Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress.

Sigma-2-ligands (S2L) are characterized by high binding affinities to their cognate sigma-2 receptor, overexpressed in rapidly proliferating tumor cells. As such, S2L were developed as imaging probes (ISO1) or as cancer therapeutics, alone (SV119 [C6], SW43 [C10]) and as delivery vehicles for cytotoxic drug cargoes (C6-Erastin, C10-SMAC). However, the exact mechanism of S2L-induced cytotoxicity remains to be fully elucidated.

Impact of Preoperative Jaundice and Biliary Drainage on Short- and Long-term Outcomes among Patients with Gallbladder Cancer.

Objectives: To characterize the prognostic implication of jaundice and preoperative biliary drainage on postoperative outcomes among patients with gallbladder cancer (GBC) undergoing surgical resection.

Methods: Patients who underwent surgical resection of GBC identified from a multicenter database between January 2000 and December 2019 were retrospectively analyzed. Data on clinical and pathological details, as well as short- and long-term overall survival (OS), were obtained and compared among patients with and without preoperative jaundice and biliary drainage.

Development of a Prognostic Nomogram and Nomogram Software Application Tool to Predict Overall Survival and Disease-Free Survival After Curative-Intent Gastrectomy for Gastric Cancer.

Background: We sought to derive and validate a prediction model of survival and recurrence among Western patients undergoing resection of gastric cancer.

Methods: Patients who underwent curative-intent surgery for gastric cancer at seven US institutions and a major Italian center from 2000 to 2020 were included. Variables included in the multivariable Cox models were identified using an automated model selection procedure based on an algorithm.

Cumulative GRAS Score as a Predictor of Survival After Resection for Adrenocortical Carcinoma: Analysis From the U.S. Adrenocortical Carcinoma Database.

Background: Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection.

Thunderbeat™ Integrated Bipolar and Ultrasonic Forceps in the Whipple Procedure: A Prospective Randomized Trial.

Thunderbeat™ is a device that uses both ultrasonic and advanced bipolar energies to achieve hemostasis. It has been evaluated in a variety of clinical contexts, but no literature exists regarding its application to pancreatic surgery. Using a prospective, randomized controlled trial, we evaluated its safety and efficacy in the Whipple procedure.

Features of synchronous versus metachronous metastasectomy in adrenal cortical carcinoma: Analysis from the US adrenocortical carcinoma database.

Background: Adrenocortical carcinoma is a rare, aggressive cancer. We compared features of patients who underwent synchronous versus metachronous metastasectomy.

Methods: Adult patients who underwent resection for metastatic adrenocortical carcinoma from 1993 to 2014 at 13 institutions of the US adrenocortical carcinoma group were analyzed retrospectively.

TMEM97 and PGRMC1 do not mediate sigma-2 ligand-induced cell death.

Sigma-2 receptors have been implicated in both tumor proliferation and neurodegenerative diseases. Recently the sigma-2 receptor was identified as transmembrane protein 97 (TMEM97). Progesterone receptor membrane component 1 (PGRMC1) was also recently reported to form a complex with TMEM97 and the low density lipoprotein (LDL) receptor, and this trimeric complex is responsible for the rapid internalization of LDL.

Staging laparoscopy among three subtypes of extra-hepatic biliary malignancy: a 15-year experience from 10 institutions.

Background: Staging laparoscopy (SL) is used to avoid resection failure and thus increase the curative resection rate. SL utilization in extra-hepatic biliary tumors (EHBT) is variable.

Methods: Data from 1090 patients with potentially resectable EHBT including gallbladder (GBC), distal (DC), and hilar (HC) subtypes were retrospectively collected from 10 academic centers (2000-2015).

Role of Additional Organ Resection in Adrenocortical Carcinoma: Analysis of 167 Patients from the U.S. Adrenocortical Carcinoma Database.

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer. This report describes factors and outcomes associated with resection of extra-adrenal organs en bloc during index adrenalectomy.

Methods: Patients who underwent ACC resection for non-metastatic disease from 1993 to 2014 at 13 participating institutions of the US-ACC Group were included in the study.

Accuracy of the ACS NSQIP Online Risk Calculator Depends on How You Look at It: Results from the United States Gastric Cancer Collaborative.

The objective of this study is to assess the accuracy of the American College of Surgeons National Surgical Quality Improvement Program online risk calculator for estimating risk after operation for gastric cancer using the United States Gastric Cancer Collaborative. Nine hundred and sixty-five patients who underwent resection of gastric adenocarcinoma between January 2000 and December 2012 at seven academic medical centers were included. Actual complication rates and outcomes for patients were compared.

The Impact of Intraoperative Re-Resection of a Positive Bile Duct Margin on Clinical Outcomes for Hilar Cholangiocarcinoma.

Background: The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA.

Methods: Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers.

Defining Early Recurrence of Hilar Cholangiocarcinoma After Curative-intent Surgery: A Multi-institutional Study from the US Extrahepatic Biliary Malignancy Consortium.

Background: Time to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection.

Methods: A total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA.

Clinicopathologic score predicting lymph node metastasis in T1 gastric cancer.

Background: Although gastrectomy with adequate regional nodal examination is considered the standard of care for invasive gastric adenocarcinoma, endoscopic resection has been adopted increasingly in select patients with T1 gastric cancer. The objective of this study was to identify preoperative predictors of lymph node metastasis in patients in the United States with T1 gastric cancer.

Methods: Patients who underwent operative resection for T1 gastric cancer between 2000 and 2012 were identified from a multi-institutional database.

Adjuvant therapy is associated with improved survival after curative resection for hilar cholangiocarcinoma: A multi-institution analysis from the U.S. extrahepatic biliary malignancy consortium.

Background: Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection.

Oncologic effects of preoperative biliary drainage in resectable hilar cholangiocarcinoma: Percutaneous biliary drainage has no adverse effects on survival.

Background And Objectives: The objective of the current study was to define long-term survival of patients with resectable hilar cholangiocarcinoma (HCCA) after preoperative percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD).

Methods: Between 2000 and 2014, 240 patients who underwent curative-intent resection for HCCA were identified at 10 major hepatobiliary centers. Postoperative morbidity and mortality, as well as disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed among patients.

Outcomes after vascular resection during curative-intent resection for hilar cholangiocarcinoma: a multi-institution study from the US extrahepatic biliary malignancy consortium.

Background: Surgical resection is the cornerstone of curative-intent therapy for patients with hilar cholangiocarcinoma (HC). The role of vascular resection (VR) in the treatment of HC in western centres is not well defined.

Methods: Utilizing data from the U.

A Novel T-Stage Classification System for Adrenocortical Carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group.

Background: The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC.

The Effects of Travel Burden on Outcomes After Resection of Extrahepatic Biliary Malignancies: Results from the US Extrahepatic Biliary Consortium.

Background: Surgical resection of extrahepatic biliary malignancies has been increasingly centralized at high-volume tertiary care centers. While this has improved outcomes overall, increased travel burden has been associated with worse survival for many other malignancies. We hypothesized that longer travel distances are associated with worse outcomes for these patients as well.

Predictors and Prognostic Implications of Perioperative Chemotherapy Completion in Gastric Cancer.

Background: Perioperative chemotherapy in gastric cancer is increasingly used since the "MAGIC" trial, while clinical practice data outside of trials remain limited. We sought to evaluate the predictors and prognostic implications of perioperative chemotherapy completion in patients undergoing curative-intent gastrectomy across multiple US institutions.

Methods: Patients who underwent curative-intent resection of gastric adenocarcinoma between 2000 and 2012 in eight institutions of the US Gastric Cancer Collaborative were identified.

Blood Transfusion and Survival for Resected Adrenocortical Carcinoma: A Study from the United States Adrenocortical Carcinoma Group.

Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included.

Impact of lymph node ratio in selecting patients with resected gastric cancer for adjuvant therapy.

Background: The impact of adjuvant chemotherapy and chemo-radiation therapy in the treatment of resectable gastric cancer remains varied. We sought to define the clinical impact of lymph node ratio on the relative benefit of adjuvant chemotherapy or chemo-radiation therapy among patients having undergone curative-intent resection for gastric cancer.

Methods: Using the multi-institutional US Gastric Cancer Collaborative database, 719 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2013 were identified.

Tumor budding in intestinal-type gastric adenocarcinoma is associated with nodal metastasis and recurrence.

Gastric adenocarcinoma (GAC) is a common cause of cancer-related death worldwide. GAC can be classified as intestinal or diffuse. Intestinal-type cancers are common and reported to have a better prognosis compared to diffuse cancers.