Comparison of open and closed hyperthermic intraperitoneal chemotherapy: Results from the United States hyperthermic intraperitoneal chemotherapy collaborative

BACKGROUND Cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)for peritoneal carcinomatosis can be performed in two ways:Open or closed abdominal technique.AIM To evaluate the impact of HIPEC method on post-operative and long-term survival outcomes.METHODS Patients undergoing CRS with HIPEC from 2000-2017 were identified in the United States HIPEC collaborative database.Post-operative,recurrence,and overall survival outcomes were compared between those who received open vs closed HIPEC.RESULTS Of the 1812 patients undergoing curative-intent CRS and HIPEC,372(21%)patients underwent open HIPEC and 1440(79%)underwent closed HIPEC.There was no difference in re-operation or severe complications between the two groups.Closed HIPEC had higher rates of 90-d readmission while open HIPEC had a higher rate of 90-d mortalities.On multi-variable analysis,closed HIPEC technique was not a significant predictor for overall survival(hazards ratio:0.75,95%confidence interval:0.51-1.10,P=0.14)or recurrence-free survival(hazards ratio:1.39,95%confidence interval:1.00-1.93,P=0.05)in the entire cohort.These findings remained consistent in the appendiceal and the colorectal subgroups.CONCLUSION In this multi-institutional analysis,the HIPEC method was not independently associated with relevant post-operative or long-term outcomes.HIPEC technique may be left to the discretion of the operating surgeon.

Regulation of antiviral innate immunity by deubiquitinase CYLD

An antiviral innate immune response involves induction of type I interferons(IFNs)and their subsequent autocrine and paracrine actions,but the underlying regulatory mechanisms are incompletely understood.Here we report that CYLD,a deubiquitinase that specifically digests lysine 63-linked ubiquitin chains,is required for antiviral host defense.Loss of CYLD renders mice considerably more susceptible to infection by vesicular stomatitis virus(VSV).Consistently,CYLD-deficient dendritic cells are more sensitive to VSV infection.This functional defect was not due to lack of type I IFN production but rather because of attenuated IFN receptor signaling.In the absence of CYLD,IFN-b is ineffective in the induction of antiviral genes and protection of cells from viral infection.These findings establish CYLD as a novel regulator of antiviral innate immunity and suggest a role for CYLD in regulating IFN receptor signaling.