A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma.

Purpose: This phase I study was conducted to determine the safety profile and maximum tolerated dose (MTD) of IMP321, a soluble lymphocyte activation gene-3 (LAG-3) Ig fusion protein and MHC Class II agonist, combined with gemcitabine in patients with advanced pancreatic adenocarcinoma.

Patients And Methods: Patients with advanced pancreatic adenocarcinoma were treated with gemcitabine (1,000 mg/m(2))(level 1), gemcitabine (1,000 mg/m(2)) plus IMP 321 at 0.5 mg (level 2) and 2.

Emerging strategies to prevent the development of pancreatic fistula after distal pancreatectomy.

Background: Pancreatic fistula occurs in approximately 30% of patients after distal pancreatectomy. Fistula formation is multifactorial in nature, influenced by patient-specific anatomic features of the pancreas and operative techniques at the time of resection.

Methods: In this article, we review past, present, and future strategies postulated to address this problem.

Therapeutic targeting of pancreatic cancer utilizing sigma-2 ligands.

One major barrier in the development of pancreas cancer therapeutics is the selective delivery of the drugs to their cellular targets. We have previously developed several sigma-2 ligands and reported the discovery of a component of the receptor for these ligands. Several sigma-2 ligands have been shown to trigger apoptosis in pancreas cancer cells.

Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.

Lysosomal membrane permeabilization is an early event in Sigma-2 receptor ligand mediated cell death in pancreatic cancer.

Background: Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden in preclinical models of human pancreatic cancer.

Mesh reinforcement of pancreatic transection decreases incidence of pancreatic occlusion failure for left pancreatectomy: a single-blinded, randomized controlled trial.

Introduction: Pancreatic leak or fistula is the most frequent complication after left pancreatectomy. We performed a single-blinded, parallel-group, randomized controlled trial comparing stapled left pancreatectomy with stapled left pancreatectomy using mesh reinforcement of the staple line with either Seamguard or Peristrips Dry.

Methods: All patients undergoing left pancreatectomy at a large tertiary hospital were eligible for participation.

Ki-67 predicts disease recurrence and poor prognosis in pancreatic neuroendocrine neoplasms.

Background: Pancreatic neuroendocrine neoplasms are rare malignancies for which the ideal staging method remains controversial. Ki-67 is a cell proliferation marker that has been shown to have some utility in predicting prognosis in neuroendocrine neoplasms. We sought to test the predictive ability of Ki-67 staining for disease recurrence and overall survival (OS) in pancreatic neuroendocrine neoplasms.

Multi-institutional analysis of pancreatic adenocarcinoma demonstrating the effect of diabetes status on survival after resection.

Background: The effect of diabetes on survival after resection pancreatic ductal carcinoma (PDAC) is unclear. The present study was undertaken to determine whether pre-operative diabetes has any predictive value for survival.

Methods: A retrospective review from seven centres was performed.

Resection of tumors of the neck of the pancreas with venous invasion: the "Whipple at the Splenic Artery (WATSA)" procedure.

Introduction: Tumors of the neck of the pancreas may involve the superior mesenteric and portal veins as well as the termination of the splenic vein. This presents a difficult problem since the pancreas cannot be transected through the neck as is standard in a Whipple procedure. Here, we present our method of resecting such tumors, which we term "Whipple at the Splenic Artery (WATSA)".

Systematic review of the clinical effectiveness of wound-edge protection devices in reducing surgical site infection in patients undergoing open abdominal surgery.

Objective: Assess the existing evidence on the clinical effectiveness of wound-edge protection devices (WEPDs) in reducing the surgical site infection (SSI) rate in patients undergoing open abdominal surgery.

Background: Surgical site infections are a common postoperative complication associated with considerable morbidity, extended hospital stay, increased health care costs, and reduced quality of life. Wound-edge protection devices have been used in surgery to reduce SSI rates for more than 40 years; however, they are yet to be cited in major clinical guidelines addressing SSI management.

Long-term results of resection of adenocarcinoma of the body and tail of the pancreas using radical antegrade modular pancreatosplenectomy procedure.

Background: The radical antegrade modular pancreatosplenectomy (RAMPS) procedure is a modification of standard distal pancreatosplenectomy. It was designed to provide the operative approach developed for cancers of the head of the pancreas to cancers of the body and tail of the pancreas, particularly with respect to the extent of node dissection and emphasis on obtaining microscopically negative tangential margins. The purpose of this report is to provide long-term survival results.

Use of multifunctional sigma-2 receptor ligand conjugates to trigger cancer-selective cell death signaling.

One major challenge in the development of cancer therapeutics is the selective delivery of the drugs to their cellular targets. In the case of pancreatic cancer, the σ-2 receptor is a unique target that triggers apoptosis upon activation. We have previously developed a series of chemical compounds with high affinity for the σ-2 receptor and showed rapid internalization of the ligands.

Reduction of surgical site infection using a novel intervention (ROSSINI): study protocol for a randomised controlled trial.

Background: Surgical site infection (SSI) is a common complication following abdominal surgery. It is associated with considerable morbidity and mortality, and its management results in significant cost to health services within both primary and secondary care. Some surgeons believe that the use of a wound-edge protection device may reduce the incidence of SSI.

Ethical management of conflict of interest: proposed standards for academic surgical societies.

Background: A significant increase in industry support of professional medical associations coupled with data suggesting that gifts from industry have significant clinical influence have prompted calls from the Institute of Medicine and physician leaders to identify and manage conflicts of interest that stem from financial support of professional medical associations by industry.

Study Design: A joint task force of members appointed by the Association for Academic Surgery and the Society of University Surgeons was convened in July 2009. Recommendations were developed regarding management of all potential conflicts of interest that can arise within the context of an academic surgical society, with specific focus on relationships with industry.

Radiologic and intraoperative detection of need for mesenteric vein resection in patients with adenocarcinoma of the head of the pancreas.

Objective: The need for mesenteric venous resection (MVR) is determined by a combination of preoperative radiologic and intraoperative surgical assessments. A single-centre review was performed to determine how efficient these processes are in evaluating the need for MVR.

Methods: A retrospective study was performed of 343 patients who received resection for adenocarcinoma of the head of the pancreas, 100 of whom underwent MVR.

A single-institution review of 157 patients presenting with benign and malignant tumors of the ampulla of Vater: management and outcomes.

Background: Although benign ampullary tumors are removed endoscopically, due to their potential to progress to malignant disease, the favored treatment for adenocarcinoma is pancreaticoduodenectomy. We reviewed our institution's experience in order to identify which patients were at highest risk of disease progression following surgical resection, as well as evaluate whether localized T1 tumors are best treated by pancreaticoduodenectomy.

Methods: We retrospectively reviewed 157 patients who presented with an ampullary mass, from 2001 to 2010, and identified 51 with benign adenoma and 106 with adenocarcinoma.

Influence of obesity and other risk factors on survival outcomes in patients undergoing pancreaticoduodenectomy for pancreatic cancer.

Objectives: Established risk factors for the development of pancreatic cancer include tobacco use, family history of pancreatic cancer, personal history of diabetes, and obesity. The impact of risk factors on prognosis in patients with pancreatic cancer, particularly obesity, has recently become controversial.

Methods: We conducted a retrospective analysis of patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy between 1995 and 2009.

Fluorescent derivatives of σ receptor ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) as a tool for uptake and cellular localization studies in pancreatic tumor cells.

Fluorescent derivatives of σ(2) high affinity ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) were synthesized. NBD or dansyl fluorescent tags were connected through a 5- or 6-atom linker in two diverse positions of 1 structure. Good σ(2) affinities were obtained when the fluorescent tag was linked to 5-methoxytetralin nucleus replacing the methyl function.

Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site.

The sigma-2 receptor, whose gene remains to be cloned, has been validated as a biomarker for tumour cell proliferation. Here we report the use of a novel photoaffinity probe, WC-21, to identify the sigma-2 receptor-binding site. WC-21, a sigma-2 ligand containing both a photoactive azide moiety and a fluorescein isothiocyanate group, irreversibly labels sigma-2 receptors in rat liver; the membrane-bound protein was identified as PGRMC1 (progesterone receptor membrane component 1).

Myeloid-derived suppressor cells: general characteristics and relevance to clinical management of pancreatic cancer.

Recent studies describe a heterogeneous population of cells of the myeloid lineage, termed myeloid derived suppressor cells (MDSC), which are observed with increased prevalence in the peripheral blood and tumor microenvironment of cancer patients, including pancreatic cancer. Accumulation of MDSC in the peripheral circulation has been related to extent of disease, and correlates with stage. MDSC have primarily been implicated in promoting tumor growth by suppressing antitumor immunity.

Potential targets for pancreatic cancer immunotherapeutics.

Pancreatic adenocarcinoma is the fourth leading cause of cancer death with an overall 5-year survival of less than 5%. As there is ample evidence that pancreatic adenocarcinomas elicit antitumor immune responses, identification of pancreatic cancer-associated antigens has spurred the development of vaccination-based strategies for treatment. While promising results have been observed in animal tumor models, most clinical studies have found only limited success.

A technique of gastrojejunostomy to reduce delayed gastric emptying after pancreatoduodenectomy.

Delayed gastric emptying (DGE) through a gastroenterostomy is a clinical problem that affects many patients who have a standard Whipple procedure. A new method, which is associated with a low rate of DGE, is described.

Analysis of 6,747 pancreatic neuroendocrine tumors for a proposed staging system.

Objectives: Currently, no reasonable staging system exists for pancreatic neuroendocrine tumors (PNET) to guide treating physicians. The aim of this study was to devise a staging system of relevant prognostic factors to better predict overall survival in PNET.

Methods: A prospective 300 patient cohort and a review of the Surveillance Epidemiology and End Results database identified 6,447 patients with PNET from 1973 to 2008.