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Hernández-Rocha C, Walshe M, Birch S, Sabic K, Korie U, Chasteau C, Miladinova VM, Sabol WB, Mengesha E, Hanna M, Pozdnyakova V, Datta L, Kohen R, Milgrom R, Stempak JM, Bitton A, Brant SR, Rioux JD, McGovern DPB, Duerr RH, Cho JH, Schumm PL, Silverberg MS, Lazarev M. Clinical Predictors of Early and Late Endoscopic Recurrence Following Ileocolonic Resection in Crohn's Disease. J Crohns Colitis 2024; 18:615-627. [PMID: 37976264 PMCID: PMC11037109 DOI: 10.1093/ecco-jcc/jjad186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND AND AIMS Multiple factors are suggested to place Crohn's disease patients at risk of recurrence after ileocolic resection with conflicting associations. We aimed to identify clinical predictors of recurrence at first [early] and further [late] postoperative colonoscopy. METHODS Crohn's disease patients undergoing ileocolic resection were prospectively recruited at six North American centres. Clinical data were collected and endoscopic recurrence was defined as Rutgeerts score ≥i2. A multivariable model was fitted to analyse variables independently associated with recurrence. RESULTS A total of 365 patients undergoing 674 postoperative colonoscopies were included with a median age of 32 years, 189 [51.8%] were male, and 37 [10.1%] were non-Whites. Postoperatively, 133 [36.4%] used anti-tumour necrosis factor [anti-TNF] and 30 [8.2%] were smokers. At first colonoscopy, 109 [29.9%] had recurrence. Male gender (odds ratio [OR] = 1.95, 95% confidence interval [CI] 1.12-3.40), non-White ethnicity [OR = 2.48, 95% CI 1.09-5.63], longer interval between surgery and colonoscopy [OR = 1.09, 95% CI 1.002-1.18], and postoperative smoking [OR = 2.78, 95% CI 1.16-6.67] were associated with recurrence, while prophylactic anti-TNF reduced the risk [OR = 0.28, 95% CI 0.14-0.55]. Postoperative anti-TNF prophylaxis had a protective effect on anti-TNF experienced patients but not on anti-TNF naïve patients. Among patients without recurrence at first colonoscopy, Rutgeerts score i1 was associated with subsequent recurrence [OR = 4.43, 95% CI 1.73-11.35]. CONCLUSIONS We identified independent clinical predictors of early and late Crohn's disease postoperative endoscopic recurrence. Clinical factors traditionally used for risk stratification failed to predict recurrence and need to be revised.
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Affiliation(s)
- Cristian Hernández-Rocha
- Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
- Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Toronto, Ontario, Canada
| | - Margaret Walshe
- Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
- Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Toronto, Ontario, Canada
| | - Sondra Birch
- Department of Public Health Sciences, University of Chicago, Chicago, IL, USA
| | - Ksenija Sabic
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ujunwa Korie
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Colleen Chasteau
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Vessela M Miladinova
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA
| | - William B Sabol
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA
| | - Emebet Mengesha
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Mary Hanna
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Valeriya Pozdnyakova
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Lisa Datta
- Department of Gastroenterology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Rita Kohen
- Inflammatory Bowel Disease Centre, Division of Gastroenterology, McGill University Health Centre, Montréal, Quebec, Canada
| | - Raquel Milgrom
- Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
| | - Joanne M Stempak
- Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
| | - Alain Bitton
- Inflammatory Bowel Disease Centre, Division of Gastroenterology, McGill University Health Centre, Montréal, Quebec, Canada
| | - Steven R Brant
- Crohn’s and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - John D Rioux
- Research Centre, Montreal Heart Institute, Montréal, Quebec, Canada
| | - Dermot P B McGovern
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Richard H Duerr
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA
| | - Judy H Cho
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Phil L Schumm
- Department of Public Health Sciences, University of Chicago, Chicago, IL, USA
| | - Mark S Silverberg
- Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
- Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Toronto, Ontario, Canada
| | - Mark Lazarev
- Department of Gastroenterology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
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Zhou J, Li W, Guo M, Huang Z, Kong D, Zhang F, Wang L, Gong J, Meng X. Mesenteric creeping fat index defined by CT enterography is associated with early postoperative recurrence in patients with Crohn's disease. Eur J Radiol 2023; 168:111144. [PMID: 37862926 DOI: 10.1016/j.ejrad.2023.111144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 09/12/2023] [Accepted: 10/05/2023] [Indexed: 10/22/2023]
Abstract
OBJECTIVES To investigate the value of mesenteric creeping fat index (MCFI) defined by computed-tomography enterography (CTE) in patients with Crohn's Disease (CD) for predicting early postoperative recurrence. METHODS A total of 110 patients with CD who underwent CTE and I-stage intestinal resection surgery from December 2013 to December 2018 were enrolled. Two radiologists independently assessed CTE parameters, including MCFI, with scores ranging from 1 to 8; bowel-wall thickening, with a scale of 1 to 3; mural hyperenhancement, mural stratification, submucosal fat deposition, mesenteric fibrofatty proliferation, mesenteric hypervascularity, mesenteric fat stranding, with a scale of 0 to 2; abscess/fistula, enlarged mesenteric lymph node, abdominal and pelvic effusion, with a scale of 0 to 1. Imaging findings associated with early recurrence were assessed using logistic regression analysis. RESULTS Within one year follow-up, early postoperative recurrence occurred in 56.4 % (62/110) patients with CD. In univariate analysis, MCFI, bowel-wall thickening, mesenteric hypervascularity, mesenteric fat stranding, abscess/fistula and mesenteric lymphadenopathy were associated with early postoperative recurrence. Among all variables, MCFI (score ≥ 4) contributes the optimal AUC (0.838 [0.758-0.919]), specificity (89.6 %), positive predictive value (90.7 %), accuracy (83.6 %), and risk ratio (OR = 32.42 [10.69-98.33], p < 0.001). In multivariate analysis, only MCFI was an independent predictor of early postoperative recurrence (OR = 25.71 [7.65-86.35], p < 0.001). CONCLUSION CTE features are useful in predicting early postoperative recurrence in patients with CD, MCFI may be a valuable tool for clinical monitoring and follow-up.
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Affiliation(s)
- Jie Zhou
- Department of Radiology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, People's Republic of China
| | - Wenru Li
- Department of Radiology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, People's Republic of China
| | - Minyi Guo
- Department of Radiology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, People's Republic of China
| | - Zicheng Huang
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, People's Republic of China; Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Decan Kong
- Department of Radiology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, People's Republic of China
| | - Fangling Zhang
- Department of Radiology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, People's Republic of China
| | - Ling Wang
- Department of Radiology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, People's Republic of China
| | - Jiaying Gong
- Department of Radiology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, People's Republic of China.
| | - Xiaochun Meng
- Department of Radiology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, People's Republic of China.
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Gisbert JP, Chaparro M. Anti-TNF Agents and New Biological Agents (Vedolizumab and Ustekinumab) in the Prevention and Treatment of Postoperative Recurrence After Surgery in Crohn's Disease. Drugs 2023; 83:1179-1205. [PMID: 37505446 PMCID: PMC10462742 DOI: 10.1007/s40265-023-01916-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2023] [Indexed: 07/29/2023]
Abstract
Surgery for Crohn's disease (CD) is not curative, as postoperative recurrence (POR) after ileocolonic resection is the rule in the absence of prophylactic treatment. In the present article, we critically review available data on the role of anti-tumour necrosis factor (TNF) agents and new biologics (including vedolizumab and ustekinumab) in the prevention and treatment of POR after surgery in CD. Several studies (summarised in various meta-analyses) have confirmed the efficacy of anti-TNFs in the prevention of POR. We identified 37 studies, including 1863 CD patients, with mean endoscopic POR at 6-12 months of 29%. Only few randomised controlled trials (RCTs) have directly compared thiopurines and anti-TNFs, with controversial results, although the superiority of the latter is supported by several meta-analyses. Infliximab and adalimumab seem equally effective. The combination of anti-TNFs and immunosuppressives should be considered in patients previously exposed to anti-TNFs. Several studies have shown that anti-TNFs remain an effective option to prevent POR also in patients with anti-TNF failure before surgery. In fact, the use of the same anti-TNF before and after surgery might be effective for the prevention of POR. Prophylactic anti-TNF treatment, once started, should be continued long term. Anti-TNFs are also effective for the treatment of established POR. Retreatment with anti-TNFs for POR is a valid strategy even after their preoperative failure. In six studies (including 156 patients) evaluating vedolizumab, mean endoscopic POR at 6-12 months was 41%. The non-randomised comparison of anti-TNFs and vedolizumab has provided controversial results. One placebo-controlled RCT confirmed that vedolizumab is quite effective in preventing POR in CD patients with increased risk of recurrence. Seven studies (including 162 patients) evaluated ustekinumab, with a mean endoscopic POR at 6-12 months of 41%. The comparative efficacy of ustekinumab and anti-TNFs is still unclear. Ustekinumab and vedolizumab seem to be equally effective, although the experience is very limited. In conclusion, to date, anti-TNFs are the most effective agents in preventing and treating POR in CD. Anti-TNFs remain an effective option to prevent POR also in patients with anti-TNF failure before surgery. Vedolizumab seems to be quite effective in the prevention of POR in patients with increased risk of recurrence. Ustekinumab is probably also effective in the postoperative setting, although the comparative efficacy with anti-TNFs or vedolizumab is still unclear.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Diego de León, 62, 28006, Madrid, Spain.
| | - María Chaparro
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Diego de León, 62, 28006, Madrid, Spain
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Urlep D, Miele E. Mercaptopurine Therapy. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:391-399. [DOI: 10.1007/978-3-031-14744-9_29] [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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Yu J, Hyun HK, Park J, Kang EA, Park SJ, Park JJ, Kim TI, Kim WH, Cheon JH. Continued Postoperative Use of Tumor Necrosis Factor-α Inhibitors for the Prevention of Crohn's Disease Recurrence. Gut Liver 2022; 16:414-422. [PMID: 34420935 PMCID: PMC9099390 DOI: 10.5009/gnl210062] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 06/12/2021] [Accepted: 06/14/2021] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND/AIMS Many patients with Crohn's disease (CD) undergo intestinal resection during the disease course. Despite surgery, postoperative recurrence (POR) commonly occurs. Although postoperative use of tumor necrosis factor α (TNF-α) inhibitors is known to be effective in preventing POR, few studies have evaluated the effectiveness of continuing the same TNF-α inhibitors postoperatively in patients who received TNF-ɑ inhibitors before surgery. METHODS This retrospective observational study was performed in a single tertiary medical center. We retrospectively reviewed patients who had undergone the first intestinal resection due to CD and divided them into two groups: TNF-α inhibitor users in both the preoperative and postoperative periods, and TNF-α inhibitor users in only the preoperative period. We compared the clinical outcomes between these two groups. RESULTS In total, 45 patients who used TNF-α inhibitors preoperatively were recruited. Among them, TNF-α inhibitors were used postoperatively in 20 patients (44.4%). The baseline characteristics except age at diagnosis were similar in both groups. The rates of surgical and endoscopic recurrence were not different between the two groups, but the cumulative clinical recurrence rate was significantly lower in the postoperative TNF-α inhibitors group (log-rank p=0.003). In multivariate Cox regression analysis, postoperative TNF-α inhibitors use was significantly associated with a decreased risk of clinical recurrence (adjusted hazard ratio, 0.204; 95% confidence interval, 0.060 to 0.691; p=0.011). CONCLUSIONS Continuing TNF-α inhibitors postoperatively in patients who were receiving TNF-α inhibitors before surgery significantly reduced the rate of clinical recurrence. For patients with CD who received TNF-α inhibitors preoperatively, continuing their use after surgery could be recommended.
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Affiliation(s)
- Jongwook Yu
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Kyung Hyun
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jihye Park
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Ae Kang
- 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
| | - Jae Jun Park
- 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
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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Tan ZV, Kosana K, Savarino J, Croft N, Naik S, Kaplan J, Giles E. Histology at diagnostic gastroscopy predicts outcome after intestinal resection in pediatric Crohn's disease. J Gastroenterol Hepatol 2020; 35:2074-2079. [PMID: 32343456 DOI: 10.1111/jgh.15080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 04/15/2020] [Accepted: 04/24/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Pediatric Crohn's disease (CD) has been shown to have a high recurrence rate following surgical resection. Risk factors for postoperative CD recurrence in children are not well known. The aim of this study was to identify factors influencing postoperative recurrence in pediatric CD. METHODS Pediatric CD patients who underwent surgical resection with primary anastomosis with a minimum follow up of 2 years were identified from databases at the Royal London Hospital and Massachusetts General Hospital. Patients were subdivided into a recurrence group defined by clinical, endoscopic, histological, radiological and/or surgical outcomes, and a nonrecurrence group. Patient demographics, initial gastroscopy and colonoscopy findings, Paris classification, and preoperative and postoperative pharmacotherapy were analyzed. RESULTS Ninety-six children who underwent an ileal or ileocolonic resection with primary anastomosis were identified. Fifty-seven children had postoperative recurrence. Recurrence was associated with abnormal initial gastroscopy findings (P = 0.0077), ileocolonic disease location (P = 0.03), and perianal disease involvement (P = 0.04). Patients with abnormal initial gastroscopy had higher rates of relapse (hazard ratio 3.42, 95% confidence interval [CI] [1.86-6.30], P = 0.001). Multivariate analysis demonstrated that abnormal diagnostic gastroscopy histology was a significant independent predictor of postoperative recurrence in this cohort (odds ratio 1.33, 95% CI [1.04-1.70], P = 0.024). The most common histological abnormality was non-Helicobacter gastritis, found in 29/46 (63%). CONCLUSION This dual-center study has shown that the presence of upper gastrointestinal tract inflammation, especially non-Helicobacter gastritis, at the time of diagnosis, is associated with an increased risk of postoperative recurrence in pediatric CD.
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Affiliation(s)
- Zien Vanessa Tan
- Department of Paediatrics, Monash University, Melbourne, Victoria, Australia
| | - Kiranmai Kosana
- Department of Paediatric Gastroenterology, Barts Health NHS Trust, London, UK
| | - Jeffrey Savarino
- Division of Pediatric Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Nicholas Croft
- Department of Neurogastroenterology, Queen Mary University of London, London, UK
| | - Sandhia Naik
- Department of Paediatric Gastroenterology, Barts Health NHS Trust, London, UK
| | - Jess Kaplan
- Division of Pediatric Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Edward Giles
- Department of Pediatrics, Monash University, Centre for Innate Immunity and Infectious Disease, Hudson Institute for Medical Research, Melbourne, Victoria, Australia
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Candia R, Bravo-Soto GA, Monrroy H, Hernandez C, Nguyen GC. Colonoscopy-guided therapy for the prevention of post-operative recurrence of Crohn's disease. Cochrane Database Syst Rev 2020; 8:CD012328. [PMID: 32746500 PMCID: PMC8094885 DOI: 10.1002/14651858.cd012328.pub2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND About half of patients with Crohn's disease (CD) require surgery within 10 years of diagnosis. Resection of the affected segment is highly effective, however the majority of patients experience clinical recurrence after surgery. Most of these patients have asymptomatic endoscopic recurrence weeks or months before starting with symptoms. This inflammation can be detected by colonoscopy and is a good predictor of poor prognosis.Therapy guided by colonoscopy could tailor the management and improve the prognosis of postoperative CD. OBJECTIVES To assess the effects of prophylactic therapy guided by colonoscopy in reducing the postoperative recurrence of CD in adults. SEARCH METHODS The following electronic databases were searched up to 17 December 2019: MEDLINE, Embase, CENTRAL, Clinical Trials.gov, WHO Trial Registry and Cochrane IBD specialized register. Reference lists of included articles, as well as conference proceedings were handsearched. SELECTION CRITERIA Randomised controlled trials (RCTs), quasi-RCTs and cohort studies comparing colonoscopy-guided management versus management non-guided by colonoscopy. DATA COLLECTION AND ANALYSIS Two review authors independently considered studies for eligibility, extracted the data and assessed study quality. Methodological quality was assessed using both the Cochrane 'Risk of bias' tool for RCTs and Newcastle-Ottawa scale (NOS) for cohort studies. The primary outcome was clinical recurrence. Secondary outcomes included: endoscopic, surgical recurrence and adverse events. We calculated the risk ratio (RR) for each dichotomous outcome and extracted the hazard ratio (HR) for time-to-event outcomes. All estimates were reported with their corresponding 95% confidence interval (CI). Data were analysed on an intention-to-treat (ITT) basis. The overall quality of the evidence was evaluated using GRADE criteria. MAIN RESULTS Two RCTs (237 participants) and five cohort studies (794 participants) met the inclusion criteria. Meta-analysis was not conducted as the studies were highly heterogeneous. We included two comparisons. Intensification of prophylactic-therapy guided by colonoscopy versus intensification guided by clinical recurrence One unblinded RCT and four retrospective cohort studies addressed this comparison. All participants received the same prophylactic therapy immediately after surgery. In the colonoscopy-based management group the therapy was intensified in case of endoscopic recurrence; in the control group the therapy was intensified only in case of symptoms. In the RCT, clinical recurrence (defined as Crohn's Disease Activity Index (CDAI) > 150 points) in the colonoscopy-based management group was 37.7% (46/122) compared to 46.1% (21/52) in the control group at 18 months' follow up (RR 0.82, 95% CI: 0.56 to 1.18, 174 participants, low-certainty evidence). There may be a reduction in endoscopic recurrence at 18 months with colonoscopy-based management (RR 0.73, 95% CI 0.56 to 0.95, 1 RCT, 174 participants, low-certainty evidence). The certainty of the evidence for surgical recurrence was very low, due to only four cohort studies with inconsistent results reporting this outcome. Adverse events at 18 months were similar in both groups, with 82% in the intervention group (100/122) and 86.5% in the control group (45/52) (RR 0.95, 95% CI:0.83 to 1.08, 1 RCT, 174 participants, low-certainty of evidence).The most common adverse events reported were alopecia, wound infection, sensory symptoms, systemic lupus, vasculitis and severe injection site reaction. Perforations or haemorrhages secondary to colonoscopy were not reported. Initiation of prophylactic-therapy guided by colonoscopy versus initiation immediately after surgery An unblinded RCT and two retrospective cohort studies addressed this comparison. The control group received prophylactic therapy immediately after surgery, and in the colonoscopy-based management group the therapy was delayed up to detection of endoscopic recurrence. The effects on clinical and endoscopic recurrence are uncertain (clinical recurrence until week 102: RR 1.16, 95% CI 0.73 to 1.84; endoscopic recurrence at week 102: RR 1.16, 95% CI 0.73 to 1.84; 1 RCT, 63 participants, very low-certainty evidence). Results from one cohort study were similarly uncertain (median follow-up 32 months, 199 participants). The effects on surgical recurrence at a median follow-up of 50 to 55 months were also uncertain in one cohort study (RR 0.79, 95% CI 0.38 to 1.62, 133 participants, very low-certainty evidence). There were fewer adverse events with colonoscopy-based management (54.8% (17/31)) compared with the control group (93.8% (30/32)) but the evidence is very uncertain (RR 0.58, 95% CI 0.42 to 0.82; 1 RCT, 63 participants). Common adverse events were infections, gastrointestinal intolerance, leukopenia, pancreatitis and skin lesions. Perforations or haemorrhages secondary to colonoscopy were not reported. AUTHORS' CONCLUSIONS Intensification of prophylactic-therapy guided by colonoscopy may reduce clinical and endoscopic postoperative recurrence of CD compared to intensification guided by symptoms, and there may be little or no difference in adverse effects. We are uncertain whether initiation of therapy guided by colonoscopy impacts postoperative recurrence and adverse events when compared to initiation immediately after surgery, as the certainty of the evidence is very low. Further studies are necessary to improve the certainty of the evidence of this review.
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Affiliation(s)
- Roberto Candia
- Departamento de Gastroenterologia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Hugo Monrroy
- Departamento de Gastroenterologia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Cristian Hernandez
- Departamento de Gastroenterologia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Geoffrey C Nguyen
- Institute of Health Policy, Management and Evaluation, University of Toronto, and Division of Gastroenterology, Department of Medicine, Mount Sinai Hospital, Toronto, Canada
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Open Source Research Collaborating Group (#OpenSourceResearch), El-Hussuna A, Myrelid P, Holubar SD, Kotze PG, Mackenzie G, Pellino G, Winter D, Davies J, Negoi I, Grewal P, Gallo G, Sahnan K, Rubio-Perez I, Clerc D, Demartines N, Glasbey J, Regueiro M, Sherif AE, Neary P, Pata F, Silverberg M, Clermont S, Chadi SA, Emile S, Buchs N, Millan M, Minaya-Bravo A, Elfeki H, De Simone V, Shalaby M, Gutierrez C, Ozen C, Yalçınkaya A, Rivadeneira D, Sturiale A, Yassin N, Spinelli A, Warusavitarne J, Ioannidis A, Wexner S, Mayol J. Biological Treatment and the Potential Risk of Adverse Postoperative Outcome in Patients With Inflammatory Bowel Disease: An Open-Source Expert Panel Review of the Current Literature and Future Perspectives. CROHN'S & COLITIS 360 2019; 1. [DOI: 10.1093/crocol/otz021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/11/2023] Open
Abstract
AbstractBackgroundThere is widespread concern that treatment with biologic agents may be associated with suboptimal postoperative outcome after surgery for inflammatory bowel diseases (IBD).AimWe aimed to search and analyze the literature regarding the potential association of biologic treatment on adverse postoperative outcome in patients with IBD. We used the subject as a case in point for surgical research. The aim was not to conduct a new systematic review.MethodThis is an updated narrative review written in a collaborative method by authors invited through Twitter via the following hashtags (#OpenSourceResearch and #SoMe4Surgery). The manuscript was presented as slides on Twitter to allow discussion of each section of the paper sequentially. A Google document was created, which was shared across social media, and comments and edits were verified by the primary author to ensure accuracy and consistency.ResultsForty-one collaborators responded to the invitation, and a total of 106 studies were identified that investigated the potential association of preoperative biological treatment on postoperative outcome in patients with IBD. Most of these studies were retrospective observational cohorts: 3 were prospective, 4 experimental, and 3 population-based studies. These studies were previously analyzed in 10 systematic/narrative reviews and 14 meta-analyses. Type of biologic agents, dose, drug concentration, antidrug antibodies, interval between last dose, and types of surgery varied widely among the studies. Adjustment for confounders and bias control ranged from good to very poor. Only 10 studies reported postoperative outcome according to Clavien–Dindo classification.ConclusionAlthough a large number of studies investigated the potential effect of biological treatment on postoperative outcomes, many reported divergent results. There is a need for randomized controlled trials. Future studies should focus on the avoiding the weakness of prior studies we identified. Seeking collaborators and sharing information via Twitter was integral to widening the contributors/authors and peer review for this article and was an effective method of collaboration.
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Affiliation(s)
| | - Alaa El-Hussuna
- Department of Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - Pär Myrelid
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
| | - Stefan D Holubar
- Director of Research, Department of Colon & Rectal Surgery, Cleveland, OH
| | - Paulo G Kotze
- Colorectal Surgery Unit, Catholic University of Parana (PUCPR), Curitiba, Brazil
| | | | - Gianluca Pellino
- Department of Surgery, Università della Campania Luigi Vanvitelli, Aversa, Italy
| | - Des Winter
- Centre for Colorectal Disease, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland
| | - Justin Davies
- Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, UK
| | - Ionut Negoi
- Carol Davila University of Medicine and Pharmacy Bucharest, Romania
| | - Perbinder Grewal
- Department of Cardiovascular, University Hospital Southampton, UK
| | - Gaetano Gallo
- Department of General Surgery, “Magna Graecia” University, Catanzaro, Italy
| | - Kapil Sahnan
- Imperial College Faculty of Medicine, Department of Surgery and St Marks Hospital, London, UK
| | - Ines Rubio-Perez
- General and Digestive Surgery Department, La Paz University Hospital, Madrid, Spain
| | - Daniel Clerc
- Department of Visceral Surgery, University Hospital CHUV, Lausanne, Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland
| | - James Glasbey
- Academic Department of Surgery, University of Birmingham Heritage Building, UK
| | - Miguel Regueiro
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, OH
| | - Ahmed E Sherif
- Department of Clinical Surgery, University of Edinburgh, UK
| | - Peter Neary
- South East Cancer Governance Lead, University Hospital Waterford/Cork, Ireland
| | - Francesco Pata
- Department of Surgery, Sant’Antonio Abate Hospital, Gallarate, Italy
| | - Mark Silverberg
- Mount Sinai Hospital Inflammatory Bowel Disease Centre, University of Toronto, ON, Canada
| | | | - Sami A Chadi
- Division of General Surgery, University Health Network, Toronto, Ontario, Canada
| | - Sameh Emile
- General Surgery Department, Mansoura Faculty of Medicine, Mansoura City, Egypt
| | - Nicolas Buchs
- Department of Surgery, University Hospitals of Geneva, Switzerland
| | - Monica Millan
- Department of Surgery, Joan XXIII University Hospital, Tarragona, Spain
| | | | - Hossam Elfeki
- Department of General Surgery, Mansoura Faculty of Medicine, Mansoura University, Egypt
| | - Veronica De Simone
- Proctology Unit, Catholic University, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
| | - Mostafa Shalaby
- Department of General Surgery, Mansoura Faculty of Medicine, Mansoura University, Egypt
| | - Celestino Gutierrez
- Department of Suregry, Centre Hospitalier de Redon Ille-et-Vilaine Bretagne-France
| | - Cihan Ozen
- Department of Surgery, Aalborg University Hospital, Aalborg, Denmark
| | | | - David Rivadeneira
- Colorectal Surgery & Surgical Services, Northwell Health in Huntington, NY, USA
| | - Alssandro Sturiale
- Proctological and Perineal Surgical Unit, Cisanello University Hospital, Pisa, Italy
| | - Nuha Yassin
- Department of surgery, Royal Wolverhampton Hoaspital, UK
| | - Antonino Spinelli
- Humanitas Clinical and Research Center, Humanitas University, Milan, Italy
| | | | - Argyrios Ioannidis
- Department of General, Laparoscopic and Robotic Surgery, Athens Medical Center
| | - Steven Wexner
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL
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9
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Suárez Ferrer C, González-Lama Y, González-Partida I, Calvo Moya M, Vera Mendoza I, Matallana Royo V, Arevalo Serrano J, Abreu Garcia L. Usefulness of Thiopurine Monotherapy for Crohn's Disease in the Era of Biologics: A Long-Term Single-Center Experience. Dig Dis Sci 2019; 64:875-879. [PMID: 30542812 DOI: 10.1007/s10620-018-5381-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 11/14/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Thiopurines are classically used in Crohn's disease (CD). Treatment fails in a proportion of patients either due to adverse events (AE) or lack of efficacy. Increasing use of anti-TNFα biologic drugs may have had impact on thiopurines usage. AIM To evaluate the evolving use of azathioprine (AZA) monotherapy in the era of biologics. METHODS The study retrospectively analyzed clinical records of all CD patients who started treatment with AZA monotherapy at our center since 1990. Dates of starting AZA and treatment failure (TF) were collected. We defined AZA TF if it was withdrawn due to lack of efficacy or AE, or biologics were added. RESULTS A total of 383 patients were included: 46.5% were males and mean age was 31 (range 17-84) years. Median follow-up was 43 (range 0.2-289) months. Overall, 147 patients (38%) experienced TF. Median cumulative survival time of AZA was 126 (95% CI 105-147) months. Proportion of patients with AZA TF increased along time: 7 patients in 1990-1995 (4.7% of all TF); 8 in 1996-2000 (5.4%); 22 in 2001-2005(15%); 41 in 2006-2010 (28%); 69 in 2011-2014 (47%) (p = 0.04). 7%, 21%, 4%, 45%, and 33.3% of patients moved to biologics in each period, respectively (χ2 = 13.07; p < 0.05). Seventy-four patients (18.4%) stopped AZA due to AE, and 73(19%) due to lack of efficacy. Regarding AZA indication, prevention of postoperative recurrence obtained better results than steroid dependency (p = 0.001); perianal fistulizing CD predicted poorer outcomes (p = 0.002). CONCLUSION An important proportion of CD patients under AZA monotherapy experienced TF in our experience. Although AZA monotherapy remains useful for CD in the era of biologics, current clinical practice is shifting to anti-TNFα biologic drugs in an increasing proportion of patients.
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Affiliation(s)
- Cristina Suárez Ferrer
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Yago González-Lama
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Irene González-Partida
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Marta Calvo Moya
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Isabel Vera Mendoza
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Virginia Matallana Royo
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Juan Arevalo Serrano
- Internal Medicine Department, Principe de Asturias University Hospital, Alcalá de Henares, Madrid, Spain
| | - Luis Abreu Garcia
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
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10
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Brown SR, Fearnhead NS, Faiz OD, Abercrombie JF, Acheson AG, Arnott RG, Clark SK, Clifford S, Davies RJ, Davies MM, Douie WJP, Dunlop MG, Epstein JC, Evans MD, George BD, Guy RJ, Hargest R, Hawthorne AB, Hill J, Hughes GW, Limdi JK, Maxwell-Armstrong CA, O'Connell PR, Pinkney TD, Pipe J, Sagar PM, Singh B, Soop M, Terry H, Torkington J, Verjee A, Walsh CJ, Warusavitarne JH, Williams AB, Williams GL, Wilson RG. The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease. Colorectal Dis 2018; 20 Suppl 8:3-117. [PMID: 30508274 DOI: 10.1111/codi.14448] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 09/17/2018] [Indexed: 12/14/2022]
Abstract
AIM There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.
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Affiliation(s)
- S R Brown
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - N S Fearnhead
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - O D Faiz
- St Mark's Hospital, Middlesex, Harrow, UK
| | | | - A G Acheson
- Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - R G Arnott
- Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK
| | - S K Clark
- St Mark's Hospital, Middlesex, Harrow, UK
| | | | - R J Davies
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - M M Davies
- University Hospital of Wales, Cardiff, UK
| | - W J P Douie
- University Hospitals Plymouth NHS Trust, Plymouth, UK
| | | | - J C Epstein
- Salford Royal NHS Foundation Trust, Salford, UK
| | - M D Evans
- Morriston Hospital, Morriston, Swansea, UK
| | - B D George
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - R J Guy
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - R Hargest
- University Hospital of Wales, Cardiff, UK
| | | | - J Hill
- Manchester Foundation Trust, Manchester, UK
| | - G W Hughes
- University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - J K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
| | | | | | - T D Pinkney
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - J Pipe
- Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK
| | - P M Sagar
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - B Singh
- University Hospitals of Leicester NHS Trust, Leicester, UK
| | - M Soop
- Salford Royal NHS Foundation Trust, Salford, UK
| | - H Terry
- Crohn's and Colitis UK, St Albans, UK
| | | | - A Verjee
- Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK
| | - C J Walsh
- Wirral University Teaching Hospital NHS Foundation Trust, Arrowe Park Hospital, Upton, UK
| | | | - A B Williams
- Guy's and St Thomas' NHS Foundation Trust, London, UK
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11
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Auzolle C, Nancey S, Tran-Minh ML, Buisson A, Pariente B, Stefanescu C, Fumery M, Marteau P, Treton X, Hammoudi N, Jouven X, Seksik P, Allez M. Male gender, active smoking and previous intestinal resection are risk factors for post-operative endoscopic recurrence in Crohn's disease: results from a prospective cohort study. Aliment Pharmacol Ther 2018; 48:924-932. [PMID: 30126030 DOI: 10.1111/apt.14944] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2018] [Revised: 06/08/2018] [Accepted: 07/21/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND After ileocaecal resection for Crohn's disease (CD), inflammatory lesions frequently recur on the anastomosis and/or on the neo-terminal ileum. AIM To identify predictors of early post-operative endoscopic recurrence. METHODS From September 2010 to September 2017, the REMIND group conducted a prospective nationwide study in nine French academic centres. Data were collected at the time of surgery and endoscopy, performed 6-12 months after surgery. Endoscopic recurrence was defined as a Rutgeerts score ≥i2. Baseline factors associated with endoscopic recurrence were searched by univariate and multivariate regression analysis. RESULTS Two hundred and eighty-nine CD patients were included. Endoscopy within 1 year following surgery was performed in 225 (78%) patients (104M/121F). Mean age and disease duration were 35 (12.2) and 8.8 (8.9) years respectively. Seventy (32%) patients were active smokers at surgery. One hundred and forty-two (63%) patients received at least one anti-TNF therapy before surgery. After surgery, 40 (18%) patients received thiopurines and 66 (29%) received an anti-TNF agent. Endoscopic recurrence occurred in 107 (47%) patients. In multivariate analysis, male gender (OR = 2.48 [IC 95% 1.40-4.46]), active smoking at surgery (OR = 2.65 [IC 95% 1.44-4.97]) and previous resection (OR = 3.03 [IC 95% 1.36-7.12]) were associated with a higher risk of endoscopic recurrence. Inversely, post-operative anti-TNF treatment decreased the risk of endoscopic recurrence (OR = 0.50 [IC 95% 0.25-0.96]). CONCLUSIONS Male gender, active smoking at surgery and previous intestinal resection are associated with a higher risk of endoscopic post-operative recurrence, while post-operative anti-TNF treatment is associated with a lower risk.
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Affiliation(s)
- Claire Auzolle
- Department of Gastroenterology, Hôpital Saint-Louis, APHP, INSERM U1160, University Denis Diderot, Paris, France.,PARCC, Paris, France
| | - Stephane Nancey
- Department of Gastroenterology, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France
| | - My-Linh Tran-Minh
- Department of Gastroenterology, Hôpital Saint-Louis, APHP, INSERM U1160, University Denis Diderot, Paris, France
| | - Anthony Buisson
- Université Clermont Auvergne, Inserm U1071, M2iSH, 3iHP, CHU Clermont-Ferrand, Service de Médecine de l'Appareil Digestif Clermont-Ferrand, Clermont-Ferrand, France
| | - Benjamin Pariente
- Department of Gastroenterology, Claude Huriez Hospital, University of Lille 2, Lille, France
| | - Carmen Stefanescu
- Hôpital Beaujon, Service de Gastroentérologie, MICI et Assistance Nutritive, Clichy, France
| | - Mathurin Fumery
- Department of Hepatogastroenterology, Amiens University Hospital, Amiens, France
| | - Philippe Marteau
- Gastroenterology, Sorbonne Universités, AP-HP, Hospital Saint-Antoine, Paris, France
| | - Xavier Treton
- Hôpital Beaujon, Service de Gastroentérologie, MICI et Assistance Nutritive, Clichy, France
| | - Nassim Hammoudi
- Department of Gastroenterology, Hôpital Saint-Louis, APHP, INSERM U1160, University Denis Diderot, Paris, France
| | | | | | - Philippe Seksik
- Gastroenterology, Sorbonne Universités, AP-HP, Hospital Saint-Antoine, Paris, France
| | - Matthieu Allez
- Department of Gastroenterology, Hôpital Saint-Louis, APHP, INSERM U1160, University Denis Diderot, Paris, France
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12
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Risk factors for anastomotic recurrence after primary ileocaecal resection in Crohn's disease. Eur J Gastroenterol Hepatol 2018; 30:1143-1147. [PMID: 30024490 DOI: 10.1097/meg.0000000000001206] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Ileocaecal resection is the most common operation performed in Crohn's disease. Our study aimed to identify the risk factors for anastomotic recurrence following primary ileocaecal resection. PATIENTS AND METHODS We retrospectively analysed data from all Crohn's disease surgical patients in a single colorectal unit between 2006 and 2016, including all patients who underwent primary ileocaecal resection. We defined anastomotic recurrence as the postoperative need for endoscopic dilatation of the ileocolic anastomosis or neoterminal ileal resection, and used Cox regression to determine the risk factors for such recurrence. RESULTS In total, 101 patients underwent primary ileocaecal resection during the study period. Nine (8.9%) patients were excluded because of follow-up less than 1 year and 12 (13.0%) patients had anastomotic recurrence. The median follow-up was 4.7 (1.3-10.8) years. At 3 years, 93.1% of patients required no neoterminal ileal resection or dilatation of the ileocolic anastomosis. Urgent primary ileocaecal resection [hazard ratio (HR)=4.98, 95% confidence interval (CI)=1.45-17.11, P=0.011], stapled anastomosis (HR=20.34, 95% CI=5.06-81.77, P<0.001) and need for postoperative corticosteroid treatment after the primary ileocaecal resection (HR=3.58, 95% CI=1.03-12.40, P=0.044) emerged as significant risk factors for anastomotic recurrence. CONCLUSION Urgent surgery and postoperative corticosteroid need represented risk factors for anastomotic recurrence. Hand-sewn anastomosis with an opening of the bowel's antimesenteric border seems to be a safe choice for ileocaecal resection.
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13
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Araki T, Okita Y, Kondo S, Hiro J, Toiyama Y, Inoue M, Ohi M, Inoue Y, Uchida K, Mohri Y, Kusunoki M. Risk factors for recurrence of Crohn's disease requiring surgery in patients receiving post-operative anti-tumor necrosis factor maintenance therapy. JOURNAL OF THE ANUS RECTUM AND COLON 2018; 1:15-21. [PMID: 31583295 PMCID: PMC6768679 DOI: 10.23922/jarc.2016-004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Accepted: 12/28/2016] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Anti-tumor necrosis factor (TNF) antibodies have shown efficacy in the prevention of recurrence of Crohn's disease after intestinal resection. However, some patients develop surgical recurrence despite this therapy. We aimed to evaluate the risk factors for recurrence of Crohn's disease requiring surgery while receiving post-operative anti-TNF therapy. METHODS We performed a retrospective evaluation of 164 patients who had received post-operative anti-TNF maintenance therapy between 2002 and 2016. We classified Crohn's disease-related re-operation as surgical recurrence and analyzed its risk factors using the Cox proportional hazard model. RESULTS Of the 164 participants, 128 had received infliximab and 36 had received adalimumab maintenance therapy. We obtained follow-up data over a mean of 60.2 months. The proportion of patients with surgical recurrence at 5 years was 14.9%. The only independent risk factor for surgical recurrence, which we identified was post-operative smoking habit (odds ratio, 5.03; 95% CI, 1.14-12.8; P=0.033). CONCLUSIONS Post-operative smoking may be a significant risk factor for post-operative surgical recurrence of Crohn's disease while receiving anti-TNF maintenance therapy.
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Affiliation(s)
- Toshimitsu Araki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yoshiki Okita
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Satoru Kondo
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Junichiro Hiro
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Mikihiro Inoue
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Masaki Ohi
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yasuhiro Inoue
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Keiichi Uchida
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yasuhiko Mohri
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Masato Kusunoki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
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14
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Guo J, Chen BL, Chen ZH, Luo XP, Qiu Y, Zhang SH, Feng R, He Y, Zeng ZR, Song XM, Ben-Horin S, Mao R, Chen MH. Thiopurines prevented surgical recurrence in patients with Crohn's disease after intestinal resection: Strategy based on risk stratification. J Gastroenterol Hepatol 2018; 33:608-614. [PMID: 28804920 DOI: 10.1111/jgh.13922] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 08/02/2017] [Accepted: 08/08/2017] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIM Thiopurines (TPs) are effective in reducing clinical and endoscopic recurrence in postoperative patients with Crohn's disease (CD). However, whether TPs could prevent surgical recurrence (SR) remains unknown. We aimed to explore whether TPs could prevent SR and identify risk factors associated with SR. METHODS This was a retrospective cohort study of 246 postoperative patients with CD. Cox proportional hazard model was used to identify risk factors for SR. Patients were stratified according to the presence of risk factors. RESULTS A total of 50 (20.3%) patients suffered SR after a mean follow up of 54.3±46.4 months. Multivariable analysis showed independent risk factors for SR were penetrating disease behavior (HR 8.628; 95% CI 1.573-47.341; P = 0.01), ileocolonic disease location (HR 2.597; 95% CI 1.047-6.445; P = 0.04) and isolated upper gastrointestinal disease (UGID) location (HR 5.082; 95% CI 1.496-17.267; P = 0.009). However, use of TPs after surgery significantly reduced the risk of SR (HR 0.120; 95% CI 0.063-0.231; P < 0.001). When stratifying patients according to risk factors, there was no statistical difference of SR between patients treated or not by TPs (P = 0.08) in low-risk group (n = 46). However, in high risk group (n = 200), patients with TPs use had a lower risk of SR than those without TPs (HR 0.093; 95% CI 0.048-0.178; P < 0.001). CONCLUSIONS Penetrating disease behavior and ileocolonic/isolated (UGID) location were associated with SR in CD patients. TPs use was beneficial in decreasing risk for SR in CD patients at high risk.
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Affiliation(s)
- Jing Guo
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Bai-Li Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhi-Hui Chen
- Department of Gastrointestinal and Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xia-Peng Luo
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yun Qiu
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Sheng-Hong Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Rui Feng
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yao He
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhi-Rong Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xin-Ming Song
- Department of Gastrointestinal and Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shomron Ben-Horin
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Min-Hu Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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15
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Abstract
Crohn's disease is a chronic inflammatory bowel disease of unknown etiology associated with an impaired immune response, with periods of activity and remission. It is characterised by patchy and transmural lesions which can affect the entire gastrointestinal tract, from the mouth to the anus. The most frequent symptoms are abdominal pain and diarrhoea, which can seriously affect patients' quality of life. The increasing incidence and prevalence of the disease in our area has had a large impact on clinical practice, with the rapid development of diagnostic and therapeutic techniques. To reduce the risk of complications, primary care physicians and gastroenterologists should be familiar with the management of the disease.
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Fay S, Ungar B, Paul S, Levartovsky A, Yavzori M, Fudim E, Picard O, Eliakim R, Ben-Horin S, Roblin X, Kopylov U. The Association Between Drug Levels and Endoscopic Recurrence in Postoperative Patients with Crohn's Disease Treated with Tumor Necrosis Factor Inhibitors. Inflamm Bowel Dis 2017; 23:1924-1929. [PMID: 28837524 DOI: 10.1097/mib.0000000000001220] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Endoscopic recurrence is associated with a risk of clinical recurrence in patients with Crohn's disease after ileocecal or small bowel resection. Drug levels and presence of antidrug antibodies are associated with important clinical and endoscopic outcomes in patients with Crohn's disease treated with tumor necrosis factor inhibitors, such association was not evaluated for endoscopic postsurgical recurrence. METHODS Consecutive patients with Crohn's disease treated with anti-tumor necrosis factors after surgery were identified in the databases of the participating centers. Anti-tumor necrosis factor levels and antidrug antibodies were correlated with Rutgeerts score on colonoscopy performed ≥6 months postoperatively. Significant endoscopic recurrence (SER) was defined as Rutgeerts score >2. RESULTS Seventy-three consecutive patients (32-infliximab, 41-adalimumab) were included in the study. The colonoscopies were performed after a median of 15 (7-43) months after surgery and 8 (6-15) months from treatment onset. SER was demonstrated in 26/73 (35.6%) of the patients. The need for dose optimization, as well as trough infliximab levels (2.4 μg/mL [0.45-4.1] versus 1.1 (0-0.6), P = 0.008) and presence of antidrug antibodies (1/18 [5.6%] versus 10/14 [71.4%], P = 0.0001) were significantly associated with a risk of SER. The optimal cutoff infliximab level for prediction of SER was 1.8 μg/mL. No association between adalimumab levels and antiadalimumab antibodies was demonstrated.
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Affiliation(s)
- Shmuel Fay
- *Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel, and Sackler Medical School, Tel Aviv University, Tel Aviv, Israel; and †Service de Gastrologie-Entérologie-Hépatologie, CHU de Saint-Etienne, Saint-Etienne, France
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17
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López-Sanromán A, Vera-Mendoza I, Domènech E, Taxonera C, Vega Ruiz V, Marín-Jiménez I, Guardiola J, Castro L, Esteve M, Iglesias E, Ceballos D, Martínez-Montiel P, Gisbert JP, Mínguez M, Echarri A, Calvet X, Barrio J, Hinojosa J, Martín-Arranz MD, Márquez-Mosquera L, Bermejo F, Rimola J, Pons V, Nos P. Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn's Disease Recurrence. A GETECCU Randomised Trial. J Crohns Colitis 2017; 11:1293-1301. [PMID: 28402454 DOI: 10.1093/ecco-jcc/jjx051] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Accepted: 04/05/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS Postoperative recurrence of Crohn's disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting. METHODS We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader. RESULTS We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions. CONCLUSIONS ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better. ClinicalTrials.gov NCT01564823.
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Affiliation(s)
| | - Isabel Vera-Mendoza
- Gastroenterology-Hepatology Unit, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain
| | - Eugeni Domènech
- Gastroenterology-Hepatology Unit, Hospital Germans Trias i Pujol, Badalona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain
| | - Carlos Taxonera
- Digestive Diseases Unit, Hospital Clínico San Carlos, Instituto Investigación Sanitaria San Carlos [IdISSC], Madrid, Spain
| | - Vicente Vega Ruiz
- General Surgery Unit, Hospital Universitario Puerto Real, Puerto Real, Spain
| | - Ignacio Marín-Jiménez
- Digestive Diseases Unit, Hospital Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón [IiSGM], Madrid, Spain
| | - Jordi Guardiola
- Gastroenterology-Hepatology Unit, Hospital Universitari de Bellvitge-IDIBELL, Barcelona, Spain
| | - Luisa Castro
- Digestive Diseases Unit, Hospital Universitario Virgen de Macarena, Sevilla, Spain
| | - María Esteve
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.,Gastroenterology-Hepatology Unit, Hospital Universitari Mutua Terrassa, Terrassa, Spain
| | - Eva Iglesias
- Digestive Diseases Unit, Hospital Reina Sofía, Córdoba, Spain
| | - Daniel Ceballos
- Gastroenterology-Hepatology Unit, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas, Spain
| | | | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.,Digestive Diseases Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa [IIS-IP], Madrid, Spain
| | - Miguel Mínguez
- Digestive Diseases Unit, Hospital Clínic de Valencia, University of Valencia, Valencia, Spain
| | - Ana Echarri
- Digestive Diseases Unit, Hospital Arquitecto Marcide, Ferrol, Spain
| | - Xavier Calvet
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.,Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Jesús Barrio
- Digestive Diseases Unit, Hospital Universitario Río Hortega, Valladolid, Spain
| | | | | | | | - Fernando Bermejo
- Digestive Diseases Unit, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain
| | - Jordi Rimola
- Radiology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Vicente Pons
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.,Digestive Diseases Unit, Hospital Universitario y Politécnico de La Fe, Valencia, Spain
| | - Pilar Nos
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.,Digestive Diseases Unit, Hospital Universitario y Politécnico de La Fe, Valencia, Spain
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18
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Holt DQ, Moore GT, Strauss BJG, Hamilton AL, De Cruz P, Kamm MA. Visceral adiposity predicts post-operative Crohn's disease recurrence. Aliment Pharmacol Ther 2017; 45:1255-1264. [PMID: 28244124 DOI: 10.1111/apt.14018] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Revised: 11/16/2016] [Accepted: 02/07/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Excessive visceral adipose tissue has been associated with poorer outcomes in patients with inflammatory bowel disease. AIM To determine whether body composition is associated with outcome in a prospective study of post-operative Crohn's disease patients. METHODS The POCER study evaluated management strategies for prevention of post-operative Crohn's disease recurrence; subjects were enrolled after resection of all macroscopic Crohn's disease and were randomised to early endoscopy and possible treatment escalation, or standard care. The primary endpoint was endoscopic recurrence at 18 months. 44 subjects with cross-sectional abdominal imaging were studied, and body composition analysis performed using established techniques to measure visceral adipose tissue area, subcutaneous adipose tissue area, and skeletal muscle area. RESULTS The body composition parameter with the greatest variance was visceral adipose tissue. Regardless of treatment, all subjects with visceral adipose tissue/height2 >1.5 times the gender-specific mean experienced endoscopic recurrence at 18 months (compared to 47%) [relative risk 2.1, 95% CI 1.5-3.0, P = 0.012]. Waist circumference correlated strongly with visceral adipose tissue area (ρ = 0.840, P < 0.001). Low skeletal muscle was prevalent (41% of patients), but did not predict endoscopic recurrence; however, appendicular skeletal muscle indices correlated inversely with faecal calprotectin (ρ = 0.560, P = 0.046). CONCLUSIONS Visceral adiposity is an independent risk factor for endoscopic recurrence of Crohn's disease after surgery. Sarcopenia correlates with inflammatory biomarkers. Measures of visceral adipose tissue may help to stratify risk in post-operative management strategies.
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Affiliation(s)
- D Q Holt
- Department of Gastroenterology & Hepatology, Monash Health, Melbourne, Vic., Australia.,Monash University, Melbourne, Vic., Australia
| | - G T Moore
- Department of Gastroenterology & Hepatology, Monash Health, Melbourne, Vic., Australia.,Monash University, Melbourne, Vic., Australia
| | | | - A L Hamilton
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Vic., Australia.,University of Melbourne, Melbourne, Vic., Australia
| | - P De Cruz
- University of Melbourne, Melbourne, Vic., Australia
| | - M A Kamm
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Vic., Australia.,University of Melbourne, Melbourne, Vic., Australia
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19
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Amil-Dias J, Kolacek S, Turner D, Pærregaard A, Rintala R, Afzal NA, Karolewska-Bochenek K, Bronsky J, Chong S, Fell J, Hojsak I, Hugot JP, Koletzko S, Kumar D, Lazowska-Przeorek I, Lillehei C, Lionetti P, Martin-de-Carpi J, Pakarinen M, Ruemmele FM, Shaoul R, Spray C, Staiano A, Sugarman I, Wilson DC, Winter H, Kolho KL. Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr 2017; 64:818-835. [PMID: 28267075 DOI: 10.1097/mpg.0000000000001562] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.
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Affiliation(s)
- Jorge Amil-Dias
- *Department of Pediatrics, Centro Hospitalar, S. João, Porto, Portugal †Children's Hospital Zagreb, Faculty of Medicine, Zagreb, Croatia ‡The Juliet Keidan Institute of Pediatric Gastroenterology & Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel §Department of Pediatrics, Hvidovre University Hospital, Hvidovre, Denmark ||Pediatric Surgery, Children's Hospital, University of Helsinki, Helsinki, Finland ¶Department of Pediatric Gastroenterology, University Hospital Southampton, Southampton, UK #Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland **Department of Pediatrics, University Hospital Motol, Prague, Czech Republic ††Queen Mary's Hospital for Children, Epsom and St Helier NHS Trust, Surrey ‡‡Chelsea and Westminster Hospital, London, UK §§Paris-Diderot Sorbonne-Paris-Cité University and Robert Debré Hospital, Paris, France ||||Pediatric Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, Ludwig Maximilians-University, Munich, Germany ¶¶St George's, University of London, London, UK ##Boston Children's Hospital and Harvard Medical School, Boston, MA ***Department NEUROFARBA, University of Florence - Meyer Hospital, Florence, Italy †††Unit for the Comprehensive Care of Pediatric Inflammatory Bowel Disease, Hospital Sant Joan de Déu, Barcelona, Spain ‡‡‡Department of Pediatric Gastroenterology, Necker Enfants Malades University Hospital, Sorbonne Paris Cité University, Paris Descartes University, Institut IMAGINE - INSERM U1163, Paris, France §§§Pediatric Gastroenterology Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel ||||||Department of Pediatric Gastroenterology, Bristol Royal Hospital for Children, Bristol, UK ¶¶¶Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy ###Department of Pediatric Surgery, Leeds Children's Hospital, Leeds General Infirmary, Leeds, UK ****Child Life and Health, University of Edinburgh, Scotland, UK ††††MassGeneral Hospital for Children, Harvard Medical School, Boston, MA ‡‡‡‡Children's Hospital, University of Helsinki, Helsinki, Finland
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20
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Mantzaris GJ. Thiopurines and Methotrexate Use in IBD Patients in a Biologic Era. ACTA ACUST UNITED AC 2017; 15:84-104. [DOI: 10.1007/s11938-017-0128-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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21
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Maguire LH, Alavi K, Sudan R, Wise PE, Kaiser AM, Bordeianou L. Surgical Considerations in the Treatment of Small Bowel Crohn's Disease. J Gastrointest Surg 2017; 21:398-411. [PMID: 27966058 DOI: 10.1007/s11605-016-3330-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Accepted: 11/15/2016] [Indexed: 01/31/2023]
Abstract
Surgery remains a cornerstone of the management of Crohn's disease (CD). Despite the rise of biologic therapy, most CD patients require surgery for penetrating, obstructing, or malignant complications. Optimal surgical therapy requires sophisticated operative judgment and medical optimization. Intraoperatively, surgeons must balance treatment of CD complications against bowel preservation and functional outcome. This demands mastery of multiple techniques for anastomosis and strictureplasty, accurate assessment of bowel integrity for margin minimization, and a comprehensive skillset for navigating adhesions and altered anatomy, controlling thickened mesentery, and safely managing the hostile abdomen. Outside of the operating room, a multi-disciplinary team is critical for pre-operative optimization, patient support, and medical management. Postoperatively, prevention and surveillance of recurrence remain a matter of research and debate, and medical options include older drugs with limited efficacy and tolerability versus biologic agents with greater effect sizes and shorter track records. The evidence base for current management is limited by the inherent challenges of studying a chronic disease marked by heterogeneity and recurrence, but also by a lack of prospective trials incorporating both medical and surgical therapies.
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Affiliation(s)
- Lillias Holmes Maguire
- Department of Surgery, Massachusetts General Hospital, 15 Parkman St, Boston, MA, 617-02114, USA
- Department of Surgery, University of Minnesota, Minneapolis, MN, USA
| | - Karim Alavi
- Department of Surgery, UMass Memorial Medical Center, Worcester, MA, USA
| | - Ranjan Sudan
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Paul E Wise
- Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Andreas M Kaiser
- Department of Colorectal Surgery, University of Southern California, Los Angeles, CA, USA
| | - Liliana Bordeianou
- Department of Surgery, Massachusetts General Hospital, 15 Parkman St, Boston, MA, 617-02114, USA.
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22
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Mowat C, Arnott I, Cahill A, Smith M, Ahmad T, Subramanian S, Travis S, Morris J, Hamlin J, Dhar A, Nwokolo C, Edwards C, Creed T, Bloom S, Yousif M, Thomas L, Campbell S, Lewis SJ, Sebastian S, Sen S, Lal S, Hawkey C, Murray C, Cummings F, Goh J, Lindsay JO, Arebi N, Potts L, McKinley AJ, Thomson JM, Todd JA, Collie M, Dunlop MG, Mowat A, Gaya DR, Winter J, Naismith GD, Ennis H, Keerie C, Lewis S, Prescott RJ, Kennedy NA, Satsangi J. Mercaptopurine versus placebo to prevent recurrence of Crohn's disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial. Lancet Gastroenterol Hepatol 2016; 1:273-282. [PMID: 28404197 PMCID: PMC6358144 DOI: 10.1016/s2468-1253(16)30078-4] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 08/02/2016] [Accepted: 08/04/2016] [Indexed: 12/24/2022]
Abstract
BACKGROUND Up to 60% of patients with Crohn's disease need intestinal resection within the first 10 years of diagnosis, and postoperative recurrence is common. We investigated whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohn's disease. METHODS We did a randomised, placebo-controlled, double-blind trial at 29 UK secondary and tertiary hospitals of patients (aged >16 years in Scotland or >18 years in England and Wales) who had a confirmed diagnosis of Crohn's disease and had undergone intestinal resection. Patients were randomly assigned (1:1) by a computer-generated web-based randomisation system to oral daily mercaptopurine at a dose of 1 mg/kg bodyweight rounded to the nearest 25 mg or placebo; patients with low thiopurine methyltransferase activity received half the normal dose. Patients and their carers and physicians were masked to the treatment allocation. Patients were followed up for 3 years. The primary endpoint was clinical recurrence of Crohn's disease (Crohn's Disease Activity Index >150 plus 100-point increase in score) and the need for anti-inflammatory rescue treatment or primary surgical intervention. Primary and safety analyses were by intention to treat. Subgroup analyses by smoking status, previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis were also done. This trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN89489788) and the European Clinical Trials Database (EudraCT number 2006-005800-15). FINDINGS Between June 6, 2008, and April 23, 2012, 240 patients with Crohn's disease were randomly assigned: 128 to mercaptopurine and 112 to placebo. All patients received at least one dose of study drug, and no randomly assigned patients were excluded from the analysis. 16 (13%) of patients in the mercaptopurine group versus 26 (23%) patients in the placebo group had a clinical recurrence of Crohn's disease and needed anti-inflammatory rescue treatment or primary surgical intervention (adjusted hazard ratio [HR] 0·54, 95% CI 0·27-1·06; p=0·07; unadjusted HR 0·53, 95% CI 0·28-0·99; p=0·046). In a subgroup analysis, three (10%) of 29 smokers in the mercaptopurine group and 12 (46%) of 26 in the placebo group had a clinical recurrence that needed treatment (HR 0·13, 95% CI 0·04-0·46), compared with 13 (13%) of 99 non-smokers in the mercaptopurine group and 14 (16%) of 86 in the placebo group (0·90, 0·42-1·94; pinteraction=0·018). The effect of mercaptopurine did not significantly differ from placebo for any of the other planned subgroup analyses (previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis). The incidence and types of adverse events were similar in the mercaptopurine and placebo groups. One patient on placebo died of ischaemic heart disease. Adverse events caused discontinuation of treatment in 39 (30%) of 128 patients in the mercaptopurine group versus 41 (37%) of 112 in the placebo group. INTERPRETATION Mercaptopurine is effective in preventing postoperative clinical recurrence of Crohn's disease, but only in patients who are smokers. Thus, in smokers, thiopurine treatment seems to be justified in the postoperative period, although smoking cessation should be strongly encouraged given that smoking increases the risk of recurrence. FUNDING Medical Research Council.
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Affiliation(s)
- Craig Mowat
- Gastrointestinal Unit, Ninewells Hospital, Dundee, UK
| | - Ian Arnott
- Gastrointestinal Unit, Western General Hospital, Edinburgh, UK
| | - Aiden Cahill
- Gastrointestinal Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - Malcolm Smith
- Gastrointestinal Unit, Aberdeen Royal Infirmary, Aberdeen, UK
| | - Tariq Ahmad
- Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK; IBD Pharmacogenetics Unit, University of Exeter, Exeter, UK
| | - Sreedhar Subramanian
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Simon Travis
- Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford, Oxford, UK
| | - John Morris
- Gastrointestinal Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - John Hamlin
- Department of Gastroenterology, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Anjan Dhar
- Department of Gastroenterology, Darlington Memorial Hospital, Darlington, UK
| | - Chuka Nwokolo
- Department of Gastroenterology, University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Cathryn Edwards
- Department of Gastroenterology, Torbay Hospital, South Devon Healthcare NHS Foundation Trust, Torbay, Devon, UK
| | - Tom Creed
- Department of Gastroenterology, Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | - Stuart Bloom
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Mohamed Yousif
- Department of Gastroenterology, Rotherham NHS Foundation Trust Hospital, Rotherham, UK
| | - Linzi Thomas
- Department of Gastroenterology, Singleton Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UK
| | - Simon Campbell
- Department of Gastroenterology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Stephen J Lewis
- Department of Gastroenterology, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth, UK
| | - Shaji Sebastian
- Department of Gastroenterology, Hull Royal Infirmary, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK
| | - Sandip Sen
- Department of Gastroenterology, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
| | - Simon Lal
- Department of Gastroenterology, Salford Royal NHS Foundation Trust Hospital, Salford, UK
| | - Chris Hawkey
- Department of Gastroenterology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Charles Murray
- Department of Gastroenterology, Royal Free London NHS Foundation Trust Hospital, London, UK
| | - Fraser Cummings
- Department of Gastroenterology, Southampton General Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Jason Goh
- Department of Gastroenterology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - James O Lindsay
- Department of Gastroenterology, Barts Health NHS Trust, Barts and the London School of Medicine, London, UK
| | - Naila Arebi
- Inflammatory Bowel Disease Unit, St Mark's Hospital, North West London Hospitals NHS Trust, London, UK
| | - Lindsay Potts
- Gastrointestinal Unit, Raigmore Hospital, Inverness, UK
| | | | - John M Thomson
- Gastrointestinal Unit, Aberdeen Royal Infirmary, Aberdeen, UK
| | - John A Todd
- Gastrointestinal Unit, Ninewells Hospital, Dundee, UK
| | - Mhairi Collie
- Colorectal Surgery, Western General Hospital, Edinburgh, UK
| | | | - Ashley Mowat
- Gastrointestinal Unit, Aberdeen Royal Infirmary, Aberdeen, UK
| | - Daniel R Gaya
- Gastrointestinal Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - Jack Winter
- Gastrointestinal Unit, Glasgow Royal Infirmary, Glasgow, UK
| | | | - Holly Ennis
- Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK
| | - Catriona Keerie
- Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK
| | - Steff Lewis
- Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh, UK
| | | | - Nicholas A Kennedy
- Gastrointestinal Unit, Western General Hospital, Edinburgh, UK; IBD Pharmacogenetics Unit, University of Exeter, Exeter, UK
| | - Jack Satsangi
- Gastrointestinal Unit, Western General Hospital, Edinburgh, UK.
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23
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Candia R, Ibañez P, Nguyen GC. Colonoscopy-guided therapy for the prevention of post-operative recurrence of Crohn’s disease. Hippokratia 2016. [DOI: 10.1002/14651858.cd012328] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Roberto Candia
- Faculty of Medicine, Pontificia Universidad Católica de Chile; Department of Gastroenterology, Evidence Based Health Care Program; Marcoleta 367 Santiago Region Metropolitana Chile
| | - Patricio Ibañez
- Clinica Las Condes; Department of Gastroenterology; Estoril 451 3rt Floor Building 3 Las Condes Santiago Chile
| | - Geoffrey C Nguyen
- Mount Sinai Hospital; 600 University Ave, Ste. 437 Toronto ON Canada M5G 1X5
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24
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Collins PD. Video capsule endoscopy in inflammatory bowel disease. World J Gastrointest Endosc 2016; 8:477-488. [PMID: 27499830 PMCID: PMC4959941 DOI: 10.4253/wjge.v8.i14.477] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Revised: 05/01/2016] [Accepted: 06/03/2016] [Indexed: 02/06/2023] Open
Abstract
Video capsule endoscopy (VCE) has evolved to become an important tool for the non-invasive examination of the small bowel, which hitherto had been relatively inaccessible to direct visualisation. VCE has been shown to play a role in monitoring the activity of small bowel Crohn’s disease and can be used to assess the response to anti-inflammatory treatment in Crohn’s disease. For those patients with Crohn’s disease who have undergone an intestinal resection, VCE has been assessed as a tool to detect post-operative recurrence. VCE may also aid in the reclassification of patients with a diagnosis of Inflammatory Bowel Disease Unclassified to Crohn’s disease. The evolution of colon capsule endoscopy (CCE) has expanded the application of this technology further. The use of CCE to assess the activity of ulcerative colitis has been described. This advance in capsule technology has also fuelled interest in its potential role as a minimally invasive tool to assess the whole of GI tract opening the possibility of its use for the panenteric assessment of Crohn’s disease. VCE is a safe procedure. However, the risk of a retained capsule is higher in patients with suspected or confirmed Crohn’s disease compared with patients having VCE examination for other indications. A retained video capsule is rare after successful passage of a patency capsule which may be utilised to pre-screen patients undergoing VCE. This paper describes the use of VCE in the assessment of inflammatory bowel disease.
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Nakase H, Keum B, Ye BD, Park SJ, Koo HS, Eun CS. Treatment of inflammatory bowel disease in Asia: the results of a multinational web-based survey in the 2(nd) Asian Organization of Crohn's and Colitis (AOCC) meeting in Seoul. Intest Res 2016; 14:231-9. [PMID: 27433145 PMCID: PMC4945527 DOI: 10.5217/ir.2016.14.3.231] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 04/06/2016] [Accepted: 04/06/2016] [Indexed: 12/20/2022] Open
Abstract
Background/Aims Inflammatory bowel disease (IBD) management guidelines have been released from Western countries, but no adequate data on the application of these guidelines in Asian countries and no surveys on the treatment of IBD in real practice exist. Since there is a growing need for a customized consensus for IBD treatment in Asian countries, Asian Organization of Crohn's and Colitis performed a multinational survey of medical doctors who treat IBD patients in Asian countries. Methods A questionnaire was developed between August 2013 and November 2013. It was composed of 4 domains: personal information, IBD diagnosis, IBD treatment, and quality of IBD care. Upon completion of the questionnaire, a web-based survey was conducted between 17 March 2014 and 12 May 2014. Results In total, 353 medical doctors treating IBD from ten Asian countries responded to the survey. This survey data suggested a difference in available medical treatments (budesonide, tacrolimus) among Asian countries. Therapeutic strategies regarding refractory IBD (acute severe ulcerative colitis [UC] refractory to intravenous steroids and refractory Crohn's disease [CD]) and active UC were coincident, however, induction therapies for mild to moderate inflammatory small bowel CD are different among Asian countries. Conclusions This survey demonstrated that current therapeutic approaches and clinical management of IBD vary among Asian countries. Based on these results and discussions, we hope that optimal management guidelines for Asian IBD patients will be developed.
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Affiliation(s)
- Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University, School of Medicine, Sapporo, Japan
| | - Bora Keum
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Byoung Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Soo Jung Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hoon Sup Koo
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Chang Soo Eun
- Department of Internal Medicine, Hanyang University Guri Hosptial, Guri, Korea
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Caccaro R, Angriman I, D’Incà R. Relevance of fecal calprotectin and lactoferrin in the post-operative management of inflammatory bowel diseases. World J Gastrointest Surg 2016; 8:193-201. [PMID: 27022446 PMCID: PMC4807320 DOI: 10.4240/wjgs.v8.i3.193] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 11/28/2015] [Accepted: 01/11/2016] [Indexed: 02/06/2023] Open
Abstract
The role of fecal lactoferrin and calprotectin has been extensively studied in many areas of inflammatory bowel disease (IBD) patients’ management. The post-operative setting in both Crohn’s disease (CD) and ulcerative colitis (UC) patients has been less investigated although few promising results come from small, cross-sectional studies. Therefore, the current post-operative management still requires endoscopy 6-12 mo after intestinal resection for CD in order to exclude endoscopic recurrence and plan the therapeutic strategy. In patients who underwent restorative proctocolectomy, endoscopy is required whenever symptoms includes the possibility of pouchitis. There is emerging evidence that fecal calprotectin and lactoferrin are useful surrogate markers of inflammation in the post-operative setting, they correlate with the presence and severity of endoscopic recurrence according to Rutgeerts’ score and possibly predict the subsequent clinical recurrence and response to therapy in CD patients. Similarly, fecal markers show a good correlation with the presence of pouchitis, as confirmed by endoscopy in operated UC patients. Fecal calprotectin seems to be able to predict the short-term development of pouchitis in asymptomatic patients and to vary according to response to medical treatment. The possibility of both fecal markers to used in the routine clinical practice for monitoring IBD patients in the post-operative setting should be confirmed in multicentric clinical trial with large sample set. An algorithm that can predict the optimal use and timing of fecal markers testing, the effective need and timing of endoscopy and the cost-effectiveness of these as a strategy of care would be of great interest.
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Kjeldsen J, Nielsen J, Larsen MD, Qvist N, Nørgård BM. Postoperative Use of Anti-TNF-α Agents in Patients with Crohn's Disease and Risk of Reoperation-A Nationwide Cohort Study. Inflamm Bowel Dis 2016; 22:599-606. [PMID: 26650149 DOI: 10.1097/mib.0000000000000647] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND Approximately 80% of patients with Crohn's disease will require surgery. Surgery for Crohn's disease is not curative, and recurrence is typical. In this cohort study, based on nationwide Danish registries, we examined the association between postoperative treatment with anti-tumor necrosis factor α (anti-TNF-α) agents and reoperation. METHODS The association was examined in cohort 1 = patients not treated with anti-TNF-α agents within 6 months before operation, cohort 2 = patients treated with anti-TNF-α agents within 6 months before operation. Within both cohorts, we defined postoperative exposure to anti-TNF-α agents as at least 1 treatment within 6 months after the first operation and the reference cohorts were those not treated. Patients were followed from 6 months after operation and until 5 years. We used Cox proportional-hazards regression to compute adjusted hazard ratios with 95% confidence intervals. RESULTS In cohort 1, 31 (1.3%) were treated with anti-TNF-α agents within 6 months after operation and compared with those not treated, the adjusted hazard ratio of reoperation among those treated with anti-TNF-α agents was 3.53 (95% confidence interval: 1.61-7.72). In cohort 2, 63 (16.3%) were treated with anti-TNF-α agents within 6 months after operation, and the corresponding adjusted hazard ratio of reoperation was 2.16 (95% confidence interval: 1.11-4.18). CONCLUSIONS Our data suggest that anti-TNF-α treatment within 6 months after the first operation is not associated with a reduction in the need for subsequent operation. Uncontrolled confounding might have influenced our results, and, furthermore, future studies are warranted to clarify whether our study population is different from populations most often associated with postoperative anti-TNF-α treatment.
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Affiliation(s)
- Jens Kjeldsen
- *Department of Medical Gastroenterology S, Odense University Hospital, and Research Unit of Medical Gastroenterology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; †Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; and ‡Department of Surgical Gastroenterology A, Odense University Hospital, and Research Unit of Surgery, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
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Roda G, Jharap B, Neeraj N, Colombel JF. Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management. Clin Transl Gastroenterol 2016; 7:e135. [PMID: 26741065 PMCID: PMC4737871 DOI: 10.1038/ctg.2015.63] [Citation(s) in RCA: 512] [Impact Index Per Article: 56.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 11/13/2015] [Indexed: 12/23/2022] Open
Abstract
Tumor necrosis factor-α (TNFα) antagonists have advanced the management of inflammatory bowel diseases patients leading to an improvement of patient's quality of life with the reduction of number of surgeries and hospitalizations. Despite these advances, many patients do not respond to the induction therapy (primary non-response-PNR) or lose response during the treatment (secondary loss of response-LOR). In this paper we will provide an overview of the definition, epidemiology and risk factors for PNR and LOR, as well as discuss the therapeutic options for managing LOR.
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Affiliation(s)
- Giulia Roda
- The Leona M. Harry B. Helmsley Inflammatory Bowel Disease Center, The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA
| | | | - Narula Neeraj
- The Leona M. Harry B. Helmsley Inflammatory Bowel Disease Center, The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Jean-Frederic Colombel
- The Leona M. Harry B. Helmsley Inflammatory Bowel Disease Center, The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA
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Lee HW, Cheon JH, Lee HJ, Park SJ, Hong SP, Kim TI, Kim WH. Postoperative Effects of Thiopurines in Patients with Intestinal Behçet's Disease. Dig Dis Sci 2015; 60:3721-3727. [PMID: 26199149 DOI: 10.1007/s10620-015-3799-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 07/04/2015] [Indexed: 12/31/2022]
Abstract
BACKGROUND No studies have heretofore specifically focused on the efficacy of postoperative thiopurine therapy in intestinal Behçet's disease (BD). We conducted this study to assess the clinical effects of postoperative thiopurines in patients with intestinal BD. METHODS We reviewed the medical records of all patients with intestinal BD who had undergone bowel resection surgery in a single tertiary academic medical center between 1991 and 2013. The cumulative probabilities of clinical recurrence were calculated using the Kaplan-Meier method, and predictive factors for recurrence were assessed by multivariate analysis. RESULTS A total of 77 patients with intestinal BD received 5-ASA (n = 50, 64.9%) or thiopurine (n = 27, 35.1%) therapy after surgery at our center. The postoperative recurrence rate was lower in patients who received postoperative thiopurines (P = 0.050). The hazard ratio for recurrence was 0.636 (95% confidence interval 0.130-1.016, P = 0.053) for postoperative thiopurine use compared with postoperative 5-ASA. However, the rates of re-operation, re-admission, and death were not significantly different between the 5-ASA and thiopurine groups. CONCLUSIONS Thiopurine therapy after surgery exhibited a modest effect in preventing recurrence in intestinal BD patients. More patients, long-term follow-up, and a randomized controlled design are necessary to validate the effectiveness of postoperative thiopurines in patients with this disease.
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Affiliation(s)
- Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
| | - Hyun Jung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Soo Jung Park
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Pil Hong
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Il Kim
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Won Ho Kim
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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Abstract
BACKGROUND Crohn's disease (CD) is increasing in incidence and prevalence in Asia, but there is a paucity of population-based studies on risk factors for surgery in Asian patients with CD. This will be useful to identify patients who may benefit from top-down treatment. This study describes the rates of abdominal surgery and identifies associated risk factors in Singaporean patients with CD. METHODS This was a retrospective observational study. The medical records of Singaporeans diagnosed with CD from 1970 to 2013 were reviewed from 8 different hospitals in Singapore. The cumulative probability of CD-related abdominal surgery was estimated using the Kaplan-Meier method. The logistic regression model was used to assess associations between independent risk factors and surgery. RESULTS The cohort of 430 Singaporean patients with CD included 63.5% Chinese, 11.9% Malay, and 24.7% Indians, with a male to female ratio of 1.6; median follow-up was 7.3 years (range, 2.9-13.0 yr) and median age at diagnosis 30.5 years (range, 19.5-43.7 yr). One hundred twelve patients (26.0%) required major abdominal surgery: the cumulative risk of surgery was 14.9% at 90 days, 21.2% at 5 years, 28.8% at 10 years, 38.3% at 20 years, and 50.6% at 30 years from diagnosis. Of the surgical patients, 75.0% were Chinese, 10.7% Malays, and 14.3% Indians; 21.4% underwent surgery for inflammatory disease, 40.2% for stricturing disease, and 38.4% for penetrating disease. Age at diagnosis (A2 17-40 yr, OR: 2.75, 95% confidence interval [CI], 1.14-7.76), ileal disease (L1 location, OR: 2.35, 95% CI, 1.14-5.0), stricturing (B2 OR: 6.09, 95% CI, 3.20-11.8), and penetrating behavior (B3 OR: 21.6, 95% CI, 9.0-58.8) were independent risk factors for CD-related abdominal surgery. Indian patients were less likely to require surgery (OR: 0.40, 95% CI, 0.19-0.78). CONCLUSIONS Age at diagnosis, L1 location, B2, and B3 disease behavior are independent risk factors for abdominal surgery. Interestingly, despite a higher prevalence of CD in Indians, a smaller proportion of Indian patients required surgery. These findings suggest that both environmental and genetic factors contribute to the risk of surgery in Asian patients with CD.
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Bodini G, Savarino V, Marabotto E, Savarino E. Anti-Tumor Necrosis Factor Antibodies for Prevention of Crohn's Disease Recurrence After Surgery: More Than a Hope. Clin Gastroenterol Hepatol 2015; 13:1856. [PMID: 25638583 DOI: 10.1016/j.cgh.2015.01.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Accepted: 01/23/2015] [Indexed: 02/07/2023]
Affiliation(s)
- Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Abstract
Crohn's disease (CD) is a chronic, persistent, and destructive disorder with different forms of clinical behavior and the disease appears to be progressive over the long term. Providing greater levels of mucosal healing and resolution of clinical symptoms may modify the course of CD. This will often necessitate long-term therapy with immunosuppressant or biological therapies. Both these classes of drugs have side-effects and the latter are also very expensive. Identification of a subgroup of patients with a low risk of relapse and validation of the relevant predictors in various cohort studies are the key points to be able to cease immunosuppressant and/or biological therapy in patients with CD in stable remission. The individual parameters 'mucosal healing', 'deep remission', 'fecal calprotectin', and 'C-reactive protein' or various combinations of these parameters seem to be promising tools for predicting successful withdrawal of maintenance therapy.
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Sartor RB. Preventing postoperative recurrence of Crohn's disease: how can we improve results? Clin Gastroenterol Hepatol 2015; 13:936-9. [PMID: 25576478 DOI: 10.1016/j.cgh.2014.12.027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 12/23/2014] [Accepted: 12/27/2014] [Indexed: 02/07/2023]
Affiliation(s)
- R Balfour Sartor
- University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Nielsen OH, Coskun M, Steenholdt C, Rogler G. The role and advances of immunomodulator therapy for inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2015; 9:177-89. [PMID: 25101818 DOI: 10.1586/17474124.2014.945914] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Immune modulating drugs such as thiopurines (azathioprine and 6-mercaptopurine) and methotrexate has been a mainstay for treatment of inflammatory bowel disease (IBD) for decades. However, despite widely used in IBD, questions still remain concerning the most rational treatment regimens of these agents. Results from a range of recent studies necessitate increased awareness on how to best use these potent drugs in the clinic. As controversy still remains regarding the most appropriate use of immunomodulators, this review is based on scrutinizing the current literature, with emphasis on randomized controlled trials and Cochrane reviews, focusing on aspects that can lead to optimal and evidence-based thiopurine and methotrexate treatment strategies in IBD.
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Affiliation(s)
- Ole Haagen Nielsen
- Department of Gastroenterology, Medical Section D112M, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark
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Yamamoto T. Letter: faecal calprotectin and lactoferrin - accurate biomarkers in post-operative Crohn's disease? Aliment Pharmacol Ther 2014; 40:321. [PMID: 25040748 DOI: 10.1111/apt.12840] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2014] [Accepted: 05/26/2014] [Indexed: 01/20/2023]
Affiliation(s)
- T Yamamoto
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie, Japan.
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Jones GR, Kennedy NA, Lees CW, Arnott ID, Satsangi J. Letter: faecal calprotectin and lactoferrin - accurate biomarkers in post-operative Crohn's disease - authors' reply. Letter: biologic therapies are effective for prevention of post-operative Crohn's disease recurrence - authors' reply. Aliment Pharmacol Ther 2014; 40:323. [PMID: 25040750 DOI: 10.1111/apt.12848] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Accepted: 06/03/2014] [Indexed: 12/16/2022]
Affiliation(s)
- G R Jones
- Department of Gastroenterology, Western General Hospital, Edinburgh, UK.
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Bodini G, De Cassan C, Savarino V, Savarino E. Letter: biological therapies are effective for prevention of post-operative Crohn's disease recurrence. Aliment Pharmacol Ther 2014; 40:322. [PMID: 25040749 DOI: 10.1111/apt.12831] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Accepted: 05/21/2014] [Indexed: 12/08/2022]
Affiliation(s)
- G Bodini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
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