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Moutzoukis M, Argyriou K, Kapsoritakis A, Christodoulou D. Endoscopic luminal stenting: Current applications and future perspectives. World J Gastrointest Endosc 2023; 15:195-215. [PMID: 37138934 PMCID: PMC10150289 DOI: 10.4253/wjge.v15.i4.195] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 01/30/2023] [Accepted: 04/04/2023] [Indexed: 04/14/2023] Open
Abstract
Endoscopic luminal stenting (ELS) represents a minimally invasive option for the management of malignant obstruction along the gastrointestinal tract. Previous studies have shown that ELS can provide rapid relief of symptoms related to esophageal, gastric, small intestinal, colorectal, biliary, and pancreatic neoplastic strictures without compromising cancer patients’ overall safety. As a result, in both palliative and neoadjuvant settings, ELS has largely surpassed radiotherapy and surgery as a first-line treatment modality. Following the abovementioned success, the indications for ELS have gradually expanded. To date, ELS is widely used in clinical practice by well-trained endoscopists in managing a wide variety of diseases and complications, such as relieving non-neoplastic obstructions, sealing iatrogenic and non-iatrogenic perforations, closing fistulae and treating post-sphincterotomy bleeding. The abovementioned development would not have been achieved without corresponding advances and innovations in stent technology. However, the technological landscape changes rapidly, making clinicians’ adaptation to new technologies a real challenge. In our mini-review article, by systematically reviewing the relevant literature, we discuss current developments in ELS with regard to stent design, accessories, techniques, and applications, expanding the research basis that was set by previous studies and highlighting areas that need to be further investigated.
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Affiliation(s)
- Miltiadis Moutzoukis
- Department of Gastroenterology, University Hospital of Ioannina, Ioannina GR45333, Greece
| | - Konstantinos Argyriou
- Department of Gastroenterology, Medical School and University Hospital of Larissa, Larissa GR41334, Greece
| | - Andreas Kapsoritakis
- Department of Gastroenterology, Medical School and University Hospital of Larissa, Larissa GR41334, Greece
| | - Dimitrios Christodoulou
- Department of Gastroenterology, Medical School and University Hospital of Ioannina, Ioannina GR45500, Greece
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De Cruz P, Hamilton AL, Burrell KJ, Gorelik A, Liew D, Kamm MA. Endoscopic Prediction of Crohn's Disease Postoperative Recurrence. Inflamm Bowel Dis 2022; 28:680-688. [PMID: 34231852 DOI: 10.1093/ibd/izab134] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The presence and severity of endoscopic recurrence after Crohn's disease intestinal resection predicts subsequent disease course. The Rutgeerts postoperative endoscopic recurrence score is unvalidated but has proven prognostically useful in many clinical studies. This study aimed to investigate the association between specific early endoscopic findings and subsequent disease course. METHODS In the setting of a randomized controlled trial (the POCER study), 85 patients underwent colonoscopy at 6 and 18 months after intestinal resection. Patients received 3 months of metronidazole, and high-risk patients received a thiopurine (or adalimumab if they were thiopurine intolerant). For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped up to a thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. Central readers confirmed Rutgeerts, Simple Endoscopic Score for Crohn's Disease, Crohn's Disease Endoscopic Index of Severity scores, and 5 newly tested endoscopic parameters: anastomotic ulcer depth (superficial vs deep), number of ulcers (0, ≤2, >2), ulcer size (1-5 mm, ≥6 mm), circumferential extent of ulceration (<25%, ≥25%), and the presence or absence of stenosis. The POCER index, based on the 6-month postoperative findings, was then developed in relation to predicting the endoscopic outcome at 18 months. RESULTS Of the 5 parameters, the combination of ulcer depth and circumference at the anastomosis at 6 months was associated with endoscopic recurrence at 18 months (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.50; P = 0.035) with an area under the receiver operating characteristic curve of 0.62 (95% CI, 0.5-0.75). The combination of these 2 parameters formed the basis of the POCER index (range, 0-4 with 0 denoting no ulcers and 4 denoting deep ulceration with >25% circumferential involvement). The new index had a strong correlation with the Rutgeerts score measured at the same time points: Spearmans' r = .80 at 6 months and r = .77 at 18 months (P < 0.001 at both time points). A POCER index of ≥2 and a Rutgeerts score of ≥i2 both had a sensitivity of 0.41 for recurrence; however, the POCER index had a higher specificity (0.8 and 0.67, respectively). The POCER index at 6 months was associated with endoscopic recurrence at 18 months (OR, 1.5; 95% CI, 1.2-2.0; P = 0.002; area under the receiver operating characteristic curve of 0.70; 95% CI, 0.57-0.82), but the Rutgeerts score was not (OR, 1.2; 95% CI, 0.8-1.8; P = 0.402). CONCLUSIONS The POCER postoperative index comprises 2 key endoscopic factors related to the anastomosis that are associated with subsequent disease progression. A higher score, comprising the adverse prognostic factors of deep or circumferentially extensive anastomotic ulceration, may help identify patients who require more intensive therapy.
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Affiliation(s)
- Peter De Cruz
- Department of Gastroenterology, St. Vincent's Hospital and Department of Medicine, The University of Melbourne, Melbourne, Australia.,Department of Gastroenterology, Austin Health, Melbourne, Australia
| | - Amy L Hamilton
- Department of Gastroenterology, St. Vincent's Hospital and Department of Medicine, The University of Melbourne, Melbourne, Australia
| | - Kathryn J Burrell
- Department of Gastroenterology, St. Vincent's Hospital and Department of Medicine, The University of Melbourne, Melbourne, Australia.,Department of Gastroenterology, Austin Health, Melbourne, Australia
| | - Alexandra Gorelik
- Department of Psychology, Australian Catholic University, Melbourne, Australia
| | - Danny Liew
- Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St. Vincent's Hospital and Department of Medicine, The University of Melbourne, Melbourne, Australia
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Movva R, Murtaza N, Giri R, Png CW, Davies J, Alabbas S, Oancea I, O'Cuiv P, Morrison M, Begun J, Florin TH. Successful Manipulation of the Gut Microbiome to Treat Spontaneous and Induced Murine Models of Colitis. GASTRO HEP ADVANCES 2022; 1:359-374. [PMID: 39131681 PMCID: PMC11307790 DOI: 10.1016/j.gastha.2021.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 12/31/2021] [Indexed: 08/13/2024]
Abstract
Background and Aims There is clinical interest in the sustainability or otherwise of prebiotic, microbial, and antibiotic treatments to both prevent and treat inflammatory bowel diseases. This study examined the role of antibiotic manipulation of the gut microbiome to treat spontaneous and induced murine models of colitis. Methods Symptomatic, histological, molecular, and microbial ecology and bioinformatic readouts were used to study the effect of a 10-day antibiotic cocktail and then follow-up over 2 months in the spontaneous Winnie colitis mouse preclinical model of ulcerative colitis and also the indirect antibiotic and Winnie microbiotic gavage effects in an acute dextran sodium sulfate-induced colitis model in wild-type mice. Results The antibiotics elicited a striking reduction in both colitis symptoms and blinded histological colitis scores, together with a convergence of the microbial taxonomy of the spontaneous colitis and wild-type control mice, toward a taxonomic phenotype usually considered to be dysbiotic. The improvement in colitis was sustained over the following 8 weeks although the microbial taxonomy changed. In vitro, fecal waters from the antibiotic-treated colitis and wild-type mice suppressed the inflammatory tenor of colonic epithelial cells, and gavaged cecal slurries from these mice moderated the acute induced colitis. Conclusion The results clearly show the possibility of a sustained remission of colitis by microbial manipulation, which is relevant to clinical management of inflammatory bowel diseases. The beneficial effects appeared to depend on the microbial metabolome rather than its taxonomy.
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Affiliation(s)
- Ramya Movva
- IBD Program, Translational Research Institute, Mater Research – University of Queensland, Brisbane, Queensland, Australia
| | - Nida Murtaza
- Translational Research Institute, Queensland University of Technology
| | - Rabina Giri
- IBD Program, Translational Research Institute, Mater Research – University of Queensland, Brisbane, Queensland, Australia
| | - Chin Wen Png
- IBD Program, Translational Research Institute, Mater Research – University of Queensland, Brisbane, Queensland, Australia
| | - Julie Davies
- IBD Program, Translational Research Institute, Mater Research – University of Queensland, Brisbane, Queensland, Australia
| | - Saleh Alabbas
- IBD Program, Translational Research Institute, Mater Research – University of Queensland, Brisbane, Queensland, Australia
| | - Iulia Oancea
- IBD Program, Translational Research Institute, Mater Research – University of Queensland, Brisbane, Queensland, Australia
| | - Páraic O'Cuiv
- Microbial Biology and Metagenomics Program, UQ Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia
| | - Mark Morrison
- Microbial Biology and Metagenomics Program, UQ Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia
| | - Jakob Begun
- IBD Program, Translational Research Institute, Mater Research – University of Queensland, Brisbane, Queensland, Australia
| | - Timothy H. Florin
- IBD Program, Translational Research Institute, Mater Research – University of Queensland, Brisbane, Queensland, Australia
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Erzin Y, Şişman G, Hatemi İ, Baca B, Hamzaoglu İ, Dirican A, Korman U, Çelik AF. Predictors of endoscopic recurrence in resected patients with Crohn's disease in a long-term follow-up cohort: History of multiple previous resections and residual synchronous disease in the remnant intestine. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:282-288. [PMID: 32412898 DOI: 10.5152/tjg.2020.136680] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIMS This study aimed to determine the predictors of endoscopic recurrence in a cohort of patients with Crohn's disease (CD) with prior intestinal resections. MATERIALS AND METHODS The charts of the patients with CD were reviewed in a retrospective manner. Eighty-three patients were eligible for the final analysis. Demographic features of these patients and time between resection and colonoscopy, presence of any macroscopic residual disease in the remnant intestine, and postoperative medications were noted. Rutgeerts score was used to define postoperative endoscopic recurrence. RESULTS The patients' mean age±SD at their final colonoscopy was 42.81±11.99 yr; and 37 of 83 patients (45%) were female. The mean follow-up time between resection and the final colonoscopy was 51.16±51.08 months. A total of 51 of 83 patients (61%) were in endoscopic remission (i0, i1); whereas 32 (39%) had an endoscopic recurrence (i2, i3, i4). History of multiple resections (χ2=6.12; p=0.013) and the presence of any postoperative residual disease in the remnant intestine (χ2=5.86; p=0.015) were risk factors; whereas the regular use of azathioprine (AZA) was significantly more common among patients without recurrence (χ2=4.515; p=0.034). In an age-sex adjusted Cox regression analysis history of multiple resections, presence of any postoperative residual disease proved to be independent risk factor for endoscopic recurrence, whereas the regular use of AZA proved to be ineffective. CONCLUSION In a retrospective long-term follow-up cohort of resected patients with CD, having multiple resections for CD and the presence of any residual synchronous disease after ileocolonic resection were identified as risk factors for endoscopic recurrence; the latter was never reported in previous studies.
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Affiliation(s)
- Yusuf Erzin
- Department of Gastroenterology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Gürhan Şişman
- Department of Gastroenterology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - İbrahim Hatemi
- Department of Gastroenterology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Bilgi Baca
- Department of General Surgery, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - İsmail Hamzaoglu
- Department of General Surgery, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Ahmet Dirican
- Department of Biostatistics, İstanbul University, İstanbul School of Medicine, İstanbul, Turkey
| | - Uğur Korman
- Department of Radiology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Aykut F Çelik
- Department of Gastroenterology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
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Wong DJ, Roth EM, Feuerstein JD, Poylin VY. Surgery in the age of biologics. Gastroenterol Rep (Oxf) 2019; 7:77-90. [PMID: 30976420 PMCID: PMC6454839 DOI: 10.1093/gastro/goz004] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 11/02/2018] [Indexed: 02/07/2023] Open
Abstract
Since the introduction of the first anti-tumor necrosis factor antibodies in the late 1990s, biologic therapy has revolutionized the medical treatment of patients with inflammatory bowel disease (IBD). Nevertheless, surgery continues to play a significant role in treating IBD patients. Rates of intestinal resection in patients with Crohn's disease or colectomy in ulcerative colitis are reducing but not substantially over the long term. An increasing variety of biologic medications are now available to treat IBD patients in various clinical situations. Consequently, a number of questions persist about how biologic medications affect the need for surgery and overall course in IBD patients. Given the trend for earlier and more frequent use of biologic medications in IBD patients, a working knowledge of the effects of these medications on surgical decision-making and outcomes is essential for the practicing colorectal surgeon and gastroenterologist. This review seeks to summarize the relevant literature surrounding biologic use and IBD surgery with a focus on the effect of biologics on the frequency, type and complications of surgery in this 'age of biologics'.
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Affiliation(s)
- Daniel J Wong
- Department of Surgery, Division of Colon & Rectum Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Eve M Roth
- Department of Surgery, Division of Colon & Rectum Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Joseph D Feuerstein
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Vitaliy Y Poylin
- Department of Surgery, Division of Colon & Rectum Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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Li Y, Ge Y, Gong J, Zhu W, Cao L, Guo Z, Gu L, Li J. Mesenteric Lymphatic Vessel Density Is Associated with Disease Behavior and Postoperative Recurrence in Crohn's Disease. J Gastrointest Surg 2018; 22:2125-2132. [PMID: 30043133 DOI: 10.1007/s11605-018-3884-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Accepted: 07/11/2018] [Indexed: 01/31/2023]
Abstract
PURPOSE The aims of the present study were to examine the density of lymphatic vessels in the mesentery and to assess the predictive value of the mesenteric lymphatic vessel density for postoperative clinical recurrence. METHODS Ileocolonic resection specimens were obtained from 53 patients with Crohn's disease and 10 non-inflammatory bowel disease control subjects. Mesentery adipose tissues adjacent to the bowel wall were used for the histological quantification of lymphatic vessels using immunohistochemistry with the D2-40 antibody. The relationships between lymphatic vessel density and disease behavior, the presence of granulomas, the presence of creeping fat, and postoperative clinical recurrence were assessed. RESULTS Median lymphatic vessel density in the mesentery adjacent to inflamed or non-inflamed intestine was lower in control subjects than in Crohn's disease patients (2.13‰; interquartile range [IQR], 1.83-2.61; 8.34‰; IQR, 6.39-10.22; 4.43‰; IQR, 3.32-5.78; P ˂ 0.001). Increased mesenteric lymphatic vessel density was significantly associated with stricturing behavior, the presence of intestinal granulomas, the presence of creeping fat, and bowel thickness. Interestingly, patients with disease recurrence had an increased mesenteric lymphatic vessel density of the proximal mesenteric margin at the time of resection compared with those who did not have disease recurrence (6.23‰; IQR, 5.43-6.75 vs. 3.28‰; IQR, 2.93-4.29; P ˂ 0.001). CONCLUSIONS In addition to its correlation with disease behavior, bowel thickness, and the presence of intestinal granulomas and creeping fat, increased mesenteric lymphatic vessel density in the proximal margin is predictive of early clinical recurrence after surgery in patients with Crohn's disease.
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Affiliation(s)
- Yi Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China
| | - Yuanyuan Ge
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China
| | - Jianfeng Gong
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China
| | - Weiming Zhu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China.
| | - Lei Cao
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China
| | - Zhen Guo
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China
| | - Lili Gu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China
| | - Jieshou Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China
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Abstract
The incidence of Crohn's disease in the pediatric population is increasing. While pediatric patients with Crohn's disease exhibit many of the characteristics of older patients, there are important differences in the clinical presentation and course of disease that can impact the clinical decisions made during treatment. The majority of children are diagnosed in the early teen years, but subgroups of very early onset and infantile Crohn's present much earlier and have a unique clinical course. Treatment paradigms follow the traditional laddered approach, but growth and development represent special considerations that must be given to pediatric-specific complications of the treatment and disease. Surgical intervention is an important component of Crohn's management and is often employed to allow improved nutritional intake or decrease reliance on medical treatments that compromise growth.
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Affiliation(s)
- Daniel von Allmen
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Hiraoka S, Takashima S, Kondo Y, Inokuchi T, Sugihara Y, Takahara M, Kawano S, Harada K, Kato J, Okada H. Efficacy of restarting anti-tumor necrosis factor α agents after surgery in patients with Crohn's disease. Intest Res 2018; 16:75-82. [PMID: 29422801 PMCID: PMC5797275 DOI: 10.5217/ir.2018.16.1.75] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Revised: 08/06/2017] [Accepted: 08/08/2017] [Indexed: 12/23/2022] Open
Abstract
Background/Aims The efficacy of anti-tumor necrosis factor α (anti-TNFα) antibodies for postoperative Crohn's disease (CD) in patients who were treated with these agents prior to surgery is largely unknown. Methods CD patients who underwent intestinal resection and received anti-TNFα agents after surgery were divided into 2 groups according to the presence or absence of preoperative anti-TNFα treatment: anti-TNFα restart group or anti-TNFα naïve group. Endoscopic recurrence after surgery was examined according to the preoperative conditions, including administration of anti-TNFα agents before surgery. Results Thirty-six patients received anti-TNFα antibody after surgery: 22 in the anti-TNFα restart group and 14 in the anti-TNFα naïve group. Endoscopic recurrence after surgery was more frequently observed in the anti-TNFα restart group than in the anti-TNFα naïve group (68% vs. 14%, P<0.001). Multivariate analysis revealed the following significant risk factors of endoscopic recurrence after surgery: anti-TNF restart group (odds ratio [OR], 28.10; 95% CI, 3.08-722.00), age at diagnosis <23 years (OR, 24.30; 95% CI, 1.67-1,312.00), serum albumin concentration at surgery <3.3 g/dL (OR, 34.10; 95% CI, 1.72-2,804.00), and presence of inflammation outside of the surgical site (OR, 21.40; 95% CI, 1.02-2,150.00). Treatment intensification for patients with endoscopic recurrence in the anti-TNFα restart group showed limited responses, with only 1 of 12 patients achieving endoscopic remission. Conclusions The efficacy of restarting anti-TNFα antibody treatment after surgery was limited, and treatment intensification or a change to different classes of biologics should be considered for those patients.
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Affiliation(s)
- Sakiko Hiraoka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shiho Takashima
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yoshitaka Kondo
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Toshihiro Inokuchi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yuusaku Sugihara
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Masahiro Takahara
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Seiji Kawano
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Keita Harada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Jun Kato
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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MR Enterography in Crohn’s disease complicated with enteroenteric fistula. Eur J Radiol 2017; 94:101-106. [DOI: 10.1016/j.ejrad.2017.06.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 06/06/2017] [Accepted: 06/18/2017] [Indexed: 02/07/2023]
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Fortinsky KJ, Kevans D, Qiang J, Xu W, Bellolio F, Steinhart H, Milgrom R, Greenberg G, Cohen Z, Macrae H, Stempak J, McLeod R, Silverberg MS. Rates and Predictors of Endoscopic and Clinical Recurrence After Primary Ileocolic Resection for Crohn's Disease. Dig Dis Sci 2017; 62:188-196. [PMID: 27778204 DOI: 10.1007/s10620-016-4351-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Accepted: 10/17/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS The utility of postoperative medical prophylaxis (POMP) and the treatment of mild endoscopic recurrence remain controversial. METHODS This study is a retrospective review of patients undergoing a primary ileocolic resection for CD at a single academic center. Endoscopic recurrence (ER) was defined using the Rutgeerts score (RS), and clinical recurrence (CR) was defined as symptoms of CD with endoscopic or radiologic evidence of neo-terminal ileal disease. RESULTS There were 171 patients who met inclusion criteria. The cumulative probability of ER (RS ≥ i-1) at 1, 2, and 5 years was 29, 51, and 77 %, respectively. The only independent predictors of ER were the absence of POMP (HR 1.50; P = 0.03) and penetrating disease behavior (HR 1.50; P = 0.05). The cumulative probability of CR at 1, 2, and 5 years was 8, 13, and 27 %, respectively. There was a higher rate of clinical recurrence in patients with RS-2 compared to RS-1 on the initial postoperative endoscopy (HR 2.50; P = 0.02). In 11 patients not exposed to POMP with i-1 on initial endoscopy, only 2 patients (18 %) progressed endoscopically during the study period while 5 patients (45 %) regressed to i-0 on subsequent endoscopy without treatment. CONCLUSIONS Postoperative medical prophylaxis decreased the likelihood of ER while certain phenotypes of CD appear to increase the risk of developing ER and CR. There may be a role for watchful waiting in patients with mild endoscopic recurrence on the initial postoperative endoscopy.
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Affiliation(s)
| | | | | | - Wei Xu
- University of Toronto, Toronto, Canada
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Comparable outcomes of the consistent use versus switched use of anti- tumor necrosis factor agents in postoperative recurrent Crohn's disease following ileocolonic resection. Int J Colorectal Dis 2016; 31:1751-1758. [PMID: 27475090 DOI: 10.1007/s00384-016-2632-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/22/2016] [Indexed: 02/04/2023]
Abstract
PURPOSE There are no published data or guidelines on whether the same anti-tumor-necrosis factor (TNF) agents used preoperatively or different anti-TNF agents are preferable to treat postoperative recurrence. Our aim was to compare the efficacy of the consistent vs. switched anti-TNF approaches in patients with recurrent Crohn's disease (CD) after their inception ileocolonic resection (ICR). METHODS Patients with CD receiving anti-TNF agents before the inception ICR who were treated for clinical recurrence with the same or different anti-TNF agents after surgical resection were included in the study. The outcome of the study was the need for the subsequent resection of ileocolonic anastomosis (ICA) as calculated with survival curves. RESULTS Eighty-five patients were included in the study. The mean age of the whole cohort at the inception ICR was 35.1 ± 13.5 years. The whole cohort consisted 42 (49.4 %) in the consistent group and 43 (50.6 %) in the switched group. No significant differences were observed in demographic and clinical variables between the two groups. During the median follow-up of 1.5 (interquartile range, 0.8-3.1) years, seven (16.7 %) patients in the consistent group and eight (18.6 %) in the switched group required the repeat resection of ICA. Similar results were found in terms of the subsequent resection of ICA-free survival (hazard ratio = 1.36, 95 % confidence interval 0.49-3.76, P = 0.54) between the consistent and switched groups. CONCLUSIONS The adherence to the same anti-TNF agent appeared to be as effective as the switching approach to different anti-TNF agent in treating postoperative recurrent CD after the inception ICR.
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Regueiro M, Feagan BG, Zou B, Johanns J, Blank MA, Chevrier M, Plevy S, Popp J, Cornillie FJ, Lukas M, Danese S, Gionchetti P, Hanauer SB, Reinisch W, Sandborn WJ, Sorrentino D, Rutgeerts P. Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease After Ileocolonic Resection. Gastroenterology 2016; 150:1568-1578. [PMID: 26946343 DOI: 10.1053/j.gastro.2016.02.072] [Citation(s) in RCA: 235] [Impact Index Per Article: 26.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Revised: 02/16/2016] [Accepted: 02/25/2016] [Indexed: 01/11/2023]
Abstract
BACKGROUND & AIMS Most patients with Crohn's disease (CD) eventually require an intestinal resection. However, CD frequently recurs after resection. We performed a randomized trial to compare the ability of infliximab vs placebo to prevent CD recurrence. METHODS We evaluated the efficacy of infliximab in preventing postoperative recurrence of CD in 297 patients at 104 sites worldwide from November 2010 through May 2012. All study patients had undergone ileocolonic resection within 45 days before randomization. Patients were randomly assigned (1:1) to groups given infliximab (5 mg/kg) or placebo every 8 weeks for 200 weeks. The primary end point was clinical recurrence, defined as a composite outcome consisting of a CD Activity Index score >200 and a ≥70-point increase from baseline, and endoscopic recurrence (Rutgeerts score ≥i2, determined by a central reader) or development of a new or re-draining fistula or abscess, before or at week 76. Endoscopic recurrence was a major secondary end point. RESULTS A smaller proportion of patients in the infliximab group had a clinical recurrence before or at week 76 compared with the placebo group, but this difference was not statistically significant (12.9% vs 20.0%; absolute risk reduction [ARR] with infliximab, 7.1%; 95% confidence interval: -1.3% to 15.5%; P = .097). A significantly smaller proportion of patients in the infliximab group had endoscopic recurrence compared with the placebo group (30.6% vs 60.0%; ARR with infliximab, 29.4%; 95% confidence interval: 18.6% to 40.2%; P < .001). Additionally, a significantly smaller proportion of patients in the infliximab group had endoscopic recurrence based only on Rutgeerts scores ≥i2 (22.4% vs 51.3%; ARR with infliximab, 28.9%; 95% confidence interval: 18.4% to 39.4%; P < .001). Patients previously treated with anti-tumor necrosis factor agents or those with more than 1 resection were at greater risk for clinical recurrence. The safety profile of infliximab was similar to that from previous reports. CONCLUSIONS Infliximab is not superior to placebo in preventing clinical recurrence after CD-related resection. However, infliximab does reduce endoscopic recurrence. ClinicalTrials.gov ID NCT01190839.
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Affiliation(s)
- Miguel Regueiro
- Inflammatory Bowel Disease Center and Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
| | - Brian G Feagan
- Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
| | - Bin Zou
- Janssen Research & Development, LLC, Spring House, Pennsylvania
| | - Jewel Johanns
- Janssen Research & Development, LLC, Spring House, Pennsylvania
| | | | - Marc Chevrier
- Janssen Research & Development, LLC, Spring House, Pennsylvania
| | - Scott Plevy
- Janssen Research & Development, LLC, Spring House, Pennsylvania
| | - John Popp
- Janssen Scientific Affairs, LLC, Horsham, Pennsylvania
| | | | | | | | - Paolo Gionchetti
- S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Stephen B Hanauer
- Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Walter Reinisch
- McMaster University, Hamilton, Ontario, Canada; Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | | | - Dario Sorrentino
- Virginia Tech, Carilion School of Medicine, Roanoke, Virginia; Department of Clinical and Experimental Pathology, University of Udine School of Medicine, Udine, Italy
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Hashash JG, Regueiro M. A Practical Approach to Preventing Postoperative Recurrence in Crohn's Disease. Curr Gastroenterol Rep 2016; 18:25. [PMID: 27086006 DOI: 10.1007/s11894-016-0499-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Postoperative Crohn's disease recurrence remains common, and preventing additional surgery remains a challenge. A critical step to postoperative management of Crohn's disease is being able to identify patients who should receive immediate postoperative therapy from the patients who can wait for recurrence prior to starting medications. All patients, regardless of their risk for recurrence, are advised to undergo a colonoscopy at 6 to 12 months after surgery to evaluate for endoscopic evidence of Crohn's disease. Further management of patients depends on symptoms and the presence or absence of endoscopic recurrence.
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Affiliation(s)
- Jana G Hashash
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Mezzanine Level, C Wing, 200 Lothrop Street, Pittsburgh, PA, 15213, USA
| | - Miguel Regueiro
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Mezzanine Level, C Wing, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
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14
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Leitner GC, Vogelsang H. Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults. World J Gastrointest Pharmacol Ther 2016; 7:5-20. [PMID: 26855808 PMCID: PMC4734954 DOI: 10.4292/wjgpt.v7.i1.5] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 12/14/2015] [Accepted: 01/08/2016] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.
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15
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Sauter B, Beglinger C, Girardin M, Macpherson A, Michetti P, Schoepfer A, Seibold F, Vavricka SR, Rogler G. Monitoring disease activity and progression in Crohn's disease. A Swiss perspective on the IBD ahead 'optimised monitoring' recommendations. Digestion 2015; 89:299-309. [PMID: 25074029 DOI: 10.1159/000360283] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS The structured IBD Ahead 'Optimised Monitoring' programme was designed to obtain the opinion, insight and advice of gastroenterologists on optimising the monitoring of Crohn's disease activity in four settings: (1) assessment at diagnosis, (2) monitoring in symptomatic patients, (3) monitoring in asymptomatic patients, and (4) the postoperative follow-up. For each of these settings, four monitoring methods were discussed: (a) symptom assessment, (b) endoscopy, (c) laboratory markers, and (d) imaging. Based on literature search and expert opinion compiled during an international consensus meeting, recommendations were given to answer the question 'which diagnostic method, when, and how often'. The International IBD Ahead Expert Panel advised to tailor this guidance to the healthcare system and the special prerequisites of each country. The IBD Ahead Swiss National Steering Committee proposes best-practice recommendations adapted for Switzerland. METHODS The IBD Ahead Steering Committee identified key questions and provided the Swiss Expert Panel with a structured literature research. The expert panel agreed on a set of statements. During an international expert meeting the consolidated outcome of the national meetings was merged into final statements agreed by the participating International and National Steering Committee members - the IBD Ahead 'Optimized Monitoring' Consensus. RESULTS A systematic assessment of symptoms, endoscopy findings, and laboratory markers with special emphasis on faecal calprotectin is deemed necessary even in symptom-free patients. The choice of recommended imaging methods is adapted to the specific situation in Switzerland and highlights the importance of ultrasonography and magnetic resonance imaging besides endoscopy. CONCLUSION The recommendations stress the importance of monitoring disease activity on a regular basis and by objective parameters, such as faecal calprotectin and endoscopy with detailed documentation of findings. Physicians should not rely on symptoms only and adapt the monitoring schedule and choice of options to individual situations.
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Abstract
In 1998, infliximab, an antitumor necrosis factor alpha (anti-TNF-α) antibody, was approved for use in the treatment of Crohn disease (CD). Since then, other biologic therapies, including adalimumab and certolizumab pegol (newer anti-TNF-α antibodies), and natalizumab, an antibody against alpha-4 integrin, have also been approved. Here, we review the published studies that examine the relationship between pre- and postoperative biologic therapy and postoperative complications in patients with CD. This body of literature is composed of numerous small, retrospective, heterogeneous studies that demonstrate conflicting and varied results. Overall, the receipt of biologic therapy in the pre- or postoperative period does not appear to significantly increase the risk of postoperative complications. It is, however, difficult to draw any firm conclusions based on the existing level of data. In the future, larger prospective studies are needed to better elucidate the true risks, if any, that the use of biologic therapy poses to patients with CD requiring operation.
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Affiliation(s)
- E Carter Paulson
- Department of Surgery, Philadelphia VA Medical Center, Philadelphia, Pennsylvania
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17
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D'Incà R, Caccaro R. Measuring disease activity in Crohn's disease: what is currently available to the clinician. Clin Exp Gastroenterol 2014; 7:151-61. [PMID: 24876789 PMCID: PMC4035027 DOI: 10.2147/ceg.s41413] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by a relapsing-remitting clinical behavior and dominated by intestinal inflammation. Being a chronic disorder that with time develops into a disabling disease, it is important to monitor the severity of inflammation to assess the efficacy of medication, rule out complications, and prevent progression. This is particularly true now that the goals of treatment are mucosal healing and deep remission. Endoscopy has always been the gold standard for assessing mucosal activity in CD, but its use is limited by its invasiveness and its inability to examine the small intestine, proximal to the terminal ileum. Enteroscopy and the less invasive small bowel capsule endoscopy enable the small bowel to be thoroughly explored and scores are emerging for classifying small bowel disease activity. Cross-sectional imaging techniques (ultrasound, magnetic resonance, computed tomography) are emerging as valid tools for monitoring CD patients, assessing inflammatory activity in the mucosa and the transmucosal extent of the disease, and for excluding extra-intestinal complications. Neither endoscopy nor imaging are suitable for assessing patients frequently, however. Noninvasive markers such as C-reactive protein, and fecal biomarkers such as calprotectin and lactoferrin, are therefore useful to confirm the inflammatory burden of the disease and to identify patients requiring further investigations.
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Affiliation(s)
- Renata D'Incà
- Department of Surgical, Oncological and Gastroenterological Sciences, Gastroenterology Section, University of Padua, Padua, Italy
| | - Roberta Caccaro
- Department of Surgical, Oncological and Gastroenterological Sciences, Gastroenterology Section, University of Padua, Padua, Italy
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Mazzuoli S, Guglielmi FW, Antonelli E, Salemme M, Bassotti G, Villanacci V. Definition and evaluation of mucosal healing in clinical practice. Dig Liver Dis 2013; 45:969-77. [PMID: 23932331 DOI: 10.1016/j.dld.2013.06.010] [Citation(s) in RCA: 105] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 05/21/2013] [Accepted: 06/26/2013] [Indexed: 12/11/2022]
Abstract
Since the introduction of biological therapy, endoscopic and histological remission, i.e. mucosal healing, has become an important therapeutic goal in Crohn's Disease and Ulcerative Colitis. Mucosal healing is associated with lower rates of hospitalization and surgery, although its role in preventing progression and changing the natural history of the disease has not been clearly demonstrated. A precise definition of mucosal healing has not yet been established, although the concept used in clinical trials is the "complete absence of all inflammatory and ulcerative lesions in all segments of gut" at endoscopy. This definition does not include mucosal improvement and does not distinguish among grades of mucosal healing. In both Crohn's Disease and Ulcerative Colitis trials, several qualitative and quantitative numeric endoscopic indices have been proposed to measure and distinguish endoscopic changes. In addition, the microscopic features associated with inflammatory bowel diseases are considerably modified by the course of the disease and the treatments adopted. However, it is not yet clear whether microscopic healing should be a primary endpoint in clinical trials. In this paper we discuss endoscopic and histological findings and the limitations of the endoscopic and histological indices as a basis for a standardised diagnosis of mucosal healing.
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Affiliation(s)
- Silvia Mazzuoli
- Gastroenterology and Artificial Nutrition Department, "San Nicola Pellegrino" Hospital Trani, BT, Italy
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19
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Hashash JG, Regueiro MD. The evolving management of postoperative Crohn's disease. Expert Rev Gastroenterol Hepatol 2012; 6:637-48. [PMID: 23061713 DOI: 10.1586/egh.12.45] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Two-thirds to three-quarters of Crohn's disease patients require intestinal surgery for medically refractory disease or complications. Surgery is not a cure and most patients develop recurrent Crohn's disease and require additional intestinal resections. There are a number of medications that have been investigated for preventing and treating recurrence. Risk factors for postoperative disease recurrence help guide the physician in determining the appropriate treatment strategy after Crohn's disease surgery. The approach to Crohn's disease treatment has evolved over the years. No longer should surgery be considered a failure of treatment, rather an important intervention to correct irreversible disease. In combination with a better understanding of postoperative medication strategies, patients with Crohn's disease may achieve longer term remission than previously realized. This review elucidates current understanding of the natural course of postoperative Crohn's disease, monitoring for recurrence, the risk factors for recurrence, and provides insight into an evolving new paradigm for postoperative Crohn's disease treatment.
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Affiliation(s)
- Jana G Hashash
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, 200 Lothrop Street-PUH, M2, C-Wing, Pittsburgh, PA 15213, USA.
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20
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Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2012; 26:33-9. [PMID: 22288068 DOI: 10.1155/2012/628268] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Intestinal fibrosis is a challenging clinical condition in several fibrostenosing enteropathies, particularly Crohn's disease. Currently, no effective preventive measures or medical therapies are available for intestinal fibrosis. Fibrosis, due to an abnormal accumulation of extracellular matrix proteins, is a chronic and progressive process mediated by cell⁄matrix⁄cytokine and growth factor interactions, but may be a reversible phenomenon. Of the several molecules regulating fibrogenesis, transforming growth factor-beta 1 (TGF-b1) appears to play a pivotal role; it is strongly induced by the local activation of angiotensin II. The levels of both TGF-b1 and angiotensin II are elevated in fibrostenosing Crohn's disease. AIMS To evaluate the in vivo effect of losartan - an angiotensin II receptor antagonist - on the course of chronic colitis-associated fibrosis and on TGF-b1 expression. METHODS Colitis was induced by intrarectal instillation of trinitrobenzene sulphonic acid (TNBS) (15 mg⁄mL) while losartan was administered orally daily by gavage (7 mg⁄kg⁄day) for 21 days. Three groups of rats were evaluated: control (n=10); TNBS treated (n=10); and TNBS + losartan treated (n=10). Inflammation and fibrosis of the colon were evaluated by macro- and microscopic score analysis. Colonic TGF-b1 levels was measured using ELISA. RESULTS Twenty-one days after induction, losartan significantly improved the macro- and microscopic scores of fibrosis in the colonic wall and reduced TGF-b1 concentration. CONCLUSIONS Prophylactic oral administration of losartan reduces the colorectal fibrosis complicating the TNBS-induced chronic colitis, an effect that appears to be mediated by a downregulation of TGF-b1 expression.
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21
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Regueiro M, El-Hachem S, Kip KE, Schraut W, Baidoo L, Watson A, Swoger J, Schwartz M, Barrie A, Pesci M, Binion D. Postoperative infliximab is not associated with an increase in adverse events in Crohn's disease. Dig Dis Sci 2011; 56:3610-5. [PMID: 21681507 DOI: 10.1007/s10620-011-1785-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2011] [Accepted: 06/04/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND Infliximab is effective treatment for Crohn's disease and has been associated with rare, but serious infectious complications. Emerging data suggest a benefit of infliximab in preventing postoperative Crohn's disease recurrence. It is not known whether administration of infliximab shortly after resective surgery for Crohn's disease increases postoperative complications. AIMS To evaluate the risk of developing postoperative complications among Crohn's disease patients receiving infliximab within 4 weeks of intestinal resection. METHODS As part of a randomized placebo-controlled infliximab postoperative prevention study, adverse events were prospectively monitored. Crohn's disease patients undergoing intestinal resection were randomized to placebo or infliximab 2-4 weeks after surgery. Study infusions were administered at 0, 2, and 6 weeks then every 8 weeks for 1 year. To evaluate whether infliximab increased postoperative complications, we analyzed all adverse events for 1 year after surgery. RESULTS Twenty-four patients were randomized to infliximab or placebo after intestinal resection for Crohn's disease. Mean time to first postoperative infusion was 20 days (range 14-25 days). Over the course of 1 year, there were 22 total adverse events, but no difference between infliximab and placebo patients (12 versus 10, respectively, P = 1.0). In the immediate postoperative period, within 8 weeks of surgery, the number of adverse events was also similar between the two groups (3 infliximab and 5 placebo patients, P = 0.68). There were no serious adverse events and no complications related to wound healing or infection. CONCLUSIONS Initiation of infliximab within 4 weeks of intestinal resection was not associated with postoperative complications.
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Affiliation(s)
- Miguel Regueiro
- Division of Gastroenterology, Hepatology and Nutrition, Inflammatory Bowel Disease Center, University of Pittsburgh School of Medicine, 200 Lothrop Street, PUH-C Wing Mezzanine Level, Pittsburgh, PA 15213, USA.
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22
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Factors associated with operative recurrence early after resection for Crohn's disease. J Gastrointest Surg 2011; 15:1354-60. [PMID: 21626229 DOI: 10.1007/s11605-011-1552-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2010] [Accepted: 04/18/2011] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Some Crohn's disease (CD) patients develop rapid disease recurrence requiring reoperation. Identification of factors associated with early operative recurrence of CD may help risk-stratify patients and prevent recurrence. METHODS Prospectively collected data of CD patients undergoing bowel resection for CD with unequivocal evidence of recurrence at reoperation were retrieved. Patients with earlier recurrence (less than median time of recurrence of study cohort) were compared with those who developed later recurrence (greater than median time of recurrence) for patient and disease characteristics and risk factors for recurrence. A multivariate logistic regression model was performed to identify factors associated with earlier operative recurrence. RESULTS Sixty-nine patients (45 female, 24 male) met the inclusion criteria. Median time to reoperation was 38 months (range, 3.3-236 months). One hundred six reoperations in the 69 patients were for abscess/fistula/perforation (n = 45), stricture/stenosis (n = 41), inflammation (n = 17), bleeding (n = 2), and dysplasia (n = 1). Factors associated with early rather than late reoperation included behavior of disease (stricturing, odds ratio (OR) 12.1; confidence interval (CI), 1.8-80.9; penetrating OR, 9.9; CI, 1.4-67.9 rather than nonstricturing nonpenetrating) and the development of postoperative complications at previous surgery (OR, 12.1; CI, 1.2-126.6). CONCLUSION Earlier recurrence of CD requiring reoperation is associated with specific disease and potentially modifiable operation-related factors such as postoperative complications, i.e., anastomotic leak or intraabdominal abscess. Strategies to reduce recurrence in such patients include the identification of factors that may reduce postoperative complications.
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Lakatos L, Lakatos PL. [Postoperative recurrence of Crohn's disease, and its prevention]. Orv Hetil 2010; 151:870-7. [PMID: 20462847 DOI: 10.1556/oh.2010.28868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Crohn's disease is a chronic, progressive disabling condition ultimately leading to stricturing and/or penetrating complications. The need for surgery may be as high as 70% in patients with severe active disease or complications. However, relapse may develop in a significant proportion of the patients after surgery leading to frequent re-operations. Despite emerging data, postoperative prevention is still controversial. After careful evaluation of the individual risk a tailored therapy should be considered. In patients with small risk for relapse mesalazine or in selected cases no-treatment may be an option. In patients with a moderate-to-high risk azathioprine should be considered together with metronidazole in the three months. Follow-up ileocolonoscopy 6-12 months after the surgery is helpful in the determination of endoscopic severity and may assist in the optimization of the therapy. In most severe cases anti-TNF agents may be appropriate for postoperative prevention and therapy.
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Affiliation(s)
- László Lakatos
- Csolnoky Ferenc Megyei Kórház, Belgyógyászati Centrum, Veszprém, Kórház u. 1. 8200.
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Pineton de Chambrun G, Peyrin-Biroulet L, Lémann M, Colombel JF. Clinical implications of mucosal healing for the management of IBD. Nat Rev Gastroenterol Hepatol 2010; 7:15-29. [PMID: 19949430 DOI: 10.1038/nrgastro.2009.203] [Citation(s) in RCA: 341] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Mucosal healing (MH) has emerged as an important treatment goal for patients with IBD. Historically, the therapeutic goals of induction and maintenance of clinical remission seemed insufficient to change the natural history of IBD. Evidence has now accumulated to show that MH can alter the course of IBD, as it is associated with sustained clinical remission, and reduced rates of hospitalization and surgical resection. In patients with ulcerative colitis, MH may represent the ultimate therapeutic goal because inflammation is limited to the mucosa. In patients with Crohn's disease, which is a transmural disease, MH could be considered as a minimum therapeutic goal. This Review focuses on the definition of MH and discusses the ability of each available IBD medication to induce and maintain MH. The importance of achieving MH is also discussed and literature that demonstrates improvement of disease course with MH is reviewed. Finally, we discuss how best to integrate the treatment end point of MH into clinical practice for the management of patients with IBD.
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Affiliation(s)
- Guillaume Pineton de Chambrun
- Clinique des maladies de l'appareil digestif et de la nutrition, Hôpital Claude Huriez, Rue Michel Polonovski, 59037 Lille Cedex, France
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El-Hachem S, Regueiro M. Postoperative Crohn's disease: prevention and treatment. Expert Rev Gastroenterol Hepatol 2009; 3:249-56. [PMID: 19485807 DOI: 10.1586/egh.09.21] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Crohn's disease is a chronic, relapsing-remitting inflammatory disease of the intestinal tract that commonly requires surgical treatment. Unfortunately, the majority of patients will ultimately develop postoperative disease recurrence and require subsequent surgery. A number of medications have been researched for the maintenance of postoperative remission. Of these, few have demonstrated consistent efficacy. A recently published randomized, controlled trial indicated that infliximab is effective in the maintenance of postoperative remission.
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Affiliation(s)
- Sandra El-Hachem
- Department of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
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26
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Clinical course of Crohn's disease first diagnosed at surgery for acute abdomen. Dig Liver Dis 2009; 41:269-76. [PMID: 18955023 DOI: 10.1016/j.dld.2008.09.010] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2008] [Revised: 09/04/2008] [Accepted: 09/04/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND The severity of clinical activity of Crohn's disease is high during the first year after diagnosis and decreases thereafter. Approximately 50% of patients require steroids and immunosuppressants and 75% need surgery during their lifetime. The clinical course of patients with Crohn's disease first diagnosed at surgery has never been investigated. AIM To assess the clinical course of Crohn's disease first diagnosed at surgery for acute abdomen and to evaluate the need for medical and surgical treatment in this subset of patients. PATIENTS AND METHODS Hospital clinical records of 490 consecutive Crohn's disease patients were reviewed. Patients were classified according to the Vienna criteria. Sex, extraintestinal manifestations, family history of inflammatory bowel diseases, appendectomy, smoking habit and medical/surgical treatments performed during the follow-up period were assessed. STATISTICAL ANALYSIS Kaplan-Meier survival method and Cox proportional hazards regression model. RESULTS Of the 490 Crohn's disease patients, 115 had diagnosis of Crohn's disease at surgery for acute abdomen (Group A) and 375 by conventional clinical, radiological, endoscopic and histologic criteria (Group B). Patients in Group A showed a low risk of further surgery (Log Rank test p<0.001) and a longer time interval between diagnosis and first operation compared to Group B (10.8 years vs. 5.8 years, p<0.01, respectively). Furthermore, patients in Group A used less steroids and immunosuppressants (OR 0.3, p<0.0001; OR 0.6, p<0.004, respectively). CONCLUSIONS Crohn's disease patients first diagnosed at surgery for acute abdomen showed a low risk for reintervention and less use of steroids and immunosuppressants during follow-up than those not operated upon at diagnosis. Early surgery may represent a valid approach in the initial management of patients with Crohn's disease, at least in the subset of patients with ileal and complicated disease.
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Abstract
Prevention of the postoperative recurrence of Crohn's disease (CD) remains a challenging clinical problem. The majority of patients with CD will need surgery for treatment of the disease, most of these patients will develop recurrent symptoms within 5 years postoperatively, and many patients will need reoperation within 10 years. In patients with an ileocolic anastomosis, endoscopic recurrence precedes clinical recurrence and the severity of endoscopic recurrence correlates with the risk of clinical recurrence. Despite multiple studies, the best postoperative prophylactic therapy remains uncertain. Numerous randomized controlled trials of 5-aminosalicylates have shown only modest effect. Antibiotics, including metronidazole and ornidazole, decrease short-term, but not long-term endoscopic recurrence and are limited by side effects. Immunomodulators have yet to be extensively evaluated, although limited data suggest possible efficacy in preventing postoperative recurrence, particularly in high-risk patients. This review will evaluate the current state of the art therapy for postoperative prophylaxis in CD, with an emphasis on critical analysis of the available randomized controlled trials.
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Affiliation(s)
- Eric Blum
- Division of Gastroenterology, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio 44106-5066, USA
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Abstract
Crohn's disease is a chronic inflammatory condition that may involve any segment of the gastrointestinal tract. Although several drugs have proven efficacy in inducing and maintaining disease in remission, resectional surgery remains as a cornerstone in the management of the disease, mainly for the treatment of its stenosing and penetrating complications. However, the occurrence of new mucosal (endoscopic) lesions in the neoterminal ileum early after surgery is almost constant, it is followed in the mid-term by clinical symptoms and, in a proportion of patients, repeated intestinal resections are required. Pathogenesis of postoperative recurrence (POR) is not fully understood, but luminal factors (commensal microbes, dietary antigens) seem to play an important role, and environmental and genetic factors may also have a relevant influence. Many studies tried to identify clinical predictors for POR with heterogeneous results, and only smoking has repeatedly been associated with a higher risk of POR. Ileocolonoscopy remains as the gold standard for the assessment of appearance and severity of POR, although the real usefulness of the available endoscopic score needs to be revisited and alternative techniques are emerging. Several drugs have been evaluated to prevent POR with limited success. Smoking cessation seems to be one of the more beneficial therapeutic measures. Aminosalicylates have only proved to be of marginal benefit, and they are only used in low-risk patients. Nitroimidazolic antibiotics, although efficient, are associated with a high rate of intolerance and might induce irreversible side effects when used for a long-term. Thiopurines are not widely used after ileocecal resection, maybe because some concerns in giving immunomodulators in asymptomatic patients still remain. In the era of biological agents and genetic testing, a well-established preventive strategy for POR is still lacking, and larger studies to identify good clinical, serological, and genetic predictors of early POR as well as more effective drugs (or drug combinations) are needed.
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Affiliation(s)
- Jonathan P Terdiman
- University of California, San Francisco, San Francisco, California 94115, USA.
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