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Pancreatic Neoplasms: HELP
Articles by Alessandro Zerbi
Based on 40 articles published since 2009
(Why 40 articles?)
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Between 2009 and 2019, A. Zerbi wrote the following 40 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms. 2014

Anonymous4750793 / Anonymous4760793 / Buscarini, Elisabetta / Pezzilli, Raffaele / Cannizzaro, Renato / De Angelis, Claudio / Gion, Massimo / Morana, Giovanni / Zamboni, Giuseppe / Arcidiacono, Paolo / Balzano, Gianpaolo / Barresi, Luca / Basso, Daniela / Bocus, Paolo / Calculli, Lucia / Capurso, Gabriele / Canzonieri, Vincenzo / Casadei, Riccardo / Crippa, Stefano / D'Onofrio, Mirko / Frulloni, Luca / Fusaroli, Pietro / Manfredi, Guido / Pacchioni, Donatella / Pasquali, Claudio / Rocca, Rodolfo / Ventrucci, Maurizio / Venturini, Silvia / Villanacci, Vincenzo / Zerbi, Alessandro / Falconi, Massimo / Anonymous4770793. ·Gastroenterology Unit, Maggiore Hospital, Crema, Italy. Electronic address: ebuscarini@rim.it. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy. · Gastroenterology Unit, CRO-National Cancer Institute, Aviano, Italy. · Gastroenterology and Hepatology Department, A.O. San Giovanni Battista/Molinette, University of Turin, Turin, Italy. · Department of Clinical Pathology, AULSS 12, Venice, Italy. · Department of Diagnostic Radiology, Ospedale Cà Foncello, Treviso, Italy. · Department of Pathology, University of Verona, Verona, Italy. · Division of Gastroenterology and Gastrointestinal Endoscopy, Vita-Salute, Italy. · Department of Surgery, San Raffaele Scientific Institute, Milan, Italy. · Gastroenterology and Endoscopy Unit, ISMETT, Palermo, Italy. · Department of Laboratory Medicine, University Hospital, Padua, Italy. · Gastroenterology Unit, Ospedale Sacro Cuore-Don Calabria, Negrar, Verona, Italy. · Department of Radiology, S. Orsola-Malpighi Hospital, Bologna, Italy. · Digestive and Liver Disease Unit, Faculty of Medicine and Psychology, Sapienza University of Rome at S. Andrea Hospital, Rome, Italy. · Division of Pathology, CRO-National Cancer Institute, IRCCS, Aviano, Italy. · Department of Surgery, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. · Department of Surgery, Pancreas Unit, Università Politecnica delle Marche, Ancona, Italy. · Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy. · Department of Surgical and Gastroenterological Sciences, University of Verona, Verona, Italy. · Department of Clinical Medicine, University of Bologna, Bologna, Italy. · Gastroenterology Unit, Maggiore Hospital, Crema, Italy. · Pathology Unit, A.O. San Giovanni Battista/Molinette, Turin, Italy. · Surgery Unit IV, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy. · Gastroenterology Unit, Mauriziano Hospital, Turin, Italy. · Department of Internal Medicine and Gastroenterology, Bentivoglio Hospital, Bologna, Italy. · 2nd Pathology Section, Spedali Civili, Brescia, Brescia, Italy. · Pancreatic Surgery, Department of Surgery, Humanitas Clinical and Research Center, Milan, Italy. ·Dig Liver Dis · Pubmed #24809235.

ABSTRACT: This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.

2 Guideline Familial pancreatic cancer in Italy. Risk assessment, screening programs and clinical approach: a position paper from the Italian Registry. 2010

Del Chiaro, Marco / Zerbi, Alessandro / Capurso, Gabriele / Zamboni, Giuseppe / Maisonneuve, Patrick / Presciuttini, Silvano / Arcidiacono, Paolo Giorgio / Calculli, Lucia / Falconi, Massimo / Anonymous7420665. ·Division of General and Transplant Surgery, Pisa University Hospital, Via Paradisa 2, 56124 Cisanello, Pisa, Italy. m.delchiaro@ao-pisa.toscana.it ·Dig Liver Dis · Pubmed #20627831.

ABSTRACT: In Italy, pancreatic cancer is the fifth leading cause of tumor related death with about 7000 new cases per year and a mortality rate of 95%. In a recent prospective epidemiological study on the Italian population, a family history was found in about 10% of patients suffering from a ductal adenocarcinoma of the pancreas (PDAC). A position paper from the Italian Registry for Familial Pancreatic Cancer was made to manage these high-risk individuals. Even though in the majority of high-risk individuals a genetic test to identify familial predisposition is not available, a screening protocol seems to be reasonable for subjects who have a >10-fold greater risk for the development of PDAC. However this kind of screening should be included in clinical trials, performed in centers with high expertise in pancreatic disease, using the least aggressive diagnostic modalities.

3 Review Pancreatic surgery in Italy. Criteria to identify the hospital units and the tertiary referral centers entitled to perform it. 2016

Bassi, Claudio / Balzano, Giampaolo / Zerbi, Alessandro / Ramera, Marco. ·Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, The Pancreas Institute, P.Le L.A. Scuro 10, 37134, Verona, Italy. Claudio.Bassi@univr.it. · Pancreas Unit, Department of Surgery, San Raffaele Scientific Institute, Milano, Italy. · Section of Pancreatic Surgery, Humanitas Research Hospital, Milano, Rozzano, Italy. · Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, The Pancreas Institute, P.Le L.A. Scuro 10, 37134, Verona, Italy. ·Updates Surg · Pubmed #27272682.

ABSTRACT: Indicators of effectiveness and quality of care are urgently needed to improve the surgical outcomes. This is particularly felt in the field of complex surgical fields, such as the HPB one. International and national studies have documented an association between the large number of pancreatic surgical procedures and the outcome quality. The aim of this paper is to suggest reliable structural requirements and surgical volume to support pancreatic surgical accreditation, preserving patient's safety. Moreover, an accreditation program is outlined.

4 Clinical Trial Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. 2018

Reni, Michele / Balzano, Gianpaolo / Zanon, Silvia / Zerbi, Alessandro / Rimassa, Lorenza / Castoldi, Renato / Pinelli, Domenico / Mosconi, Stefania / Doglioni, Claudio / Chiaravalli, Marta / Pircher, Chiara / Arcidiacono, Paolo Giorgio / Torri, Valter / Maggiora, Paola / Ceraulo, Domenica / Falconi, Massimo / Gianni, Luca. ·Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: reni.michele@hsr.it. · Department of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Pancreatic Surgery, Humanitas University, Humanitas Clinical and Research Center, Milan, Italy. · Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan, Italy. · Department of Surgery, Papa Giovanni XXIII Hospital, Bergamo, Italy. · Onco-Hematology Department, Oncology Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy. · Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Pathology Unit, Vita-Salute San Raffaele University, Milan, Italy. · Pancreato-Biliary Endoscopy and Endosonography Division, IRCCS San Raffaele Scientific Institute, Milan, Italy. · IRCCS Mario Negri Institute for Pharmacological Research, Milan, Italy. · Department of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Pancreatic Surgery, Vita-Salute San Raffaele University, Milan, Italy. ·Lancet Gastroenterol Hepatol · Pubmed #29625841.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma are known to metastasise early and a rationale exists for the investigation of preoperative chemotherapy in patients with resectable disease. We aimed to assess the role of combination chemotherapy in this setting in the PACT-15 trial. METHODS: We did this randomised, open-label, phase 2-3 trial in ten hospitals in Italy. We report the phase 2 part here. Patients aged 18-75 years who were previously untreated for pancreatic ductal adenocarcinoma, with Karnofsky performance status of more than 60, and pathologically confirmed stage I-II resectable disease were enrolled. Patients were randomly assigned (1:1:1), with a minimisation algorithm that stratified treatment allocation by centre and concentrations of carbohydrate antigen 19-9 (CA19-9 ≤5 × upper limit of normal [ULN] vs >5 × ULN), to receive surgery followed by adjuvant gemcitabine 1000 mg/m FINDINGS: Between Oct 5, 2010, and May 30, 2015, 93 patients were randomly allocated to treatment. One centre was found to be non-compliant with the protocol, and all five patients at this centre were excluded from the study. Thus, 88 patients were included in the final study population: 26 in group A, 30 in group B, and 32 in group C. In the per-protocol population, six (23%, 95% CI 7-39) of 30 patients in group A were event-free at 1 year, as were 15 (50%, 32-68) of 30 in group B and 19 (66%, 49-83) of 29 in group C. The main grade 3 toxicities were neutropenia (five [28%] of 18 in group A, eight [38%] of 21 in group B, eight [28%] of 29 in group C before surgery, and ten [48%] of 21 in group C after surgery), anaemia (one [6%] in group A, four [19%] in group B, eight [28%] in group C before surgery, and five [24%] in group C after surgery), and fatigue (one [6%] in group A, three [14%] in group B, two [7%] in group C before surgery, and one [5%] in group C after surgery). The main grade 4 toxicity reported was neutropenia (two [11%] in group A, four [19%] in group B, none in group C). Febrile neutropenia was observed in one patient (3%) before surgery in group C. No treatment-related deaths were observed. INTERPRETATION: Our results provide evidence of the efficacy of neoadjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma. Since the trial began, the standard of care for adjuvant therapy has altered, and other chemotherapy regimens developed. Thus, we decided to not continue with the phase 3 part of the PACT-15. We are planning a phase 3 trial of this approach with different chemotherapy regimens. FUNDING: PERLAVITA ONLUS and MyEverest ONLUS.

5 Clinical Trial Can Stereotactic Body Radiation Therapy Be a Viable and Efficient Therapeutic Option for Unresectable Locally Advanced Pancreatic Adenocarcinoma? Results of a Phase 2 Study. 2017

Comito, Tiziana / Cozzi, L / Clerici, E / Franzese, C / Tozzi, A / Iftode, C / Navarria, P / D'Agostino, G / Rimassa, L / Carnaghi, C / Personeni, N / Tronconi, M C / De Rose, F / Franceschini, D / Ascolese, A M / Fogliata, A / Tomatis, S / Santoro, A / Zerbi, A / Scorsetti, M. ·1 Radiotherapy, Istituto Clinico Humanitas, Milano, Italy. · 2 Oncology and Hematology, Istituto Clinico Humanitas, Milano, Italy. · 3 Pancreatic Surgery, Istituto Clinico Humanitas, Milano, Italy. ·Technol Cancer Res Treat · Pubmed #27311310.

ABSTRACT: PURPOSE: To assess the efficacy of stereotactic body radiotherapy in patients with unresectable locally advanced pancreatic cancer. MATERIALS AND METHODS: All patients received a prescription dose of 45 Gy in 6 fractions. Primary end point was freedom from local progression. Secondary end points were overall survival, progression-free survival, and toxicity. Actuarial survival analysis and univariate or multivariate analysis were investigated. RESULTS: Forty-five patients were enrolled in a phase 2 trial. Median follow-up was 13.5 months. Freedom from local progression was 90% at 2 years. On univariate ( P < .03) and multivariate analyses ( P < .001), lesion size was statistically significant for freedom from local progression. Median progression-free survival and overall survival were 8 and 13 months, respectively. On multivariate analysis, tumor size ( P < .001) and freedom from local progression ( P < .002) were significantly correlated with overall survival. Thirty-two (71%) patients with locally advanced pancreatic cancer received chemotherapy before stereotactic body radiotherapy. Median overall survival from diagnosis was 19 months. Multivariate analysis showed that freedom from local progression ( P < .035), tumor diameter ( P < .002), and computed tomography before stereotactic body radiotherapy ( P < .001) were significantly correlated with overall survival from diagnosis. CONCLUSION: Stereotactic body radiotherapy is a safe and effective treatment for patients with locally advanced pancreatic cancer with no G3 toxicity or greater and could be a promising therapeutic option in multimodality treatment regimen.

6 Clinical Trial Adjuvant PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) or gemcitabine followed by chemoradiation in pancreatic cancer: a randomized phase II trial. 2012

Reni, Michele / Balzano, Gianpaolo / Aprile, Giuseppe / Cereda, Stefano / Passoni, Paolo / Zerbi, Alessandro / Tronconi, Maria Chiara / Milandri, Carlo / Saletti, Piercarlo / Rognone, Alessia / Fugazza, Clara / Magli, Alessandro / Di Muzio, Nadia / Di Carlo, Valerio / Villa, Eugenio. ·Department of Oncology, S. Raffaele Scientific Institute, Milan, Italy. reni.michele@hsr.it ·Ann Surg Oncol · Pubmed #22237835.

ABSTRACT: BACKGROUND: Information from randomized trials on the role of combination chemotherapy in the adjuvant treatment of pancreatic adenocarcinoma is limited. This randomized phase II trial aimed to identify the most promising regimen warranting phase III evaluation. METHODS: Therapy-naive patients, age 18-75 years, Karnofsky Performance Status (KPS)>60, gross total resection of stage IB-III pancreatic adenocarcinoma, stratified for center and surgical margins, were randomly assigned to receive either gemcitabine 1 g/m2 weekly on days 1, 8, and 15 (arm A) or the PEFG regimen (cisplatin and epirubicin 40 mg/m2, day 1; gemcitabine 600 mg/m2, days 1, 8; 5-fluorouracil 200 mg/m2 daily, days 1-28) (arm B). Chemotherapy was administered every 4 weeks for 3 months and followed by irradiation concurrent to continuous infusion of 5-fluorouracil 250 mg/m2 daily. Primary endpoint was the probability of being disease-free at 1 year from surgery. Assuming P0=35% and P1=55%, α=.05 and β=.10, the study was to enroll 51 patients per arm. RESULTS: A total of 102 patients were randomized; 100 were eligible (arm A: 51; arm B: 49). Baseline characteristic (A/B) were: Median age was 61/60 years; 75% had KPS>80 75/76%; 36% grade 3 tumor 29/43%, 79% stage IIB/III 75/84%, 31% R1 resection 35/29%. Survival figures (A/B) were: Median disease-free survival was 11.7 and 15.2 months; 1-year disease-free survival 49.0% (95% confidence interval [95% CI] 35-63%) and 69.4% (95% CI 56-83%); median survival 24.8 and 28.9 months. Combination chemotherapy produced more hematological toxicity without relevant differences in nonhematological toxicities. CONCLUSIONS: The 4-drug regimen deserves further assessment in resectable pancreatic cancer.

7 Clinical Trial Intraoperative ultrasound with contrast medium in resective pancreatic surgery: a pilot study. 2011

Spinelli, Antonino / Del Fabbro, Daniele / Sacchi, Matteo / Zerbi, Alessandro / Torzilli, Guido / Lutman, Fabio R / Laghi, Luigi / Malesci, Alberto / Montorsi, Marco. ·Unità Operativa e Cattedra di Chirurgia Generale, Università degli Studi di Milano, Istituto Clinico Humanitas-IRCCS, Via Alessandro Manzoni 56, 20089, Rozzano, Milan, Italy. antonino.spinelli@humanitas.it ·World J Surg · Pubmed #21882034.

ABSTRACT: BACKGROUND: The introduction of contrast-enhanced ultrasound has been a major innovation in liver and pancreatic imaging. Previous studies have validated its intraoperative use during liver surgery, while there is a lack of data regarding its use during pancreatic surgery. The purpose of the present study was to prospectively evaluate the possible role of contrast-enhanced intraoperative ultrasound (CEIOUS) during resective pancreatic surgery for primary lesion characterization and intraoperative staging. MATERIALS AND METHODS: Thirty-four patients (70% males, mean age 67.9 years) were selected for pancreatic surgery between October 2006 and July 2009. All patients underwent intraoperative ultrasound with intravenous injection of 4.8 mL sulfur-hexafluoride microbubbles. Location of the primary tumor, relation to the main vessels, contrast medium uptake modalities, presence of liver metastases, and multifocal pancreatic involvement were evaluated. The majority of operations were pancreatoduodenectomies (70.6%) performed for pancreatic ductal adenocarcinoma (64.7%). RESULTS: Additional lesions were detected by ultrasound in six patients (17.6%: liver metastases in four patients, a hemangioma in one patient, and a further pancreatic lesion in one patient). In five of these patients (5/34, 14.7%) surgical management was modified by these findings. All these new findings were diagnosed before injection of contrast medium, except for a metastasis from a neuroendocrine tumor; the characterization of the hemangioma was possible only after contrast injection. Intraoperative findings regarding location of primary tumor, relation to the main vessels, and lesion characterization did not differ from those obtained with preoperative imaging. CONCLUSIONS: In our experience intraoperative ultrasound is a valid technique for intraoperative staging prior to pancreatic resection; it is unclear whether, in pancreatic surgery, the addition of contrast enhancement adds any benefit to traditional intraoperative ultrasound.

8 Clinical Trial Clinicopathological features of pancreatic endocrine tumors: a prospective multicenter study in Italy of 297 sporadic cases. 2010

Zerbi, Alessandro / Falconi, Massimo / Rindi, Guido / Delle Fave, Gianfranco / Tomassetti, Paola / Pasquali, Claudio / Capitanio, Vanessa / Boninsegna, Letizia / Di Carlo, Valerio / Anonymous6020648. ·Department of Surgery, Pancreas Unit, San Raffaele Scientific Institute, Milan, Italy. zerbi.alessandro@hsr.it ·Am J Gastroenterol · Pubmed #20087335.

ABSTRACT: OBJECTIVES: Information on pancreatic endocrine tumors (PETs) comes mostly from small, retrospective, uncontrolled studies conducted on highly selected patients. The aim of the study was to describe the clinical and pathological features of PETs in a prospective, multicenter study. METHODS: Newly diagnosed, histologically proven, sporadic PETs observed from June 2004 to March 2007 in 24 Italian centers were included in a specific data set. RESULTS: Two hundred ninety-seven patients (mean age 58.6+/-14.7 years, females 51.2%, males 48.8%) were analyzed. In 73 cases (24.6%), the tumor was functioning (F) (53 insulinomas, 15 gastrinomas, 5 other syndromes) and in 232 (75.4%) it was non-functioning (NF); in 115 cases (38.7%), the diagnosis was incidental. The median tumor size was 20 mm (range 2-150). NF-PETs were significantly more represented among carcinomas (P<0.001). Nodal and liver metastases were detected in 84 (28.3%) and 85 (28.6%) cases, respectively. The presence of liver metastases was significantly higher in the NF-PETs than in the F-PETs (32.1% vs. 17.8%; P<0.05), and in the symptomatic than in the asymptomatic patients (34.6% vs. 19.1%; P<0.005). At the time of recruitment, the majority of patients (251, 84.5%) had undergone surgery, with complete resection in 209 cases (83.3%). CONCLUSIONS: This study points out the high number of new cases of PETs observed in Italy, with a high prevalence of NF and incidentally discovered forms. The size of the tumor was smaller and the rate of metastasis was lower than usually reported, suggesting a trend toward an earlier diagnosis.

9 Clinical Trial Outcome of upfront combination chemotherapy followed by chemoradiation for locally advanced pancreatic adenocarcinoma. 2009

Reni, Michele / Cereda, S / Balzano, G / Passoni, P / Rognone, A / Zerbi, A / Nicoletti, R / Mazza, E / Arcidiacono, P G / Di Carlo, V / Villa, E. ·Department of Oncology, S. Raffaele Scientific Institute, via Olgettina 60, Milan 20132, Italy. reni.michele@hsr.it ·Cancer Chemother Pharmacol · Pubmed #19381632.

ABSTRACT: PURPOSE: The role and timing of chemotherapy and radiation for treating stage III pancreatic adenocarcinoma remains controversial. METHODS: Treatment-naive patients with stage III non-resectable pancreatic adenocarcinoma were treated with PEFG/PEXG (cisplatin, epirubicin, 5-fluorouracil (F)/capecitabine (X), gemcitabine) or PDXG (docetaxel substituting epirubicin) regimen for 6 months followed by radiotherapy (50-60 Gy) with concurrent F or X or G. RESULTS: Ninety-one patients were registered between April 1997 and December 2007. Forty-three patients (47%) had a partial remission and 38 (42%) had a stable disease. Thirteen patients (14%) were radically resected yielding one pathologic complete remission. Median survival (OS) was 16.2 months. Median progression-free survival was 9.9 months. Pattern of failure consisted of isolated local failure (N = 26, 35%); both local and systemic failure (N = 14, 19%); isolated systemic failure (N = 35, 47%). CONCLUSION: Combination chemotherapy with four-drug regimens followed by chemoradiation was a feasible strategy showing relevant results in stage III pancreatic adenocarcinoma.

10 Article Pancreatic Neuroendocrine Tumours: The Role of Endoscopic Ultrasound Biopsy in Diagnosis and Grading Based on the WHO 2017 Classification. 2019

Di Leo, Milena / Poliani, Laura / Rahal, Daoud / Auriemma, Francesco / Anderloni, Andrea / Ridolfi, Cristina / Spaggiari, Paola / Capretti, Giovanni / Di Tommaso, Luca / Preatoni, Paoletta / Zerbi, Alessandro / Carnaghi, Carlo / Lania, Andrea / Malesci, Alberto / Repici, Alessandro / Carrara, Silvia. ·Humanitas Clinical and Research Center, IRCCS, Digestive Endoscopy Unit, Division of Gastroenterology, Milan, Italy, milena.di_leo@hunimed.eu. · Humanitas University, Department of Biomedical Sciences, Milan, Italy, milena.di_leo@hunimed.eu. · Humanitas Clinical and Research Center, IRCCS, Digestive Endoscopy Unit, Division of Gastroenterology, Milan, Italy. · Department of Pathology, Humanitas Clinical and Research Center, IRCCS, Milan, Italy. · Humanitas Clinical and Research Center, IRCCS, Pancreatic Surgery Unit, Milan, Italy. · Humanitas University, Department of Biomedical Sciences, Milan, Italy. · Humanitas Clinical and Research Center, IRCCS, Division of Gastroenterology, Milan, Italy. · Humanitas Clinical and Research Center, IRCCS, Division of Oncology, Milan, Italy. · Humanitas Clinical and Research Center, IRCCS, Division of Endocrinology, Milan, Italy. ·Dig Dis · Pubmed #30897588.

ABSTRACT: BACKGROUND: One of the controversial issues in the diagnosis of pancreatic neuroendocrine tumours (pNETs) is the accurate prediction of their clinical behaviour. OBJECTIVES: The aim of the study was to evaluate the role of endoscopic ultrasound (EUS) biopsy in the diagnosis and grading of pNETs in a certified ENETS Center. METHODS: A prospectively maintained database of EUS biopsy procedures was retrospectively reviewed to identify all consecutive patients referred to a certified ENETS Center with a suspicion of pNET between June 2014 and April 2017. The cytological and/or histological specimens were stained and the Ki-67 labeling index was evaluated. In patients undergoing surgery, the grade obtained with EUS-guided biopsy was compared with the final histological grade. The grade was evaluated according to the 2017 WHO classifications and grading. RESULTS: The study population included 59 patients. EUS biopsy material reached an adequacy of 98.3% and was adequate for Ki-67 evaluation in 84.7% of cases. Twenty-nine patients (49.2%) underwent surgery. Of these, 25 patients had Ki-67 evaluated on EUS biopsy: the agreement between EUS biopsy grading and surgical specimen grading was 84%. CONCLUSION: EUS biopsy is an accurate method for the diagnosis and grading of pNETs based on the WHO 2017 Ki-67 labelling scheme.

11 Article Evaluation of the MDACC clinical classification system for pancreatic cancer patients in an European multicenter cohort. 2019

Uzunoglu, F G / Welte, M-N / Gavazzi, F / Maggino, L / Perinel, J / Salvia, R / Janot, M / Reeh, M / Perez, D / Montorsi, M / Zerbi, A / Adham, M / Uhl, W / Bassi, C / Izbicki, J R / Malleo, G / Bockhorn, M. ·Department of General, Visceral and Thoracic Surgery, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. · Department of General Surgery, Humanitas Research Hosptital and University, Istituto Clinico Humanitas IRCCS, Milan, Italy. · Department of Surgery and Oncology, Unit of General and Pancreatic Surgery, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy. · Hospices Civils de Lyon & Lyon Sud Faculty of Medicine, UCBL1, E. Herriot Hospital, Department of Digestive Surgery, Lyon, France. · Department of Surgery, St. Josef-Hospital Bochum, Hospital of the Ruhr- University, Bochum, Germany. · Department of General, Visceral and Thoracic Surgery, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. Electronic address: m.bockhorn@uke.de. ·Eur J Surg Oncol · Pubmed #30585172.

ABSTRACT: BACKGROUND: The MDACC group recommends to extend the current borderline classification for pancreatic cancer into three groups: type A patients with resectable/borderline tumor anatomy, type B with resectable/borderline resectable tumor anatomy and clinical findings suspicious for extrapancreatic disease and type C with borderline resectable and marginal performance status/severe pre-existing comorbidity profile or age>80. This study intents to evaluate the proposed borderline classification system in a multicenter patient cohort without neoadjuvant treatment. METHODS: Evaluation was based on a multicenter database of pancreatic cancer patients undergoing surgery from 2005 to 2016 (n = 1020). Complications were classified based on the Clavien-Dindo classification. χ RESULTS: Most patients (55.1%) were assigned as type A patients, followed by type C (35.8%) and type B patients (9.1%). Neither the complication rate, nor the mortality rate revealed a correlation to any subgroup. Type B patients had a significant worse progression free (p < 0.001) and overall survival (p = 0.005). Type B classification was identified as an independent prognostic marker for progression free survival (p = 0.005, HR 1.47). CONCLUSION: The evaluation of the proposed classification in a cohort without neoadjuvant treatment did not justify an additional medical borderline subgroup. A new subgroup based on prognostic borderline patients might be the main target group for neoadjuvant protocols in future.

12 Article Impact of Sarcopenic Obesity on Failure to Rescue from Major Complications Following Pancreaticoduodenectomy for Cancer: Results from a Multicenter Study. 2018

Pecorelli, Nicolò / Capretti, Giovanni / Sandini, Marta / Damascelli, Anna / Cristel, Giulia / De Cobelli, Francesco / Gianotti, Luca / Zerbi, Alessandro / Braga, Marco. ·Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. pecorelli.nicolo@hsr.it. · Pancreatic Surgery Unit, Humanitas University, Humanitas Research Hospital, Rozzano, Italy. · Unit of Hepato-biliary-pancreatic Surgery, School of Medicine and Surgery, Milano-Bicocca University, San Gerardo Hospital, Monza, Italy. · Department of Radiology, Vita-Salute San Raffaele University Hospital, Milan, Italy. · Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. ·Ann Surg Oncol · Pubmed #29116490.

ABSTRACT: BACKGROUND: Failure to rescue (FTR) is a quality-of-care indicator in pancreatic surgery, but may also identify patients who may not tolerate major postoperative complications despite being treated with best available care. Previous studies found that high visceral adipose tissue-to-skeletal muscle ratio is associated with poor outcomes following pancreaticoduodenectomy (PD). The aim of the study is to assess the impact of sarcopenic obesity on occurrence of FTR from major complications in cancer patients undergoing PD. METHODS: Prospectively collected data from three high-volume hospitals were reviewed. Total abdominal muscle area (TAMA) and visceral fat area (VFA) were assessed at preoperative staging computed tomography scan. Sarcopenic obesity was defined as high VFA/TAMA ratio. FTR was defined as postoperative mortality following major complication. RESULTS: 120 patients with major complications were included. FTR occurred in 23 (19.2%) patients. The "seminal" complications leading to FTR were pancreatic or biliary fistula-related sepsis (n = 14), postoperative pancreatic fistula (POPF)-related hemorrhage (n = 5), and duodenojejunal anastomosis leak-related sepsis (n = 1). On univariate analysis, older age [odds ratio (OR) 3.5, p = 0.034], American Society of Anesthesiologists (ASA) score 3+ (OR 4.2, p = 0.005), cardiovascular disease (OR 3.3, p = 0.013), low serum albumin (OR 2.6, p = 0.042), sarcopenic obesity (OR 4.2, p = 0.009), POPF (OR 3.1, p = 0.027), and cardiorespiratory complications (OR 3.7, p = 0.011) were significantly associated with FTR. On multivariate analysis, sarcopenic obesity [OR 5.7, 95% confidence interval (CI) 1.6-20.7, p = 0.008], ASA score 3+ (OR 4.1, 95% CI 1.2-14.3, p = 0.025), and pancreatic fistula (OR 3.2, 95% CI 1.0-10.2, p = 0.045) were independently associated with FTR. CONCLUSION: Sarcopenic obesity, low preoperative physical status, and occurrence of pancreatic fistula are associated with significantly higher risk of FTR from major complications after PD.

13 Article Consequences of Increases in Antibiotic Resistance Pattern on Outcome of Pancreatic Resection for Cancer. 2017

Gianotti, Luca / Tamini, Nicolò / Gavazzi, Francesca / Mariani, Anna / Sandini, Marta / Ferla, Fabio / Cereda, Marco / Capretti, Giovanni / Di Sandro, Stefano / Bernasconi, Davide Paolo / De Carlis, Luciano / Zerbi, Alessandro. ·Department of Surgery, San Gerardo Hospital, School of Medicine and Surgery, Milano-Bicocca University, Via Pergolesi 33, 20900, Monza, Italy. luca.gianotti@unimib.it. · Department of Surgery, San Gerardo Hospital, School of Medicine and Surgery, Milano-Bicocca University, Via Pergolesi 33, 20900, Monza, Italy. · Pancreatic Surgery Unit, Department of Surgery, Humanitas Research Hospital, Rozzano, Milan, Italy. · Department of General Surgery and Transplantation, Niguarda Cá Granda Hospital, Milan, Italy. · School of Medicine and Surgery, Centre of Biostatistics for Clinical Epidemiology, Milano-Bicocca University, Monza, Italy. ·J Gastrointest Surg · Pubmed #28681215.

ABSTRACT: BACKGROUND: The role of drug-resistance infections on surgical outcomes is controversial. The aim of the study was to determine whether increase antibiotic resistance was an independent risk factor for development of major non-infectious postoperative complications. METHODS: This work included a multicenter cohort study of patients who underwent pancreatic resections for cancer over a 3-year interval. The primary outcome was major non-infectious complication rate developing after the occurrence of multi-drug sensitive (MDS) infection, multi-drug-resistant infection (MDR), and extensive drug-resistant (XDR) infection. Multivariate logistic regression models were used to adjust for patient and operative effects. RESULTS: Eligible patients (517) were selected for the analysis. One hundred and thirteen (21.8%) patients had major non-infectious complications with a rate of 12.9% in the no infection group, 29.3% in the MSD, 41.5% in the MDR, and 58.8% in the XDR (p < 0.001). The median time of infection occurrence was postoperative days 4 (2-7 IQR) and 7 (3-12 IQR) non-infectious complications. At multivariate analysis, the risk of having major non-infectious complications was 2.67 (95% CI 1.24-5.77, P = 0.012) for MDR, 5.04 (95% CI 2.35-10.80, P < 0.001) for MDR, and 9.64 (95% CI 2.71-34.28, P < 0.001) for XDR. CONCLUSION: Antimicrobial resistance is significantly associated with the risk of major non-infectious morbidity.

14 Article Clinical results of stereotactic body radiotherapy (SBRT) in the treatment of isolated local recurrence of pancreatic cancer after R0 surgery: A retrospective study. 2017

Comito, T / Cozzi, L / Zerbi, A / Franzese, C / Clerici, E / Tozzi, A / Iftode, C / Navarria, P / D'Agostino, G / Fogliata, A / Mancosu, P / Tomatis, S / Carnaghi, C / Personeni, N / Santoro, A / Scorsetti, M. ·Radiotherapy and Radiosurgery, Istituto Clinico Humanitas, Rozzano, Italy. Electronic address: Tiziana.comito@humanitas.it. · Radiotherapy and Radiosurgery, Istituto Clinico Humanitas, Rozzano, Italy. · Pancreatic Surgery, Istituto Clinico Humanitas, Rozzano, Italy. · Oncology and Hematology, Istituto Clinico Humanitas, Rozzano, Italy. · Radiotherapy and Radiosurgery, Istituto Clinico Humanitas, Rozzano, Italy; Dept. of Biomedical Sciences, Humanitas University, Rozzano, Italy. ·Eur J Surg Oncol · Pubmed #28131670.

ABSTRACT: OBJECTIVE: To evaluate the efficacy and the feasibility of SBRT for selected patients with isolated local recurrence of pancreatic cancer after radical surgery. METHODS: A retrospective analysis was performed on patients treated with SBRT for isolated local recurrence from resected pancreatic adenocarcinoma, after multidisciplinary board evaluation. Prescription dose was 45 Gy in 6 fractions for all patients. Primary end-point was freedom from local progression (FFLP). Secondary end-points were overall survival (OS), progression free survival (PFS) and toxicity. Local control was defined according to RECIST criteria. Acute and late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS: Between January 2011 and February 2015, 31 patients with isolated local recurrence of resected pancreatic cancer were treated with SBRT. Pancreato-duodenectomy (PD) was performed on 24 patients and distal pancreatectomy (DP) in 7 cases, all with radical resection (R0). Median local recurrence disease free interval (DFI) was 14 months. Median follow-up was 12 months. FFLP was 91% and 82% at 1 and 2-years, respectively. Median PFS was 9 months. Median OS was 18 months. At univariate analysis, OS was correlated with a DFI>18 months. No cases of acute G3 toxicity or greater occurred. CONCLUSIONS: SBRT seems to be an effective and safe therapeutic option for isolated local recurrence of pancreatic cancer after surgery. Encouraging local control rate, very low toxicity profile and effective pain control suggest the crucial role of SBRT in the treatment of these long-survivors selected patients.

15 Article The Golden Compass to the Depths. 2016

Carrara, Silvia / Di Leo, Milena / Zerbi, Alessandro. ·Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano Milan, Italy. · Pancreatic Surgery Unit, Humanitas Research Hospital, Rozzano Milan, Italy. ·Gastroenterology · Pubmed #27713050.

ABSTRACT: -- No abstract --

16 Article Parenchyma-sparing surgery for pancreatic endocrine tumors. 2016

Uccelli, Fara / Gavazzi, F / Capretti, G / Virdis, M / Montorsi, M / Zerbi, A. ·Pancreatic Surgery Unit-Hospital Health Direction, Humanitas Research Hospital, Rozzano, MI, Italy. fara.uccelli@humanitas.it. · Pancreatic Surgery Unit-Hospital Health Direction, Humanitas Research Hospital, Rozzano, MI, Italy. · Chancellor of Humanitas University, Chief of Department of Surgery, Humanitas Research Hospital, Rozzano, Italy. ·Updates Surg · Pubmed #27709476.

ABSTRACT: Enucleation (EN) and middle pancreatectomy (MP) have been proposed as a treatment for G1 and G2 pancreatic neuroendocrine tumors (PNET). The aim of this study is to analyze the outcomes of parenchyma-sparing surgery (PSS) for PNET in an Italian high-volume center. All patients with a histological diagnosis of PNET who underwent surgical resection in our center between January 2010 and January 2016 were included in the study. Demographic, perioperative, and discharge data were collected in a prospective database. Follow-up was considered until March 31, 2016. 99 patients were included. PSS was performed in 22 cases (22.2 %), 18 EN (82 %), and 4 MP (18 %). 89.8 % patients were staged with CT scan, 69.6 % with endoscopic ultrasonography, 48.4 % with MRI, and 47.4 % with 68Ga-PET. Pre-operative histological diagnosis was obtained in 68.6 %. Most of PSS tumors were G1 (n = 15; 68 %) and there were no G3. Nodal sampling was performed in every PSS. Only two patients showed nodal metastatic disease. The median post-operative length of stay was 7 days after PSS. Eleven (50 %) of these patients developed a complication; two (18.2 %) were major complications. Pancreatic fistula developed in ten patients (45.5 %); two (20 %) were type B. There were no type C fistula and no re-operations after PSS. Readmission rate was 9 %. All patients submitted to PSS are alive and free of recurrence. PSS is a safe technique for G1 and G2 PNETs, but it has to be conducted in experienced centers and an extensive nodal sampling and a long follow-up are required for the best oncologic outcome.

17 Article Synchronous resections of hepatic oligometastatic pancreatic cancer: Disputing a principle in a time of safe pancreatic operations in a retrospective multicenter analysis. 2016

Tachezy, Michael / Gebauer, Florian / Janot, Monika / Uhl, Waldemar / Zerbi, Alessandro / Montorsi, Marco / Perinel, Julie / Adham, Mustapha / Dervenis, Christos / Agalianos, Christos / Malleo, Giuseppe / Maggino, Laura / Stein, Alexander / Izbicki, Jakob R / Bockhorn, Maximilian. ·Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany. · Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany. Electronic address: fgebauer@uke.de. · Department of General and Visceral Surgery, St. Josef-Hospital Bochum, Hospital of the Ruhr-University, Bochum, Germany. · Department of General Surgery, University of Milan, Instituto Clinico Humanitas IRCCS, Milan, Italy. · Department of Hepato-Biliary and Pancreatic Surgery, Edouard Herriot Hospital, HCL, Lyon Faculty of Medicine - UCBL1, Lyon, France. · Department of Surgery, Agia Olga Hospital, Athens, Greece. · Department of Surgery, Unit of Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Oncology, Hematology, BMT with section Pneumology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany. ·Surgery · Pubmed #27048934.

ABSTRACT: BACKGROUND: The prognosis of patients with liver metastasis is generally considered dismal, and combined resections of the primary tumor and metastasectomies are not recommended. In highly selected patients, however, resections are performed. The evidence for this indication is limited. The aim of the current study was to assess the operative and oncologic outcomes of patients with combined pancreatic and liver resections of synchronous liver metastases. METHODS: In a retrospective analysis of 6 European pancreas centers, we identified 69 patients with pancreatic ductal adenocarcinoma and synchronous liver metastasis who underwent simultaneous pancreas and liver metastasis resections. Patients receiving exploration without tumor resection served as the control group. RESULTS: Overall survival (OS) appeared to be prolonged in the group of resected patients (median 14 vs 8 months, P < .001). Subgroup analysis revealed that the survival benefit of the resected patients was driven by pancreatic ductal adenocarcinomas localized in the pancreatic head (median OS 13.6 vs 7 months, P < .001). Body/tail pancreatic ductal adenocarcinomas showed no benefit of resection (median OS 14 vs 15 months, P = .312). In the multivariate analysis, tumor resection was the only independent prognosticator for OS (hazard ratio 2.044, 95% confidence interval 1.342-3.114). CONCLUSION: The data of this retrospective and selective patient cohort suggested a clear survival benefit for patients undergoing synchronous pancreas and liver resections for pancreatic ductal adenocarcinoma, but due to the limitations of this retrospective study and very strong potential for selection bias, a strong conclusion for resection cannot be drawn. Prospective trials must validate these data and investigate the use of combined operative and systemic treatments in case of resectable metastatic pancreatic cancer. Is it time for a multicenter, prospective trial?

18 Article Role of preoperative biliary stents, bile contamination and antibiotic prophylaxis in surgical site infections after pancreaticoduodenectomy. 2016

Gavazzi, Francesca / Ridolfi, Cristina / Capretti, Giovanni / Angiolini, Maria Rachele / Morelli, Paola / Casari, Erminia / Montorsi, Marco / Zerbi, Alessandro. ·Pancreatic Surgery Unit, Department of Surgery, Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy. francesca.gavazzi@humanitas.it. · Pancreatic Surgery Unit, Department of Surgery, Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy. · Infectious Diseases Unit, Hospital Health Direction, Humanitas Research Hospital, Rozzano, Italy. · Microbiology Unit, Analysis Laboratory, Humanitas Research Hospital, Rozzano, Italy. · Chancellor of Humanitas University, Chief of Department of Surgery, Humanitas Research Hospital, Rozzano, Italy. ·BMC Gastroenterol · Pubmed #27036376.

ABSTRACT: BACKGROUND: The routine use of preoperative biliary drainage before pancreaticoduodenectomy (PD) remains controversial. This observational retrospective study compared stented and non-stented patients undergoing PD to assess any differences in post-operative morbidity and mortality. METHODS: A total of 180 consecutive patients who underwent PD and had intra-operative bile cultures performed between January 2010 and February 2013 were retrospectively identified. All patients received peri-operative intravenous antibiotic prophylaxis, primarily cefazolin. RESULTS: Overall incidence of post-operative surgical complications was 52.3 %, with no difference between stented and non-stented patients (53.4 % vs. 51.1 %; p = 0.875). However, stented patients had a significantly higher incidence of deep incisional surgical site infections (SSIs) (p = 0.038). In multivariate analysis, biliary stenting was confirmed as a risk factor for deep incisional SSIs (p = 0.044). Significant associations were also observed for cardiac disease (p = 0.010) and BMI ≥25 kg/m(2) (p = 0.045). Enterococcus spp. were the most frequent bacterial isolates in bile (74.5 %) and in drain fluid (69.1 %). In antimicrobial susceptibilty testing, all Enterococci isolates were cefazolin-resistant. CONCLUSION: Given the increased risk of deep incisional SSIs, preoperative biliary stenting in patients underging PD should be used only in selected patients. In stented patients, an antibiotic with anti-enterococcal activity should be chosen for PD prophylaxis.

19 Article Dissection of transcriptional and cis-regulatory control of differentiation in human pancreatic cancer. 2016

Diaferia, Giuseppe R / Balestrieri, Chiara / Prosperini, Elena / Nicoli, Paola / Spaggiari, Paola / Zerbi, Alessandro / Natoli, Gioacchino. ·Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy. · Division of Pancreatic Surgery, Humanitas Clinical Institute, Milan, Italy. · Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy gioacchino.natoli@ieo.eu. ·EMBO J · Pubmed #26769127.

ABSTRACT: The histological grade of carcinomas describes the ability of tumor cells to organize in differentiated epithelial structures and has prognostic and therapeutic impact. Here, we show that differential usage of the genomic repertoire of transcriptional enhancers leads to grade-specific gene expression programs in human pancreatic ductal adenocarcinoma (PDAC). By integrating gene expression profiling, epigenomic footprinting, and loss-of-function experiments in PDAC cell lines of different grade, we identified the repertoires of enhancers specific to high- and low-grade PDACs and the cognate set of transcription factors acting to maintain their activity. Among the candidate regulators of PDAC differentiation, KLF5 was selectively expressed in pre-neoplastic lesions and low-grade primary PDACs and cell lines, where it maintained the acetylation of grade-specific enhancers, the expression of epithelial genes such as keratins and mucins, and the ability to organize glandular epithelia in xenografts. The identification of the transcription factors controlling differentiation in PDACs will help clarify the molecular bases of its heterogeneity and progression.

20 Article Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours. 2016

Vitali, Eleonora / Cambiaghi, Valeria / Zerbi, Alessandro / Carnaghi, Carlo / Colombo, Piergiuseppe / Peverelli, Erika / Spada, Anna / Mantovani, Giovanna / Lania, Andrea G. ·Laboratory of Cellular and Molecular EndocrinologyIRCCS Clinical and Research Institute Humanitas, Via Manzoni 56, 20089 Rozzano, Milan, ItalyPancreas Surgery UnitIRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, ItalyMedical Oncology and Hematology UnitCancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, ItalyPathology UnitIRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, ItalyFondazione IRCCS Ospedale Maggiore PoliclinicoEndocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Via F Sforza 35, 20100 Milan, ItalyDepartment of Biomedical SciencesHumanitas University, Rozzano, Milan, ItalyEndocrinology UnitHumanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy. · Laboratory of Cellular and Molecular EndocrinologyIRCCS Clinical and Research Institute Humanitas, Via Manzoni 56, 20089 Rozzano, Milan, ItalyPancreas Surgery UnitIRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, ItalyMedical Oncology and Hematology UnitCancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, ItalyPathology UnitIRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, ItalyFondazione IRCCS Ospedale Maggiore PoliclinicoEndocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Via F Sforza 35, 20100 Milan, ItalyDepartment of Biomedical SciencesHumanitas University, Rozzano, Milan, ItalyEndocrinology UnitHumanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy Laboratory of Cellular and Molecular EndocrinologyIRCCS Clinical and Research Institute Humanitas, Via Manzoni 56, 20089 Rozzano, Milan, ItalyPancreas Surgery UnitIRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, ItalyMedical Oncology and Hematology UnitCancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, ItalyPathology UnitIRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, ItalyFondazione IRCCS Ospedale Maggiore PoliclinicoEndocrinology and Diabetology Unit, Department of Clinical Sciences and Community Health, University of Milan, Via F Sforza 35, 20100 Milan, ItalyDepartment of Biomedical SciencesHumanitas University, Rozzano, Milan, ItalyEndocrinology UnitHumanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy andrea.lania@humanitas.it. ·Endocr Relat Cancer · Pubmed #26733502.

ABSTRACT: Somatostatin receptor type 2 (SST2) is the main pharmacological target of somatostatin (SS) analogues widely used in patients with pancreatic neuroendocrine tumours (P-NETs), this treatment being ineffective in a subset of patients. Since it has been demonstrated that Filamin A (FLNA) is involved in mediating GPCR expression, membrane anchoring and signalling, we investigated the role of this cytoskeleton protein in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in human P-NETs and in QGP1 cell line. We demonstrated that FLNA silencing was not able to affect SST2 expression in P-NET cells in basal conditions. Conversely, a significant reduction in SST2 expression (-43 ± 21%, P < 0.05 vs untreated cells) was observed in FLNA silenced QGP1 cells after long term SST2 activation with BIM23120. Moreover, the inhibitory effect of BIM23120 on cyclin D1 expression (-46 ± 18%, P < 0.05 vs untreated cells), P-ERK1/2 levels (-42 ± 14%; P < 0.05 vs untreated cells), cAMP accumulation (-24 ± 3%, P < 0.05 vs untreated cells), VEGF expression (-31 ± 5%, P < 0.01 vs untreated cells) and in vitro release (-40 ± 24%, P < 0.05 vs untreated cells) was completely lost after FLNA silencing. Interestingly, BIM23120 promoted cell adhesion (+86 ± 45%, P < 0.05 vs untreated cells) and inhibited cell migration (-24 ± 2%, P < 0.00001 vs untreated cells) in P-NETs cells and these effects were abolished in FLNA silenced cells. In conclusion, we demonstrated that FLNA plays a crucial role in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in P-NETs and in QGP1 cell line, suggesting a possible role of FLNA in determining the different responsiveness to SS analogues observed in P-NET patients.

21 Article A Bone in the Pancreas. 2016

Carrara, Silvia / Spaggiari, Paola / Zerbi, Alessandro. ·Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano Milan, Italy. · Department of Pathology, Humanitas Research Hospital, Rozzano Milan, Italy. · Pancreatic Surgery Unit, Humanitas Research Hospital, Rozzano Milan, Italy. ·Gastroenterology · Pubmed #26718169.

ABSTRACT: -- No abstract --

22 Article Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy. 2016

Di Caro, Giuseppe / Cortese, Nina / Castino, Giovanni Francesco / Grizzi, Fabio / Gavazzi, Francesca / Ridolfi, Cristina / Capretti, Giovanni / Mineri, Rossana / Todoric, Jelena / Zerbi, Alessandro / Allavena, Paola / Mantovani, Alberto / Marchesi, Federica. ·Department of Immunology and Inflammation, Humanitas Clinical and Research Center, Rozzano, Italy. · Section of Pancreatic Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Italy. · Molecular Biology Section, Clinical Investigation Laboratory, Humanitas Clinical and Research Center, Rozzano, Italy. · Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, San Diego, California, USA. ·Gut · Pubmed #26156960.

ABSTRACT: OBJECTIVE: Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. DESIGN: In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. RESULTS: In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. CONCLUSIONS: Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX.

23 Article Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas). 2016

Jais, B / Rebours, V / Malleo, G / Salvia, R / Fontana, M / Maggino, L / Bassi, C / Manfredi, R / Moran, R / Lennon, A M / Zaheer, A / Wolfgang, C / Hruban, R / Marchegiani, G / Fernández Del Castillo, C / Brugge, W / Ha, Y / Kim, M H / Oh, D / Hirai, I / Kimura, W / Jang, J Y / Kim, S W / Jung, W / Kang, H / Song, S Y / Kang, C M / Lee, W J / Crippa, S / Falconi, M / Gomatos, I / Neoptolemos, J / Milanetto, A C / Sperti, C / Ricci, C / Casadei, R / Bissolati, M / Balzano, G / Frigerio, I / Girelli, R / Delhaye, M / Bernier, B / Wang, H / Jang, K T / Song, D H / Huggett, M T / Oppong, K W / Pererva, L / Kopchak, K V / Del Chiaro, M / Segersvard, R / Lee, L S / Conwell, D / Osvaldt, A / Campos, V / Aguero Garcete, G / Napoleon, B / Matsumoto, I / Shinzeki, M / Bolado, F / Fernandez, J M Urman / Keane, M G / Pereira, S P / Acuna, I Araujo / Vaquero, E C / Angiolini, M R / Zerbi, A / Tang, J / Leong, R W / Faccinetto, A / Morana, G / Petrone, M C / Arcidiacono, P G / Moon, J H / Choi, H J / Gill, R S / Pavey, D / Ouaïssi, M / Sastre, B / Spandre, M / De Angelis, C G / Rios-Vives, M A / Concepcion-Martin, M / Ikeura, T / Okazaki, K / Frulloni, L / Messina, O / Lévy, P. ·Department of Gastroenterology and Pancreatology, Beaujon Hospital, AP-HP, Clichy, France. · The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, Verona, Italy. · Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Division of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Departments of Surgery and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. · First Department of Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan. · Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. · Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. · Department of Surgery, Yonsei University College of Medicine, Pancreaticobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea. · Pancreatic Surgery Unit, Department of Surgery, Polytechnic University of Marche Region, Ancona-Torrette, Italy. · NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, Padua, Italy. · Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. · Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Hepato-Pancreato-Biliary Unit, Pederzoli Hospital, Peschiera del Garda, Italy. · Department of Gastroenterology, Hepatopancreatology and GI Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China. · Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Department of Pathology, Gyeongsang National University School of Medicine, Jinju, Korea. · Hepato-Pancreato-Biliary Unit, Freeman Hospital, Newcastle upon Tyne, UK. · National Institute of Surgery and Transplantology named after Shalimov, Kiev, Ukraine. · Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet at Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. · Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. · Hôpital Privé Mermoz, Gastroentérologie, Lyon, France. · Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. · Gastroenterology Department, Hospital de Navarra, Pamplona, Spain. · Department of Gastroenterology and Hepatology, University College Hospital, London, UK. · Department of Gastroenterology, Hospital Clinic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain. · Department of Pancreatic Surgery, Humanitas Research Hospital, Rozzano, Milan, Italy. · Gastroenterology and Liver Services, Concord Hospital, Sydney, New South Wales, Australia. · Radiological Department, General Hospital Cá Foncello, Treviso, Italy. · Division of Gastroenterology and Gastrointestinal Endoscopy, San Raffaele Scientific Institute, Milan, Italy. · Department of Internal Medicine, Digestive Disease Center and Research Institute, SoonChunHyang University School of Medicine, Bucheon, Korea. · Department of Gastroenterology, Bankstown-Lidcombe Hospital, Bankstown, New South Wales, Australia. · Department of Digestive Surgery, Timone Hospital, Marseille, France. · Gastrohepatology Department, San Giovanni Battista Molinette Hospital, University of Turin, Turin, Italy. · Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Institut de Reçerca-IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. · The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan. · Department of Medicine, Pancreas Center, University of Verona, Verona, Italy. ·Gut · Pubmed #26045140.

ABSTRACT: OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

24 Article Morphohistological features of pancreatic stump are the main determinant of pancreatic fistula after pancreatoduodenectomy. 2014

Ridolfi, Cristina / Angiolini, Maria Rachele / Gavazzi, Francesca / Spaggiari, Paola / Tinti, Maria Carla / Uccelli, Fara / Madonini, Marco / Montorsi, Marco / Zerbi, Alessandro. ·Section of Pancreatic Surgery, Department of General Surgery, Humanitas Research Hospital, University of Milan School of Medicine, Via Manzoni 56, Rozzano, 20089 Milan, Italy. · Department of Pathology, Humanitas Research Hospital, Rozzano, 20089 Milan, Italy. ·Biomed Res Int · Pubmed #24900974.

ABSTRACT: INTRODUCTION: Pancreatic surgery is challenging and associated with high morbidity, mainly represented by postoperative pancreatic fistula (POPF) and its further consequences. Identification of risk factors for POPF is essential for proper postoperative management. AIM OF THE STUDY: Evaluation of the role of morphological and histological features of pancreatic stump, other than main pancreatic duct diameter and glandular texture, in POPF occurrence after pancreaticoduodenectomy. PATIENTS AND METHODS: Between March 2011 and April 2013, we performed 145 consecutive pancreaticoduodenectomies. We intraoperatively recorded morphological features of pancreatic stump and collected data about postoperative morbidity. Our dedicated pathologist designed a score to quantify fibrosis and inflammation of pancreatic tissue. RESULTS: Overall morbidity was 59,3%. Mortality was 4,1%. POPF rate was 28,3%, while clinically significant POPF were 15,8%. Male sex (P = 0.009), BMI ≥ 25 (P = 0.002), prolonged surgery (P = 0.001), soft pancreatic texture (P < 0.001), small pancreatic duct (P < 0.001), pancreatic duct decentralization on stump anteroposterior axis, especially if close to the posterior margin (P = 0.031), large stump area (P = 0.001), and extended stump mobilization (P = 0.001) were related to higher POPF rate. Our fibrosis-and-inflammation score is strongly associated with POPF (P = 0.001). DISCUSSION AND CONCLUSIONS: Pancreatic stump features evaluation, including histology, can help the surgeon in fitting postoperative management to patient individual risk after pancreaticoduodenectomy.

25 Article Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis. 2013

Celesti, G / Di Caro, G / Bianchi, P / Grizzi, F / Marchesi, F / Basso, G / Rahal, D / Delconte, G / Catalano, M / Cappello, P / Roncalli, M / Zerbi, A / Montorsi, M / Novelli, F / Mantovani, A / Allavena, P / Malesci, A / Laghi, L. ·Laboratory of Molecular Gastroenterology, Department of Gastroenterology, Humanitas Clinical and Research Center, Via Manzoni, 56, 20089 Rozzano, Milan, Italy. ·Br J Cancer · Pubmed #24084767.

ABSTRACT: BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1 expression occurs early in PDAC and correlates with tumour features other than PNI. METHODS: We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in 104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and in PdxCre/LSL-Kras(G12D) mouse model of PDAC. CX3CR1 expression in vitro was studied by a spheroid model, and in vivo by syngenic mouse graft of tumour cells. RESULTS: In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45 (43.3%) both. CX3CR1 expression was independently associated with tumour glandular differentiation (P=0.005) and PNI (P=0.01). Pancreatic Intraepithelial Neoplasias were more frequently CX3CR1+ (80.3%, P<0.001) and CX3CL1+ (86.8%, P=0.002) than matched cancers. The survival of PDAC patients was better in those with CX3CR1+ tumour (P=0.05). Mouse PanINs were also CX3CR1(+) and -CL1(+). In vitro, cytokines significantly increased CX3CL1 but not CX3CR1 expression. Differently, CX3CR1 was upregulated in tumour spheroids, and in vivo only in well-differentiated tumours. CONCLUSION: Tumour differentiation, rather than inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1 expression pattern suggests its early involvement in PDAC progression, outlining a potential target for interfering with the PanIN transition to invasive cancer.

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