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Isolation of Proximal Fluids to Investigate the Tumor Microenvironment of Pancreatic Adenocarcinoma

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death, and soon to become the second. There is an urgent need of variables ...

Humanitas Clinical and Research Center-IRCCS

Humanitas University

The ISGPS classification of post-operative pancreatic fistula (POPF) was recently revised, introducing the concept of biochemical leak (BL) which replaced grade A POPF. More recently, an additional distinction on three different subclasses for grade B (B1-B3) POPF was proposed. The aim of this study was to evaluate the impact of these modifications in clinical practice.

The evolution of post-operative pancreatic fistula (POPF) classification: A single-center experience.

Trans-duodenal ampullectomy (TDA) is a surgical option for the treatment of selected ampullary neoplasms. The aim of this study was to evaluate our experience with TDA for the treatment of ampullary neoplasms, focusing on indications, technical aspects, and short- and long-term outcomes.

Trans-duodenal ampullectomy for ampullary neoplasms: early and long-term outcomes in 36 consecutive patients.

Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancreatic disorders. We investigated, by H nuclear magnetic resonance, the metabolomic fingerprint of pancreatic juice (the biofluid that collects pancreatic products) in 40 patients with different pancreatic diseases. Metabolic variables discriminated PDAC from other less aggressive pancreatic diseases and identified metabolic clusters of patients with distinct clinical behaviors. PDAC specimens were overtly glycolytic, with significant accumulation of lactate, which was probed as a disease-specific variable in pancreatic juice from a larger cohort of 106 patients. In human PDAC sections, high expression of the glucose transporter GLUT-1 correlated with tumor grade and a higher density of PD-1 T cells, suggesting their accumulation in glycolytic tumors. In a preclinical model, PD-1 CD8 tumor-infiltrating lymphocytes differentially infiltrated PDAC tumors obtained from cell lines with different metabolic consumption, and tumors metabolically rewired by knocking down the phosphofructokinase () gene displayed a decrease in PD-1 cell infiltration. Collectively, we introduced pancreatic juice as a valuable source of metabolic variables that could contribute to differential diagnosis. The correlation of metabolic markers with immune infiltration suggests that upfront evaluation of the metabolic profile of PDAC patients could foster the introduction of immunotherapeutic approaches for pancreatic cancer.

Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1 Cells.

The inability to comply with enhanced recovery protocols (ERp) after pancreaticoduodenectomy (PD) is a real but understated issue. Our goal is to report our experience and a potential tool to predict ERp failure in order to better characterize this problem.

Enhanced Recovery After Pancreatic Surgery Does One Size Really Fit All? A Clinical Score to Predict the Failure of an Enhanced Recovery Protocol After Pancreaticoduodenectomy.

Resection margin status and lymph node (LN) involvement are known prognostic factors for patients who undergo pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). This study aimed to compare overall survival (OS) and disease-free survival (DFS) by resection margin status in patients with PDAC and LN involvement.

Prognostic value of positive histological margins in patients with pancreatic head ductal adenocarcinoma and lymph node involvement: an international multicentric study.

Gennaro Nappo

Section of Pancreatic Surgery

Humanitas Clinical and Research Center-IRCCS

Isolation of Proximal Fluids to Investigate the Tumor Microenvironment of Pancreatic Adenocarcinoma

Gennaro Nappo

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Section of Pancreatic Surgery

Humanitas Clinical and Research Center-IRCCS

Isolation of Proximal Fluids to Investigate the Tumor Microenvironment of Pancreatic Adenocarcinoma

Section of Pancreatic Surgery