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Dudek P, Talar-Wojnarowska R. Current Approach to Risk Factors and Biomarkers of Intestinal Fibrosis in Inflammatory Bowel Disease. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:305. [PMID: 38399592 PMCID: PMC10889938 DOI: 10.3390/medicina60020305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/31/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024]
Abstract
Inflammatory bowel disease (IBD), especially Crohn's disease (CD), characterized by a chronic inflammatory process and progressive intestinal tissue damage, leads to the unrestrained proliferation of mesenchymal cells and the development of bowel strictures. Complications induced by fibrosis are related to high rates of morbidity and mortality and lead to a substantial number of hospitalizations and surgical procedures, generating high healthcare costs. The development of easily obtained, reliable fibrogenesis biomarkers is essential to provide an important complementary tool to existing diagnostic and prognostic methods in IBD management, guiding decisions on the intensification of pharmacotherapy, proceeding to surgical methods of treatment and monitoring the efficacy of anti-fibrotic therapy in the future. The most promising potential markers of fibrosis include cartilage oligomeric matrix protein (COMP), hepatocyte growth factor activator (HGFA), and fibronectin isoform- extra domain A (ED-A), as well as antibodies against granulocyte macrophage colony-stimulating factor (GM-CSF Ab), cathelicidin (LL-37), or circulatory miRNAs: miR-19a-3p and miR-19b-3p. This review summarizes the role of genetic predisposition, and risk factors and serological markers potentially contributing to the pathophysiology of fibrotic strictures in the course of IBD.
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Burisch J, Lophaven S, Langholz E, Munkholm P. The clinical course of Crohn's disease in a Danish population-based inception cohort with more than 50 years of follow-up, 1962-2017. Aliment Pharmacol Ther 2022; 55:73-82. [PMID: 34543457 DOI: 10.1111/apt.16615] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 08/22/2021] [Accepted: 09/09/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND Few population-based studies have investigated the long-term prognosis of Crohn's disease (CD). AIM To determine the long-term natural disease course of CD with regard to surgery, cancer and mortality in a population-based cohort followed for more than 50 years. METHODS All patients diagnosed with CD from 1962 to 1987 in Copenhagen County, Denmark were included in a population-based cohort. Information about surgeries, cancers and mortality was collected from patient files from 1962 to 1987 and from the Danish National Patient Registry, Cancer Registry, and from the Register of Causes of Death, 1987-2017. Patients were matched with individuals from the general population. RESULTS A total of 373 patients were followed for a median of 33 years (range: 0-56 years). The cumulative probability of surgery 10, 20, 30, 40 and 50 years after diagnosis was 62% (CI 95%: 57%-67%), 71% (CI 95%: 66%-75%), 72% (CI 95%: 67%-76%), 74% (CI 95%: 69%-79%) and 74% (CI 95%: 69%-79%), respectively. A total of 142 patients (54%) were operated upon at least twice: 69 (26%) needing two surgeries and 73 (28%) needing three or more. Patients with CD were found to be at increased risk of intestinal (small bowel, rectum and anus) and extra-intestinal (respiratory organs and skin) cancer. All-cause mortality among CD patients was higher than among controls (RR: 1.22, CI 95%: 1.04-1.43), whereas mortality due to gastrointestinal cancer was not. CONCLUSION After 50 years of follow-up, 75% CD patients had undergone surgery, with most needing repeat surgery. The risk of intestinal and extra-intestinal cancers, as well as mortality, was higher among CD patients than the background population.
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Affiliation(s)
- Johan Burisch
- Department of Gastroenterology, North Zealand Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | - Ebbe Langholz
- Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.,Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Pia Munkholm
- Department of Gastroenterology, North Zealand Hospital, University of Copenhagen, Copenhagen, Denmark
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Abstract
Twenty-five years ago the field was revolutionized by the introduction of infliximab as the first hybrid anti-TNF-antibody. Subsequently, other humanized anti-TNFs were developed and marketed, followed by antibodies to new targets including integrins (vedolizumab) and interleukin 12/23 (ustekinumab). All these so-called biologicals were shown in registrational trials to induce remission superior to placebo but consistently were effective in only a minority of patients. Even though in most trials only the responders were selected to continue on the respective medication for maintenance, many experienced a secondary loss of response and only a minority of usually <25% of the initial cohort achieved long-term (1 year) remission. In 'real life studies', the outcome was somewhat better, probably due to proper selection of patients and open, mostly retrospective study designs. A clear benefit of biologicals is apparent in otherwise treatment refractory patients, in extraintestinal manifestations and in Crohn´s disease (CD) with fistulizing complications. Biologicals achieve mucosal healing (MH) more often than corticosteroids or thiopurines, and MH is associated with improved prognosis. However, this does not justify escalating treatment until MH is reached since controlled trials proving this point of 'treat to target' are lacking both in ulcerative colitis and CD. Surgical rates have decreased with increasing use of biologicals, but disease progression has not been proven to improve. With the exception of opportunistic infections, serious adverse events are rare. In conclusion, biologicals have changed the scene considerably and expanded our armamentarium, but there is also a marketing hype fostering expectations without evidence.
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Sicilia B, García-López S, González-Lama Y, Zabana Y, Hinojosa J, Gomollón F. GETECCU 2020 guidelines for the treatment of ulcerative colitis. Developed using the GRADE approach. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 43 Suppl 1:1-57. [PMID: 32807301 DOI: 10.1016/j.gastrohep.2020.07.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Since the first edition of the Guidelines was published in 2013, much information has been generated around the treatment of ulcerative colitis, and new drugs and action protocols have been introduced. Clinical practice has changed substantially, warranting new approaches and a comprehensive review and update of the evidence. MATERIAL AND METHODS Once again, we used the GRADE approach, supported by an electronic tool (https://gradepro.org). The clinical scenarios are the same as in the previous version (induction and maintenance in severe and mild-moderate flare-ups), as are the variables and their evaluation. However, in the updated guidelines, three questions have been deleted, 14 added and 30 maintained, making a total of 44 clinical questions. After an exhaustive review of the evidence, the recommendations are now updated. RESULTS Of the 44 questions analysed, no recommendation could be established in two due to the very low quality of the evidence, while in the other 42, based on different degrees of quality of evidence, recommendations were made according to the GRADE system. In 25 of these questions the final recommendation is strongly in favour, in six strongly against, in seven weakly in favour and in four weakly against. According to the scenarios and recommendations, six algorithms are proposed as a simple guide for practical decision-making. CONCLUSIONS The aim of this update of the 2013 guidelines is to provide answers, based on the GRADE approach, to the different questions we ask ourselves daily when deciding the most appropriate treatment for our patients with ulcerative colitis in the different clinical scenarios.
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Affiliation(s)
- Beatriz Sicilia
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Burgos, España
| | - Santiago García-López
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigaciones Sanitarias de Aragón, Zaragoza, España.
| | - Yago González-Lama
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, España
| | - Yamile Zabana
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo Hospital Universitario Mútua Terrassa Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
| | - Joaquín Hinojosa
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital de Manises, Valencia, España
| | - Fernando Gomollón
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Instituto de Investigaciones Sanitarias de Aragón, Hospital Clínico Universitario Lozano Blesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Zaragoza, España
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Teich N, Grümmer H, Jörgensen E, Liceni T, Holtkamp-Endemann F, Fischer T, Hohenberger S. Golimumab improves work productivity in patients suffering from moderate to severe ulcerative colitis: results of a prospective study over 24 months. BMC Gastroenterol 2021; 21:161. [PMID: 33845784 PMCID: PMC8042988 DOI: 10.1186/s12876-021-01747-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 03/30/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory bowel disease with recurrent episodes of debilitating symptoms negatively affecting work productivity and health-related quality of life (HRQoL). The use of biologics in UC treatment improves work and HRQoL but prospective long-term data concerning the treatment with TNFα inhibitor golimumab in UC patients are still rare. Therefore, our study aimed to evaluate the change in work productivity, capacity for daily activities and HRQoL in UC patients treated with golimumab in Germany. METHODS Using the Work Productivity and Activity Impairment questionnaire, the change in work productivity and in capacity for daily activities after 3 months and over the whole observational period of 24 months were assessed (both primary endpoints). Disease-specific and health-related quality of life (QoL) were analyzed with the Inflammatory Bowel Disease Questionnaire (IBDQ), the Short-Form 12 Health Survey Questionnaire (SF-12), and the Partial Mayo Score (secondary endpoints). Further, disease-related hospitalization rates were assessed. RESULTS This prospective non-interventional study included 286 patients. Thereof, 212 patients were employed at baseline (modified intention to treat analysis set employed at baseline, mITTe). 61.3% of the mITTe patients had moderate and 17.0% had severe UC. Three months after initiation of golimumab therapy, total work productivity impairment (TWPI) score and activity impairment score improved significantly from baseline with a mean change of - 17.3% (p < 0.0001) and - 14.4% (p < 0.0001), respectively. Results persisted over 24 months (mean change TWPI score: - 24.5%, mean change activity impairment score: - 30.0%). Disease- and health-related QoL also improved significantly under golimumab treatment as indicated by increased IBDQ [mean change: 28.0 (SD: ± 36.1, month 3), 42.1 (SD: ± 39.5, month 24)] and SF-12 scores [PCS-12: 45.9 (SD: ± 8.5), MCS-12: 4.9 (SD: ± 10.6, month 3), PCS-12: 5.9 (SD: ± 9.0), MCS-12: 6.4 (SD: ± 11.1, month 24)]. Disease-related hospitalization rate decreased from 16.0% (BL) to 4.3% at month 24 and the mean number of missed working days due to UC decreased from 8.2 (SD: 17.6, BL) to 0.7 (SD: 2.1) after golimumab induction. CONCLUSIONS Golimumab leads to notable long-term improvements in work productivity, daily activity, HRQoL, and disease-related hospitalization rates in patients with moderate to severe UC. TRIAL REGISTRATION PEI (Paul-Ehrlich-Institute, Langen, Germany) Registration Nr: NIS#255 ( https://www.pei.de/SharedDocs/awb/nis-0201-0300/0255.html ).
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Affiliation(s)
- Niels Teich
- Internistische Gemeinschaftspraxis Für Verdauungs- Und Stoffwechselkrankheiten Leipzig Und Schkeuditz, Nordstraße 21, 04105, Leipzig, Sachsen, Germany.
| | - Harald Grümmer
- Praxis Für Innere Medizin/Gastroenterologie, Allee Nach Sanssouci 7, 14471, Potsdam, Germany
| | - Eric Jörgensen
- Magen-Darm-Zentrum Remscheid, Rosenhügelerstraße 2, 42859, Remscheid, Germany
| | - Thomas Liceni
- MVZ Für Gastroenterologie Am Bayerischen Platz, Innsbrucker Straße 58, 10825, Berlin, Germany
| | - Frank Holtkamp-Endemann
- Gastroenterologische Gemeinschaftspraxis Am Germania-Campus, An der Germania Brauerei 6, 48159, Münster, Germany
| | - Tim Fischer
- Medical Affairs, MSD Sharp & Dohme GmbH, Lindenplatz 1, 85540, Haar, Germany
| | - Susanne Hohenberger
- Medical Affairs, MSD Sharp & Dohme GmbH, Lindenplatz 1, 85540, Haar, Germany
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Teich N, Bläker M, Holtkamp-Endemann F, Jörgensen E, Stallmach A, Hohenberger S. Effect of Originator Infliximab Treatment on Disease-Related Hospitalizations, Work Productivity and Activity Impairment, and Health Resource Utilization in Patients with Crohn's Disease in a Real-Life Setting: Results of a Prospective Multicenter Study in Germany. Inflamm Intest Dis 2020; 6:48-60. [PMID: 33850839 DOI: 10.1159/000512159] [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: 06/02/2020] [Accepted: 10/08/2020] [Indexed: 11/19/2022] Open
Abstract
Introduction Infliximab (IFX) therapy is efficacious for inducing and maintaining symptomatic remission in patients with Crohn's disease (CD), but whether this benefit results in reduced hospitalization rates and therefore may improve patients' quality of life in an economically sensible way is conflicting so far. Methods We conducted a noninterventional, multicenter, open-label, prospective study to evaluate the effect of originator IFX treatment on patient-reported outcomes and disease-related hospitalizations in adult CD patients in Germany treated for the first time with IFX according to label. Results Two hundred and ninety-four patients were included in the study. We observed a statistically significant reduction in the number of CD-related hospitalizations from the year before baseline (mean 1.00 per patient, SD ± 0.93) to the mean value of the 1st (0.62, SD ± 0.95) and 2nd year (0.32, SD ± 0.75) of the observation period (p < 0.0001). After 3 months of IFX therapy, work productivity and activity increased by an average of 12.6 and 17.1%, respectively. Patient's clinical outcome was markedly improved as the total CD activity index (CDAI) sum score continuously decreased from baseline to month 24 and the mean score of the total inflammatory bowel disease questionnaire (IBDQ) changed substantially from 141 at baseline to 172 after 24 months of IFX treatment. Additionally, the number of work incapacity days declined. Recently, no new safety issues of IFX have been identified. Conclusion In this large, prospective, multicenter study on disease-related hospitalization rates, work productivity, capacity for daily activities, and HRQoL in patients with CD, IFX significantly reduces their hospitalization rates and improves work productivity, daily activity, and quality of life over 24 months.
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Affiliation(s)
- Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten Leipzig und Schkeuditz, Leipzig, Germany
| | - Michael Bläker
- Gastroenterologie/Gastropraxis Eppendorfer Baum, Hamburg, Germany
| | | | | | - Andreas Stallmach
- Klinik für Innere Medizin IV, Gastroenterologie, Hepatologie, Infektiologie, Interdisziplinäre Endoskopie, Universitätsklinikum Jena, Jena, Germany
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Teich N, Grümmer H, Jörgensen E, Liceni T, Holtkamp-Endemann F, Fischer T, Hohenberger S. Golimumab in real-world practice in patients with ulcerative colitis: Twelve-month results. World J Gastroenterol 2020; 26:2852-2863. [PMID: 32550760 PMCID: PMC7284175 DOI: 10.3748/wjg.v26.i21.2852] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 05/08/2020] [Accepted: 05/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The introduction of biologics has revolutionized the management of the chronic inflammatory bowel disease, ulcerative colitis (UC), with many patients experiencing significant improvements not only in their symptoms but in other outcomes relevant to individuals and society as a whole. In Germany, there are no prospective data > 3 mo that assess the work productivity, daily activities and quality of life (QoL) of patients with moderate-to-severe UC treated with golimumab. AIM To assess change in work productivity, capacity for daily activities and QoL in UC patients treated with golimumab in Germany. METHODS The validated Work Productivity Activity Impairment (WPAI) Questionnaire was used to analyze the change in work productivity, the capacity for daily activities after three months (primary endpoint) and disease specific and health related QoL (HRQoL) up to 1 year (secondary endpoints). The changes in work productivity and activity impairment were evaluated every three months until month twelve compared to baseline. Disease-specific and health-related QoL were assessed with the inflammatory bowel disease questionnaire and with the short-form 12 health survey questionnaire (SF-12). RESULTS This prospective non-interventional study included 287 patients. The analysis population was comprised of 282 patients who had completed at least two visits. At baseline, 61% of patients had moderate UC and 18% had severe UC. Furthermore, 75% of patients worked full-time or part-time at baseline. A total of 212 patients who were employed at the start of the study (employed population) were evaluated for the primary endpoint. Golimumab significantly reduced all WPAI sub-scores compared to baseline after three, six, nine and twelve months after the start of treatment (P < 0.0001). In addition, disease-specific QoL and HRQoL, as measured by the SF-12 questionnaire, improved significantly with golimumab at all evaluation times (P < 0.0001 in each case vs baseline). CONCLUSION Treatment of moderate-to-severe UC with golimumab leads to significant improvements in patient´s work productivity, daily activity and QoL over twelve months.
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Affiliation(s)
- Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs-und Stoffwechselkrankheiten Leipzig und Schkeuditz, Leipzig 04105, Germany
| | - Harald Grümmer
- Praxis für Innere Medizin/Gastroenterologie, Potsdam 14471, Germany
| | | | - Thomas Liceni
- MVZ für Gastroenterologie am Bayerischen Platz, Berlin 10825, Germany
| | | | - Tim Fischer
- Medical Affairs, MSD Sharp and Dohme GmbH, Haar 85540, Germany
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Kalman TD, Everhov ÅH, Nordenvall C, Sachs MC, Halfvarson J, Ekbom A, Ludvigsson JF, Myrelid P, Olén O. Decrease in primary but not in secondary abdominal surgery for Crohn's disease: nationwide cohort study, 1990–2014. Br J Surg 2020; 107:1529-1538. [PMID: 32452553 DOI: 10.1002/bjs.11659] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 03/25/2020] [Accepted: 04/04/2020] [Indexed: 12/15/2022]
Abstract
AbstractBackgroundTreatment of patients with Crohn's disease has evolved in recent decades, with increasing use of immunomodulatory medication since 1990 and biologicals since 1998. In parallel, there has been increased use of active disease monitoring. To what extent these changes have influenced the incidence of primary and repeat surgical resection remains debated.MethodsIn this nationwide cohort study, incident patients of all ages with Crohn's disease, identified in Swedish National Patient Registry between 1990 and 2014, were divided into five calendar periods of diagnosis: 1990–1995 and 1996–2000 with use of inpatient registries, 2001, and 2002–2008 and 2009–2014 with use of inpatient and outpatient registries. The cumulative incidence of first and repeat abdominal surgery (except closure of stomas), by category of surgical procedure, was estimated using the Kaplan–Meier method.ResultsAmong 21 273 patients with Crohn's disease, the cumulative incidence of first abdominal surgery within 5 years of Crohn's disease diagnosis decreased continuously from 54·8 per cent in 1990–1995 to 40·4 per cent in 1996–2000 (P < 0·001), and again from 19·8 per cent in 2002–2008 to 17·3 per cent in 2009–2014 (P < 0·001). Repeat 5-year surgery rates decreased from 18·9 per cent in 1990–1995 to 16·0 per cent in 1996–2000 (P = 0·009). After 2000, no further significant decreases were observed.ConclusionThe 5-year rate of surgical intervention for Crohn's disease has decreased significantly, but the rate of repeat surgery has remained stable despite the introduction of biological therapy.
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Affiliation(s)
- T D Kalman
- Division of Surgery, Department of Clinical and Experimental Medicine, Faulty of Health Sciences, Linköping University, Department of Surgery, County Council of Östergötland, Linköping, Sweden
| | - Å H Everhov
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
- Division of Clinical Epidemiology, Department of Medicine Solna, Stockholm, Sweden
| | - C Nordenvall
- Department of Molecular Medicine and Surgery, Stockholm, Sweden
- Centre for Digestive Disease, Division of Coloproctology, Karolinska University Hospital, Stockholm, Sweden
| | - M C Sachs
- Division of Clinical Epidemiology, Department of Medicine Solna, Stockholm, Sweden
| | - J Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - A Ekbom
- Division of Clinical Epidemiology, Department of Medicine Solna, Stockholm, Sweden
| | - J F Ludvigsson
- Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Paediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden
- Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA
| | - P Myrelid
- Division of Surgery, Department of Clinical and Experimental Medicine, Faulty of Health Sciences, Linköping University, Department of Surgery, County Council of Östergötland, Linköping, Sweden
| | - O Olén
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
- Division of Clinical Epidemiology, Department of Medicine Solna, Stockholm, Sweden
- Department of Paediatric Gastroenterology and Nutrition, Sachs' Children and Youth Hospital, Stockholm, Sweden
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Lee S, Crowe M, Seow CH, Kotze PG, Kaplan GG, Metcalfe A, Ricciuto A, Benchimol EI, Kuenzig ME. The impact of surgical therapies for inflammatory bowel disease on female fertility. Cochrane Database Syst Rev 2019; 7:CD012711. [PMID: 31334846 PMCID: PMC6647933 DOI: 10.1002/14651858.cd012711.pub2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Women with inflammatory bowel disease (IBD) may require surgery, which may result in higher risk of infertility. Restorative proctocolectomy with ileal anal pouch anastomosis (IPAA) may increase infertility, but the degree to which IPAA affects infertility remains unclear, and the impact of other surgical interventions on infertility is unknown. OBJECTIVES Primary objective• To determine the effects of surgical interventions for IBD on female infertility.Secondary objectives• To evaluate the impact of surgical interventions on the need for assisted reproductive technology (ART), time to pregnancy, miscarriage, stillbirth, prematurity, mode of delivery (spontaneous vaginal, instrumental vaginal, or Caesarean section), infant requirement for resuscitation and neonatal intensive care, low and very low birth weight, small for gestational age, antenatal and postpartum hemorrhage, retained placenta, postpartum depression, gestational diabetes, and gestational hypertension/preeclampsia. SEARCH METHODS We searched MEDLINE, Embase, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to September 27, 2018, to identify relevant studies. We also searched references of relevant articles, conference abstracts, grey literature, and trials registers. SELECTION CRITERIA We included observational studies that compared women of reproductive age (≥ 12 years of age) who underwent surgery to women with IBD who had a different type of surgery or no surgery (i.e. treated medically). We also included studies comparing women before and after surgery. Any type of IBD-related surgery was permitted. Infertility was defined as an inability to become pregnant following 12 months of unprotected intercourse. Infertility at 6, 18, and 24 months was included as a secondary outcome. We excluded studies that included women without IBD and those comparing women with IBD to women without IBD.. DATA COLLECTION AND ANALYSIS Two review authors independently screened studies and extracted data. We used the Newcastle-Ottawa Scale to assess bias and GRADE to assess the overall certainty of evidence. We calculated the pooled risk ratio (RR) and 95% confidence interval (CI) using random-effects models. When individual studies reported odds ratios (ORs) and did not provide raw numbers, we pooled ORs instead. MAIN RESULTS We identified 16 observational studies for inclusion. Ten studies were included in meta-analyses, of which nine compared women with and without a previous IBD-related surgery and the other compared women with open and laparoscopic IPAA. Of the ten studies included in meta-analyses, four evaluated infertility, one evaluated ART, and seven reported on pregnancy-related outcomes. Seven studies in which women were compared before and after colectomy and/or IPAA were summarized qualitatively, of which five included a comparison of infertility, three included the use of ART, and three included other pregnancy-related outcomes. One study included a comparison of women with and without IPAA, as well as before and after IPAA, and was therefore included in both the meta-analysis and the qualitative summary. All studies were at high risk of bias for at least two domains.We are very uncertain of the effect of IBD surgery on infertility at 12 months (RR 5.45, 95% CI 0.41 to 72.57; 114 participants; 2 studies) and at 24 months (RR 3.59, 95% CI 1.32 to 9.73; 190 participants; 1 study). Infertility was lower in women who received laparoscopic surgery compared to open restorative proctocolectomy at 12 months (RR 0.70, 95% CI 0.38 to 1.27; 37 participants; 1 study).We are very uncertain of the effect of IBD surgery on pregnancy-related outcomes, including miscarriage (OR 2.03, 95% CI 1.14 to 3.60; 776 pregnancies; 5 studies), use of ART (RR 25.09, 95% CI 1.56 to 403.76; 106 participants; 1 study), delivery via Caesarean section (RR 2.23, 95% CI 1.00 to 4.95; 20 pregnancies; 1 study), stillbirth (RR 1.96, 95% CI 0.42 to 9.18; 246 pregnancies; 3 studies), preterm birth (RR 1.91, 95% CI 0.67 to 5.48; 194 pregnancies; 3 studies), low birth weight (RR 0.61, 95% CI 0.08 to 4.83), and small for gestational age (RR 2.54, 95% CI 0.80 to 8.01; 65 pregnancies; 1 study).Studies comparing infertility before and after IBD-related surgery reported numerically higher rates of infertility at six months (before: 1/5, 20.0%; after: 9/15, 60.0%; 1 study), at 12 months (before: 68/327, 20.8%; after: 239/377, 63.4%; 5 studies), and at 24 months (before: 14/89, 15.7%; after: 115/164, 70.1%; 2 studies); use of ART (before: 5.3% to 42.2%; after: 30.3% to 34.3%; proportions varied across studies due to differences in which women were identified as at risk of using ART); and delivery via Caesarean section (before: 8/73, 11.0%; after: 36/75, 48.0%; 2 studies). In addition, women had a longer time to conception after surgery (two to five months; 2 studies) than before surgery (5 to 16 months; 2 studies). The proportions of women experiencing miscarriage (before: 19/123, 15.4%; after: 21/134, 15.7%; 3 studies) and stillbirth (before: 2/38, 5.3%; after: 3/80: 3.8%; 2 studies) were similar before and after surgery. Fewer women experienced gestational diabetes after surgery (before: 3/37, 8.1%; after: 0/37; 1 study), and the risk of preeclampsia was similar before and after surgery (before: 2/37, 5.4%; after: 0/37; 1 study). We are very uncertain of the effects of IBD-related surgery on these outcomes due to poor quality evidence, including confounding bias due to increased age of women after surgery.We rated evidence for all outcomes and comparisons as very low quality due to the observational nature of the data, inclusion of small studies with imprecise estimates, and high risk of bias among included studies. AUTHORS' CONCLUSIONS The effect of surgical therapy for IBD on female infertility is uncertain. It is also uncertain if there are any differences in infertility among those undergoing open versus laparoscopic procedures. Previous surgery was associated with higher risk of miscarriage, use of ART, Caesarean section delivery, and giving birth to a low birth weight infant, but was not associated with risk of stillbirth, preterm delivery, or delivery of a small for gestational age infant. These findings are based on very low-quality evidence. As a result, definitive conclusions cannot be made, and future well-designed studies are needed to fully understand the impact of surgery on infertility and pregnancy outcomes.
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Affiliation(s)
- Sangmin Lee
- University of CalgaryCommunity Health SciencesCalgaryABCanada
| | - Megan Crowe
- University of OttawaSchool of Epidemiology and Public HealthOttawaONCanada
| | - Cynthia H Seow
- University of CalgaryDepartment of MedicineTRW Building Rm 6D183280 Hospital Drive NWCalgaryABCanadaT2N 4Z6
| | - Paulo G Kotze
- Catholic University of Paraná (PUCPR)IBD Outpatients Clinic, Colorectal Surgery UnitCuritibaBrazil
| | - Gilaad G Kaplan
- University of CalgaryDepartment of MedicineTRW Building Rm 6D183280 Hospital Drive NWCalgaryABCanadaT2N 4Z6
| | - Amy Metcalfe
- University of CalgaryDepartment of Obstetrics & GynecologyCalgaryAlbertaCanada
| | - Amanda Ricciuto
- The Hospital for Sick ChildrenDivision of Gastroenterology, Hepatology & NutritionTorontoONCanada
| | - Eric I Benchimol
- The Children's Hospital of Eastern OntarioDivision of Gastroenterology Hepatology & Nutrition401 Smyth RoadOttawaONCanadaK1H 8L1
- University of OttawaDepartment of PediatricsOttawaONCanada
| | - M Ellen Kuenzig
- The Children's Hospital of Eastern OntarioDivision of Gastroenterology Hepatology & Nutrition401 Smyth RoadOttawaONCanadaK1H 8L1
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10
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Koliani-Pace JL, Siegel CA. Prognosticating the Course of Inflammatory Bowel Disease. Gastrointest Endosc Clin N Am 2019; 29:395-404. [PMID: 31078243 DOI: 10.1016/j.giec.2019.02.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Both Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) that can lead to progressive irreversible bowel damage. Selecting the most appropriate therapy for patients is a challenge because not all patients diagnosed with IBD have complications, and the amount of time to develop a complication is different for individuals. Models using patient characteristics, genetics, and immune responses help identify those patients who require early aggressive therapy with a goal to modify their disease course. Future research will help identify the role that the microbiome, metagenomics, metaproteomics, and microRNAs play in a patient prognosis.
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Affiliation(s)
- Jenna L Koliani-Pace
- Inflammatory Bowel Disease Center, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Dartmouth-Hitchcock, 1 Medical Center Drive, Lebanon, NH 03766, USA
| | - Corey A Siegel
- Inflammatory Bowel Disease Center, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
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11
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Lee HW, Park SJ, Jeon SR, Ye BD, Park JJ, Cheon JH, Kim TI, Kim WH. Long-Term Outcomes of Endoscopic Balloon Dilation for Benign Strictures in Patients with Inflammatory Bowel Disease. Gut Liver 2019; 12:530-536. [PMID: 29730904 PMCID: PMC6143444 DOI: 10.5009/gnl17396] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 01/08/2018] [Accepted: 02/09/2018] [Indexed: 12/14/2022] Open
Abstract
Background/Aims Benign intestinal strictures are common complications in patients with inflammatory bowel disease (IBD). This study aimed to assess the long-term prognosis of endoscopic balloon dilation (EBD) to treat benign strictures in IBD patients. Methods Patients with IBD who had benign strictures and who underwent EBD in four tertiary referral university hospitals between January 2004 and February 2014 were retrospectively reviewed. Technical success was defined as the ability to pass the scope through the stricture after balloon dilation, and clinical success was defined as improved obstructive symptoms. Results Forty-two benign strictures were identified in 30 patients (15 males and 15 females). Technical success was achieved in 26 patients (86.7%) at the first EBD attempt and in all 30 patients (100%) at the second EBD attempt. Clinical success was seen in 28 patients (93.3%). The median follow-up duration was 134.8 months (range, 10.2 to 252.0 months), and recurrence occurred in eight patients (26.7%), who required repeat EBD. The median duration to relapse was 1.7 months (range, 0.2 to 6.3 months). During repeat EBD, perforation occurred in two cases (6.7%), which were both clipped successfully. Finally, only one patient (3.3%) underwent surgery for the relief of recurrent obstructive symptoms during the follow-up period. Conclusions The experience of 10 years shows that EBD is safe and effective for the treatment of benign strictures in IBD patients. Importantly, EBD may allow long-term effective palliation of the symptoms associated with benign intestinal strictures in IBD patients.
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Affiliation(s)
- Hye Won Lee
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Soo Jung Park
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Seong Ran Jeon
- Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Jun Park
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Il Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Won Ho Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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12
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Kerur B, Machan JT, Shapiro JM, Cerezo CS, Markowitz J, Mack DR, Griffiths AM, Otley AR, Pfefferkorn MD, Rosh JR, Keljo DJ, Boyle B, Oliva-Hemker M, Kay MH, Saeed SA, Grossman AB, Sudel B, Kappelman MD, Schaefer M, Tomer G, Bousvaros A, Lerer T, Hyams JS, LeLeiko NS. Biologics Delay Progression of Crohn's Disease, but Not Early Surgery, in Children. Clin Gastroenterol Hepatol 2018; 16:1467-1473. [PMID: 29486253 DOI: 10.1016/j.cgh.2018.02.027] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 02/09/2018] [Accepted: 02/16/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from diagnosis. We investigated the recent risk of bowel surgery in an inception cohort of pediatric patients with CD and whether early use of biologics (tumor necrosis factor antagonists) alters later disease course. METHODS We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group registry on 1442 children (age, ≤16 y) diagnosed with CD from January 2002 through December 2014. Data were collected at diagnosis, 30 days following diagnosis, and then quarterly and during hospitalizations for up to 12 years. Our primary aim was to determine the 10-year risk for surgery in children with CD. Our secondary aim was to determine whether early use of biologics (<3 mo of diagnosis) affected risk of disease progression. RESULTS The 10-year risk of first bowel surgery was 26%. The 5-year risk of bowel surgery did not change from 2002 through 2014, and remained between 13% and 14%. Most surgeries occurred within 3 years from diagnosis. The only predictor of surgery was disease behavior at diagnosis. CD with inflammatory behavior had the lowest risk of surgery compared to stricturing disease, penetrating disease, or both. We associated slowing of disease progression to stricturing or penetrating disease (but not surgery) with early use of biologics, but this effect only became evident after 5 years of disease. Our results indicate that biologics slow disease progression over time (hazard ratio, 0.85; 95% CI, 0.76-0.95). CONCLUSIONS In an analysis of data from a registry of pediatric patients with CD, we found that among those with significant and progressing disease at or shortly after presentation, early surgery is difficult to prevent, even with early use of biologics. Early use of biologics (<3 mo of diagnosis) can delay later disease progression to stricturing and/or penetrating disease, but this affect could become evident only years after initial management decisions are made.
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Affiliation(s)
- Basavaraj Kerur
- Pediatric Gastroenterology and Nutrition, Hasbro Children Hospital, Providence, Rhode Island; The Warren Alpert Medical School, Brown University, Providence, Rhode Island
| | - Jason T Machan
- The Warren Alpert Medical School, Brown University, Providence, Rhode Island; Lifespan Biostatistics Core, Rhode Island Hospital, Providence, Rhode Island
| | - Jason M Shapiro
- Pediatric Gastroenterology and Nutrition, Hasbro Children Hospital, Providence, Rhode Island; The Warren Alpert Medical School, Brown University, Providence, Rhode Island
| | - Carolina S Cerezo
- Pediatric Gastroenterology and Nutrition, Hasbro Children Hospital, Providence, Rhode Island; The Warren Alpert Medical School, Brown University, Providence, Rhode Island
| | - James Markowitz
- Steven & Alexandra Cohen Children's Medical Center, Lake Success, New York
| | - David R Mack
- Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | | | | | | | - Joel R Rosh
- Goryeb Children's Hospital/Atlantic Health, Morristown, New Jersey
| | - David J Keljo
- Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | | | | | - Marsha H Kay
- The Cleveland Clinic Foundation, Cleveland, Ohio
| | | | | | - Boris Sudel
- University of Minnesota, Minneapolis, Minnesota
| | | | - Marc Schaefer
- Penn State Hershey Children's Hospital, Hershey, Pennsylvania
| | - Gitit Tomer
- Children's Hospital at Montefiore, Bronx, New York
| | | | - Trudy Lerer
- Connecticut Children's Medical Center, Hartford, Connecticut
| | - Jeffrey S Hyams
- Connecticut Children's Medical Center, Hartford, Connecticut
| | - Neal S LeLeiko
- Pediatric Gastroenterology and Nutrition, Hasbro Children Hospital, Providence, Rhode Island; The Warren Alpert Medical School, Brown University, Providence, Rhode Island.
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13
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Age at disease onset of inflammatory bowel disease is associated with later extraintestinal manifestations and complications. Eur J Gastroenterol Hepatol 2018; 30:598-607. [PMID: 29360691 DOI: 10.1097/meg.0000000000001072] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION A small but increasing number of patients with inflammatory bowel disease are diagnosed during childhood or adolescence, and disease distribution and severity at onset vary according to the age at diagnosis. Clinical factors present at the time of diagnosis can be predictive of the disease course. AIM The aim of this study was to characterize disease behavior and the cumulative complications and extraintestinal manifestations 10 years after the diagnosis and to assess their association with age at diagnosis. PATIENTS AND METHODS Data of patients participating with the Swiss IBD cohort study registry, a disease duration of 10 years and a complete data set were analyzed. The outcome was defined as the cumulative change of disease behavior, the occurrence of extra-intestinal manifestations or complications, and the necessity for medical or surgical interventions. RESULTS A total of 481 patients with Crohn's disease (CD) and 386 patients with ulcerative colitis (UC), grouped according to disease onset before 10, 17, 40, or after 40 years of age, were analyzed. Despite differences in sex, initial disease location, and smoking habits, at 10 years after the diagnosis, no difference was found regarding disease behavior in CD or regarding progression of disease extension in UC. Similarly, no age-of-onset-dependent cumulative need for medical or surgical therapies was found. However, higher rates of anemia and lower rates of arthralgia and osteopenia were found in both pediatric-onset CD and UC, and a tendency toward higher rates of stomatitis in pediatric-onset CD, and of primary sclerosing cholangitis and ankylosing spondylitis in pediatric-onset UC. CONCLUSION After 10 years of disease evolution, age at disease onset is not anymore associated with disease behavior but only with a small difference in the occurrence of specific extraintestinal manifestations and complications.
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14
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Pernat Drobež C, Ferkolj I, Potočnik U, Repnik K. Crohn's Disease Candidate Gene Alleles Predict Time to Progression from Inflammatory B1 to Stricturing B2, or Penetrating B3 Phenotype. Genet Test Mol Biomarkers 2018; 22:143-151. [PMID: 29446656 DOI: 10.1089/gtmb.2017.0210] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM Crohn's disease (CD) patients are mostly diagnosed with the uncomplicated inflammatory form of disease; however, the majority will progress to complicated stricturing or penetrating disease over time. It is important to identify patients at risk for disease progression at an early stage. The aim of our study was to examine the role of 33 candidate CD genes as possible predictors of disease progression and their influence on time to progression from an inflammatory to a stricturing or penetrating phenotype. METHODS Patients with an inflammatory phenotype at diagnosis were followed for 10 years and 33 CD-associated polymorphisms were genotyped. To test for association with CD, 449 healthy individuals were analyzed as the control group. RESULTS Ten years after diagnosis, 39.1% of patients had not progressed beyond an inflammatory phenotype, but 60.9% had progressed to complicated disease, with average time to progression being 5.91 years. Association analyses of selected single nucleotide polymorphisms (SNPs) confirmed associations with CD for 12 SNPs. Furthermore, seven loci were associated with disease progression, out of which SNP rs4263839 in the gene TNFSF15 showed the strongest association with disease progression and the frameshift mutation rs2066847 in the gene NOD2 showed the strongest association with time to progression. CONCLUSIONS The results of our study identified specific genetic biomarkers as useful predictors of both disease progression and speed of disease progression in patients with CD.
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Affiliation(s)
- Cvetka Pernat Drobež
- 1 Department of Gastroenterology, University Medical Centre Maribor , Maribor, Slovenia
| | - Ivan Ferkolj
- 2 Department of Gastroenterology, Division of Internal Medicine, University Medical Centre Ljubljana , Ljubljana, Slovenia
| | - Uroš Potočnik
- 3 Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor , Maribor, Slovenia .,4 Laboratory for Biochemistry, Molecular Biology and Genomics, Faculty for Chemistry and Chemical Engineering, University of Maribor , Maribor, Slovenia
| | - Katja Repnik
- 3 Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor , Maribor, Slovenia .,4 Laboratory for Biochemistry, Molecular Biology and Genomics, Faculty for Chemistry and Chemical Engineering, University of Maribor , Maribor, Slovenia
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15
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Nasiri S, Kuenzig ME, Benchimol EI. Long-term outcomes of pediatric inflammatory bowel disease. Semin Pediatr Surg 2017; 26:398-404. [PMID: 29126510 DOI: 10.1053/j.sempedsurg.2017.10.010] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The incidence and prevalence of childhood-onset inflammatory bowel diseases (IBD), including subtypes Crohn's disease and ulcerative colitis, have risen dramatically in recent years, and have emerged globally as important pediatric chronic diseases. Therefore, health care providers are more frequently encountering very young children with IBD, a chronic and incurable condition requiring life-long therapy. These children are living long lives with IBD and therefore knowledge of long-term outcomes is increasingly important to better counsel families and determine the best course of treatment. This review summarizes the current knowledge and literature surrounding long-term outcomes of pediatric IBD, with emphasis on the following areas: need for surgery due to complicated disease behavior, risk of disease remission and recurrence, mental health and psychosocial well-being, educational outcomes, linear growth impairment, cancer risk, and mortality. In addition, we review recent research about predicting negative long-term outcomes in children with IBD.
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Affiliation(s)
- Soheila Nasiri
- Division of Gastroenterology, Hepatology and Nutrition, CHEO Inflammatory Bowel Disease Centre, Children's Hospital of Eastern Ontario, 401 Smyth Rd, Ottawa, Canada K1H 8L1
| | - Mary Ellen Kuenzig
- Division of Gastroenterology, Hepatology and Nutrition, CHEO Inflammatory Bowel Disease Centre, Children's Hospital of Eastern Ontario, 401 Smyth Rd, Ottawa, Canada K1H 8L1; Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, Canada; Institute for Clinical Evaluative Sciences, Ottawa, Canada
| | - Eric I Benchimol
- Division of Gastroenterology, Hepatology and Nutrition, CHEO Inflammatory Bowel Disease Centre, Children's Hospital of Eastern Ontario, 401 Smyth Rd, Ottawa, Canada K1H 8L1; Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, Canada; Institute for Clinical Evaluative Sciences, Ottawa, Canada; Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.
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16
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Keihanian S, Moss AC. Crohn’s disease stricture evaluation and management. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2016; 18:136-144. [DOI: 10.1016/j.tgie.2016.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Ahmed I, Roy BC, Khan SA, Septer S, Umar S. Microbiome, Metabolome and Inflammatory Bowel Disease. Microorganisms 2016; 4:microorganisms4020020. [PMID: 27681914 PMCID: PMC5029486 DOI: 10.3390/microorganisms4020020] [Citation(s) in RCA: 134] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 05/25/2016] [Accepted: 06/06/2016] [Indexed: 12/17/2022] Open
Abstract
Inflammatory Bowel Disease (IBD) is a multifactorial disorder that conceptually occurs as a result of altered immune responses to commensal and/or pathogenic gut microbes in individuals most susceptible to the disease. During Crohn’s Disease (CD) or Ulcerative Colitis (UC), two components of the human IBD, distinct stages define the disease onset, severity, progression and remission. Epigenetic, environmental (microbiome, metabolome) and nutritional factors are important in IBD pathogenesis. While the dysbiotic microbiota has been proposed to play a role in disease pathogenesis, the data on IBD and diet are still less convincing. Nonetheless, studies are ongoing to examine the effect of pre/probiotics and/or FODMAP reduced diets on both the gut microbiome and its metabolome in an effort to define the healthy diet in patients with IBD. Knowledge of a unique metabolomic fingerprint in IBD could be useful for diagnosis, treatment and detection of disease pathogenesis.
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Affiliation(s)
- Ishfaq Ahmed
- Department of Surgery, University of Kansas Medical Center, 3901 Rainbow Blvd, 4028 Wahl Hall East, Kansas City, KS 66160, USA.
| | - Badal C Roy
- Department of Surgery, University of Kansas Medical Center, 3901 Rainbow Blvd, 4028 Wahl Hall East, Kansas City, KS 66160, USA.
| | - Salman A Khan
- Department of Internal Medicine and Department of Pediatrics, University of Missouri, Kansas City, MO 64110, USA.
| | - Seth Septer
- Department of Internal Medicine and Department of Pediatrics, University of Missouri, Kansas City, MO 64110, USA.
| | - Shahid Umar
- Department of Surgery, University of Kansas Medical Center, 3901 Rainbow Blvd, 4028 Wahl Hall East, Kansas City, KS 66160, USA.
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Vutcovici M, Bitton A, Ernst P, Kezouh A, Suissa S, Brassard P. Inflammatory bowel disease and risk of mortality in COPD. Eur Respir J 2016; 47:1357-64. [PMID: 26869671 DOI: 10.1183/13993003.01945-2015] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Accepted: 01/06/2016] [Indexed: 12/24/2022]
Abstract
Patients with chronic obstructive pulmonary disease (COPD) have higher incidence and prevalence of other chronic inflammatory diseases, including inflammatory bowel disease (IBD). We assessed whether IBD onset increases mortality risk in patients with COPD or asthma-associated COPD.Two population-based cohorts of COPD and asthma-COPD subjects were identified using the administrative health databases in Québec, Canada, 1990-2007. Death records were retrieved from the death certificate registry. Cox proportional hazards models were used to assess the impact of newly developed IBD on mortality risk.The COPD and asthma-COPD cohorts included 273 208 and 26 575 patients, respectively, of which 697 and 119 developed IBD. IBD increased the risk of all-cause mortality in both COPD (hazard ratio 1.23, 95% CI 1.09-1.4) and asthma-COPD (hazard ratio 1.65, 95% CI 1.23-2.22). In asthma-COPD patients, IBD increased the risk of mortality from respiratory conditions (hazard ratio 2.18, 95% CI 1.31-3.64); in COPD patients, IBD increased the risk of death from digestive conditions (hazard ratio 4.45, 95% CI 2.39-8.30).IBD is a risk factor for mortality in patients with pre-existing COPD or asthma-COPD. IBD increased mortality by respiratory and digestive conditions in patients with asthma-COPD and COPD, respectively.
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Affiliation(s)
- Maria Vutcovici
- Division of Gastroenterology, McGill University Health Centre, Montréal, QC, Canada
| | - Alain Bitton
- Division of Gastroenterology, McGill University Health Centre, Montréal, QC, Canada Faculty of Medicine, McGill University, Montréal, QC, Canada
| | - Pierre Ernst
- Faculty of Medicine, McGill University, Montréal, QC, Canada Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
| | - Abbas Kezouh
- Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
| | - Samy Suissa
- Faculty of Medicine, McGill University, Montréal, QC, Canada Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
| | - Paul Brassard
- Faculty of Medicine, McGill University, Montréal, QC, Canada Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
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Abstract
Introduction The present review serves to provide a concise overview of the current knowledge on therapeutic strategies with regard to fibrostenotic lesions in Crohn's disease. Methods A literature search was performed focusing on the last 5 years, and current concepts of pathophysiology, epidemiology, and treatment have been summarized. Results Fibrostenotic lesions in Crohn's disease are currently considered to be a consequence of the chronic inflammatory nature of the disease. Hence, therapeutic strategies are limited to the concept that early treatment of the inflammatory lesions can prevent structural changes, and to various endoscopic and surgical approaches. Direct targeting of the fibrostenotic lesion itself has not been the focus until now. This review will provide an overview of the pathophysiology and epidemiology of fibrostenotic lesions including current therapeutic approaches. Since research with regard to other organ systems and fibrosis is far more advanced, current strategies from available studies in these areas will be discussed. The results and the potential impact for Crohn's disease will be considered. Conclusion The vision of these approaches is to reverse structural changes and restore normal function.
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Affiliation(s)
- Britta Siegmund
- Medical Department (Gastroenterology, Infectious Diseases, Rheumatology), Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany
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20
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Orofacial granulomatosis in children: think about Crohn's disease. Dig Liver Dis 2015; 47:338-41. [PMID: 25618553 DOI: 10.1016/j.dld.2014.12.012] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 12/17/2014] [Accepted: 12/21/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND The term orofacial granulomatosis is conventionally used to describe patients with granulomatous lesions affecting the orofacial tissues, in absence of intestinal lesions. Lip swelling and facial swelling are the most common clinical signs. Despite the fact that histologically it is not distinguishable from Crohn's disease, and that both diseases have a chronic/recurrent course, the relationship between orofacial granulomatosis and Crohn's disease is still debated. METHODS Herein we present five cases of orofacial granulomatosis. RESULTS All patients presented concomitant Crohn's disease, supporting the hypothesis that orofacial granulomatosis and Crohn's disease may be one single disease. Thalidomide was effective in inducing remission of oral and intestinal symptoms in all five cases and could be considered a valid treatment opportunity for these patients. CONCLUSIONS Orofacial granulomatosis and Crohn's disease may be part of the same disease; both may respond to thalidomide.
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21
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Fowler SA, Ananthakrishnan AN, Gardet A, Stevens CR, Korzenik JR, Sands BE, Daly MJ, Xavier RJ, Yajnik V. SMAD3 gene variant is a risk factor for recurrent surgery in patients with Crohn's disease. J Crohns Colitis 2014; 8:845-51. [PMID: 24461721 PMCID: PMC4237062 DOI: 10.1016/j.crohns.2014.01.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 12/12/2013] [Accepted: 01/03/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS More than 80% of Crohn's disease (CD) patients will require surgery. Surgery is not curative and rates of re-operation are high. Identification of genetic variants associated with repeat surgery would allow risk stratification of patients who may benefit from early aggressive therapy and/or post-operative prophylactic treatment. METHODS CD patients who had at least one CD-related bowel resection were identified from the Prospective Registry in IBD Study at Massachusetts General Hospital (PRISM). The primary outcome was surgical recurrence. Covariates and potential interactions were assessed using the Cox proportional hazard model. Kaplan-Meier curves for time to surgical recurrence were developed for each genetic variant and analyzed with the log-rank test. RESULTS 194 patients were identified who had at least 1 resection. Of these, 69 had two or more resections. Clinical predictors for repeat surgery were stricturing (HR 4.18, p=0.022) and penetrating behavior (HR 3.97, p=0.024). Smoking cessation was protective for repeat surgery (HR 0.45, p=0.018). SMAD3 homozygosity for the risk allele was also independently associated with increased risk of repeat surgery (HR 4.04, p=0.001). NOD2 was not associated with increased risk of surgical recurrence. CONCLUSION Stricturing and penetrating behavior were associated with increased risk of surgical recurrence, while smoking cessation was associated with a decreased risk. A novel association between SMAD3 and increased risk of repeat operation and shorter time to repeat surgery was observed. This finding is of particular interest as SMAD3 may represent a new therapeutic target specifically for prevention of post-surgical disease recurrence.
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Affiliation(s)
- Sharyle A Fowler
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | | | - Agnes Gardet
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA,Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA
| | | | - Joshua R Korzenik
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Bruce E Sands
- Division of Gastroenterology, Mount Sinai School of Medicine, New York, NY
| | - Mark J Daly
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA
| | - Ramnik J Xavier
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA,Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA
| | - Vijay Yajnik
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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22
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Gomollón F, García-López S, Sicilia B, Gisbert JP, Hinojosa J. [Therapeutic guidelines on ulcerative colitis: a GRADE methodology based effort of GETECCU]. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 36:e1-47. [PMID: 24215088 DOI: 10.1016/j.gastrohep.2012.11.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Tsui FW, Tsui HW, Akram A, Haroon N, Inman RD. The genetic basis of ankylosing spondylitis: new insights into disease pathogenesis. APPLICATION OF CLINICAL GENETICS 2014; 7:105-15. [PMID: 24971029 PMCID: PMC4070859 DOI: 10.2147/tacg.s37325] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Ankylosing spondylitis (AS) is a complex disease involving multiple risk factors, both genetic and environmental. AS patients are predominantly young men, and the disease is characterized by inflammation and ankylosis, mainly at the cartilage–bone interface and enthesis. HLA-B27 has been known to be the major AS-susceptibility gene for more than 40 years. Despite advances made in the past few years, progress in the search for non-human leukocyte antigen susceptibility genes has been hampered by the heterogeneity of the disease. Compared to other complex diseases, such as inflammatory bowel disease (IBD), fewer susceptibility loci have been identified in AS. Furthermore, non-major histocompatibility-complex susceptibility loci discovered, such as ERAP1 and IL23R, are likely contributors to joint inflammation. Identification and confirmation of functional variants remains a significant challenge of investigations involving genome-wide association studies (GWAS). It remains unclear why none of the AS-susceptibility genes identified in GWAS appear to be directly involved in the ankylosing process. Numerous reviews have recently been published on the genetics of AS. Therefore, aside from a brief summary of what AS GWAS has successfully achieved thus far, this review will focus on directions that could address unanswered questions raised by GWAS.
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Affiliation(s)
- Florence Wl Tsui
- Genetics and Development Division, Toronto Western Research Institute, University Health Network ; Department of Immunology
| | - Hing Wo Tsui
- Genetics and Development Division, Toronto Western Research Institute, University Health Network
| | - Ali Akram
- Genetics and Development Division, Toronto Western Research Institute, University Health Network ; Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Nigil Haroon
- Genetics and Development Division, Toronto Western Research Institute, University Health Network ; Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Robert D Inman
- Genetics and Development Division, Toronto Western Research Institute, University Health Network ; Institute of Medical Science, University of Toronto, Toronto, ON, Canada
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Moran GW, Dubeau MF, Kaplan GG, Yang H, Seow CH, Fedorak RN, Dieleman LA, Barkema HW, Ghosh S, Panaccione R. Phenotypic features of Crohn's disease associated with failure of medical treatment. Clin Gastroenterol Hepatol 2014; 12:434-42.e1. [PMID: 23978351 DOI: 10.1016/j.cgh.2013.08.026] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 08/08/2013] [Accepted: 08/13/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There is conflicting evidence on the effects of thiopurines (azathioprine or mercaptopurine) and anti-tumor necrosis factor (TNF) therapies on rates of surgery among patients with Crohn's disease (CD). We aimed to identify factors that identify patients who are unlikely to respond to medical therapy and will therefore require surgery. METHODS We performed a retrospective study using the Alberta Inflammatory Bowel Disease Consortium registry to identify 425 patients diagnosed with CD who received a prescription of a thiopurine and/or an anti-TNF agent from a referral center, from July 1, 1975, through September 13, 2012. We collected data on CD-related abdominal surgery after therapy and disease features when therapy was instituted. Cox proportional regression models were used to associate disease features with outcomes after adjusting for potential confounders. Risk estimates were presented as hazard rate ratios (HRRs) with 95% confidence intervals (CIs). RESULTS Among patients given thiopurines, stricturing disease (adjusted HR, 4.63; 95% CI, 2.00-10.71), ileal location (adjusted HR, 6.20; 95% CI, 1.64-23.42), and ileocolonic location (adjusted HR, 3.71; 95% CI, 1.08-12.74) at the time of prescription were associated significantly with the need for surgery. Prescription of an anti-TNF agent after prescription of a thiopurine reduced the risk for surgery, compared with patients prescribed only a thiopurine (adjusted HR, 0.41; 95% CI, 0.22-0.75). Among patients given anti-TNF agents, stricturing (adjusted HR, 6.17; 95% CI, 2.81-13.54) and penetrating disease (adjusted HR, 3.39; 95% CI, 1.45-7.92) at the time of prescription were associated significantly with surgery. Older age at diagnosis (17-40 y) reduced the risk for abdominal surgery (adjusted HR, 0.41; 95% CI, 0.21-0.80) compared with a younger age group (≤16 y). Surgery before drug prescription reduced the risk for further surgeries among patients who received thiopurines (adjusted HR, 0.33; 95% CI, 0.13-0.68) or anti-TNF agents (adjusted HR, 0.49; 95% CI, 0.25-0.96). Terminal ileal disease location was not associated with a stricturing phenotype. CONCLUSIONS Based on a retrospective database analysis, patients prescribed thiopurine or anti-TNF therapy when they have a complicated stage of CD are more likely to require surgery. Better patient outcomes are achieved by treating CD at early inflammation stages; delayed treatment increases rates of treatment failure.
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Affiliation(s)
- Gordon W Moran
- Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada; Division of Gastroenterology, University of Calgary, Alberta, Canada; Department of Medicine, University of Calgary, Alberta, Canada; Nottingham Digestive Diseases Centre, Biomedical Research Unit, University of Nottingham, Nottingham, United Kingdom
| | - Marie-France Dubeau
- Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada; Division of Gastroenterology, University of Calgary, Alberta, Canada; Department of Medicine, University of Calgary, Alberta, Canada
| | - Gilaad G Kaplan
- Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada; Division of Gastroenterology, University of Calgary, Alberta, Canada; Department of Medicine, University of Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Alberta, Canada
| | - Hong Yang
- Department of Community Health Sciences, University of Calgary, Alberta, Canada
| | - Cynthia H Seow
- Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada; Division of Gastroenterology, University of Calgary, Alberta, Canada; Department of Medicine, University of Calgary, Alberta, Canada
| | - Richard N Fedorak
- Division of Gastroenterology, Department of Medicine University of Alberta, Edmonton, Alberta, Canada
| | - Levinus A Dieleman
- Division of Gastroenterology, Department of Medicine University of Alberta, Edmonton, Alberta, Canada
| | - Herman W Barkema
- Department of Community Health Sciences, University of Calgary, Alberta, Canada; Department of Production Animal Health, University of Calgary, Alberta, Canada
| | - Subrata Ghosh
- Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada; Division of Gastroenterology, University of Calgary, Alberta, Canada; Department of Medicine, University of Calgary, Alberta, Canada
| | - Remo Panaccione
- Inflammatory Bowel Disease Clinic, University of Calgary, Alberta, Canada; Division of Gastroenterology, University of Calgary, Alberta, Canada; Department of Medicine, University of Calgary, Alberta, Canada.
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Frolkis AD, Dykeman J, Negrón ME, Debruyn J, Jette N, Fiest KM, Frolkis T, Barkema HW, Rioux KP, Panaccione R, Ghosh S, Wiebe S, Kaplan GG. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology 2013; 145:996-1006. [PMID: 23896172 DOI: 10.1053/j.gastro.2013.07.041] [Citation(s) in RCA: 643] [Impact Index Per Article: 53.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2013] [Revised: 07/12/2013] [Accepted: 07/24/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The inflammatory bowel diseases (IBDs) are chronic diseases that often require surgery. However, the risk of requirement of surgery over time has not been well characterized. We performed a systematic review and meta-analysis to establish the cumulative risk of surgery among patients with IBD and evaluated how this risk has changed over time. METHODS We searched Medline, EMBASE, PubMed, and conference proceedings (2009-2012) on May 8, 2013, for terms related to IBD and intestinal surgery. Two reviewers screened 8338 unique citations to identify 486 for full-text review. The analysis included population-based studies published as articles (n = 26) and abstracts (n = 4) that reported risks of surgery at 1, 5, or 10 years after a diagnosis of Crohn's disease and/or ulcerative colitis. The trend in risk of surgery over time was analyzed by meta-regression using mixed-effect models. RESULTS Based on all population-based studies, the risk of surgery 1, 5, and 10 years after diagnosis of Crohn's disease was 16.3% (95% confidence interval [CI], 11.4%-23.2%), 33.3% (95% CI, 26.3%-42.1%), and 46.6% (95% CI, 37.7%-57.7%), respectively. The risk of surgery 1, 5, and 10 years after diagnosis of ulcerative colitis was 4.9% (95% CI, 3.8%-6.3%), 11.6% (95% CI, 9.3%-14.4%), and 15.6% (95% CI, 12.5%-19.6%), respectively. The risk of surgery 1, 5, and 10 years after diagnosis of Crohn's disease and 1 and 10 years after diagnosis of ulcerative colitis has decreased significantly over the past 6 decades (P < .05). CONCLUSIONS Based on systematic review and meta-analysis of population-based studies, the risk of intestinal surgery among patients with IBD has decreased over the past 6 decades.
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Affiliation(s)
- Alexandra D Frolkis
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences and Institute of Public Health, University of Calgary, Calgary, Alberta, Canada
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Mortality and cancer in pediatric-onset inflammatory bowel disease: a population-based study. Am J Gastroenterol 2013; 108:1647-53. [PMID: 23939626 DOI: 10.1038/ajg.2013.242] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Accepted: 01/31/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Although the incidence of pediatric inflammatory bowel disease (IBD) continues to rise in Northern France, the risks of death and cancer in this population have not been characterized. METHODS All patients <17 years, recorded in EPIMAD registry, and diagnosed between 1988 and 2004 with Crohn's disease (CD) or ulcerative colitis (UC) were included. The observed incidences of death and cancer were compared with those expected in the regional general population obtained by French Statistical Institute (INSEE) and the cancer Registry from Lille. Comparisons were performed using Fisher's exact test and were expressed using the standardized mortality ratios (SMRs) and standardized incidence ratios. RESULTS A total of 698 patients (538 with CD and 160 with UC) were identified; 360 (52%) were men, the median age at IBD diagnosis was 14 years (12-16) and the median follow-up time was 11.5 years (7-15). During follow-up, the mortality rate was 0.84% (6/698) and did not differ from that in the reference population (SMR=1.4 (0.5-3.0); P=0.27). After a median follow-up of 15 years (10-17), 1.3% of patients (9/698) had a cancer: colon (n=2), biliary tract (cholangiocarcinoma; n=1), uterine cervix (n=1), prepuce (n=1), skin (basal cell carcinoma (n=2), hematological (acute leukemia; n=1), and small bowel carcinoid (n=1). There was a significantly increased risk of cancer regardless of gender and age (standardized incidence ratio=3.0 (1.3-5.9); P<0.02). Four out of nine patients who developed a cancer had received immunosuppressants or anti-tumor necrosis factor-α therapy (including combination therapy in three patients). CONCLUSIONS In this large pediatric population-based IBD cohort, mortality did not differ from that of the general population but there was a significant threefold increased risk of neoplasia.
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Senanayake SM, Fernandopulle ANR, Niriella MA, Wijesinghe NT, Ranaweera A, Mufeena MN, Pathmeswaran A, Nawarathne NM, de Silva AP, de Silva HJ. The long-term outcomes of a cohort of Sri Lankan patients with ulcerative colitis: a retrospective study at two national referral centers and review of literature. Clin Exp Gastroenterol 2013; 6:195-200. [PMID: 24068873 PMCID: PMC3782511 DOI: 10.2147/ceg.s49202] [Citation(s) in RCA: 6] [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] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Inflammatory bowel disease, especially ulcerative colitis, is increasing in many "non-Western" countries, including Sri Lanka. The aim was to evaluate long-term outcomes of ulcerative colitis in a Sri Lankan population. METHODS A retrospective cohort study was conducted at the gastroenterology clinics of the Colombo North Teaching Hospital, Ragama and the National Hospital of Sri Lanka, Colombo; the two major referral centers for ulcerative colitis. All cases had histological confirmation of ulcerative colitis. Three outcomes: colectomy, development of colorectal carcinoma, and death were assessed. Patients not attending the clinic during the previous 4 weeks, or their families, were contacted to obtain clinical details and survival status. In those who had died, the cause of death was confirmed from clinical records and death certificates. RESULTS Details of 348/425 (81.9%) patients with ulcerative colitis (mean age 45.6 [standard deviation {SD} 14.3] years, male/female ratio = 1.00:1.03) were available. The mean follow-up was 6.8 (SD 6.5) years. The cumulative colectomy rates at 1, 5, 10, and 15 years were 1.5%, 4.0%, 5.5%, and 9.3% respectively. The cumulative probability of colorectal cancer in this cohort after 10 and 15 years was 0.47% and 2.36% respectively. The cumulative survival rate after 1, 5, 10, and 15 years was 99.7%, 98.9%, 98.1%, and 94.5% respectively. Patients with pancolitis were more likely to have disease-related death (P = 0.05). Multivariate analysis (Cox proportional hazards model) showed that an older age at diagnosis was associated with long-term mortality (hazard ratio, 1.11; P = 0.001). CONCLUSION In this cohort, colectomy, colorectal carcinoma, and death rates were low, suggesting a relatively benign disease course for ulcerative colitis.
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Ciacci C, Siniscalchi M, Bucci C, Zingone F, Morra I, Iovino P. Life events and the onset of celiac disease from a patient's perspective. Nutrients 2013; 5:3388-98. [PMID: 23989754 PMCID: PMC3798910 DOI: 10.3390/nu5093388] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2013] [Revised: 08/09/2013] [Accepted: 08/12/2013] [Indexed: 02/06/2023] Open
Abstract
Stressful events have been investigated in various immune-mediated diseases but not in celiac disease. Our aim was to examine the relationship of stressful events assessed by the standardized interview of Paykel with the diagnosis of celiac disease in comparison to patients, with a diagnosis of gastroesophageal reflux disease used as the control group. Adults with celiac disease (n = 186) reported more frequent and more severe life events in the years prior to the diagnosis than control patients (n = 96) (67.2% vs. 37.5%, p < 0.001, mean Paykel score 11.5 vs. 13.4, p = 0.001, respectively). Findings were not significantly different between celiac disease and control patients for the time lapse between the event and the diagnosis (mean 5.5 vs. 5.7 months). Pregnancy was defined as a negative event by 20.3% of celiac women, but never by control women. Findings were confirmed when analyses were repeated in the subgroup of patients of both groups with diagnosis made within one year of onset of symptoms. Data indicate that, before diagnosis, the number of stressful events in celiac disease was more frequent although less severe than in the control group suggesting that life events may favor the clinical appearance of celiac disease or accelerate its diagnosis.
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Affiliation(s)
- Carolina Ciacci
- Department of Medicine and Surgery, University of Salerno, via S.Allende 84081, Salerno 84081, Italy.
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Ryan JD, Silverberg MS, Xu W, Graff LA, Targownik LE, Walker JR, Carr R, Clara I, Miller N, Rogala L, Bernstein CN. Predicting complicated Crohn's disease and surgery: phenotypes, genetics, serology and psychological characteristics of a population-based cohort. Aliment Pharmacol Ther 2013; 38:274-83. [PMID: 23725363 DOI: 10.1111/apt.12368] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Revised: 02/20/2013] [Accepted: 05/16/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND Predictors of complicated Crohn's disease (CD), defined as stricturing or penetrating behaviour, and surgery have largely been derived from referral centre populations. AIM To investigate whether serological markers, susceptibility genes or psychological characteristics are associated with complicated CD or surgery in a population-based cohort. METHODS One hundred and eighty-two members of the Manitoba IBD Cohort with CD phenotyped using the Montreal classification underwent genetic and serological analysis at enrolment and after 5 years. One hundred and twenty-seven had paired sera at baseline and 5 years later and their data were used to predict outcomes at a median of 9.3 years. Serological analysis consisted of a seven antibody panel, and DNA was tested for CD-associated NOD2 variants (rs2066845,rs2076756,rs2066847), ATG16L1 (rs3828309, rs2241880) and IL23R (rs11465804). Psychological characteristics were assessed using semi-structured interviews and validated survey measures. RESULTS Sixty-five per cent had complicated CD and 42% underwent surgery. Multivariate analysis indicated that only ASCA IgG-positive serology was predictive of stricturing/penetrating behaviour (OR = 3.01; 95% CI: 1.28-7.09; P = 0.01) and ileal CD (OR = 2.2; 95% CI: 1.07-4.54, P = 0.03). Complicated CD behaviour was strongly associated with surgery (OR = 5.6; 95% CI: 2.43-12.91; P < 0.0001), whereas in multivariate analysis, only ASCA IgG was associated (OR = 2.66; 95% CI, 1.40-5.06, P = 0.003). ASCA titre results were similar at baseline and follow-up. Psychological characteristics were not significantly associated with disease behaviour, serological profile or genotype. CONCLUSIONS ASCA IgG at baseline was significantly associated with stricturing/penetrating disease at 9-10 years from diagnosis. Stricturing/penetrating disease was significantly associated with surgery. In a model including serology, the genotypes assessed did not significantly associate with complicated disease or surgery.
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Affiliation(s)
- J D Ryan
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
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Abstract
The occurrence of strictures as a complication of Crohn's disease is a significant clinical problem. No specific antifibrotic therapies are available. This systematic review comprehensively addresses the pathogenesis, epidemiology, prediction, diagnosis and therapy of this disease complication. We also provide specific recommendations for clinical practice and summarise areas that require future investigation.
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Affiliation(s)
- Florian Rieder
- Department of Pathobiology, Lerner Research Institute, NC22, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
| | - Ellen M Zimmermann
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Feza H Remzi
- Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
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Novak KL, Wilson SR. The Role of Ultrasound in the Evaluation of Inflammatory Bowel Disease. Semin Roentgenol 2013; 48:224-33. [DOI: 10.1053/j.ro.2013.03.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Abstract
BACKGROUND The aims of the present study are twofold. First, to describe labor participation rates of people with inflammatory bowel disease (IBD) in the Netherlands compared with the total Dutch population and to people with chronic illness in general. Second, to explore differences in labor participation among IBD patients and assess the potential impact of a number of characteristics of IBD patients on labor participation. METHODS Data were obtained from a nationwide survey of individuals with IBD in the Netherlands. In all, 1115 respondents completed the survey. Univariate, bivariate, and multinomial logistic regression analysis were conducted to identify factors predicting the number of hours worked by IBD patients. RESULTS People with IBD do not participate less often in the labor market compared with the total Dutch population age 15 to 64. However, male patients age 45 to 64 less often have a fulltime job compared with age- and gender-matched reference groups from the general population. People with IBD are more likely to participate in the labor market than people with chronic illness in general. Gender, age, duration of illness, having a stoma or pouch, comorbidity, vitality, pain, and perceived personal control appear to be significant predictors of the number of hours worked. CONCLUSIONS People with IBD in the Netherlands are as often employed as the general population, but among some gender/age categories fewer people work fulltime. Besides sociodemographic and illness characteristics, the perception of personal control over the illness explains differences in the number of hours worked. Strengthening IBD patients' control perceptions deserves attention.
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Affiliation(s)
- Justine E Netjes
- NIVEL, Netherlands Institute for Health Services Research, Utrecht, The Netherlands.
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Kalafateli M, Triantos C, Theocharis G, Giannakopoulou D, Koutroumpakis E, Chronis A, Sapountzis A, Margaritis V, Thomopoulos K, Nikolopoulou V. Health-related quality of life in patients with inflammatory bowel disease: a single-center experience. Ann Gastroenterol 2013; 26:243-248. [PMID: 24714279 PMCID: PMC3959431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Accepted: 01/30/2013] [Indexed: 10/28/2022] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) has a negative impact on health-related quality of life (HRQoL). The aim of the study was to assess HRQoL of IBD patients in South-Western Greece. METHODS 89 IBD patients [38 (42.7%) Crohn's disease (CD), 51 (57.3%) ulcerative colitis (UC)] were included. HRQoL was assessed using IBD questionnaire (IBDQ), which tests four health domains: bowel symptoms (BS), systemic symptoms (SS), emotional function (EF) and social function (SF). Total score (TS) ranges from 32 to 224. Disease activity was measured using Crohn's Disease Activity Index (CDAI) (CD), and Truelove and Witts classification (UC). The impact of epidemiological and disease-specific characteristics on IBDQ was studied. RESULTS No statistically significant difference was found in all IBDQ scores between UC and CD patients. No correlation was found regarding age, sex, smoking, anemia, disease duration and use of corticosteroids, 5-aminosalicylates or immunosuppressives with HRQoL. The factors found to have a major negative impact on all IBDQ scores was disease severity both in CD and UC, and education on bowel symptoms in CD. On multivariate analysis, only high disease activity had significant effects on total and dimensional scores of IBDQ in UC (TS, P=0.005; BS, P<0.001; SS, P=0.004; EF, P=0.05; SF, P=0.001), whereas in CD, only CDAI (TS, P=0.001; BS, P=0.004; SS, P=0.001; EF, P=0.003; SF, P=0.003) and education (TS, P=0.047; BS, P=0.004; SS, P=0.03) had significant effects. CONCLUSIONS IBD patients in remission experience better HRQoL than patients with active disease. Induction of remission should become the mainstay of care regarding improvement in HRQoL.
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Affiliation(s)
- Maria Kalafateli
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece
| | - Christos Triantos
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece
| | - Georgios Theocharis
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece
| | | | | | - Aristidis Chronis
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece
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Abstract
Stricture formation is a common complication of Crohn’s disease, occurring in approximately one third of all patients with this condition. While the traditional management of such strictures has been largely surgical, there have been case series going back three decades highlighting the potential role of endoscopic balloon dilation in this clinical setting. This review article summarizes the stricture pathogenesis, focusing on known clinical and genetic risk factors. It then highlights the endoscopic balloon dilation research to date, with particular emphasis on three large recent case series. It concludes by describing the literature consensus regarding specific methodology and presenting avenues for future investigations.
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Affiliation(s)
- Raluca Vrabie
- Raluca Vrabie, Gerald L Irwin, David Friedel, Winthrop University Hospital, 259 First Street, Mineola, NY 11501, United States
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Modesto I, Perricone G, Orlando A, Cottone M. Methodology for high-quality studies on course and prognosis of inflammatory bowel disease. World J Gastroenterol 2012; 18:3800-5. [PMID: 22876030 PMCID: PMC3413050 DOI: 10.3748/wjg.v18.i29.3800] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2012] [Revised: 05/10/2012] [Accepted: 05/26/2012] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are characterized by a chronic course with an alternation of relapses and remissions. Questions about prognosis are important for the patient who wants to know how the disease will affect his/her life and also for clinicians to make management decisions. Correct selection of the patients is the basis for good methodological studies on the course of IBD. A great proportion of data on the course of IBD is derived from a limited number of cohort studies. Studies help to define the endpoints for clinical trials and to identify subsets of patients in whom the prognosis of the disease can be stratified according to clinical features. Specific scientific requirements for high-quality studies on prognosis are the following: use of inception cohort, description of referral patterns, completeness of follow-up, objective outcome criteria, blind outcome assessment, adjustment for extraneous prognostic factors and statistical issues. We analyzed each of these requirements in studies on IBDs. To date, prospective and population-based cohort studies are the standard for an unbiased assessment of prognosis. A better knowledge of the course of disease of chronic disorders ideally requires: (1) data from population-based studies, to avoid selection bias from referral centers in which patients with a more severe disease are usually treated; (2) inclusion of patients seen at the onset of the disease excluding misdiagnosed cases; and (3) follow-up from the onset of the disease to the end without dropouts.
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Fréour T, Miossec C, Bach-Ngohou K, Dejoie T, Flamant M, Maillard O, Denis MG, Barriere P, Bruley des Varannes S, Bourreille A, Masson D. Ovarian reserve in young women of reproductive age with Crohn's disease. Inflamm Bowel Dis 2012; 18:1515-22. [PMID: 21936034 DOI: 10.1002/ibd.21872] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2011] [Accepted: 08/02/2011] [Indexed: 12/20/2022]
Abstract
BACKGROUND Crohn's disease (CD) mainly affects young adults of reproductive age. Whereas a large amount of data is available concerning pregnancy in young CD women, no study has been conducted on their ovarian reserve status. This study aimed to investigate the potential effect of CD on ovarian reserve in young women in remission, as reflected by serum anti-Müllerian hormone (AMH). METHODS This retrospective case-control study was conducted in the University Hospital of Nantes, France. Serum levels of AMH were retrospectively measured in 50 women with CD in remission and in 163 control women with normal ovarian reserve, matched by age. RESULTS No statistical difference was found between mean serum AMH levels in CD and control women. Serum AMH levels remained comparable between CD and control women <30 years, but they were significantly lower in CD women ≥ 30 years compared to the control group. Furthermore, the negative correlation between age and AMH level tended to be more pronounced in CD than control women. Multivariate analysis of CD patients' clinical and demographic characteristics showed that serum AMH level was influenced by disease location, with a colonic location of the disease being independently associated with a high risk of altered ovarian reserve. CONCLUSIONS Women with CD do not have severe ovarian reserve alterations compared to a control population. However, age ≥ 30 years and a colonic location of the disease could be associated with an accelerated loss of follicles. These data could encourage gastroenterologists to inform CD women of the risk of delaying childbirth.
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Affiliation(s)
- Thomas Fréour
- Department of Human Reproduction, University Hospital of Nantes, Nantes, France.
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Abstract
Phenotypically, the transition from early to late Crohn's disease is characterized by the occurrence of complications including strictures, intra-abdominal fistulas and perianal fistulas, all of them leading to various types of surgeries and currently non-reversible tissue damage. It must, however, be kept in mind that this transition is not at all a uniform and linear process. According to these simple phenotypic criteria, Crohn's disease can already be a late disease at diagnosis while in other patients, it can still be an early disease after 20 years of evolution. This simply highlights the relativity of time in this field, actually reflecting the nature, location and severity of the inflammatory process. The risk over time of the development of these complications has been described, first in cohort studies and then in population-based studies. Globally, at diagnosis, between 19 and 38% only of Crohn's disease patients have complicated Crohn's disease. After 10 years, between 56 and 65% of patients have developed either stricturing or penetrating complications. After 20 years, these numbers are between 61 and 88%. In parallel to these structural changes, changes in the immunobiology of the disease also seem to occur; the latter seem to happen quicker with major modification already within 2 years of the diagnosis. Beside these general figures, important questions remain pending. First, the real timing of these changes is still unclear. Second, the precise role of genetics and environment in the development of these changes remains to be clarified. Third, the correlation between changes in immunobiology and intestinal structural damages has not been specifically studied.
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Affiliation(s)
- Edouard Louis
- Gastroenterology Department, University Hospital of Liège, Liège, Belgium.
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Small bowel diagnostics: current place of small bowel endoscopy. Best Pract Res Clin Gastroenterol 2012; 26:209-20. [PMID: 22704565 DOI: 10.1016/j.bpg.2012.03.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Accepted: 03/08/2012] [Indexed: 01/31/2023]
Abstract
The small intestine has been difficult to examine by traditional endoscopic and radiologic techniques. Until the end of the last century, the small bowel follow through was the primary diagnostic tool for suspected small bowel disease. In recent years capsule endoscopy, deep enteroscopy using balloon-assisted or spiral techniques, computerized tomography and magnetic resonance enteroclysis or enterography have facilitated the diagnosis, monitoring, and management of patients with small bowel diseases. These technologies are complementary, each with its advantages and limitations. In the present article, we will discuss the different options and indications for modern diagnostic methods for visualization of the small bowel. We also try to provide a clinical rationale for the use of these different diagnostic options in less established, newly emerging, indications for small bowel evaluation.
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Eberle I, Moslem M, Henschler R, Cantz T. Engineered MSCs from Patient-Specific iPS Cells. ADVANCES IN BIOCHEMICAL ENGINEERING/BIOTECHNOLOGY 2012; 130:1-17. [PMID: 22915200 DOI: 10.1007/10_2012_156] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Mesenchymal stroma/stem cells (MSCs) represent a heterogenic cell population that can be isolated from various tissues of the body or can be generated from pluripotent stem cells by in vitro differentiation. Various promising pre-clinical and clinical studies suggest that MSCs might stimulate endogenous regeneration and/or act as anti-inflammatory agents, which could be of high therapeutic relevance for a number of diseases, including graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, inflammatory bowel diseases, or some forms of liver failure. Notably, conflicting results of various studies illustrated that the source of MSCs, the cultivation condition, and the way of administration have important effects on the desired clinical effect. Some of the involved molecular pathways have recently been elucidated and an artificial modulation of these pathways by engineered MSCs might result in superfunctional MSCs for enhanced endogenous regeneration or anti-inflammatory response. In this review, we summarize important findings of conventional MSCs for applications in gastroenterology and we describe the state-of-the-art for the generation of patient-derived iPS cells that eventually might provide genetically engineered superfunctional iPS cells for advanced cell therapies.
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Affiliation(s)
- Irina Eberle
- Junior Research Group Stem Cell Biology, OE 8881, Cluster-of-Excellence REBIRTH, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
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Lichtenstein GR, Targan SR, Dubinsky MC, Rotter JI, Barken DM, Princen F, Carroll S, Brown M, Stachelski J, Chuang E, Landers CJ, Stempak JM, Singh S, Silverberg MS. Combination of genetic and quantitative serological immune markers are associated with complicated Crohn's disease behavior. Inflamm Bowel Dis 2011; 17:2488-96. [PMID: 21391291 PMCID: PMC4203682 DOI: 10.1002/ibd.21661] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2010] [Accepted: 12/15/2010] [Indexed: 12/16/2022]
Abstract
BACKGROUND Treatment of Crohn's disease (CD) with biologics may alter disease progression, leading to fewer disease-related complications, but cost and adverse event profiles often limit their effective use. Tools identifying patients at high risk of complications, who would benefit the most from biologics, would be valuable. Previous studies suggest that biomarkers may aid in determining the course of CD. We aimed to determine if combined serologic immune responses and NOD2 genetic markers are associated with CD complications. METHODS In this cross-sectional study, banked blood from well-characterized CD patients (n = 593; mean follow-up: 12 years) from tertiary and community centers was analyzed for six serological biomarkers (ASCA-IgA, ASCA-IgG, anti-OmpC, anti-CBir1, anti-I2, pANCA). In a patient subset (n = 385), NOD2 (SNP8, SNP12, SNP13) genotyping was performed. Complications included stricturing and penetrating disease behaviors. A logistic regression model for the risk of complications over time was constructed and evaluated by cross-validation. RESULTS For each serologic marker, complication rates were stratified by quartile. Complication frequency was significantly different across quartiles for each marker (P trend ≤ 0.001). Patients with SNP13 NOD2 risk alleles experienced increased complications versus patients without NOD2 mutations (P ≤ 0.001). A calibration plot of modeled versus observed complication rates demonstrated good agreement (R = 0.973). Performance of the model integrating serologic and genetic markers was demonstrated by area under the receiver operating characteristic curve (AUC = 0.801; 95% confidence interval: 0.757-0.846). CONCLUSIONS This model combining serologic and NOD2 genetic markers may provide physicians with a tool to assess the probability of patients developing a complication over the course of CD.
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Affiliation(s)
- Gary R. Lichtenstein
- Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Stephan R. Targan
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California,Cedars-Sinai Inflammatory Bowel and Immunobiology Research Institute, Los Angeles, California
| | - Marla C. Dubinsky
- Cedars-Sinai Inflammatory Bowel and Immunobiology Research Institute, Los Angeles, California,Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California
| | - Jerome I. Rotter
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California,Cedars-Sinai Medical Genetics Institute, Los Angeles, California
| | - Derren M. Barken
- Research and Development, Prometheus Laboratories Inc., San Diego, California
| | - Fred Princen
- Research and Development, Prometheus Laboratories Inc., San Diego, California
| | - Susan Carroll
- Research and Development, Prometheus Laboratories Inc., San Diego, California
| | - Michelle Brown
- Research and Development, Prometheus Laboratories Inc., San Diego, California
| | - Jordan Stachelski
- Research and Development, Prometheus Laboratories Inc., San Diego, California
| | - Emil Chuang
- Research and Development, Prometheus Laboratories Inc., San Diego, California
| | - Carol J. Landers
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California,Cedars-Sinai Inflammatory Bowel and Immunobiology Research Institute, Los Angeles, California
| | - Joanne M. Stempak
- Mount Sinai Hospital IBD Group, Zane Cohen Centre for Digestive Diseases, University of Toronto, Toronto, Ontario, Canada
| | - Sharat Singh
- Research and Development, Prometheus Laboratories Inc., San Diego, California
| | - Mark S. Silverberg
- Mount Sinai Hospital IBD Group, Zane Cohen Centre for Digestive Diseases, University of Toronto, Toronto, Ontario, Canada
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Buchanan J, Wordsworth S, Ahmad T, Perrin A, Vermeire S, Sans M, Taylor J, Jewell D. Managing the long term care of inflammatory bowel disease patients: The cost to European health care providers. J Crohns Colitis 2011; 5:301-16. [PMID: 21683300 DOI: 10.1016/j.crohns.2011.02.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2010] [Revised: 02/02/2011] [Accepted: 02/02/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Inflammatory Bowel Disease (which includes Crohn's Disease and Ulcerative Colitis), is a chronic condition characterised by substantial morbidity. Inflammatory Bowel Disease patients are considered expensive to manage, hence accurate estimates of care costs are crucial to help healthcare providers plan clinical management. The aim of this study is to estimate the cost of care for Crohn's Disease and Ulcerative Colitis patients in the United Kingdom and Western mainland Europe. METHODS Decision models were built to simulate the natural disease history of Crohn's Disease and Ulcerative Colitis, informed by United Kingdom and European clinical pathways. A healthcare provider perspective was adopted, model inputs were informed by published sources and expert opinion, and UK healthcare costs were used (2008 prices). Cohorts of 25 year old patients presenting with symptoms of varying severity were modelled over ten years, and annual treatment costs calculated per patient. RESULTS The average annual cost of care per Crohn's Disease/Ulcerative Colitis patient was £631/£762 (United Kingdom) and £838/£796 (Europe). Most costs were incurred immediately following diagnosis, particularly in European Crohn's patients, reflecting the earlier use of more aggressive treatments. Surgery, hospitalisation, and the use of biological therapies and mesalazine (in Ulcerative Colitis) were key cost drivers. The total annual cost to the United Kingdom National Health Service of caring for Inflammatory Bowel Disease patients was estimated to be £131million. CONCLUSIONS This study confirms that Inflammatory Bowel Disease patients are expensive to manage and illustrates the importance of differentiating between alternative clinical management scenarios.
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Affiliation(s)
- James Buchanan
- Health Economics Research Centre, University of Oxford, Oxford, UK.
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Nguyen GC, Nugent Z, Shaw S, Bernstein CN. Outcomes of patients with Crohn's disease improved from 1988 to 2008 and were associated with increased specialist care. Gastroenterology 2011; 141:90-7. [PMID: 21458455 DOI: 10.1053/j.gastro.2011.03.050] [Citation(s) in RCA: 144] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2010] [Revised: 02/06/2011] [Accepted: 03/18/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS We investigated factors that affect long-term outcomes in Crohn's disease (CD). METHODS We performed a retrospective study of 3403 patients with CD, diagnosed between 1988 and 2008 in Manitoba, Canada. Subjects were assigned to cohorts based on diagnosis year: cohort I (before 1996), cohort II (1996-2000), or cohort III (2001 and after). We compared risks for surgery and hospitalization among the cohorts and assessed use of immunomodulators and specialists. RESULTS The 5-year risks of first surgery were 30%, 22%, and 18% for cohorts I, II, and III, respectively. The adjusted hazard ratios for first surgery in cohorts II and III, compared with cohort I, were 0.72 (95% confidence interval [CI], 0.62-0.84) and 0.57 (95% CI, 0.48-0.68), respectively. The adjusted hazard ratio for cohort III, compared with cohort II, was 0.79 (95% CI, 0.65-0.97). There was a higher prevalence of visits to a gastroenterologist within the first year of diagnosis among cohorts II and III (cohort I, 53%; cohort II, 72%; and cohort III, 88%; P<.0001), which was associated with a reduced need for surgery (hazard ratio, 0.83; 95% CI, 0.71-0.98) and contributed to differences in surgery rates among the cohorts. The association between early gastroenterology care and lower risk for surgery was most evident 2 years after diagnosis (hazard ratio, 0.66; 95% CI, 0.53-0.82). Use of immunomodulators within the first year of diagnosis was higher in cohort III than in cohort II (20% vs 11%; P<.0001). CONCLUSIONS Risk of surgery decreased among patients with CD diagnosed after, compared with before, 1996, and was associated with specialist care. Specialist care within 1 year of diagnosis might improve outcomes in CD.
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Affiliation(s)
- Geoffrey C Nguyen
- Mount Sinai Hospital IBD Centre, University of Toronto, Toronto, Ontario, Canada.
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Jäghult S, Saboonchi F, Johansson UB, Wredling R, Kapraali M. Identifying predictors of low health-related quality of life among patients with inflammatory bowel disease: comparison between Crohn's disease and ulcerative colitis with disease duration. J Clin Nurs 2011; 20:1578-87. [PMID: 21418363 DOI: 10.1111/j.1365-2702.2010.03614.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
AIM To identify predictors of low health-related quality of life among patients with inflammatory bowel disease and make a comparison between Crohn's disease and ulcerative colitis with disease duration. BACKGROUND Studies have shown that patients with inflammatory bowel disease rate their health-related quality of life lower, as compared with a general population. DESIGN Survey. METHODS In this study, 197 patients in remission were included and divided into a Crohn's disease group and an ulcerative colitis group. Each group was also divided into separate groups whether the patients had short disease duration or long disease duration. Generic instruments, combined with disease-specific questionnaires, were used for measuring health-related quality of life. RESULTS The analysis showed a non-significant effect for diagnosis, but a significant effect for disease duration showing that the patients with short disease duration had lower scores of health-related quality of life compared with patients with long disease duration. A significant interaction between diagnosis and disease duration was also revealed. CONCLUSION Patients with longer disease duration experienced a better health-related quality of life than patients with short disease duration. Patients with Crohn's disease and short disease duration have the lowest health-related quality of life and are in greatest need of education and support. RELEVANCE TO CLINICAL PRACTICE It is important to identify which patients' are in the greatest need of education and support.
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Affiliation(s)
- Susanna Jäghult
- Division of Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
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Yorulmaz E, Adali G, Yorulmaz H, Ulasoglu C, Tasan G, Tuncer I. Metabolic syndrome frequency in inflammatory bowel diseases. Saudi J Gastroenterol 2011; 17:376-82. [PMID: 22064334 PMCID: PMC3221110 DOI: 10.4103/1319-3767.87177] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIM Metabolic syndrome (MetS) is a clinical condition characterized by central obesity, elevated triglycerides, low-high density lipoproteins, impaired fasting glucose, and hypertension. There is insufficient data on the prevalence of MetS in patients with inflammatory bowel disease (IBD). This study sought to determine the prevalence of MetS in a Turkish cohort of patients with IBD and the association between insulin resistance (IR) and the MetS parameters, in this population. PATIENTS AND METHODS A total of 177 patients over 18 years of age (62 with Crohn's disease (CD) and 115 with ulcerative colitis (UC)) were enrolled in the study. The presence of at least three criteria of the International Diabetes Federation (IDF) was accepted for the diagnosis of MetS. The Homeostasis Model Assessment (HOMA) was used to determine IR. HOMA values < 1 were considered normal and values > 2.5 indicated a high probability of IR. RESULTS MetS frequency was higher in patients n=34 (29.5%) with UC than in patients n=11 (17.7%) with CD (P < 0.01). MetS was detected in 12 of the 117 patients (10.3%) with IBD, under 45 years of age, and in 33 of 60 patients (55%) over 45 years of age. HOMA value in n=31 patients (27%) with UC was > 2.5. Body mass index, insulin (P < 0.001), waist circumference, fasting plasma glucose, leukocyte count (P < 0.01), triglycerides, C-reactive protein, and uric acid values (P < 0.05) were significantly higher in UC patients with IR than those without IR. CONCLUSION Frequent occurrence of MS with increasing age in IBD, particularly in UC, showed the importance of early diagnosis and treatment of cardiovascular disease risk factors in the long-term follow-up of these diseases.
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Affiliation(s)
- Elif Yorulmaz
- Department of Gastroenterology, Goztepe, Training and Research Hospital, Istanbul, Turkey.
| | - Gupse Adali
- Department of Gastroenterology, Goztepe, Training and Research Hospital, Istanbul, Turkey
| | - Hatice Yorulmaz
- Department of Nursing, Halic University School of Nursing, Istanbul, Turkey
| | - Celal Ulasoglu
- Department of Gastroenterology, Goztepe, Training and Research Hospital, Istanbul, Turkey
| | - Guralp Tasan
- Department of Gastroenterology, Goztepe, Training and Research Hospital, Istanbul, Turkey
| | - Ilyas Tuncer
- Department of Gastroenterology, Goztepe, Training and Research Hospital, Istanbul, Turkey
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Prevalence of metabolic syndrome is comparable between inflammatory bowel disease patients and the general population. J Gastroenterol 2010; 45:1008-13. [PMID: 20414788 DOI: 10.1007/s00535-010-0247-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2009] [Accepted: 03/25/2010] [Indexed: 02/04/2023]
Abstract
BACKGROUND Metabolic syndrome (MS) is associated with an increased risk of cardiovascular disease. However, its prevalence in inflammatory bowel disease (IBD) patients remains largely unknown. This study was planned to determine the prevalence of MS in Japanese IBD patients. METHODS The prevalence of MS among outpatients with IBD aged 18 or older was studied using the modified National Cholesterol Education Program Adult Treatment Panel III definition. RESULTS A total of 107 quiescent IBD patients, including 76 ulcerative colitis (UC) patients and 31 Crohn's disease (CD) patients, were studied. Sufficient data were collected from a total of 102 patients. Prevalence of MS was significantly higher in UC (23.0%) patients compared to CD patients (7.1%). MS prevalence was substantially higher among male IBD patients (21.1%) compared to female IBD patients (12.9%), particularly in patients over 30 years of age. No difference was observed in the prevalence of MS between our IBD cohort and the general population in both males and females aged 40 years and older (P = 0.707 in males, P = 0.328 in females). IBD patients with MS were also older than those without (50.2 ± 15.0 vs. 38.0 ± 11.9 years, P = 0.013). In a logistic regression analysis, age was the statistically significant predictor of MS among IBD patients. The odds ratio (95% confidence interval) was 1.064 (1.017-1.114). CONCLUSIONS Prevalence of metabolic syndrome in our IBD patients was comparable to that of the general population. Because age was the independent risk factor for developing MS, evaluation for MS is needed for elderly IBD patients.
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van Langenberg DR, Lange K, Hetzel DJ, Holtmann GJ, Andrews JM. Adverse clinical phenotype in inflammatory bowel disease: a cross sectional study identifying factors potentially amenable to change. J Gastroenterol Hepatol 2010; 25:1250-8. [PMID: 20594252 DOI: 10.1111/j.1440-1746.2010.06302.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM A significant proportion with inflammatory bowel disease (IBD) exhibit an adverse clinical phenotype reflected in endpoints like surgery and hospitalizations. We sought to identify clinico-demographic factors associated with these adverse consequences that may be amenable to change. METHODS Over 6 months IBD patients visiting a metropolitan center were prospectively identified and given a comprehensive survey addressing patient knowledge, mental health and satisfaction with medical care along with other clinical data. Logistic regression analyses assessed for associations between clinico-demographic variables and adverse clinical endpoints (previous surgery [ever] and/or recent inpatient admission over a 16 month observation period). RESULTS Of 256 IBD patients, 162 responded (response rate 63%); 95 (59%) had Crohn's disease (CD), 63 (40%) ulcerative colitis (UC), four indeterminate colitis; 53% were female. Factors associated with a greater likelihood of hospitalization included moderate/severe disease activity, psychological co-morbidity, numbers of medications and outpatient visits (odds ratio [OR] 7.09 [2.83-17.76], 4.13 [1.25-13.61], 1.26 [1.03-1.54], 1.17 [1.00-1.37] respectively; all P < 0.05). Post-surgical patients were more likely to have CD, more currently active disease and longer disease duration (OR 8.55 [2.43-29.4], 3.52 [1.26, 9.87], 1.14 [1.08, 1.21] respectively; all P < 0.02), yet were less likely to have previously seen a gastroenterologist, OR 0.25 [0.08-0.76] (P = 0.01). CONCLUSIONS 'At risk' patients (those previously operated, with ongoing disease activity, dissatisfaction and/or psychological comorbidities) may benefit from early identification and more intensive management. Specialist gastroenterology care appears to be under-utilized in operated patients yet may reduce future IBD morbidity.
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Affiliation(s)
- Daniel R van Langenberg
- Department of Gastroenterology & Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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Barreiro-de Acosta M, Magro F, Carpio D, Lago P, Echarri A, Cotter J, Pereira S, Gonçalves R, Lorenzo A, Carvalho L, Castro J, Barros L, Dias JA, Rodrigues S, Portela F, Dias C, da Costa-Pereira A. Ulcerative colitis in northern Portugal and Galicia in Spain. Inflamm Bowel Dis 2010; 16:1227-38. [PMID: 19924807 DOI: 10.1002/ibd.21170] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Clinical and therapeutic patterns of ulcerative colitis (UC) are variable in different world regions. The purpose of this study was to examine two close independent southern European UC populations from 2 bordering countries and observe how demographic and clinical characteristics of patients can influence the severity of UC. METHODS A cross-sectional study was conducted during a 15-month period (September 2005 to December 2006) based on data of 2 Web registries of UC patients. Patients were stratified according to the Montreal Classification and disease severity was defined by the type of treatment taken. RESULTS A total of 1549 UC patients were included, 1008 (65%) from northern Portugal and 541 (35%) from Galicia (northwest Spain). A female predominance (57%) was observed in Portuguese patients (P < 0.001). The median age at diagnosis was 35 years and median years of disease was 7. The majority of patients (53%) were treated only with mesalamine, while 15% had taken immunosuppressant drugs, and 3% biologic treatment. Most patients in both groups were not at risk for aggressive therapy. Extensive colitis was a predictive risk factor for immunosuppression in northern Portugal and Galicia (odds ratio [OR] 2.737, 95% confidence interval [CI]: 1.846-4.058; OR 5.799, 95% CI: 3.433-9.795, respectively) and biologic treatment in Galicia (OR 6.329, 95% CI: 2.641-15.166). Younger patients presented a severe course at onset with more frequent use of immunosuppressors in both countries. CONCLUSIONS In a large population of UC patients from two independent southern European countries, most patients did not require aggressive therapy, but extensive colitis was a clear risk factor for more severe disease.
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Mensink PBF, Aktas H, Zelinkova Z, West RL, Kuipers EJ, van der Woude CJ. Impact of double-balloon enteroscopy findings on the management of Crohn's disease. Scand J Gastroenterol 2010; 45:483-9. [PMID: 20059403 DOI: 10.3109/00365520903563774] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE It is estimated that 10%-30% of Crohn's disease (CD) patients have small-bowel lesions, but the exact frequency and clinical relevance of these findings are unknown. Double-balloon enteroscopy (DBE) enables endoscopic visualization of the small bowel. The aim of this study was to evaluate the use of DBE for detecting small-bowel lesions in CD patients suspected of having small-bowel involvement. Furthermore, the clinical impact of adjusting treatment in these patients was assessed. MATERIAL AND METHODS A prospective study was performed in a tertiary referral center. CD patients suspected of small-bowel involvement and in whom distal activity had previously been excluded were included. All patients underwent DBE, followed by step-up therapy in patients with small-bowel lesions. The presence of small-bowel lesions during DBE was noted and clinical outcome was assessed after adjusting therapy. RESULTS Thirty-five patients (70%) showed small-bowel lesions; these lesions could not be assessed by conventional endoscopy in 23 (46%). At 1-year follow-up, step-up therapy in 26 patients (74%) led to clinical remission in 23 (88%). This was confirmed by a significant decrease in Crohn's disease activity index and mucosal repair on second DBE. CONCLUSIONS DBE showed a high frequency of small-bowel lesions in known CD patients with clinically suspected small-bowel activity. Most of these lesions were not accessible for conventional endoscopy. Adjusting treatment in patients with small-bowel CD involvement led to clinical remission and mucosal repair in the majority of cases.
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Affiliation(s)
- Peter B F Mensink
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
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Abstract
OBJECTIVES Natural history studies provide invaluable data on the disease course. First, they help define the end points for clinical trials that are designed to test drugs for the end point of disease modification in chronic disabling diseases. Natural history studies can also help to identify subsets of patients in whom the disease prognosis can be stratified according to clinical features. This comprehensive review summarizes our current knowledge of the natural history of Crohn's disease in adults as reported in population-based studies that include long-term follow-up results. METHODS We conducted a literature search of English and non-English language publications listed in the electronic databases of MEDLINE (source PUBMED, 1935 to December 2008). RESULTS One-third of the patients had ileitis, colitis, or ileocolitis at the time of diagnosis. Disease location remained broadly stable over time. Up to one-third of the patients had evidence of a stricturing or penetrating intestinal complication at diagnosis, and half of all patients had experienced an intestinal complication within 20 years after diagnosis. Ten percent of the patients had prolonged clinical remission. Steroid dependency occurred in one-third of the patients, and surgery was required in one-third after initiation of steroid therapy. The annual incidence of hospitalizations was 20%. Half of the patients required surgery within 10 years after diagnosis. The risk of postoperative recurrence was 44-55% after 10 years. CONCLUSIONS Crohn's disease is a disabling condition over time. The impact of changing treatment paradigms with increased use of immunosuppressants and biological agents on its natural history is poorly known.
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Van Assche G, Vermeire S, Rutgeerts P. The potential for disease modification in Crohn's disease. Nat Rev Gastroenterol Hepatol 2010; 7:79-85. [PMID: 20134489 DOI: 10.1038/nrgastro.2009.220] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The natural history of Crohn's disease is characterized by progression to complicated and disabling disease, often necessitating surgical interventions. There is either circumstantial or direct evidence to support the disease-modifying potential of several therapeutic agents. Healing of endoscopic lesions is an emerging surrogate marker of disease modification, as mucosal lesions are considered to reflect ongoing inflammation and tissue damage that lead to the formation of fistulas and fibrotic strictures, which are the main indications for surgery. In contrast to systemic steroids, both azathioprine and anti-tumor necrosis factor (TNF) agents have demonstrated the potential of mucosal healing. Prevention of hospitalization and surgery in the short and medium term has been demonstrated for the anti-TNF agents infliximab and adalimumab. The evidence supporting a role for medical therapy in the prevention of fibrotic wall thickening and in the obliteration of fistula tracks is limited and should be the focus of further prospective studies. These studies should validate predictors of complicated disease and randomized studies should be performed in high-risk groups to investigate whether early introduction of immunosuppressive agents or biologic therapies slows down disease progression and alters the natural history of the disease.
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Affiliation(s)
- G Van Assche
- Department of Gastroenterology, University Hospital Leuven, 3000 Leuven, Belgium.
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