maconi
- Gastroenterology Unit, 'Luigi Sacco' University Hospital, Milan, Italy
| | - Kerri Novak
- Department of Radiology and Medicine, Division of Gastroenterology, University of Calgary, Alberta, Canada
| | - Søren R Rafaelsen
- Department of Radiology, University Hospital of Southern Denmark, Vejle, Denmark
| | - Martina Scharitzer
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, Milan, Italy.,IRCCS Humanitas Research Hospital, Division of Colon and Rectal Surgery, via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Jordi Rimola
- IBD unit, Radiology Department, Hospital Clínic Barcelona, Barcelona, Catalonia, Spain
| |
Collapse
|
|
17
|
Schwartz DA, Peyrin-Biroulet L, Lasch K, Adsul S, Danese S. Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn's Disease: ENTERPRISE Study. Clin Gastroenterol Hepatol 2022; 20:1059-1067.e9. [PMID: 34597729 DOI: 10.1016/j.cgh.2021.09.028] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 09/17/2021] [Accepted: 09/22/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Fistulizing Crohn's disease (CD) is challenging to treat. We report results from ENTERPRISE, a randomized, double-blind, phase 4 trial evaluating 2 vedolizumab intravenous dosing regimens in patients with fistulizing CD. METHODS Patients with moderately to severely active CD and 1-3 active perianal fistulae (identified on magnetic resonance imaging [MRI]) received vedolizumab 300 mg intravenously at weeks 0, 2, 6, 14, and 22 (VDZ) or the same regimen plus an additional vedolizumab dose at week 10 (VDZ + wk10). Reduction from baseline in draining perianal fistulae and disease activity, MRI assessments, health-related quality of life (HRQoL), and safety were evaluated. Enrollment was stopped prematurely because of recruitment challenges; analyses are descriptive. RESULTS Of 32 patients with ≥1 active fistulae at baseline per MRI and postbaseline fistulae healing assessment, 28 (14 per dosing regimen) had ≥1 draining fistulae at baseline (assessed by gentle finger compression during clinical exam). Rapid and sustained fistula closure was observed; 53.6% (VDZ, 64.3%; VDZ + wk10, 42.9%) and 42.9% (VDZ, 50.0%; VDZ + wk10, 35.7%) of patients achieved ≥50% decrease in draining fistulae and 100% fistulae closure, respectively, at week 30. Mean (standard deviation) CD and Perianal Disease Activity Index scores decreased by 51.1 (78.3) and 4.1 (3.3), respectively, at week 30. HRQoL improved throughout the study. No new safety signals were observed. CONCLUSIONS Sustained improvements in fistulizing CD were seen with both vedolizumab regimens. An additional dose at week 10 does not appear to alter treatment outcomes. Safety profile was consistent with other vedolizumab studies. CLINICALTRIALS gov no: NCT02630966; EudraCT: 2015-000852-12.
Collapse
Affiliation(s)
- David A Schwartz
- Inflammatory Bowel Disease Center, Vanderbilt University Medical Center, Nashville, Tennessee.
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Nancy, France; Inserm U1256 NGERE, Lorraine University, Nancy, France
| | - Karen Lasch
- Takeda Pharmaceuticals USA Inc, Lexington, Massachusetts
| | - Shashi Adsul
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
| | - Silvio Danese
- IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy
| |
Collapse
|
|
18
|
Mamie C, Bruckner RS, Lang S, Shpigel NY, Turina M, Rickenbacher A, Cabalzar-Wondberg D, Chvatchko Y, Rogler G, Scharl M. MMP9 expression in intestinal fistula from patients with fistulizing CD and from human xenograft mouse model. Tissue Barriers 2022; 10:1994350. [PMID: 34709129 PMCID: PMC9067458 DOI: 10.1080/21688370.2021.1994350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 10/07/2021] [Accepted: 10/10/2021] [Indexed: 10/20/2022] Open
Abstract
Fistula treatment represents a major unmet medical need in the therapy of Crohn's disease (CD). Current medical therapies, such as anti-TNF antibody treatments, are often insufficient and do not achieve permanent fistula closure. Previously published data point toward a critical role for metalloproteinase-9 (MMP-9)/gelatinase B in fistula pathogenesis. The aim of this project was to investigate in detail MMP-9 expression in different fistula types and to confirm that MMP-9 is a potential target for fistula therapy in CD patients.Immunohistochemistry for total and active MMP-9, Cytokeratin 8 (CK-8) and co-staining of active MMP-9/CK-8 was performed in specimen derived from perianal fistulas, entero-enteric fistulas and fistulas from patients not responding to anti-TNF therapy. In addition, fistulas from the xenograft mouse model (anti-TNF treated or untreated) were analyzed.Total and active MMP-9 protein was detectable in cells lining the tracts of perianal and entero-enteric fistulas. Of note, total and active MMP-9 was also expressed in fistulas of CD patients non-responding to anti-TNF treatment. Interestingly, we detected considerable co-staining of active MMP-9 and CK-8 in particular in cells lining the fistula tract and in transitional cells around the fistulas. Furthermore, total and active MMP-9 are detectable in both anti-TNF treated and untreated xenograft fistulas.Taken together, our data suggest that MMP-9 is involved in fistula pathogenesis in CD patients, in fistulas of different origins and particularly in patients non-responding to anti-TNF therapy. Our xenograft fistula model is suitable for in vivo studies investigating a possible therapeutic role for MMP-9 targeting as fistula therapy.
Collapse
Affiliation(s)
- Céline Mamie
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Ramona S. Bruckner
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Silvia Lang
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Nahum Y. Shpigel
- Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Matthias Turina
- Department of Visceral and Transplantation Surgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Andreas Rickenbacher
- Department of Visceral and Transplantation Surgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Daniela Cabalzar-Wondberg
- Department of Visceral and Transplantation Surgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | | | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| |
Collapse
|
|
19
|
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.
Collapse
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
| |
Collapse
|
|
20
|
Geldof J, Iqbal N, Warusavitarne J, Hart A. The Essential Role of a Multidisciplinary Approach in Inflammatory Bowel Diseases: Combined Medical-Surgical Treatment in Complex Perianal Fistulas in CD. Clin Colon Rectal Surg 2022; 35:21-31. [PMID: 35069027 PMCID: PMC8763455 DOI: 10.1055/s-0041-1740035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Perianal fistulizing Crohn's disease (PFCD) represents a challenging and complex disease phenotype. Patients typically suffer a more severe disease course than those without perianal complications and are often managing debilitating symptoms. Etiology is understood to be multifactorial, with genetic predisposition, microbiological insult, aberrant immunity, and mechanical factors all implicated. As a result, multimodal treatment strategies must be employed to achieve disease control and fistula closure. This requires the complimentary involvement of medical and surgical disciplines in order to ensure thorough assessment and treatment tailored to the individual scenario and patient goals. The aim of this article is to describe an overview of the various treatment strategies available for PFCD, focusing on how a synergistic approach is required to ensure maximal chances of success.
Collapse
Affiliation(s)
- Jeroen Geldof
- IBD Unit, St. Mark's Hospital, Harrow, United Kingdom,Gastroenterology Department, University Hospital Ghent, Ghent, Belgium,Address for correspondence Jeroen Geldof, MD IBD Unit, St. Mark's HospitalWatford Road, Harrow HA1 3UJUnited Kingdom
| | - Nusrat Iqbal
- Robin Phillips Fistula Research Unit, St. Mark's Hospital, Harrow, United Kingdom
| | | | - Ailsa Hart
- IBD Unit, St. Mark's Hospital, Harrow, United Kingdom,Robin Phillips Fistula Research Unit, St. Mark's Hospital, Harrow, United Kingdom
| |
Collapse
|
|
21
|
Nazari H, Naei VY, Tabasi AH, Badripour A, Akbari Asbagh R, Keramati MR, Sharifi A, Behboudi B, Kazemeini A, Abbasi M, Keshvari A, Ahmadi Tafti SM. Advanced Regenerative Medicine Strategies for Treatment of Perianal Fistula in Crohn's Disease. Inflamm Bowel Dis 2022; 28:133-142. [PMID: 34291798 DOI: 10.1093/ibd/izab151] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Indexed: 12/15/2022]
Abstract
Regenerative medicine is an emerging therapeutic method that aims to reconstruct tissues and organs. This advanced therapeutic approach has demonstrated great potential in addressing the limitations of medical and surgical procedures for treating perineal fistula in patients with Crohn's disease. Recent developments in stem cell technology have led to a massive good manufacturing practices (GMPs) production of various stem cells, including mesenchymal and embryonic cells, along with induction of pluripotent stem cells to repair damaged tissues in the fistula. The recent advances in separation and purification of exosomes, as biologic nanovesicles carrying anti-inflammatory and regenerative agents, have made them powerful tools to treat this inflammatory disease. Further, tremendous advances in nanotechnology, biomaterials, and scaffold fabrication methods enable tissue engineering methods to synthesize tissue-like structures to assist surgical techniques. This review focuses on advanced regenerative-based methods including stem cell therapy, exosome therapy, and tissue engineering used in the treatment of perianal fistula. Relevant in vitro and in vivo studies and the latest innovations in implementation of regenerative medicine for this disease are also separately reviewed. Additionally, current challenges regarding implementation of g stem cells, exosomes, and tissue engineering methods for bridging the gaps between laboratory findings and clinic application will be discussed.
Collapse
Affiliation(s)
- Hojjatollah Nazari
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.,Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Vahid Yaghoubi Naei
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Asieh Heirani Tabasi
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.,Department of Cell Therapy and Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Abolfazl Badripour
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Akbari Asbagh
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Keramati
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirsina Sharifi
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Behnam Behboudi
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Kazemeini
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Amir Keshvari
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Mohsen Ahmadi Tafti
- Division of Colorectal Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.,Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
22
|
Khan MR, Ulrich JA, Hull NC, Inoue A, Harmsen WS, Faubion WA, Fletcher JG, Absah I. Perianal magnetic resonance imaging findings and their potential impact on outcome in children with perianal fistulizing Crohn disease. Pediatr Radiol 2021; 51:2481-2491. [PMID: 34490496 DOI: 10.1007/s00247-021-05158-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 05/25/2021] [Accepted: 07/20/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND Children with perianal fistulizing Crohn disease require intensive medical management but also have a higher risk for subsequent surgical interventions. OBJECTIVE We performed a retrospective study to identify patient factors and perianal anatomical features by pelvic MR that are associated with surgical interventions in these children. MATERIALS AND METHODS We included children with Crohn disease and perianal fistula who underwent pelvic MR with available, archived images and collected demographic, clinical and laboratory data. Radiologists reviewed pelvic MR exams and identified Park classification and additional anatomical features of perianal fistulas, including fistula branching, horseshoe ramifications, abscess, inflammatory mass, supralevator extension, anal sphincter damage, proctitis and posterior anal space involvement. We performed univariate and subsequent multivariate analysis to determine features associated with subsequent surgical intervention. RESULTS Ninety-nine children with Crohn disease underwent pelvic MR. In this cohort, 69 children had no surgical interventions prior to baseline MRI, with subsequent median clinical follow-up of 5.5 years. Univariate analysis demonstrated that branching (P=0.009), supralevator extension (P=0.015) and anal sphincter damage (P=0.031) were significantly associated with subsequent surgical intervention. Age at baseline MRI was also associated with intervention (hazard ratio [HR] every 5 years: 2.13; 95% confidence interval [CI]: 1.18-3.83; P=0.012). A multivariable model identified only fistula branching (HR: 2.31; 95% CI: 1.28-4.15; P=0.005) and age (HR: 5.18; CI: 1.57-17.14; P=0.007) as independent predictors of subsequent surgery. No demographic, clinical or laboratory parameter predicted subsequent surgical intervention. CONCLUSION Age and anatomical MR features indicating fistula complexity (branching, supralevator extension) and sphincter damage confer a higher risk of subsequent surgical intervention in children with perianal Crohn disease.
Collapse
Affiliation(s)
- Muhammad Rehan Khan
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine at Peoria, Children's Hospital of Illinois, 530 NE Glen Oak Ave., Peoria, IL, 61637, USA. .,Department of Pediatrics & Child Health, Aga Khan University, Karachi, Pakistan.
| | | | - Nathan C Hull
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Akitoshi Inoue
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - William S Harmsen
- Department of Biomedical Statistics and informatics, Mayo Clinic, Rochester, MN, USA
| | - William A Faubion
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | - Imad Absah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.,Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
23
|
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.
Collapse
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.)
| |
Collapse
|
|
24
|
van Rijn KL, Meima-van Praag EM, Bossuyt PM, D’Haens GR, Gecse KB, Horsthuis K, Snijder HJ, Tielbeek JAW, Buskens CJ, Stoker J. Fibrosis and MAGNIFI-CD Activity Index at Magnetic Resonance Imaging to Predict Treatment Outcome in Perianal Fistulizing Crohn's Disease Patients. J Crohns Colitis 2021; 16:708-716. [PMID: 34644395 PMCID: PMC9228904 DOI: 10.1093/ecco-jcc/jjab168] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Characteristic magnetic resonance imaging [MRI] features associated with long-term perianal fistula closure are still being discussed. This study evaluated the predictive value of degree of fibrosis and disease activity (MAGNIFI-CD index) at MRI for long-term clinical closure of Crohn's perianal fistulas. METHODS Crohn's disease [CD] patients treated with surgical closure following anti-tumour necrosis factor [anti-TNF] induction or anti-TNF alone for high perianal fistulas as part of a patient preference randomized controlled trial [PISA-II] between 2013 and 2020 with a post-treatment MRI and long-term clinical follow-up data were retrospectively included. Two radiologists scored the degree of fibrosis and MAGNIFI-CD index at pre- and post-treatment MRI. The accuracy of post-treatment MRI findings in predicting long-term clinical closure [12 months after the MRI] was evaluated using receiver operating characteristics [ROC] analysis. RESULTS Fifty patients were included: 31 female, median age 33 years (interquartile range [IQR] 26-45). Fourteen patients showed a 100% fibrotic fistula at post-treatment MRI, all of which had long-term clinical closure. Median MAGNIFI-CD index at post-treatment MRI was 0 [IQR 0-5] in 25 patients with long-term clinical closure and 16 [IQR 10-20] in 25 patients without. ROC analysis showed an area under the curve of 0.90 (95% confidence interval [CI] 0.82-0.99) for degree of fibrosis and 0.95 [95% CI 0.89-1.00] for the MAGNIFI-CD index, with a Youden cut-off point of 6 [91% specificity, 87% sensitivity]. CONCLUSIONS Degree of fibrosis and MAGNIFI-CD index at post-treatment MRI are accurate in predicting long-term clinical closure and seem valuable in follow-up of perianal CD. A completely fibrotic tract at MRI is a robust indicator for long-term fistula closure. EUDRACT 2013-002932-25 and 2018-002064-15.
Collapse
Affiliation(s)
- Kyra L van Rijn
- Corresponding author: Kyra L. van Rijn, MD, Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Tel: +31 (0) 20 7320783;
| | - Elise M Meima-van Praag
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Patrick M Bossuyt
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Geert R D’Haens
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Krisztina B Gecse
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Karin Horsthuis
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, De Boelelaan 1117, Amsterdam, The Netherlands
| | - Harmanna J Snijder
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Jeroen A W Tielbeek
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands,Department of Radiology, Spaarne Gasthuis, Haarlem, The Netherlands
| | - Christianne J Buskens
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, Meibergdreef 9, Amsterdam, the Netherlands
| |
Collapse
|
|
25
|
Caron B, D'Amico F, Danese S, Peyrin-Biroulet L. Endpoints for Perianal Crohn's Disease Trials: Past, Present and Future. J Crohns Colitis 2021; 15:1387-1398. [PMID: 33550374 DOI: 10.1093/ecco-jcc/jjab026] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Since the 1980s, many studies have evaluated the efficacy of therapies to improve the outcomes of patients with perianal Crohn's disease. We performed a systematic review to describe the evolution of endpoints in perianal fistulizing Crohn's disease. Efficacy outcomes, definitions and measurement tools were assessed. METHODS Electronic databases were searched up to November 1, 2020. All published randomized placebo-controlled trials enrolling patients with perianal fistula and Crohn's disease were eligible for inclusion. Ongoing randomized clinical trials were also described. RESULTS Nineteen randomized controlled trials were included. Clinical efficacy endpoints were reported in all trials. Clinical response was the most frequent primary endpoint [6/19 studies, 31.6%], followed by clinical remission in four studies [21%]. Clinical response was defined as closure of at least 50% of fistulas, while remission was defined as closure of all fistulas. A combined clinical and radiological primary endpoint was used to assess fistula healing in four studies [21%]. The Perianal Disease Activity Index was a primary endpoint in only one study [5.5%]. In addition, eight ongoing controlled trials were identified. Combined clinical and radiological remission was the most frequent primary endpoint in these studies [4/8, 50%]. CONCLUSION In this systematic review, significant changes in outcomes used in randomized clinical trials of perianal Crohn's disease were observed. Radiological endpoints are increasingly used in perianal fistulizing Crohn's disease trials.
Collapse
Affiliation(s)
- Bénédicte Caron
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Ferdinando D'Amico
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Department of Gastroenterology, IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Department of Gastroenterology, IBD Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| |
Collapse
|
|
26
|
Higher Postinduction Infliximab Concentrations Are Associated With Improved Clinical Outcomes in Fistulizing Crohn's Disease: An ACCENT-II Post Hoc Analysis. Am J Gastroenterol 2021; 116:1007-1014. [PMID: 33929379 PMCID: PMC8095681 DOI: 10.14309/ajg.0000000000001111] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 11/18/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION There are only limited data regarding the role of therapeutic drug monitoring in fistulizing Crohn's disease (CD). We investigated the association between both induction and maintenance serum infliximab concentrations and favorable therapeutic outcomes in patients with fistulizing CD. METHODS This was a post hoc analysis of the ACCENT-II trial evaluating patients with fistulizing CD receiving induction (n = 282) and maintenance infliximab therapy (n = 139). Investigated therapeutic outcomes at both week 14 and week 54 included fistula response, complete fistula response, C-reactive protein (CRP) normalization (≤5 mg/L) in patients with an elevated baseline CRP, and a more stringent outcome of composite remission, defined as combined complete fistula response and CRP normalization. Associations between serum infliximab concentrations and outcomes were assessed by multivariable logistic regression models. RESULTS Higher week 14 infliximab concentrations were independently associated with week 14 fistula response (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.02-1.32; P = 0.019), and composite remission (OR: 2.32; 95% CI: 1.55-3.49; P < 0.001). Higher week 14 infliximab concentrations were also independently associated with week 54 composite remission (OR: 2.05; 95% CI: 1.10-3.82; P = 0.023). Based on receiver operating characteristic curve analysis, week 14 infliximab concentrations thresholds with combined maximal sensitivity and specificity of ≥20.2 μg/mL at week 2, ≥15 μg/mL at week 6, and ≥7.2 μg/mL at week 14 were associated with week 14 composite remission. DISCUSSION Higher post-induction infliximab concentrations are associated with early and long-term favorable therapeutic outcomes in patients with fistulizing CD.
Collapse
|
|
27
|
Effectiveness of Infliximab on Deep Radiological Remission in Chinese Patients with Perianal Fistulizing Crohn's Disease. Dig Dis Sci 2021; 66:1658-1668. [PMID: 32524415 DOI: 10.1007/s10620-020-06398-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 06/03/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Information concerning deep radiological healing of perianal fistulas in Chinese patients with CD is limited. The present study aimed to establish the effectiveness of infliximab on CD-related perianal fistulas using magnetic resonance imaging (MRI) and identify predictors of deep radiological remission of fistulas. METHODS We retrospectively reviewed patients with CD with draining perianal fistulas treated with infliximab and included only those who underwent clinical assessment and MRI before and after infliximab therapy. RESULTS Among 178 patients who underwent repeated MRI and clinical assessment, 65.2% had complex fistulas. Post-infliximab therapy, 55.1% of patients with perianal fistulizing CD showed clinical remission and 26.4% presented a clinical response; 38.2% had deep radiological remission, and 34.3% had a partial response based on the Ng score; the Van Assche scores decreased obviously compared with baseline. Prolonged infliximab infusion (18 times) presented higher radiological remission rates in patients with CD with complex fistulas. Concomitant treatment with azathioprine increased the fistula healing rate compared with infliximab alone (50% vs. 36.9%, P < 0.001). Younger age at diagnosis of CD, proctitis and requiring perianal surgery were identified as predictors of poor deep radiological remission of fistulas. Eight of ten patients who stopped infliximab and switched to an alternative agent retained a status of fistula healing in the first year of follow-up. CONCLUSIONS Infliximab induced deep radiological remission of perianal fistulas in Chinese patients with CD. Routine MRI should be used to monitor fistula healing. Patients with younger age at diagnosis of CD, proctitis, and/or requiring perianal surgery should receive combined therapy and careful monitoring.
Collapse
|
|
28
|
Cao WT, Huang R, Jiang KF, Qiao XH, Wang JJ, Fan YH, Xu Y. Predictive value of blood concentration of biologics on endoscopic inactivity in inflammatory bowel disease: A systematic review. World J Gastroenterol 2021; 27:886-907. [PMID: 33727776 PMCID: PMC7941861 DOI: 10.3748/wjg.v27.i9.886] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 12/25/2020] [Accepted: 01/12/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease (IBD) patients, complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.
AIM To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.
METHODS We searched PubMed/MEDLINE, Embase, and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.
RESULTS A total of 23 articles with 30 clinical studies and 1939 IBD patients were included. The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6 μg/mL in IBD. Blood concentration of infliximab reaching 5.0-12.7 μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease. Blood concentration of adalimumab reaching 7.2-16.2 μg/mL or more could predict mucosal healing in IBD. The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8 μg/mL in perianal fistulizing Crohn's disease. Blood concentration of vedolizumab surpassing 25.0 μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9 μg/mL.
CONCLUSION Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies, whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.
Collapse
Affiliation(s)
- Wan-Ting Cao
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Rong Huang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Ke-Fang Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Xue-Hui Qiao
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Jing-Jing Wang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Yi-Hong Fan
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| | - Yi Xu
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Gastrointestinal Diseases Pathophysiology, Hangzhou 310006, Zhejiang Province, China
| |
Collapse
|
|
29
|
Lansdorp CA, Gecse KB, Buskens CJ, Löwenberg M, Stoker J, Bemelman WA, D’Haens GR, van Hulst RA. Hyperbaric oxygen therapy for the treatment of perianal fistulas in 20 patients with Crohn's disease. Aliment Pharmacol Ther 2021; 53:587-597. [PMID: 33326623 PMCID: PMC7898636 DOI: 10.1111/apt.16228] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/24/2020] [Accepted: 12/02/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Positive effects of hyperbaric oxygen on perianal fistulas in Crohn's disease have been reported. AIM To assess efficacy, safety and feasibility of hyperbaric oxygen in Crohn's disease patients with therapy-refractory perianal fistulas. METHODS Twenty consecutive patients were recruited at the out-patient fistula clinic of the Amsterdam UMC. Crohn's disease patients with high perianal fistula(s) failing conventional treatment for over 6 months were included. Exclusion criteria were presence of a stoma, rectovaginal fistula(s) and recent changes in treatment regimens. Patients received treatment with 40 hyperbaric oxygen sessions and outcome parameters were assessed at Week 16. RESULTS Seven women and 13 men were included (median age 34 years). At Week 16, median scores of perianal disease activity index and modified van Assche index (co-primary outcome parameters) decreased from 7.5 (95% CI 6-9) to 4 (95% CI 3-6, P < 0.001), and from 9.2 (95% CI 7.3-11.2) to 7.3 (95% CI 6.9-9.7, P = 0.004) respectively. Perianal disease activity index scores ≤4 (representing inactive perianal disease) were observed in 13/20 patients (65%). Twelve patients showed a clinical response (60%) and four (20%) clinical remission, assessed with fistula drainage assessment. Median C-reactive protein and faecal calprotectin levels decreased from 4.2 mg/mL (95% CI 1.6-8) to 2.2 (95% CI 0.9-4.3, P = 0.003) and from 399 µg/g (95% CI 52-922) to 31 (95% CI 16-245, P = 0.001), respectively. CONCLUSIONS We found significant clinical, radiological and biochemical improvement in Crohn's disease patients with therapy-refractory perianal fistulas after treatment with hyperbaric oxygen. CLINICAL TRIAL REGISTRATION www.trialregister.nl/trial/6489.
Collapse
Affiliation(s)
- Corine A. Lansdorp
- Department of Anesthesiology/Hyperbaric MedicineAmsterdam UMC, location AMCAmsterdamThe Netherlands
| | - Krisztina B. Gecse
- Department of Gastroenterology and HepatologyAmsterdam UMC, location AMCAmsterdamThe Netherlands
| | | | - Mark Löwenberg
- Department of Gastroenterology and HepatologyAmsterdam UMC, location AMCAmsterdamThe Netherlands
| | - Jaap Stoker
- Department of Radiology and Nuclear MedicineAmsterdam UMC, location AMCAmsterdamThe Netherlands
| | - Willem A. Bemelman
- Department of SurgeryAmsterdam UMC, location AMCAmsterdamThe Netherlands
| | - Geert R.A.M. D’Haens
- Department of Gastroenterology and HepatologyAmsterdam UMC, location AMCAmsterdamThe Netherlands
| | - Rob A. van Hulst
- Department of Anesthesiology/Hyperbaric MedicineAmsterdam UMC, location AMCAmsterdamThe Netherlands
| |
Collapse
|
|
30
|
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] [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.
Collapse
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
| |
Collapse
|
|
31
|
Villiger R, Cabalzar-Wondberg D, Zeller D, Frei P, Biedermann L, Schneider C, Scharl M, Rogler G, Turina M, Rickenbacher A, Misselwitz B. Perianal fistulodesis – A pilot study of a novel minimally invasive surgical and medical approach for closure of perianal fistulae. World J Gastrointest Surg 2021; 13:187-197. [PMID: 33643538 PMCID: PMC7898183 DOI: 10.4240/wjgs.v13.i2.187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/20/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Perianal fistulae strongly impact on quality of life of affected patients.
AIM To challenge and novel minimally invasive treatment options are needed.
METHODS Patients with Crohn’s disease (CD) in remission and patients without inflammatory bowel disease (non-IBD patients) were treated with fistulodesis, a method including curettage of fistula tract, flushing with acetylcysteine and doxycycline, Z-suture of the inner fistula opening, fibrin glue instillation, and Z-suture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks. Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included. The primary end point was fistula healing, defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk.
RESULTS Fistulodesis was performed in 17 non-IBD and 3 CD patients, with a total of 22 fistulae. After 24 wk, all fistulae were healed in 4 non-IBD and 2 CD patients (overall 30%) and fistula remained closed until the end of follow-up at 10-25 mo. In a secondary per-fistula analysis, 7 out of 22 fistulae (32%) were closed. Perianal disease activity index (PDAI) improved in patients with fistula healing. Low PDAI was associated with favorable outcome (P = 0.0013). No serious adverse events were observed.
CONCLUSION Fistulodesis is feasible and safe for perianal fistula closure. Overall success rates is at 30% comparable to other similar techniques. A trend for better outcomes in patients with low PDAI needs to be confirmed.
Collapse
Affiliation(s)
- Roxanne Villiger
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
| | | | - Daniela Zeller
- Department of Surgery, Zeller Surgery, Zurich 8008, Switzerland
| | - Pascal Frei
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Christian Schneider
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Michael Scharl
- Department of Gastroenterology, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Matthias Turina
- Visceral- and Transplant Surgery, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Andreas Rickenbacher
- Visceral- and Transplant Surgery, University Hospital of Zurich, Zurich 8091, Switzerland
| | - Benjamin Misselwitz
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich 8091, Switzerland
- Visceral Surgery and Medicine, University Hospital of Bern, Bern 3010, Switzerland
| |
Collapse
|
|
32
|
The use of magnetic resonance imaging technique and 3D printing in order to develop a three-dimensional fistula model for patients with Crohn's disease: personalised medicine. GASTROENTEROLOGY REVIEW 2020; 16:83-88. [PMID: 33986892 PMCID: PMC8112265 DOI: 10.5114/pg.2020.101629] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 12/12/2019] [Indexed: 11/30/2022]
Abstract
Introduction Preoperative evaluation of magnetic resonance (MR) images may not be sufficient for the precise planning of anal fistula surgery or for stem cell therapy. Three-dimensional (3D) printing allows one to obtain spatial structures in a 1 : 1 scale with unprecedented precision. Aim To combine magnetic resonance imaging (MRI) with 3D printing for more precise visualisation of perianal Crohn’s disease. Material and methods MRI at 1.5T and a 3D printer were used. DICOM (Digital imaging and communications in medicine) images were imported into 3D Slicer v.4.8.0. Firstly, anal fistula was modelled on the basis of axial images. Fistula locations, the anus and anal canal, were marked with different coloured markers. The last step was to mark the skin that was connected to the anus and contact areas of the fistula with the skin. The prepared models were then exported to an STL format file. The anal fistula model was printed using a 3D printer. The development of the model, including printing, took approximately 6 h. Results and conclusions The accessibility of a rotatable 3D model before surgery allows for a more precise detection of the location and the degree of perianal disease. Moreover, this may also lower the inter-observer bias connected with interpretation of complex MR imaging before planned surgery. Development of MRI image transfer to 3D printing and the decreasing cost of 3D printers suggests a promising future of this technology in medical applications.
Collapse
|
|
33
|
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]
|
|
34
|
Adegbola SO, Sahnan K, Twum-Barima C, Iqbal N, Reza L, Lung P, Warusavitarne J, Tozer P, Hart A. Current review of the management of fistulising perianal Crohn's disease. Frontline Gastroenterol 2020; 12:515-523. [PMID: 34712470 PMCID: PMC8515276 DOI: 10.1136/flgastro-2020-101489] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 07/03/2020] [Accepted: 07/05/2020] [Indexed: 02/04/2023] Open
Abstract
Perianal manifestations of Crohn's disease constitute a distinct disease phenotype commonly affecting patients and conferring an increased risk of disability and disease burden. Much research has gone into management of fistulising manifestations, with biological therapy changing the landscape of treatment. In this article, we discuss the up-to-date surgical and medical management of perianal fistulas, highlighting current consensus management guidelines and the evidence behind them, as well as future directions in management.
Collapse
Affiliation(s)
- Samuel O Adegbola
- St Mark's Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Kapil Sahnan
- St Mark's Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Charlene Twum-Barima
- St Mark's Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Nusrat Iqbal
- St Mark's Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Lillian Reza
- St Mark's Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Phillip Lung
- St Mark's Hospital and Academic Institute, Harrow, UK
| | - Janindra Warusavitarne
- St Mark's Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Phil Tozer
- St Mark's Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Ailsa Hart
- St Mark's Hospital and Academic Institute, Harrow, UK
- Department of Surgery and Cancer, Imperial College London, London, UK
| |
Collapse
|
|
35
|
Boscá MM, Alós R, Maroto N, Gisbert JP, Beltrán B, Chaparro M, Nos P, Mínguez M, Hinojosa J. Recommendations of the Crohn's Disease and Ulcerative Colitis Spanish Working Group (GETECCU) for the treatment of perianal fistulas of Crohn's disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:155-168. [PMID: 31870681 DOI: 10.1016/j.gastrohep.2019.09.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 09/12/2019] [Accepted: 09/21/2019] [Indexed: 02/06/2023]
Abstract
Recommendations are advice that is given and considered to be beneficial; however, they are still suggestions and are therefore open to different interpretations. In this sense, the final objective of the review has been to try to homogenize, with the evidence available, the approach to the diagnosis and medical/surgical treatment of one of the most complex manifestations of Crohn's disease, such as simple and complex perianal fistulas.
Collapse
Affiliation(s)
- Marta M Boscá
- Servicio de Medicina Digestiva, Hospital Clínico Universitario, Valencia, España
| | - Rafael Alós
- Servicio de Cirugía General y Digestiva, Hospital Universitario La Fe, Valencia, España
| | - Nuria Maroto
- Servicio de Medicina Digestiva, Hospital Universitario de Manises, Manises, Valencia, España
| | - Javier P Gisbert
- Servicio de Medicina Digestiva, Hospital Universitario de La Princesa, Madrid, España
| | - Belén Beltrán
- Servicio de Medicina Digestiva, Hospital Universitario La Fe, Valencia, España
| | - María Chaparro
- Servicio de Medicina Digestiva, Hospital Universitario de La Princesa, Madrid, España
| | - Pilar Nos
- Servicio de Medicina Digestiva, Hospital Universitario La Fe, Valencia, España
| | - Miguel Mínguez
- Servicio de Medicina Digestiva, Hospital Clínico Universitario, Valencia, España
| | - Joaquín Hinojosa
- Servicio de Medicina Digestiva, Hospital Universitario de Manises, Manises, Valencia, España.
| |
Collapse
|
|
36
|
Recommendations of the Crohn’s Disease and Ulcerative Colitis Spanish Working Group (GETECCU) for the treatment of perianal fistulas of Crohn’s disease. ACTA ACUST UNITED AC 2020. [DOI: 10.1016/j.gastre.2019.09.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
|
|
37
|
|
|
38
|
Zhang M, Wang X, Jiang X, Yang X, Wen C, Zhi M, Gao X, Hu P, Liu H. Polymorphisms of the TNF Gene and Three Susceptibility Loci Are Associated with Crohn's Disease and Perianal Fistula Crohn's Disease: A Study among the Han Population from South China. MEDICAL SCIENCE MONITOR : INTERNATIONAL MEDICAL JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2019; 25:9637-9650. [PMID: 31844038 PMCID: PMC6929548 DOI: 10.12659/msm.917244] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Background Although 90 susceptibility loci of Crohn’s disease (CD) have been confirmed in the Asian population, susceptibility genes for perianal fistula of CD (pCD) in this population remain unknown. This study explored susceptibility genes for CD and pCD in the Han population from South China. Material/Methods In total, 490 patients diagnosed with CD between July 2012 and June 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were included and divided into the CD group (n=240) and the pCD group (n=250). The healthy control group was composed of 260 volunteers. Peripheral blood samples were taken, and single nucleotide polymorphism (SNP) locus sequencing was used to screen for susceptibility loci. SNPs were sequenced using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Results Nine SNPs in TNFSF1 on chromosome 9 were associated with CD. Among them, the rs6478106 locus is a risk locus for CD. The distribution frequency of the T allele of the rs6478106 SNP was significantly different between cases and controls (32.49% versus 18.27%, P<0.001). Rs72553867, located in the IRGM gene on chromosome 5, rs4409764, located in the NKX2–3 gene on chromosome 10, and rs3731772, located in the AOX1 gene on chromosome 2, were susceptibility factors for pCD. Nine SNPs located in TNFSF15 on chromosome 9 were related to CD in Han individuals from Southern China. Conclusions The rs6478106 T allele is associated with the risk of CD in the investigated population. SNPs rs72553867 (IRGM gene), rs4409764 (NKX2–3 gene), and rs3731772 (AOX1 gene) increase the risk of pCD.
Collapse
Affiliation(s)
- Min Zhang
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland)
| | - Xiaoyan Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland).,Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)
| | - Xiaodong Jiang
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland)
| | - Xiangling Yang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland).,Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)
| | - Chuangyu Wen
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland).,Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)
| | - Min Zhi
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland)
| | - Xiang Gao
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland)
| | - Pinjin Hu
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland)
| | - Huanliang Liu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland).,Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)
| |
Collapse
|
|
39
|
Hindryckx P, Jairath V, Zou G, Feagan BG, Sandborn WJ, Stoker J, Khanna R, Stitt L, van Viegen T, Shackelton LM, Taylor SA, Santillan C, Mearadji B, D'Haens G, Richard MP, Panes J, Rimola J. Development and Validation of a Magnetic Resonance Index for Assessing Fistulas in Patients With Crohn's Disease. Gastroenterology 2019; 157:1233-1244.e5. [PMID: 31336124 DOI: 10.1053/j.gastro.2019.07.027] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 07/12/2019] [Accepted: 07/16/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS There is no validated magnetic resonance imaging (MRI) index for assessment of perianal fistulas in patients with Crohn's disease (CD). We developed and internally validated a new instrument. METHODS We used paired baseline and week-24 MRI scans from 160 participants in a randomized placebo-controlled trial of stem cell therapy for patients with perianal fistulizing CD. Four radiologists scored disease activity using index items identified during previous studies and exploratory items. Reliability was assessed using intraclass correlation coefficients. We developed an index using backward elimination linear regression analysis, in which potential independent variables were items having intraclass correlation coefficients of at least 0.4 and the dependent variable was perianal fistulizing disease activity, measured on a 100-mm visual analogue scale. The final model was internally validated using the .632 bootstrap method to correct model optimism and quantify calibration accuracy. We evaluated responsiveness of the index by assessing longitudinal validity and estimating standardized effect sizes. RESULTS We developed the magnetic resonance novel index for fistula imaging in CD (MAGNIFI-CD) using 6 items. The optimism-corrected R2 of the model was 0.71, which was comparable to R2 for the original sample (0.74). The calibration slope for the model was 0.98. Compared with the original and modified versions of the Van Assche Index, the MAGNIFI-CD had improved operating characteristics. Estimates of intraclass correlation coefficients for MAGNIFI-CD, the modified Van Assche Index, and Van Assche Index were 0.85 (95% confidence interval [CI], 0.77-0.90), 0.81 (95% CI, 0.74-0.86), and 0.81 (95% CI, 0.71-0.86) for intra-rater reliability, and 0.74 (95% CI, 0.63-0.80), 0.67 (95% CI, 0.55-0.75) and 0.68 (95% CI, 0.56-0.77) for inter-rater reliability. Corresponding standardized effect size estimates were 1.02 (95% CI, 0.65-1.39), 0.84 (95% CI, 0.48-1.21), and 0.68 (95% CI, 0.33-1.03). CONCLUSIONS We developed an index called the MAGNIFI-CD, which is based on 6 items. It assesses MRI data and determines perianal fistulizing CD activity with improved operating characteristics compared to previous indices. This index may be used as an outcome measure in clinical trials comparing treatment effects in patients with perianal fistulizing CD. Although the performance of the MAGNIFI-CD indicates its stability and reasonable external validity, external validation is needed.
Collapse
Affiliation(s)
- Pieter Hindryckx
- Robarts Clinical Trials, Inc, London, Ontario, Canada; Department of Gastroenterology, University of Ghent, Ghent, Belgium
| | - Vipul Jairath
- Robarts Clinical Trials, Inc, London, Ontario, Canada; Department of Medicine, Division of Gastroenterology, University of Western Ontario, London, Ontario, Canada; Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada.
| | - Guangyong Zou
- Robarts Clinical Trials, Inc, London, Ontario, Canada; Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
| | - Brian G Feagan
- Robarts Clinical Trials, Inc, London, Ontario, Canada; Department of Medicine, Division of Gastroenterology, University of Western Ontario, London, Ontario, Canada; Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
| | - William J Sandborn
- Robarts Clinical Trials, Inc, London, Ontario, Canada; Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Reena Khanna
- Robarts Clinical Trials, Inc, London, Ontario, Canada; Department of Medicine, Division of Gastroenterology, University of Western Ontario, London, Ontario, Canada
| | - Larry Stitt
- Robarts Clinical Trials, Inc, London, Ontario, Canada; Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
| | | | | | - Stuart A Taylor
- Centre for Medical Imaging, University College London, London, UK
| | - Cynthia Santillan
- Department of Radiology, University of California San Diego, La Jolla, California
| | - Banafsche Mearadji
- Department of Radiology and Nuclear Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Geert D'Haens
- Robarts Clinical Trials, Inc, London, Ontario, Canada; Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, The Netherlands
| | | | - Julian Panes
- Department of Gastroenterology, Hospital Clínic de Barcelona, The August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Barcelona, Spain
| | - Jordi Rimola
- Department of Radiology, Hospital Clínic de Barcelona, Barcelona, Spain
| |
Collapse
|
|
40
|
Rencz F, Stalmeier PFM, Péntek M, Brodszky V, Ruzsa G, Gönczi L, Palatka K, Herszényi L, Schäfer E, Banai J, Rutka M, Gulácsi L, Lakatos PL. Patient and general population values for luminal and perianal fistulising Crohn's disease health states. THE EUROPEAN JOURNAL OF HEALTH ECONOMICS : HEPAC : HEALTH ECONOMICS IN PREVENTION AND CARE 2019; 20:91-100. [PMID: 31102158 PMCID: PMC6544586 DOI: 10.1007/s10198-019-01065-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 04/13/2019] [Indexed: 05/04/2023]
Abstract
BACKGROUND In patients with Crohn's disease (CD), luminal disease activity paralleled by perianal fistulas may seriously impair health-related quality of life (HRQoL). Health utility values are not available from patients with CD that reflect the health loss associated with both luminal and perianal CD. OBJECTIVE To generate utilities for luminal and concomitant perianal fistulising CD health states directly from patients and from members of the general public. METHODS A cross-sectional survey was undertaken enrolling CD patients and a convenience sample of members of the general population. Respondents were asked to evaluate four common CD heath states [severe luminal disease (sCD), mild luminal disease (mCD), severe luminal disease with active perianal fistulas (sPFCD), and mild luminal disease with active perianal fistulas (mPFCD)] by 10-year time trade-off (TTO). In addition, patients assessed their current HRQoL by the TTO method. RESULTS Responses of 206 patients (40.8% with perianal fistulas) and 221 members of the general population were analysed. Mean ± SD utilities among patients for sPFCD, sCD, mPFCD and mCD states were 0.69 ± 0.33, 0.73 ± 0.31, 0.80 ± 0.29 and 0.87 ± 0.26. Corresponding values in the general public were: 0.59 ± 0.31, 0.65 ± 0.29, 0.80 ± 0.26 and 0.88 ± 0.25. Patients with active perianal fistulas, previous non-resection surgeries, and higher pain intensity scores valued their current health as worse (p < 0.05). CONCLUSIONS TTO is a feasible method to assess HRQoL in patients with perianal fistulising disease, often not captured by health status questionnaires. Utilities from this study are intended to support the optimization of treatment-related decision making in patients with luminal disease paralleled by active perianal fistulas.
Collapse
Affiliation(s)
- Fanni Rencz
- Department of Health Economics, Corvinus University of Budapest, Fővám tér 8, 1093, Budapest, Hungary.
- Premium Postdoctoral Research Program, Hungarian Academy of Sciences, Nádor u. 7, 1051, Budapest, Hungary.
| | - Peep F M Stalmeier
- Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Márta Péntek
- Department of Health Economics, Corvinus University of Budapest, Fővám tér 8, 1093, Budapest, Hungary
| | - Valentin Brodszky
- Department of Health Economics, Corvinus University of Budapest, Fővám tér 8, 1093, Budapest, Hungary
| | - Gábor Ruzsa
- Doctoral School of Psychology, Institute of Psychology, Eötvös Loránd University of Sciences, Izabella u. 46, 1064, Budapest, Hungary
- Department of Statistics, Corvinus University of Budapest, Fővám tér 8, 1093, Budapest, Hungary
| | - Lóránt Gönczi
- 1st Department of Medicine, Semmelweis University, Korányi Sándor u. 2/a, 1083, Budapest, Hungary
| | - Károly Palatka
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary
| | - László Herszényi
- Medical Centre, Hungarian Defence Forces, Podmaniczky u. 109-111, 1062, Budapest, Hungary
| | - Eszter Schäfer
- Medical Centre, Hungarian Defence Forces, Podmaniczky u. 109-111, 1062, Budapest, Hungary
| | - János Banai
- Medical Centre, Hungarian Defence Forces, Podmaniczky u. 109-111, 1062, Budapest, Hungary
| | - Mariann Rutka
- 1st Department of Internal Medicine, University of Szeged, Korányi fasor 8-10, 6720, Szeged, Hungary
| | - László Gulácsi
- Department of Health Economics, Corvinus University of Budapest, Fővám tér 8, 1093, Budapest, Hungary
| | - Peter L Lakatos
- 1st Department of Medicine, Semmelweis University, Korányi Sándor u. 2/a, 1083, Budapest, Hungary
- Division of Gastroenterology, McGill University, MUHC, Montreal General Hospital, 1650 Ave. Cedar, D16.173.1, Montreal, QC, H3G 1A4, Canada
| |
Collapse
|
|
41
|
Park SH, Aniwan S, Scott Harmsen W, Tremaine WJ, Lightner AL, Faubion WA, Loftus EV. Update on the Natural Course of Fistulizing Perianal Crohn's Disease in a Population-Based Cohort. Inflamm Bowel Dis 2019; 25:1054-1060. [PMID: 30346531 PMCID: PMC6505440 DOI: 10.1093/ibd/izy329] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND This study sought to re-estimate the cumulative incidence of perianal or rectovaginal fistulas and the associated proctectomy rate in the prebiologic era vs the biologic era using a population-based cohort of Crohn's disease (CD) patients. METHODS The medical records of 414 residents of Olmsted County, Minnesota, who were diagnosed with CD between 1970 and 2010 were reviewed. The cumulative incidence of perianal or rectovaginal fistulas from time of CD diagnosis and the cumulative rate of proctectomy from date of first perianal or rectovaginal fistula diagnosis were estimated using the Kaplan-Meier method. RESULTS Eighty-five patients (20.5%) diagnosed with CD between 1970 and 2010 had at least 1 perianal or rectovaginal fistula episode between January 1, 1970, and June 30, 2016. The cumulative incidence of perianal or rectovaginal fistulas was 18% after 10 years, 23% after 20 years, and 24% after 30-40 years from CD diagnosis. The cumulative incidence of perianal or rectovaginal fistulas was significantly lower in patients diagnosed in 1998 or after than in patients diagnosed before 1998 (P = 0.03, log-rank). Among 85 patients developing perianal or rectovaginal fistulas, 16 patients (18.8%) underwent proctectomy for the treatment of perianal or rectovaginal fistulas during follow-up. CONCLUSIONS In a population-based inception cohort of CD, one-fifth of patients were diagnosed with at least 1 perianal or rectovaginal fistula. The cumulative probability of perianal or rectovaginal fistulizing disease has decreased over time.
Collapse
Affiliation(s)
- Sang Hyoung Park
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota,Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Satimai Aniwan
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota,Division of Gastroenterology, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - W Scott Harmsen
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - William J Tremaine
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Amy L Lightner
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - William A Faubion
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota,Address correspondence to: Edward V. Loftus Jr., MD, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905 ()
| |
Collapse
|
|
42
|
Deep remission on magnetic resonance imaging impacts outcomes of perianal fistulizing Crohn's disease. Dig Liver Dis 2019; 51:358-363. [PMID: 30612820 DOI: 10.1016/j.dld.2018.12.010] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 12/11/2018] [Accepted: 12/12/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND The long-term management of perianal Crohn's disease for patients on anti-TNF-α therapy remains challenging. AIM To evaluate the long-term course and complications of patients with perianal fistulas treated with anti-TNF-α based on their clinical remission and healing on MRI. METHODS Patients were evaluated clinically and by MRI. Deep remission was defined as clinical remission associated with the absence of contrast enhancement and T2 hyperintensity on MRI. Flare-free survival, surgery and hospitalizations were compared based on the presence or not of deep remission. RESULTS Forty-eight consecutive patients were included with a median follow-up of 62 months after anti-TNF-α first administration. Deep remission was observed in 16 patients (33.4%). For patients in deep remission, the median time to any perianal event was 116 months (95-130) versus 42 months (8-72) in patients with pathological MRI (p < 0.001). Sixteen patients (50%) with pathological MRI had perianal surgery versus 2 (12.5%) in the deep remission group (p < 0.05). The mean duration of cumulative hospital stays was 0.75 ± 0.52 days in the deep remission group versus 19.7 ± 7.4 in the pathological group (p < 0.05). CONCLUSIONS Higher flare-free survival and lower rates of surgery and hospitalization were found in patients achieving deep remission.
Collapse
|
|
43
|
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.
Collapse
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
| | | | | |
Collapse
|
|
44
|
Álvarez JP, Coloma R, Leiva A, Berry M, Urrutia L, Yañez S, Galecio J, Ramos G, Cárcamo M, Fernández A, Guerrero M. Efecto de ketamina intraoperatoria sobre consumo de morfina durante 24 horas postoperatorias de pacientes obesos sometidos a gastrectomía en manga por videolaparoscopía. Ensayo Clínico Controlado Aleatorizado. REVISTA MÉDICA CLÍNICA LAS CONDES 2018. [DOI: 10.1016/j.rmclc.2018.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
|
|
45
|
Ibáñez P, Quera R, Lubascher J, Figueroa C, Pizarro G, Kronberg U, Flores L, Simian D. Algoritmos de tratamiento de la enfermedad de Crohn desde una experiencia local. REVISTA MÉDICA CLÍNICA LAS CONDES 2018. [DOI: 10.1016/j.rmclc.2018.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
46
|
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] [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.
Collapse
|
|
47
|
Yan X, Zhu M, Feng Q, Yan Y, Peng J, Xu X, Xu A, Ran Z. Evaluating the effectiveness of infliximab on perianal fistulizing Crohn's disease by magnetic resonance imaging. Gastroenterol Rep (Oxf) 2018; 7:50-56. [PMID: 30792866 PMCID: PMC6375345 DOI: 10.1093/gastro/goy036] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 06/11/2018] [Accepted: 07/05/2018] [Indexed: 12/23/2022] Open
Abstract
Background and aim Data on the radiologic evaluation of perianal fistulizing Crohn’s disease (PFCD) naïve to anti-tumor necrosis factor therapy are scarce, especially in Asian populations. We assessed the effectiveness of infliximab (IFX) on PFCD and explored predictors of ‘deep remission’ based on clinical and radiologic assessments. Methods Patients with Crohn’s disease and active anal fistulas attending our care center for IFX therapy were prospectively enrolled. Each patient underwent clinical examination according to the Fistula Drainage Assessment Index, endoscopy for assessment of Crohn’s Disease Activity Index (CDAI) and Perianal Crohn’s Disease Activity Index (PCDAI), magnetic resonance imaging (MRI) to determine Van Assche score and Ng score, and laboratory tests up to 2 weeks prior to the start of and up to 2 weeks after the sixth IFX therapy (Week 32). Results Among 38 patients treated with IFX, 52.6% achieved clinical remission based on the Fistula Drainage Assessment Index and 42.1% achieved deep remission based on Ng score. Van Assche score (from 14.5 ± 4.26 to 7.36 ± 7.53), CDAI (from 170 ± 92 to 71 ± 69) and PCDAI (from 7.45 ± 2.65 to 2.44 ± 3.20) decreased significantly after six IFX treatments. The only predictor of deep remission was simple fistula (P = 0.004, odds ratio = 3.802, 95% confidence interval: 1.541–9.383). Conclusions IFX has been shown to have appreciable effectiveness in Chinese patients with PFCD. MRI is the gold standard for evaluating PFCD, but Van Assche score has some limitations.
Collapse
Affiliation(s)
- Xiaohan Yan
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; Shanghai Inflammatory Bowel Disease Research Center; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Mingming Zhu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; Shanghai Inflammatory Bowel Disease Research Center; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qi Feng
- Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yunqi Yan
- Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jiangchen Peng
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; Shanghai Inflammatory Bowel Disease Research Center; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xitao Xu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; Shanghai Inflammatory Bowel Disease Research Center; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Antao Xu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; Shanghai Inflammatory Bowel Disease Research Center; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhihua Ran
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; Shanghai Inflammatory Bowel Disease Research Center; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| |
Collapse
|
|
48
|
Gecse KB, Vermeire S. Differential diagnosis of inflammatory bowel disease: imitations and complications. Lancet Gastroenterol Hepatol 2018; 3:644-653. [PMID: 30102183 DOI: 10.1016/s2468-1253(18)30159-6] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 04/23/2018] [Accepted: 04/24/2018] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel disease (IBD) is characterised by episodes of relapse and periods of remission. However, the clinical features, such as abdominal pain, diarrhoea, and rectal bleeding, are not specific. Therefore, the differential diagnosis can include a broad spectrum of inflammatory or infectious diseases that mimic IBD, as well as others that might complicate existing IBD. In this Review, we provide an overview of ileocolitis of diverse causes that are relevant in the differential diagnosis of IBD. We highlight the importance of accurate patient profiling and give a practical approach to identifying factors that should trigger the search for a specific cause of intestinal inflammation. Mimics of IBD include not only infectious causes of colitis-and particular attention is required for patients from endemic areas of tuberculosis-but also vascular diseases, diversion colitis, diverticula or radiation-related injuries, drug-induced inflammation, and monogenic diseases in very-early-onset refractory disease. A superinfection with cytomegalovirus or Clostridium difficile can aggravate intestinal inflammation in IBD, especially in patients who are immunocompromised. Special consideration should be made to the differential diagnosis of perianal disease.
Collapse
Affiliation(s)
- Krisztina B Gecse
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands
| | - Severine Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
| |
Collapse
|
|
49
|
Tozer PJ, Lung P, Lobo AJ, Sebastian S, Brown SR, Hart AL, Fearnhead N. Review article: pathogenesis of Crohn's perianal fistula-understanding factors impacting on success and failure of treatment strategies. Aliment Pharmacol Ther 2018; 48:260-269. [PMID: 29920706 DOI: 10.1111/apt.14814] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Revised: 01/22/2018] [Accepted: 04/30/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Evidence from groups who have studied fistula aetiology and extrapolation from interventional studies supports a multifactorial hypothesis of Crohn's perianal fistula, with several pathophysiological elements that may contribute to fistula formation, persistence and resistance to treatment. AIM An evidence synthesis of current understanding of pathophysiological factors underlying Crohn's perianal fistula is presented, exploring the fundamental reasons why some treatments succeed and others fail, as a means of focussing clinical knowledge on improving treatment of Crohn's perianal fistula. METHODS Evidence to support this review was gathered via the Pubmed database. Studies discussing pathophysiological factors underpinning perianal fistula, particularly in Crohn's disease, were reviewed and cross-referenced for additional reports. RESULTS Pathophysiological factors that impact on success or failure of interventions for Crohn's perianal fistulae include the high-pressure zone, obliterating the dead space, disconnecting the track from the anus, removing epithelialisation, eradicating sepsis and by-products of bacterial colonisation, correcting abnormalities in wound repair and removing the pro-inflammatory environment which allows fistula persistence. Most current interventions for Crohn's perianal fistulae tend to focus on a single, or at best two, aspects of the pathophysiology of Crohn's anal fistulae; as a result, failure to heal fully is common. CONCLUSIONS For an intervention or combination of interventions to succeed, multiple factors must be addressed. We hypothesise that correct, timely and complete attention to all of these factors in a multimodal approach represents a new direction that may enable the creation of an effective treatment algorithm for Crohn's anal fistula.
Collapse
Affiliation(s)
- P J Tozer
- St Mark's Hospital and Imperial College London, London, UK
| | - P Lung
- St Mark's Hospital and Imperial College London, London, UK
| | - A J Lobo
- Academic Unit of Gastroenterology, University of Sheffield, Sheffield, UK
| | - S Sebastian
- IBD Unit, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK
| | - S R Brown
- Sheffield Teaching Hospitals, Sheffield, UK
| | - A L Hart
- St Mark's Hospital and Imperial College London, London, UK
| | - N Fearnhead
- Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| |
Collapse
|
|
50
|
Adegbola SO, Pisani A, Sahnan K, Tozer P, Ellul P, Warusavitarne J. Medical and surgical management of perianal Crohn's disease. Ann Gastroenterol 2018; 31:129-139. [PMID: 29507460 PMCID: PMC5825943 DOI: 10.20524/aog.2018.0236] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 11/24/2017] [Indexed: 12/16/2022] Open
Abstract
Crohn's disease is increasingly thought to encompass multiple possible phenotypes. Perianal manifestations account for one such phenotype and represent an independent disease modifier. In its more severe form, perianal Crohn's disease confers a higher risk of a severe and disabling disease course, relapses, hospital admissions and operations. This, in turn, imposes a considerable burden and disability on patients. Identification of the precise manifestation is important, as management is nuanced, with both medical and surgical components, and is best undertaken in a multidisciplinary setting for both diagnosis and ongoing treatment. The introduction of biologic medication has heralded a significant addition to the management of fistulizing perianal Crohn's disease in particular, albeit with modest results. It remains a very challenging condition to treat and further work is required to optimize management in this group of patients.
Collapse
Affiliation(s)
- Samuel O. Adegbola
- Department of Colorectal Surgery St. Mark’s Hospital, Harrow, United Kingdom (Samuel O. Adegbola, Kapil Sahnan, Phil Tozer, Janindra Warusavitarne)
- Department of Surgery and Cancer, Imperial College, London, United Kingdom (Samuel O. Adegbola, Kapil Sahnan, Phillip Tozer, Janindra Warusavitarne)
| | - Anthea Pisani
- Department of Gastroenterology, Mater dei Hospital, Malta (Pierre Ellul)
| | - Kapil Sahnan
- Department of Colorectal Surgery St. Mark’s Hospital, Harrow, United Kingdom (Samuel O. Adegbola, Kapil Sahnan, Phil Tozer, Janindra Warusavitarne)
- Department of Surgery and Cancer, Imperial College, London, United Kingdom (Samuel O. Adegbola, Kapil Sahnan, Phillip Tozer, Janindra Warusavitarne)
| | - Phil Tozer
- Department of Colorectal Surgery St. Mark’s Hospital, Harrow, United Kingdom (Samuel O. Adegbola, Kapil Sahnan, Phil Tozer, Janindra Warusavitarne)
- Department of Surgery and Cancer, Imperial College, London, United Kingdom (Samuel O. Adegbola, Kapil Sahnan, Phillip Tozer, Janindra Warusavitarne)
| | - Pierre Ellul
- Department of Gastroenterology, Mater dei Hospital, Malta (Pierre Ellul)
| | - Janindra Warusavitarne
- Department of Colorectal Surgery St. Mark’s Hospital, Harrow, United Kingdom (Samuel O. Adegbola, Kapil Sahnan, Phil Tozer, Janindra Warusavitarne)
- Department of Surgery and Cancer, Imperial College, London, United Kingdom (Samuel O. Adegbola, Kapil Sahnan, Phillip Tozer, Janindra Warusavitarne)
| |
Collapse
|