Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial.

Background: About 25% of pancreatic cancers harbour actionable molecular alterations, defined as molecular alterations for which there is clinical or strong preclinical evidence of a predictive benefit from a specific therapy. The Know Your Tumor (KYT) programme includes US patients with pancreatic cancer and enables patients to undergo commercially available multi-omic profiling to provide molecularly tailored therapy options and clinical trial recommendations. We sought to determine whether patients with pancreatic cancer whose tumours harboured such actionable molecular alterations and who received molecularly matched therapy had a longer median overall survival than similar patients who did not receive molecularly matched therapy.

Advanced Endoscopic Rescue of a Complication (Duodenojejunostomy Leak) After a Pylorus-Preserving Pancreaticoduodenectomy in a Post-Esophagectomy Patient with Pancreatic Adenocarcinoma: A Case Report and Review of the Literature.

Approximately 4% of patients develop a second upper gastrointestinal cancer after esophagectomy, and nearly 60,000 people are diagnosed with pancreatic cancer in the United States each year. The need for a Whipple procedure after esophagectomy is rarely reported. Post-esophagectomy anatomy, particularly the vascular supply, makes this a complex operation.

Effect of Hypercapnia, an Element of Obstructive Respiratory Disorder, on Pancreatic Cancer Chemoresistance and Progression.

Background: Chronic obstructive respiratory disorders (ORDs) are linked to increased rates of cancer-related deaths. Little is known about the effects of hypercapnia (elevated CO) on development of pancreatic ductal adenocarcinoma (PDAC) and drug resistance.

Study Design: Two PDAC cell lines were exposed to normocapnic (5% CO) and hypercapnic (continuous/intermittent 10% CO) conditions, physiologically similar to patients with active ORD.

Pylorus-Preserving Total Pancreatectomy for Intraductal Papillary Mucinous Neoplasm in the Setting of Previous Roux-en-Y Cystjejunostomy for Pancreatic Pseudocyst.

Intraductal papillary mucinous neoplasms (IPMNs) are cystic lesions of the pancreas with malignant potential. The Sendai and Fukuoka criteria offer guidelines for surgical management of an IPMN. A 69-year-old patient with a history of recurrent pancreatitis presented with steatorrhea and unintentional weight loss.

Understanding and targeting the disease-related RNA binding protein human antigen R (HuR).

Altered gene expression is a characteristic feature of many disease states such as tumorigenesis, and in most cancers, it facilitates cancer cell survival and adaptation. Alterations in global gene expression are strongly impacted by post-transcriptional gene regulation. The RNA binding protein (RBP) HuR (ELAVL1) is an established regulator of post-transcriptional gene regulation and is overexpressed in most human cancers.

Optimizing cancer cure dialog: an analysis of pancreatic cancer patients' views regarding survival and cure.

Background: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. Clinicians commonly refer to surgical therapy as resection with curative intent. However, PDA cure rates after resection remain unknown and the definition of cure remains vague.

ATM Dysfunction in Pancreatic Adenocarcinoma and Associated Therapeutic Implications.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid malignancies with very few therapeutic options to treat advanced or metastatic disease. The utilization of genomic sequencing has identified therapeutically relevant alterations in approximately 25% of PDAC patients, most notably in the DNA damage response and repair (DDR) genes, rendering cancer cells more sensitive to DNA-damaging agents and to DNA damage response inhibitors, such as PARP inhibitors. ATM is one of the most commonly mutated DDR genes, with somatic mutations identified in 2% to 18% of PDACs and germline mutations identified in 1% to 34% of PDACs.

Intraoperative Pancreatic Ductoscopy for Ampullary Adenocarcinoma During Pancreatic Resection: A Case Report.

Periampullary neoplasms can be challenging to work up and diagnose preoperatively. Herein, we report the case of a patient whose preoperative workup failed to detect a malignancy, yet, underwent a pylorus-preserving pancreaticoduodenectomy (PPPD) with intraoperative pancreatic ductoscopy (IPD) and was ultimately found to have an ampullary adenocarcinoma. A 78-year-old woman presented with 4 weeks of nausea, weight loss, jaundice, and light-colored stools.

Abemaciclib Is Effective Against Pancreatic Cancer Cells and Synergizes with HuR and YAP1 Inhibition.

Mutation or promoter hypermethylation of is found in over 90% of pancreatic ductal adenocarcinomas (PDAC) and leads to loss of function of cell-cycle inhibitors p16 (INK4A) and p14 (ARF) resulting in unchecked proliferation. The CDK4/6 inhibitor, abemaciclib, has nanomolar ICs in PDAC cell lines and decreases growth through inhibition of phospho-Rb (pRb), G cell-cycle arrest, apoptosis, and the senescent phenotype detected with β-galactosidase staining and relevant mRNA elevations. Daily abemaciclib treatments in mouse PDAC xenograft studies were safe and demonstrated a 3.

Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer.

Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have an average survival of less than 1 year, underscoring the importance of evaluating novel targets with matched targeted agents. We recently identified that poly (ADP) ribose glycohydrolase (PARG) is a strong candidate target due to its dependence on the pro-oncogenic mRNA stability factor HuR (). Here, we evaluated PARG as a target in PDAC models using both genetic silencing of PARG and established small-molecule PARG inhibitors (PARGi), PDDX-01/04.

The Sustained Induction of c-MYC Drives Nab-Paclitaxel Resistance in Primary Pancreatic Ductal Carcinoma Cells.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited and, very often, ineffective medical and surgical therapeutic options. The treatment of patients with advanced unresectable PDAC is restricted to systemic chemotherapy, a therapeutic intervention to which most eventually develop resistance. Recently, nab-paclitaxel (n-PTX) has been added to the arsenal of first-line therapies, and the combination of gemcitabine and n-PTX has modestly prolonged median overall survival.

Corrigendum: Metabolic Dependencies in Pancreatic Cancer.

[This corrects the article DOI: 10.3389/fonc.2018.

Genetic Drivers of Pancreatic Cancer Are Identical Between the Primary Tumor and a Secondary Lesion in a Long-Term (>5 Years) Survivor After a Whipple Procedure.

A new mass in the remnant pancreas of a patient with previously resected pancreatic ductal adenocarcinoma (PDA) typically represents either a recurrence of the initial primary tumor or a second primary tumor. Recent advances in next-generation sequencing (NGS) strategies allow us to compare the genetic makeup of primary and secondary lesions. A 50-year-old Caucasian female presented for a surgical evaluation of a new biopsy-proven PDA at the junction of the body and tail of the pancreas.

Enhancing Patient Outcomes while Containing Costs after Complex Abdominal Operation: A Randomized Controlled Trial of the Whipple Accelerated Recovery Pathway.

Background: This study was designed to determine whether a standardized recovery pathway could reduce post-pancreaticoduodenectomy hospital length of stay to 5 days without increasing complication or readmission rates.

Study Design: Pancreaticoduodenectomy patients (high-risk patients excluded) were enrolled in an IRB-approved, prospective, randomized controlled trial (NCT02517268) comparing a 5-day Whipple accelerated recovery pathway (WARP) with our traditional 7-day pathway (control). Whipple accelerated recovery pathway interventions included early discharge planning, shortened ICU stay, modified postoperative dietary and drain management algorithm, rigorous physical therapy with in-hospital gym visit, standardized rectal suppository administration, and close telehealth follow-up post discharge.

Completion Pancreaticoduodenectomy for Hereditary Pancreatitis After Prior Puestow Procedure: A Case Report.

Hereditary pancreatitis (HP) is an uncommon condition resulting from an imbalance of pancreatic proteases. Most commonly, protease serine 1 genetic mutations are causative for HP and often result in recurrent early onset episodes of acute pancreatitis typically progressing to chronic pancreatitis, with a high risk of pancreatic cancer. A 46-year-old female with HP, confirmed by genetic testing, presented with a 7-month history of recurrent pancreatitis.

Duodenal Adenocarcinoma in a Patient with Partial Intestinal Malrotation.

Small bowel cancers, specifically duodenal cancer, occur at very low rates but require aggressive surgical resection when diagnosed. An even rarer finding is the presence of intestinal malrotation. We present the unique case of a patient with both duodenal cancer and partial intestinal malrotation undergoing pancreaticoduodenectomy.

Precious Data: Interim Report from the Jefferson Pancreas Tumor Registry.

The Jefferson Pancreas Tumor Registry (JPTR) is a voluntary hospital-based registry of persons with pancreas and related periampullary cancers, premalignant lesions, and nonaffected family members (NAFMs). The ultimate goals of the JPTR are to provide a link between family history, gene mutations, and precision medicine therapy, and to identify high-risk NAFMs for potential surveillance screening. The JPTR is an Institutional Review Board approved longitudinal epidemiological study housed in the Department of Surgery at Thomas Jefferson University Hospital.

Metabolic Dependencies in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer with a long-term survival rate under 10%. Available cytotoxic chemotherapies have significant side effects, and only marginal therapeutic efficacy. FDA approved drugs currently used against PDA target DNA metabolism and DNA integrity.

Evaluation of Post-transcriptional Gene Regulation in Pancreatic Cancer Cells: Studying RNA Binding Proteins and Their mRNA Targets.

Post-transcriptional regulation of gene expression through interaction between RNA binding proteins (RBPs) and target mRNAs have gained considerable interest over the last decade. Altered expression of RBPs as detected in pancreatic ductal adenocarcinoma (PDAC) cells alters mRNA processing, and in turn, the entire transcriptome and proteome. Thus, this gene regulatory mechanism can regulate important pro-oncogenic signaling pathways (e.

Host Gene Status Influences Tumor Progression and Radiotherapy Response in -Driven Sporadic Pancreatic Cancers.

Purpose: Heritable genetic variations can affect the inflammatory tumor microenvironment, which can ultimately affect cancer susceptibility and clinical outcomes. Recent evidence indicates that IDO2, a positive modifier in inflammatory disease models, is frequently upregulated in pancreatic ductal adenocarcinoma (PDAC). A unique feature of in humans is the high prevalence of two inactivating single-nucleotide polymorphisms (SNP), which affords the opportunity to carry out loss-of-function studies directly in humans.

Clinical Implications of Extensive Lymph Node Metastases for Resected Pancreatic Cancer.

Background: Outcomes of patients with resected pancreatic ductal adenocarcinoma (PDA) and extensive lymph node metastases have not been fully characterized.

Methods: A total of 637 patients underwent resection for pancreatic ductal adenocarcinoma (PDA) between 2002 and 2014 at the Thomas Jefferson University. Positive lymph node count (LNC) and positive lymph node ratio (LNR) were analyzed as predictors of cancer-specific outcomes, with a focus on outcomes of patients with extensive lymph node burden.

RNA binding protein HuR regulates extracellular matrix gene expression and pH homeostasis independent of controlling HIF-1α signaling in nucleus pulposus cells.

Nucleus pulposus (NP) cells reside in the hypoxic niche of the intervertebral disc. Studies have demonstrated that RNA-binding protein HuR modulates hypoxic signaling in several cancers, however, its function in the disc is unknown. HuR did not show cytoplasmic translocation in hypoxia and its silencing did not alter levels of Hif-1α or HIF-targets in NP cells.

Molecular Profiling of Patients with Pancreatic Cancer: Initial Results from the Know Your Tumor Initiative.

To broaden access to and implementation of precision medicine in the care of patients with pancreatic cancer, the Know Your Tumor (KYT) program was initiated using a turn-key precision medicine system. Patients undergo commercially available multiomic profiling to determine molecularly rationalized clinical trials and off-label therapies. Tumor samples were obtained for 640 patients from 287 academic and community practices covering 44 states.

A phase 2 study of the PARP inhibitor veliparib plus temozolomide in patients with heavily pretreated metastatic colorectal cancer.

Background: Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors such as veliparib are potent sensitizing agents and have been safely combined with DNA-damaging agents such as temozolomide. The sensitizing effects of PARP inhibitors are magnified when cells harbor DNA repair defects.

Methods: A single-arm, open-label, phase 2 study was performed to investigate the disease control rate (DCR) after 2 cycles of veliparib plus temozolomide in patients with metastatic colorectal cancer (mCRC) refractory to all standard therapies.