Front Cover Image,Volume 121, Number 6, May 1, 2020

The treatment for perihilar cholangiocarcinoma (PHC) is a challenge for the surgeon requiring complex resections with a reported perioperative mortality rate between 15% and 48%. In PHC patients with future liver remnant (FLR) less than 30%, it is advised that hepatectomy can be safely performed after the FLR is modified. Associating Liver Partition and Portal vein ligation for Staged Hepatectomy (ALPPS) procedure is criticized heavily due to its high morbidity and mortality rate in this setting. Hereby, we are reporting a modification of ALPPS procedure for PHC. Clinical presentation, preoperative work-up as well as operation and postoperative course of two cases were described in detail. Both patients were jaundiced preoperatively, stage 1 partial-ALPPS procedures were performed laparoscopically, there was sufficient remnant hypertrophy during the interval stage and there was no posthepatectomy liver failure after the second stage (Supporting Information Video). We have followed patients with a mean follow up of 35 months without any recurrence. Here we describe the key technical aspects of this approach that are discussed in three parts: minimally invasive first stage, biliary drainage of both FLR, and deportalized liver at first stage and biliary reconstruction at the second stage. This technique, in selected patients, can extend the indication of ALPPS procedure for PHC with preoperative jaundice.     

Cover Image,Volume 62, Issue 2

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks targeted therapies. Previous studies have shown that TNBC cells are highly sensitive to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), making it a promising agent for treating TNBC. However, the development of TRAIL resistance limits its further clinical development, and the underlying mechanisms are not fully understood. In this study, we report the role of PD-L1 in TRAIL resistance. Specifically, we found that TRAIL treatment increases PD-L1 expression in TRAIL-sensitive cells and that basal PD-L1 expression is increased in acquired TRAIL-resistant cells. Mechanistically, we found that increased PD-L1 expression was accompanied by increased extracellular signal-regulated kinase (ERK) activation. Using both genetic and pharmacological approaches, we showed that knockdown of ERK by siRNA or inhibition of ERK activation by the mitogen-activated protein kinase kinase inhibitor U0126 decreased PD-L1 expression and increased TRAIL-induced cell death. Furthermore, we found that knockout or knockdown of PD-L1 enhances TRAIL-induced apoptosis, suggesting that PD-L1-mediated TRAIL resistance is independent of its ability to evade immune suppression. Therefore, this study identifies a noncanonical mechanism by which PD-L1 promotes TRAIL resistance, which can be potentially exploited for immune checkpoint therapy.