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Hjälte V, Myrelid P, Hjortswang H, Rejler M, Ludvigsson JF, Forss A, Bendtsen M, Olén O, Everhov ÅH, Eberhardson M. Substantial Reduction of Systemic Corticosteroid Use After Primary Ileocaecal Resection in Swedish Patients With Crohn's Disease: A Population-Based Cohort Study. Aliment Pharmacol Ther 2025; 61:1649-1661. [PMID: 40065562 PMCID: PMC12013787 DOI: 10.1111/apt.70069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 10/25/2024] [Accepted: 02/24/2025] [Indexed: 04/23/2025]
Abstract
BACKGROUND The corticosteroid-sparing effects of ileocaecal resection have not been thoroughly investigated in a population-based cohort. AIM To investigate systemic corticosteroid use before and after primary ileocaecal resection in patients with Crohn's disease. METHODS Through nationwide registries, we identified 1565 patients with Crohn's disease undergoing primary ileocaecal resection in Sweden 2006-2019. We stratified patients according to mean annual systemic corticosteroid (prednisolone equivalents) use in the last 5 years before surgery and compared Crohn's disease treatment after surgery. RESULTS Some 19% (290/1565) of the patients had a mean annual corticosteroid use of ≥ 1000 mg up to 5 years pre-operatively, of whom 33% (97/290) had ≥ 2000 mg. Mean annual pre-operative CS use did not decrease during the study period (p = 0.35). Compared with patients with < 1000 mg/year pre-operative steroid use, patients with ≥ 1000 mg/year had more frequent previous bowel surgery (10% vs. 16%), exposure to biologics (29% vs. 38%), and immunomodulators (56% vs. 83%). Patients with a pre-operative mean annual corticosteroid use of ≥ 1000 mg had a mean annual reduction in corticosteroid use of 1354 mg after ileocaecal resection (1847 mg pre-operative versus 493 mg post-operative). During follow-up (median 6.8 years), exposure to biologics was similar among patients with different levels of pre-operative corticosteroid use. CONCLUSION Our results suggest a significant corticosteroid-sparing effect of ileocaecal resection in Crohn's disease patients with high pre-operative use, indicating a beneficial outcome of earlier surgical intervention. Despite increasing use of biologics, pre-operative corticosteroid use was consistent over the study period.
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Affiliation(s)
- Vilhelm Hjälte
- Department of Gastroenterology and HepatologyUniversity HospitalLinköpingSweden
- Department of Health, Medicine and Caring SciencesLinköping UniversityLinköpingSweden
| | - Pär Myrelid
- Department of Surgery and Department of Biomedical and Clinical Sciences, Faculty of Health SciencesLinköping UniversityLinköpingSweden
| | - Henrik Hjortswang
- Department of Gastroenterology and HepatologyUniversity HospitalLinköpingSweden
- Department of Health, Medicine and Caring SciencesLinköping UniversityLinköpingSweden
| | - Martin Rejler
- Jönköping Academy for Improvement of Health and WelfareJönköping UniversityJönköpingSweden
- Futurum‐Academy for Healthcare, Region Jönköping CountyJönköpingSweden
| | - Jonas F. Ludvigsson
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
- Department of PediatricsÖrebro University HospitalÖrebroSweden
| | - Anders Forss
- Clinical Epidemiology Division, Department of Medicine SolnaKarolinska InstitutetStockholmSweden
| | - Marcus Bendtsen
- Department of Health, Medicine and Caring SciencesLinköping UniversityLinköpingSweden
| | - Ola Olén
- Clinical Epidemiology Division, Department of Medicine SolnaKarolinska InstitutetStockholmSweden
| | - Åsa H. Everhov
- Clinical Epidemiology Division, Department of Medicine SolnaKarolinska InstitutetStockholmSweden
- Department of Clinical Science and Education SödersjukhusetStockholmSweden
| | - Michael Eberhardson
- Department of Health, Medicine and Caring SciencesLinköping UniversityLinköpingSweden
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Diao N, Zheng W, Chen H, Tang J. Exclusive enteral nutrition combined with continuous succus entericus reinfusion for high-output stoma in patients with Crohn's disease: a case report. Gastroenterol Rep (Oxf) 2024; 12:goae100. [PMID: 39464419 PMCID: PMC11513195 DOI: 10.1093/gastro/goae100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 08/03/2024] [Accepted: 10/10/2024] [Indexed: 10/29/2024] Open
Affiliation(s)
- Na Diao
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Wenyou Zheng
- Department of Gastroenterology, People’s hospital of Taishan, Jiangmen, Guangdong, P. R. China
| | - Huiping Chen
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Jian Tang
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Zhou Z, Yu C, Liu B, Yao D, Huang Y, Wang P, Li Y. Landscape of surgery in Crohn's disease across twenty years: insights from machine learning. Transl Gastroenterol Hepatol 2024; 9:64. [PMID: 39503021 PMCID: PMC11535804 DOI: 10.21037/tgh-23-113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 06/26/2024] [Indexed: 11/08/2024] Open
Abstract
Background Crohn's disease continues to be a major component of inflammatory bowel disease with increasing incidence and prevalence. Increasing publications of surgery in Crohn's disease have significantly expanded the research scope. The aim of this study is to characterize main topics and a full landscape of surgery in Crohn's disease. Methods Studies of surgery in Crohn's disease from 2000 to 2020 were screened and retrieved from the Web of Science Core Collection database. Latent Dirichlet allocation (LDA), one of machine-learning algorithms for natural language processing, was employed for topic modeling. All the studies were processed, analyzed and visualized by R software, CiteSpace and Gephi. Results A total of 3,697 original publications were identified from the database. USA was the leading country with the most top institutions such as Cleveland Clin Florida and Mayo Clinic and Mayo Foundation. Increasing impact of institutions from Korea and China was also noticed. Bo Shen was the leading author in publication. A machine learning based topic modeling identified major clusters, including disease assessment, surgical treatment and complications, risk factors and epidemiology, disease development and diagnosis, target treatment and recurrence. Three topics attracted continuous high research attention, including expression of intestinal cell, perianal fistula and laparoscopic and open operation. Conclusions This study identified key topics relating to the development of surgery in Crohn's disease, and provided bibliometric insights and perspectives for future development in the field of surgery in Crohn's disease.
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Affiliation(s)
- Zhiyuan Zhou
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chaoran Yu
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bin Liu
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Danhua Yao
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhua Huang
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Pengfei Wang
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yousheng Li
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Geng Z, Li J, Zuo L, Zhang X, Wang L, Xia Y, Yang J, Yin L, Song X, Wang Y, Chai D, Deng M, Ge Y, Wu R, Hu J. Intestinal Adipocytes Transdifferentiate into Myofibroblast-like Cells and Contribute to Fibrosis in Crohn's Disease. J Crohns Colitis 2024; 18:1292-1304. [PMID: 38466138 DOI: 10.1093/ecco-jcc/jjae036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 03/02/2024] [Accepted: 03/09/2024] [Indexed: 03/12/2024]
Abstract
BACKGROUND AND AIMS Intestinal fibrotic stenosis is a major reason for surgery in Crohn's disease [CD], but the mechanism is unknown. Thus, we asked whether intestinal adipocytes contribute to intestinal fibrosis. Adipocytes were found to transdifferentiate into myofibroblasts and confirmed to be involved in mesenteric fibrosis in our recent study. Here, we investigated the role and possible mechanisms of intestinal adipocytes in intestinal fibrosis in CD. METHODS The intestinal tissue of patients with CD with or without fibrotic stenosis [CDS or CDN] and normal intestinal tissue from individuals without CD were obtained to assess alterations in submucosal adipocytes in CDS and whether these cells transdifferentiated into myofibroblasts and participated in the fibrotic process. Human primary adipocytes and adipose organoids were used to evaluate whether adipocytes could be induced to transdifferentiate into myofibroblasts and to investigate the fibrotic behaviour of adipocytes. LPS/TLR4/TGF-β signalling was also studied to explore the underlying mechanism. RESULTS Submucosal adipocytes were reduced in number or even absent in CDS tissue, and the extent of the reduction correlated negatively with the degree of submucosal fibrosis. Interestingly, submucosal adipocytes in CDS tissue transdifferentiated into myofibroblast-like cells and expressed collagenous components, possibly due to stimulation by submucosally translocated bacteria. Lipopolysaccharide [LPS]-stimulated human primary adipocytes and adipose organoids also exhibited transdifferentiation and profibrotic behaviour. Mechanistically, TLR4-mediated TGF-β signalling was associated with the transdifferentiation and profibrotic behaviour of intestinal adipocytes in CDS tissue. CONCLUSIONS Intestinal adipocytes transdifferentiate into myofibroblasts and participate in the intestinal fibrosis process in CD, possibly through LPS/TLR4/TGF-β signalling.
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Affiliation(s)
- Zhijun Geng
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu Medical University, Bengbu, China
- Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Jing Li
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu Medical University, Bengbu, China
- Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Lugen Zuo
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu Medical University, Bengbu, China
- Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Xiaofeng Zhang
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu Medical University, Bengbu, China
- Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Lian Wang
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu Medical University, Bengbu, China
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Yongsheng Xia
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Jingjing Yang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
| | - Lixia Yin
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Xue Song
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu Medical University, Bengbu, China
- Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Yueyue Wang
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu Medical University, Bengbu, China
- Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Damin Chai
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu Medical University, Bengbu, China
- Department of Pathology, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Min Deng
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu Medical University, Bengbu, China
- Department of Gastroenterology, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Yuanyuan Ge
- Department of Colorectal Surgery, Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Rong Wu
- Department of General Surgery, Zhongda Hospital, Southeast University, Nanjing, China
| | - Jianguo Hu
- Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu Medical University, Bengbu, China
- Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu, China
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Weissman S, Aziz M, Bangolo A, Nagesh VK, Aung H, Mathew M, Garcia L, Chandar SA, Karamthoti P, Bawa H, Alshimari A, Kejela Y, Mehdi N, Joseph CA, Kodali A, Kumar R, Goyal P, Satheesha S, Nivedita F, Tesoro N, Sethi T, Singh G, Belal A, Intisar A, Khalid H, Cornwell S, Suresh SB, Ahmed K, Marole KK, Anand OP, Reshi RB, Mehta TI, Elias S, Feuerstein JD. Global geoepidemiology of gastrointestinal surgery rates in Crohn's disease. World J Gastrointest Surg 2024; 16:1835-1844. [PMID: 38983343 PMCID: PMC11230035 DOI: 10.4240/wjgs.v16.i6.1835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 04/09/2024] [Accepted: 04/24/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Data regarding the worldwide gastrointestinal surgery rates in patients with Crohn's disease (CD) remains limited. AIM To systematically review the global variation in the rates of surgery in CD. METHODS A comprehensive search analysis was performed using multiple electronic databases from inception through July 1, 2020, to identify all full text, randomized controlled trials and cohort studies pertaining to gastrointestinal surgery rates in adult patients with CD. Outcomes included continent based demographic data, CD surgery rates over time, as well as the geoepidemiologic variation in CD surgery rates. Statistical analyses were conducted using R. RESULTS Twenty-three studies spanning four continents were included. The median proportion of persons with CD who underwent gastrointestinal surgery in studies from North America, Europe, Asia, and Oceania were 30% (range: 1.7%-62.0%), 40% (range: 0.6%-74.0%), 17% (range: 16.0%-43.0%), and 38% respectively. No clear association was found regarding the proportion of patients undergoing gastrointestinal surgery over time in North America (R 2 = 0.035) and Europe (R 2 = 0.100). A moderate, negative association was seen regarding the proportion of patients undergoing gastrointestinal surgery over time (R 2 = 0.520) in Asia. CONCLUSION There appears to be significant inter-continental variation regarding surgery rates in CD. Homogenous evidence-based guidelines accounting for the geographic differences in managing patients with CD is prudent. Moreover, as a paucity of data on surgery rates in CD exists outside the North American and European continents, future studies, particularly in less studied locales, are warranted.
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Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Muhammad Aziz
- Division of Gastroenterology and Hepatology, University of Toledo Medical Center, Toledo, OH 43614, United States
| | - Ayrton Bangolo
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Vignesh K Nagesh
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Htat Aung
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Midhun Mathew
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Lino Garcia
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Shiva A Chandar
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Praveena Karamthoti
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Harinder Bawa
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Aseel Alshimari
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Yabets Kejela
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Nazish Mehdi
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Chrishanti A Joseph
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Athri Kodali
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Rohan Kumar
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Priya Goyal
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Sanya Satheesha
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Fnu Nivedita
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Nicole Tesoro
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Tanni Sethi
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Gurpreet Singh
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Areej Belal
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Alina Intisar
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Hirra Khalid
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Samuel Cornwell
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Suchith B Suresh
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Kareem Ahmed
- Department of Medicine, University of Washington, Seattle, WA 98195, United States
| | - Karabo K Marole
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Om P Anand
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Rahat B Reshi
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Tej I Mehta
- Department of Radiology, Johns Hopkins University Hospital, Baltimore, MD 21218, United States
| | - Sameh Elias
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Joseph D Feuerstein
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
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Wang W, Li K, Bai D, Wu J, Xiao W. Pterostilbene: a potential therapeutic agent for fibrotic diseases. Inflammopharmacology 2024; 32:975-989. [PMID: 38429613 DOI: 10.1007/s10787-024-01440-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 01/19/2024] [Indexed: 03/03/2024]
Abstract
Fibrosis is a prevailing pathology in chronic diseases and accounts for 45% of deaths in developed countries. This condition is primarily identified by the transformation of fibroblasts into myofibroblasts and the overproduction of extracellular matrix (ECM) by myofibroblasts. Pterostilbene (PTS) is a natural analogue of resveratrol and is most commonly found in blueberries. Research has shown that PTS exerts a wide range of pharmacological effects, such as antioxidant, anti-inflammatory, and anticancer effects. As a result, PTS has the potential to prevent and cure numerous diseases. Emerging evidence has indicated that PTS can alleviate myocardial fibrosis, renal fibrosis, pulmonary fibrosis, hepatic fibrosis, and colon fibrosis via the inhibition of inflammation, oxidative stress, and fibrogenesis effects in vivo and in vitro, and the potential mechanisms are linked to various pathways, including transforming growth factor-β1 (TGF-β1)/small mother against decapentaplegic proteins (Smads) signalling, the reactive oxygen species (ROS)-driven Pitx2c/mir-15b pathway, nuclear factor kappa B (NF-κB) signalling, Kelch-like epichlorohydrin-associated protein-1 (Keap-1)/NF-E2-related factor-2 (Nrf2) cascade, the NLR family pyridine structure domain 3 (NLRP3) pathway, the Janus kinase-2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, and the Src/STAT3 pathway. In this review, we comprehensively summarize the antifibrotic effects of PTS both in vivo and in vitro and the pharmacological mechanisms, pharmacokinetics, and toxicology of PTS and provide insights into and strategies for exploring promising agents for the treatment of fibrosis.
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Affiliation(s)
- Wenhong Wang
- The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, 200438, China
- Shanghai Key Lab of Human Performance, Shanghai University of Sport, Yangpu District, 650 Qingyuan Ring Road, Shanghai, 200438, China
| | - Ke Li
- The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, 200438, China
- Shanghai Key Lab of Human Performance, Shanghai University of Sport, Yangpu District, 650 Qingyuan Ring Road, Shanghai, 200438, China
| | - Dandan Bai
- The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, 200438, China
- Shanghai Key Lab of Human Performance, Shanghai University of Sport, Yangpu District, 650 Qingyuan Ring Road, Shanghai, 200438, China
| | - Jiabin Wu
- The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, 200438, China
- Shanghai Key Lab of Human Performance, Shanghai University of Sport, Yangpu District, 650 Qingyuan Ring Road, Shanghai, 200438, China
| | - Weihua Xiao
- The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, 200438, China.
- Shanghai Key Lab of Human Performance, Shanghai University of Sport, Yangpu District, 650 Qingyuan Ring Road, Shanghai, 200438, China.
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7
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Biel C, Faber KN, Bank RA, Olinga P. Matrix metalloproteinases in intestinal fibrosis. J Crohns Colitis 2024; 18:462-478. [PMID: 37878770 PMCID: PMC10906956 DOI: 10.1093/ecco-jcc/jjad178] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 10/03/2023] [Accepted: 10/24/2023] [Indexed: 10/27/2023]
Abstract
Intestinal fibrosis is a common complication in patients with inflammatory bowel disease [IBD], in particular Crohn's disease [CD]. Unfortunately, at present intestinal fibrosis is not yet preventable, and cannot be treated by interventions other than surgical removal. Intestinal fibrosis is characterized by excessive accumulation of extracellular matrix [ECM], which is caused by activated fibroblasts and smooth muscle cells. Accumulation of ECM results from an imbalanced production and degradation of ECM. ECM degradation is mainly performed by matrix metalloproteinases [MMPs], enzymes that are counteracted by tissue inhibitors of MMPs [TIMPs]. In IBD patients, MMP activity [together with other protease activities] is increased. At the same time, CD patients have a generally lower MMP activity compared to ulcerative colitis patients, who usually do not develop intestinal strictures or fibrosis. The exact regulation and role[s] of these MMPs in fibrosis are far from understood. Here, we review the current literature about ECM remodelling by MMPs in intestinal fibrosis and their potential role as biomarkers for disease progression or druggable targets.
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Affiliation(s)
- Carin Biel
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, the Netherlands
| | - Klaas Nico Faber
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
| | - Ruud A Bank
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
| | - Peter Olinga
- Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, the Netherlands
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Halloran BP, Reeson M, Teshima C, Kroeker K, Huang V, Dieleman L, Holmes P, Baumgart DC, Wong K, Hoentjen F, Peerani F, Zepeda-Gomez S. Stricture dilation via balloon-assisted endoscopy in Crohn's disease: approach and intraprocedural outcomes with the single-balloon and double-balloon systems. Therap Adv Gastroenterol 2024; 17:17562848241230904. [PMID: 38425369 PMCID: PMC10903206 DOI: 10.1177/17562848241230904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 01/17/2024] [Indexed: 03/02/2024] Open
Abstract
Background Despite recent emerging literature involving the utility of endoscopic balloon dilation (EBD) of strictures via balloon-assisted endoscopy (BAE), specifically regarding the management of Crohn's disease (CD), the optimal clinical approach with balloon systems has been largely neglected in academic literature. Objectives This study assesses the intra-procedural success and safety of EBD via BAE for small bowel CD strictures while detailing our clinical approach and technique. Secondarily, we compare the single-balloon endoscope (SBE) and double-balloon endoscope (DBE) systems for EBD-related outcomes. Design Retrospective consecutive patient cohort analysis. Methods We retrospectively assessed a consecutive small bowel CD patient cohort undergoing BAE at the University of Alberta Hospital endoscopy unit from 2013 to 2020. The primary endpoint discerned the safety and immediate success rate of EBD during endoscopy, and comparisons of the dilation parameters and efficacy of SBE versus DBE were assessed as secondary outcomes. Results During the study period, 87 patients (44 male) with a mean age of 56 ± 14.7 years underwent 179 endoscopic procedures (92 DBE and 87 SBE). Of 358 strictures encountered, 320 (89.4%) were successfully dilated and traversed. The mean maximum dilation diameter was 15.76 ± 2.10 mm. There were no perforations or major adverse events. Conclusion EBD via BAE is a safe procedure in small bowel CD with a high intraprocedural success rate. Overall, SBE had a higher success rate in traversing strictures before and after dilation using our technique. This analysis is limited by the retrospective nature of our study and must be balanced against the inherent benefits of the DBE system.
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Affiliation(s)
- Brendan P. Halloran
- Director of the Small Endoscopy Bowel Program, Division of Gastroenterology, Department of Medicine, University of Alberta, 130 University Campus NW, Edmonton, AB, Canada T6G2X8
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Matthew Reeson
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | | | - Karen Kroeker
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Vivian Huang
- Division of Gastroenterology, Mount Sinai Hospital, Toronto, ON, Canada
| | - Levinus Dieleman
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Peter Holmes
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Daniel C. Baumgart
- Division of Gastroenterology
- Charité Medical Center – Virchow Hospital Berlin, Berlin, Germany
| | - Karen Wong
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Frank Hoentjen
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Farhad Peerani
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
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Cantorna MT, Arora J. Vitamin D, microbiota, and inflammatory bowel disease. FELDMAN AND PIKE'S VITAMIN D 2024:1057-1073. [DOI: 10.1016/b978-0-323-91338-6.00047-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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10
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Ueda T, Koyama F, Sugita A, Ikeuchi H, Futami K, Fukushima K, Nezu R, Iijima H, Mizushima T, Itabashi M, Watanabe K, Hata K, Shinagawa T, Matsuoka K, Takenaka K, Sasaki M, Nagayama M, Yamamoto H, Shinozaki M, Fujiya M, Kato J, Ueno Y, Tanaka S, Okita Y, Hashimoto Y, Kobayashi T, Koganei K, Uchino M, Fujii H, Suzuki Y, Hisamatsu T. Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study. J Crohns Colitis 2023; 17:1968-1979. [PMID: 37450892 DOI: 10.1093/ecco-jcc/jjad116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Indexed: 07/18/2023]
Abstract
BACKGROUND AND AIMS Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients. METHODS We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis. RESULTS In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions. CONCLUSIONS Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.
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Affiliation(s)
- Takeshi Ueda
- Department of Surgery, Nara Medical University, Kashihara, Japan
- Sai Gastroenterology and Proctology Clinic, Fujiidera, Japan
| | - Fumikazu Koyama
- Department of Surgery, Nara Medical University, Kashihara, Japan
- Division of Endoscopy, Nara Medical University Hospital, Kashihara, Japan
| | - Akira Sugita
- Department of Inflammatory Bowel Disease, Yokohama Municipal Citizen's Hospital, Yokohama, Japan
| | - Hiroki Ikeuchi
- Department of Gastroenterological Surgery, Division of Inflammatory Bowel Disease Surgery, Hyogo Medical University, Nishinomiya, Japan
| | - Kitaro Futami
- Department of Surgery, Fukuoka University Chikushi Hospital, Chikusino, Japan
| | | | - Riichiro Nezu
- Department of Surgery, Osaka Central Hospital, Osaka, Japan
| | - Hideki Iijima
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, and Department of Gastroenterology, Department of Gastroenterology, Osaka Police Hospital, Osaka, Japan
| | - Tsunekazu Mizushima
- Department of Therapeutics for Inflammatory Bowel Diseases, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Michio Itabashi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Kazuhiro Watanabe
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
- Nihonbashi Muromachi Mitsui Tower Midtown Clinic, Tokyo, Japan
| | | | - Katsuyoshi Matsuoka
- Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kento Takenaka
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Makoto Sasaki
- Division of Gastroenterology, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Manabu Nagayama
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Hironori Yamamoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Masaru Shinozaki
- Department of Surgery, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan, and Saitama Gastroenterological Clinic, Saitama, Japan
| | - Mikihiro Fujiya
- Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Jun Kato
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yoshitaka Ueno
- Department of Endoscopy and Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Shinji Tanaka
- Department of Endoscopy and Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Yoshiki Okita
- Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | | | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Kazutaka Koganei
- Department of Inflammatory Bowel Disease, Yokohama Municipal Citizen's Hospital, Yokohama, Japan
| | - Motoi Uchino
- Department of Gastroenterological Surgery, Division of Inflammatory Bowel Disease Surgery, Hyogo Medical University, Nishinomiya, Japan
| | - Hisao Fujii
- Gastrointestinal Endoscopy and IBD Center, Yoshida Hospital, Nara, Japan
| | - Yasuo Suzuki
- Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan
- Ginza Central Clinic, Tokyo, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
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Li X, Peng Z, An K, Xue M, Wang Z, Xia J, Qi Z, Shu X. Temsirolimus is a promising immunomodulatory agent for enhanced transplantation outcomes. Transpl Immunol 2023; 81:101952. [PMID: 37918580 DOI: 10.1016/j.trim.2023.101952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 10/30/2023] [Accepted: 10/30/2023] [Indexed: 11/04/2023]
Abstract
BACKGROUND Identifying effective immunosuppressive strategies is critical for addressing immunological rejection following organ transplantation. This study explores the potential immunosuppressive effects and mechanisms of temsirolimus, a rapamycin derivative, in organ transplantation. METHODS A mouse cardiac allograft model was established using a cervical cannula technique with BALB/c donors and C57BL/6 recipients. Mice were administered temsirolimus intragastrically and graft survival was evaluated. Histological staining was used to assess pathological changes. The BrdU assay was used to measure splenic T cell proliferation. Flow cytometry was used to quantify regulatory T cells (Tregs), CD4+ T cells, and CD8+ T cells. ELISA and qPCR assays were used to determine Foxp3, IL-4, IFN-γ, and TGF-β expression. RESULTS Temsirolimus displayed potent immunosuppressive effects at 20 mg/kg/day, significantly inhibiting T cell proliferation (84.6%, P < 0.0001) and prolonging graft survival (median 49 days vs. 8.5 days in controls, P < 0.0001). However, median survival decreased to 34.5 days upon withdrawal. Temsirolimus also reduced splenic CD4+ and CD8+ T cells (2.85% and 2.92%, P < 0.001) and antibody levels (IgM, IgG1, IgG2) by 11.85-29.09% (P < 0.0001) and increased Tregs, Foxp3, IL-4 (P < 0.01), and TGF-β (P < 0.05), while decreasing IFN-γ (P < 0.001). CONCLUSIONS Temsirolimus exhibited potent immunosuppressive effects, emerging as a strong candidate to mitigate organ transplant rejection.
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Affiliation(s)
- Xianguo Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Zuojie Peng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Ke An
- Department of Physiology, Xuzhou Medical University, Xuzhou 221009, China
| | - Mengjiao Xue
- Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Zhenzhen Wang
- Department of Pharmacy, Zhoukou Central Hospital, Zhoukou 466000, China
| | - Junjie Xia
- Organ Transplantation Institute, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen 361100, China.
| | - Zhongquan Qi
- Medical College of Guangxi University, Guangxi University, Nanning 530004, China.
| | - Xiaogang Shu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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Minordi LM, Larosa L, Bevere A, D’Angelo FB, Pierro A, Cilla S, Del Ciello A, Scaldaferri F, Barbaro B. Imaging of Strictures in Crohn's Disease. Life (Basel) 2023; 13:2283. [PMID: 38137884 PMCID: PMC10745118 DOI: 10.3390/life13122283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 11/15/2023] [Accepted: 11/27/2023] [Indexed: 12/24/2023] Open
Abstract
Crohn's disease (CD) is a chronic inflammation of the digestive tract, and it frequently affects young patients. It can involve any intestinal segment, even though it frequently affects the distal ileum. Up to 80% of patients with CD present with inflammatory behavior, and 5% to 28% develop stricturing disease. Based on the predominant mechanism causing them, strictures can be categorized as inflammatory, fibrotic, or mixed. Determining the relative amounts of inflammation and fibrosis in a stricture can influence treatment decisions. Imaging is an extremely useful tool in patients with small bowel stricturing CD to confirm the diagnosis and to evaluate disease characteristics, usually using CT or MRI. The aim of this paper is to describe how imaging can evaluate a patient with small bowel CD stricture.
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Affiliation(s)
- Laura Maria Minordi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Roma, Italy; (L.M.M.); (A.D.C.); (B.B.)
| | - Luigi Larosa
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Roma, Italy; (L.M.M.); (A.D.C.); (B.B.)
| | - Antonio Bevere
- Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy; (A.B.)
| | | | - Antonio Pierro
- Radiology Unit, San Timoteo Hospital, 86039 Termoli, Italy;
| | - Savino Cilla
- Medical Physics Unit, Responsible Research Hospital, 86100 Campobasso, Italy;
| | - Annemilia Del Ciello
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Roma, Italy; (L.M.M.); (A.D.C.); (B.B.)
| | - Franco Scaldaferri
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy;
| | - Brunella Barbaro
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Roma, Italy; (L.M.M.); (A.D.C.); (B.B.)
- Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy; (A.B.)
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He X, Ye H, Zhao R, Lu M, Chen Q, Bao L, Lv T, Li Q, Wu F. Advanced machine learning model for predicting Crohn's disease with enhanced ant colony optimization. Comput Biol Med 2023; 163:107216. [PMID: 37399742 DOI: 10.1016/j.compbiomed.2023.107216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 06/13/2023] [Accepted: 06/25/2023] [Indexed: 07/05/2023]
Abstract
Changes in human lifestyles have led to a dramatic increase in the incidence of Crohn's disease worldwide. Predicting the activity and remission of Crohn's disease has become an urgent research problem. In addition, the influence of each attribute in the test sample on the prediction results and the interpretability of the model still deserves further investigation. Therefore, in this paper, we proposed a wrapper feature selection classification model based on a combination of the improved ant colony optimization algorithm and the kernel extreme learning machine, called bIACOR-KELM-FS. IACOR introduces an evasive strategy and astrophysics strategy to balance the exploration and exploitation phases of the algorithm and enhance its optimization capabilities. The optimization capability of the proposed IACOR was validated on the IEEE CEC2017 benchmark test function. And the prediction was performed on Crohn's disease dataset. The results of the quantitative analysis showed that the prediction accuracy of bIACOR-KELM-FS for predicting the activity and remission of Crohn's disease reached 98.98%. The analysis of important attributes improved the interpretability of the model and provided a reference for the diagnosis of Crohn's disease. Therefore, the proposed model is considered a promising adjunctive diagnostic method for Crohn's disease.
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Affiliation(s)
- Xixi He
- Department of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
| | - Huajun Ye
- Department of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
| | - Rui Zhao
- Department of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
| | - Mengmeng Lu
- Department of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
| | - Qiwen Chen
- Department of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
| | - Lishimeng Bao
- The Second Clinical College, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
| | - Tianmin Lv
- Department of Nursing Wenzhou Heping International Hospital, Wenzhou, Zhejiang, 325000, China.
| | - Qiang Li
- School of Computer Science and Technology, Beijing Institute of Technology, Beijing, 100081, China.
| | - Fang Wu
- Department of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
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14
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Yamamoto A, Toiyama Y, Ikeuchi H, Uchino M, Futami K, Okamoto K, Ogino T, Ishihara S, Ajioka Y, Sugihara K. Oncological outcomes of Crohn's disease-associated cancers focusing on disease behavior. Ann Gastroenterol Surg 2023; 7:615-625. [PMID: 37416732 PMCID: PMC10319610 DOI: 10.1002/ags3.12653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 12/20/2022] [Accepted: 12/23/2022] [Indexed: 01/20/2023] Open
Abstract
Background The overall risk of colorectal cancer in Crohn's disease (CD) is higher than in the general population, and CD-associated cancer (CDAC) has poorer prognosis than sporadic cancer. Developing treatment strategies for improving the prognosis of CDAC, we evaluated the characteristics of CDAC according to the underlying disease behavior, namely stricturing and penetrating. Methods This multicenter retrospective study comprises 316 CDAC patients who underwent surgery between 1985 and 2019. Clinicopathological findings including disease behavior and oncological outcomes were investigated. Results There was no association between the preoperative course of CDAC patients and disease behavior; however, postoperative information revealed distinctly different characteristics between CDAC patients with stricturing behavior and those with penetrating behavior (stricturing with lymphatic invasion and peritoneal dissemination recurrence, and penetrating with histologically poorly differentiated and local recurrence). Oncological outcome of patients with CDAC was distinctly different according to disease behavior, as penetrating provided a poor outcome (overall survival [OS]: p = 0.02; relapse-free survival [RFS]: p = 0.002) whereas stricturing had no effect. Furthermore, penetrating behavior was identified as one of the independent risk factors for poor OS and RFS (OS: hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.16-3.09, p = 0.01; RFS: HR 2.15, 95% CI 1.28-3.63, p = 0.004). Conclusions Our study highlights the different characteristics of CDAC according to the underlying disease behavior and substantiates the poor prognosis of CDAC patients with penetrating behavior. Treatment planning including screening, surgical procedures, and postoperative treatment, with awareness of these findings, may contribute to improved prognosis for CDAC patients.
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Affiliation(s)
- Akira Yamamoto
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative MedicineInstitute of Life Sciences, Mie University Graduate School of MedicineTsuJapan
| | - Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative MedicineInstitute of Life Sciences, Mie University Graduate School of MedicineTsuJapan
| | - Hiroki Ikeuchi
- Department of Inflammatory Bowel Disease SurgeryHyogo College of MedicineNishinomiyaJapan
| | - Motoi Uchino
- Department of Inflammatory Bowel Disease SurgeryHyogo College of MedicineNishinomiyaJapan
| | - Kitaro Futami
- Department of SurgeryFukuoka University Chikushi HospitalChikushinoJapan
| | - Kinya Okamoto
- Department of ColoproctologyTokyo Yamate Medical CenterTokyoJapan
| | - Takayuki Ogino
- Department of Gastroenterological Surgery, Graduate School of MedicalOsaka UniversityOsakaJapan
| | | | - Yoichi Ajioka
- Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
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Sassaki LY, Martins AL, Galhardi-Gasparini R, Saad-Hossne R, Ritter AMV, Barreto TB, Marcolino T, Balula B, Yang-Santos C. Intestinal complications in patients with Crohn’s disease in the Brazilian public healthcare system between 2011 and 2020. World J Clin Cases 2023; 11:3224-3237. [PMID: 37274050 PMCID: PMC10237144 DOI: 10.12998/wjcc.v11.i14.3224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/27/2023] [Accepted: 04/06/2023] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND This is a secondary database study using the Brazilian public healthcare system database.
AIM To describe intestinal complications (ICs) of patients in the Brazilian public healthcare system with Crohn’s disease (CD) who initiated and either only received conventional therapy (CVT) or also initiated anti-tumor necrosis factor (anti-TNF) therapy between 2011 and 2020.
METHODS This study included patients with CD [international classification of diseases – 10th revision (ICD-10): K50.0, K50.1, or K50.8] (age: ≥ 18 years) with at least one claim of CVT (sulfasalazine, azathioprine, mesalazine, or methotrexate). IC was defined as a CD-related hospitalization, pre-defined procedure codes (from rectum or intestinal surgery groups), and/or associated disease (pre-defined ICD-10 codes), and overall (one or more type of ICs).
RESULTS In the 16809 patients with CD that met the inclusion criteria, the mean follow-up duration was 4.44 (2.37) years. In total, 14697 claims of ICs were found from 4633 patients. Over the 1- and 5-year of follow-up, 8.3% and 8.2% of the patients with CD, respectively, presented at least one IC, of which fistula (31%) and fistulotomy (48%) were the most commonly reported. The overall incidence rate (95%CI) of ICs was 6.8 (6.5–7.04) per 100 patient years for patients using only-CVT, and 9.2 (8.8–9.6) for patients with evidence of anti-TNF therapy.
CONCLUSION The outcomes highlighted an important and constant rate of ICs over time in all the CD populations assessed, especially in patients exposed to anti-TNF therapy. This outcome revealed insights into the real-world treatment and complications relevant to patients with CD and highlights that this disease remains a concern that may require additional treatment strategies in the Brazilian public healthcare system.
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Affiliation(s)
- Ligia Yukie Sassaki
- Department of Internal Medicine, São Paulo State University - UNESP, Medical School, 18618687, Botucatu, Brazil
| | - Adalberta Lima Martins
- Department of Gastroenterology, State Office for Pharmaceutical Assistance at Espírito Santo Health Office, Vitoria 29017-010, Espirito Santo, Brazil
| | | | - Rogerio Saad-Hossne
- Department of Surgery, São Paulo State University - UNESP, Medical School, 18618687, Botucatu, Brazil
| | | | | | - Taciana Marcolino
- Medical Affairs, Takeda Pharmaceuticals Brazil, 04794-000, Sao Paulo, Brazil
| | - Bruno Balula
- Real World Evidence, IQVIA Brazil, 04719-002, Sao Paulo, Brazil
| | - Claudia Yang-Santos
- Clinical Research, Takeda Pharmaceuticals Brazil, 04794-000, Sao Paulo, Brazil
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Li L, Shapiro RL, Joo MK, Josyula A, Hsueh HT, Gutierrez OB, Halpert G, Akshintala V, Chen H, Curtis S, Better M, Davison C, Hu H, Almario JAN, Steinway SN, Hunt K, Del Sesto RE, Izzi J, Salimian KJ, Ensign LM, Selaru FM. Injectable, Drug-Eluting Nanocrystals Prevent Fibrosis and Stricture Formation In Vivo. Gastroenterology 2023; 164:937-952.e13. [PMID: 36657529 PMCID: PMC10151160 DOI: 10.1053/j.gastro.2023.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 12/07/2022] [Accepted: 01/10/2023] [Indexed: 01/21/2023]
Abstract
BACKGROUND & AIMS Tissue fibrosis results from uncontrolled healing responses leading to excessive mesenchymal cell activation and collagen and other extracellular matrix deposition. In the gastrointestinal tract, fibrosis leads to narrowing of the lumen and stricture formation. A drug treatment to prevent fibrosis and strictures in the gastrointestinal tract would be transformational for patient care. We aimed to develop a stricture treatment with the following characteristics and components: a small molecule with strong antifibrotic effects that is delivered locally at the site of the stricture to ensure correct lesional targeting while protecting the systemic circulation, and that is formulated with sustained-release properties to act throughout the wound healing processes. METHODS A high-throughput drug screening was performed to identify small molecules with antifibrotic properties. Next, we formulated an antifibrotic small molecule for sustained release and tested its antifibrotic potential in 3 animal models of fibrosis. RESULTS Sulconazole, a US Food and Drug Administration-approved drug for fungal infections, was found to have strong antifibrotic properties. Sulconazole was formulated as sulconazole nanocrystals for sustained release. We found that sulconazole nanocrystals provided superior or equivalent fibrosis prevention with less frequent dosing in mouse models of skin and intestinal tissue fibrosis. In a patient-like swine model of bowel stricture, a single injection of sulconazole nanocrystals prevented stricture formation. CONCLUSIONS The current data lay the foundation for further studies to improve the management of a range of diseases and conditions characterized by tissue fibrosis.
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Affiliation(s)
- Ling Li
- Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland
| | - Rachel L Shapiro
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland
| | - Min Kyung Joo
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Aditya Josyula
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland
| | - Henry T Hsueh
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland
| | - Olaya Brewer Gutierrez
- Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland
| | - Gilad Halpert
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Venkata Akshintala
- Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland
| | - Haiming Chen
- Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland
| | - Samuel Curtis
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Marina Better
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Charlotte Davison
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland
| | - Haijie Hu
- Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland
| | - Jose Antonio Navarro Almario
- Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland
| | - Steven N Steinway
- Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland
| | - Kelton Hunt
- Department of Chemistry and Biochemistry, Utah Tech University, St George, Utah
| | - Rico E Del Sesto
- Department of Chemistry and Biochemistry, Utah Tech University, St George, Utah
| | - Jessica Izzi
- Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, Maryland
| | - Kevan J Salimian
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Laura M Ensign
- Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Division of Infectious Diseases, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Sidney Kimmel Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
| | - Florin M Selaru
- Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, Sidney Kimmel Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Institute for Nanobiotechnology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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17
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Menchén L. Transmural or mucosal healing in Crohn´s disease. Which is the goal to be pursued? REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115. [PMID: 36809915 DOI: 10.17235/reed.2023.9492/2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2023]
Abstract
In their original report of regional ileitis, Crohn, Ginzburg and Oppenheimer already described that inflammation involved not only the ileal mucosa: "the submucosal and, to a much lesser extent, the muscular layers of the bowel are the seat of marked inflammatory hyperplastic and exudative changes", they wrote 1. Ninety years later it is well established that the inflammatory process that characterizes Crohn´s disease (CD) involves all the layers of the intestinal wall; this fact is directly related with the development of progressive digestive tract damage related to disabling complications such as strictures, fistulae, perforation, and perianal or abdominal abscesses.
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Affiliation(s)
- Luis Menchén
- Digestive Diseases, Hospital General Universitario Gregorio Marañón, España
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18
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Irwin J, Lord A, Ferguson E, Simms LA, Hanigan K, Montoya CA, Radford-Smith G. A Method Using Longitudinal Laboratory Data to Predict Future Intestinal Complication in Patients with Crohn's Disease. Dig Dis Sci 2023; 68:596-607. [PMID: 36125595 PMCID: PMC9905172 DOI: 10.1007/s10620-022-07639-w] [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: 05/12/2022] [Accepted: 07/20/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Stenosis, fistulization, and perforation of the bowel are severe outcomes which can occur in patients with Crohn's disease. Accurate prediction of these events may enable clinicians to alter treatment strategies and avoid these outcomes. AIMS To study the correlation between longitudinal laboratory testing and subsequent intestinal complications in patients with Crohn's disease. METHODS An observational cohort of patients with Crohn's disease at a single center were analyzed between 01/01/1994 and 06/30/2016. A complication was defined as the development of an intestinal fistula, stenosis, or perforation. Exploratory analysis using Cox regression was performed to select the best statistical method to represent longitudinal laboratory data. Cox regression was used to identify laboratory variables independently associated with the development of a subsequent complication. A clinical scoring tool was designed. RESULTS In 246 patients observed over a median of 5.72 years, 134 complications occurred. Minimum or maximum value in a preceding window period of one year was most strongly associated with subsequent complication. A Longitudinal Laboratory score of ≥ 2 (maximum albumin level < 39 g/L = 1, maximum mean cell volume < 88 fL = 1, minimum platelet count > 355 × 109/L = 1, minimum C reactive protein > 5 mg/L = 1) was 62% sensitive and 91% specific in identifying patients who develop a subsequent complication. CONCLUSION A consistent reduction in serum albumin and mean cell volume, and a consistent increase in platelet count and C reactive protein were associated with a subsequent complication in patients with Crohn's disease. Longitudinal laboratory tests may be used as described in this paper to provide a rational for earlier escalation of therapy.
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Affiliation(s)
- James Irwin
- QIMR Berghofer Medical Research Institute, Brisbane, Australia.
- Faculty of Medicine, The University of Queensland, Brisbane, Australia.
- Department of Gastroenterology, Palmerston North Hospital, 50 Ruahine Street, Palmerston North, 4442, New Zealand.
| | - Anton Lord
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Emma Ferguson
- Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Lisa A Simms
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | | | - Carlos A Montoya
- Smart Foods Innovation Centre of Excellence, AgResearch Limited, Te Ohu Rangahau Kai Facility, Palmerston North, 4474, New Zealand
- Riddet Institute, Massey University, Te Ohu Rangahau Kai Facility, Palmerston North, 4474, New Zealand
| | - Graham Radford-Smith
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, Australia
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Australia
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19
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King D, Coupland B, Dosanjh A, Cole A, Ward S, Reulen RC, Adderley NJ, Patel P, Trudgill N. The risk of subsequent surgery following bowel resection for Crohn's disease in a national cohort of 19 207 patients. Colorectal Dis 2023; 25:83-94. [PMID: 36097792 DOI: 10.1111/codi.16331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 02/14/2022] [Accepted: 04/07/2022] [Indexed: 02/02/2023]
Abstract
AIM Surgery is required for most patients with Crohn's disease (CD) and further surgery may be necessary if medical treatment fails to control disease activity. The aim of this study was to characterize the risk of, and factors associated with, further surgery following a first resection for Crohn's disease. METHODS Hospital Episode Statistics from England were examined to identify patients with CD and a first recorded bowel resection between 2007 and 2016. Multivariable logistic regression was used to examine risk factors for further resectional surgery within 5 years. Prevalence-adjusted surgical rates for index CD surgery over the study period were calculated. RESULTS In total, 19 207 patients (median age 39 years, interquartile range 27-53 years; 55% women) with CD underwent a first recorded resection during the study period. 3141 (16%) underwent a further operation during the study period. The median time to further surgery was 2.4 (interquartile range 1.2-4.6) years. 3% of CD patients had further surgery within 1 year, 14% by 5 years and 23% by 10 years. Older age (≥58), index laparoscopic surgery and index elective surgery (adjusted OR 0.65, 95% CI 0.54-0.77; 0.77, 0.67-0.88; and 0.77, 0.69-0.85; respectively) were associated with a reduced risk of further surgery by 5 years. Prior surgery for perianal disease (1.60, 1.37-1.87), an extraintestinal manifestation of CD (1.51, 1.22-1.86) and index surgery in a high-volume centre for CD surgery (1.20, 1.02-1.40) were associated with an increased risk of further surgery by 5 years. A 25% relative and 0.3% absolute reduction in prevalence-adjusted index surgery rates for CD was observed over the study period. CONCLUSIONS Further surgery following an index operation is common in CD. This risk was particularly seen in patients with perianal disease, extraintestinal manifestations and those who underwent index surgery in a high-volume centre.
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Affiliation(s)
- Dominic King
- Department of Gastroenterology, Sandwell and West Birmingham NHS Trust, West Bromwich, Birmingham, UK.,Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Benjamin Coupland
- Health Informatics, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Amandeep Dosanjh
- Health Informatics, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Andrew Cole
- Department of Gastroenterology, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK
| | - Stephen Ward
- Department of Colorectal Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Raoul C Reulen
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Nicola J Adderley
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Prashant Patel
- Health Informatics, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Nigel Trudgill
- Department of Gastroenterology, Sandwell and West Birmingham NHS Trust, West Bromwich, Birmingham, UK
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20
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Xia K, Gao RY, Wu XC, Yin L, Chen CQ. Timing of individualized surgical intervention in Crohn’s disease. World J Gastrointest Surg 2022; 14:1320-1328. [PMID: 36632120 PMCID: PMC9827570 DOI: 10.4240/wjgs.v14.i12.1320] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/24/2022] [Accepted: 12/01/2022] [Indexed: 12/27/2022] Open
Abstract
Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with an increasing incidence worldwide. Comprehensive therapy for CD focuses on symptom control and healing the intestinal mucosa to improve the quality of life and prevent complications. Surgical intervention plays a vital role in comprehensive therapy. However, deciding the optimal timing for surgical intervention has long been a focus of controversy. This review provides insights into the timing of surgery for CD and guides clinicians in daily treatment.
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Affiliation(s)
- Kai Xia
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Ren-Yuan Gao
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Xiao-Cai Wu
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Lu Yin
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Chun-Qiu Chen
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
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21
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Zuo L, Li J, Zhang X, Geng Z, Song X, Wang Y, Ge S, Shi R, Zhou Y, Ge Y, Wu R, Hu J. Aberrant Mesenteric Adipose Extracellular Matrix Remodelling is Involved in Adipocyte Dysfunction in Crohn's Disease: The Role of TLR-4-mediated Macrophages. J Crohns Colitis 2022; 16:1762-1776. [PMID: 35708752 DOI: 10.1093/ecco-jcc/jjac087] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Hypertrophic mesenteric adipose tissue [htMAT] is involved in the disease progression of Crohn's disease [CD] through expressing proinflammatory adipokines from dysfunctional adipocytes by unknown mechanism. Adipocyte function is affected by dynamic adipose tissue extracellular matrix [ECM] remodelling that is mainly mediated by macrophages, and our study aimed to reveal whether aberrant ECM remodelling was present in CD-htMAT and its effects on adipocyte dysfunction, as well as the mechanism. METHODS ECM remodelling was examined in MAT samples from CD patients and controls. Mice with dinitrobenzene sulphonic acid [DNBS]-induced colitis were used in vivo study, and lipopolysaccharide [LPS]-induced remodelling behaviour in macrophages was examined in vitro. Macrophages or TLR4 inhibition were used to analyse ECM remodelling mechanisms and their effects on adipocyte function. RESULTS Aberrant ECM remodelling: was observed in CD-htMAT, which was characterised by a widened and deformed ECM structure accompanied by dysregulated matrix synthesis and degradation; served as a reservoir for inflammatory factors/cells dominated by macrophages; and was involved in adipocyte dysfunction. In addition, macrophages were the main source of ECM remodelling regulatory factors with activation of Toll-like receptor 4 [TLR4] in htMAT. In vivo, macrophage depletion or TLR4 inhibition largely attenuated mesenteric ECM remodelling while improving mesenteric adipocyte dysfunction during chronic enteritis. In vitro, antagonizing TLR4 significantly inhibited LPS-induced macrophage ECM remodelling behavior. CONCLUSIONS The aberrant ECM remodelling in CD-htMAT contributed to mesenteric adipocyte dysfunction, which may be caused at least partly by TLR4-mediated macrophage remodelling behavior. Inhibiting ECM remodelling may be a potential therapeutic strategy for CD.
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Affiliation(s)
- Lugen Zuo
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Jing Li
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xiaofeng Zhang
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Zhijun Geng
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xue Song
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Yueyue Wang
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Sitang Ge
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Ruohan Shi
- Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China
| | - Yueqing Zhou
- Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China
| | - Yuanyuan Ge
- Department of Colorectal Surgery, Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Rong Wu
- Department of General Surgery, Southeast University Zhongda Hospital, Nanjing, China
| | - Jianguo Hu
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.,Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China
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22
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Afrin S, Simms LA, Lord A, Radford‐Smith GL. Nudix hydrolase 15 (NUDT15) loss-of-function variants in an Australian inflammatory bowel disease population. Intern Med J 2022; 52:1971-1977. [PMID: 35289057 PMCID: PMC9796699 DOI: 10.1111/imj.15746] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 03/01/2022] [Accepted: 03/07/2022] [Indexed: 01/07/2023]
Abstract
BACKGROUND Thiopurine-related adverse events such as leukopenia, liver dysfunction and pancreatitis are associated with variants in the NUDT15 gene. Loss-of-function (low or no enzyme activity) alleles are more common in Asian and Hispanic populations. The prevalence of these variants in the Australian inflammatory bowel disease (IBD) population has not yet been reported. AIM To evaluate the presence of NUDT15 loss-of-function alleles *2,*3,*9 in the Australian IBD population. METHODS The NUDT15 screening cohort included 423 IBD patients from Brisbane, Australia. Study patients were recruited by: (i) retrospective review of clinical charts for thiopurine-related severe adverse events; (ii) pathology data (white blood cell (WBC) and neutrophil counts). NUDT15 genotyping was performed using polymerase chain reaction (PCR)-high-resolution melt (HRM), TaqMan genotyping and Sanger sequencing. RESULTS NUDT15 mutation R139C (allele *3) was identified in 8 of 423 (1.9%) IBD patients. Seven of eight patients were R139C heterozygous (C/T) and one patient was R139C homozygous (T/T). One of the C/T group and the T/T patient developed thiopurine-induced myelosuppression (TIM) within 60 days of dosing. One patient in the C/T group developed TIM after 60 days of thiopurine dosing. The remaining five patients in the C/T group did not show TIM; however, other thiopurine-related events could not be ruled out and therefore careful monitoring over a long period is recommended. CONCLUSIONS This is the first study to report the frequency of NUDT15 haplotypes *2,*3,*9 in an Australian IBD population. The most common variant detected was the R139C mutation. PCR and Sanger sequencing are efficient and cost-effective approaches for NUDT15 genotyping.
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Affiliation(s)
- Sadia Afrin
- Gut Health Research GroupQIMR Berghofer Medical Research InstituteBrisbaneQueenslandAustralia
| | - Lisa A. Simms
- Gut Health Research GroupQIMR Berghofer Medical Research InstituteBrisbaneQueenslandAustralia
| | - Anton Lord
- Gut Health Research GroupQIMR Berghofer Medical Research InstituteBrisbaneQueenslandAustralia
| | - Graham L. Radford‐Smith
- Gut Health Research GroupQIMR Berghofer Medical Research InstituteBrisbaneQueenslandAustralia
- Department of Gastroenterology and HepatologyRoyal Brisbane and Women's HospitalBrisbaneQueenslandAustralia
- Faculty of MedicineUniversity of QueenslandBrisbaneQueenslandAustralia
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23
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Szczepanski HE, Flannigan KL, Mainoli B, Alston L, Baruta GM, Lee JW, Venu VKP, Shearer J, Dufour A, Hirota SA. NR4A1 modulates intestinal smooth muscle cell phenotype and dampens inflammation-associated intestinal remodeling. FASEB J 2022; 36:e22609. [PMID: 36250380 DOI: 10.1096/fj.202101817rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 09/16/2022] [Accepted: 09/30/2022] [Indexed: 11/11/2022]
Abstract
Stricture formation is a common complication of Crohn's disease (CD), driven by enhanced deposition of extracellular matrix (ECM) and expansion of the intestinal smooth muscle layers. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an orphan nuclear receptor that exhibits anti-proliferative effects in smooth muscle cells (SMCs). We hypothesized that NR4A1 regulates intestinal SMC proliferation and muscle thickening in the context of inflammation. Intestinal SMCs isolated from Nr4a1+/+ and Nr4a1-/- littermates were subjected to shotgun proteomic analysis, proliferation, and bioenergetic assays. Proliferation was assessed in the presence and absence of NR4A1 agonists, cytosporone-B (Csn-B) and 6-mercaptopurine (6-MP). In vivo, we compared colonic smooth muscle thickening in Nr4a1+/+ and Nr4a1-/- mice using the chronic dextran sulfate sodium (DSS) model of colitis. Second, SAMP1/YitFc mice (a model of spontaneous ileitis) were treated with Csn-B and small intestinal smooth muscle thickening was assessed. SMCs isolated from Nr4a1-/- mice exhibited increased abundance of proteins related to cell proliferation, metabolism, and ECM production, whereas Nr4a1+/+ SMCs highly expressed proteins related to the regulation of the actin cytoskeleton and contractile processes. SMCs isolated from Nr4a1-/- mice exhibited increased proliferation and alterations in cellular metabolism, whereas activation of NR4A1 attenuated proliferation. In vivo, Nr4a1-/- mice exhibited increased colonic smooth muscle thickness following repeated cycles of DSS. Activating NR4A1 with Csn-B, in the context of established inflammation, reduced ileal smooth muscle thickening in SAMP1/YitFc mice. Targeting NR4A1 may provide a novel approach to regulate intestinal SMC phenotype, limiting excessive proliferation that contributes to stricture development in CD.
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Affiliation(s)
- Holly E Szczepanski
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Kyle L Flannigan
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Barbara Mainoli
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.,Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, Canada
| | - Laurie Alston
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Grace M Baruta
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Joshua W Lee
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Vivek Krishna Pulakazhi Venu
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Jane Shearer
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.,Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, Canada.,Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Antoine Dufour
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.,Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, Canada.,McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada
| | - Simon A Hirota
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.,Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.,Department of Immunology, Microbiology & Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
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24
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Pray C, Wong ECL, Aruljothy A, Dulai PS, Marshall JK, Reinisch W, Narula N. Ulcer Size After Induction Therapy Performs Better Than Symptom Assessment for Prediction of One Year Endoscopic Remission in Crohn's Disease: A Post Hoc Analysis. Inflamm Bowel Dis 2022:6732190. [PMID: 36179118 DOI: 10.1093/ibd/izac210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND We evaluated whether postinduction ulcer size and patient-reported outcome (PRO) severity are associated with the achievement of 1-year endoscopic remission (ER) in patients with Crohn's disease (CD). METHODS This post hoc analysis combined data from several clinical trials including 283 patients with baseline ulcers ≥5 mm with repeat endoscopy after ustekinumab or adalimumab induction therapy. Patient-reported outcomes including stool frequency (SF) and abdominal pain (AP) were measured by the Crohn's Disease Activity Index. Thresholds of SF ≥4 and/or AP ≥2 indicated moderately to severely active CD. Endoscopic remission was defined as Simple Endoscopic Score for CD (SES-CD) <3. Multivariate logistic regression models adjusted for confounders (including disease duration and treatment allocation) evaluated the relationships between postinduction ulcer size, PRO symptoms, and achievement of 1-year ER. RESULTS Among the 131 CD patients who continued to have ulcers ≥5 mm after induction therapy, 48 (36.6%) achieved 1-year ER. Patients with postinduction ulcers ≥5 mm were approximately 5 times less likely to achieve 1-year ER than the 152 individuals who had small or no postinduction ulcers (odds ratio [OR], 0.20; 95% CI, 0.08-0.51, P = .001). In patients with ulcers ≥5 mm after induction, postinduction PRO scores (including PRO2 and PRO3) did not predict 1-year ER. CONCLUSIONS Crohn's disease patients with ulcers ≥5 mm after induction therapy are less likely to achieve 1-year ER. Postinduction PRO severity does not offer additional prognostic information. This may suggest that objective measures of disease such as endoscopic ulcer size should be considered over symptom assessments for determining clinical response to therapy and utilized in trials for maintenance therapy.
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Affiliation(s)
- Cara Pray
- Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Emily C L Wong
- Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Achuthan Aruljothy
- Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Parambir S Dulai
- Division of Gastroenterology, Northwestern University, Chicago, IL, USA
| | - John K Marshall
- Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Walter Reinisch
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria
| | - Neeraj Narula
- Department of Medicine, Division of Gastroenterology, and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
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25
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Ngollo M, Perez K, Hammoudi N, Gorelik Y, Delord M, Auzolle C, Bottois H, Cazals-Hatem D, Bezault M, Nancey S, Nachury M, Treton X, Fumery M, Buisson A, Barnich N, Seksik P, Shen-Orr SS, Le Bourhis L, Allez M. Identification of Gene Expression Profiles Associated with an Increased Risk of Post-Operative Recurrence in Crohn's Disease. J Crohns Colitis 2022; 16:1269-1280. [PMID: 35143619 DOI: 10.1093/ecco-jcc/jjac021] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 12/07/2021] [Accepted: 02/02/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Ileocolonic resection is frequently needed in the course of Crohn's disease [CD] treatment and post-operative recurrence is extremely common. Our main objective was to analyse gene expression in the mucosa of CD patients at the time of surgery and at post-operative endoscopy, in order to identify predictors and mechanisms of early endoscopic recurrence. METHODS We conducted transcriptome analyses on ileal mucosa samples collected from inflamed sections of the surgical specimens [n = 200], from ileal resection margins [n = 149] and in the neo-terminal ileum 6 months after surgery [n = 122]; these were compared with non-inflammatory bowel disease controls [n = 25]. The primary endpoint was post-operative endoscopic recurrence at 6 months. We applied regression models to identify gene signatures predicting endoscopic recurrence. RESULTS Chronic inflammation was associated with strong expression of inflammatory genes [IL-6, IL-8, IL-1B] and decreased expression of genes involved in metabolic processes, but with a high inter-individual heterogeneity. Gene signatures associated with early endoscopic recurrence were mainly characterized by upregulation of TNFα, IFNγ, IL23A and IL17A. Pathway analyses showed that upregulation of mitochondrial dysfunction within the inflamed sections and JAK/STAT at the ileal margin were predictive of post-operative recurrence. A combined model integrating these top pathway signatures improved the prediction of endoscopic recurrence [area under the curve of 0.79]. STAT3 phosphorylation at the surgical ileal margin was associated with severe recurrence at 6 months. CONCLUSION We identified several biological pathways in surgical ileal mucosa specimens associated with an increased risk of disease recurrence. Integration of the JAK/STAT and mitochondrial dysfunction pathways in the clinical model improved the prediction of post-operative recurrence.
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Affiliation(s)
- Marjolaine Ngollo
- Université de Paris, Institut de Recherche Saint-Louis, EMily, INSERM U1160, F-75010, Paris, France
| | - Kevin Perez
- Université de Paris, Institut de Recherche Saint-Louis, EMily, INSERM U1160, F-75010, Paris, France
| | - Nassim Hammoudi
- Université de Paris, Institut de Recherche Saint-Louis, EMily, INSERM U1160, F-75010, Paris, France.,Gastroenterology Department, Hôpital Saint-Louis - APHP, F-75010, Paris, France
| | - Yuri Gorelik
- Faculty of Medicine, Technion-Israel Institute of Technology, 3109601, Haifa, Israel
| | - Marc Delord
- Université de Paris, Institut de Recherche Saint-Louis, F-75010, Paris, France
| | - Claire Auzolle
- Université de Paris, Institut de Recherche Saint-Louis, EMily, INSERM U1160, F-75010, Paris, France.,Gastroenterology Department, Hôpital Saint-Louis - APHP, F-75010, Paris, France
| | - Hugo Bottois
- Université de Paris, Institut de Recherche Saint-Louis, EMily, INSERM U1160, F-75010, Paris, France
| | | | | | - Stéphane Nancey
- Gastroenterology Department, Hospices Civils De Lyon, F-69002, Lyon, France
| | - Maria Nachury
- Gastroenterology Department, Hôpital Claude Huriez, Université De Lille 2, F-59000, Lille, France
| | - Xavier Treton
- Gastroenterology Department, Hôpital Beaujon, MICI et Assistance Nutritive, F-92110, Clichy, France
| | - Mathurin Fumery
- Hepato-Gastroenterology Department, CHU d'Amiens, F-80000, Amiens, France
| | - Anthony Buisson
- Hepato-Gastroenterology Department, CHU de Clermont-Ferrand, F-6300, Clermont-Ferrand, France
| | - Nicolas Barnich
- Université Clermont Auvergne, INSERM U1071, M2iSH, USC-INRA 2018, F-63000, Clermont-Ferrand, France
| | - Philippe Seksik
- Gastroenterology Department, Hôpital Saint-Antoine, Université de la Sorbonne, AP-HP, F-75012, Paris, France
| | | | - Shai S Shen-Orr
- Faculty of Medicine, Technion-Israel Institute of Technology, 3109601, Haifa, Israel
| | - Lionel Le Bourhis
- Université de Paris, Institut de Recherche Saint-Louis, EMily, INSERM U1160, F-75010, Paris, France
| | - Matthieu Allez
- Université de Paris, Institut de Recherche Saint-Louis, EMily, INSERM U1160, F-75010, Paris, France.,Gastroenterology Department, Hôpital Saint-Louis - APHP, F-75010, Paris, France.,REMIND group, Hôpital Saint-Louis, F-75010, Paris, France
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26
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Julien C, Anakok E, Treton X, Nachury M, Nancey S, Buisson A, Fumery M, Filippi J, Maggiori L, Panis Y, Zerbib P, François Y, Dubois A, Sabbagh C, Rahili A, Seksik P, Allez M, Lefevre JH, Le Corff S, Bonnet A, Beyer-Berjot L, Sokol H. Impact of the Ileal Microbiota on Surgical Site Infections in Crohn's Disease: A Nationwide Prospective Cohort. J Crohns Colitis 2022; 16:1211-1221. [PMID: 35218661 DOI: 10.1093/ecco-jcc/jjac026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 12/24/2021] [Accepted: 02/25/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Surgery is performed in 50-70% of Crohn's disease [CD] patients, and its main risk is surgical site infection [SSI]. The microbiota has been extensively assessed in CD but not as a potential risk factor for septic morbidity. The objective of this study was to assess the impact of the gut microbiota on SSI in CD. METHODS We used the multicentric REMIND prospective cohort to identify all patients who experienced SSI after ileocolonic resection for CD, defined as any postoperative local septic complication within 90 days after surgery: wound abscess, intra-abdominal collection, anastomotic leakage or enterocutaneous fistula. The mucosa-associated microbiota of the ileal resection specimen was analysed by 16S gene sequencing in 149 patients. The variable selection and prediction were performed with random forests [R package VSURF] on clinical and microbiotal data. The criterion of performance that we considered was the area under the Receiver Operating Characteristic [ROC] curve [AUC]. RESULTS SSI occurred in 24 patients [16.1%], including 15 patients [10.1%] with major morbidity. There were no significant differences between patients with or without SSI regarding alpha and beta diversity. The top selected variables for the prediction of SSI were all microbiota-related. The maximum AUC [0.796] was obtained with a model including 14 genera, but an AUC of 0.78 had already been obtained with a model including only six genera [Hungatella, Epulopiscium, Fusobacterium, Ruminococcaceae_ucg_009, Actinomyces and Ralstonia]. CONCLUSION The gut microbiota has the potential to predict SSI after ileocolonic resection for CD. It might play a role in this frequent postoperative complication.
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Affiliation(s)
- Clément Julien
- Department of Gastrointestinal Surgery, Hôpital Nord, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille Univ., Chemin des Bourrely, 13015 Marseille, France
| | - Emré Anakok
- Sorbonne Université, UMR CNRS 8001, LPSM, 75005 Paris, France.,Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012 Paris, France
| | - Xavier Treton
- Gastroenterology Department Hôpital Beaujon, MICI et Assistance Nutritive, Clichy, France
| | - Maria Nachury
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Stéphane Nancey
- Gastroenterology Department, Lyon Sud Hospital, Hospices Civils de Lyon, and INSERM U1111, CIRI, Lyon, France
| | - Anthony Buisson
- Gastroenterology Department, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Mathurin Fumery
- Hepatogastroenterology Department, Amiens University Hospital, Amiens, France
| | - Jérôme Filippi
- Gastroenterology Department, Hopital Archet 2, Nice, France
| | - Léon Maggiori
- Digestive, Oncologic, and Endocrine Surgery Department, Hôpital Saint-Louis, AP-HP, Université de Paris, Paris, France
| | - Yves Panis
- Department of Colorectal Surgery, Beaujon Hospital and University of Paris, France
| | - Philippe Zerbib
- Digestive Surgery and Transplantation, Claude Huriez Hospital, CHRU de Lille, Lille Université Nord de France, Lille, France
| | - Yves François
- Surgery Department, Lyon Sud Hospital, Hospices Civils de Lyon , Lyon, France
| | - Anne Dubois
- Surgery Department, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Charles Sabbagh
- Surgery Department, Amiens University Hospital, Amiens, France
| | - Amine Rahili
- Surgery Department, Hopital Archet 2, Nice, France
| | - Philippe Seksik
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012 Paris, France.,Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France
| | - Matthieu Allez
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis, Paris, France
| | - Jérémie H Lefevre
- Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France.,Sorbonne Université, Department of Digestive Surgery, AP-HP, Hôpital Saint Antoine, F-75012, Paris, France
| | | | - Sylvain Le Corff
- Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France.,Samovar, Télécom SudParis, Institut Polytechnique de Paris , Paris, France
| | - Anna Bonnet
- Sorbonne Université, UMR CNRS 8001, LPSM, 75005 Paris, France.,Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France
| | - Laura Beyer-Berjot
- Department of Gastrointestinal Surgery, Hôpital Nord, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille Univ., Chemin des Bourrely, 13015 Marseille, France.,Laboratoire de biomécanique appliquée (LBA), UMR T24, Aix-Marseille Univ/Université Gustave Eiffel, Boulevard Pierre Dramard, Marseille, France.,Centre for Surgical Teaching and Research (CERC), Aix-Marseille Univ, Boulevard Pierre Dramard, Marseille, France
| | - Harry Sokol
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012 Paris, France.,Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France.,INRA, UMR1319 Micalis & AgroParisTech, Jouy en Josas, France
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27
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Everhov ÅH, Kalman TD, Söderling J, Nordenvall C, Halfvarson J, Ekbom A, Ludvigsson JF, Olén O, Myrelid P. Probability of Stoma in Incident Patients With Crohn's Disease in Sweden 2003-2019: A Population-based Study. Inflamm Bowel Dis 2022; 28:1160-1168. [PMID: 34618020 PMCID: PMC9340520 DOI: 10.1093/ibd/izab245] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND Surgery rates in patients with Crohn's disease have decreased during the last few decades, and use of antitumor necrosis agents (anti-TNF) has increased. Whether these changes correlate with a decreased probability of stoma is unknown. The objective of this study was to investigate the incidence of stoma in patients with Crohn's disease over time. METHODS Through linkage of national registers, we identified patients who were diagnosed with Crohn's disease in 2003-2014 and were followed through 2019. We compared formation and closure of stomas over the calendar periods of diagnosis (2003-2006, 2007-2010, and 2011-2014). RESULTS In a nationwide cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. This was mostly performed in conjunction with ileocolic resection (39%). The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods (P = .61). Less than half of the patients (44%) had their stoma reversed. Stomas were more common in elderly-onset compared with pediatric-onset disease: 5-year cumulative incidence 3.6% vs 1.3%. Ileostomies were most common (64%), and 24.5% of the patients who underwent stoma surgery had perianal disease at end of follow-up. Within 5 years of diagnosis, 0.8% of the incident patients had a permanent stoma, and 0.05% had undergone proctectomy. The time from diagnosis to start of anti-TNF treatment decreased over calendar periods (P < .001). CONCLUSIONS Despite increasing use of anti-TNF and a low rate of proctectomy, the cumulative incidence of stoma formation within 5 years of Crohn's disease diagnosis has not decreased from 2003 to 2019.
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Affiliation(s)
- Åsa H Everhov
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Thordis Disa Kalman
- Division of surgery, Department of Clinical and Experimental Medicine, Faulty of Health Sciences, Linköping University and Department of Surgery, County Council of Östergötland Linköping, Sweden
| | - Jonas Söderling
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Caroline Nordenvall
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Anders Ekbom
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Jonas F Ludvigsson
- Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden
- Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Ola Olén
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatric Gastroenterology and Nutrition, Sachs’ Children and Youth Hospital, Stockholm, Sweden
| | - Pär Myrelid
- Division of surgery, Department of Clinical and Experimental Medicine, Faulty of Health Sciences, Linköping University and Department of Surgery, County Council of Östergötland Linköping, Sweden
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28
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Romero RK, Magro DO, Queiroz NSF, Damião AOMC, Teixeira FV, Nones RB, Sassaki LY, Saad-Hossne R, Kotze PG. Perception and clinical decisions from inflammatory bowel diseases' specialists towards positioning of new therapies in Crohn's disease and ulcerative colitis: A national web-based survey from the Brazilian IBD study group (GEDIIB). GASTROENTEROLOGIA Y HEPATOLOGIA 2022; 45:499-506. [PMID: 34634427 DOI: 10.1016/j.gastrohep.2021.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 09/21/2021] [Accepted: 09/27/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND In the last decade, new therapies with different mechanisms of action have been approved for the treatment of moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). Due to the lack of comparative head-to-head trials, the ideal positioning of agents as the most appropriate first- or second-line therapies remains to be defined. OBJECTIVE This survey aimed to evaluate the perception and decisions of Brazilian Inflammatory Bowel Diseases (IBD) specialists in positioning of new therapies (vedolizumab [VEDO], ustekinumab [UST] and tofacitinib [TOFA]) in the management of IBD in different clinical scenarios. METHODOLOGY An anonymous national web-based questionnaire was used to determine the positioning of treatment options in different clinical scenarios (using Google Forms platform), which involved different age ranges, phenotypes, clinical situations and previous exposure to anti-TNF agents (14 scenarios for CD and 10 scenarios for UC). In CD, physicians could choose between UST or VEDO, whilst in UC, between UST, VEDO or TOFA. Six reasons for the specific choice were proposed, such as mechanism of action, safety, method of administration or onset of action. Statistical analysis was carried out with chi-square and t-tests. RESULTS A total of 150 out of 672 GEDIIB IBD specialists (22.32%) responded to the survey. In CD scenarios, UST was the most dominant choice (11/14 scenarios), with VEDO dominating only 3 clinical situations. In UC scenarios, VEDO was the dominant choice (8/10), with UST being chosen for scenarios that included extraintestinal manifestations. Among the reasons for specific choices, the most commonly chosen were the higher efficacy due to the intrinsic mechanism of action and safety profile. CONCLUSIONS UST was the dominant choice as compared to VEDO in CD in most scenarios, especially due to its mechanism of action and safety. VEDO was the dominant choice as compared to UST and TOFA in UC scenarios, mainly for reasons also related to its mechanism of action and safety profile. Comparative studies including patient outcomes are needed to better define the positioning of new IBD therapeutic options in our country.
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29
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Battat R, Sandborn WJ. Advances in the Comprehensive Management of Postoperative Crohn's Disease. Clin Gastroenterol Hepatol 2022; 20:1436-1449. [PMID: 33819666 DOI: 10.1016/j.cgh.2021.03.048] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 03/21/2021] [Accepted: 03/30/2021] [Indexed: 02/06/2023]
Abstract
Patients with postoperative Crohn's disease are difficult to manage because of their risk of experiencing a more severe course, multiple symptom confounders, and poor sensitivity of symptomatic remission to rule out intestinal inflammation. In this group, data are lacking on biologic therapeutic efficacy, and recommendations are lacking for those with multiple medication failures. Novel noninvasive testing can simultaneously exclude alternate causes of symptoms (serum C4, fecal fat, small intestinal bowel overgrowth breath testing) and assess intestinal inflammation (fecal calprotectin, endoscopic healing index). In addition, endoscopy-based disease activity assessment and management are required. Endoscopy should be performed within 6 months of surgery, and aggressive disease activity monitoring can be considered with colonoscopy every 1-2 years subsequently to ensure late recurrence is detected. Patients with multiple resections should be screened for short bowel syndrome. Predictive biomarkers are needed to guide medication selection in this high-risk population. Postoperative prophylactic biologic therapy is prudent for patients with preoperative biologic failure. However, there are no high-quality data to guide which agent should be selected. Selecting biologics with an alternative mechanism of action in those who had failed a biologic with adequate drug concentrations and selection of different agents in those with previous intolerance are reasonable. Significantly more study is required to assess the efficacy of therapies in this setting.
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Affiliation(s)
- Robert Battat
- Jill Roberts Center for IBD, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York.
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California
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30
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Banerjee R, Pal P, Hilmi I, Ghoshal UC, Desai DC, Rahman MM, Dutta U, Mohiuddin SA, Al Mohannadi M, Philip M, Ramesh GN, Niriella MA, De Silva AP, de Silva HJ, Pisespongsa P, Limsrivilai J, Aniwan S, Nawarathne M, Fernandopulle N, Aye TT, Ni N, Al Awadhi S, Joshi N, Ngoc PTV, Kieu TV, Nguyen AD, Abdullah M, Ali E, Zeid A, Sollano JD, Saberi B, Omar M, Mohsin MN, Aftab H, Wai TM, Shastri YM, Chaudhuri S, Ahmed F, Bhatia SJ, Travis SPL. Emerging inflammatory bowel disease demographics, phenotype, and treatment in South Asia, South-East Asia, and Middle East: Preliminary findings from the Inflammatory Bowel Disease-Emerging Nations' Consortium. J Gastroenterol Hepatol 2022; 37:1004-1015. [PMID: 35178742 DOI: 10.1111/jgh.15801] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 01/04/2022] [Accepted: 01/23/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. METHODS We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. RESULTS Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. CONCLUSIONS The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.
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Affiliation(s)
- Rupa Banerjee
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Partha Pal
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Ida Hilmi
- University of Malaya Medical Centre, Kuala Lumpur, Malaysia
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Devendra C Desai
- Department of Gastroenterology, P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
| | | | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Syed A Mohiuddin
- Division of Gastroenterology, Department of Medicine, Hamad General Hospital, Doha, Qatar
| | - Munnera Al Mohannadi
- Division of Gastroenterology, Department of Medicine, Hamad General Hospital, Doha, Qatar
| | - Mathew Philip
- Lisie Institute of Gastroenterology, Lisie Hospital, Kochi, India
| | | | - Madunil A Niriella
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka
| | - Arjuna P De Silva
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka
| | | | | | - Julajak Limsrivilai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | | | | | | | - Than Than Aye
- Department of Gastroenterology, Thingangyun General Hospital, University of Medicine 2, Yangon, Myanmar
| | - Nwe Ni
- Department of Gastroenterology, Mandalay General Hospital and University of Medicine, Mandalay, Myanmar
| | - Sameer Al Awadhi
- Digestive Disease Unit, Rashid Hospital, Dubai, United Arab Emirates
| | | | | | | | | | - Murdani Abdullah
- Department of Internal Medicine, Cipto Mangunkusumo National Hospital, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Ezzat Ali
- Department of Internal Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Ahmed Zeid
- Department of Internal Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Jose D Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | | | | | - Mostafa Noor Mohsin
- Department of Gastroenterology, Chittagong Medical College, Chittagong, Bangladesh
| | - Hafeza Aftab
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh
| | - Tin Moe Wai
- Department of Gastroenterology, Yangon General Hospital, University of Medicine (1), Yangon, Myanmar
| | - Yogesh M Shastri
- Department of Gastroenterology, NMC Specialty Hospital, Abu Dhabi, United Arab Emirates
| | | | - Faruque Ahmed
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh
| | | | - Simon P L Travis
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
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31
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Wu X, Zhang Y, Zhang W, Liu G, Huang H, Jiang H, Zhang X. The Prevalence and Associated Risk Factors of Erectile Dysfunction in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Sex Med 2022; 19:950-960. [PMID: 35491378 DOI: 10.1016/j.jsxm.2022.03.615] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 03/19/2022] [Accepted: 03/27/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Erectile dysfunction (ED) may be common in patients with inflammatory bowel disease (IBD), but its prevalence and risk factors still remain debatable. AIM To evaluate the prevalence of ED in the IBD population and the potential role of risk factors in the development of ED. METHODS An extensive search in the PubMed, Cochrane Library, and Web of Science was performed to identify relevant English-language articles published up to December 2021 that evaluated the prevalence of ED on IBD patients. The included studies were evaluated by 2 independent reviewers for eligibility. We used an adapted Assessment Tool for Prevalence Studies to evaluate the quality of enrolled studies. Data were analyzed and graphed using the STATA software (version 16.0; Stata Corporation, College Station, TX, USA). The ORs with 95% CIs were pooled using a fixed or random-effects model according to heterogeneity. Subgroup analysis was performed to explore the source of heterogeneity. Sensitivity analysis was conducted to evaluate the stability of the results. OUTCOMES The pooled prevalence of ED in IBD patients was calculated, and the OR value and 95% CIs were used to assess the strength of the association between IBD-related risk factors and ED. RESULTS Fourteen studies included 32,858 individuals totally were enrolled for this meta-analysis. The overall pooled prevalence estimate of ED in IBD patients was 27% (95% CI: 20-34%). Operation (OR 1.28; 95% CI: 1.17-1.39; P < .00001; I2 = 0.0%), disease activity (OR 2.06; 95% CI: 1.07-3.05; P < .00001), and depression (crude OR 3.31; 95% CI: 1.08-5.54; P = .004; I2 = 0.0%) significantly increase the risk of ED in people with IBD. The association of depression and ED was further confirmed by calculating the pooled estimates of adjusted OR (1.58; 95% CI: 0.05-3.12; P < .05; I2 = 0.0%). The pooled prevalence estimates of ED were 30, 33, and 17% in the age <40, IIEF diagnostic tool, and IPAA surgery subgroups, respectively. CLINICAL IMPLICATIONS IBD patients had a significantly increased prevalence of ED, indicating that erectile function in men with IBD should be concerned by clinicians. STRENGTHS & LIMITATIONS The strength of this study is that this is the first meta-analysis to assess the global prevalence and risk factors of ED in IBD patients. A limitation is that the results after pooling the included articles showed significant heterogeneity. CONCLUSION The results of our meta-analysis and systematic review provide evidence of the high prevalence and risk factors of ED in IBD patients. Wu X, Zhang Y, Zhang W, et al. The Prevalence and Associated Risk Factors of Erectile Dysfunction in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Sex Med 2022;19:950-960.
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Affiliation(s)
- Xu Wu
- The Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yuyang Zhang
- The Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wei Zhang
- The Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Guodong Liu
- The Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Houbao Huang
- Department of Urology, The First Affiliated hospital of Wannan Medical College, Anhui Province, China.
| | - Hui Jiang
- The Department of Urology, Peking University Third Hospital, Beijing, China.
| | - Xiansheng Zhang
- The Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
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Chiarello MM, Pepe G, Fico V, Bianchi V, Tropeano G, Altieri G, Brisinda G. Therapeutic strategies in Crohn's disease in an emergency surgical setting. World J Gastroenterol 2022; 28:1902-1921. [PMID: 35664965 PMCID: PMC9150057 DOI: 10.3748/wjg.v28.i18.1902] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 02/28/2022] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Crohn's disease (CD) remains a chronic, incurable disorder that presents unique challenges to the surgeon. Multiple factors must be considered to allow development of an appropriate treatment plan. Medical therapy often precedes or complements the surgical management. The indications for operative management of CD include acute and chronic disease complications and failed medical therapy. Elective surgery comes into play when patients are refractory to medical treatment if they have an obstructive phenotype. Toxic colitis, acute obstruction, perforation, acute abscess, or massive hemorrhage represent indications for emergency surgery. These patients are generally in critical conditions and present with intra-abdominal sepsis and a preoperative status of immunosuppression and malnutrition that exposes them to a higher risk of complications and mortality. A multidisciplinary team including surgeons, gastroenterologists, radiologists, nutritional support services, and enterostomal therapists are required for optimal patient care and decision making. Management of each emergency should be individualized based on patient age, disease type and duration, and patient goals of care. Moreover, the recurrent nature of disease mandates that we continue searching for innovative medical therapies and operative techniques that reduce the need to repeat surgical operations. In this review, we aimed to discuss the acute complications of CD and their treatment.
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Affiliation(s)
- Maria Michela Chiarello
- Department of Surgery, San Giovanni in Fiore Hospital, Azienda Sanitaria Provinciale di Cosenza, Cosenza 87100, Italy
| | - Gilda Pepe
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Valeria Fico
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Valentina Bianchi
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Giuseppe Tropeano
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Gaia Altieri
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Giuseppe Brisinda
- Department of Surgery, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Medical and Surgical Science, Università Cattolica del Sacro Cuore, Rome 00168, Italy
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Estrada HQ, Patel S, Rabizadeh S, Casero D, Targan SR, Barrett RJ. Development of a Personalized Intestinal Fibrosis Model Using Human Intestinal Organoids Derived From Induced Pluripotent Stem Cells. Inflamm Bowel Dis 2022; 28:667-679. [PMID: 34918082 PMCID: PMC9074870 DOI: 10.1093/ibd/izab292] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Intestinal fibrosis is a serious complication of Crohn's disease. Numerous cell types including intestinal epithelial and mesenchymal cells are implicated in this process, yet studies are hampered by the lack of personalized in vitro models. Human intestinal organoids (HIOs) derived from induced pluripotent stem cells (iPSCs) contain these cell types, and our goal was to determine the feasibility of utilizing these to develop a personalized intestinal fibrosis model. METHODS iPSCs from 2 control individuals and 2 very early onset inflammatory bowel disease patients with stricturing complications were obtained and directed to form HIOs. Purified populations of epithelial and mesenchymal cells were derived from HIOs, and both types were treated with the profibrogenic cytokine transforming growth factor β (TGFβ). Quantitative polymerase chain reaction and RNA sequencing analysis were used to assay their responses. RESULTS In iPSC-derived mesenchymal cells, there was a significant increase in the expression of profibrotic genes (Col1a1, Col5a1, and TIMP1) in response to TGFβ. RNA sequencing analysis identified further profibrotic genes and demonstrated differential responses to this cytokine in each of the 4 lines. Increases in profibrotic gene expression (Col1a1, FN, TIMP1) along with genes associated with epithelial-mesenchymal transition (vimentin and N-cadherin) were observed in TGFβ -treated epithelial cells. CONCLUSIONS We demonstrate the feasibility of utilizing iPSC-HIO technology to model intestinal fibrotic responses in vitro. This now permits the generation of near unlimited quantities of patient-specific cells that could be used to reveal cell- and environmental-specific mechanisms underpinning intestinal fibrosis.
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Affiliation(s)
- Hannah Q Estrada
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Shachi Patel
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Shervin Rabizadeh
- Division of Pediatric Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USAand
| | - David Casero
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Stephan R Targan
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Robert J Barrett
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Lamb CA, Saifuddin A, Powell N, Rieder F. The Future of Precision Medicine to Predict Outcomes and Control Tissue Remodeling in Inflammatory Bowel Disease. Gastroenterology 2022; 162:1525-1542. [PMID: 34995532 PMCID: PMC8983496 DOI: 10.1053/j.gastro.2021.09.077] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/20/2021] [Accepted: 09/23/2021] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease is characterized by significant interindividual heterogeneity. With a wider selection of pharmacologic and nonpharmacologic interventions available and in advanced developmental stages, a priority for the coming decade is to determine accurate methods of predicting treatment response and disease course. Precision medicine strategies will allow tailoring of preventative and therapeutic decisions to individual patient needs. In this review, we consider the future of precision medicine in inflammatory bowel disease. We discuss the critical need to extend from research focused on short-term symptomatic response to integrative multi-omic systems biology strategies to identify and validate biomarkers that underpin precision approaches. Crucially, the international community has collective responsibility to provide well-phenotyped and -curated longitudinal datasets for scientific discovery and validation. Research must also study broader aspects of the immune response, including components of the extracellular matrix, to better understand biological pathways initiating and perpetuating tissue fibrosis and longer-term disease complications.
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Affiliation(s)
- Christopher A Lamb
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Department of Gastroenterology, Newcastle upon Tyne Hospitals National Health Service Foundation Trust, Newcastle upon Tyne, United Kingdom.
| | - Aamir Saifuddin
- St Mark's Academic Institute, London North West University Hospitals National Health Service Trust, London, United Kingdom; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| | - Nick Powell
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| | - Florian Rieder
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio
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Rossi F, Amadoro C, Gasperi M, Colavita G. Lactobacilli Infection Case Reports in the Last Three Years and Safety Implications. Nutrients 2022; 14:nu14061178. [PMID: 35334835 PMCID: PMC8954171 DOI: 10.3390/nu14061178] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/09/2022] [Accepted: 03/09/2022] [Indexed: 12/27/2022] Open
Abstract
Lactobacilli constitute the dominant microbiota in many fermented foods and comprise widely used probiotics. However, these bacteria cause rare infections mostly in diabetic and immunocompromised subjects in presence of risk factors such as prosthetic hearth valves and dental procedures or caries. The scope of this survey was re-assessing the pathogenic potential of lactobacilli based on the infection case reports published in the last three years. In 2019, 2020, and 2021, total of 17, 15, and 16 cases, respectively, including endocarditis, bacteremia, and other infections, were reported. These annual numbers are higher than those observed previously. Lacticaseibacillus rhamnosus (13 cases), comprising strain GG (ATCC 53103) with established applications in healthcare, L. paracasei (7 cases), Lactobacillus acidophilus (5 cases), L. jensenii (5 cases), Lactiplantibacillus plantarum (3 cases), L. paraplantarum, L. delbrueckii subsp. delbrueckii, L. gasseri, L. paragasseri, Limosilactobacillus fermentum, and L. reuteri (1 case each) were involved. Virulence characterization of two strains that caused infections, a derivative of L. rhamnosus GG and L. paracasei LP10266, indicated that increased biofilm-forming capacity favors pathogenicity and it is determined by variable genetic traits. This survey highlights that the strains of lactobacilli that cause infections are little characterized genetically. Instead, to avoid that these bacteria become a hazard, genetic stability should be periodically re-evaluated by whole genome sequencing (WGS) to ensure that only non-pathogenic variants are administered to vulnerable individuals.
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Affiliation(s)
- Franca Rossi
- Diagnostica Specialistica, Sezione di Campobasso, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “G. Caporale”, Via Garibaldi 155, 86100 Campobasso, Italy
- Correspondence:
| | - Carmela Amadoro
- Medicine and Health Science Department “V. Tiberio”, University of Molise, Via de Santis, 86100 Campobasso, Italy; (C.A.); (M.G.); (G.C.)
| | - Maurizio Gasperi
- Medicine and Health Science Department “V. Tiberio”, University of Molise, Via de Santis, 86100 Campobasso, Italy; (C.A.); (M.G.); (G.C.)
| | - Giampaolo Colavita
- Medicine and Health Science Department “V. Tiberio”, University of Molise, Via de Santis, 86100 Campobasso, Italy; (C.A.); (M.G.); (G.C.)
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D'Alessio S, Ungaro F, Noviello D, Lovisa S, Peyrin-Biroulet L, Danese S. Revisiting fibrosis in inflammatory bowel disease: the gut thickens. Nat Rev Gastroenterol Hepatol 2022; 19:169-184. [PMID: 34876680 DOI: 10.1038/s41575-021-00543-0] [Citation(s) in RCA: 109] [Impact Index Per Article: 36.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/27/2021] [Indexed: 12/11/2022]
Abstract
Intestinal fibrosis, which is usually the consequence of chronic inflammation, is a common complication of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. In the past few years, substantial advances have been made in the areas of pathogenesis, diagnosis and management of intestinal fibrosis. Of particular interest have been inflammation-independent mechanisms behind the gut fibrotic process, genetic and environmental risk factors (such as the role of the microbiota), and the generation of new in vitro and in vivo systems to study fibrogenesis in the gut. A huge amount of work has also been done in the area of biomarkers to predict or detect intestinal fibrosis, including novel cross-sectional imaging techniques. In parallel, researchers are embarking on developing and validating clinical trial end points and protocols to test novel antifibrotic agents, although no antifibrotic therapies are currently available. This Review presents the state of the art on the most recently identified pathogenic mechanisms of this serious IBD-related complication, focusing on possible targets of antifibrotic therapies, management strategies, and factors that might predict fibrosis progression or response to treatment.
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Affiliation(s)
| | - Federica Ungaro
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Daniele Noviello
- Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Sara Lovisa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,IBD Centre, Laboratory of Gastrointestinal Immunopathology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Laurent Peyrin-Biroulet
- INSERM NGERE, University of Lorraine, Vandoeuvre-les-Nancy, Nancy, France.,Nancy University Hospital, Vandoeuvre-les-Nancy, Nancy, France
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy. .,University Vita-Salute San Raffaele, Milan, Italy.
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Watanabe D, Kamada N. Contribution of the Gut Microbiota to Intestinal Fibrosis in Crohn's Disease. Front Med (Lausanne) 2022; 9:826240. [PMID: 35198577 PMCID: PMC8859331 DOI: 10.3389/fmed.2022.826240] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 01/13/2022] [Indexed: 12/16/2022] Open
Abstract
In Crohn's disease (CD), intestinal fibrosis is a critical determinant of a patient's prognosis. Although inflammation may be a prerequisite for the initiation of intestinal fibrosis, research shows that the progression or continuation of intestinal fibrosis can occur independently of inflammation. Thus, once initiated, intestinal fibrosis may persist even if medical treatment controls inflammation. Clearly, an understanding of the pathophysiological mechanisms of intestinal fibrosis is required to diminish its occurrence. Accumulating evidence suggests that the gut microbiota contributes to the pathogenesis of intestinal fibrosis. For example, the presence of antibodies against gut microbes can predict which CD patients will have intestinal complications. In addition, microbial ligands can activate intestinal fibroblasts, thereby inducing the production of extracellular matrix. Moreover, in various animal models, bacterial infection can lead to the development of intestinal fibrosis. In this review, we summarize the current knowledge of the link between intestinal fibrosis in CD and the gut microbiota. We highlight basic science and clinical evidence that the gut microbiota can be causative for intestinal fibrosis in CD and provide valuable information about the animal models used to investigate intestinal fibrosis.
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Affiliation(s)
- Daisuke Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Nobuhiko Kamada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
- WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
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Huang M, Jiang W, Luo C, Yang M, Ren Y. Atractylenolide III inhibits epithelial‑mesenchymal transition in small intestine epithelial cells by activating the AMPK signaling pathway. Mol Med Rep 2022; 25:98. [PMID: 35088892 PMCID: PMC8809054 DOI: 10.3892/mmr.2022.12614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 09/17/2021] [Indexed: 11/28/2022] Open
Abstract
Compared with the available drugs for the treatment of fibrosis in other organs, the development of intestinal anti-fibrosis drugs is limited. Therefore, it is of practical significance to examine novel drugs to delay or block the development of intestinal fibrosis. The present study aimed to investigate the effect of atractylenolide III (ATL-III) on intestinal fibrosis. An MTT assay was used to detect the effect of ATL-III on the activity of IEC-6 cells. The migration and invasion of fibrotic cells stimulated with TGF-β were determined via wound healing and Transwell assays. An immunofluorescence assay and western blotting were conducted to assess the expression levels of protein associated with epithelial-mesenchymal transition (EMT). The role of the AMP-activated protein kinase (AMPK) pathway was verified using compound C (an AMPK inhibitor) treatment. The results of the present study indicated that ATL-III had no effect on the cells at a dose of 1–20 µmol/l. Moreover, ATL-III can inhibit the invasion and migration of cells induced by TGF-β1, as well as block the EMT process. It was found that ATL-III could also activate the AMPK pathway. Furthermore, compound C reduced the inhibitory effect of ATL-III on stimulated cells, which indicated that the AMPK pathway plays a role in the inhibition process. In conclusion, ATL-III may inhibit the EMT of IEC-6 cells stimulated with TGF-β1 by activating the AMPK signaling pathway.
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Affiliation(s)
- Mingjin Huang
- College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, P.R. China
| | - Wenwen Jiang
- College of Pharmaceutical Science, Guizhou University, Guiyang, Guizhou 550025, P.R. China
| | - Chunli Luo
- College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, P.R. China
| | - Min Yang
- College of Pharmaceutical Science, Guizhou University, Guiyang, Guizhou 550025, P.R. China
| | - Yan Ren
- College of Pharmaceutical Science, Guizhou University, Guiyang, Guizhou 550025, P.R. China
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Guo X, Huang C, Xu J, Xu H, Liu L, Zhao H, Wang J, Huang W, Peng W, Chen Y, Nie Y, Zhou Y, Zhou Y. Gut Microbiota Is a Potential Biomarker in Inflammatory Bowel Disease. Front Nutr 2022; 8:818902. [PMID: 35127797 PMCID: PMC8814525 DOI: 10.3389/fnut.2021.818902] [Citation(s) in RCA: 71] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 12/29/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is characterized by relapse and remission alternately. It remains a great challenge to diagnose and assess disease activity during IBD due to the lack of specific markers. While traditional biomarkers from plasma and stool, such as C-reactive protein (CRP), fecal calprotectin (FC), and S100A12, can be used to measure inflammation, they are not specific to IBD and difficult to determine an effective cut-off value. There is consensus that gut microbiota is crucial for intestinal dysbiosis is closely associated with IBD etiopathology and pathogenesis. Multiple studies have documented differences in the composition of gut microbiota between patients with IBD and healthy individuals, particularly regarding microbial diversity and relative abundance of specific bacteria. Patients with IBD have higher levels of Proteobacteria and lower amounts of Bacteroides, Eubacterium, and Faecalibacterium than healthy individuals. This review summarizes the pros and cons of using traditional and microbiota biomarkers to assess disease severity and treatment outcomes and addresses the possibility of using microbiota-focused interventions during IBD treatment. Understanding the role of microbial biomarkers in the assessment of disease activity and treatment outcomes has the potential to change clinical practice and lead to the development of more personalized therapies.
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Affiliation(s)
- Xue Guo
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Chen Huang
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Jing Xu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Haoming Xu
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Le Liu
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Hailan Zhao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Jiaqi Wang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Wenqi Huang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Wu Peng
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Ye Chen
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Yuqiang Nie
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yongjian Zhou
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Youlian Zhou
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
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Bushara O, Escobar DJ, Weinberg SE, Sun L, Liao J, Yang GY. The Possible Pathogenic Role of IgG4-Producing Plasmablasts in Stricturing Crohn's Disease. Pathobiology 2022; 89:187-197. [PMID: 35026755 DOI: 10.1159/000521259] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 11/26/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Crohn's disease (CD) is a condition on the spectrum of inflammatory bowel disease that affects up to 20 people per 100,000 in the US annually, and with incidence increasing. One of the most significant sources of morbidity in CD is the formation of strictures, with resultant intestinal blockage a common indication for hospitalization and surgical intervention in these patients. The pathophysiology of stricture formation is not fully understood. However, the fibroplasia that leads to fibrostenotic stricture formation may have shared pathophysiology with IgG4-related fibrosis. SUMMARY Initial intestinal inflammation recruits innate immune cells, such as neutrophils, that secrete IL-1β and IL-23, which induces a type 17 CD4+ T-helper T-cell (Th17)-mediated adaptive immune response. These CD4+ Th17 T cells also contribute to inflammation by secreting proinflammatory cytokines such as IL-17 and IL-21. IL-21 recruits and stimulates CD4+ T follicular helper (Tfh) cells, which secrete more IL-21. This causes ectopic germinal center formation, recruiting and stimulating naïve B cells. The IL-17 and IL-21 produced by Th17 cells and Tfh cells also induce IgG4 plasmablast differentiation. Finally, these IgG4-producing plasmablasts secrete platelet-derived growth factor (PDGF), which activates local PDGF-receptor expressing fibroblasts and myofibroblasts, resulting in uncontrolled fibroplasia.
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Affiliation(s)
- Omar Bushara
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - David Joseph Escobar
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Samuel Edward Weinberg
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Leyu Sun
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jie Liao
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Guang-Yu Yang
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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O'Moráin N, Doherty J, Stack R, Doherty GA. Mucosal Healing in Crohn's Disease: Bull's Eye or Bust? "The Pro Position". Inflamm Intest Dis 2022; 7:36-41. [PMID: 35224016 PMCID: PMC8820165 DOI: 10.1159/000519521] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 09/06/2021] [Indexed: 10/10/2023] Open
Abstract
BACKGROUND Crohn's disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications. SUMMARY Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge. KEY MESSAGES Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention.
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Affiliation(s)
| | - Jayne Doherty
- Centre for Colorectal Disease, St. Vincent's University Hospital & School of Medicine, University College Dublin, Dublin, Ireland
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Dehghan M, Wong G, Neuberger E, Kin C, Rieder F, Park KT. Worse outcomes and higher costs of care in fibrostenotic Crohn's disease: a real-world propensity-matched analysis in the USA. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000781. [PMID: 34930755 PMCID: PMC8689124 DOI: 10.1136/bmjgast-2021-000781] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 11/16/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with Crohn's disease (CD) may develop fibrostenotic strictures. No currently available therapies prevent or treat fibrostenotic CD (FCD), making this a critical unmet need. AIM To compare health outcomes and resource utilisation between CD patients with and without fibrostenotic disease. METHODS Patients aged ≥18 years with FCD and non-FCD between 30 October 2015 and 30 September 2018 were identified in the Truven MarketScan Commercial Claims and Encounters Database. We conducted 1:3 nearest neighbour propensity score matching on age, sex, malnutrition, payer type, anti-tumour necrosis factor use, and Charlson Comorbidity Index score. Primary outcomes up to 1 year from the index claim were ≥1 hospitalisation, ≥1 procedure, ≥1 surgery, and steroid dependency (>100 day supply). Associations between FCD diagnosis and outcomes were estimated with a multivariable logistic regression model. This study was exempt from institutional review board approval. RESULTS Propensity score matching yielded 11 022 patients. Compared with non-FCD, patients with FCD had increased likelihood of hospitalisations (17.1% vs 52.4%; p<0.001), endoscopic procedures (4.4% vs 8.6%; p<0.001), IBD-related surgeries (4.7% vs 9.1%; p<0.001), steroid dependency (10.0% vs 15.7%; p<0.001), and greater mean annual costs per patient ($47 575 vs $77 609; p<0.001). FCD was a significant risk factor for ≥1 hospitalisation (adjusted OR (aOR), 6.1), ≥1 procedure (aOR, 2.1), ≥1 surgery (aOR, 2.0), and steroid dependency (aOR, 1.7). CONCLUSIONS FCD was associated with higher risk for hospitalisation, procedures, abdominal surgery, and steroid dependency. Patients with FCD had a greater mean annual cost per patient. FCD represents an ongoing unmet medical need.
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Affiliation(s)
| | - Gabriel Wong
- Genentech Inc, South San Francisco, California, USA
| | | | - Cindy Kin
- Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Florian Rieder
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - K T Park
- Genentech Inc, South San Francisco, California, USA
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Tieranu C, Olteanu A, Preda C, Bacalbasa N, Milanesi E, Dobre M, Tieranu I, Manuc T, Klimko A, Becheanu G, Ionescu E. Mucosal gene expression profile of stricturing Crohn's disease: A preliminary study. Exp Ther Med 2021; 23:149. [DOI: 10.3892/etm.2021.11072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 10/21/2021] [Indexed: 11/06/2022] Open
Affiliation(s)
- Cristian Tieranu
- Department of Gastroenterology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Andrei Olteanu
- Department of Gastroenterology, ‘Elias’ Emergency University Hospital, 011461 Bucharest, Romania
| | - Carmen Preda
- Department of Gastroenterology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Nicolae Bacalbasa
- Department of Gastroenterology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Elena Milanesi
- Department of Radiobiology, ‘Victor Babeş’ National Institute of Pathology, 050096 Bucharest, Romania
| | - Maria Dobre
- Department of Pathology, ‘Victor Babeş’ National Institute of Pathology, 050096 Bucharest, Romania
| | - Ioana Tieranu
- Department of Gastroenterology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Teodora Manuc
- Department of Gastroenterology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Artsiom Klimko
- Department of Gastroenterology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Gabriel Becheanu
- Department of Gastroenterology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Elena Ionescu
- Department of Gastroenterology, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
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Lin SN, Mao R, Qian C, Bettenworth D, Wang J, Li J, Bruining D, Jairath V, Feagan B, Chen M, Rieder F. Development of Anti-fibrotic Therapy in Stricturing Crohn's Disease: Lessons from Randomized Trials in Other Fibrotic Diseases. Physiol Rev 2021; 102:605-652. [PMID: 34569264 DOI: 10.1152/physrev.00005.2021] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Intestinal fibrosis is considered an inevitable complication of Crohn's disease (CD) that results in symptoms of obstruction and stricture formation. Endoscopic or surgical treatment is required to treat the majority of patients. Progress in the management of stricturing CD is hampered by the lack of effective anti-fibrotic therapy; however, this situation is likely to change because of recent advances in other fibrotic diseases of the lung, liver and skin. In this review, we summarized data from randomized controlled trials (RCT) of anti-fibrotic therapies in these conditions. Multiple compounds have been tested for the anti-fibrotic effects in other organs. According to their mechanisms, they were categorized into growth factor modulators, inflammation modulators, 5-hydroxy-3-methylgultaryl-coenzyme A (HMG-CoA) reductase inhibitors, intracellular enzymes and kinases, renin-angiotensin system (RAS) modulators and others. From our review of the results from the clinical trials and discussion of their implications in the gastrointestinal tract, we have identified several molecular candidates that could serve as potential therapies for intestinal fibrosis in CD.
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Affiliation(s)
- Si-Nan Lin
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States.,Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, United States
| | - Ren Mao
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States.,Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, United States
| | - Chenchen Qian
- Department of Internal Medicine, UPMC Pinnacle, Harrisburg, Pennsylvania, United States
| | - Dominik Bettenworth
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Jie Wang
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States.,Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, United States.,Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, Henan Province, China
| | - Jiannan Li
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States.,Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, United States
| | - David Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States
| | - Vipul Jairath
- Alimentiv Inc., London, ON, Canada.,Department of Medicine, Western University, London, ON, Canada.,Department of Biostatistics and Epidemiology, Western University, London, ON, Canada
| | - Brian Feagan
- Alimentiv Inc., London, ON, Canada.,Department of Medicine, Western University, London, ON, Canada.,Department of Biostatistics and Epidemiology, Western University, London, ON, Canada
| | - Minhu Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | | | - Florian Rieder
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States.,Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, United States
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45
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Prevalence and risk factors of sexual dysfunction in patients with inflammatory bowel disease: systematic review and meta-analysis. Int J Colorectal Dis 2021; 36:2027-2038. [PMID: 34050786 DOI: 10.1007/s00384-021-03958-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/20/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE Sexual dysfunction (SD) is increasingly identified in patients with inflammatory bowel disease (IBD), but there are few systematic reviews and meta-analyses of the studies of SD in IBD patients. The purpose of the study is to further quantify the association between IBD and SD. METHODS MEDLINE (OVID), EMBASE (OVID), and the Cochrane Library (OVID) were searched (until August 2020) to identify observational studies that reported the prevalence and risk factors of SD in IBD patients. Pooled prevalence, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. RESULTS Of the 945 citations evaluated, 18 studies (including 36,676 subjects) reporting the prevalence of SD in the IBD population were included for analysis. The overall pooled prevalence was 39% (95% CI 37-40%, P < 0.001). The prevalence of SD in women was 53% (95% CI 50-55%, P < 0.001), and it was 27% (95% CI 25-29%, P < 0.001) in men. The prevalence was higher in conjunction with operation (OR, 1.33, 95% CI 1.22-1.45, P < 0.001), depression (OR 6.14, 95% CI 3.51-10.76, P < 0.001), disease activity (OR 2.73, 95% CI 1.32-5.64, P = 0.007), comorbidities (OR 3.21, 95% CI 2.06-5.00, P < 0.001), age < 50 years (OR 3.85, 95% CI 2.41-6.14, P < 0.001), and the need for corticosteroids (OR 2.62, 95% CI 1.48-4.66, P = 0.001). CONCLUSION SD occurred frequently in the IBD population. Operation, depression, disease activity, comorbidities, age < 50 years, and the need for corticosteroids were risk factors for SD in IBD patients. SD screening might be recommended in IBD patients with the aforementioned factors.
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Pulakazhi Venu VK, Alston L, Iftinca M, Tsai YC, Stephens M, Warriyar K V V, Rehal S, Hudson G, Szczepanski H, von der Weid PY, Altier C, Hirota SA. Nr4A1 modulates inflammation-associated intestinal fibrosis and dampens fibrogenic signaling in myofibroblasts. Am J Physiol Gastrointest Liver Physiol 2021; 321:G280-G297. [PMID: 34288735 DOI: 10.1152/ajpgi.00338.2019] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Intestinal fibrosis is a common complication of the inflammatory bowel diseases (IBDs), contributing to tissue stiffening and luminal narrowing. Human nuclear receptor 4A 1 (NR4A1) was previously reported to regulate mesenchymal cell function and dampen fibrogenic signaling. NR4A1 gene variants are associated with IBD risk, and it has been shown to regulate intestinal inflammation. Here, we tested the hypothesis that NR4A1 acts as a negative regulator of intestinal fibrosis through regulating myofibroblast function. Using the SAMP1/YitFc mouse, we tested whether two pharmacological agents known to enhance NR4A1 signaling, cytosporone B (Csn-B) or 6-mercaptopurine (6-MP), could reduce fibrosis. We also used the dextran sulfate sodium (DSS) model of colitis and assessed the magnitude of colonic fibrosis in mouse nuclear receptor 4A 1 (Nr4a1-/-) and their wild-type littermates (Nr4a1+/+). Lastly, intestinal myofibroblasts isolated from Nr4a1-/- and Nr4a1+/+ mice or primary human intestinal myofibroblasts were stimulated with transforming growth factor-β1 (TGF-β1), in the presence or absence of Csn-B or 6-MP, and proliferation and ECM gene expression assessed. Csn-B or 6-MP treatment significantly reduced ileal thickness, collagen, and overall ECM content in SAMP1/YitFc mice. This was associated with a reduction in proliferative markers within the mesenchymal compartment. Nr4a1-/- mice exposed to DSS exhibited increased colonic thickening and ECM content. Nr4a1-/- myofibroblasts displayed enhanced TGF-β1-induced proliferation. Furthermore, Csn-B or 6-MP treatment was antiproliferative in Nr4a1+/+ but not Nr4a1-/- cells. Lastly, activating NR4A1 in human myofibroblasts reduced TGF-β1-induced collagen deposition and fibrosis-related gene expression. Our data suggest that NR4A1 can attenuate fibrotic processes in intestinal myofibroblasts and could provide a valuable clinical target to treat inflammation-associated intestinal fibrosis.NEW & NOTEWORTHY Fibrosis and increased muscle thickening contribute to stricture formation and intestinal obstruction, a complication that occurs in 30%-50% of patients with CD within 10 yr of disease onset. More than 50% of those who undergo surgery to remove the obstructed bowel will experience stricture recurrence. To date, there are no drug-based approaches approved to treat intestinal strictures. In the current submission, we identify NR4A1 as a novel target to treat inflammation-associated intestinal fibrosis.
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Affiliation(s)
- Vivek Krishna Pulakazhi Venu
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, Canada
| | - Laurie Alston
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, Canada
| | - Mircea Iftinca
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, Canada
| | - Yi-Cheng Tsai
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, Canada
| | - Matthew Stephens
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, Canada
| | - Vineetha Warriyar K V
- Faculty of Kinesiology, Sport Injury Prevention Research Centre, University of Calgary, Calgary, Alberta, Canada
| | - Sonia Rehal
- Department of Advanced Diagnostics, University Health Network, Toronto, Ontario, Canada
| | - Grace Hudson
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, Canada
| | - Holly Szczepanski
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, Canada
| | - Pierre-Yves von der Weid
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, Canada
| | - Christophe Altier
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, Canada.,Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Simon A Hirota
- Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.,Department of Immunology, Microbiology & Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.,Snyder Institute for Chronic Disease, University of Calgary, Calgary, Alberta, Canada.,Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
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Abstract
Mouse models are essential for investigation of underlying disease mechanisms that drive intestinal fibrosis, as well as assessment of potential therapeutic approaches to either prevent or resolve fibrosis. Here we describe several common mouse models of intestinal inflammation and fibrosis, including chemically driven colitis models, a bacterially triggered colitis model, and spontaneous intestinal inflammation in genetically susceptible mouse strains. Detailed protocols are provided for dextran sodium sulfate (DSS) colitis, 2,4,6-trinitro-benzene sulfonic acid (TNBS) colitis, adherent-invasive Escherichia coli (AIEC)-triggered colitis, the interleukin-10 knockout (IL-10KO) mouse model of spontaneous colitis, and the SAMP/YitFc model of spontaneous ileocolitis.
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48
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Ford MM. Crohn's Disease Obstructions. Clin Colon Rectal Surg 2021; 34:227-232. [PMID: 34305471 DOI: 10.1055/s-0041-1729926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Obstruction from stricturing Crohn's disease remains one of the most common reasons for intervention. Acute inflammation is often responsive to medications, but chronic fibrosis is unlikely to respond and will generally go on to require additional treatment. Newer methods, such as endoscopic balloon dilation, are gaining grounds in strictures that are amenable, but with high recurrence and strictures that may not be endoscopically accessible, surgery still plays a key role in the treatment of obstructing Crohn's disease.
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Affiliation(s)
- Molly M Ford
- Department of General Surgery, Colon & Rectal Surgery, Nashville, Tennessee
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49
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Navaratne L, Hurndall KH, Richardson DM, Stephenson R, Power N, Gillott H, Ruiz Sánchez S, Khodatars K, Chan CLH. Risk factors for symptomatic anastomotic postoperative recurrence following ileo-colic resection in Crohn's disease. Colorectal Dis 2021; 23:1184-1192. [PMID: 33448576 DOI: 10.1111/codi.15530] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 12/08/2020] [Accepted: 01/07/2021] [Indexed: 02/08/2023]
Abstract
AIM Crohn's disease is a chronic inflammatory bowel disease characterized by alternating periods of exacerbation and remission. Surgical resection is not curative and postoperative recurrence (POR) remains a challenge in these patients. The aim of this study was to identify clinical variables that influence the risk of symptomatic anastomotic POR in patients with ileo-colonic Crohn's disease. METHOD A retrospective study of Crohn's disease patients who had undergone ileo-colic resection between January 2014 and December 2018 was performed. For each patient, data including demographic information, Crohn's disease clinical setting, preoperative radiological data, operative and histological data, pre- and postoperative medication history and postoperative clinical course, including recurrence of disease, were extracted. Symptomatic anastomotic POR was defined as symptoms of Crohn's disease in the presence of confirmed anastomotic POR (endoscopic and/or radiological POR). RESULTS For the study period, 104 patients were eligible and included for analysis. The cumulative probability of symptomatic anastomotic POR was 14%, 30%, 42%, 50% and 50% at 1, 2, 3, 4 and 5 years, respectively. Two clinical variables on multivariate analysis were associated with increased risk of symptomatic anastomotic POR, namely age <17 years at diagnosis [hazard ratio (HR) 2.17, p = 0.019] and gastrointestinal involvement (extent) >30 cm (HR 1.85, p = 0.048). CONCLUSION This study describes the natural history of POR after ileo-colic resection for Crohn's disease, as defined by endoscopic, radiological and clinical outcomes. Age <17 years at diagnosis and gastrointestinal involvement (extent) >30 cm were independent risk factors for symptomatic anastomotic POR.
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Affiliation(s)
- Lalin Navaratne
- Department of Colorectal Surgery, Barts Health NHS Trust, The Royal London Hospital, London, UK
| | | | - Daniel M Richardson
- Department of Colorectal Surgery, Barts Health NHS Trust, The Royal London Hospital, London, UK
| | - Robert Stephenson
- Department of Radiology, Barts Health NHS Trust, The Royal London Hospital, London, UK
| | - Niall Power
- Department of Radiology, Barts Health NHS Trust, The Royal London Hospital, London, UK
| | - Holly Gillott
- Department of Colorectal Surgery, Barts Health NHS Trust, The Royal London Hospital, London, UK
| | - Susana Ruiz Sánchez
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, St George's Hospital, London, UK
| | - Kuresh Khodatars
- Department of Colorectal Surgery, Barts Health NHS Trust, The Royal London Hospital, London, UK
| | - Christopher L H Chan
- Department of Colorectal Surgery, Barts Health NHS Trust, The Royal London Hospital, London, UK
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50
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Ueda T, Koyama F, Nakamoto T, Obara S, Inoue T, Sasaki Y, Kuge H, Fujii H, Sho M. Endoscopic Features of Postoperative Anastomotic Lesions in Patients with Crohn's Disease Compared with Right-side Colon Cancer: Are Anastomotic Linear Superficial Ulcers Recurrent in Crohn's Disease? J Anus Rectum Colon 2021; 5:158-166. [PMID: 33937556 PMCID: PMC8084541 DOI: 10.23922/jarc.2020-088] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 01/14/2021] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVES Many patients have endoscopic evidence of recurrent Crohn's disease (CD) 1 year after intestinal resection, and endoscopic lesions predict future clinical recurrence. The aim of this study was to describe some anastomotic lesions including changes in endoscopic features in CD patients and to discuss recurrence. We also compared anastomotic lesions in CD patients and in right-side colon cancer (rt-CC) patients. METHODS We enrolled patients with CD and rt-CC who underwent surgical resection between 2008 and 2014. Eleven CD patients underwent postoperative endoscopy at least twice, with the first time being from 6 months to 1 year after surgery and the second time being from 2 to 3 years after surgery. Eighty-six patients with rt-CC underwent postoperative endoscopy after approximately one year. RESULTS A total of 90.9% of CD patients had postoperative lesions around the anastomosis at the first postoperative ileocolonoscopy, which was markedly higher than that in rt-CC patients (3.5%, p<0.001). Many of these lesions in CD required enhanced treatment. However, linear superficial ulcers at the anastomotic line at the first ileocolonoscopy did not worsen with the same treatment (18.1%). CONCLUSIONS Postoperative anastomotic lesions were detected at a higher rate in CD cases than that in rt-CC cases. Many anastomotic lesions were recognized as recurrent disease and required enhanced treatment, whereas linear superficial ulcers did not require treatment changes. Therefore, linear superficial ulcers might not be recurrent disease. As this issue is related to recurrence, it should be further explored with the accumulation of more cases in a multicenter analysis.
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Affiliation(s)
- Takeshi Ueda
- Department of Surgery, Nara Medical University, Kashihara, Japan
- Department of Surgery, Minami-Nara General Medical Center, Yoshino, Japan
| | - Fumikazu Koyama
- Department of Surgery, Nara Medical University, Kashihara, Japan
- Division of Endoscopy, Nara Medical University Hospital, Kashihara, Japan
| | | | - Shinsaku Obara
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Takashi Inoue
- Department of Surgery, Nara Medical University, Kashihara, Japan
- Division of Endoscopy, Nara Medical University Hospital, Kashihara, Japan
| | - Yoshiyuki Sasaki
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Hiroyuki Kuge
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Hisao Fujii
- Gastrointestinal Endoscopy and IBD Center, Yoshida Hospital, Nara, Japan
| | - Masayuki Sho
- Department of Surgery, Nara Medical University, Kashihara, Japan
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