Talar Tatarian

Cytoplasmic HuR Status Predicts Disease-free Survival in Resected Pancreatic Cancer A Post-hoc Analysis From the International Phase III ESPAC-3 Clinical Trial

Objectives: We tested cytoplasmic HuR (cHuR) as a predictive marker for response to chemotherapy by examining tumor samples from the international European Study Group of Pancreatic Cancer-3 trial, in which patients with resected pancreatic ductal adenocarcinoma (PDA) received either gemcitabine (GEM) or 5-fluorouracil (5-FU) adjuvant monotherapy. Background: Previous studies have implicated the mRNA-binding protein, HuR (ELAVL1), as a predictive marker for PDA treatment response in the adjuvant setting. These studies were, however, based on small cohorts of patients outside of a clinical trial, or a clinical trial in which patients received multimodality therapy with concomitant radiation. Methods: Tissue samples from 379 patients with PDA enrolled in the European Study Group of Pancreatic Cancer-3 trial were immunolabeled with an anti-HuR antibody and scored for cHuR expression. Patients were dichotomized into groups of high versus low cHuR expression. Results: There was no association between cHuR expression and prognosis in the overall cohort [disease-free survival (DFS), P = 0.44; overall survival, P = 0.41). Median DFS for patients with high cHuR was significantly greater for patients treated with 5-FU compared to GEM [20.1 months, confidence interval (CI): 8.3–36.4 vs 10.9 months, CI: 7.5–14.2; P = 0.04]. Median DFS was similar between the treatment arms in patients with low cHuR (5-FU, 12.8 months, CI: 10.6–14.6 vs GEM, 12.9 months, CI: 11.2–15.4). Conclusions: Patients with high cHuR-expressing tumors may benefit from 5-FU-based adjuvant therapy as compared to GEM, whereas those patients with low cHuR appear to have no survival advantage with GEM compared with 5-FU. Further studies are needed to validate HuR as a biomarker in both future monotherapy and multiagent regimens.

Genetics of Pancreatic Cancer and Its Implications on Therapy

Over the past decade, emerging technologies have provided new insights into the genomic landscape of pancreatic ductal adenocarcinoma (PDA). In addition to the commonly recognized genetic drivers of pancreatic carcinogenesis (KRAS, CDKN2A, TP53, SMAD4), new genes and pathways have been implicated. However, these efforts have not identified any new high-frequency actionable mutations, limiting the success of mutation-targeted therapy in PDA. This article provides a report on the current landscape of pancreas cancer genetics and targeted therapeutics.

A Modern Approach to the Surgical Treatment of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common disorder that can cause a variety of typical and atypical symptoms. Although most patients can be rendered asymptomatic with medical treatment, some experience persistent breakthrough symptoms. A long history of GERD is associated with the risk for the development of Barretts esophagus and ultimately esophageal carcinoma. Although often underutilized, minimally invasive antireflux surgery can help manage these patients. However, thorough evaluation and accurate diagnosis of GERD and its underlying pathophysiology are critical in ensuring successful surgical treatment. This review offers a stepwise approach to the diagnostic workup of GERD and how to appropriately tailor available surgical treatments to specific patient subgroups.

Fundamentals of Gastrointestinal Anastomoses

The creation of a gastrointestinal anastomosis is a fundamental skill essential to general surgery. This chapter will detail the history of gastrointestinal anastomoses, will provide general principles to be used when joining segments in the gastrointestinal tract, and will review key technical considerations that the general surgeon should keep in mind when constructing some of the most common intestinal anastomoses. A brief review of current controversial areas is also provided.

Acute Complications of Antireflux Surgery

Laparoscopic antireflux surgery (LARS) is considered the gold standard for the surgical management of severe gastroesophageal reflux disease. While underutilized for fear of occasional long-term side effects, it remains a safe operation with a very low complication rate. The prevention of acute and chronic complications begins with appropriate patient selection, surgical plan, and surgeon experience. Additionally, there are several potential error traps that are encountered during LARS that can contribute to acute intraoperative or early postoperative complications. This chapter will serve as a step-by-step review of the acute complications that can occur in the perioperative period of LARS.