{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T08:47:56Z","timestamp":1782204476916,"version":"3.54.5"},"reference-count":163,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Programme","award":["351058"],"award-info":[{"award-number":["351058"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Inflammatory bowel disease (IBD) includes Crohn\u2019s disease (CD) and ulcerative colitis (UC), chronic immune-mediated conditions of the gastrointestinal tract characterized by alternating periods of disease activity and remission with a complex multifactorial pathogenesis. Persistent intestinal inflammation in IBD is a key driver of disease progression and is strongly associated with the development of complications such as dysplasia, colorectal cancer (CRC), intestinal strictures, and fistulas. It may also result in changes in anorectal function, identifiable and classifiable using high-resolution anorectal manometry. Histologic and endoscopic assessments are essential for the evaluation of intestinal inflammation. Cumulative inflammatory burden (CIB) is an important concept that quantifies inflammatory exposure in IBD over time by integrating the severity and duration of histologic inflammation across the disease course, highlighting the importance of long-term inflammatory activity in the development of CRC. Histologic healing may be an important therapeutic target in IBD to reduce the risk of long-term complications. In parallel, emerging precision medicine approaches aim to improve risk stratification and enable early, individualized interventions to reduce disease-related outcomes. Endoscopy also plays a fundamental role in monitoring high-risk patients and guiding treatment decisions. This review aims to characterize the main intestinal complications extending beyond the mucosa that are associated with cumulative chronic inflammation in patients with IBD, including dysplasia, CRC, strictures, fistulas, and anorectal dysfunction in an era increasingly focused on achieving complete mucosal healing. Particular attention is drawn to the significant role of persistent histologic and endoscopic inflammation in disease progression and development of complications, highlighting the specific features and associated risk factors of these disease-related outcomes. Throughout, this review emphasizes the fundamental role of endoscopy in the timely detection, monitoring, and therapeutic management of IBD-related complications, thereby reinforcing its role in comprehensive patient care.<\/jats:p>","DOI":"10.3390\/medicina62061208","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:13:37Z","timestamp":1782195217000},"page":"1208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond the Intestinal Mucosa in Long-Standing Inflammatory Bowel Disease: Consequences of Chronic Inflammation and Endoscopic Approaches to Diagnosis and Management"],"prefix":"10.3390","volume":"62","author":[{"given":"Sabina Gabriela","family":"Luca","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Institute of Gastroenterology and Hepatology, \u201cSt. Spiridon\u201d University Hospital, 700111 Iasi, Romania"},{"name":"Doctoral School, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana Cristina","family":"Petrea","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Institute of Gastroenterology and Hepatology, \u201cSt. Spiridon\u201d University Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-5961","authenticated-orcid":false,"given":"Cristina","family":"Muzica","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Institute of Gastroenterology and Hepatology, \u201cSt. Spiridon\u201d University Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5621-548X","authenticated-orcid":false,"given":"Ana Maria","family":"Singeap","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Institute of Gastroenterology and Hepatology, \u201cSt. Spiridon\u201d University Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"Buzuleac","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Institute of Gastroenterology and Hepatology, \u201cSt. Spiridon\u201d University Hospital, 700111 Iasi, Romania"},{"name":"Doctoral School, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Dunca","sequence":"additional","affiliation":[{"name":"Doctoral School, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru Sebastian","family":"Cotle\u021b","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Institute of Gastroenterology and Hepatology, \u201cSt. Spiridon\u201d University Hospital, 700111 Iasi, Romania"},{"name":"Doctoral School, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Stefania","family":"Juncu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Institute of Gastroenterology and Hepatology, \u201cSt. Spiridon\u201d University Hospital, 700111 Iasi, Romania"},{"name":"Doctoral School, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9144-5520","authenticated-orcid":false,"given":"Anca","family":"Trifan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cGrigore T. 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Based Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3748\/wjg.v20.i1.91","article-title":"Inflammatory bowel disease: Pathogenesis","volume":"20","author":"Zhang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3390\/immuno4040026","article-title":"Gut Microbiome as a Target of Intervention in Inflammatory Bowel Disease Pathogenesis and Therapy","volume":"4","author":"Hetta","year":"2024","journal-title":"Immuno"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1053\/j.gastro.2021.10.035","article-title":"Colorectal Cancer in Inflammatory Bowel Disease: Mechanisms and Management","volume":"162","author":"Shah","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rubin, D.C., Shaker, A., and Levin, M.S. (2012). Chronic intestinal inflammation: Inflammatory bowel disease and colitis-associated colon cancer. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00107"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1053\/j.gastro.2022.01.023","article-title":"What Does Disease Progression Look Like in Ulcerative Colitis, and How Might It Be Prevented?","volume":"162","author":"Torres","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109938","DOI":"10.3748\/wjg.v31.i33.109938","article-title":"Risk factors and long-term prognosis for colorectal strictures in ulcerative colitis","volume":"31","author":"Shao","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1016\/j.cgh.2021.01.028","article-title":"Incidence of and Risk Factors for Colorectal Strictures in Ulcerative Colitis: A Multicenter Study","volume":"19","author":"Laurain","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.3748\/wjg.v29.i7.1157","article-title":"Mucosal healing and inflammatory bowel disease: Therapeutic implications and new targets","volume":"29","author":"Otte","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.dld.2025.01.039","article-title":"Histological healing in IBD: Ready for prime time?","volume":"57","author":"Villanacci","year":"2025","journal-title":"Dig. Liver Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1756284818816956","DOI":"10.1177\/1756284818816956","article-title":"Current perspectives on the diagnosis and management of functional anorectal disorders in patients with inflammatory bowel disease","volume":"11","author":"Nigam","year":"2018","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s002689900354","article-title":"Role of nitric oxide in the colon of patients with ulcerative colitis","volume":"22","author":"Tomita","year":"1998","journal-title":"World J. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Albuquerque, A., Casey, J., Fairlamb, G., Houghton, L.A., and Selinger, C. (2021). Evaluation of anorectal function in perianal crohn\u2019s disease: A pilot study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10245909"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/1751-2980.12540","article-title":"Potential roles of neutrophils in regulating intestinal mucosal inflammation of inflammatory bowel disease","volume":"18","author":"Zhou","year":"2017","journal-title":"J. Dig. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Vespa, E., D\u2019amico, F., Sollai, M., Allocca, M., Furfaro, F., Zilli, A., Buono, A.D., Gabbiadini, R., Danese, S., and Fiorino, G. (2022). Histological Scores in Patients with Inflammatory Bowel Diseases: The State of the Art. J. Clin. Med., 11.","DOI":"10.3390\/jcm11040939"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Angyal, D., Balogh, F., Bessissow, T., Wetwittayakhlang, P., Ilias, A., Gonczi, L., and Lakatos, P.L. (2025). The Role of Histology Alongside Clinical and Endoscopic Evaluation in the Management of IBD\u2014A Narrative Review. J. Clin. Med., 14.","DOI":"10.3390\/jcm14072485"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1093\/ecco-jcc\/jjac006","article-title":"ECCO Position on Harmonisation of Crohn\u2019s Disease Mucosal Histopathology","volume":"16","author":"Magro","year":"2022","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/ibd\/izaa047","article-title":"Cumulative Histologic Inflammation Predicts Colorectal Neoplasia in Ulcerative Colitis: A Validation Study","volume":"27","author":"Yvellez","year":"2021","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1136\/gutjnl-2017-314190","article-title":"Cumulative burden of inflammation predicts colorectal neoplasia risk in ulcerative colitis: A large single-centre study","volume":"68","author":"Choi","year":"2019","journal-title":"Gut"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1053\/j.gastro.2007.08.001","article-title":"Histologic Inflammation Is a Risk Factor for Progression to Colorectal Neoplasia in Ulcerative Colitis: A Cohort Study","volume":"133","author":"Gupta","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103269","DOI":"10.1016\/j.eclinm.2025.103269","article-title":"Colorectal cancer risk in ulcerative colitis: An updated population-based systematic review and meta-analysis","volume":"84","author":"Zhang","year":"2025","journal-title":"eClinicalMedicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/apt.12651","article-title":"Systematic review with meta-Analysis: The declining risk of colorectal cancer in ulcerative colitis","volume":"39","author":"Chaparro","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1136\/gut.48.4.526","article-title":"The risk of colorectal cancer in ulcerative colitis: A meta-analysis","volume":"48","author":"Eaden","year":"2001","journal-title":"Gut"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Nardone, O.M., Zammarchi, I., Santacroce, G., Ghosh, S., and Iacucci, M. (2023). Inflammation-Driven Colorectal Cancer Associated with Colitis: From Pathogenesis to Changing Therapy. Cancers, 15.","DOI":"10.3390\/cancers15082389"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fanizza, J., Bencardino, S., Allocca, M., Furfaro, F., Zilli, A., Parigi, T.L., Fiorino, G., Peyrin-Biroulet, L., Danese, S., and D\u2019Amico, F. (2024). Inflammatory Bowel Disease and Colorectal Cancer. Cancers, 16.","DOI":"10.20944\/preprints202407.2568.v1"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sato, Y., Tsujinaka, S., Miura, T., Kitamura, Y., Suzuki, H., and Shibata, C. (2023). Inflammatory Bowel Disease and Colorectal Cancer: Epidemiology, Etiology, Surveillance, and Management. Cancers, 15.","DOI":"10.3390\/cancers15164154"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1053\/j.gastro.2010.02.007","article-title":"Inflammatory Bowel Disease Confers a Lower Risk of Colorectal Cancer to Females Than to Males","volume":"138","author":"Granath","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1053\/j.gastro.2020.12.036","article-title":"Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis","volume":"160","author":"Wijnands","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1093\/ecco-jcc\/jjv141","article-title":"European evidence-based consensus: Inflammatory bowel disease and malignancies","volume":"9","author":"Annese","year":"2015","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hisamatsu, T., Miyoshi, J., Oguri, N., Morikubo, H., Saito, D., Hayashi, A., Omori, T., and Matsuura, M. (2025). Inflammation-Associated Carcinogenesis in Inflammatory Bowel Disease: Clinical Features and Molecular Mechanisms. Cells, 14.","DOI":"10.3390\/cells14080567"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/gastro\/goy039","article-title":"Risk factors for colorectal neoplasia in patients with underlying inflammatory bowel disease: A multicenter study","volume":"7","author":"Wu","year":"2019","journal-title":"Gastroenterol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1056\/NEJM199011013231802","article-title":"Ulcerative colitis and colorectal cancer. A population-based study","volume":"323","author":"Ekbom","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/0016-5085(79)90279-8","article-title":"Cancer in universal and left-sided ulcerative colitis: Factors determining risk","volume":"77","author":"Greenstein","year":"1979","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S140","DOI":"10.1016\/S1590-8658(22)00430-3","article-title":"T.06.7 Incident Colorectal Cancer in Inflammatory Bowel Disease","volume":"54","author":"Neri","year":"2022","journal-title":"Dig. Liver Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pitoni, D., Dal Buono, A., Gabbiadini, R., Ronca, V., Colapietro, F., Pugliese, N., Ribaldone, D.G., Bezzio, C., Lleo, A., and Armuzzi, A. (2025). Navigating Neoplasm Risk in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis. Cancers, 17.","DOI":"10.3390\/cancers17132165"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/MEG.0000000000000576","article-title":"Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: A meta-analysis of 16 observational studies","volume":"28","author":"Zheng","year":"2016","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jhep.2023.09.031","article-title":"Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two?","volume":"80","author":"Bergquist","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.jhep.2011.10.025","article-title":"Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: A systematic review","volume":"56","author":"Boonstra","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/j.cgh.2021.08.039","article-title":"Epidemiology, Natural History, and Outcomes of Primary Sclerosing Cholangitis: A Systematic Review of Population-based Studies","volume":"20","author":"Trivedi","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_41","first-page":"316","article-title":"Primary sclerosing cholangitis and inflammatory bowel disease: Intestine-liver interrelation","volume":"42","author":"Quera","year":"2019","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_42","first-page":"2302","article-title":"Increased Risk of Colorectal Cancer Among Family Members of All Ages, Regardless of Age of Index Case at Diagnosis","volume":"13","author":"Samadder","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1097\/01.meg.0000437202.78275.4a","article-title":"How is the increased risk of colorectal cancer in first-degree relatives of patients communicated?","volume":"26","author":"Sulz","year":"2014","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1002\/cac2.70059","article-title":"Risk of colorectal cancer by family history of both colorectal carcinomas and colorectal polyps: A nationwide cohort study","volume":"45","author":"Hu","year":"2025","journal-title":"Cancer Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1053\/gast.2001.24052","article-title":"Family history as a risk factor for colorectal cancer in inflammatory bowel disease","volume":"120","author":"Askling","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5363261","DOI":"10.1155\/2019\/5363261","article-title":"Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis","volume":"2019","author":"Zhou","year":"2019","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jcol.2016.06.005","article-title":"Crohn\u2019s disease: Risk factor for colorectal cancer","volume":"37","author":"Barbosa","year":"2017","journal-title":"J. Coloproctology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"G7","DOI":"10.1152\/ajpgi.00079.2004","article-title":"Inflammation and cancer\u2014IV. Colorectal cancer in inflammatory bowel disease: The role of inflammation","volume":"287","author":"Itzkowitz","year":"2004","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9872","DOI":"10.3748\/wjg.v20.i29.9872","article-title":"Colorectal cancer in inflammatory bowel disease: The risk, pathogenesis, prevention and diagnosis","volume":"20","author":"Kim","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/0016-5085(92)91185-7","article-title":"DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis","volume":"103","author":"Rubin","year":"1992","journal-title":"Gastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1053\/j.gastro.2017.08.031","article-title":"Association of Aneuploidy and Flat Dysplasia With Development of High-Grade Dysplasia or Colorectal Cancer in Patients With Inflammatory Bowel Disease","volume":"153","author":"Tsai","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/s41379-019-0419-1","article-title":"Nonconventional dysplasia in patients with inflammatory bowel disease and colorectal carcinoma: A multicenter clinicopathologic study","volume":"33","author":"Choi","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1111\/his.14298","article-title":"Non-conventional dysplasia in inflammatory bowel disease is more frequently associated with advanced neoplasia and aneuploidy than conventional dysplasia","volume":"78","author":"Lee","year":"2021","journal-title":"Histopathology"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lucaf\u00f2, M., Curci, D., Franzin, M., Decorti, G., and Stocco, G. (2021). Inflammatory Bowel Disease and Risk of Colorectal Cancer: An Overview From Pathophysiology to Pharmacological Prevention. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.772101"},{"key":"ref_55","first-page":"3942","article-title":"Hypermethylation of the p16INK4a promoter in colectomy specimens of patients with long-standing and extensive ulcerative colitis","volume":"58","author":"Hsieh","year":"1998","journal-title":"Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1053\/j.gastro.2005.04.011","article-title":"Molecular phenotype of inflammatory bowel disease-associated neoplasms with microsatellite instability","volume":"129","author":"Schulmann","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_57","first-page":"4864","article-title":"Microsatellite instability in inflammatory bowel disease-associated neoplastic lesions is associated with hypermethylation and diminished expression of the DNA mismatch repair gene, hMLH1","volume":"60","author":"Fleisher","year":"2000","journal-title":"Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5126048","DOI":"10.1155\/2017\/5126048","article-title":"The Role of Proinflammatory Pathways in the Pathogenesis of Colitis-Associated Colorectal Cancer","volume":"2017","author":"Luo","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"110516","DOI":"10.1016\/j.abb.2025.110516","article-title":"The role of COX-2 and its use as a therapeutic target in IBD and related colorectal cancer","volume":"771","author":"Yang","year":"2025","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/onc.2009.421","article-title":"The role of COX-2 in intestinal inflammation and colorectal cancer","volume":"29","author":"Wang","year":"2010","journal-title":"Oncogene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/0016-5085(94)90246-1","article-title":"Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas","volume":"107","author":"Eberhart","year":"1994","journal-title":"Gastroenterology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/35094017","article-title":"Colorectal Cancer Prevention of Cyclooxygenase-2","volume":"1","author":"Gupta","year":"2001","journal-title":"Nat. Rev. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.canlet.2008.03.004","article-title":"Pro-inflammatory prostaglandins and progression of colorectal cancer","volume":"267","author":"Wang","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1054-3589(08)60067-8","article-title":"Colorectal cancer and nonsteroidal anti-inflammatory drugs","volume":"39","author":"Smalley","year":"1997","journal-title":"Adv. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1093\/bjs\/znad231","article-title":"Aspirin chemoprevention in colorectal cancer: Network meta-analysis of low, moderate, and high doses","volume":"110","author":"Shah","year":"2023","journal-title":"Br. J. Surg."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3679","DOI":"10.3748\/wjg.v22.i13.3679","article-title":"Does aspirin or non-aspirin non-steroidal anti-inflammatory drug use prevent colorectal cancer in inflammatory bowel disease?","volume":"22","author":"Burr","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Agustsson, A.S., and Bjornsson, E.S. (2025). Chemoprevention of Colorectal Cancer\u2014With Emphasis on Low-Dose Aspirin and Anticoagulants. Pharmaceuticals, 18.","DOI":"10.3390\/ph18060811"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1097\/FJC.0b013e318157f72d","article-title":"COX-2 inhibitors and cardiovascular risk","volume":"50","author":"Funk","year":"2007","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.2174\/138161207781368774","article-title":"Mechanisms underlying the cardiovascular effects of COX-inhibition: Benefits and risks","volume":"13","author":"Badimon","year":"2007","journal-title":"Curr. Pharm. Des."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2004.07.013","article-title":"IKK\u03b2 links inflammation and tumorigenesis in a mouse model of colitis-associated cancer","volume":"118","author":"Greten","year":"2004","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s41423-025-01310-w","article-title":"NF-\u03baB in inflammation and cancer","volume":"22","author":"Mao","year":"2025","journal-title":"Cell Mol. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41392-020-00312-6","article-title":"Targeting NF-\u03baB pathway for the therapy of diseases: Mechanism and clinical study","volume":"5","author":"Yu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2008.01.020","article-title":"Shared Principles in NF-\u03baB Signaling","volume":"132","author":"Hayden","year":"2008","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Frigerio, S., Lartey, D.A., D\u2019haens, G.R., and Grootjans, J. (2021). The role of the immune system in ibd-associated colorectal cancer: From pro to anti-tumorigenic mechanisms. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312739"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"26243","DOI":"10.1074\/jbc.M403286200","article-title":"Regulation of the NF-\u03baB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation","volume":"279","author":"Liao","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1159\/000341698","article-title":"Interleukin-6 trans-signaling and colonic cancer associated with inflammatory bowel disease","volume":"30","author":"Chalaris","year":"2012","journal-title":"Dig. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S1074-7613(00)80334-9","article-title":"Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment","volume":"6","author":"Romano","year":"1997","journal-title":"Immunity"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1136\/gut.2006.115402","article-title":"The IL23 axis plays a key role in the pathogenesis of IBD","volume":"56","author":"McGovern","year":"2007","journal-title":"Gut"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s00535-017-1350-1","article-title":"TGF-\u03b2 in inflammatory bowel disease: A key regulator of immune cells, epithelium, and the intestinal microbiota","volume":"52","author":"Ihara","year":"2017","journal-title":"J. Gastroenterol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s10238-024-01476-z","article-title":"MicroRNA signatures in the pathogenesis and therapy of inflammatory bowel disease","volume":"24","author":"Ramadan","year":"2024","journal-title":"Clin. Exp. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"157153","DOI":"10.1016\/j.phymed.2025.157153","article-title":"Lianweng formula restores intestinal barrier function in ulcerative colitis through the \u03b2-arrestin 1\/NF-\u03baB signaling axis","volume":"146","author":"Lv","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Mestrovic, A., Perkovic, N., Bozic, D., Kumric, M., Vilovic, M., and Bozic, J. (2024). Precision Medicine in Inflammatory Bowel Disease: A Spotlight on Emerging Molecular Biomarkers. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071520"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"i1927","DOI":"10.1093\/ecco-jcc\/jjae190.1219","article-title":"Clinical: Therapy and Observation Abstract citation ID: Jjae190. 1219 Treat-smart study: Leveraging individual inflammatory markers for personalized therapy in patients with","volume":"19","author":"Medhat","year":"2025","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"35","DOI":"10.4212\/cjhp.v67i1.1318","article-title":"Safety of 5-Aminosalicylic Acid Derivatives in Patients with Sensitivity to Acetylsalicylic Acid and Nonsteroidal Anti-inflammatory Drugs","volume":"67","author":"Poh","year":"2014","journal-title":"Can. J. Hosp. Pharm."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"840","DOI":"10.5009\/gnl210479","article-title":"Chemoprevention of Colitis-Associated Dysplasia or Cancer in Inflammatory Bowel Disease","volume":"16","author":"Hsiao","year":"2022","journal-title":"Gut Liver"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Fousekis, F.S., Mpakogiannis, K., Filis, P., Skamnelos, A., Christodoulou, D.K., Mauri, D., and Katsanos, K.H. (2025). Exploring Chemoprevention in Colorectal Cancer for Patients with Inflammatory Bowel Disease: Mechanisms of Action and Clinical Aspects. Cancers, 17.","DOI":"10.3390\/cancers17020229"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.cgh.2013.06.023","article-title":"Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: A case-control study","volume":"11","author":"Rubin","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1111\/apt.14023","article-title":"Systematic review with meta-analysis: Use of 5-aminosalicylates and risk of colorectal neoplasia in patients with inflammatory bowel disease","volume":"45","author":"Bonovas","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.18632\/oncotarget.13715","article-title":"Chemopreventive effects of 5-aminosalicylic acid on inflammatory bowel disease-associated colorectal cancer and dysplasia: A systematic review with meta-analysis","volume":"8","author":"Qiu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Zhao, L.N., Li, J.Y., Yu, T., Chen, G.C., Yuan, Y.H., and Chen, Q.K. (2014). 5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: An updated meta-analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094208"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1046\/j.1365-2036.2000.00698.x","article-title":"Colorectal cancer prevention in ulcerative colitis: A case-control study","volume":"14","author":"Eaden","year":"2000","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/apt.14436","article-title":"Systematic review with meta-analysis: Thiopurines decrease the risk of colorectal neoplasia in patients with inflammatory bowel disease","volume":"47","author":"Lu","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1093\/ecco-jcc\/jjae089","article-title":"ECCO Guidelines on Therapeutics in Crohn\u2019s Disease: Surgical Treatment","volume":"18","author":"Adamina","year":"2024","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/ecco-jcc\/jjab177","article-title":"ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment","volume":"16","author":"Spinelli","year":"2022","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00384-020-03735-3","article-title":"Effects of 5-aminosalicylates or thiopurines on the progression of low-grade dysplasia in patients with inflammatory bowel disease: A systematic review and meta-analysis","volume":"36","author":"Zeng","year":"2021","journal-title":"Int. J. Color. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/ecco-jcc\/jjab178","article-title":"ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment","volume":"16","author":"Raine","year":"2022","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1093\/ecco-jcc\/jjae091","article-title":"ECCO Guidelines on Therapeutics in Crohn\u2019s Disease: Medical Treatment","volume":"18","author":"Gordon","year":"2024","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/ecco-jcc\/jjz180","article-title":"ECCO Guidelines on Therapeutics in Crohn\u2019s Disease: Medical Treatment","volume":"14","author":"Torres","year":"2020","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1093\/ecco-jcc\/jjab184","article-title":"Impact of Anti-tumour Necrosis Factor Agents on the Risk of Colorectal Cancer in Patients with Ulcerative Colitis: Nationwide French Cohort Study","volume":"16","author":"Charkaoui","year":"2022","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_100","first-page":"560","article-title":"Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis","volume":"118","author":"Popivanova","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/nrc1751","article-title":"Statins and cancer prevention","volume":"5","author":"Demierre","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"24F","DOI":"10.1016\/j.amjcard.2005.06.009","article-title":"Effects of statins on 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition beyond low-density lipoprotein cholesterol","volume":"96","author":"Liao","year":"2005","journal-title":"Am. J. Cardiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.cgh.2016.02.017","article-title":"Statin Use Is Associated With Reduced Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases","volume":"14","author":"Ananthakrishnan","year":"2016","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1002\/cncr.25731","article-title":"Risk of colorectal cancer in self-reported inflammatory bowel disease and modification of risk by statin and NSAID use","volume":"117","author":"Samadder","year":"2011","journal-title":"Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"54","DOI":"10.5009\/gnl18178","article-title":"Statin Exposure Is Not Associated with Reduced Prevalence of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease","volume":"13","author":"Shah","year":"2019","journal-title":"Gut Liver"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"102055","DOI":"10.1016\/j.bpg.2025.102055","article-title":"Advances in endoscopy in IBD diagnostics and management","volume":"78","author":"Roseira","year":"2025","journal-title":"Best Pr. Res. Clin. Gastroenterol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Schiavone, S.C., Biancone, L., Fiorillo, M., Divizia, A., Mancone, R., and Neri, B. (2025). Colitis-Associated Dysplasia in Inflammatory Bowel Disease: Features and Endoscopic Management. Cancers, 17.","DOI":"10.3390\/cancers17050784"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1111\/apt.16832","article-title":"Adherence to endoscopic surveillance for advanced lesions and colorectal cancer in inflammatory bowel disease: An AEG and GETECCU collaborative cohort study","volume":"55","author":"Ballester","year":"2022","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/jgh.16438","article-title":"Adherence to endoscopic surveillance guidelines for patients with inflammatory bowel disease: An Australian cohort study","volume":"39","author":"Picardo","year":"2024","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s12664-024-01621-2","article-title":"Endoscopic approaches to the management of dysplasia in inflammatory bowel disease: A state-of-the-art narrative review","volume":"43","author":"Singh","year":"2024","journal-title":"Indian J. Gastroenterol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Fasulo, E., D\u2019Amico, F., Zilli, A., Furfaro, F., Cicerone, C., Parigi, T.L., Peyrin-Biroulet, L., Danese, S., and Allocca, M. (2025). Advancing Colorectal Cancer Prevention in Inflammatory Bowel Disease (IBD): Challenges and Innovations in Endoscopic Surveillance. Cancers, 17.","DOI":"10.3390\/cancers17010060"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1002\/ueg2.70017","article-title":"Endoscopic Techniques for Colorectal Neoplasia Surveillance in Inflammatory Bowel Disease: A Systematic Review and Network Meta-Analysis","volume":"13","author":"Huang","year":"2025","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1016\/j.cgh.2024.11.008","article-title":"Comparative Efficacy and Safety of Endoscopic Modalities for Colorectal Cancer Screening in Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis","volume":"23","author":"Sinopoulou","year":"2025","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"508","DOI":"10.3748\/wjg.v29.i3.508","article-title":"Artificial intelligence and inflammatory bowel disease: Where are we going?","volume":"29","author":"Spadaccini","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1053\/j.gastro.2019.08.058","article-title":"Application of Artificial Intelligence to Gastroenterology and Hepatology","volume":"158","author":"Sandborn","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Mignini, I., Blasi, V., Termite, F., Esposto, G., Borriello, R., Laterza, L., Scaldaferri, F., Ainora, M.E., Gasbarrini, A., and Zocco, M.A. (2024). Fibrostenosing Crohn\u2019s Disease: Pathogenetic Mechanisms and New Therapeutic Horizons. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126326"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1136\/gutjnl-2012-304353","article-title":"Crohn\u2019s disease complicated by strictures: A systematic review","volume":"62","author":"Rieder","year":"2013","journal-title":"Gut"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000458144","article-title":"Risk Factors for the Development of Fistulae and Stenoses in Crohn Disease Patients in the Swiss Inflammatory Bowel Disease Cohort","volume":"1","author":"Zeitz","year":"2017","journal-title":"Inflamm. Intest. Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1053\/j.gastro.2005.12.019","article-title":"Predictors of crohn\u2019s disease","volume":"130","author":"Beaugerie","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/S0016-5085(98)70420-2","article-title":"Clinical course of colorectal Crohn\u2019s disease: A 35-year follow-up study of 507 patients","volume":"114","author":"Lapidus","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1177\/2050640620901960","article-title":"Natural history, diagnosis and treatment approach to fibrostenosing Crohn\u2019s disease","volume":"8","author":"Click","year":"2020","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1136\/gutjnl-2011-301397","article-title":"Hospitalisations and surgery in Crohn\u2019s disease","volume":"61","author":"Bernstein","year":"2012","journal-title":"Gut"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Ma, D., Li, Y., Li, L., and Yang, L. (2024). Risk factors for endoscopic postoperative recurrence in patients with Crohn\u2019s Disease: A protocol for systematic review and meta-analysis. BMC Gastroenterol., 24.","DOI":"10.1186\/s12876-024-03301-z"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.giec.2014.04.002","article-title":"Surgical management of nonpolypoid colorectal lesions and strictures in colonic inflammatory bowel disease","volume":"24","author":"Coviello","year":"2014","journal-title":"Gastrointest. Endosc. Clin. N. Am."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"601","DOI":"10.5009\/gnl19229","article-title":"Risk factors of colorectal stricture associated with developing high-grade dysplasia or cancer in ulcerative colitis: A multicenter long-term follow-up study","volume":"14","author":"Xu","year":"2020","journal-title":"Gut Liver"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"goae075","DOI":"10.1093\/gastro\/goae075","article-title":"Interventional endoscopy in inflammatory bowel disease: A comprehensive review","volume":"12","author":"Pal","year":"2024","journal-title":"Gastroenterol. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.gie.2024.08.034","article-title":"Endoscopic diagnosis and management of adult inflammatory bowel disease: A consensus document from the American Society for Gastrointestinal Endoscopy IBD Endoscopy Consensus Panel","volume":"101","author":"Shen","year":"2025","journal-title":"Gastrointest. Endosc."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1111\/apt.16326","article-title":"Review article: Investigation and management of internal fistulae in Crohn\u2019s disease","volume":"53","author":"Tjandra","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1111\/den.14429","article-title":"Guidelines for endoscopic balloon dilation in treating Crohn\u2019s disease-associated small intestinal strictures (supplement to the Clinical Practice Guidelines for Enteroscopy)","volume":"34","author":"Yamamoto","year":"2022","journal-title":"Dig. Endosc."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.3748\/wjg.v24.i17.1859","article-title":"Endoscopic management of Crohn\u2019s strictures","volume":"24","author":"Bessissow","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1093\/ibd\/izac153","article-title":"Endoscopic Stenting in Crohn\u2019s Disease-related Strictures: A Systematic Review and Meta-Analysis of Outcomes","volume":"29","author":"Chandan","year":"2023","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"otaa069","DOI":"10.1093\/crocol\/otaa069","article-title":"Endoscopic stricturotomy is an efficacious option for management of strictures in patients with inflammatory bowel disease","volume":"2","author":"Kochhar","year":"2020","journal-title":"Crohn\u2019s Colitis 360"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/gastro\/goz051","article-title":"Endoscopic stricturotomy in the treatment of anastomotic strictures in inflammatory bowel disease (IBD) and non-IBD patients","volume":"8","author":"Zhang","year":"2020","journal-title":"Gastroenterol. Rep."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.gie.2018.02.034","article-title":"Endoscopic fistulotomy in inflammatory bowel disease","volume":"88","author":"Kochhar","year":"2018","journal-title":"Gastrointest. Endosc."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/ncpgasthep1340","article-title":"Diagnosis and management of fistulizing Crohn\u2019s disease","volume":"6","author":"Nielsen","year":"2009","journal-title":"Nat. Clin. Pract. Gastroenterol. Hepatol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1053\/gast.2002.32362","article-title":"The natural history of fistulizing Crohn\u2019s disease in Olmsted County, Minnesota","volume":"122","author":"Schwartz","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4291\/wjgp.v5.i3.205","article-title":"Pathophysiology of fistula formation in Crohn\u2019s disease","volume":"5","author":"Scharl","year":"2014","journal-title":"World J. Gastrointest. Pathophysiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/mi.2017.107","article-title":"Epithelial-mesenchymal transition in Crohn\u2019s disease","volume":"11","author":"Jiang","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"20202","DOI":"10.1074\/jbc.M110.102012","article-title":"Identification of epithelial to mesenchymal transition as a novel source of fibroblasts in intestinal fibrosis","volume":"285","author":"Flier","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcmgh.2022.09.011","article-title":"Pathogenesis of Fistulating Crohn\u2019s Disease: A Review","volume":"15","author":"McGregor","year":"2023","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.diagmicrobio.2012.09.012","article-title":"Assessment of microbiota and peptidoglycan in perianal fistulas","volume":"75","author":"Mitalas","year":"2013","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Munster, L.J., M\u00f6nnink, G.L.E., van Dieren, S., Mundt, M.W., D\u2019Haens, G.R.A.M., Bemelman, W.A., Buskens, C.J., and van der Bilt, J.D.W. (2024). Fistulizing Perianal Disease as a First Manifestation of Crohn\u2019s Disease: A Systematic Review and Meta-Analysis. J. Clin. Med., 13.","DOI":"10.3390\/jcm13164734"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1186\/s12955-020-01622-7","article-title":"Burden of disease and adaptation to life in patients with Crohn\u2019s perianal fistula: A qualitative exploration","volume":"18","author":"Adegbola","year":"2020","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1038\/ctg.2017.33","article-title":"Fistulizing Crohn\u2019s Disease","volume":"8","author":"Scharl","year":"2017","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.cgh.2024.05.029","article-title":"Perianal Fistulizing Crohn\u2019s Disease\u2013Associated Anorectal and Fistula Cancers: Systematic Review and Expert Consensus","volume":"23","author":"Wong","year":"2025","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1093\/ecco-jcc\/jjab057","article-title":"Perianal Fistula-Associated Carcinoma in Crohn\u2019s Disease: A Multicentre Retrospective Case Control Study","volume":"15","author":"Palmieri","year":"2021","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"56","DOI":"10.5217\/ir.2024.00009","article-title":"The prevalence of pouch fistulas in ulcerative colitis following restorative proctocolectomy: A systematic review and meta-analysis","volume":"23","author":"Lo","year":"2025","journal-title":"Intest. Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1111\/codi.15553","article-title":"The pouch behaving badly: Management of morbidity after ileal pouch\u2013anal anastomosis","volume":"23","author":"Deputy","year":"2021","journal-title":"Color. Dis."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/codi.14904","article-title":"Management of pouch-vaginal fistulas\u2014Experience from our institution","volume":"22","author":"Sivathondan","year":"2020","journal-title":"Color. Dis."},{"key":"ref_150","first-page":"34","article-title":"Systematic review on the management of ileoanal pouch-vaginal fistulas after restorative proctocolectomy in the treatment of ulcerative colitis","volume":"23","author":"Machin","year":"2021","journal-title":"Color. Dis. Off. J. Assoc. Coloproctology Gt. Br. Irel."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/codi.15418","article-title":"Revisional ileoanal pouch surgery: A systematic literature review assessing outcomes over the last 40 years","volume":"23","author":"Carpenter","year":"2021","journal-title":"Color. Dis."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.giec.2022.05.006","article-title":"Endoscopic Therapy for Fistulas and Abscesses in Crohn\u2019s Disease","volume":"32","author":"Lan","year":"2022","journal-title":"Gastrointest. Endosc. Clin. N. Am."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Buscail, E., Le Cosquer, G., Gross, F., Lebrin, M., Bugarel, L., Deraison, C., Vergnolle, N., Bournet, B., Gilletta, C., and Buscail, L. (2021). Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn\u2019s Disease: Rationale, Clinical Results and Perspectives. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189967"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.sopen.2025.11.002","article-title":"The efficacy of adipose-derived stem cell therapy for complex perianal fistulas in Crohn\u2019s disease patients: A systematic review","volume":"29","author":"Aldakhil","year":"2026","journal-title":"Surg. Open Sci."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3600","DOI":"10.1007\/s10620-013-2850-3","article-title":"Dyssynergic defecation: A treatable cause of persistent symptoms when inflammatory bowel disease is in remission","volume":"58","author":"Perera","year":"2013","journal-title":"Dig. Dis. Sci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1177\/0192623313505929","article-title":"Effects of inflammation on the innervation of the colon","volume":"42","author":"Moynes","year":"2014","journal-title":"Toxicol. Pathol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1177\/2050640614548096","article-title":"Colonic motility in ulcerative colitis","volume":"2","author":"Bassotti","year":"2014","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1111\/j.1365-2982.2008.01146.x","article-title":"Enteric nervous system abnormalities in inflammatory bowel diseases","volume":"20","author":"Villanacci","year":"2008","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/nmo.12327","article-title":"The neurochemical changes in the innervation of human colonic mesenteric and submucosal blood vessels in Ulcerative colitis and Crohn\u2019s disease","volume":"26","author":"Brookes","year":"2014","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1172\/JCI76306","article-title":"Colitis-induced neuroplasticity disrupts motility in the inflamed and post-inflamed colon","volume":"125","author":"Mawe","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1053\/gast.1996.v110.pm8566588","article-title":"Inhibition of progressing primary esophageal peristalsis by pharyngeal water stimulation in humans","volume":"110","author":"Trifan","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/0016-5085(95)90072-1","article-title":"Inhibition of resting lower esophageal sphincter pressure by pharyngeal water stimulation in humans","volume":"108","author":"Trifan","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.12998\/wjcc.v7.i18.2675","article-title":"High-resolution colonic manometry and its clinical application in patients with colonic dysmotility: A review","volume":"7","author":"Li","year":"2019","journal-title":"World J. Clin. 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