Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Alessandro Zerbi
Based on 45 articles published since 2010
(Why 45 articles?)
||||

Between 2010 and 2020, A. Zerbi wrote the following 45 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

Anonymous4770793 / Anonymous4780793 / 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 / Anonymous4790793. ·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 Article FOXA2 controls the cis-regulatory networks of pancreatic cancer cells in a differentiation grade-specific manner. 2019

Milan, Marta / Balestrieri, Chiara / Alfarano, Gabriele / Polletti, Sara / Prosperini, Elena / Spaggiari, Paola / Zerbi, Alessandro / Diaferia, Giuseppe R / Natoli, Gioacchino. ·Humanitas University, Milano, Italy. · Humanitas Clinical Research Center IRCCS, Milano, Italy. · Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, Italy. ·EMBO J · Pubmed #31531882.

ABSTRACT: Differentiation of normal and tumor cells is controlled by regulatory networks enforced by lineage-determining transcription factors (TFs). Among them, TFs such as FOXA1/2 bind naïve chromatin and induce its accessibility, thus establishing new gene regulatory networks. Pancreatic ductal adenocarcinoma (PDAC) is characterized by the coexistence of well- and poorly differentiated cells at all stages of disease. How the transcriptional networks determining such massive cellular heterogeneity are established remains to be determined. We found that FOXA2, a TF controlling pancreas specification, broadly contributed to the cis-regulatory networks of PDACs. Despite being expressed in both well- and poorly differentiated PDAC cells, FOXA2 displayed extensively different genomic distributions and controlled distinct gene expression programs. Grade-specific functions of FOXA2 depended on its partnership with TFs whose expression varied depending on the differentiation grade. These data suggest that FOXA2 contributes to the regulatory networks of heterogeneous PDAC cells via interactions with alternative partner TFs.

10 Article Thrombosis of the dorsal vein of the penis as first clinical presentation of pancreatic cancer metastatic to the penis. 2019

Virdis, Matteo / Bonifacio, Cristiana / Brambilla, Tatiana / Capretti, Giovanni / De Nittis, Pasquale / Uccelli, Fara / Zerbi, Alessandro. ·1 Pancreatic Surgery Unit, Hospital Health Direction, Humanitas Research Hospital, Rozzano (MI), Italy. · 2 Unit of Diagnostic Radiology, Humanitas Research Hospital, Rozzano (MI), Italy. · 3 Pathology, Humanitas Research Hospital, Rozzano (MI), Italy. · 4 General Surgery, Humanitas University, Rozzano (MI), Italy. ·Tumori · Pubmed #31072230.

ABSTRACT: INTRODUCTION: Though metastatic disease is a common presentation of pancreatic adenocarcinoma, localization to the penis is an extremely rare event despite its abundant vascularization. Primary cancers responsible for penile metastases usually occur in prostate and rectum and are often associated with disseminated malignancy and poor prognosis. CASE DESCRIPTION: A 66-year-old man was diagnosed with adenocarcinoma of the tail of the pancreas after the onset of thrombosis of the dorsal vein of the penis; pubis ultrasound and total body computed tomography scan were negative for metastases at other sites. The patient was submitted to distal pancreatectomy with splenectomy for a pT3 N1 G4 pancreatic ductal adenocarcinoma. Three weeks after discharge, the patient returned to the outpatient clinic complaining of a painful permanent turgidity of the penis shaft. Ultrasound revealed a complete replacement of the cavernosal bodies by multiple nodular masses and a penile biopsy confirmed metastases from the primary pancreatic cancer. The patient started chemotherapy with NAB-paclitaxel and gemcitabine, with excellent control of symptoms. However, the disease progressed to bone and liver and the patient died 9 months after surgery. CONCLUSIONS: Penile localization is an extremely rare event and a standard of care has not been elaborated. Treatments are palliative and mainly aimed at pain relief and can comprise chemotherapy, radiotherapy, and surgery. Identification of venous thrombosis as an early sign of involvement could potentially offer patients an earlier diagnosis and a better treatment option.

11 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.

12 Article Computed tomography based radiomic signature as predictive of survival and local control after stereotactic body radiation therapy in pancreatic carcinoma. 2019

Cozzi, Luca / Comito, Tiziana / Fogliata, Antonella / Franzese, Ciro / Franceschini, Davide / Bonifacio, Cristiana / Tozzi, Angelo / Di Brina, Lucia / Clerici, Elena / Tomatis, Stefano / Reggiori, Giacomo / Lobefalo, Francesca / Stravato, Antonella / Mancosu, Pietro / Zerbi, Alessandro / Sollini, Martina / Kirienko, Margarita / Chiti, Arturo / Scorsetti, Marta. ·Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy. · Radiotherapy and Radiosurgery, Humanitas Clinical and Research Center, Rozzano (Milan), Italy. · Diagnostic Radiology, Humanitas Clinical and Research Center, Rozzano (Milan), Italy. · Pancreatic Surgery, Humanitas Clinical and Research Center, Rozzano (Milan), Italy. · Nuclear Medicine, Humanitas Clinical and Research Center, Rozzano (Milan), Italy. ·PLoS One · Pubmed #30657785.

ABSTRACT: PURPOSE: To appraise the ability of a radiomics signature to predict clinical outcome after stereotactic body radiation therapy (SBRT) for pancreas carcinoma. METHODS: A cohort of 100 patients was included in this retrospective, single institution analysis. Radiomics texture features were extracted from computed tomography (CT) images obtained for the clinical target volume. The cohort of patients was randomly divided into two separate groups for the training (60 patients) and validation (40 patients). Cox regression models were built to predict overall survival and local control. The significant predictors at univariate analysis were included in a multivariate model. The quality of the models was appraised by means of area under the curve and concordance index. RESULTS: A clinical-radiomic signature associated with Overall Survival (OS) was found significant in both training and validation sets (p = 0.01 and 0.05 and concordance index 0.73 and 0.75 respectively). Similarly, a signature was found for Local Control (LC) with p = 0.007 and 0.004 and concordance index 0.69 and 0.75. In the low risk group, the median OS and LC in the validation group were 14.4 and 28.6 months while in the high-risk group were 9.0 and 17.5 months respectively. CONCLUSION: A CT based radiomic signature was identified which correlate with OS and LC after SBRT and allowed to identify low and high-risk groups of patients.

13 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.

14 Article Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA): A Pan-European Propensity Score Matched Study. 2019

van Hilst, Jony / de Rooij, Thijs / Klompmaker, Sjors / Rawashdeh, Majd / Aleotti, Francesca / Al-Sarireh, Bilal / Alseidi, Adnan / Ateeb, Zeeshan / Balzano, Gianpaolo / Berrevoet, Frederik / Björnsson, Bergthor / Boggi, Ugo / Busch, Olivier R / Butturini, Giovanni / Casadei, Riccardo / Del Chiaro, Marco / Chikhladze, Sophia / Cipriani, Federica / van Dam, Ronald / Damoli, Isacco / van Dieren, Susan / Dokmak, Safi / Edwin, Bjørn / van Eijck, Casper / Fabre, Jean-Marie / Falconi, Massimo / Farges, Olivier / Fernández-Cruz, Laureano / Forgione, Antonello / Frigerio, Isabella / Fuks, David / Gavazzi, Francesca / Gayet, Brice / Giardino, Alessandro / Groot Koerkamp, Bas / Hackert, Thilo / Hassenpflug, Matthias / Kabir, Irfan / Keck, Tobias / Khatkov, Igor / Kusar, Masa / Lombardo, Carlo / Marchegiani, Giovanni / Marshall, Ryne / Menon, Krish V / Montorsi, Marco / Orville, Marion / de Pastena, Matteo / Pietrabissa, Andrea / Poves, Ignaci / Primrose, John / Pugliese, Raffaele / Ricci, Claudio / Roberts, Keith / Røsok, Bård / Sahakyan, Mushegh A / Sánchez-Cabús, Santiago / Sandström, Per / Scovel, Lauren / Solaini, Leonardo / Soonawalla, Zahir / Souche, F Régis / Sutcliffe, Robert P / Tiberio, Guido A / Tomazic, Aleš / Troisi, Roberto / Wellner, Ulrich / White, Steven / Wittel, Uwe A / Zerbi, Alessandro / Bassi, Claudio / Besselink, Marc G / Abu Hilal, Mohammed / Anonymous5620925. ·Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. · Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom. · Department of Surgery, San Raffaele Hospital, Milan, Italy. · Department of Surgery, Morriston Hospital, Swansea, United Kingdom. · Department of Surgery, Virginia Mason Medical Center, Seattle, United States. · Department of Surgery, Karolinska Institute, Stockholm, Sweden. · Department of General and HPB surgery and liver transplantation, Ghent University Hospital, Ghent, Belgium. · Department of Surgery, Linköping University, Linköping, Sweden. · Department of Surgery, Universitá di Pisa, Pisa, Italy. · Department of Surgery, Pederzoli Hospital, Peschiera, Italy. · Department of Surgery, S. Orsola-Malpighi Hospital, Bologna, Italy. · Department of Surgery, Universitätsklinikum Freiburg, Freiburg, Germany. · Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands. · Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy. · Department of Surgery, Hospital of Beaujon, Clichy, France. · Department of Surgery, Oslo University Hospital and Institute for Clinical Medicine, Oslo, Norway. · Department of Surgery, Erasmus MC, Rotterdam, the Netherlands. · Department of Surgery, Hopital Saint Eloi, Montpellier, France. · Department of Surgery, Hospital Clínic de Barcelona, Barcelona, Spain. · Department of Surgery, Niguarda Ca' Granda Hospital, Milan, Italy. · Department of Surgery, Institut Mutualiste Montsouris, Paris, France. · Department of Surgery, Humanitas University Hospital, Milan, Italy. · Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Department of Surgery, Oxford University Hospital NHS Foundation Trust, Oxford, United Kingdom. · Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany. · Department of Surgery, Moscow Clinical Scientific Center, Moscow, Russian Federation. · Department of Surgery, University Medical Center Ljubljana, Ljubljana, Slovenia. · Department of Surgery, King's College Hospital NHS Foundation Trust, London, United Kingdom. · Department of Surgery, University hospital Pavia, Pavia, Italy. · Department of Surgery, Hospital del Mar, Barcelona, Spain. · Department of Surgery, University Hospital Birmingham, Birmingham, United Kingdom. · Surgical Clinic, Department of clinical and experimental sciences, University of Brescia, Brescia, Italy. · Department of Surgery, The Freeman Hospital Newcastle Upon Tyne, Newcastle, United Kingdom. ·Ann Surg · Pubmed #29099399.

ABSTRACT: OBJECTIVE: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC. METHODS: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival. RESULTS: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200 mL (60-400) vs 300 mL (150-500), P = 0.001] and hospital stay [8 (6-12) vs 9 (7-14) days, P < 0.001] were lower after MIDP. Clavien-Dindo grade ≥3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P > 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P < 0.001) and lymph node retrieval [14 (8-22) vs 22 (14-31), P < 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22-34] versus 31 (95% CI, 26-36) months (P = 0.929). CONCLUSIONS: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.

15 Article Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study. 2018

Rindi, Guido / Klersy, Catherine / Albarello, Luca / Baudin, Eric / Bianchi, Antonio / Buchler, Markus W / Caplin, Martyn / Couvelard, Anne / Cros, Jérôme / de Herder, Wouter W / Delle Fave, Gianfranco / Doglioni, Claudio / Federspiel, Birgitte / Fischer, Lars / Fusai, Giuseppe / Gavazzi, Francesca / Hansen, Carsten P / Inzani, Frediano / Jann, Henning / Komminoth, Paul / Knigge, Ulrich P / Landoni, Luca / La Rosa, Stefano / Lawlor, Rita T / Luong, Tu V / Marinoni, Ilaria / Panzuto, F / Pape, Ulrich-Frank / Partelli, Stefano / Perren, Aurel / Rinzivillo, Maria / Rubini, Corrado / Ruszniewski, Philippe / Scarpa, Aldo / Schmitt, Anja / Schinzari, Giovanni / Scoazec, Jean-Yves / Sessa, Fausto / Solcia, Enrico / Spaggiari, Paola / Toumpanakis, Christos / Vanoli, Alessandro / Wiedenmann, Bertram / Zamboni, Giuseppe / Zandee, Wouter T / Zerbi, Alessandro / Falconi, Massimo. ·Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italyguido.rindi@unicatt.it. · Service of Biometry and Clinical Epidemiology, Research Department, and IRCCS Fondazione Policlinico San Matteo, Pavia, Italy. · Pathology Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Oncology, Cancer Campus, Villejuif, France. · Department of Endocrinology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Surgery, University Hospital Heidelberg, Neu Heidelberg, Germany. · Neuroendocrine Tumour Unit, Centre for Gastroenterology, London, United Kingdom. · Department of Pathology, Hopital Beaujon, Paris ENETS Center of Excellence, Clichy, France. · Section Endocrinology, Department of Internal Medicine, Erasmus University Medical Center and and Erasmus MC Cancer Institute Rotterdam, Rotterdam ENETS Center of Excellence, Rotterdam, The Netherlands. · Digestive and Liver Disease Unit, Sant'Andrea University Hospital, Roma ENETS Center of Excellence, Rome, Italy. · Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen ENETS Center of Excellence, Copenhagen, Denmark. · Department of Surgery, University College, Royal Free Hospital, London ENETS Center of Excellence, London, United Kingdom. · Pancreatic Surgery, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy. · Department of Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen ENETS Center of Excellence, Copenhagen, Denmark. · Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Hepatology and Gastroenterology, Charité, Campus Virchow Klinikum and Charite Mitte, University Medicine Berlin, Berlin ENETS Center of Excellence, Berlin, Germany. · Institute of Pathology, Stadtspital Triemli, Zurich, Switzerland. · Department of Surgery and Oncology, General and Pancreatic Surgery, The Pancreas Institute, Verona ENETS Center of Excellence, Verona, Italy. · Department of Pathology, Ospedale di Circolo, Università dell'Insubria, Varese, Italy. · Section of Pathology and ARC-Net Research Centre, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona ENETS Center of Excellence, Verona, Italy. · Department of Pathology, University College, Royal Free Hospital, London ENETS Center of Excellence, London, United Kingdom. · Institute of Pathology, University of Bern, Bern, Switzerland. · Pancreatic Surgery Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Pathology, Marche Polytechnic University, Ancona, Italy. · Department of Gastroenterology and Pancreatology, Hopital Beaujon, Paris ENETS Center of Excellence, Clichy, France. · Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Medical Biology and Pathology, Cancer Campus, Villejuif, France. · Department of Molecular Medicine, University of Pavia, Pavia, Italy. · Pathology Department, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy. · Department of Pathology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy. ·Neuroendocrinology · Pubmed #30300897.

ABSTRACT: BACKGROUND: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). OBJECTIVES: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. METHOD: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. RESULTS: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. CONCLUSIONS: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

16 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.

17 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.

18 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.

19 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 --

20 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.

21 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?

22 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.

23 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.

24 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.

25 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 --

Next