Controversies in IPAA for Ulcerative Colitis: A Systematic Review of Different Anastomotic Techniques.

BACKGROUND: Available techniques for IPAA in ulcerative colitis include handsewn, double-stapled, and single-stapled anastomoses. There are controversies, indications, and different outcomes regarding these techniques. OBJECTIVE: To describe technical details, indications, and outcomes of 3 specific types of anastomoses in restorative proctocolectomy. DATA SOURCE: Systematic literature review for articles in the PubMed database according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. STUDY SELECTION: Studies describing outcomes of the 3 different types of anastomoses, during pouch surgery, in patients undergoing restorative proctocolectomy for ulcerative colitis. INTERVENTION: IPAA technique. MAIN OUTCOME MEASURES: Postoperative outcomes (anastomotic leaks, overall complication rates, and pouch function). RESULTS: Twenty-one studies were initially included: 6 studies exclusively on single-stapled IPAA, 2 exclusively on double-stapled IPAA, 6 studies comparing single-stapled to double-stapled techniques, 6 comparing double-stapled to handsewn IPAA, and 1 comprising single-stapled to handsewn IPAA. Thirty-seven studies were added according to authors' discretion as complementary evidence. Between 1990 and 2015, most studies were related to double-stapled IPAA, either only analyzing the results of this technique or comparing it with the handsewn technique. Studies published after 2015 were mostly related to transanal approaches to proctectomy for IPAA, in which a single-stapled anastomosis was introduced instead of the double-stapled anastomosis, with some studies comparing both techniques. LIMITATIONS: A low number of studies with handsewn IPAA technique and a large number of studies added at authors' discretion were the limitations of this strudy. CONCLUSIONS: Handsewn IPAA should be considered if a mucosectomy is performed for dysplasia or cancer in the low rectum or, possibly, for re-do surgery. Double-stapled IPAA has been more widely adopted for its simplicity and for the advantage of preserving the anal transition zone, having lower complications, and having adequate pouch function. The single-stapled IPAA offers a more natural design, is feasible, and is associated with reasonable outcomes compared to double-stapled anastomosis. See video from symposium.

IRF4 instructs effector Treg differentiation and immune suppression in human cancer.

The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non-small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. In contrast to the IRF4- counterparts, IRF4+ Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for immunosuppression in tumors. Accordingly, deletion of Irf4 exclusively in Tregs resulted in delayed tumor growth in mice while the abundance of IRF4+ Tregs correlated with poor prognosis in patients with multiple human cancers. Thus, a common mechanism underlies immunosuppression in the tumor microenvironment irrespective of the tumor type.