Postoperative Global Period Cost Reduction Using 3 Successive Risk-Stratified Pancreatectomy Clinical Pathways.

Background: We hypothesized that iterative revisions of our original 2016 risk-stratified pancreatectomy clinical pathways would be associated with decreased 90-day perioperative costs.

Study Design: From a single-institution retrospective cohort study of consecutive patients with 3 iterations: "version 1" (V1) (October 2016 to January 2019), V2 (February 2019 to October 2020), and V3 (November 2020 to February 2022), institutional data were aggregated using revenue codes and adjusted to constant 2022-dollar value. Grand total perioperative costs (primary endpoint) were the sum of pancreatectomy, inpatient care, readmission, and 90-day global outpatient care.

Utilizing risk-stratified pathways to personalize post-hepatectomy discharge planning: A contemporary analysis of 1,354 patients.

Background: While risk-stratified post-hepatectomy pathways (RSPHPs) reduce length-of-stay, can they stratify hepatectomy patients by risk of early postoperative events.

Methods: 90-day outcomes from consecutive hepatectomies were analyzed (1/1/2017-12/31/2021). Pre/post-pathway analysis was performed for pathways: minimally invasive surgery ("MIS"); non-anatomic resection/left hepatectomy ("low-intermediate risk"); right/extended hepatectomy ("high-risk"); "Combination" operations.

Prognostic significance of trophoblastic cell surface antigen 2 expression and pathologic parameters in patients with ampullary adenocarcinoma.

Trophoblastic cell surface antigen 2 (TROP2) has been reported to be up-regulated in several types of carcinomas and is associated with aggressive behavior and poor survival. However, TROP2 expression and its clinical significance in ampullary adenocarcinoma (AA) have not been investigated. We examined TROP2 expression by immunohistochemistry in 112 patients with AAs.

A decade's experience of managing suspected pancreatic adenocarcinoma at a tertiary cancer center.

Background: We present our experience and established management strategy for endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in diagnosing suspected pancreatic neoplasms at a tertiary referral cancer hospital.

Method: Relevant data were extracted from our database for patients who underwent EUS-FNA for suspected pancreatic neoplasms at our institution between 2007 and 2016.

Results: Among the 309 patients, the median age was 67 years and 56% were men.

3D imaging analysis on an organoid-based platform guides personalized treatment in pancreatic ductal adenocarcinoma.

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.

Nab-Paclitaxel, Capecitabine, and Radiation Therapy After Induction Chemotherapy in Treating Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer: Phase 1 Trial and Imaging-based Biomarker Validation.

Purpose: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response.

AJCC 8th edition pathologic nodal staging of resected pancreatic adenocarcinoma predicts survival regardless of treatment sequencing.

Objective: The primary aim was to compare overall survival (OS) between neoadjuvant therapy (NT) and surgery-first (SF) patients with pancreatic adenocarcinoma (PDAC) by nodal stage using the American Joint Commission on Cancer 8th Edition (AJCC8).

Background: Rates of nodal positivity are consistently lower following NT versus SF sequencing. It's unclear whether post-NT nodal stage (ypNx) has similar survival compared to SF (pNx) using AJCC8.

GRP78 expression and prognostic significance in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant therapy versus surgery first.

Background: Glucose-regulated protein 78 (GRP78) plays an essential role in protein folding, transportation, and degradation, thus regulates ER homeostasis and promotes cell survival, proliferation and invasion. GRP78 expression in PDAC patients who received neoadjuvant therapy has not been reported.

Methods: This retrospective study of resected PDAC patients included 125 patients treated with neoadjuvant therapy (NAT) and 140 patients treated with surgery first (SF).

DDR1-induced neutrophil extracellular traps drive pancreatic cancer metastasis.

Pancreatic ductal adenocarcinoma (PDAC) tumors are characterized by a desmoplastic reaction resulting in dense deposition of collagen that is known to promote cancer progression. A central mediator of protumorigenic collagen signaling is the receptor tyrosine kinase discoid domain receptor 1 (DDR1). DDR1 is a critical driver of a mesenchymal and invasive cancer cell PDAC phenotype.

Progression vs Cyst Stability of Branch-Duct Intraductal Papillary Mucinous Neoplasms After Observation and Surgery.

Importance: The progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas to malignant disease is still poorly understood. Observational and surgical series have failed to provide comprehensive information.

Objective: To identify dynamic variables associated with the development of malignant neoplasms by combining pathological features with data from preoperative repeated observations.

Overexpression of CD73 in pancreatic ductal adenocarcinoma is associated with immunosuppressive tumor microenvironment and poor survival.

Background: CD73, a newly recognized immune checkpoint mediator, is expressed in several types of malignancies. However, CD73 expression and its impact on tumor microenvironment and clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) remain unclear.

Methods: This study included two cohorts: 138 patients from our institution (MDA) and 176 patients from TCGA dataset.

Characterisation of circulating tumour cell phenotypes identifies a partial-EMT sub-population for clinical stratification of pancreatic cancer.

Background: Limited accessibility of the tumour precludes longitudinal characterisation for therapy guidance in pancreatic ductal adenocarcinoma (PDAC).

Methods: We utilised dielectrophoresis-field flow fractionation (DEP-FFF) to isolate circulating tumour cells (CTCs) in 272 blood draws from 74 PDAC patients (41 localised, 33 metastatic) to non-invasively monitor disease progression.

Results: Analysis using multiplex imaging flow cytometry revealed four distinct sub-populations of CTCs: epithelial (E-CTC), mesenchymal (M-CTC), partial epithelial-mesenchymal transition (pEMT-CTC) and stem cell-like (SC-CTC).

An international study of interobserver variability of "string sign" of pancreatic cysts among experienced endosonographers.

Background And Objectives: No single optimal test reliably determines the pancreatic cyst subtype. Following EUS-FNA, the "string sign" test can differentiate mucinous from nonmucinous cysts. However, the interobserver variability of string sign results has not been studied.

CT features predictive of nodal positivity at surgery in pancreatic cancer patients following neoadjuvant therapy in the setting of dual energy CT.

Purpose: Evaluate utility of dual energy CT iodine material density images to identify preoperatively nodal positivity in pancreatic cancer patients who underwent neoadjuvant therapy.

Methods: This IRB approved retrospective study evaluated 62 patients between 2012 and 2016 with proven pancreatic ductal adenocarcinoma, who underwent neoadjuvant therapy, tumor resection and both baseline and preoperative assessment with pancreatic multiphasic rapid switching dual energy CT. Three radiologists in consensus identified on imaging nodes > 0.

Clinicopathological correlation of radiologic measurement of post-therapy tumor size and tumor volume for pancreatic ductal adenocarcinoma.

Objectives: Tumor size measurement is critical for accurate tumor staging in patients with pancreatic ductal adenocarcinoma (PDAC). However, accurate tumor size measurement is challenging in patients who received neoadjuvant therapy before resection, due to treatment-induced fibrosis and tumor invasion beyond the grossly identified tumor area. In this study, we evaluated the correlation between the tumor size and tumor volume measured on post-therapy computed tomography (CT) scans and the pathological measurement.

CES2 Expression in Pancreatic Adenocarcinoma Is Predictive of Response to Irinotecan and Is Associated With Type 2 Diabetes.

Purpose: The combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has provided clinically meaningful improvement for pancreatic ductal adenocarcinoma (PDAC). We previously uncovered a role for the serine hydrolase carboxylesterase 2 (CES2) in mediating intratumoral activation of the prodrug irinotecan, a constituent of FOLFIRINOX. We aimed to further test the predictive value of CES2 for response to irinotecan using patient-derived xenograft (PDX) models and to elucidate the determinants of CES2 expression and response to FOLFIRINOX treatment among patients with PDAC.

Circulating levels of hydroxylated bradykinin function as an indicator of tissue HIF-1α expression.

The critical roles of oxygen homeostasis in metabolism are indisputable and hypoxic responses are correlated with the pathogenesis of gastrointestinal, pulmonary, renal diseases and cancers. Evaluating tissue hypoxia to predict treatment outcome is challenging, however, due to the lack of rapid, accurate and non-invasive methods. Hypoxia enhances prolyl-4-hydroxylase α1 (P4HA1) expression, which can convert bradykinin (BK) to hydroxyprolyl-BK (Hyp-BK), leading us to hypothesize that circulating Hyp-BK/BK ratios may reflect tissue hypoxia and predict treatment outcomes.

Early postoperative drain fluid amylase in risk-stratified patients promotes tailored post-pancreatectomy drain management and potential for accelerated discharge.

Background: First postoperative day drain fluid amylase (DFA1) <5000 U/L is commonly used for early drain removal. We manage patients with risk-stratified pancreatectomy care pathways determined preoperatively by risk for postoperative pancreatic fistula. We hypothesized that preoperative risk stratification would yield unique DFA1/DFA3 cutoffs for safe early drain removal.

Expression of Epithelial-Mesenchymal Transition Markers in Treated Pancreatic Ductal Adenocarcinoma.

Objectives: Epithelial-mesenchymal transition (EMT) plays an important role in the progression, metastasis, and chemoresistance of pancreatic duct adenocarcinoma (PDAC); however, the expression of EMT markers and their clinical significance in PDAC patients who received neoadjuvant therapy (NAT) are unclear.

Methods: We examined the expression of EMT markers, including Zeb-1 (zinc finger E-box-binding homeobox 1), E-cadherin, and vimentin by immunohistochemistry in 120 PDAC patients who received NAT and pancreatectomy from 1999 to 2007. The results were correlated with clinicopathologic parameters and survival.

Gastric cancer in the remnant stomach after pancreaticoduodenectomy: A case series.

Background: Gastric cancer (GC) occasionally develops in the remnant stomach following pancreaticoduodenectomy (PD). In those who have undergone PD for adenocarcinoma, however, the interval and frequency of anastomotic GC are unknown.

Methods: We searched our institutional database for patients who had undergone PD for adenocarcinoma and subsequently developed GC between 1994 and 2018 and found six patients.

Is early-stage pancreatic adenocarcinoma truly early: stage migration on final pathology with surgery-first versus neoadjuvant therapy sequencing.

Background: Neoadjuvant therapy (NT) remains controversial in early-stage pancreatic ductal adenocarcinoma (PDAC), defined as clinical (c)Stage I-II. Our aim was to analyze rates of pathologic upstaging/downstaging for resectable PDAC treated with surgery-first (SF) vs. NT.

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.

Chemoresistance Transmission via Exosome-Mediated EphA2 Transfer in Pancreatic Cancer.

Exosomes are small extracellular vesicles secreted by most cells that are found in blood and other bodily fluids, and which contain cytoplasmic material and membrane factors corresponding to their cell type of origin. Exosome membrane factors and contents have been reported to alter adjacent and distant cell behavior in multiple studies, but the impact of cancer-derived exosomes on chemoresistance is less clear. Exosomes isolated from three pancreatic cancer (PC) cell lines displaying variable gemcitabine (GEM) resistance (PANC-1, MIA PaCa-2, and BxPC-3) were tested for their capacity to transmit chemoresistance among these cell lines.