isolation-proximal-fluids-to-investigate-tumor-microenvironment

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 value of minimally invasive pancreatic surgery (MIPS) is still debated. To assess the diffusion of MIPS in Italy and identify the barriers preventing wider implementation, a questionnaire was developed under the auspices of three Scientific Societies (AISP, It-IHPBA, SICE) and was sent to the largest possible number of Italian surgeons also using the mailing list of the two main Italian Surgical Societies (SIC and ACOI). The questionnaire consisted of 25 questions assessing: centre characteristics, facilities and technologies, type of MIPS performed, surgical techniques employed and opinions on the present and future value of MIPS. Only one reply per unit was considered. Fifty-five units answered the questionnaire. While 54 units (98.2%) declared to perform MIPS, the majority of responders were not dedicated to pancreatic surgery. Twenty-five units (45.5%) performed < 20 pancreatic resections/year and 39 (70.9%) < 10 MIPS per year. Forty-nine units (89.1%) performed at least one minimally invasive (MI) distal pancreatectomy (DP), and 10 (18.2%) at least one MI pancreatoduodenectomy (PD). Robotic assistance was used in 18 units (31.7%) (14 DP, 7 PD). The major constraints limiting the diffusion of MIPS were the intrinsic difficulty of the technique and the lack of specific training. The overall value of MIPS was highly rated. Our survey illustrates the current diffusion of MIPS in Italy and underlines the great interest for this approach. Further diffusion of MIPS requires the implementation of standardized protocols of training. Creation of a prospective National Registry should also be considered.

Application of minimally invasive pancreatic surgery: an Italian survey.

To evaluate whether perioperative bioimpedance vector analysis (BIVA) predicts the occurrence of surgery-related morbidity.

Perioperative Interstitial Fluid Expansion Predicts Major Morbidity Following Pancreatic Surgery: Appraisal by Bioimpedance Vector Analysis.

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.

Treatment options for neuroendocrine tumors (NETs) are rarely curative, as NETs frequently show resistance to medical therapy. The use of everolimus, an mTOR inhibitor, is limited by the development of resistance, probably due to the activation of Akt signaling. In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination.

Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment.

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.

Pancreatic cancer is one of the main causes of cancer-related death worldwide, with a survival rate around 9%. In Italy 13,500 new cases of pancreatic cancer occurred in 2019. It is estimated that at least 5% have a hereditary background. Surveillance is advisable for healthy individuals with specific genetic syndromes with or without family history of pancreatic cancer or members of families with multiple cases of pancreatic cancer, irrespective of genetic syndromes. In 2010 the Italian Association for the Study of the Pancreas (AISP) defined criteria to include individuals in such surveillance programs with the first-round results published in 2019. In order to include other categories at high-risk and increase the diagnostic yield of surveillance, these criteria have recently been modified. The present position paper presents the updated criteria of the Italian Registry of Families at Risk of Pancreatic Cancer (IRFARPC) with their diagnostic yield calculation. Also, AISP priority projects concerning: (a) increasing awareness of citizens and primary care physicians through a dedicated App; (b) increasing access to germline testing to personalize surveillance; (c) measuring psychological impact of surveillance; (d) investigating the role of risk-modifiers and (e) evaluating the cost-effectiveness and ability to save lives of the program are briefly presented.

Italian registry of families at risk of pancreatic cancer: AISP Familial Pancreatic Cancer Study Group.

The original version of this article has an error in the affiliations of all the authors. The authors affiliations are corrected.

Correction to: Emergency endovascular treatments for delayed hemorrhage after pancreaticobiliary surgery: indications, outcomes, and follow‑up of a retrospective cohort.

Article	Year
Application of minimally invasive pancreatic surgery: an Italian survey. Updates in surgery\| PubMed ID: 29770922	2019
Perioperative Interstitial Fluid Expansion Predicts Major Morbidity Following Pancreatic Surgery: Appraisal by Bioimpedance Vector Analysis. Annals of surgery\| PubMed ID: 31592889	2019
Trans-duodenal ampullectomy for ampullary neoplasms: early and long-term outcomes in 36 consecutive patients. Surgical endoscopy\| PubMed ID: 31646438	2020
Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1 Cells. Cancer immunology research\| PubMed ID: 32019781	2020
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. World journal of surgery\| PubMed ID: 32734454	2020
Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment. Cancers\| PubMed ID: 32748870	2020
Prognostic value of positive histological margins in patients with pancreatic head ductal adenocarcinoma and lymph node involvement: an international multicentric study. HPB : the official journal of the International Hepato Pancreato Biliary Association\| PubMed ID: 32782224	2020
Italian registry of families at risk of pancreatic cancer: AISP Familial Pancreatic Cancer Study Group. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver\| PubMed ID: 32819857	2020
Correction to: Emergency endovascular treatments for delayed hemorrhage after pancreaticobiliary surgery: indications, outcomes, and follow‑up of a retrospective cohort. Abdominal radiology (New York)\| PubMed ID: 32902657	2020
Endoscopic ultrasound guided gastroenterostomy for efferent jeunal loop obstruction in a patient with previous pancreaticoduodenectomy and ascites. Endoscopy international open\| PubMed ID: 33015348	2020

Alessandro Zerbi

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