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Anand E, Pelly T, Joshi S, Shakweh E, Hanna LN, Hart A, Tozer P, Lung P. Current practice and innovations in diagnosing perianal fistulizing Crohn's disease (pfCD): a narrative review. Tech Coloproctol 2025; 29:102. [PMID: 40232330 PMCID: PMC12000175 DOI: 10.1007/s10151-025-03122-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 02/23/2025] [Indexed: 04/16/2025]
Abstract
Perianal fistulizing Crohn's disease (pfCD) represents a severe manifestation of Crohn's disease (CD) that often leads to significant morbidity. Clinical examination alone of perianal fistulae is unlikely to be sufficient in the context of complex pfCD, as patients are likely to have complex disease and are more likely to experience complications, treatment failure, and recurrent disease. Furthermore, the relapsing-remitting nature of Crohn's disease and our limited understanding of the pathogenesis of this potentially destructive disease necessitate regular examination and radiological assessment, often in the form of magnetic resonance imaging (MRI). Recent advancements in diagnostic techniques have enhanced the accuracy and timeliness of pfCD diagnosis, facilitating better patient outcomes. A growing appreciation of isolated perianal Crohn's disease has prompted a recent attempt to develop consensus recommendations on diagnosing and treating this group of patients who would previously not have been offered CD medications. This narrative review aims to summarize current practice and the latest developments in the diagnosis of pfCD, highlighting: 1. Clinical examination and assessment tools 2. Current imaging practices 3. Innovations in imaging and biomarkers 4. The diagnosis of isolated perianal Crohn's disease.
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Affiliation(s)
- E Anand
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK.
- Imperial College London, London, UK.
| | - T Pelly
- Imperial College London, London, UK
| | - S Joshi
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
- Imperial College London, London, UK
| | - E Shakweh
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
- Imperial College London, London, UK
| | - L N Hanna
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
- Imperial College London, London, UK
| | - A Hart
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
- Imperial College London, London, UK
| | - P Tozer
- St Mark's The National Bowel Hospital, Central Middlesex, Acton Lane, London, UK
- Imperial College London, London, UK
| | - P Lung
- Imperial College London, London, UK
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Anand E, Joshi S, Reza L, Sahnan K, Lung P, Hart A, Tozer P. A systematic review of outcome measurement instruments used in pouch anal and vaginal fistulae: a COSMIN-based analysis. Qual Life Res 2025:10.1007/s11136-025-03911-4. [PMID: 40024986 DOI: 10.1007/s11136-025-03911-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2025] [Indexed: 03/04/2025]
Abstract
PURPOSE Pouch-related fistulae are devastating complications of ileoanal pouch surgery, which is performed to improve the quality of life (QoL) for patients who have had a proctocolectomy. Their management is limited by inconsistent evidence, including using poorly and heterogeneously defined outcomes. This study aims to identify all Outcome Measurement Instruments (OMIs) used in pouch fistula research, including Patient-Reported Outcome Measures (PROMs) and Clinician-Reported Outcome Measures (ClinROMs) and evaluate their quality using COSMIN guidelines to help select the best tool for a standardised core outcome measurement set in a future consensus study. METHODS A systematic review was conducted to identify all OMIs used in ileo-anal pouch fistulae studies, from MEDLINE, Embase, and the Cochrane Library. We evaluated existing OMIs based on COSMIN guidelines and used the GRADE approach to assess evidence quality. Results were synthesized narratively. RESULTS Among 91 studies, 13 OMIs were reviewed. Pouch-specific instruments performed poorly in key domains of reliability, validity, and responsiveness. Only 17.6% of studies assessed QoL using PROMs. The best-performing instruments were the SF-36 and IBDQ. The Ileoanal Pouch Syndrome Severity Score was the only pouch-specific instrument that involved patients in its development and although useful for pouch dysfunction, it lacks specific QoL assessment and was not validated in pouch-fistulae patients. CONCLUSION Existing OMIs for pouch-related fistulae lack adequate measurement properties, with no PROMs specifically validated for QoL in this population and very few instruments involving patients in their development. There is an unmet need for a validated PROM specifically for QoL in pouch-related fistulae.
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Affiliation(s)
- Easan Anand
- St Mark's the National Bowel Hospital, Acton Lane, London, UK.
- Imperial College London, Exhibition Road, London, UK.
| | - Shivani Joshi
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
| | - Lillian Reza
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
| | - Kapil Sahnan
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
| | - Phillip Lung
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
| | - Ailsa Hart
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
| | - Phil Tozer
- St Mark's the National Bowel Hospital, Acton Lane, London, UK
- Imperial College London, Exhibition Road, London, UK
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Bhalla A, Shahi A, Maity M, Safa F, Srividya V, Clementina R, Anugu GR, Younas S. Inflammatory Bowel Disease in Children: Current Diagnosis and Treatment Strategies. Cureus 2025; 17:e78462. [PMID: 40051947 PMCID: PMC11883196 DOI: 10.7759/cureus.78462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2025] [Indexed: 03/09/2025] Open
Abstract
Pediatric inflammatory bowel disease (PIBD), including Crohn's disease and ulcerative colitis, has emerged as a significant global health challenge with rising incidence rates. Unlike adult inflammatory bowel disease, PIBD presents complexities, including growth impairment, nutritional deficiencies, and psychosocial challenges that necessitate tailored management strategies. This article reviews current diagnostic and emerging treatment strategies to highlight the evolution from traditional therapies such as aminosalicylates, corticosteroids, and immunomodulators to advanced biologic agents like infliximab and adalimumab. Emerging biological therapies, including vedolizumab and ustekinumab, show promise, while novel small molecule therapies such as Janus kinase (JAK) inhibitors are under investigation for potential use in the pediatric population. Supportive treatments, including exclusive enteral nutrition, modified diets, and probiotics, play a critical role in comprehensive disease management. Stem cell therapy and fecal microbiota transplant represent innovative approaches still under clinical evaluation. The review underscores the significance of holistic care, incorporating mind-body interventions and psychosocial support to improve patient quality of life. Key challenges persist, such as infection risks associated with long-term biological therapy use, gaps in pediatric-specific guidelines, and the limited inclusion of children in clinical trials. Future recommendations emphasize the importance of structured transition programs bridging pediatric and adult care, regular updates to clinical guidelines, and the integration of precision medicine to personalize treatment plans. Continued research and collaboration are essential for advancing the understanding and management of PIBD, ensuring that pediatric patients benefit from the most effective, evidence-based care available.
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Affiliation(s)
- Akshita Bhalla
- Internal Medicine, Punjab Institute of Medical Sciences, Jalandhar, IND
| | - Anushka Shahi
- Internal Medicine, Sri Aurobindo Institute of Medical Sciences, Indore, IND
| | - Madhurima Maity
- Critical Care Medicine, Sir H.N Reliance Foundation Hospital, Mumbai, IND
| | - Fnu Safa
- Internal Medicine, Osmania Medical College, Hyderabad, IND
| | | | | | | | - Salma Younas
- Pharmacy, Punjab University College of Pharmacy, Lahore, PAK
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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.
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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
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Karki C, Hantsbarger G, Turkstra E, Fenu E, Genenz K, Gilaberte I, Panés J. Predictive modeling to evaluate long-term treatment effectiveness of darvadstrocel in patients with complex perianal fistulas in Crohn's disease. BMC Gastroenterol 2024; 24:479. [PMID: 39736547 DOI: 10.1186/s12876-024-03513-3] [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: 02/14/2024] [Accepted: 11/12/2024] [Indexed: 01/01/2025] Open
Abstract
BACKGROUND Current therapies for complex Crohn's perianal fistulas (CPF) have a limited ability to achieve long-term healing. Darvadstrocel (DVS) is an expanded allogeneic adipose-derived mesenchymal stem cell therapy that has demonstrated efficacy in treating complex CPF in clinical trials. There are, however, limited long-term comparative data with standard of care (SoC). The aim of this study was to combine clinical trial data and real-world evidence using statistical methodologies to predict long-term effectiveness of DVS versus SoC in patients with CPF. METHODS Data were pooled from a clinical trial (ADMIRE-CD) and two retrospective chart review studies (INSPECT and PREFACE). Predictive statistical models extrapolated clinical outcomes beyond observed follow-up using parametric curves, which were implemented into a semi-Markov model to obtain the number of patients in remission. The setting was multinational and multicenter. ADMIRE-CD was conducted in 49 hospitals in 7 European countries and Israel. INSPECT used data from the ADMIRE study. PREFACE involved patients from Belgium, France, Germany, Italy, and Spain. The participants were patients with complex CPF treated with DVS or SoC. Times to remission and relapse (clinical, and clinical plus patient-centric remission) were analyzed. Additionally, the proportion of patients in clinical and patient-centric remission was examined. RESULTS In total, 513 patients were included in the analysis (ADMIRE-CD [N = 200] and PREFACE [N = 313]). Patients in ADMIRE-CD and PREFACE were similar in age (median [interquartile range, IQR], 36 [20.0] versus 36 [22.0] years, respectively) and gender (males, 54% and 52%, respectively). The median (IQR) duration of Crohn's disease was 9.4 [11.3] years for patients in ADMIRE-CD and 6.5 [12.9] years for patients in PREFACE. The estimated time to remission was shorter for patients treated with DVS versus SoC. The estimated time to relapse was longer for patients treated with DVS versus SoC. A higher estimated proportion of patients treated with DVS versus SoC had clinical and patient-centric remission at 24 months (48% and 35%, respectively) and 48 months (49% and 32%, respectively). CONCLUSION This novel approach enabled pooled data from a clinical trial and real-world settings to predict long-term effectiveness of DVS versus SoC in patients with complex CPF.
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Affiliation(s)
| | | | | | | | - Ken Genenz
- Takeda Pharmaceuticals, Zurich, Switzerland
| | | | - Julián Panés
- Formerly Gastroenterology Department, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Hospital Clínic de Barcelona, Barcelona, Spain.
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Greveson K, Haj O, Hart A, Geransar P, Zmora O. Management of Perianal Fistulas Associated with Crohn Disease: A Nurse's Perspective. Gastroenterol Nurs 2024; 47:428-446. [PMID: 39186387 DOI: 10.1097/sga.0000000000000833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 05/01/2024] [Indexed: 08/28/2024] Open
Abstract
Crohn disease perianal fistulas are associated with considerable morbidity and impaired quality of life. Nurses who specialize in inflammatory bowel disease (IBD) play a vital role in the management of Crohn disease perianal fistulas from diagnosis to long-term care; however, there is little evidence available to inform Crohn associated perianal fistula management strategies for nurses. This narrative review aims to provide IBD nurses with an up-to-date overview of Crohn perianal fistulas. It discusses the vital role IBD nurses play within the multidisciplinary team; the physical, social, and psychological impacts of Crohn perianal fistulas on patients; available treatment options; and how IBD nurses can support patients in their perianal fistula journey to enable optimum outcomes for patients. It also reviews diagnostic techniques and IBD nurses' involvement in Crohn perianal fistula diagnosis. While this article is aimed at IBD nurses, it is relevant to all nurses irrespective of their role (unit, clinic, community, and stoma) who interact with patients with Crohn perianal fistulas because awareness of the signs and symptoms of this condition will enable timely referrals and diagnosis.
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Affiliation(s)
- Kay Greveson
- About the authors: Kay Greveson, RN, is at The London IBD Clinic, London, United Kingdom; Ola Haj, RN, MPH, is at the IBD Clinic, Gastroenterology Department, Sheba Medical Center, Derech Sheba 2, Ramat Gan, Israel; Ailsa Hart, MD, PhD, is a Professor at the IBD Department, St Mark's Hospital, Harrow, London, United Kingdom; Parnia Geransar, BPharm, PhD, was a Senior Global Medical Director, Global Medical Affairs - Rare GI at Takeda Pharmaceuticals International AG, Glattpark-Opfikon, Zurich, Switzerland at the time of manuscript development; and Oded Zmora, MD, is a Professor at the Department of Surgery, Shamir Medical Center, Be'er Ya'akov, Tel Aviv, Israel
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Piotrowicz G, Kot J, Babicki A, Banaszkiewicz P, Piotrowicz A, Rzeszutek M, Rudnik A, Zientara P, Adamska-Mieruszewska J, Rydzewska G. The effects of hyperbaric treatment on perianal fistula activity in patients with Crohn's disease. PRZEGLAD GASTROENTEROLOGICZNY 2024; 19:321-332. [PMID: 39802967 PMCID: PMC11718499 DOI: 10.5114/pg.2024.143439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 02/11/2024] [Indexed: 01/16/2025]
Abstract
Introduction Crohn's disease is a chronic, complex inflammatory disorder of the gastrointestinal tract. Among its most challenging complications are perianal fistulas. Aim This study aims to explore the efficacy of hyperbaric oxygen therapy (HBOT) in reducing the activity of perianal fistulas in Crohn's disease patients. Material and methods This study enrolled patients diagnosed with Crohn's disease-associated perianal fistulas, with a disease duration of at least 3 years. Participants underwent HBOT in conjunction with standard medical therapy. The therapeutic effects were assessed at predetermined intervals using the Crohn's Disease Activity Index (CDAI), and laboratory parameters including faecal calprotectin levels, C-reactive protein (CRP) activity, serum iron concentration, and peripheral blood haemoglobin levels. Additionally, the Simple Endoscopic Score for Crohn's Disease (SESCD) and the Perianal Disease Activity Index (PDAI) were employed for evaluation. Results The adjunctive use of HBOT with conventional therapy yielded significant clinical improvements in patients with Crohn's disease complicated by perianal fistulas. This was shown by an 81.8% improvement in CDAI scores and a 54.5% clinical remission rate, as determined by SESCD and PDAI. Notably, the beneficial effects of HBOT on SESCD, PDAI, and faecal calprotectin levels were statistically significant and persisted for 6 weeks post-HBOT, with sustained improvements observed in a follow-up assessment approximately 9 months after treatment. Conclusions The findings of this study suggest that HBOT may be a viable therapeutic adjunct in the management of complex cases of Crohn's disease, particularly those with recurrent symptoms and limited responsiveness to conventional treatments. HBOT demonstrated potential in improving clinical outcomes and achieving remission rates exceeding 50%, indicating its promise as a treatment modality in this patient population.
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Affiliation(s)
- Grażyna Piotrowicz
- Department of Gastroenterology, Self-Dependent Health Care Unit of Ministry of Interior and Administration, Gdansk, Poland
| | - Jacek Kot
- National Centre for Hyperbaric Medicine Institute of Maritime and Tropical Medicine in Gdynia, Medical University of Gdansk, Poland
- Department of Hyperbaric Medicine and Sea Rescue, University Centre for Maritime and Tropical Medicine, Gdynia, Poland
| | - Andrzej Babicki
- Department of Surgery, Self-Dependent Health Care Unit of Ministry of Interior and Administration, Gdansk, Poland
| | - Piotr Banaszkiewicz
- Department of Gastroenterology, Self-Dependent Health Care Unit of Ministry of Interior and Administration, Gdansk, Poland
| | - Adam Piotrowicz
- Department of Surgery, Self-Dependent Health Care Unit of Ministry of Interior and Administration, Gdansk, Poland
| | - Magdalena Rzeszutek
- Department of Gastroenterology, Self-Dependent Health Care Unit of Ministry of Interior and Administration, Gdansk, Poland
| | - Agata Rudnik
- Department of Gastroenterology, Self-Dependent Health Care Unit of Ministry of Interior and Administration, Gdansk, Poland
- Institute of Psychology, University of Gdansk, Gdansk, Poland
| | - Piotr Zientara
- Faculty of Economics, University of Gdansk, Gdansk, Poland
| | | | - Grażyna Rydzewska
- Department of Internal Medicine and Gastroenterology, Central Clinical Hospital of the Ministry of Interior and Administration, Warsaw, Poland
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
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Lightner AL, Irving PM, Lord GM, Betancourt A. Stem Cells and Stem Cell-Derived Factors for the Treatment of Inflammatory Bowel Disease with a Particular Focus on Perianal Fistulizing Disease: A Minireview on Future Perspectives. BioDrugs 2024; 38:527-539. [PMID: 38914783 PMCID: PMC11247053 DOI: 10.1007/s40259-024-00661-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/14/2024] [Indexed: 06/26/2024]
Abstract
Inflammatory bowel disease remains a difficult disease to effectively treat, especially fistulizing Crohn's disease. Perianal fistulas in the setting of Crohn's disease remain an area of unmet need with significant morbidity in this patient population. Up to one third of Crohn's patients will have perianal fistulizing disease and current medical and surgical interventions are of limited efficacy. Thus, most patients experience significant morbidity, narcotic use, and loss of employment and end up with multiple surgical interventions. Mesenchymal stem cells (MSCs) have shown efficacy in phase 3 clinical trials, but considerable infrastructure challenges make MSCs limited with regard to scalability in clinical practice. Extracellular vesicles, being derived from MSCs and capturing the secretome functionality of MSCs, offer similar physiological utility regarding mechanism, while also providing an off the shelf regenerative medicine product that could be widely used in daily clinical practice.
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Affiliation(s)
- Amy L Lightner
- Surgery, Scripps Clinic, 10667 N Torrey Pines Rd, La Jolla, CA, 92037, USA.
- Molecular Medicine, Scripps Research Institute, La Jolla, USA.
| | - Peter M Irving
- Guy's and St Thomas' Hospital, London, UK
- King's College London, London, UK
| | | | - Aline Betancourt
- Vitabolus Inc, San Diego, CA, USA
- Medicine, Tulane University School of Medicine, New Orleans, LA, USA
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Sohrabi M, Bahrami S, Mosalli M, Khaleghian M, Obaidinia M. Perianal Fistula; from Etiology to Treatment - A Review. Middle East J Dig Dis 2024; 16:76-85. [PMID: 39131109 PMCID: PMC11316198 DOI: 10.34172/mejdd.2024.373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 01/18/2024] [Indexed: 08/13/2024] Open
Abstract
Anal fistula has been a challenging clinical issue for years due to its complex pathogenesis. The risk of frequent recurrence and incontinence complicates long-term treatment. Recent scientific literature has reviewed new techniques used for anal fistula treatment in recent years, assessing the advantages and disadvantages of each based on clinical outcomes. Although surgery is the main method used to treat anal fistula, there is no simple technique that can completely heal complex anal fistula. The surgical treatment should consider the healing outcome and the protection of anal function comprehensively. Several innovative techniques have emerged in recent years, such as combined techniques based on drainage seton and LIFT-plug, which appear to be relatively effective therapies. However, more multi-center prospective trials with long-term follow-up are needed to validate their effectiveness. In some situations, medical treatment may also be considered.
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Affiliation(s)
- Masoudreza Sohrabi
- Gastrointestinal and liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Somayeh Bahrami
- Gastrointestinal and liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mozhdeh Mosalli
- Gastrointestinal and liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Khaleghian
- Gastrointestinal and liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of General Surgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mobin Obaidinia
- Gastrointestinal and liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
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Cheng F, Zhong H, Huang Z, Li Z. Up-to-date meta-analysis of long-term evaluations of mesenchymal stem cell therapy for complex perianal fistula. World J Stem Cells 2023; 15:866-875. [PMID: 37700821 PMCID: PMC10494567 DOI: 10.4252/wjsc.v15.i8.866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 06/21/2023] [Accepted: 07/19/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Local mesenchymal stem cell (MSC) therapy for complex perianal fistulas (PFs) has shown considerable promise. But, the long-term safety and efficacy of MSC therapy in complex PFs remain unknown. AIM To explore the long-term effectiveness and safety of local MSC therapy for complex PFs. METHODS Sources included the PubMed, EMBASE, and Cochrane Library databases. A standard meta-analysis was performed using RevMan 5.3. RESULTS After screening, 6 studies met the inclusion criteria. MSC therapy was associated with an improved long-term healing rate (HR) compared with the control condition [odds ratio (OR) = 2.13; 95% confidence interval (95%CI): 1.34 to 3.38; P = 0.001]. Compared with fibrin glue (FG) therapy alone, MSC plus FG therapy was associated with an improved long-term HR (OR = 2.30; 95%CI: 1.21 to 4.36; P = 0.01). When magnetic resonance imaging was used to evaluate fistula healing, MSC therapy was found to achieve a higher long-term HR than the control treatment (OR = 2.79; 95%CI: 1.37 to 5.67; P = 0.005). There were no significant differences in long-term safety (OR = 0.77; 95%CI: 0.27 to 2.24; P = 0.64). CONCLUSION Our study indicated that local MSC therapy promotes long-term and sustained healing of complex PFs and that this method is safe.
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Affiliation(s)
- Fang Cheng
- Division of Gastroenterology, Zigong First People's Hospital, Zigong 643000, Sichuan Province, China
- Department of Gastroenterology, Zigong First People's Hospital, Zigong 643000, Sichuan Province, China.
| | - Huang Zhong
- Department of Gastroenterology, Zigong First People's Hospital, Zigong 643000, Sichuan Province, China
| | - Zhong Huang
- Department of Gastroenterology, Zigong First People's Hospital, Zigong 643000, Sichuan Province, China
| | - Zhi Li
- Department of Gastroenterology, Zigong First People's Hospital, Zigong 643000, Sichuan Province, China
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Podmore B, Beier D, Burisch J, Genestin E, Haeckl D, Nagel O, Qizilbash N, Schwartz DA, Vavricka SR, Bennett D, Dignass A. Malignancy rates in Crohn's disease patients with perianal fistula: A German retrospective cohort study. United European Gastroenterol J 2023. [PMID: 37140403 DOI: 10.1002/ueg2.12396] [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: 12/22/2022] [Accepted: 03/30/2023] [Indexed: 05/05/2023] Open
Abstract
BACKGROUND Patients with inflammatory bowel disease are at increased risk of colorectal and extra-intestinal cancer. However, the overall cancer risk in patients with Crohn's disease (CD) with perianal fistulas (PF) (CPF) and those with CD without PF (non-PF CD) is unclear. OBJECTIVE To describe the prevalence and incidence of cancer in patients with CPF and non-PF CD, and to estimate incidence rate ratio (IRR) of cancer between CPF and non-PF CD groups. METHODS A retrospective cohort study was conducted using the German InGef (Institute for Applied Health Research Berlin) research database. Patients with a CD record and PF from 1 January 2013 to 31 December 2014 were identified and followed up from 1 January 2015 until the first occurrence of cancer, end of health insurance contributing data, death, or end of study period (31 December 2020). Prevalence of any type of cancer including patients with CD diagnosed with cancer in the selection period and incidence of cancer excluding patients with CD diagnosed with cancer in the selection period were calculated. RESULTS In total, 10,208 patients with CD were identified. Of 824 patients with CPF (8.1%), 67 had had a malignancy (6-year period crude malignancy prevalence 8.13% [95% confidence interval (CI) 6.36%-10.21%]), which was lower than patients with non-PF CD (19.8% [95% CI 19%-20.6%]). Incidence (per 100,000 person-years) in patients with CPF was 1184 (95% CI 879-1561) and in non-PF CD was 2365 (95% CI 2219-2519). There was no significant difference in the adjusted IRR of cancer for the CPF group compared with the non-PF CD group (0.83 [95% CI 0.62-1.10]; p = 0.219). CONCLUSION There was no significant difference in the incidence of any cancer in patients with CPF compared with non-PF CD. However, patients with CPF had a higher numerical risk of cancer than the general German population.
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Affiliation(s)
| | - Dominik Beier
- InGef - Institute for Applied Health Research Berlin GmbH, Berlin, Germany
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital, Amager and Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | | | - Dennis Haeckl
- WIG2 GmbH, Leipzig, Germany
- Faculty of Economics and Management Science, Leipzig University, Leipzig, Germany
| | - Oliver Nagel
- InGef - Institute for Applied Health Research Berlin GmbH, Berlin, Germany
| | | | - David A Schwartz
- Vanderbilt University Medical Center in Nashville, Nashville, Tennessee, USA
| | - Stephan R Vavricka
- Center of Gastroenterology and Hepatology, Zürich, Switzerland
- Department of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland
| | - Dimitri Bennett
- Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Frankfurt, Germany
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12
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Panés J, Bouma G, Ferrante M, Kucharzik T, Nachury M, de la Portilla de Juan F, Reinisch W, Selvaggi F, Tschmelitsch J, Brett NR, Ladouceur M, Binek M, Hantsbarger G, Campbell-Hill S, Karki C, Buskens C. INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn's Disease Treated in the ADMIRE-CD Trial. Inflamm Bowel Dis 2022; 28:1737-1745. [PMID: 35099555 PMCID: PMC9629463 DOI: 10.1093/ibd/izab361] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND The efficacy of a single administration of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells) for treating complex perianal fistulas in patients with Crohn's disease was demonstrated in a randomized, double-blind trial (ADMIRE-CD [Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn\'s Disease] trial). The current chart review study (INSPECT [A retrospectIve chart review study evaluatINg the longer-term effectiveneSs of darvadstrocel in PatiEnts who CompleTed ADMIRE-CD]) evaluated the longer-term effectiveness and safety of darvadstrocel. METHODS Eligible patients had completed at least 52 weeks in the ADMIRE-CD trial. Data on clinical remission and fistula relapse outcomes were collected retrospectively at 104 and 156 weeks after treatment. Adverse events of special interest (tumorigenicity and ectopic tissue formation) were collected up to 208 weeks after treatment. RESULTS Eighty-nine patients were included (43 darvadstrocel patients, 46 control subjects). At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively. In patients with clinical remission at week 52, this remission was sustained at 104 and 156 weeks after treatment in 19 (65.5%) of 29 and 16 (55.2%) of 29 darvadstrocel-treated patients and in 17 (70.8%) of 24 and 13 (54.2%) of 24 control subjects, respectively. Time to fistula relapse and incidence of fistula relapse or new fistula occurrence were not significantly different between groups. Tumorigenicity was reported for 1 (2.2%) patient in the control group (malignant epidermoid carcinoma). No ectopic tissue formation was reported. CONCLUSIONS Real-world follow-up of patients from the ADMIRE-CD trial indicates that clinical remission of complex perianal fistulas can be sustained in the long term irrespective of whether it is achieved through darvadstrocel administration or maintenance treatment regimens and confirms a favorable long-term safety profile of darvadstrocel.
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Affiliation(s)
- Julian Panés
- Inflammatory Bowel Disease Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Gerd Bouma
- Amsterdam Gastroenterology Endocrinology and Metabolism, Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam, the Netherlands
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Torsten Kucharzik
- Department of Internal Medicine and Gastroenterology, University Teaching Hospital Lüneburg, University of Hamburg, Lüneburg, Germany
| | - Maria Nachury
- U1286 - INFINITE - Institute for Translational Research in Inflammation, Centre Hospitalier Universitaire de Lille, University of Lille, Lille, France
| | | | - Walter Reinisch
- Department for Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology, McMaster University, Hamilton, ON, Canada
| | - Francesco Selvaggi
- Unit of Colorectal Surgery, Department of Medical, Surgical, Neurological, Metabolic and Ageing Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Jörg Tschmelitsch
- Department of Surgery, Hospital Barmherzige Brüder, Sankt Veit an der Glan, Austria
| | | | | | - Matthias Binek
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
| | | | | | - Chitra Karki
- Takeda Pharmaceutical Company Limited, Cambridge, MA, USA
| | - Christianne Buskens
- Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, the Netherlands
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13
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Garcia-Olmo D, Gilaberte I, Binek M, D´Hoore AJ, Lindner D, Selvaggi F, Spinelli A, Panés J. Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel (Mesenchymal Stem Cell Treatment) in Patients With Perianal Fistulizing Crohn's Disease: ADMIRE-CD Phase 3 Randomized Controlled Trial. Dis Colon Rectum 2022; 65:713-720. [PMID: 34890373 PMCID: PMC8985696 DOI: 10.1097/dcr.0000000000002325] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Darvadstrocel is an expanded allogeneic adipose-derived mesenchymal stem cell therapy for the treatment of complex perianal fistulas in patients with Crohn's disease. Safety and efficacy outcomes from the clinical trial known as "Adipose derived mesenchymal stem cells for induction of remission in perianal fistulizing Crohn's disease," or ADMIRE-CD (NCT01541579), from up to 52 weeks posttreatment were previously reported. Here, the outcomes from an extended 104-week follow-up are reported. OBJECTIVE The goal of this study was to assess the long-term safety and efficacy of darvadstrocel at 2 years post-treatment in patients with Crohn's disease and complex perianal fistulas. DESIGN This was a phase 3 double-blind randomized controlled study (ADMIRE-CD) in patients with perianal fistulizing Crohn's disease. SETTINGS This study extension was conducted in multiple hospitals across 7 European countries and Israel. PATIENTS Forty patients entered the extended follow-up period: 25 patients in the darvadstrocel treatment group and 15 in the control group. INTERVENTIONS Darvadstrocel or saline solution (control group) was administered once, locally, after fistula tract curettage and internal opening closure (with previous seton placement). All patients were permitted to continue ongoing medical treatments for fistulas. MAIN OUTCOME MEASURES Treatment-emergent serious adverse events were recorded through week 104. Clinical remission, defined as closure of all treated external openings that were draining at baseline despite gentle finger compression, was assessed at week 104. RESULTS Of 40 patients, 37 completed the extended follow-up. Through week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between weeks 52 and 104. At week 104, clinical remission was reported in 14/25 (56%) patients in the darvadstrocel group and 6/15 (40%) patients in the control group. LIMITATIONS Limitations include the small number of patients who entered the extended follow-up period, and no imaging examinations were performed at the 104-week time point. CONCLUSIONS Darvadstrocel was well tolerated and clinical remission after treatment with darvadstrocel may be sustained for up to 104 weeks in patients with perianal fistulizing Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B812.ClinicalTrials.gov No: NCT01541579. ESTUDIO DE SEGUIMIENTO PARA EVALUAR LA SEGURIDAD Y EFICACIA A LARGO PLAZO DE DARVADSTROCEL TRATAMIENTO CON CLULAS MADRE MESENQUIMALES EN PACIENTES CON ENFERMEDAD DE CROHN PERIANAL FISTULIZANTE ENSAYO CONTROLADO ALEATORIZADO DE FASE ADMIRECD ANTECEDENTES:Darvadstrocel es una terapia con células madre mesenquimales alogénicas expandidas derivadas de tejido adiposo para el tratamiento de fístulas perianales complejas en pacientes con enfermedad de Crohn. Los resultados del ensayo clínico conocido como "Células madre mesenquimales derivadas de tejido adiposo para la inducción de la remisión en la enfermedad de Crohn fistulizante perianal" o ADMIRE-CD (NCT01541579), en cuanto a la seguridad y eficacia hasta 52 semanas después del tratamiento, fueron previamente informados. Seguidamente, se presentan los resultados de un seguimiento extendido de 104 semanas.OBJETIVO:Evaluar la seguridad y eficacia a largo plazo de darvadstrocel a dos años del tratamiento en pacientes con enfermedad de Crohn y fístulas perianales complejas.DISEÑO:Este fue un estudio de fase 3, aleatorizado, a doble ciego, controlado (ADMIRE-CD) en pacientes con enfermedad de Crohn perianal fistulizante.DESARROLLO:Esta extensión del estudio se realizó en varios hospitales de siete países europeos e Israel.PACIENTES:Cuarenta pacientes participaron en la extensión de seguimiento: tratamiento con darvadstrocel (n = 25); grupo control (n = 15).INTERVENCIONES:Se administró Darvadstrocel o solución salina (grupo control) una vez, localmente, tras el legrado del trayecto fístuloso y cierre del orificio interno (con la colocación previa de setón). A todos los pacientes se les permitió continuar con los tratamientos médicos en curso para las fístulas.PRINCIPALES MEDIDAS DE RESULTADO:Los eventos de efectos adversos graves derivados del tratamiento se registraron hasta la semana 104. La remisión clínica, definida como el cierre de todas las aberturas externas tratadas que drenaban al inicio espontáneamente o por compresión suave de los dedos, fue evaluado en la semana 104.RESULTADOS:Del total de 40 pacientes, 37 completaron la extensión de seguimiento. Hasta la semana 104, se reportaron 7 eventos de efectos adversos graves resultantes del tratamiento, de los cuales 4 ocurrieron entre las semanas 52 y 104. En la semana 104, se reportó remisión clínica en 14/25 (56%) pacientes en el grupo de darvadstrocel y 6/15 (40%) pacientes en el grupo de control.LIMITACIONES:Solo una pequeña cantidad de pacientes participaron en el período de seguimiento extendido y no se realizaron exámenes por técnicas de imagen en la visita a 104 semanas.CONCLUSIONES:Darvadstrocel fue bien tolerado y la remisión clínica después del tratamiento con darvadstrocel puede mantenerse hasta 104 semanas en pacientes con enfermedad de Crohn perianal fistulizante. Consulte Video Resumen en http://links.lww.com/DCR/B812. (Traducción-Dr Osvaldo Gauto and Dr Julian Panés.)ClinicalTrials.gov No. NCT01541579.
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Affiliation(s)
- Damián Garcia-Olmo
- Universidad Autónoma de Madrid, Fundación Jiménez Díaz, University Hospital, Madrid, Spain
| | | | - Matthias Binek
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
| | | | - Dirk Lindner
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
| | - Francesco Selvaggi
- Colon and Rectal Surgery Unit, Department of Advanced Medical and Surgery Sciences, Luigi Vanvitelli University, Naples, Italy
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- IRCCS Humanitas Research Hospital, Division of Colon and Rectal Surgery, Rozzano Milan, Italy
| | - Julian Panés
- Inflammatory Bowel Disease Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
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14
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Tabari A, Kaplan JL, Huh SY, Moran CJ, Gee MS. Clinical characteristics and MRI-based phenotypes of perianal abscess formation in children with fistulizing Crohn's Disease. Front Pediatr 2022; 10:1045583. [PMID: 36507146 PMCID: PMC9731150 DOI: 10.3389/fped.2022.1045583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 10/18/2022] [Indexed: 11/19/2022] Open
Abstract
PURPOSE The aim of this study was to explore potential correlation of the MR imaging features and clinical characteristics with formation of perianal abscess in children with Crohn's perianal fistulas (CPF). METHODS From 2010 to 2020, pediatric patients with CPF diagnosis on their first pelvic MRI were identified retrospectively. All patients were divided into two groups based on the presence or absence of perianal abscess. Baseline clinical and MRI characteristics were recorded for each patient. All the statistical calculations were performed using R (version 3.6.3). RESULTS A total of 60 patients [F:M 17:43, median age 14 years (IQR 10-15), ranging 3-18 years] were included in this study. Forty-four abscesses were identified in 36/60 children (mean volume 3 ± 8.6 ml, median 0.3 ml). In 24/60 patients with perianal disease, no abscess was detected on the MRI. Ten patients (28%) showed perianal abscess on pelvic MRI at the initial diagnosis. The rate of active disease on colonoscopy (visible ulcerations/aphthous ulcers) was similar in both groups (95% vs. 94%). With regards to disease location, the majority of patients (40/60, 66.6%) in both groups had ileocolonic CD. All patients without abscess had a single perianal fistula (n = 24; 3 simple and 21 complex fistulae), however, patients with perianal abscess tended to have >1 fistulous tracts (n = 50 fistulas; all complex, 27 single, 10 double and 1 triple). Intersphincteric fistula was the most common fistula type in both groups (79% and 66%, p = 0.1). The total length of fistula (3.8 ± 1.7 vs. 2.8 ± 0.8 cm, p = 0.006) and presence of multiple external openings (n = 25 vs. 7, p = 0.019) were significantly higher in patients with abscesses, and fistula length >3.3 cm showed 80% specificity and 83% PPV for the presence of perianal abscess. Fistulas were symptomatic (pain, bleeding or drainage) at similar rates in both groups (68% and 70%, p = 0.1). CONCLUSION Pediatric patients with CPF who develop perianal abscess have a distinct imaging phenotype defined by longer fistula length (>3.3 cm), multiple skin openings and multiple fistulous tracts (≥2) on MRI. Patients who have these features but does not have an abscess on imaging may merit more aggressive treatment (and close monitoring) to prevent the development of an abscess.
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Affiliation(s)
- Azadeh Tabari
- Division of Pediatric Imaging, Department of Radiology, MassGeneral Hospital, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Jess L Kaplan
- Harvard Medical School, Boston, MA, USA.,Division of Pediatric Gastroenterology, MassGeneral Hospital for Children, Boston, MA, USA
| | - Susanna Y Huh
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.,Takeda Pharmaceuticals International Co, Cambridge, MA, USA
| | - Christopher J Moran
- Harvard Medical School, Boston, MA, USA.,Division of Pediatric Gastroenterology, MassGeneral Hospital for Children, Boston, MA, USA
| | - Michael S Gee
- Division of Pediatric Imaging, Department of Radiology, MassGeneral Hospital, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
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15
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Cho YJ, Kwon H, Kwon YJ, Kim KM, Oh SH, Kim DY. Efficacy and safety of autologous adipose tissue-derived stem cell therapy for children with refractory Crohn's complex fistula: a Phase IV clinical study. Ann Surg Treat Res 2021; 101:58-64. [PMID: 34235117 PMCID: PMC8255577 DOI: 10.4174/astr.2021.101.1.58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 03/10/2021] [Accepted: 03/30/2021] [Indexed: 12/01/2022] Open
Abstract
Purpose Autologous adipose tissue-derived stem cells (ASCs) have been proposed for patients with refractory Crohn disease, but research is lacking in pediatric patients. This Phase IV study evaluated the efficacy and safety of ASCs in children with refractory Crohn's fistulae. Methods Patients with a refractory Crohn's fistula who did not have conventional therapy for more than 3 months or with a recurrent complex Crohn's fistula were included. All patients were at least 14 years old. Patients with infection, poor condition, or active Crohn disease with a disease activity index of 450 and above were excluded. Five patients were treated with ASCs from 2014 to 2015 in Asan Medical Center. ASC administration was adjusted according to fistula size (1 mL per cm2). We evaluated the efficacy and safety 8 weeks after injection and followed patients for 6 months. Results Fistulae were healed in 4 patients by 8 weeks after ASC injection. Of these 4 patients, 1 had complete fistula closure and sustainability after 6 months. The other 3 with healing effects had less than 50% fistula closure by 6 months. None of these 4 patients have persistent fistulae. One patient had no healing effect, and seton ligation was performed 8 months after ASC injection. There were no adverse effects related to ASC administration. Conclusion ASC therapy is a simple and well-tolerated therapeutic option for children with refractory Crohn's complex fistulae. Complete closure was well-sustained. However, more data from a larger number of patients are needed.
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Affiliation(s)
- Yu Jeong Cho
- Department of Pediatric Surgery, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyunhee Kwon
- Department of Pediatric Surgery, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Jae Kwon
- Department of Pediatric Surgery, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung Mo Kim
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Seak Hee Oh
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Dae Yeon Kim
- Department of Pediatric Surgery, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
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16
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Khalid A, Faisal MF. Endoscopic Ultrasound-Guided Transrectal Drainage of Perirectal Abscess in a Patient with Crohn Disease. AMERICAN JOURNAL OF CASE REPORTS 2021; 22:e930698. [PMID: 34099613 PMCID: PMC8202418 DOI: 10.12659/ajcr.930698] [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] [Indexed: 01/06/2023]
Abstract
Patient: Male, 58-year-old Final Diagnosis: Perirectal abscess Symptoms: Body aches • chills • intermittent pyrexia • myalgias • perirectal pain Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology
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Affiliation(s)
- Ayesha Khalid
- Department of Gastroenterology, Deaconess Gateway Hospital, Evansville, IN, USA
| | - Mir Fahad Faisal
- Department of Gastroenterology, Deaconess Gateway Hospital, Evansville, IN, USA
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17
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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: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 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.
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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
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18
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Zittan E, Gralnek IM, Berns MS. The New Proactive Approach and Precision Medicine in Crohn's Disease. Biomedicines 2020; 8:biomedicines8070193. [PMID: 32635316 PMCID: PMC7400127 DOI: 10.3390/biomedicines8070193] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 06/23/2020] [Accepted: 06/28/2020] [Indexed: 12/11/2022] Open
Abstract
The proactive approach to Crohn's disease (CD) management advocates moving toward algorithmic tight-control scenarios that are designed for each CD phenotype to guide remission induction, maintenance therapy, active monitoring, and multidisciplinary care to manage the complexities of each inflammatory bowel disease (IBD) patient. This requires accurate initial clinical, laboratory, radiological, endoscopic, and/or tissue diagnosis for proper phenotypic stratification of each CD patient. A substantial proportion of patients in symptomatic remission have been reported to demonstrate evidence of active disease, with elevated fecal calprotectin(FC) and C-reactive protein (CRP) levels as a hallmark for mucosal inflammation. Active mucosal inflammation, and elevated CRP and fecal calprotectin (FC) have been shown to be good predictors of clinical relapse, disease progression, and complications in IBD patients. The next frontier of treatment is personalized medicine or precision medicine to help solve the problem of IBD heterogeneity and variable responses to treatment. Personalized medicine has the potential to increase the efficacy and/or reduce potential adverse effects of treatment for each CD phenotype. However, there is currently an unmet need for better elucidation of the inflammatory biopathways and genetic signatures of each IBD phenotype, so personalized medicine can specifically target the underlying cause of the disease and provide maximal efficacy to each patient.
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Affiliation(s)
- Eran Zittan
- Ellen and Pinchas Mamber Institute of Gastroenterology and Liver Diseases, IBD unit, Emek Medical Center, Afula 1834111, Israel;
- Correspondence:
| | - Ian M. Gralnek
- Ellen and Pinchas Mamber Institute of Gastroenterology and Liver Diseases, IBD unit, Emek Medical Center, Afula 1834111, Israel;
- Rappaport Faculty of Medicine Technion-Israel Institute of Technology, Haifa 31096, Israel;
| | - Marc S. Berns
- Rappaport Faculty of Medicine Technion-Israel Institute of Technology, Haifa 31096, Israel;
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19
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Waheed KB, Shah WJ, Altaf B, Amjad M, Hameed F, Wasim S, UlHassan MZ, Abuabdullah ZM, Rajamonickam SN, Arulanatham ZJ. Magnetic resonance imaging findings in patients with initial manifestations of perianal fistulas. Ann Saudi Med 2020; 40:42-48. [PMID: 32026703 PMCID: PMC7012033 DOI: 10.5144/0256-4947.2020.42] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Crohn's disease (CD) is a serious cause of perianal disease and the incidence is increasing in Saudi Arabia. MR imaging may document specific features that may help to foresee Crohn's disease in patients making an initial presentation. OBJECTIVE Present MR imaging findings of perianal fistulas in patients making an initial presentation. DESIGN Retrospective, observational. SETTING Radiology clinic in in Dhahran. PATIENTS AND METHODS All previously undiagnosed and untreated patients who presented for the first time to the outpatient clinics from September 2015-2018 with perianal fistulas were retrospectively evaluated. Previously diagnosed CD patients, post-surgical or intervention cases were excluded. Fistulas were categorized as low or high anal, simple or complex, and were graded per St. James University Hospital Classification. Imaging was interpreted by two experienced readers based on the Van Assche score. MAIN OUTCOME MEASURES Fistula features on MR imaging and diagnosis of CD. SAMPLE SIZE 171 patients. RESULTS Of 171 patients, 139 (81.3%) were males with mean age of 37.2 (12.7) years; the 32 females had a mean age of 35.8 (10.6) years. Twenty-one patients (12.3%) had CD. Fourteen (40.4%) patients with complex fistulas had CD in comparison to only 5 (4.8%) simple fistula patients ( P=.0005). More than half of patients with complex and high anal fistulas had CD ( P=.0005). Females were more affected than males ( P=.0005). CONCLUSION Complex or high anal fistula on MR imaging may be the initial presentation of CD and warrant further work up to establish the diagnosis. LIMITATIONS Retrospective, small sample, single center, and short duration study. CONFLICT OF INTEREST None.
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Affiliation(s)
- Khawaja Bilal Waheed
- From the Department of Radiology, King Fahd Military Medical Complex, Dhahran, Saudi Arabia
| | - Waseem Jan Shah
- From the Department of Pediatric Surgery, King Fahd Military Medical Complex, Dhahran, Saudi Arabia
| | - Bilal Altaf
- From the Department of General Surgery, King Fahd Military Medical Complex, Dhahran, Saudi Arabia
| | - Muhammad Amjad
- From the Department of Internal Medicine, King Fahd Military Medical Complex, Dhahran, Saudi Arabia
| | - Fawad Hameed
- From the Department of General Surgery, King Fahd Military Medical Complex, Dhahran, Saudi Arabia
| | - Sana Wasim
- From the Department of Radiology, Rawalpindi Medical College, Rawalpindi, Pakistan
| | - Muhammad Zia UlHassan
- From the Department of Radiology, King Fahd Military Medical Complex, Dhahran, Saudi Arabia
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Haddow JB, Musbahi O, MacDonald TT, Knowles CH. Comparison of cytokine and phosphoprotein profiles in idiopathic and Crohn’s disease-related perianal fistula. World J Gastrointest Pathophysiol 2019; 10:42-53. [PMID: 31750007 PMCID: PMC6854389 DOI: 10.4291/wjgp.v10.i4.42] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 09/28/2019] [Accepted: 10/18/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Perianal fistulae are either primary (idiopathic) or secondary [commonly associated with Crohn’s disease, (CD)]. It is assumed, although not proven, that the pathophysiology differs.
AIM To systematically compare the clinical phenotypes, cytokine and phosphoprotein profiles of idiopathic and CD-related perianal fistulae.
METHODS Sixty-one patients undergoing surgery for perianal fistula were prospectively recruited (48 idiopathic, 13 CD) into a cohort study. Clinical data, including the Perineal Disease Activity Index (PDAI) and EQ-5D-5L were collected. Biopsies of the fistula tract, granulation tissue, internal opening mucosa and rectal mucosa were obtained at surgery. Concentrations of 30 cytokines and 39 phosphoproteins were measured in each biopsy using a magnetic bead multiplexing instrument and a chemiluminescent antibody array respectively. Over 12000 clinical and 23500 laboratory measurements were made.
RESULTS The PDAI was significantly higher (indicating more active disease) in the CD group with a mean difference of 2.40 (95%CI: 0.52-4.28, P = 0.01). Complex pathoanatomy was more prevalent in the CD group, namely more multiple fistulae, supralevator extensions, collections and rectal thickening. The IL-12p70 concentration at the internal opening specimen site was significantly higher (median difference 19.7 pg/mL, 99%CI: 0.2-40.4, P = 0.008) and the IL-1RA/IL-1β ratio was significantly lower in the CD group at the internal opening specimen site (median difference 15.0, 99%CI = 0.4-50.5, P = 0.008). However in the remaining 27 cytokines and all 39 of the phosphoproteins across the four biopsy sites, no significant differences were found between the groups.
CONCLUSION CD-related perianal fistulae are more clinically severe and anatomically complex than idiopathic perianal fistulae. However, overall there are no major differences in cytokine and phosphoprotein profiles.
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Affiliation(s)
- James B Haddow
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 5AT, United Kingdom
| | - Omar Musbahi
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 5AT, United Kingdom
| | - Thomas T MacDonald
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 5AT, United Kingdom
| | - Charles H Knowles
- Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 5AT, United Kingdom
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21
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Carvello M, Lightner A, Yamamoto T, Kotze PG, Spinelli A. Mesenchymal Stem Cells for Perianal Crohn's Disease. Cells 2019; 8:cells8070764. [PMID: 31340546 PMCID: PMC6679174 DOI: 10.3390/cells8070764] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Revised: 07/14/2019] [Accepted: 07/17/2019] [Indexed: 12/24/2022] Open
Abstract
Perianal fistulizing Crohn’s disease (PFCD) is associated with significant morbidity and might negatively impact the quality of life of CD patients. In the last two decades, the management of PFCD has evolved in terms of the multidisciplinary approach involving gastroenterologists and colorectal surgeons. However, the highest fistula healing rates, even combining surgical and anti-TNF agents, reaches 50% of treated patients. More recently, the administration of mesenchymal stem cells (MSCs) have shown notable promising results in the treatment of PFCD. The aim of this review is to describe the rationale and the possible mechanism of action of MSC application for PFCD and the most recent results of randomized clinical trials. Furthermore, the unmet needs of the current administration process and the expected next steps to improve the outcomes will be addressed.
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Affiliation(s)
- Michele Carvello
- Colon and Rectal Surgery Unit, Humanitas Clinical and Research Center, 20089 Rozzano, Italy
| | - Amy Lightner
- Department of Colon and Rectal Surgery, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Takayuki Yamamoto
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie 510-0016, Japan
| | - Paulo Gustavo Kotze
- Colorectal Surgery Unit, Cajuru University Hospital, Catholic University of Paraná, Curitiba 80215-901, Brazil
| | - Antonino Spinelli
- Colon and Rectal Surgery Unit, Humanitas Clinical and Research Center, 20089 Rozzano, Italy.
- Department of Biomedical Sciences, Humanitas University, 20089 Rozzano, Italy.
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22
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Abstract
During the past 30 years, classifications and scoring systems have been developed in order to evaluate and objectify the degree and activity of anorectal fistulas. Only a few of these disease-specific instruments have been adopted into daily clinical routine. Generally, clinicians tend to use global medical judgement rather than numeric activity indices, which often seem complex and time consuming. Activity scores in Crohn disease, however, appeared to be very useful in clinical trials regarding evaluation of therapy response. Thus, activity indices must be simple and reproducible. The years 1976 and 1995, in which the Parks Classification and Perianal Disease Activity Index (PDAI) were established, can be considered milestone years for classifying patients with anorectal fistulizing disease. These instruments should be recognized at present as the gold standard for evaluating the complexity as well as the severity of anorectal fistulas and perianal Crohn disease.
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23
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Knyazev OV, Fadeeva NA, Kagramanova AV, Belyakov NI, Orlova NV, Lishchinskaya AA, Konoplyannikov AG, Parfenov AI. Stem Cell Therapy for Perianal Crohn's Disease. TERAPEVT ARKH 2019; 90:60-66. [PMID: 30701858 DOI: 10.26442/terarkh201890360-66] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
AIM To compare the effectiveness of the effect of combination therapy (local and systemic administration) with bone marrow mesenchymal stromal cells (MSC), anticlitokine therapy with infliximab (IFX), and antibiotic (AB)/immunosuppressive (IS) therapy on the frequency of healing of simple perianal fistulas in Crohn's disease. MATERIALS AND METHODS In our study, the 1-st group of patients aged 19 to 58 years (Me-29) (n = 12) received MSCs culture systemically according to the scheme and locally. The 2-nd group of patients with CD (n = 10) from 20 to 68 years old (Me-36) received anticytokine therapy with infliximab (IFX) according to the scheme. The 3-d group of patients with CD (n=14) from 20 to 62 years old (Me-28) received antibiotics (AB) and immunosuppressors (IS). Efficacy was assessed by the index of perianal activity of Crohn's disease (PCDAI) and the frequency of relapses. RESULTS After 12 weeks among patients of the 1-st group, healing of simple fistulas was noted in 8/12 patients (66.6%), in the 2-nd group in 6/10 (60.0%) In the 3-d group, in 1/14 patients (7.14%). After 6 months in the 1-st group of patients, healing of simple fistulas was preserved in 8/12 (66.6%), in the 2-nd group - in 6/10 (60.0%). In the 3-d group - in 1/14 patients (7.14%). After 12 months in the 1-st group, healing of simple fistulas was preserved in 7/12 (58.3%), in the second group - in 6/10 (60.0%). In the 3-d group - in 2/14 patients (14.3%). After 24 months, among the patients of the 1-st group, fistula closure was maintained in 5/12 patients (41.6%), in the 2-nd group - in 4/10 (40.0%). In the 3-d group - in 0/14 patients (0.0%). CONCLUSION Combined cellular and anticytokine therapy of CD with perianal lesions significantly contributes to the more frequent and prolonged closure of simple fistulas, as compared to antibiotics/immunosuppressors, and to a decrease in the frequency of recurrence of the disease.
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Affiliation(s)
- O V Knyazev
- Moscow Clinical Research Center, Moscow, Russia
| | - N A Fadeeva
- Moscow Clinical Research Center, Moscow, Russia
| | | | | | - N V Orlova
- Moscow Clinical Research Center, Moscow, Russia
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24
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Lopez N, Ramamoorthy S, Sandborn WJ. Recent advances in the management of perianal fistulizing Crohn's disease: lessons for the clinic. Expert Rev Gastroenterol Hepatol 2019; 13:563-577. [PMID: 31023087 PMCID: PMC6545251 DOI: 10.1080/17474124.2019.1608818] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Managing fistulizing perianal disease is among the most challenging aspects of treating patients with Crohn's disease. Perianal fistulas are indicative of poor long-term prognosis. They are commonly associated with significant morbidities and can have detrimental effects on quality of life. While durable fistula closure is ideal, it is uncommon. In optimal circumstances, reported long-term fistula healing rates are only slightly higher than 50% and recurrence is common. Achieving these results requires a combined medical and surgical approach, highlighting the importance of a highly skilled and collaborative multidisciplinary team. In recent years, advances in imaging, biologic therapies and surgical techniques have lent to growing enthusiasm amongst treatment teams, however the most advantageous approach is yet to be determined. Areas covered: Here we review current management approaches, incorporating recent guidelines and novel therapies. Additionally, we discuss recently published and ongoing studies that will likely impact practice in the coming years. Expert opinion: Investing in concerted collaborative multi-institutional efforts will be necessary to better define optimal timing and dosing of medical therapy, as well as to identify ideal timing and approach of surgical interventions. Standardizing outcome measures can facilitate these efforts. Clearly, experienced multidisciplinary teams will be paramount in this process.
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Affiliation(s)
- Nicole Lopez
- Division of Colon and Rectal Surgery, University of California San Diego, California, USA
| | - Sonia Ramamoorthy
- Division of Colon and Rectal Surgery, University of California San Diego, California, USA
| | - Willam J. Sandborn
- Inflammatory Bowel Disease Center, University of California San Diego, California, USA,Division of Gastroenterology, University of California San Diego, California, USA
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25
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Chudy-Onwugaje KO, Christian KE, Farraye FA, Cross RK. A State-of-the-Art Review of New and Emerging Therapies for the Treatment of IBD. Inflamm Bowel Dis 2019; 25:820-830. [PMID: 30445504 PMCID: PMC6468492 DOI: 10.1093/ibd/izy327] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Indexed: 12/12/2022]
Abstract
Over the last 2 decades, novel therapies targeting several immune pathways have been developed for the treatment of patients with inflammatory bowel disease (IBD). Although anti-tumor necrosis factor (anti-TNF) agents remain the firstline treatment for moderate to severe Crohn's disease and ulcerative colitis, many patients will require alternative agents, due to nonresponse, loss of response, or intolerance of anti-TNFs. Furthermore, patients may request newer therapies due to improved safety profiles or improved administration (ie, less frequent injection, oral therapy). This review will focus on new and emerging therapies for the treatment of IBD, with a special focus on their adverse effects. Although many of the agents included in this paper have been approved for use in IBD, a few are still in development but have been shown to be effective in phase II clinical trials. 10.1093/ibd/izy327_video1 izy327.video1 5967364908001.
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Affiliation(s)
- Kenechukwu O Chudy-Onwugaje
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| | - Kaci E Christian
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| | - Francis A Farraye
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts
| | - Raymond K Cross
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland,Address correspondence to: Raymond K. Cross, MD, MS, 685 West Baltimore Street, Suite 8-00, Baltimore, MD 21201 ()
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26
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Panes J, Reinisch W, Rupniewska E, Khan S, Forns J, Khalid JM, Bojic D, Patel H. Burden and outcomes for complex perianal fistulas in Crohn's disease: Systematic review. World J Gastroenterol 2018; 24:4821-4834. [PMID: 30479468 PMCID: PMC6235801 DOI: 10.3748/wjg.v24.i42.4821] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 09/24/2018] [Accepted: 10/21/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To systematically review the literature on epidemiology, disease burden, and treatment outcomes for Crohn's disease (CD) patients with complex perianal fistulas. METHODS PubMed, Embase, and Cochrane were searched for relevant articles (published 2000-November 2016) and congress abstracts (published 2011-November 2016). RESULTS Of 535 records reviewed, 62 relevant sources were identified (mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14% (follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment (failure and relapse rates, respectively: medical, 12%-73% and 0%-41%; surgical: 0%-100% and 11%-20%; combined medical/surgical: 0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies (1 of infliximab; 3 of surgical interventions) have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD. CONCLUSION Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to anti-tumour necrosis factor-α agents, as evidenced by high failure and relapse rates.
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Affiliation(s)
- Julian Panes
- Department of Gastroenterology, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona 08036, Spain
| | | | - Ewa Rupniewska
- RTI Health Solutions, Manchester M20 2LS, United Kingdom
| | - Shahnaz Khan
- RTI Health Solutions, Research Triangle Park, NC 27709, United States
| | - Joan Forns
- RTI Health Solutions, Barcelona 08028, Spain
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27
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Ruemmele FM, Rosh J, Faubion WA, Dubinsky MC, Turner D, Lazar A, Eichner S, Maa JF, Alperovich G, Robinson AM, Hyams JS. Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2. J Crohns Colitis 2018; 12:1249-1254. [PMID: 29939254 PMCID: PMC6225974 DOI: 10.1093/ecco-jcc/jjy087] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND AIMS Adalimumab has been shown to be more effective than placebo in healing fistulae in adults with moderately to severely active Crohn's disease. The efficacy and safety of adalimumab in healing fistulae in children/adolescents with Crohn's disease from the 52-week IMAgINE 1 clinical trial, and its open-label extension IMAgINE 2, are reported. METHODS Children/adolescents with perianal fistulae at baseline of IMAgINE 1 were assessed for fistula closure and improvement during IMAgINE 1 [Weeks 0-52] and from Week 0 of IMAgINE 2 [Week 52 of IMAgINE 1] through to Week 240 of IMAgINE 2 using non-responder imputation. RESULTS A total of 36 children/adolescents had fistulae at baseline of IMAgINE 1 and were included in the analysis. Fistula closure and improvement were observed in 44.4% and 52.8%, respectively, at Week 12. Rates of closure and improvement were maintained throughout the analysis period to Week 292. No new safety signals were identified. CONCLUSIONS In children/adolescents with moderately to severely active, fistulizing Crohn's disease, adalimumab induced perianal fistula closure and improvement within 12 weeks of treatment, with rates that were sustained for more than 5 years. The safety profile of adalimumab in patients with fistulae at baseline was similar to that of the overall population in IMAgINE 1/2. ClinicalTrials.gov identifiers: IMAgINE 1 (NCT00409682); IMAgINE 2 (NCT00686374).
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Affiliation(s)
- Frank M Ruemmele
- Université Sorbonne Paris Cité, Paris Descartes, APHP Hôpital Necker-Enfants Malades, Paris, France
| | - Joel Rosh
- Goryeb Children’s Hospital/Atlantic Health, Morristown, NJ, USA
| | | | | | - Dan Turner
- Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Andreas Lazar
- AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany
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28
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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.
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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)
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29
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Cruz A, Chen D, Hsu P, Pandit V, Omesiete P, Vij P, Nfonsam V. Racial and gender disparities in the incidence of anal cancer: analysis of the Nationwide Inpatient Sample (NIS). J Gastrointest Oncol 2018; 10:37-41. [PMID: 30788157 DOI: 10.21037/jgo.2018.10.09] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background Racial and gender disparities have been shown in other gastrointestinal cancers. However, there is a paucity of data on racial and gender disparities in anal cancer (AC). The aim of this study was to assess racial and gender disparities among patients with AC. Methods We analyzed data from the National Inpatient Sample (NIS) 2011 database of patients diagnosed with AC with age ≥18. Demographic data including age, race and gender were assessed. Patients were stratified based on race and gender. Log binomial regression was used to generate risk ratios. Results A total of 6,013,105 patients were assessed and 1,956 (0.03%) patients had AC. Female patients were more at risk of developing AC [relative risk (RR): 1.14, P=0.02]. Whites and Blacks had the highest incidence followed by Asians/Pacific Islanders. Black males had increased risk of AC (RR: 1.43, P<0.01). Amongst Hispanics; both males (RR: 0.69, P=0.05) and females (RR: 0.46, P<0.0001) had decreased risk of developing AC. Finally, we saw that Asian females had a much lower risk of developing AC (RR: 0.33, P<0.01). Conclusions Racial disparities and gender differences exist in the incidence of AC. Potential causes for this disparity are disparate access to healthcare, lack of education, and lack of awareness. Greater understanding of the racial disparity in AC can help identify at risk population and eventually lead to improved preventative measures to ultimately reduce the incidence of AC.
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Affiliation(s)
- Alejandro Cruz
- Department of Surgery, The University of Arizona, Tucson, AZ, USA
| | - Debbie Chen
- Department of Surgery, The University of Arizona, Tucson, AZ, USA
| | - Paul Hsu
- Department of Biostatistics and Epidemiology, Mel and Enid Zuckerman College of Public Health, The University of Arizona, Tucson, AZ, USA
| | - Viraj Pandit
- Department of Surgery, The University of Arizona, Tucson, AZ, USA
| | - Pamela Omesiete
- Department of Surgery, The University of Arizona, Tucson, AZ, USA
| | - Priyanka Vij
- Department of Surgery, The University of Arizona, Tucson, AZ, USA
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30
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Bermejo F, Guerra I, Algaba A, López-Sanromán A. Pharmacological Approach to the Management of Crohn's Disease Patients with Perianal Disease. Drugs 2018; 78:1-18. [PMID: 29139091 DOI: 10.1007/s40265-017-0842-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Perianal localization of Crohn's disease involves significant morbidity, affects quality of life and results in an increased use of healthcare resources. Medical and surgical therapies contribute to its management. The objective of this review is to address the current understanding in the management of perianal Crohn's disease, with the main focus in reviewing pharmacological therapies, including stem cells. In complex fistulas, once local sepsis has been controlled by surgical drainage and/or antibiotics, anti-TNF drugs (infliximab, adalimumab) are the first-line therapy, with or without associated immunomodulators. Combining surgery and anti-TNF therapy has additional benefits for healing. However, response is inadequate in up to half of cases. A possible role of new biological drugs in this context (vedolizumab, ustekinumab) is an area of ongoing investigation, as is the local application of autologous or allogeneic mesenchymal stem cells. These are non-hematopoietic multipotent cells with anti-inflammatory and immunomodulatory properties, the use of which may successfully treat refractory patients, and seem to be a promising and safe alternative to achieving fistula healing in Crohn's disease, without known systemic effects.
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Affiliation(s)
- Fernando Bermejo
- Department of Gastroenterology, University Hospital of Fuenlabrada, Madrid, Spain.
- Department of Medicine and Surgery, Universidad Rey Juan Carlos, Madrid, Spain.
| | - Iván Guerra
- Department of Gastroenterology, University Hospital of Fuenlabrada, Madrid, Spain
| | - Alicia Algaba
- Department of Gastroenterology, University Hospital of Fuenlabrada, Madrid, Spain
| | - Antonio López-Sanromán
- Department of Gastroenterology and Hepatology, University Hospital Ramón y Cajal, Madrid, Spain
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Fan XL, Yu LJ, Gao J. Clinical effects of comfort nursing in perianal abscess patients with postoperative pain. Shijie Huaren Xiaohua Zazhi 2017; 25:832-836. [DOI: 10.11569/wcjd.v25.i9.832] [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] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the clinical effects of comfort nursing in patients with perianal abscess.
METHODS Ninety perianal abscess patients with postoperative pain treated at our hospital were selected and divided into either a control group to receive routine nursing care alone or a study group to receive routine nursing care plus comfort nursing, with 45 cases in each group. Pain, anxiety and sleep quality of the two groups were compared between the two groups.
RESULTS The numeric pain rating scale scores at different time points in the study group were significantly lower than those in the control group (t = 9.67, 13.53, 15.83, and 10.46, P < 0.05). The self-rating anxiety scale score were significantly lower in the study group than in the control group (t = 2.31, -18.04, P < 0.05); and the Pittsburgh sleep quality index were also significantly lower in the study group than in the control group (t = 9.47, P < 0.05).
CONCLUSION The application of comfort nursing is helpful to reduce postoperative pain, relieve anxiety, and improve sleep quality in patients with perianal abscess.
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