Secure Ileal Pouch–Anal Anastomosis for Histologic Indeterminate Colitis

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’s 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, “the restorative proctocolectomy with ileal pouch–anal anastomosis (PRC-IPAA)”. Transforming the distinction between UC and CC in otherwise IC into authentic UC and CC requires priority attention when considering a patient’s 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) “colonic ileal metaplasia” 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.