Intratumoral Cell Neighborhoods Coordinate Outcomes in Pancreatic Ductal Adenocarcinoma.

Background & Aims: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease characterized by a spatially heterogeneous tumor microenvironment. Within the PDA microenvironment, cells organize into communities where cell fate is influenced by neighboring cells of diverse ontogeny and function. However, it remains unclear how cell neighborhoods in the tumor microenvironment evolve with treatment and impact clinical outcomes.

Multianalyte Serum Biomarker Panel for Early Detection of Pancreatic Adenocarcinoma.

Purpose: We determined whether a large, multianalyte panel of circulating biomarkers can improve detection of early-stage pancreatic ductal adenocarcinoma (PDAC).

Materials And Methods: We defined a biologically relevant subspace of blood analytes on the basis of previous identification in premalignant lesions or early-stage PDAC and evaluated each in pilot studies. The 31 analytes that met minimum diagnostic accuracy were measured in serum of 837 subjects (461 healthy, 194 benign pancreatic disease, and 182 early-stage PDAC).

Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception.

Purpose: Intraductal papillary mucinous neoplasms (IPMN) are bona fide precursors to pancreatic ductal adenocarcinoma (PDAC). While genomic alterations during multistep IPMN progression have been well cataloged, the accompanying changes within the tumor immune microenvironment (TIME) have not been comprehensively studied. Herein, we investigated TIME-related alterations during IPMN progression, using multiplex immunofluorescence (mIF) coupled with high-resolution image analyses.

Value Analysis of Methods of Inguinal Hernia Repair.

Objective: Value is defined as health outcomes important to patients relative to cost of achieving those outcomes: Value = Quality/Cost. For inguinal hernia repair, Level 1 evidence shows no differences in long-term functional status or recurrence rates when comparing surgical approaches. Differences in value reside within differences in cost.

Detection of circulating tumor DNA without a tumor-informed search using next-generation sequencing is a prognostic biomarker in pancreatic ductal adenocarcinoma.

The confounding effects of next-generation sequencing (NGS) noise on detection of low frequency circulating tumor DNA (ctDNA) without a priori knowledge of solid tumor mutations has limited the applications of circulating cell-free DNA (ccfDNA) in clinical oncology. Here, we use a 118 gene panel and leverage ccfDNA technical replicates to eliminate NGS-associated errors while also enhancing detection of ctDNA from pancreatic ductal adenocarcinomas (PDACs). Pre-operative ccfDNA and tumor DNA were acquired from 14 patients with PDAC (78.

Hospital Costs Following Surgical Complications: A Value-driven Outcomes Analysis of Cost Savings Due to Complication Prevention.

Objective: Surgical complications have substantial impact on healthcare costs. We propose an analysis of the financial impact of postoperative complications.

Summary Of Background Data: Both complications and preoperative patient risk have been shown to increase costs following surgery.

Size and Importance of Socioeconomic Status-Based Disparities in Use of Surgery in Nonadvanced Stage Gastrointestinal Cancers.

Background: The size and importance of socioeconomic status (SES)-based disparities in use of surgery for non-advanced stage gastrointestinal (GI) cancers have not been quantified.

Methods: The exposure in this study of patients age 18-80 with one of nine non-advanced stage GI cancers in the 2007-2015 SEER database was a census tract-level SES composite. Multivariable models assessed associations of SES with use of surgery.

Adrenocorticotropin Hormone Secreting Carcinoma of the Pancreas: A Case Report.

Adrenocorticotropin hormone (ACTH) secreting pancreatic neuroendocrine neoplasms (pNENs) are rare. The clinical and biological behavior of pNENs is poorly understood. Patients often present at an advanced stage of disease and outcomes remain poor.

County-level Variation in Use of Surgery and Cancer-specific Survival for Stage I-II Pancreatic Adenocarcinoma.

Objective: The aim of the study was to describe county-level variation in use of surgery for stage I-II pancreatic ductal adenocarcinoma (PDAC) and the association between county surgery rates and cancer-specific survival (CSS).

Background: The degree of small geographic area variation in use of surgery for stage I-II PDAC and the association between area surgery rates and CSS remain incompletely defined.

Methods: This is a retrospective cohort study of patients aged 18 to 80 years in the 2007 to 2015 Surveillance, Epidemiology, and End Results database with stage I-II PDAC without contraindications to surgery or refusal.

Exosomes harbor B cell targets in pancreatic adenocarcinoma and exert decoy function against complement-mediated cytotoxicity.

Although B cell response is frequently found in cancer, there is little evidence that it alters tumor development or progression. The process through which tumor-associated antigens trigger humoral response is not well delineated. We investigate the repertoire of antigens associated with humoral immune response in pancreatic ductal adenocarcinoma (PDAC) using in-depth proteomic profiling of immunoglobulin-bound proteins from PDAC patient plasmas and identify tumor antigens that induce antibody response together with exosome hallmark proteins.

Disparities in utilization of treatment for clinical stage I-II pancreatic adenocarcinoma by area socioeconomic status and race/ethnicity.

Background: Utilization of multimodality therapy for clinical stage I-II pancreatic ductal adenocarcinoma is associated with meaningful prolongation of survival. Although the qualitative existence of disparities in treatment utilization by socioeconomic status and race/ethnicity is well documented, the absolute magnitudes of these disparities have not been previously quantified.

Methods: The exposures in this retrospective cohort study of the 2010-2015 National Cancer Database were a 7-value area-level socioeconomic status index and race/ethnicity.

Lymph Node Ratio in Pancreatic Adenocarcinoma After Preoperative Chemotherapy vs. Preoperative Chemoradiation and Its Utility in Decisions About Postoperative Chemotherapy.

Background: Single-center studies in pancreatic adenocarcinoma have suggested that preoperative chemotherapy (PCT) is associated with higher lymph node ratio (LNR) than preoperative chemoradiation (PCRT). The association of postoperative chemotherapy with overall survival (OS) in patients treated with PCT and PCRT remains unclear. Our objectives were to investigate whether (1) PCT is associated with higher LNR than PCRT and (2) postoperative chemotherapy is associated with longer OS after PCT and PCRT in LNR-stratified cohorts.

Surgical overtreatment of pancreatic intraductal papillary mucinous neoplasms: Do the 2017 International Consensus Guidelines improve clinical decision making?

Background: Significant overtreatment of intraductal papillary mucinous neoplasms can be attributed to low specificity of the current International Consensus Guidelines as well as nonconformity with the guidelines. We compare the ability of the 2012 and revised 2017 intraductal papillary mucinous neoplasms International Consensus Guidelines to predict high-grade dysplasia/invasive cancer and to determine the preoperative variables that predict resection of benign or low-grade dysplasia in tertiary care centers.

Methods: Clinical, radiographic, and pathologic data for resected intraductal papillary mucinous neoplasms at 3 high-volume National Cancer Institute Cancer Centers were reviewed and the 2012 and 2017 consensus criteria were retrospectively applied.

Causes of Death and Conditional Survival Estimates of Medium- and Long-term Survivors of Pancreatic Adenocarcinoma.

This population-based study investigates the survival and causes of death in patients with pancreatic adenocarcinoma to 21 years after diagnosis.

Pancreatic cancer as a sentinel for hereditary cancer predisposition.

Background: Genes associated with hereditary breast and ovarian cancer (HBOC) and colorectal cancer (CRC) predisposition have been shown to play a role in pancreatic cancer susceptibility. Growing evidence suggests that pancreatic cancer may be useful as a sentinel cancer to identify families that could benefit from HBOC or CRC surveillance, but to date pancreatic cancer is only considered an indication for genetic testing in the context of additional family history.

Methods: Preliminary data generated at the Huntsman Cancer Hospital (HCH) included variants identified on a custom 34-gene panel or 59-gene panel including both known HBOC and CRC genes for respective sets of 66 and 147 pancreatic cancer cases, unselected for family history.

Association of time-to-surgery with outcomes in clinical stage I-II pancreatic adenocarcinoma treated with upfront surgery.

Background: Time-to-surgery from cancer diagnosis has increased in the United States. We aimed to determine the association between time-to-surgery and oncologic outcomes in patients with resectable pancreatic ductal adenocarcinoma undergoing upfront surgery.

Methods: The 2004-2012 National Cancer Database was reviewed for patients undergoing curative-intent surgery without neoadjuvant therapy for clinical stage I-II pancreatic ductal adenocarcinoma.

Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

Objective: To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals.

Background: Curative-intent surgery for potentially resectable PDAC is underutilized in the United States.

Methods: Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database.

Sequential Validation of Blood-Based Protein Biomarker Candidates for Early-Stage Pancreatic Cancer.

Background: CA19-9, which is currently in clinical use as a pancreatic ductal adenocarcinoma (PDAC) biomarker, has limited performance in detecting early-stage disease. We and others have identified protein biomarker candidates that have the potential to complement CA19-9. We have carried out sequential validations starting with 17 protein biomarker candidates to determine which markers and marker combination would improve detection of early-stage disease compared with CA19-9 alone.

Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

Background: Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival.

Methods: The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012.

Biomarkers in pancreatic adenocarcinoma: current perspectives.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection.

Initial Misdiagnosis of Proximal Pancreatic Adenocarcinoma Is Associated with Delay in Diagnosis and Advanced Stage at Presentation.

Introduction: Delay in diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with decreased survival. The effect of an initial misdiagnosis on delay in diagnosis and stage of PDAC is unknown.

Methods: This study is a retrospective review (2000-2010) from a University-based cancer center of new diagnoses of proximal PDAC.

Early detection of sporadic pancreatic cancer: summative review.

Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society.

Defective apical extrusion signaling contributes to aggressive tumor hallmarks.

When epithelia become too crowded, some cells are extruded that later die. To extrude, a cell produces the lipid, Sphingosine 1-Phosphate (S1P), which activates S1P₂ receptors in neighboring cells that seamlessly squeeze the cell out of the epithelium. Here, we find that extrusion defects can contribute to carcinogenesis and tumor progression.

Value Driven Outcomes (VDO): a pragmatic, modular, and extensible software framework for understanding and improving health care costs and outcomes.

Objective: To develop expeditiously a pragmatic, modular, and extensible software framework for understanding and improving healthcare value (costs relative to outcomes).

Materials And Methods: In 2012, a multidisciplinary team was assembled by the leadership of the University of Utah Health Sciences Center and charged with rapidly developing a pragmatic and actionable analytics framework for understanding and enhancing healthcare value. Based on an analysis of relevant prior work, a value analytics framework known as Value Driven Outcomes (VDO) was developed using an agile methodology.

Factors associated with improved survival after resection of pancreatic adenocarcinoma: a multivariable model.

Background: Several retrospective studies suggest that perioperative care and anesthetic management for cancer resection may influence cancer recurrence or patient survival. Various intraoperative techniques such as paravertebral blocks, decreased opioid use, immunomodulation, and perioperative antiinflammatory administration, have previously been assessed for improved patient survival. The aim of this study was to assess associations between perioperative management and survival in patients undergoing resection of pancreatic adenocarcinoma.