{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:05:39Z","timestamp":1787162739782,"version":"build-2736575974"},"reference-count":130,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Meharry Medical College Morphology Core NIH","award":["U01NS041071"],"award-info":[{"award-number":["U01NS041071"]}]},{"name":"Meharry Medical College Morphology Core NIH","award":["U54RR026140"],"award-info":[{"award-number":["U54RR026140"]}]},{"name":"Meharry Medical College Morphology Core NIH","award":["U54CA091408"],"award-info":[{"award-number":["U54CA091408"]}]},{"name":"Meharry Medical College Morphology Core NIH","award":["S10RR0254970"],"award-info":[{"award-number":["S10RR0254970"]}]},{"name":"NCRR\/NIH","award":["UL1 RR024975-01"],"award-info":[{"award-number":["UL1 RR024975-01"]}]},{"name":"Cooperative Human Tissue Network","award":["5U01CA094664-09"],"award-info":[{"award-number":["5U01CA094664-09"]}]},{"name":"Research Foundation, American Society of Colon and Rectal Surgeons, Limited Project","award":["LPG 086"],"award-info":[{"award-number":["LPG 086"]}]},{"name":"National Institute of Health","award":["5R21DK095186"],"award-info":[{"award-number":["5R21DK095186"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Indeterminate colitis (IC) is an erroneous diagnosis for predominantly colonic inflammatory bowel disease (IBD) when there is a non-definitive foundation of the benchmark for ulcerative colitis (UC) and Crohn\u2019s colitis (CC) after a combined state-of-the-art classification system of clinical, endoscopic, radiologic, and histologic tools are used. This confounds an effective surgical regimen; specifically pouch surgery, \u201cthe restorative proctocolectomy with ileal pouch\u2013anal anastomosis (PRC-IPAA)\u201d. Transforming the distinction between UC and CC in otherwise IC into authentic UC and CC requires priority attention when considering a patient\u2019s candidacy for RPC-IPAA. RPC-IPAA is the accepted standard curative surgical procedure in the treatment for UC (and Familial Adenomatous Polyposis (FAP)). Further, inapproximate\/incorrect diagnosis and treatment can sustain potential long-term morbidity from inaccurate and unnecessary surgery and cost. Methods: In trying to resolve these diagnostic ambiguities, the current study advances our understanding by showing the expression of human alpha defensin 5 (DEFA5 alias HD5) restricted in the colon crypt mucosal lining areas, and by identifying the cells of the small intestine (ileum) \u201ccolonic ileal metaplasia\u201d in CC that may serve as a biomarker to portray\/ascertain authentic CC and UC among IC cohorts, with a positive predictive value (PPV) of 96 percent. Results: Hence, the imprecise diagnosis of IC largely would be circumvented. This new diagnostic tool offers instant tangible benefits over existing diagnostic pathways. The journey toward its widespread clinical use is now subject to logistical and regulatory defiance, which all emerging molecular diagnostic technologies inevitably encounter. Conclusions: The aim of this communication is to provide a summary of the currently available diagnostic advances relating to surgical management for IC in clinical settings, and the related challenges. Further, I briefly discuss aspects of its pathophysiology, surveillance, and diagnostic assay development.<\/jats:p>","DOI":"10.3390\/jcm14238390","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:56:34Z","timestamp":1764165394000},"page":"8390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Secure Ileal Pouch\u2013Anal Anastomosis for Histologic Indeterminate Colitis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1728-8456","authenticated-orcid":false,"given":"Amosy E.","family":"M\u2019Koma","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College School of Medicine, Nashville, TN 37208-3500, USA"},{"name":"Department of Pathology, Anatomy and Cell Biology, Meharry Medical College School of Medicine, Nashville General Hospital, Nashville, TN 37208-3599, USA"},{"name":"Division of General Surgery, Section of Colon and Rectal Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232-0260, USA"},{"name":"The American Society of Colon and Rectal Surgeons (ASCRS), 2549 Waukegan Road, #210, Bannockburn, IL 600015, USA"},{"name":"International Society of University Colon and Rectal Surgeons, 109 Partin Street, Chapel Hill, NC 27514, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Williams, A.D., Korolkova, O.Y., Sakwe, A.M., Geiger, T.M., James, S.D., Muldoon, R.L., Herline, A.J., Goodwin, J.S., Izban, M.G., and Washington, M.K. (2017). Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189551"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3748\/wjg.v21.i1.21","article-title":"Differential diagnosis in inflammatory bowel disease colitis: State of the art and future perspectives","volume":"21","author":"Tontini","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6383","DOI":"10.2147\/JIR.S268262","article-title":"Indeterminate Colitis\u2014Update on Treatment Options","volume":"14","author":"Venkateswaran","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1159\/000501519","article-title":"An Overview of Inflammatory Bowel Disease Unclassified in Children","volume":"4","author":"Thurgate","year":"2019","journal-title":"Inflamm. Intest. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"M\u2019Koma, A.E. (2022). Inflammatory Bowel Disease: Clinical Diagnosis and Surgical Treatment-Overview. Medicina, 58.","DOI":"10.3390\/medicina58050567"},{"key":"ref_6","first-page":"18103","article-title":"Inflammatory Bowel Disease: Clinical Diagnosis and Pharmaceutical Management of Inflammatory Bowel Disease","volume":"11","year":"2023","journal-title":"Med. Res. Arch."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1097\/MIB.0000000000001061","article-title":"Results at Up to 30 Years After Ileal Pouch\u2013Anal Anastomosis for Chronic Ulcerative Colitis","volume":"23","author":"Lightner","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1097\/MIB.0000000000000712","article-title":"Crohn\u2019s Disease of the Ileoanal Pouch","volume":"22","author":"Lightner","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/DCR.0000000000001918","article-title":"IPAA in Known Preoperative Crohn\u2019s Disease: A Systematic Review","volume":"64","author":"Lightner","year":"2020","journal-title":"Dis. Colon Rectum"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"465","DOI":"10.33145\/2304-8336-2024-29-465-472","article-title":"Synchronous Colon Cancer Associated with Idiopathic Thrombocytopenic Purpura. Clinical Case","volume":"29","author":"Lytvynenko","year":"2024","journal-title":"Probl. Radiat. Med. Radiobiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1858","DOI":"10.1590\/0102-6720202400064e1858","article-title":"Management of Synchronic Large Liver Metastasis in a Non-Occlusive Colon Tumor","volume":"37","author":"Ramos","year":"2024","journal-title":"Arq. Bras. Cir. Dig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"260","DOI":"10.4236\/jct.2013.41033","article-title":"Adenocarcinomas after Prophylactic Surgery for Familial Adenomatous Polyposis","volume":"4","author":"Smith","year":"2013","journal-title":"J. Cancer Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1002\/bjs.1800670802","article-title":"Proctocolectomy with ileal reservoir and anal anastomosis","volume":"67","author":"Parks","year":"1980","journal-title":"Br. J. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1136\/bmj.2.6130.85","article-title":"Proctocolectomy without ileostomy for ulcerative colitis","volume":"2","author":"Parks","year":"1978","journal-title":"Br. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/0002-9610(83)90171-X","article-title":"Restorative proctocolectomy with ileal reservoir and ileoanal anas-tomosis","volume":"145","author":"Rothenberger","year":"1983","journal-title":"Am. J. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1136\/gut.34.5.680","article-title":"An audit of restorative proctocolectomy","volume":"34","author":"Keighley","year":"1993","journal-title":"Gut"},{"key":"ref_17","first-page":"27","article-title":"The final diagnosis in pouch patients for presumed ulcerative colitis may change to Crohn\u2019s disease: Patients should be warned of the consequences","volume":"47","author":"Keighley","year":"2000","journal-title":"Acta Chir. Iugosl."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s003840050007","article-title":"Outcome of ileal pouch after secondary diagnosis of Crohn\u2019s disease","volume":"15","author":"Francois","year":"2000","journal-title":"Int. J. Color. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1007\/s00384-007-0331-x","article-title":"Evolution of the restorative proctocolectomy and its effects on gastrointestinal hormones","volume":"22","author":"Wise","year":"2007","journal-title":"Int. J. Color. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1097\/00000658-199210000-00013","article-title":"Continuing Evolution of the Pelvic Pouch Procedure","volume":"216","author":"Cohen","year":"1992","journal-title":"Ann. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0002-9610(97)89634-1","article-title":"Stapled ileal pouch anal anastomoses are safer than handsewn anastomoses in patients with ulcerative colitis","volume":"171","author":"Ziv","year":"1996","journal-title":"Am. J. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/BF02140892","article-title":"Outcome of the pelvic pouch procedure in patients with prior perianal disease","volume":"40","author":"Richard","year":"1997","journal-title":"Dis. Colon Rectum"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1007\/s10350-005-0059-z","article-title":"Crohn\u2019s Disease and Indeterminate Colitis and the Ileal Pouch-Anal Anastomosis: Outcomes and Patterns of Failure","volume":"48","author":"Brown","year":"2005","journal-title":"Dis. Colon Rectum"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/BF02049696","article-title":"Indeterminate colitis predisposes to perineal complications after ileal pouch-anal anastomosis","volume":"34","author":"Koltun","year":"1991","journal-title":"Dis. Colon Rectum"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1007\/BF02236726","article-title":"Ileal pouch-anal anastomosis in patients with indeterminate colitis: Long-term results","volume":"43","author":"Yu","year":"2000","journal-title":"Dis. Colon Rectum"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/00000658-200207000-00008","article-title":"Equivalent Function, Quality of Life and Pouch Survival Rates After Ileal Pouch-Anal Anastomosis for Indeterminate and Ulcerative Colitis","volume":"236","author":"Delaney","year":"2002","journal-title":"Ann. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1097\/00054725-200209000-00010","article-title":"Is Ileoanal the Proper Operation for Indeterminate Colitis","volume":"8","author":"McLeod","year":"2002","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF02236894","article-title":"Is Ileal pouch-anal anastomosis really the procedure of choice for patients with ulcerative colitis?","volume":"41","author":"Jimmo","year":"1998","journal-title":"Dis. Colon Rectum"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S159","DOI":"10.1002\/ibd.20594","article-title":"What is the incidence, prevalence, and natural history of indeterminate colitis?","volume":"14","author":"Meucci","year":"2008","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1097\/01.mcg.0000123991.13937.7e","article-title":"Indeterminate colitis: Clinical spectrum of disease","volume":"38","author":"Burakoff","year":"2004","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1136\/jcp.2003.015214","article-title":"Indeterminate colitis","volume":"57","author":"Guindi","year":"2004","journal-title":"J. Clin. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1097\/00054725-200309000-00007","article-title":"Indeterminate colitis","volume":"9","author":"Geboes","year":"2003","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1136\/jcp.2008.059311","article-title":"Inflammatory bowel disease unclassified and indeterminate colitis: The role of the pathologist","volume":"62","author":"Geboes","year":"2008","journal-title":"J. Clin. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"208","DOI":"10.4240\/wjgs.v6.i11.208","article-title":"Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics","volume":"6","year":"2014","journal-title":"World J. Gastrointest. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1136\/jcp.31.6.567","article-title":"Overlap in the spectrum of non-specific inflammatory bowel disease\u2014\u2018Colitis indeterminate\u2019","volume":"31","author":"Price","year":"1978","journal-title":"J. Clin. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1136\/gut.35.7.961","article-title":"Observer variation and discriminatory value of biopsy features in inflammatory bowel disease","volume":"35","author":"Theodossi","year":"1994","journal-title":"Gut"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/ibd.21371","article-title":"Utilization of healthcare resources by U.S. children and adults with inflammatory bowel disease","volume":"17","author":"Kappelman","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, Colitis Foundation of America, Bousvaros, A., Antonioli, D.A., Colletti, R.B., Dubinsky, M.C., Glickman, J.N., Gold, B.D., Griffiths, A.M., Jevon, G.P., and Higuchi, L.M. (2007). Differentiating Ulcerative Colitis from Crohn Disease in Children and Young Adults: Report of a Working Group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn\u2019s and Colitis Foundation of America. J. Pediatr. Gastroenterol. Nutr., 44, 653\u2013674.","DOI":"10.1097\/MPG.0b013e31805563f3"},{"key":"ref_39","first-page":"82","article-title":"Crohn\u2019s disease. The problem of early diagnosis","volume":"64","author":"Loginov","year":"1992","journal-title":"Ter. Arkh."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1365-2036.2006.03159.x","article-title":"Review article: Indeterminate colitis\u2014Definition, diagnosis and management","volume":"25","author":"Tremaine","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s11894-012-0244-x","article-title":"Is Indeterminate Colitis Determinable?","volume":"14","author":"Tremaine","year":"2012","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s10151-007-0337-y","article-title":"Indeterminate colitis","volume":"11","author":"Mitchell","year":"2007","journal-title":"Tech. Coloproctology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1007\/s10350-004-6461-0","article-title":"Indeterminate colitis: The real story","volume":"45","author":"Rudolph","year":"2002","journal-title":"Dis. Colon Rectum"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.2214\/ajr.184.6.01841843","article-title":"Crohn\u2019s Disease in the Ileal Pouch After Total Colectomy for Ulcerative Colitis: Findings on Pouch Enemas in Six Patients","volume":"184","author":"Levine","year":"2005","journal-title":"Am. J. Roentgenol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"670","DOI":"10.4253\/wjge.v7.i7.670","article-title":"Gastrointestinal endoscopy biopsy derived proteomic patterns predict indeterminate colitis into ulcerative colitis and Crohn\u2019s colitis","volume":"7","author":"Ballard","year":"2015","journal-title":"World J. Gastrointest. Endosc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.autrev.2014.01.028","article-title":"Diagnosis and classification of ulcerative colitis","volume":"13","author":"Conrad","year":"2014","journal-title":"Autoimmun. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.autrev.2014.01.029","article-title":"Diagnosis and classification of Crohn\u2019s disease","volume":"13","author":"Laass","year":"2014","journal-title":"Autoimmun. Rev."},{"key":"ref_48","first-page":"174","article-title":"Endoscopic and histologic findings in pediatric inflammatory bowel disease","volume":"6","author":"Jevon","year":"2010","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ejogrb.2013.08.011","article-title":"Surgical repair of rectovaginal fistulas in patients with Crohn\u2019s disease","volume":"171","author":"Nosti","year":"2013","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_50","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. Pr. Gastroenterol. Hepatol."},{"key":"ref_51","unstructured":"Nicholls, R.J., Bartolo, D., and Mortensen, N. (1993). Restorative Proctocolectomy, Blackwell Scientific Publications."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/bjs.1800780214","article-title":"Natural history of indeterminate colitis","volume":"78","author":"Wells","year":"1991","journal-title":"Br. J. Surg."},{"key":"ref_53","first-page":"4188","article-title":"Ubiquitous Colonic Ileal Metaplasia Consistent with the Diagnosis of Crohn\u2019s Colitis among Indeterminate Colitis Cohorts","volume":"11","author":"Breaux","year":"2023","journal-title":"Med. Res. Arch."},{"key":"ref_54","unstructured":"McDowell, C., Farooq, U., and Haseeb, M. (1988). Pathology of idiopathic inflammatory bowel disease. Inflammatory Bowel Disease, StatPearls."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/0002-9610(94)90248-8","article-title":"Restorative proctocolectomy and indeterminate colitis","volume":"167","author":"Atkinson","year":"1994","journal-title":"Am. J. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1097\/MPG.0000000000001032","article-title":"Endoscopic Versus Histological Disease Extent at Presentation of Paediatric Inflammatory Bowel Disease","volume":"62","author":"Ashton","year":"2016","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/ibd.20661","article-title":"Crohn\u2019s disease of the ileal pouch: Reality, diagnosis, and management","volume":"15","author":"Shen","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/his.12263","article-title":"Ulcerative colitis or Crohn\u2019s disease? Pitfalls and problems","volume":"64","author":"Feakins","year":"2013","journal-title":"Histopathology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/1751-2980.12278","article-title":"Surgical and medical treatment in patients with acute severe ulcerative colitis","volume":"16","author":"Fornaro","year":"2015","journal-title":"J. Dig. Dis."},{"key":"ref_60","first-page":"99","article-title":"Recent advances in medical and surgical treatment of ulcerative colitis","volume":"116","author":"Sugita","year":"2015","journal-title":"Nihon Geka Gakkai Zasshi"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/BF02053988","article-title":"Long-term results of ileal pouch-anal anastomosis in patients with Crohn\u2019s disease","volume":"39","author":"Sagar","year":"1996","journal-title":"Dis. Colon Rectum"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1097\/DCR.0000000000003894","article-title":"Improvement in Functional Outcomes Following Ileal Pouch-Anal Anastomosis: Results from the United States Ileal Pouch-Anal Anastomosis Study","volume":"68","author":"Zuckerman","year":"2025","journal-title":"Dis. Colon Rectum"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/ibd.20409","article-title":"Risk factors for pouch failure in patients with different phenotypes of Crohn\u2019s disease of the pouch","volume":"14","author":"Shen","year":"2008","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cgh.2007.11.006","article-title":"A Proposed Classification of Ileal Pouch Disorders and Associated Complications After Restorative Proctocolectomy","volume":"6","author":"Shen","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1007\/BF02047380","article-title":"Crohn\u2019s disease as a contraindication to Kock pouch (continent ileostomy)","volume":"36","author":"Handelsman","year":"1993","journal-title":"Dis. Colon Rectum"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/ibd.22955","article-title":"Surgical Outcome of Ileal Pouch\u2014Anal Anastomosis When Used Intentionally for Well-Defined Crohn\u2019s Disease","volume":"19","author":"Le","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/j.1365-2036.2009.04227.x","article-title":"Natural history of Crohn\u2019s disease in patients who underwent intentional restorative proctocolectomy with ileal pouch-anal anastomosis","volume":"31","author":"Shen","year":"2010","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_68","first-page":"69","article-title":"Ileal pouch-anal anastomosis for Crohn\u2019s disease. Current status","volume":"85","year":"2009","journal-title":"Cirugia Espanola"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/00054725-200305000-00004","article-title":"Long-Term Results of Ileal Pouch\u2013Anal Anastomosis in Crohn\u2019s Disease","volume":"9","author":"Biondo","year":"2003","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/ibd.21442","article-title":"Proteomic profiling of mucosal and submucosal colonic tissues yields protein signatures that differentiate the inflammatory colitides","volume":"17","author":"Seeley","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_71","unstructured":"M\u2019Koma, A.E., Wise, P.E., Schwartz, D.A., Washington, M.K., Muldoon, R.L., El-Rifai, W.M., and Herline, A.J. (2010, January 15\u201319). Gene Expression of Colonic Submucosa Differs Between the Inflammatory Colitides. Proceedings of the Annual Congress\u2014The American Society of Colon and Rectal Surgeons, Minneapolis, MN, USA."},{"key":"ref_72","unstructured":"M\u2019Koma, A.E., Seeley, E.H., Wise, P.E., Washingtoin, M.K., Schwartz, D.A., Caprioli, R.M., Muldon, R.L., and Herline, A.J. (October, January 30). Proteomic Patterns of Colonic Submucosa Discriminates Inflammatory Colitides. Proceedings of the Annual Congress\u2014The American Society of Colon and Rectal Surgeons, Hollywood, FL, USA."},{"key":"ref_73","first-page":"A-349","article-title":"M1096 Proteomic Analysis of Colonic Submucosa Differentiates Crohn\u2019s and Ulcerative Colitis","volume":"136","author":"Seeley","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_74","first-page":"S-525","article-title":"Human Alpha Defensins are Differentially Expressed Between the Inflammatory Colitides","volume":"138","author":"Wise","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/prca.201200107","article-title":"Proteomic patterns of colonic mucosal tissues delineate Crohn\u2019s colitis and ulcerative colitis","volume":"7","author":"Seeley","year":"2013","journal-title":"Proteom. Clin. Appl."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4137\/CGast.S20612","article-title":"Characterization of Serum Cytokine Profile in Predominantly Colonic Inflammatory Bowel Disease to Delineate Ulcerative and Crohn\u2019s Colitides","volume":"8","author":"Korolkova","year":"2015","journal-title":"Clin. Med. Insights Gastroenterol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S1079-2104(96)80150-8","article-title":"Attenuation of the natural course of herpes simplex virus infection in human oral epithelial cell cultures by smokeless tobacco extracts suggests the possibility of a synergistic mechanism for carcinogenesis","volume":"81","author":"Murrah","year":"1996","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1007\/s10350-005-0083-z","article-title":"Safety of One-Stage Restorative Proctocolectomy for Ulcerative Colitis","volume":"48","author":"Ikeuchi","year":"2005","journal-title":"Dis. Colon Rectum"},{"key":"ref_79","first-page":"109","article-title":"Surgery for ulcerative colitis","volume":"116","author":"Ikeuchi","year":"2015","journal-title":"Nihon Geka Gakkai Zasshi"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s00011-024-01970-w","article-title":"Functional characterization of novel anti-DEFA5 monoclonal antibody clones 1A8 and 4F5 in inflammatory bowel disease colitis tissues","volume":"74","author":"Thangaiyan","year":"2025","journal-title":"Inflamm. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/hmg\/10.5.445","article-title":"Ulcerative colitis and Crohn\u2019s disease: Distinctive gene expression profiles and novel susceptibility candidate genes","volume":"10","author":"Lawrance","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.taap.2003.09.005","article-title":"Surrogate tissue analysis: Monitoring toxicant exposure and health status of inaccessible tissues through the analysis of accessible tissues and cells","volume":"194","author":"Rockett","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/j.1572-0241.2007.01556.x","article-title":"Noninvasive Markers in the Assessment of Intestinal Inflammation in Inflammatory Bowel Diseases: Performance of Fecal Lactoferrin, Calprotectin, and PMN-Elastase, CRP, and Clinical Indices","volume":"103","author":"Langhorst","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1111\/j.1572-0241.2007.01699.x","article-title":"IgG Oligosaccharide Alterations Are a Novel Diagnostic Marker for Disease Activity and the Clinical Course of Inflammatory Bowel Disease","volume":"103","author":"Shinzaki","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/j.1572-0241.2005.40819.x","article-title":"Protein Microarray Analysis of Disease Activity in Pediatric Inflammatory Bowel Disease Demonstrates Elevated Serum PLGF, IL-7, TGF-beta1, and IL-12p40 Levels in Crohn\u2019s Disease and Ulcerative Colitis Patients in Remission versus Active Disease","volume":"100","author":"Kader","year":"2005","journal-title":"Am. J. Gastroenterol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2353\/jmoldx.2006.050079","article-title":"Molecular Classification of Crohn\u2019s Disease and Ulcerative Colitis Patients Using Transcriptional Profiles in Peripheral Blood Mononuclear Cells","volume":"8","author":"Burczynski","year":"2006","journal-title":"J. Mol. Diagn."},{"key":"ref_87","first-page":"33","article-title":"Perinuclear Antineutrophil Cytoplasmic Autoantibodies and Anti-Saccharomyces Cerevisiae Antibodies as Serological Markers Are Not Specific in the Identification of Crohn\u2019s Disease and Ulcerative Colitis","volume":"22","author":"Anand","year":"2008","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_88","first-page":"167","article-title":"Serologic markers in inflammatory bowel disease: State of the art","volume":"4","author":"Sandborn","year":"2004","journal-title":"Rev. Gastroenterol. Disord."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1097\/00054725-200309000-00002","article-title":"Inflammatory Bowel Disease-Associated Gene Expression in Intestinal Epithelial Cells by Differential cDNA Screening and mRNA Display","volume":"9","author":"Fukushima","year":"2003","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1021\/pr060433m","article-title":"Differential Protein Expression Profile in the Intestinal Epithelium from Patients with Inflammatory Bowel Disease","volume":"6","author":"Shkoda","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.prp.2004.02.002","article-title":"Proteomics and chronic inflammatory bowel diseases","volume":"200","year":"2004","journal-title":"Pathol. Res. Pr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1373\/clinchem.2005.058560","article-title":"Serologic Markers in Inflammatory Bowel Disease","volume":"52","author":"Bossuyt","year":"2006","journal-title":"Clin. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1136\/gut.2004.043406","article-title":"Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn\u2019s disease","volume":"54","author":"Costa","year":"2005","journal-title":"Gut"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1136\/gut.1.2.87","article-title":"Crohn\u2019s Disease (Regional Enteritis) of the Large Intestine and its Distinction from Ulcerative Colitis","volume":"1","author":"Morson","year":"1960","journal-title":"Gut"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1136\/gut.5.6.493","article-title":"Crohn\u2019s Disease of the Large Intestine","volume":"5","author":"Morson","year":"1964","journal-title":"Gut"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1136\/bmj.284.6309.91","article-title":"Diagnosis of inflammatory bowel disease: An international multicentre scoring system","volume":"284","author":"Clamp","year":"1982","journal-title":"Br. Med. J."},{"key":"ref_97","first-page":"173","article-title":"Indeterminate colitis in the spectrum of inflammatory bowel-disease","volume":"103","author":"Lee","year":"1979","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0016-5085(66)80054-9","article-title":"Granulomatous colitis and atypical ulcerative colitis","volume":"50","author":"Lewin","year":"1966","journal-title":"Gastyroenterology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1136\/jcp.48.8.749","article-title":"Histological discrimination of idiopathic inflammatory bowel disease from other types of colitis","volume":"48","author":"Berre","year":"1995","journal-title":"J. Clin. Pathol."},{"key":"ref_100","first-page":"120","article-title":"Is \u201cindeterminate colitis\u201d Crohn\u2019s disease in the long-term follow-up?","volume":"79","author":"Kangas","year":"1994","journal-title":"Int. Surg."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/BF01647703","article-title":"The differential diagnosis of idiopathic inflammatory disease by colorectal biopsy","volume":"2","author":"Hamilton","year":"1987","journal-title":"Int. J. Color. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/BF02555768","article-title":"Outcome of \u201cindeterminant\u201d colitis following ileal pouch-anal anastomosis","volume":"32","author":"Pezim","year":"1989","journal-title":"Dis. Colon Rectum"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/BF02049932","article-title":"Results of the pelvic-pouch procedure in patients with Crohn\u2019s disease","volume":"34","author":"Deutsch","year":"1991","journal-title":"Dis. Colon Rectum"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1136\/gut.34.10.1384","article-title":"Outcome of restorative proctocolectomy when the diagnosis is suggestive of Crohn\u2019s disease","volume":"34","author":"Grobler","year":"1993","journal-title":"Gut"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1007\/BF02234634","article-title":"How does pouch construction for a final diagnosis of Crohn\u2019s disease compare with ileoproctostomy for established Crohn\u2019s proctocolitis?","volume":"44","author":"Mylonakis","year":"2001","journal-title":"Dis. Colon Rectum"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1007\/s11894-001-0069-5","article-title":"Medical management of postoperative complications of inflammatory bowel disease: Pouchitis and crohn\u2019s disease recurrence","volume":"3","author":"Achkar","year":"2001","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_107","first-page":"173","article-title":"Indeterminate colitis\u2014Definition, diagnosis, characteristics and management","volume":"3","author":"Telakis","year":"2008","journal-title":"Ann. Gastroenterol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2147\/CEG.S44700","article-title":"The natural course of inflammatory bowel disease-indeterminate from childhood to adulthood: Within a 25 year period","volume":"6","author":"Malaty","year":"2013","journal-title":"Clin. Exp. Gastroenterol."},{"key":"ref_109","first-page":"293","article-title":"Chronic inflammatory bowel disease in children and adolescents in Sweden","volume":"13","author":"Hildebrand","year":"1991","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/j.1651-2227.1994.tb13098.x","article-title":"Incidence and prevalence of inflammatory bowel disease in children in South-Western Sweden","volume":"83","author":"Hildebrand","year":"2008","journal-title":"Acta Paediatr."},{"key":"ref_111","first-page":"259","article-title":"Inflammatory bowel disease in children and adolescents in Sweden, 1984\u20131995","volume":"30","author":"Lindberg","year":"2000","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/MPG.0b013e3181b99baa","article-title":"Rising Incidence of Inflammatory Bowel Disease Among Children: A 12-year Study","volume":"50","author":"Malaty","year":"2010","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1067\/S0022-3476(03)00444-X","article-title":"Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in wisconsin: A statewide population-based study","volume":"143","author":"Kugathasan","year":"2003","journal-title":"J. Pediatr."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1053\/j.gastro.2004.01.063","article-title":"Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences","volume":"126","author":"Loftus","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1097\/00054725-200608000-00002","article-title":"Incidence of inflammatory bowel disease in Finnish chil-dren, 1987\u20132003","volume":"12","author":"Turunen","year":"2006","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1097\/MCG.0b013e318247c32f","article-title":"Natural History of Pediatric-onset Inflammatory Bowel Disease: A systematic review","volume":"46","author":"Abraham","year":"2012","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_117","first-page":"S14","article-title":"Indeterminate IBD: The magnitude of the problem","volume":"6","author":"Ekbom","year":"2000","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0041-624X(77)90087-7","article-title":"Tumour detection by ultrasonic Doppler blood-flow signals","volume":"15","author":"Wells","year":"1977","journal-title":"Ultrasonics"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1001\/archsurg.137.6.690","article-title":"Similar Functional Results and Complications After Ileal Pouch\u2013Anal Anastomosis in Patients with Indeterminate vs Ulcerative Colitis","volume":"137","author":"Dayton","year":"2002","journal-title":"Arch. Surg."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/01.MIB.0000215093.62245.b9","article-title":"Indeterminate colitis: A significant subgroup of pediatric IBD","volume":"12","author":"Carvalho","year":"2006","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1097\/00042737-199908000-00018","article-title":"Frequency and clinical evolution of indeterminate colitis: A retrospective multi-centre study in northern Italy. GSMII (Gruppo di Studio per le Malattie Infiammatorie Intestinali)","volume":"11","author":"Meucci","year":"1999","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_122","first-page":"2081","article-title":"Long-term outcomes of ileal pouch-anal canal anastomosis in children with ulcerative colitis","volume":"110","author":"Tatsumi","year":"2013","journal-title":"Nihon Shokakibyo Gakkai Zasshi (Jpn. J. Gastro-Enterol.)"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"S56","DOI":"10.1016\/j.ijsu.2014.08.380","article-title":"Restorative proctocolectomy with ileal pouch-anal anastomosis is safe and effective in selected very elderly patients suffering from ulcerative colitis","volume":"12","author":"Pellino","year":"2014","journal-title":"Int. J. Surg."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1007\/s00383-013-3425-2","article-title":"Role of surgery in pediatric ulcerative colitis","volume":"29","author":"Ceriati","year":"2013","journal-title":"Pediatr. Surg. Int."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/DCR.0000000000000282","article-title":"National Trends of 3- Versus 2-Stage Restorative Proctocolectomy for Chronic Ulcerative Colitis","volume":"58","author":"Bikhchandani","year":"2015","journal-title":"Dis. Colon Rectum"},{"key":"ref_126","first-page":"340341","article-title":"Functional Outcomes and Quality of Life after Restorative Proctocolectomy in Paediatric Patients: A Case-Control Study","volume":"2014","author":"Pellino","year":"2014","journal-title":"Gastroenterol. Res. Pr."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/01.dcr.0000437691.52109.f2","article-title":"Do Clinical Characteristics of de Novo Pouch Crohn\u2019s Disease After Restorative Proctocolectomy Affect Ileal Pouch Retention?","volume":"57","author":"Gu","year":"2014","journal-title":"Dis. Colon Rectum"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1016\/S0300-2977(98)00123-5","article-title":"Is there a place for ileal pouch-anal anastomosis in patients with Crohn\u2019s colitis?","volume":"53","author":"Panis","year":"1998","journal-title":"Neth. J. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/S0140-6736(96)91344-6","article-title":"Ileal pouch\/anal anastomosis for Crohn\u2019s disease","volume":"347","author":"Panis","year":"1996","journal-title":"Lancet"},{"key":"ref_130","first-page":"446","article-title":"Histoclinic of \u201cindeterminate colitis\u201d","volume":"22","author":"Koktysz","year":"2007","journal-title":"Pol. Merkur. Lek. Organ Pol. Tow. Lek."}],"updated-by":[{"DOI":"10.3390\/jcm15041519","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000}}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/23\/8390\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:41:50Z","timestamp":1771231310000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/23\/8390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":130,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["jcm14238390"],"URL":"https:\/\/doi.org\/10.3390\/jcm14238390","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}