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Yang L, Liu G, Zhang Y, Yao B, Wu Q, Peng L, Wang X, Yuan L. Quantitative analysis of adipose tissue for predicting Crohn's disease postoperative endoscopic recurrence and anastomotic ulcer. Int J Colorectal Dis 2023; 38:170. [PMID: 37328584 DOI: 10.1007/s00384-023-04456-z] [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] [Accepted: 05/25/2023] [Indexed: 06/18/2023]
Abstract
OBJECTIVE Inflammation and ulcers at the anastomotic site are frequently observed after intestinal resection surgery for Crohn's disease (CD), which often signify postoperative recurrence. Crohn's disease causes abnormalities in whole-body fat metabolism, and alterations in subcutaneous and visceral fat are potential indicators of disease development. This study aimed to quantify the areas of subcutaneous (SFA) and visceral fat (VFA) and investigate the relationship between fat tissue and endoscopic recurrence and anastomotic ulceration after Crohn's disease surgery. METHODS We conducted a retrospective analysis of clinical data from 279 patients diagnosed with Crohn's disease. Using abdominal CT (Computed Tomography) scans at the level of the umbilicus, we measured the area of subcutaneous and visceral fat, and calculated the Mesenteric Fat Index (MFI), which is defined as the ratio of the area of visceral fat to subcutaneous fat. We compared the changes in fat tissue between surgical Crohn's disease patients and non-surgical patients in remission, as well as changes in fat tissue before and after surgery, and between patients with and without endoscopic recurrence after surgery. RESULTS The MFI value of the surgical group was higher than that of the non-surgical group(0.88(1.27 ± 1.26) VS 0.39(0.44 ± 0.21), P < 0.001), while the SFA value was lower(70.16(92.97 ± 78.23) VS 157.64(175.96 ± 101.58), P < 0.001). Of the 134 surgical patients who underwent abdominal CT examination after surgery, the SFA value was significantly higher after surgery(143.61 ± 81.86 VS 90.87 ± 71.93, P < 0.001), and the MFI value decreased accordingly(0.57 ± 0.36 VS 1.30 ± 1.35, P < 0.001). Multivariate Cox analysis indicated that high VFA and MFI values, smoking history, and preoperative biologic therapy were all risk factors for postoperative endoscopic recurrence(p < 0.05), while high MFI values and preoperative biologic therapy were also risk factors for anastomotic ulcers(p < 0.05). The Kaplan-Meier analysis showed that these factors increased the risk of reaching the endpoint with time(p < 0.05). The ROC curve results showed that MFI value had high diagnostic value for postoperative endoscopic recurrence [AUC:0.831, 95% CI: 0.75-0.91, p < 0.001] and anastomotic ulcers [AUC:0.801, 95% CI: 0.71-0.89, p < 0.001]. CONCLUSIONS Surgical CD patients have significantly higher MFI values but the values decline after surgery. When the preoperative MFI value is > 0.82, the risk of postoperative endoscopic recurrence increases significantly, and when the MFI value is ≥ 1.10, the risk of anastomotic ulceration after surgery increases significantly. Meanwhile, biologic therapy preoperatively also is a high-risk factor for early postoperative endoscopic recurrence or anastomotic ulcers after intestinal resection surgery.
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Affiliation(s)
- Lichao Yang
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
- Department of Geriatric Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Ganglei Liu
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
- Department of Geriatric Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Yawei Zhang
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
- Department of Geriatric Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Baojia Yao
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
- Department of Geriatric Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Qiang Wu
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
- Department of Geriatric Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Liangxin Peng
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
- Department of Geriatric Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Xuehong Wang
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, 410011, China.
| | - Lianwen Yuan
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China.
- Department of Geriatric Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China.
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Early Post-Operative Endoscopy Is Associated with Lower Surgical Recurrence of Crohn's Disease: A Retrospective Study of Three Successive Cohorts. Gastroenterol Res Pract 2022; 2022:6341069. [PMID: 36388633 PMCID: PMC9643063 DOI: 10.1155/2022/6341069] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 09/26/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The severity of endoscopic recurrence during the first year after intestinal resection for Crohn's disease is predictive of clinical recurrence. The aim of our study was to assess the impact of the implementation of an ileocolonoscopy during the first year after surgery on surgical recurrence. METHODS All patients who underwent a first intestinal resection for Crohn's disease between 1992 and 2018 at the University Hospital of Liège were retrospectively included. The time to surgical recurrence was compared in three successive groups of patients operated on in the period 1992-2001 (group A), 2002-2011 (group B), and 2012-2020 (group C) using the Kaplan-Meier method and the Log-Rank test. To identify independent prognostic factors, a multivariate analysis was used via the Cox model. RESULTS 223 patients (group A = 69, group B = 94, group C = 60) were included. Probabilities of surgical recurrence were significantly lower in group C (2.2% and 4.7% at 3 and 5 years, respectively) compared with group B (4.2% and 7.6% at 3 and 5 years, respectively) and with group A (9% and 18.2% at 3 and 5 years, respectively) (p = 0.0089). Ileocolonoscopy during the year after surgery was associated with a significantly reduced surgical recurrence rate in univariate and multivariate analysis (HR = 0.31, p = 0.0049). CONCLUSION The implementation of an early ileocolonoscopy after surgery for Crohn's disease since early 2000 has been associated with a reduced surgical recurrence over the last 30 years.
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Alexdottir MS, Bourgonje AR, Karsdal MA, Pehrsson M, Loveikyte R, van Dullemen HM, Visschedijk MC, Festen EAM, Weersma RK, Faber KN, Dijkstra G, Mortensen JH. Serological Biomarkers of Extracellular Matrix Turnover and Neutrophil Activity Are Associated with Long-Term Use of Vedolizumab in Patients with Crohn's Disease. Int J Mol Sci 2022; 23:ijms23158137. [PMID: 35897710 PMCID: PMC9329899 DOI: 10.3390/ijms23158137] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/21/2022] [Accepted: 07/22/2022] [Indexed: 02/01/2023] Open
Abstract
Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal (GI) tract characterized by increased extracellular matrix (ECM) remodeling. The introduction of the α4β7-integrin inhibitor vedolizumab (VEDO) has improved disease management, although there is a high rate of primary non-response in patients with CD. We studied whether ECM biomarkers of neutrophil activity and mucosal damage could predict long-term response to VEDO in patients with CD. Serum levels of human neutrophil elastase (HNE)-derived fragments of calprotectin (CPa9-HNE), and matrix metalloproteinase (MMP)-derived fragments of type I (C1M), III (C3M), IV (C4M), and VI (C6Ma3) collagen, type III collagen formation (PRO-C3), basement membrane turnover (PRO-C4) and T-cell activity (C4G), were measured using protein fingerprint assays in patients with CD (n = 32) before VEDO therapy. Long-term response was defined as VEDO treatment of at least 12 months. CPa9-HNE was significantly increased at baseline in non-responders compared with responders (p < 0.05). C1M, C3M, C4M, C6Ma3, and PRO-C4 were also significantly increased at baseline in non-responders compared with responders (all p < 0.05). All biomarkers were associated with response to VEDO (all p < 0.05). To conclude, baseline levels of serum biomarkers for neutrophil activity and mucosal damage are linked to the pathology of CD, and are associated with long-term use of VEDO in patients with CD. Therefore, these biomarkers warrant further validation and could aid in therapeutic decision-making concerning vedolizumab therapy.
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Affiliation(s)
- Marta S. Alexdottir
- Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark; (M.A.K.); (M.P.); (J.H.M.)
- Correspondence:
| | - Arno R. Bourgonje
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (A.R.B.); (R.L.); (H.M.v.D.); (M.C.V.); (E.A.M.F.); (R.K.W.); (K.N.F.); (G.D.)
| | - Morten A. Karsdal
- Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark; (M.A.K.); (M.P.); (J.H.M.)
| | - Martin Pehrsson
- Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark; (M.A.K.); (M.P.); (J.H.M.)
| | - Roberta Loveikyte
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (A.R.B.); (R.L.); (H.M.v.D.); (M.C.V.); (E.A.M.F.); (R.K.W.); (K.N.F.); (G.D.)
| | - Hendrik M. van Dullemen
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (A.R.B.); (R.L.); (H.M.v.D.); (M.C.V.); (E.A.M.F.); (R.K.W.); (K.N.F.); (G.D.)
| | - Marijn C. Visschedijk
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (A.R.B.); (R.L.); (H.M.v.D.); (M.C.V.); (E.A.M.F.); (R.K.W.); (K.N.F.); (G.D.)
| | - Eleonora A. M. Festen
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (A.R.B.); (R.L.); (H.M.v.D.); (M.C.V.); (E.A.M.F.); (R.K.W.); (K.N.F.); (G.D.)
| | - Rinse K. Weersma
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (A.R.B.); (R.L.); (H.M.v.D.); (M.C.V.); (E.A.M.F.); (R.K.W.); (K.N.F.); (G.D.)
| | - Klaas Nico Faber
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (A.R.B.); (R.L.); (H.M.v.D.); (M.C.V.); (E.A.M.F.); (R.K.W.); (K.N.F.); (G.D.)
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (A.R.B.); (R.L.); (H.M.v.D.); (M.C.V.); (E.A.M.F.); (R.K.W.); (K.N.F.); (G.D.)
| | - Joachim H. Mortensen
- Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark; (M.A.K.); (M.P.); (J.H.M.)
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The Role of Inflammation in Crohn's Disease Recurrence after Surgical Treatment. J Immunol Res 2020; 2020:8846982. [PMID: 33426097 PMCID: PMC7781709 DOI: 10.1155/2020/8846982] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 12/04/2020] [Accepted: 12/08/2020] [Indexed: 02/08/2023] Open
Abstract
Introduction Postoperative recurrence after surgery for Crohn's disease (CD) is virtually inevitable, and its mechanism is poorly known. Aim To review the numerous factors involved in CD postoperative recurrence (POR) pathogenesis, focusing on single immune system components as well as the immune system as a whole and highlighting the clinical significance in terms of preventive strategies and future perspectives. Methods A systematic literature search on CD POR, followed by a review of the main findings. Results The immune system plays a pivotal role in CD POR, with many different factors involved. Memory T-lymphocytes retained in mesenteric lymph nodes seem to represent the main driving force. New pathophysiology-based preventive strategies in the medical and surgical fields may help reduce POR rates. In particular, surgical strategies have already been developed and are currently under investigation. Conclusions POR is a complex phenomenon, whose driving mechanisms are gradually being unraveled. New preventive strategies addressing these mechanisms seem promising.
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Hao X, Feng T, Yang Y, Shi Y, Jing R, Liu S, Luo Y, Qiao Y, Zhong M, Yu M. Laparoscopic bowel resection combined with infliximab treatment (LaRIC) versus infliximab for terminal ileitis in Crohn's disease: a randomised, controlled, open-label trial. BMJ Open 2020; 10:e038429. [PMID: 33199421 PMCID: PMC7670938 DOI: 10.1136/bmjopen-2020-038429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 09/15/2020] [Accepted: 09/26/2020] [Indexed: 11/07/2022] Open
Abstract
INTRODUCTION Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract with an increasing incidence and prevalence worldwide. The early use of anti--tumour necrosis factor agents, such as infliximab, in patients with an aggressive form of Crohn's disease has become part of routine practice. However, infliximab has limitations, and early surgery might benefit patients more. The objective of this study was to compare laparoscopic bowel resection with infliximab treatment in patients with moderately or severely active Crohn's disease with respect to endoscopic remission. The laparoscopic bowel resection combined with infliximab treatment trial is the first randomised controlled trial to demonstrate if early surgery can improve the outcome of patients with Crohn's disease with limited non-stricturing disease treated with infliximab. METHODS AND ANALYSIS This is a randomised, open-label, controlled trial at Renji Hospital. In this study, a total of 106 adult patients aged 18-80 years with moderately or severely active and steroid-dependent or steroid-resistant Crohn's disease of the distal ileum will be randomly assigned in a 1:1 ratio to the control and surgery groups. The primary outcome is 12-month endoscopic remission measured by the Simple Endoscopic Score for Crohn's Disease in the control group and the Rutgeerts score in the surgery group. The secondary outcomes are clinical remission, surgery rate, quality of life, Crohn's disease-related medical costs and Crohn's disease-related morbidity. The patients will be followed up every 6 months after randomisation through intestinal magnetic resonance enterography and colonoscopy for either 3 years or until clinical remission. ETHICS AND DISSEMINATION All participants will provide informed consent. The protocol has been approved by the Medical Ethical Committee of the Academic Medical Center in Shanghai (No KY2019-180). Results will be disseminated through peer-reviewed journals and scientific conference presentations. TRIAL REGISTRATION NUMBER ChiCTR2000029323.
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Affiliation(s)
- Xiuxiu Hao
- Department of Gastrointestinal Surgery, Shanghai Jiao Tong University School of Medicine Affiliated to Renji Hospital, Shanghai, China
| | - Tienan Feng
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yang Yang
- Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China
| | - Yuan Shi
- Department of Gastrointestinal Surgery, Shanghai Jiao Tong University School of Medicine Affiliated to Renji Hospital, Shanghai, China
| | - Ran Jing
- Department of Gastrointestinal Surgery, Shanghai Jiao Tong University School of Medicine Affiliated to Renji Hospital, Shanghai, China
| | - Sailiang Liu
- Department of Gastrointestinal Surgery, Shanghai Jiao Tong University School of Medicine Affiliated to Renji Hospital, Shanghai, China
| | - Yang Luo
- Department of Gastrointestinal Surgery, Shanghai Jiao Tong University School of Medicine Affiliated to Renji Hospital, Shanghai, China
| | - Yuqi Qiao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University School of Medicine Affiliated to Renji Hospital, Shanghai, China
| | - Ming Zhong
- Department of Gastrointestinal Surgery, Shanghai Jiao Tong University School of Medicine Affiliated to Renji Hospital, Shanghai, China
| | - Minhao Yu
- Department of Gastrointestinal Surgery, Shanghai Jiao Tong University School of Medicine Affiliated to Renji Hospital, Shanghai, China
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Tang S, Liu W, Qi W, Yu T, Cao Q, Ge X, Zhou W. Real-World Experience with AGA Guidelines in the Management of Crohn's Disease following Ileocolonic Resection: A Retrospective Cohort Study. Gastroenterol Res Pract 2020; 2020:8618574. [PMID: 32382273 PMCID: PMC7189305 DOI: 10.1155/2020/8618574] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 03/23/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Postoperative endoscopic recurrence (PER) is common in patients with Crohn's disease (CD) after surgery. The impact of the American Gastroenterological Association (AGA) guideline adherence on PER in real life remains unclear. METHODS The postoperative management of CD patients undergoing ileocolonic resection with anastomosis from 2017 to 2018 was conducted based on the AGA guidelines. Colonoscopies were performed within one year after surgery. Clinical data and risk factors for endoscopic recurrence were analyzed focusing on postoperative pharmacological prophylaxis. RESULTS All patients were at a high risk of postoperative recurrence according to the AGA guidelines. PER occurred in 29 (28.7%) of these patients. The overall PER rate was 39.2% at one year. The PER rate in patients treated with nitroimidazole, thiopurines, infliximab, or a combination of thiopurines and infliximab for postoperative prophylaxis was 88.1%, 34.1%, 20.5%, and 0%, respectively. Cox regression showed that smoking at the time of surgery and AGA guideline adherence were independent factors associated with PER (HR: 3.75, 95% CI: 1.36-10.33, P = 0.01; HR: 0.36, 95% CI: 0.15-0.86, P = 0.02). In addition, further investigation revealed that educational background was the main factor related to patients' nonadherence to AGA guidelines. CONCLUSIONS The majority of CD patients who undergo surgery in clinical practice may be at a high risk of disease recurrence. Thiopurines and infliximab are effective in preventing endoscopic recurrence. Guideline nonadherence is associated with PER at one year, thus indicating that there is room for improvement in adherence to the AGA guidelines.
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Affiliation(s)
- Shasha Tang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wei Liu
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Weilin Qi
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Tunan Yu
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Qian Cao
- Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaolong Ge
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wei Zhou
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MCE, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68:s1-s106. [PMID: 31562236 PMCID: PMC6872448 DOI: 10.1136/gutjnl-2019-318484] [Citation(s) in RCA: 1436] [Impact Index Per Article: 239.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 06/10/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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Affiliation(s)
- Christopher Andrew Lamb
- Newcastle University, Newcastle upon Tyne, UK
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Nicholas A Kennedy
- Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
- University of Exeter, Exeter, UK
| | - Tim Raine
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Philip Anthony Hendy
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
- Imperial College London, London, UK
| | - Philip J Smith
- Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Bu'Hussain Hayee
- King's College Hospital NHS Foundation Trust, London, UK
- King's College London, London, UK
| | - Miranda C E Lomer
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Gareth C Parkes
- Barts Health NHS Trust, London, UK
- Barts and the London School of Medicine and Dentistry, London, UK
| | - Christian Selinger
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Leeds, Leeds, UK
| | | | - R Justin Davies
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
- University of Cambridge, Cambridge, UK
| | - Cathy Bennett
- Systematic Research Ltd, Quorn, UK
- Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | | | - Malcolm G Dunlop
- University of Edinburgh, Edinburgh, UK
- Western General Hospital, Edinburgh, UK
| | - Omar Faiz
- Imperial College London, London, UK
- St Mark's Hospital, Harrow, UK
| | - Aileen Fraser
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | | | | | - Miles Parkes
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Jeremy Sanderson
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Daniel R Gaya
- Glasgow Royal Infirmary, Glasgow, UK
- University of Glasgow, Glasgow, UK
| | - Tariq H Iqbal
- Queen Elizabeth Hospital Birmingham NHSFoundation Trust, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - Stuart A Taylor
- University College London, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Melissa Smith
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
- Brighton and Sussex Medical School, Brighton, UK
| | - Matthew Brookes
- Royal Wolverhampton NHS Trust, Wolverhampton, UK
- University of Wolverhampton, Wolverhampton, UK
| | - Richard Hansen
- Royal Hospital for Children Glasgow, Glasgow, UK
- University of Glasgow, Glasgow, UK
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Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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A Meta-Analysis of Efficacy and Safety of Infliximab for Prevention of Postoperative Recurrence in Patients with Crohn's Disease. BIOMED RESEARCH INTERNATIONAL 2019; 2018:2615978. [PMID: 30643797 PMCID: PMC6311309 DOI: 10.1155/2018/2615978] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 08/13/2018] [Indexed: 01/06/2023]
Abstract
Objective We sought to investigate the efficacy and safety of Infliximab for prevention of postoperative recurrence in patients with Crohn's disease (CD), in a meta-analysis of clinical trial results. Methods The Medline, Embase, PubMed, and Web of Science databases were systematically searched for suitable studies. A meta-analysis of enrolled studies was performed to analyze the efficacy of Infliximab on outcomes regarding the prevention of postoperative recurrence of CD. A Galbraith radial plot was used to quantify the heterogeneity. Funnel plot and Egger test were performed to describe the bias of publication. A Forest plot was prepared to indicate the efficacy outcomes. Results A total of 7 prospective trials were included in our meta-analysis (N=455). The Funnel plot and Egger test showed there was no significant bias in the included publications. The Cochrane collaboration tool indicated that all 7 prospective trials were of high quality. The results of Galbraith radial plot showed that no study was the source of heterogeneity. Compared with the placebo group, Infliximab decreased the rates of endoscopic recurrence (RR =0.421; 95% CI 0.328 to 0.539; p<0.001), and there was a significant reduction in rates of clinical recurrence in the Infliximab-treated group (RR =0.519; 95% CI 0.349 to 0.774; p=0.001). Furthermore, Infliximab treatment did not show adverse effects as other systematic therapeutic drugs, indicating that Infliximab treatment is effective and well tolerated. Conclusion Compared with the controls, Infliximab is a promising therapeutic agent for the management of CD patients.
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Milassin Á, Sejben A, Tiszlavicz L, Reisz Z, Lázár G, Szűcs M, Bor R, Bálint A, Rutka M, Szepes Z, Nagy F, Farkas K, Molnár T. Analysis of risk factors - especially different types of plexitis - for postoperative relapse in Crohn’s disease. World J Gastrointest Surg 2017; 9:167-173. [PMID: 28824749 PMCID: PMC5545135 DOI: 10.4240/wjgs.v9.i7.167] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 04/25/2017] [Accepted: 05/24/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the presence of submucosal and myenteric plexitis and its role in predicting postoperative recurrence.
METHODS Data from all patients who underwent Crohn’s disease (CD)-related resection at the University of Szeged, Hungary between 2004 and 2014 were analyzed retrospectively. Demographic data, smoking habits, previous resection, treatment before and after surgery, resection margins, neural fiber hyperplasia, submucosal and myenteric plexitis were evaluated as possible predictors of postoperative recurrence. Histological samples were analyzed blinded to the postoperative outcome and the clinical history of the patient. Plexitis was evaluated based on the appearance of the most severely inflamed ganglion or nerve bundle. Patients underwent regular follow-up with colonoscopy after surgery. Postoperative recurrence was defined on the basis of endoscopic and clinical findings, and/or the need for additional surgical resection.
RESULTS One hundred and four patients were enrolled in the study. Ileocecal, colonic, and small bowel resection were performed in 73.1%, 22.1% and 4.8% of the cases, respectively. Mean disease duration at the time of surgery was 6.25 years. Twenty-six patients underwent previous CD-related surgery. Forty-three point two percent of the patients were on 5-aminosalicylate, 20% on corticosteroid, 68.3% on immunomodulant, and 4% on anti-tumor necrosis factor-alpha postoperative treatment. Postoperative recurrence occurred in 61.5% of the patients; of them 39.1% had surgical recurrence. 92.2% of the recurrences developed within the first five years after the index surgery. Mean disease duration for endoscopic relapse was 2.19 years. The severity of submucosal plexitis was a predictor of the need for second surgery (OR = 1.267, 95%CI: 1.000-1.606, P = 0.050). Female gender (OR = 2.21, 95%CI: 0.98-5.00, P = 0.056), stricturing disease behavior (OR = 3.584, 95%CI: 1.344-9.559, P = 0.011), and isolated ileal localization (OR = 2.671, 95%CI: 1.033-6.910, P = 0.043) were also predictors of postoperative recurrence. No association was revealed between postoperative recurrence and smoking status, postoperative prophylactic treatment and the presence of myenteric plexitis and relapse.
CONCLUSION The presence of severe submucosal plexitis with lymphocytes in the proximal resection margin is more likely to result in postoperative relapse in CD.
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Kim EK, Cho JH, Kim E, Kim YJ. Ursodeoxycholic acid inhibits the proliferation of colon cancer cells by regulating oxidative stress and cancer stem-like cell growth. PLoS One 2017; 12:e0181183. [PMID: 28708871 PMCID: PMC5510851 DOI: 10.1371/journal.pone.0181183] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 06/27/2017] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION The regulation of reactive oxygen species (ROS) exists as a therapeutic target for cancer treatments. Previous studies have shown that ursodeoxycholic acid (UDCA) suppresses the proliferation of colon cancer cells. The aim of this study was to evaluate the effect of UDCA upon the proliferation of colon cancer cells as a direct result of the regulation of ROS. METHOD Colon cancer cell lines (HT29 and HCT116) were treated with UDCA. The total number of cells and the number of dead cells were determined using cell counters. A fluorescein isothiocyanate-bromodeoxyuridine flow kit was used to analyze cell cycle variations. Upon exposure to UDCA, the protein levels of p27, p21, CDK2, CDK4 and CDK6 were determined using western blotting, and qRT-PCR was used to determine levels of mRNA. We preformed dichlorofluorescindiacetate (DCF-DA) staining to detect alteration of intracellular ROS using fluorescence activated cell sorting (FACS). Colon cancer stem-like cell lines were generated by tumorsphere culture and treated with UDCA for seven days. The total number of tumorspheres was determined using microscopy. RESULTS We found that UDCA reduced the total number of colon cancer cells, but did not increase the number of dead cells. UDCA inhibited the G1/S and G2/M transition phases in colon cancer cells. UDCA induced expression of cell cycle inhibitors such as p27 and p21. However, it was determined that UDCA suppressed levels of CDK2, CDK4, and CDK6. UDCA regulated intracellular ROS generation in colon cancer cells, and induced activation of Erk1/2. Finally, UDCA inhibited formation of colon cancer stem-like cells. CONCLUSION Our results indicate that UDCA suppresses proliferation through regulation of oxidative stress in colon cancer cells, as well as colon cancer stem-like cells.
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Affiliation(s)
- Eun-Kyung Kim
- Division of Gastroenterology, Department of Internal medicine, Gachon University Gil Medical Center, Incheon, the Republic of Korea
- Gachon Medical Research Institute, Gachon University Gil Medical Center, Incheon, the Republic of Korea
| | - Jae Hee Cho
- Division of Gastroenterology, Department of Internal medicine, Gachon University Gil Medical Center, Incheon, the Republic of Korea
| | - EuiJoo Kim
- Division of Gastroenterology, Department of Internal medicine, Gachon University Gil Medical Center, Incheon, the Republic of Korea
| | - Yoon Jae Kim
- Division of Gastroenterology, Department of Internal medicine, Gachon University Gil Medical Center, Incheon, the Republic of Korea
- * E-mail:
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