The MYTHS of De novo Crohn's Disease After Restorative Proctocolectomy with Ileal Pouch-anal Anastomosis for Ulcerative Colitis

Abstract

Background: 1.1.Inflammatory Bowel Disease (IBD) are the manifestation of overzealous dys-regulated immune response in the intestinal tract, directed primarily against the indigenous microbes combined with defective functioning of anti-inflammatory pathways. Finding a trustable lead to predicting de novo Crohn's Disease (CD) prior to performing "pouch surgery", Restorative Proctocolectomy (RPC) with Ileal Pouch-Anal Anastomosis (IPAA) for UC and/or Indeterminate Colitis (IC) is clinically important and remains debatable. De novo CD is a subsequent long-term postoperative complication in IBD patients with Ulcerative Colitis (UC) undergoing IPAA. Herewith we discuss this understanding in laboratory-based basic science research, with its molecular application as a possible corner stone tool for clinical progress and success in the IBD Clinic. Crypt Paneth cell (PCs) secreted enteroendocrine alpha-defensin 5 (DEFA5)" if developed properly is likely to solve diagnostic and prognostic difficulty in IBD Clinics. DEFA5 has shown the ability to differentiate the predominant subtypes of colonic IBD (CC vs. UC) at first endoscopy biopsy, avoiding diagnosis delay prior to colectomy. In addition, DEFA5 accurately circumvents indeterminate colitis (IC) patients into accurate IBD subtype (UC or CC). Further, DEFA5 can be used in selecting CC patients that may have positive outcomes after IPAA surgery [1]. Furthermore, likewise, DEFA5 can predict UC patients likely to have positive or poor outcome, e.g. those patients that are likely to transform/ convert and adhere to de novo Crohn's after IPAA can be picked up in endoscopy biopsy before surgery.

Aim: 1.2.To assessed comprehensive state-of-the-art understanding domains on the de novo Crohn's disease subsequent to IPAA surgery for ulcerative colitis.

Methods: 1.3.A literature search based on preferred reporting items for over-review and meta-analysis protocols (PRISMA-P) was performed. A comprehensive current search of PubMed, MEDLINE, CINAHL, Embase, Google^® search engine and Cochrane Database of collected reviews was performed from January 1990 through December 2018. The search consists of retrospective studies and case reports of reporting postoperative de novo CD incidence and adverse events. Secondary and hand/manual searches of reference lists, other studies cross-indexed by authors, reviews, commentaries, books and meeting abstracts were also performed. Studies were included only if the diagnosis of de novo CD was established clinically and histologically based on inflammation of afferent limb(s) or perianal disease. The search excluded non-English language and non-human studies as well as editorials.

Results: 1.4.Published data on de novo CD developing after RPC with IPAA are still limited. A total of three hundred and sixty-five (#365) patients in 13 publications reported de novo CD after a median follow-up of 66 (range: 3-236) months. All patients were diagnosed with clinically active pouch CD during follow-up surveillance after IPAA for UC or IC. A de novo CD diagnosis depended on either inflammation in the mucosa involving the small intestine proximal to the ileal pouch any time after IPAA surgery and/or when perianal complications developed after closure of a temporary diverting loop ileostomy. Successful management is facilitated by co-operation within a multidisciplinary team of gastroenterologists and colorectal surgeons and closely involving the patient in therapeutic decisions. Awareness of symptoms leads to timely consultation, diagnosis, treatment and restoration of intestinal continuity.

Conclusion: 1.5.The nature history and risk of de novo CD after IPAA for UC remains debatable. Chronic pouchitis and/or pouch failure often precedes a diagnosis of de novo CD. A successful management is facilitated by a triad cooperation between gastroenterologists, colorectal surgeons and the patient.

Keywords: Change of diagnosis; Conversion; De novo Crohn’s Disease; Human alpha-defensin 5; Ileal pouch-anal anastomosis; Proctocolectomy; Transformation; Ulcerative colitis.

Figure 1:

Kaplan-Meier estimated plot showing probability of surgery-free survival in relation to time after index dilatation in patients with anastomotic or de novo strictures (p = 0.86). This analysis is restricted to 83 patients having repeated dilatations only for strictures causing symptoms of bowel obstruction. Adapted with permission from “Endoscopic dilatation is an efficacious and safe treatment of intestinal strictures in Crohn’s disease”, by Gustavsson et al., Aliment Pharmacol Ther 2012;36:151–158 [24].

Figure 2:

Kaplan-Meier estimated plot showing probability of surgery-free survival in relation to time after index dilatation in patients with anastomotic or F strictures (p = 0.86). This analysis is restricted to 83 patients having repeated dilatations only for strictures causing symptoms of bowel obstruction. Adapted with permission from “Endoscopic dilatation is an efficacious and safe treatment of intestinal strictures in Crohn’s disease”, by Gustavsson et al., Aliment Pharmacol Ther 2012;36:151–158 [24].

Figure 3:

Kaplan-Meier estimated pouch survival in patients developing fistulas vs. without fistulas at the time of diagnosis of de novo Crohn’s disease. Adapted with permission from “Do clinical characteristics of de novo pouch Crohn’s disease after restorative proctocolectomy affect ileal pouch retention?” by Gu et al., Dis Colon Rectum 2014;57:76–82 [25].

Figure 4:

Kaplan-Meier estimated pouch survival in patients with different time interval from IPAA to de novo Crohn’s disease. Adapted with permission from “Do clinical characteristics of de novo pouch Crohn’s disease after restorative proctocolectomy affect ileal pouch retention? by Gu et al., Dis Colon Rectum 2014;57:76–82 [25].