A Randomized, Controlled Trial Evaluating Perioperative Risk-Stratification and Risk-Based, Protocol-Driven Management After Elective Major Cancer Surgery.

Objective: We evaluated the efficacy of risk-based, protocol-driven management versus (vs) usual management after elective major cancer surgery to reduce 30-day rates of postoperative death or serious complications (DSC) .

Summary Background Data: Major cancer surgery is associated with significant perioperative risks which result in worse long-term outcomes.

Methods: Adults scheduled for elective major cancer surgery were stratified/randomized to risk-based escalating levels of care, monitoring, and co-management vs usual management.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies.

The effect of social determinants of health on utilization of surgical treatment for hepatocellular carcinoma patients.

Background: A paucity of data exists on how social determinants of health (SDOH) influence treatment for Hepatocellular carcinoma (HCC). We investigated associations between SDOH (healthcare access, education, social/community context, economic stability, and built/neighborhood environment) and receipt of surgery.

Methods: The Pennsylvania Liver Cancer Registry was linked with neighborhood SDOH from the American Community Survey.

Discrepancies in survival after conversion to open in minimally invasive pancreatoduodenectomy.

Background: The extent by which conversion to open (CTO) during minimally invasive procedures for pancreatic cancer impact survival outcomes is not fully understood.

Methods: The 2010-2017 National Cancer Database identified 12,424 non-metastatic patients who underwent pancreatoduodenectomy for ductal adenocarcinoma. Patients were stratified into three cohorts: open (OPD), completed MIPD (cMIPD), and CTO.

Risk of Lymph Node Metastasis in T1b Gastric Cancer: An International Comprehensive Analysis from the Global Gastric Group (G3) Alliance.

Objective: We sought to define criteria associated with low lymph node metastasis risk in patients with submucosal (pT1b) gastric cancer from 3 Western and 3 Eastern countries.

Summary Background Data: Accurate prediction of lymph node metastasis risk is essential when determining the need for gastrectomy with lymph node dissection following endoscopic resection. Under present guidelines, endoscopic resection is considered definitive treatment if submucosal invasion is only superficial, but this is not routinely assessed.

Combined Blockade of MEK and CDK4/6 Pathways Induces Senescence to Improve Survival in Pancreatic Ductal Adenocarcinoma.

Activating mutations, a defining feature of pancreatic ductal adenocarcinoma (PDAC), promote tumor growth in part through the activation of cyclin-dependent kinases (CDK) that induce cell-cycle progression. p16 (p16), encoded by the gene , is a potent inhibitor of CDK4/6 and serves as a critical checkpoint of cell proliferation. Mutations in and subsequent loss of the p16 gene occur in PDAC at a rate higher than that reported in any other tumor type and results in Rb inactivation and unrestricted cellular growth.

Src kinase inhibition restores E-cadherin expression in dasatinib-sensitive pancreatic cancer cells.

The Src family of non-receptor tyrosine kinases are frequently activated in pancreatic ductal adenocarcinoma (PDAC), contributing to disease progression through downregulation of E-cadherin and induction of epithelial-to-mesenchymal transition (EMT). The purpose of this study was to examine the efficacy of Src kinase inhibition in restoring E-cadherin levels in PDAC. Immunohistochemical analysis of human PDAC samples showed Src activation is inversely correlated with E-cadherin levels.

Urolithin A, a Novel Natural Compound to Target PI3K/AKT/mTOR Pathway in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy and is highly resistant to standard treatment regimens. Targeted therapies against , a mutation present in an overwhelming majority of PDAC cases, have been largely ineffective. However, inhibition of downstream components in the KRAS signaling cascade provides promising therapeutic targets in the management of PDAC and warrants further exploration.

Tobacco Carcinogen-Induced Production of GM-CSF Activates CREB to Promote Pancreatic Cancer.

Although smoking is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC), the molecular mechanisms underlying PDAC development and progression in smokers are still unclear. Here, we show the role of cyclic AMP response element-binding protein (CREB) in the pathogenesis of smoking-induced PDAC. Smokers had significantly higher levels of activated CREB when compared with nonsmokers.

Inverse Correlation of STAT3 and MEK Signaling Mediates Resistance to RAS Pathway Inhibition in Pancreatic Cancer.

Major contributors to therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC) include mutations, a dense desmoplastic stroma that prevents drug delivery to the tumor, and activation of redundant signaling pathways. We have previously identified a mechanistic rationale for targeting STAT3 signaling to overcome therapeutic resistance in PDAC. In this study, we investigate the molecular mechanisms underlying the heterogeneous response to STAT3 and RAS pathway inhibition in PDAC.

Adiponectin receptor agonists inhibit leptin induced pSTAT3 and pancreatic tumor growth.

Obesity is a significant risk factor for pancreatic cancer, harboring a chronic inflammatory condition characterized by dysregulation of the adipokines, leptin and adiponectin, that in turn alter oncogenic signaling pathways. We and others have shown that leptin promotes the proliferation and an invasive potential of pancreatic cancer cells through STAT3 mediated signaling. However, the role of adiponectin on the tumorigenicity of pancreatic cancer has not been elucidated.

Pancreatic stellate cell secreted IL-6 stimulates STAT3 dependent invasiveness of pancreatic intraepithelial neoplasia and cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is a dynamic tumor supported by several stromal elements such as pancreatic stellate cells (PSC). Significant crosstalk exists between PSCs and tumor cells to stimulate oncogenic signaling and malignant progression of PDAC. However, how PSCs activate intercellular signaling in PDAC cells remains to be elucidated.

Implementation of a Telephone Postoperative Clinic in an Integrated Health System.

Background: Earlier work suggested that telephone follow-up could be used in lieu of in-person follow-up after surgery, saving patients time and travel and maximizing use of scarce surgeon and facility resources. We report our experience implementing and evaluating telephone postoperative follow-up within an integrated health system.

Study Design: We conducted a pre-post evaluation of a general surgery telephone postoperative clinic at a tertiary care Veterans Affairs facility from April 2015 to February 2016.

Optical Imaging of Drug-Induced Metabolism Changes in Murine and Human Pancreatic Cancer Organoids Reveals Heterogeneous Drug Response.

Objectives: Three-dimensional organoids derived from primary pancreatic ductal adenocarcinomas are an attractive platform for testing potential anticancer drugs on patient-specific tissue. Optical metabolic imaging (OMI) is a novel tool used to assess drug-induced changes in cellular metabolism, and its quantitative end point, the OMI index, is evaluated as a biomarker of drug response in pancreatic cancer organoids.

Methods: Optical metabolic imaging is used to assess both malignant cell and fibroblast drug response within primary murine and human pancreatic cancer organoids.

Signal Transducer and Activator of Transcription 3, Mediated Remodeling of the Tumor Microenvironment Results in Enhanced Tumor Drug Delivery in a Mouse Model of Pancreatic Cancer.

Background & Aims: A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence of a dense desmoplastic reaction (stroma) that impedes drug delivery to the tumor. Attempts to deplete the tumor stroma have resulted in formation of more aggressive tumors. We have identified signal transducer and activator of transcription (STAT) 3 as a biomarker of resistance to cytotoxic and molecularly targeted therapy in PDAC.

Strategies for Management of Synchronous Colorectal Metastases.

The management of synchronous presentation of colorectal cancer and liver metastases has long been a topic of debate and discussion for surgeons due to the unique dilemma of balancing operative timing along with treatment strategy. Operative strategies for resection include staged resection with colon first approach, "reverse" staged resection with liver metastases resected first, and one-stage, or simultaneous, resection of both the primary tumor and liver metastases approach. These operative strategies can be further augmented with perioperative chemotherapy and other novel approaches that may improve resectability and patient survival.

Intensity of follow-up after pancreatic cancer resection.

The prognosis of patients diagnosed with pancreatic adenocarcinoma remains dismal. Of the 15-20 % of patients who are candidates for potentially curative resection, 66-92 % will develop recurrent disease. Although guidelines for surveillance in the postoperative setting exist, they are not evidence based, and there is wide variability of strategies utilized.

Emerging targets in pancreatic cancer: epithelial-mesenchymal transition and cancer stem cells.

Pancreatic ductal adenocarcinoma is one of the most aggressive solid malignancies and is characterized by poor response to current therapy and a dismal survival rate. Recent insights regarding the role of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) in tumorigenesis have brought further understanding to the field and have highlighted new therapeutic targets. CSCs are a distinct subset of cancer cells, with the ability to differentiate into other cell types and self-renew in order to fuel the maintenance of tumor amplification.

Adjuvant chemoradiation therapy for pancreatic adenocarcinoma: who really benefits?

Background: The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients.

Study Design: Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included.