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Pancreatic Neoplasms: HELP
Articles by Giuseppe Malleo
Based on 69 articles published since 2010
(Why 69 articles?)
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Between 2010 and 2020, G. Malleo wrote the following 69 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: Recommendations of Verona Consensus Meeting. 2016

Adsay, Volkan / Mino-Kenudson, Mari / Furukawa, Toru / Basturk, Olca / Zamboni, Giuseppe / Marchegiani, Giovanni / Bassi, Claudio / Salvia, Roberto / Malleo, Giuseppe / Paiella, Salvatore / Wolfgang, Christopher L / Matthaei, Hanno / Offerhaus, G Johan / Adham, Mustapha / Bruno, Marco J / Reid, Michelle D / Krasinskas, Alyssa / Klöppel, Günter / Ohike, Nobuyuki / Tajiri, Takuma / Jang, Kee-Taek / Roa, Juan Carlos / Allen, Peter / Fernández-del Castillo, Carlos / Jang, Jin-Young / Klimstra, David S / Hruban, Ralph H / Anonymous6190823. ·*Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA †Department of Pathology, Massachusetts General Hospital, Boston, MA ‡Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan §Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY ¶Department of Pathology, University of Verona, Verona, Italy ||Department of Surgery, Massachusetts General Hospital, Boston, MA **Department of Surgery, University of Verona, Verona, Italy ††Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD ‡‡Departments of Surgery, University of Bonn, Bonn, Germany §§Departments of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands ¶¶Department of Surgery, Edouard Herriot Hospital, HCL, Lyon, France ||||Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands ***Departments of Pathology, Technical University, Munich, Germany †††Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan ‡‡‡Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan §§§Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea ¶¶¶Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile ||||||Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY ****Department of Surgery, Massachusetts General Hospital, Boston, MA ††††Department of Surgery, Seoul National University Hospital, Seoul, Korea ‡‡‡‡Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. ·Ann Surg · Pubmed #25775066.

ABSTRACT: BACKGROUND: There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). DESIGN: An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. RESULTS: (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤ 0.5, > 0.5-≤ 1, > 1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intra-biliary/cholecystic). CONCLUSIONS: These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms.

2 Editorial Dynamic Behavior of Ca 19-9 and Pancreatic Cancer Recurrence: Enough Data to Drive Salvage Therapy? 2018

Malleo, Giuseppe. ·Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, G.B. Rossi Hospital, Verona, Italy. giuseppe.malleo@aovr.veneto.it. ·Ann Surg Oncol · Pubmed #30128901.

ABSTRACT: -- No abstract --

3 Review Prognostic Role of High-Grade Tumor Budding in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis with a Focus on Epithelial to Mesenchymal Transition. 2019

Lawlor, Rita T / Veronese, Nicola / Nottegar, Alessia / Malleo, Giuseppe / Smith, Lee / Demurtas, Jacopo / Cheng, Liang / Wood, Laura D / Silvestris, Nicola / Salvia, Roberto / Scarpa, Aldo / Luchini, Claudio. ·ARC-Net Research Center, University and Hospital Trust of Verona, 37134 Verona, Italy. ritateresa.lawlor@univr.it. · National Institute of Gastroenterology-Research Hospital, IRCCS "S. de Bellis", 70013 Castellana Grotte, Italy. ilmannato@gmail.com. · Department of Surgery, Section of Pathology, San Bortolo Hospital, 36100 Vicenza, Italy. alessia.nottegar@gmail.com. · Department of General and Pancreatic Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37142 Verona, Italy. giuseppe.malleo@univr.it. · Cambridge Centre for Sport and Excercise Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UK. Lee.Smith@anglia.ac.uk. · Primary Care Department, Azienda USL Toscana Sud Est, 58100 Grosseto, Italy. eritrox7@gmail.com. · Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. liang_cheng@yahoo.com. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. ldelong1@jhmi.edu. · Medical Oncology Unit, IRCCS Cancer Institute "Giovanni Paolo II" of Bari, 70124 Bari, Italy. silvestrisnicola@gmail.com. · Department of General and Pancreatic Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37142 Verona, Italy. roberto.salvia@univr.it. · ARC-Net Research Center, University and Hospital Trust of Verona, 37134 Verona, Italy. aldo.scarpa@univr.it. · Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy. aldo.scarpa@univr.it. · Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy. claudio.luchini@univr.it. ·Cancers (Basel) · Pubmed #30669452.

ABSTRACT: This study aims at clarifying the prognostic role of high-grade tumor budding (TB) in pancreatic ductal adenocarcinoma (PDAC) with the first systematic review and meta-analysis on this topic. Furthermore, we analyzed with a systematic review the relationship between TB and a recently suggested TB-associated mechanism: the epithelial to mesenchymal transition (EMT). Analyzing a total of 613 patients, 251 of them (40.9%) with high grade-TB, we found an increased risk of all-cause mortality (RR, 1.46; 95% CI, 1.13⁻1.88,

4 Review Pancreatic Cancer in the Era of Neoadjuvant Therapy: A Narrative Overview. 2018

Casciani, Fabio / Marchegiani, Giovanni / Malleo, Giuseppe / Bassi, Claudio / Salvia, Roberto. · ·Chirurgia (Bucur) · Pubmed #29981662.

ABSTRACT: Pancreatic adenocarcinoma is an aggressive systemic disease with around 30% of patient presenting locally advanced disease at diagnosis and being not candidate to surgical resection. Pioneering experiences with neoadjuvant treatment for locally advanced pancreatic cancer (LAPC) were undertaken more than 25 years ago and this strategy kept on gaining consensus over time. In recent years two main breakthroughs have been done: first, clear definitions of resectable, borderline resectable and locally advanced unresectable disease were released, and, soon after, two different chemotherapy regimens (namely, FOLFIRINOX and Gemcitabine plus Nab-Paclitaxel) were introduced in the clinical practice for LAPC after their effectiveness in metastatic patients was demonstrated. This article reviews papers regarding the administration of neoadjuvant chemotherapy, with or without radiation therapy, published from 2011 through 2017 with particular significance been given to reported results in term of resection rates, complete resection (R0) rates and Overall Survival, and briefly summarizes recommendations provided by the most recent guidelines for the treatment of non-metastatic pancreatic cancer.

5 Review Screening/surveillance programs for pancreatic cancer in familial high-risk individuals: A systematic review and proportion meta-analysis of screening results. 2018

Paiella, Salvatore / Salvia, Roberto / De Pastena, Matteo / Pollini, Tommaso / Casetti, Luca / Landoni, Luca / Esposito, Alessandro / Marchegiani, Giovanni / Malleo, Giuseppe / De Marchi, Giulia / Scarpa, Aldo / D'Onofrio, Mirko / De Robertis, Riccardo / Pan, Teresa Lucia / Maggino, Laura / Andrianello, Stefano / Secchettin, Erica / Bonamini, Deborah / Melisi, Davide / Tuveri, Massimiliano / Bassi, Claudio. ·General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. Electronic address: salvatore.paiella@univr.it. · General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Gastroenterology B Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy; ARC-NET Research Center, University and Hospital Trust of Verona, Verona, Italy. · Department of Radiology, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Radiology, Casa di Cura Pederzoli Hospital, Peschiera del Garda, Italy. · Oncology Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. ·Pancreatology · Pubmed #29709409.

ABSTRACT: BACKGROUND/OBJECTIVES: Screening/surveillance programs for pancreatic cancer (PC) in familial high-risk individuals (FPC-HRI) have been widely reported, but their merits remain unclear. The data reported so far are heterogeneous-especially in terms of screening yield. We performed a systematic review and meta-analysis of currently available data coming from screening/surveillance programs to evaluate the proportion of screening goal achievement (SGA), overall surgery and unnecessary surgery. METHODS: We searched MEDLINE, Embase, PubMed and the Cochrane Library database from January 2000 to December 2016to identify studies reporting results of screening/surveillance programs including cohorts of FPC-HRI. The main outcome measures were weighted proportion of SGA, overall surgery, and unnecessary surgery among the FPC-HRI cohort, using a random effects model. SGA was defined as any diagnosis of resectable PC, PanIN3, or high-grade dysplasia intraductal papillary mucinous neoplasm (HGD-IPMN). Unnecessary surgery was defined as any other final pathology. RESULTS: In a meta-analysis of 16 studies reporting on 1551 FPC-HRI cases, 30 subjects (1.82%), received a diagnosis of PC, PanIN3 or HGD-IPMNs. The pooled proportion of SGA was 1.4%(95% CI 0.8-2, p < 0.001, I CONCLUSIONS: The weighted proportion of SGA of screening/surveillance programs published thus far is excellent. However, the probability of receiving surgery during the screening/surveillance program is non-negligible, and unnecessary surgery is a potential negative outcome.

6 Review Systematic review, meta-analysis, and a high-volume center experience supporting the new role of mural nodules proposed by the updated 2017 international guidelines on IPMN of the pancreas. 2018

Marchegiani, Giovanni / Andrianello, Stefano / Borin, Alex / Dal Borgo, Chiara / Perri, Giampaolo / Pollini, Tommaso / Romanò, Giorgia / D'Onofrio, Mirko / Gabbrielli, Armando / Scarpa, Aldo / Malleo, Giuseppe / Bassi, Claudio / Salvia, Roberto. ·General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Radiology, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Gastroenterology and Digestive Endoscopy, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Pathology, ARCNet Research Center, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. Electronic address: roberto.salvia@univr.it. ·Surgery · Pubmed #29454468.

ABSTRACT: BACKGROUND: Mural nodules (MNs) have a predominant role in the 2016 revision of the international guidelines on intraductal papillary mucinous neoplasms (IPMN) of the pancreas. The aim of this study was to evaluate MNs as predictors of invasive cancer (iCa) or high-grade dysplasia (HGD) in IPMNs and to investigate the role of MN size in risk prediction. METHODS: A PRISMA-compliant systematic review of the literature and meta-analysis on selected studies were conducted. The random effect model was adopted, and the pooled SMD (standardized mean difference) obtained. The surgical series of IPMNs at a single high-volume institution was reviewed. RESULTS: This review included 70 studies and 2297 resected IPMNs. MNs have a positive predictive value for malignancy of 62.2%. The meta-analysis suggested that MN size has a considerable effect on predicting IPMNs with both iCa or HGD with a mean SMD of 0.79. All studies included in the meta-analysis used contrast-enhanced endosonography (CE-EUS) to assess MNs. Due to the heterogeneity of the proposed thresholds, no reliable MN size cut-off was identified. Of 317 IPMNs resected at our institution, 102 (32.1%) had a preoperative diagnosis of MN. Multivariate analysis showed that MN is the only independent predictor of iCa and HGD for all types of IPMNs. CONCLUSION: MNs are reliable predictors of iCa and HGD in IPMNs as proposed by the 2016 IAP guidelines. CE-EUS seems to be the best tool for characterizing size and has the best accuracy for predicting malignancy. Further studies should determine potential MN dimensional cut-offs.

7 Review Pancreaticoduodenectomy for pancreatic cancer: the Verona experience. 2011

Malleo, Giuseppe / Marchegiani, Giovanni / Salvia, Roberto / Butturini, Giovanni / Pederzoli, Paolo / Bassi, Claudio. ·Department of Surgery, General Surgery B, G.B. Rossi Hospital, P.Le L.A. Scuro 10, 37134, Verona, Italy. ·Surg Today · Pubmed #21431477.

ABSTRACT: Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related mortality in the Western world. The current treatment is multimodal, and in resectable patients radical surgery represents the key-step toward long-term survival. Pancreaticoduodenectomy (PD) is the most widely performed operation, because the majority of ductal carcinomas arise in the head of the pancreas. Once considered extremely hazardous, PD has evolved into a safe procedure, with mortality below 5% and morbidity rates in the range from 20% to 60% at high-volume centers. Verona is regarded as one of the most prominent institutions for pancreatic surgery in Europe. More than 5500 patients with pancreatic diseases have been managed, and the surgical case load has increased substantially, with more than 1350 PDs performed. This review discusses this center's experience in surgical treatment of pancreatic head cancer. Furthermore, the preliminary results of radiofrequency thermal ablation of locally advanced ductal cancer are presented.

8 Review Clinicopathological features of adenosquamous pancreatic cancer. 2011

Regi, Paolo / Butturini, Giovanni / Malleo, Giuseppe / Pedica, Federica / D'Onofrio, Mirko / Bassi, Claudio. ·Surgical and Gastroenterological Department, University of Verona, Policlinico Borgo Roma, Piazzale LA Scuro #10, 37134 Verona, Italy. paoloregi@tiscali.it ·Langenbecks Arch Surg · Pubmed #20617336.

ABSTRACT: PURPOSE: Adenosquamous pancreatic cancer represents 0.9-4.4% of exocrine pancreatic neoplasms and is generally thought to be associated with a worse prognosis than the more common ductal adenocarcinoma. The aim of the current study is to describe the outcome of patients with adenosquamous pancreatic cancer in our institution who were managed in a multidisciplinary environment. METHODS: In a retrospective analysis between February 1990 and February 2010, we identified from our database of 890 pancreatic lesions resected for malignancy six cases (0.67%) of adenosquamous cancer. We assessed the demographics, clinical and radiological features, surgical approach, histological details and follow-up data. RESULTS: All patients underwent pylorus-preserving pancreatoduodenectomy. Two patients, one male and one female, died in the preoperative period due to sepsis and myocardial infarction, respectively. The remaining four patients received adjuvant chemotherapy. One male patient died with local recurrence after 13 months; however, one female and two male patients are still alive with Karnofsky status of 80-90% at 15, 14 and 39 months after the operation, respectively. CONCLUSIONS: The prognosis of adenosquamous pancreatic cancer remains very poor, apparently worse than ductal pancreatic cancer. Nevertheless, our report and the review of literature seem to show that "curative" surgical resection associated with adjuvant treatment may offer the best results with a similar survival rate than ductal pancreatic cancer.

9 Review Pancreatic cystic tumours: when to resect, when to observe. 2010

Salvia, R / Crippa, S / Partelli, S / Malleo, G / Marcheggiani, G / Bacchion, M / Butturini, G / Bassi, C. ·Department of Surgery, Chirurgia Generale B, Policlinico "GB Rossi", University of Verona, Verona, Italy. ·Eur Rev Med Pharmacol Sci · Pubmed #20496554.

ABSTRACT: BACKGROUND AND OBJECTIVES: In recent years there has been an increase in the diagnosis of cystic tumors of the pancreas. In this setting, difficult diagnostic problems and different therapeutic management can be proposed. MATERIAL AND METHODS: A review of the literature and authors experience were undertaken. RESULTS: Cystic tumors of the pancreas include different neoplasms with a different biological behaviour. While most serous cystadenomas (SCAs) can be managed nonoperatively, patients with mucinous cystic neoplasms (MCNs), solid pseudopapillary tumors (SPTs), main-duct intraductal papillary mucinous neoplasms (IPMNs) should undergo surgical resection. Branch-duct IPMNs can be observed with radiological and clinical follow-up when asymptomatic, < 3 cm in size and without radiologic features of malignancy (i.e. nodules). CONCLUSIONS: Cystic tumors of the pancreas are common. Differential diagnosis among the different tumor-types is of paramount importance for appropriate management. Nonoperative management seems appropriate for most SCAs and for well-selected branch-duct IPMNs.

10 Article International validation and update of the Amsterdam model for prediction of survival after pancreatoduodenectomy for pancreatic cancer. 2019

van Roessel, Stijn / Strijker, Marin / Steyerberg, Ewout W / Groen, Jesse V / Mieog, J Sven / Groot, Vincent P / He, Jin / De Pastena, Matteo / Marchegiani, Giovanni / Bassi, Claudio / Suhool, Amal / Jang, Jin-Young / Busch, Olivier R / Halimi, Asif / Zarantonello, Laura / Groot Koerkamp, Bas / Samra, Jaswinder S / Mittal, Anubhav / Gill, Anthony J / Bolm, Louisa / van Eijck, Casper H / Abu Hilal, Mohammed / Del Chiaro, Marco / Keck, Tobias / Alseidi, Adnan / Wolfgang, Christopher L / Malleo, Giuseppe / Besselink, Marc G. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. · Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK. · Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. · Pancreatic Surgery Unit, Division of Surgery, Karolinska Institute at Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, Erasmus Medical Center, Erasmus University Rotterdam, Rotterdam, the Netherlands. · Department of Surgery, Royal North Shore Hospital, St Leonards, University of Sydney, Sydney, NSW, Australia. · Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research and University of Sydney, Sydney, NSW, Australia. · Department of Surgery, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany. · Division of Surgical Oncology, Department of Surgery, University of Colorado at Denver-Anschutz Medical Campus, Aurora, CO, USA. · Section of Hepato-Pancreato-Biliary & Endocrine Surgery, Virginia Mason Medical Center, Seattle, WA, USA. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address: m.g.besselink@amsterdamumc.nl. ·Eur J Surg Oncol · Pubmed #31924432.

ABSTRACT: BACKGROUND: The objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of overall survival (OS) after pancreatoduodenectomy for pancreatic cancer. METHODS: We included consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000 and 2017 at 11 tertiary centers in 8 countries (USA, UK, Germany, Italy, Sweden, the Netherlands, Korea, Australia). Model performance for prediction of OS was evaluated by calibration statistics and Uno's C-statistic for discrimination. Validation followed the TRIPOD statement. RESULTS: Overall, 3081 patients (53% male, median age 66 years) were included with a median OS of 24 months, of whom 38% had N2 disease and 77% received adjuvant chemotherapy. Predictions of 3-year OS were fairly similar to observed OS with a calibration slope of 0.72. Statistical updating of the model resulted in an increase of the C-statistic from 0.63 to 0.65 (95% CI 0.64-0.65), ranging from 0.62 to 0.67 across different countries. The area under the curve for the prediction of 3-year OS was 0.71 after updating. Median OS was 36, 25 and 15 months for the low, intermediate and high risk group, respectively (P < 0.001). CONCLUSIONS: This large international study validated and updated the Amsterdam model for survival prediction after pancreatoduodenectomy for pancreatic cancer. The model incorporates readily available variables with a fairly accurate model performance and robustness across different countries, while novel markers may be added in the future. The risk groups and web-based calculator www.pancreascalculator.com may facilitate use in daily practice and future trials.

11 Article Residual pancreatic function after pancreaticoduodenectomy is better preserved with pancreaticojejunostomy than pancreaticogastrostomy: A long-term analysis. 2019

Benini, Luigi / Gabbrielli, Armando / Cristofori, Chiara / Amodio, Antonio / Butturini, Giovanni / Cardobi, Nicolò / Sozzi, Carlo / Frulloni, Luca / Mucelli, Roberto Pozzi / Crinò, Stefano / Bassi, Claudio / Marchegiani, Giovanni / Andrianello, Stefano / Malleo, Giuseppe / Salvia, Roberto. ·Gastroenterology B, Department of Medicine, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Radiology, Department of Diagnosis and of Pathology, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. Electronic address: claudio.bassi@univr.it. ·Pancreatology · Pubmed #31005377.

ABSTRACT: BACKGROUND: Pancreatico-enteric anastomosis after pancreaticoduodenectomy can be performed using either a pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG). Differences in surgical outcomes are still a matter of debate, and less is known about long-term functional outcomes. METHODS: Twelve years after the conclusion of a comparative study evaluating the surgical outcomes of PJ and PG (Bassi et al., Ann Surg 2005), available patients underwent morphological and functional pancreatic assessment: pancreatic volume and duct diameter measured by MRI, impaired secretion after secretin, fecal fat, fecal elastase-1 (FE-1), serum vitamin D and endocrine function. Quality of life and symptom scores were evaluated with the EORTC QLQ-C30 questionnaire. RESULTS: Only 34 patients were available for assessment. No differences were found in terms of BMI variation, endocrine function, quality of life or symptoms. Exocrine function was more severely impaired after PG than after PJ (fecal fats 26.6 ± 4.1 vs 18.2 ± 3.6 g/day; FE-1 121.4 ± 6.7 vs 170.2 ± 25.5 μg/g, vitamin D 18.1 ± 1.8 vs. 23.2 ± 3.1 ng/mL). MRI assessment identified a lower pancreatic volume (26 ± 3.1 vs. 36 ± 4.1 cm CONCLUSION: Compared to PJ, PG is associated with a more severely impaired exocrine function long-term, but they result similar endocrine function and quality of life. In patients with a long life expectancy, this should be taken into account.

12 Article Reinforced stapler versus ultrasonic dissector for pancreatic transection and stump closure for distal pancreatectomy: A propensity matched analysis. 2019

Pulvirenti, Alessandra / Landoni, Luca / Borin, Alex / De Pastena, Matteo / Fontana, Martina / Pea, Antonio / Esposito, Alessandro / Casetti, Luca / Tuveri, Massimiliano / Paiella, Salvatore / Marchegiani, Giovanni / Malleo, Giuseppe / Salvia, Roberto / Bassi, Claudio. ·Unit of General and Pancreatic Surgery, University of Verona Hospital Trust, Italy. · Unit of General and Pancreatic Surgery, University of Verona Hospital Trust, Italy. Electronic address: Roberto.salvia@univr.it. ·Surgery · Pubmed #30975498.

ABSTRACT: BACKGROUND: Postoperative pancreatic fistula is the primary contributor to morbidity after distal pancreatectomy. To date, no techniques used for the transection and closure of the pancreatic stump have shown clear superiority over the others. This study aimed to compare the rate of postoperative pancreatic fistula after pancreatic transection conducted with a reinforced stapler versus an ultrasonic dissector after a distal pancreatectomy. METHOD: Prospectively collected data of consecutive patients who underwent distal pancreatectomy from 2014 to 2017 were reviewed retrospectively. We included distal pancreatectomies in which pancreatic transection was performed by reinforced stapler or ultrasonic dissector; we excluded extended distal pancreatectomies. To overcome the absence of randomization, we conducted a propensity matching analysis according to risk factors for postoperative pancreatic fistula. RESULTS: Overall, 200 patients met the inclusion criteria. The reinforced stapler was employed in 108 patients and the ultrasonic dissector in 92 cases. After one-to-one propensity matching, 92 patients were selected from each group. The matched reinforced stapler and ultrasonic dissector cohort had no differences in baselines characteristics except for the mini-invasive approach, which was more common in the ultrasonic dissector group (34% vs 51%, P = .025). Overall, 48 patients (26%) developed a postoperative pancreatic fistula, 46 (25%) a grade B postoperative pancreatic fistula, and 2 (1%) a grade C postoperative pancreatic fistula. In the reinforced stapler group, the rate of postoperative pancreatic fistula was 12% (n = 11) and in the ultrasonic dissector group 40% (n = 37) with a P < .001. CONCLUSION: The results of this study suggest that the use of reinforced stapler for pancreatic transection decreases the risk of postoperative pancreatic fistula. A randomized trial is required to confirm these preliminary data.

13 Article Dislocation of intra-abdominal drains after pancreatic surgery: results of a prospective observational study. 2019

Marchegiani, Giovanni / Ramera, Marco / Viviani, Elena / Lombardo, Fabio / Cybulski, Adam / Chincarini, Marco / Malleo, Giuseppe / Bassi, Claudio / Zamboni, Giulia A / Salvia, Roberto. ·Department of General and Pancreatic Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Radiology, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of General and Pancreatic Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. claudio.bassi@univr.it. · Department of General and Pancreatic Surgery, "GB Rossi" Hospital, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. claudio.bassi@univr.it. ·Langenbecks Arch Surg · Pubmed #30771076.

ABSTRACT: PURPOSE: The use of intra-abdominal drains after major surgical procedures represents a well-established but controversial practice. No data are available regarding both the occurrence and the potential impact of their postoperative accidental dislocation. The aim of this study is to assess the actual rate of dislocation of intra-abdominal drains postoperatively and to evaluate its clinical impact. METHODS: This is a prospective observational study using major pancreatic surgery as a model. Ninety-one consecutive patients undergoing pancreatoduodenectomy (PD) or distal pancreatectomy (DP) underwent low-dose, non-enhanced computed tomography (LDCT) on postoperative days (POD) 1 and 3 in a blinded fashion to assess the position of drains. We compared the outcomes of patients with dislocated and correctly placed drains. RESULTS: Overall, drains were dislocated in 30 patients (33%), without differences between PD and DP. Most of dislocations were already present on POD 1 (77%). Postoperative complications occurred in 57% of patients, and the rate of postoperative pancreatic fistula (POPF) was 27%. The dislocated cohort had lesser morbidity (40% vs. 66%; relative risk (RR), 0.35; 95% CI, 0.14-0.86; P = 0.020), and the rate of POPF (3% vs. 39%, respectively; RR, 0.05; 95% CI, 0.01-0.42; P < 0.001). After PD, patients with dislocated drains had a shorter hospital stay (12 vs. 20 days; P = 0.015). No significant differences in terms of need for percutaneous drainage procedures, abdominal collections, or grade C POPFs were found between the groups. CONCLUSIONS: Dislocation of intra-abdominal drains is an early and frequent event after major pancreatic resection. Its occurrence might protect against the negative effects of maintaining drainage, eventually leading to better postoperative outcomes. This data reinforces the knowledge that surgical drains might be detrimental in selected cases.

14 Article Correlation between appearance of the retroportal fat plane at preoperative CT and pathology findings in resected adenocarcinoma of the pancreatic head. 2019

Lombardo, F / Zamboni, G A / Bonatti, M / Chincarini, M / Ambrosetti, M C / Marchegiani, G / Malleo, G / Mansueto, G / Pozzi Mucelli, R. ·Department of Radiology, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. Electronic address: fabio.lombardo@me.com. · Department of Radiology, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. · Department of Radiology, Ospedale Centrale di Bolzano, Via L. Boehler 5, 39100 Bolzano, Italy. · Department of Surgery, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. ·Clin Radiol · Pubmed #30691733.

ABSTRACT: AIM: To correlate the appearance of the retroportal fat plane at preoperative computed tomography (CT) and the pathology findings in resected adenocarcinoma of the pancreatic head (PDAC). MATERIAL AND METHODS: Forty-eight patients with resected PDAC of the pancreatic head were included (24 men, 24 women, mean age 63 years, median BMI 24.1). All patients underwent CT <30 days before surgery. The state of the retroperitoneal resection margin and the presence of lymphatic or perineural invasion were obtained from pathology reports. CT images were reviewed independently by two radiologists for assessment of the retroportal fat plane and graded in two categories (clear/effaced). Inter-reader discrepancies were solved in consensus. Interobserver agreement was calculated and Fisher's test was used to assess the correlation between CT and pathology findings. Visceral fat areas were measured and correlated with CT findings. RESULTS: A clear retroportal fat plane was significantly associated with a negative retroperitoneal margin at pathology with 100% specificity and PPV (p=0.0001). No association was observed between the appearance of the fat plane at CT and the presence of lymphatic or perineural invasion (p=ns). Interobserver agreement for retroportal fat plane evaluation was good (0.741). False-positive cases had a significantly lower visceral fat area than the correctly classified patients (p=0.0480). CONCLUSIONS: A clear retroportal fat plane is significantly associated with negative retroperitoneal resection margins at pathology. The lack of visceral adipose tissue can lead to overestimation of retroportal fat plane involvement at preoperative CT.

15 Article A Case Report of Insulinoma Relapse on Background Nesidioblastosis: A Rare Cause of Adult Hypoglycemia. 2019

Dauriz, Marco / Maneschi, Chiara / Castelli, Claudia / Tomezzoli, Anna / Fuini, Arnaldo / Landoni, Luca / Malleo, Giuseppe / Ferdeghini, Marco / Bonora, Enzo / Moghetti, Paolo. ·Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy. · Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy. · Gastroenterology and Digestive Endoscopy Unit, University and Hospital Trust of Verona, Verona, Italy. · Department of General and Pancreatic Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Nuclear Medicine Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy. ·J Clin Endocrinol Metab · Pubmed #30597028.

ABSTRACT: Context: Nesidioblastosis is a rare cause of adult hypoglycemia. Current medical therapy can mitigate disease symptoms. However, side effects and limited efficacy may prevent long-term disease management. Case Description: A 63-year-old white woman presented at our institution on April 2017 with a history of distal spleno-pancreatectomy for well-differentiated insulinoma in 2013. Hypoglycemic events did not resolve after surgery, and residual nesidioblastosis near the pancreatic resection margins was identified. Hypoglycemic episodes increased in frequency and severity despite high-dose diazoxide (DZX) therapy. On April 2016, octreotide was introduced but soon discontinued for inefficacy. When the patient arrived at our attention, add-on pasireotide was started and glucose levels monitored by subcutaneous sensor. Compared with DZX, 225 mg/d alone, sensor glucose during pasireotide + DZX 75 mg/d showed occurrence of severe hypoglycemia. Pasireotide was discontinued, and the instrumental workup (68Ga-DOTATOC CT/positron emission tomography, 99mTc-nanocolloid scintigraphy and echo-endoscopy + fine-needle aspiration biopsy) identified an insulinoma relapse. Subtotal pancreatectomy was performed without further recurrence of hypoglycemia over 9 months of follow-up. Conclusions: Although insulinoma relapses on background nesidioblastosis rarely occur, they should be considered as an alternate diagnosis when medical therapy fails to prevent hypoglycemia. Further studies are warranted to test whether the immunophenotypic signature of nesidioblastosis/insulinoma may provide insights for a tailored use of pasireotide.

16 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.

17 Article The Actual Prevalence of Symptoms in Pancreatic Cystic Neoplasms: A Prospective Propensity Matched Cohort Analysis. 2019

Marchegiani, Giovanni / Andrianello, Stefano / Miatello, Chiara / Pollini, Tommaso / Secchettin, Erica / Tedesco, Giorgia / D'Onofrio, Mirko / Malleo, Giuseppe / Bassi, Claudio / Salvia, Roberto. ·Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Radiology, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy, roberto.salvia@univr.it. ·Dig Surg · Pubmed #30541002.

ABSTRACT: BACKGROUND: The prevalence of symptoms in pancreatic cystic neoplasms (PCNs) is mainly based on retrospective surgical series. The aim of this study is to describe the actual prevalence of symptoms in PCNs under surveillance. METHODS: Patients with PCNs under surveillance observed from 2015 to 2017 were submitted to magnetic resonance imaging (MRI) and a specific interview. An identical survey was carried out on a control population matched for age, sex, and comorbidities in which any pancreatic disease was excluded by MRI. RESULTS: Two groups of 184 individuals were compared. Patients with PCNs have a similar prevalence of abdominal pain when compared to controls (35.2 vs. 28.8, p = 0.2). PCNs in the distal pancreas experienced a significantly increased prevalence of abdominal pain (42.3 vs. 28.8%, p = 0.04), whereas size and presumed connection with the ductal system did not affect the prevalence of abdominal pain. PCNs associated with abdominal pain did not differ in terms of clinical and radiological features from asymptomatic ones. CONCLUSION: Patients with PCNs under surveillance have a similar prevalence of abdominal pain when compared to a matched population of controls. Abdominal pain might not correlate with radiological signs of malignancy.

18 Article Patterns of Recurrence after Resection for Pancreatic Neuroendocrine Tumors: Who, When, and Where? 2019

Marchegiani, Giovanni / Landoni, Luca / Andrianello, Stefano / Masini, Gaia / Cingarlini, Sara / D'Onofrio, Mirko / De Robertis, Riccardo / Davì, Mariavittoria / Capelli, Paola / Manfrin, Erminia / Amodio, Antonio / Paiella, Salvatore / Malleo, Giuseppe / Damoli, Isacco / Miotto, Marco / Bianchi, Beatrice / Nessi, Chiara / Vivani, Elena / Scarpa, Aldo / Salvia, Roberto / Bassi, Claudio. ·Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Oncology, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Radiology, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Medicine, University of Verona Hospital Trust, Verona, Italy. · Pathology, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Gastroenterology, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy, roberto.salvia@univr.it. ·Neuroendocrinology · Pubmed #30481765.

ABSTRACT: BACKGROUND/AIMS: Pancreatic neuroendocrine tumors (pan-NENs) represent an increasingly common indication for pancreatic resection, but there are few data regarding possible recurrence after surgery. The aim of the study was to describe the frequency, timing, and patterns of recurrence after resection for pan-NENs with consequent implications for postoperative follow-up. METHODS: We performed a retrospective analysis of pan-NENs resected between 1990 and 2015 at The Pancreas Institute, University of Verona Hospital Trust. Predictors of recurrence were assessed. Survival analysis was conducted using the Kaplan-Meier and conditional survival (CS) methods. RESULTS: The cohort consisted of 487 patients with a median follow-up of 71 months. Recurrence developed in 12.3%: 54 (11.1%) liver metastases, 11 (2.3%) local recurrence, 10 (2.1%) nodal recurrence, and 8 (1.6%) metastases in other organs. Thirty-one (6.4%) died due to disease recurrence. Size > 21 mm, G3 grade, nodal metastasis, and vascular infiltration were independent predictors of overall recurrence. Recurrence occurred either during the first year of follow-up (n = 9), or after 10 years (n = 4). CS analysis revealed that nonfunctioning G1 pan-NEN ≤20 mm without nodal metastasis or vascular invasion had a negligible risk of developing recurrence. In the present series, after 5 years of follow-up without developing recurrence, tumor recurrence occurred only in the form of liver metastases. CONCLUSIONS: Recurrence of pan-NENs is rare and is predicted by tumor size, nodal metastasis, grading, and vascular invasion. Patients with G1 pan-NEN without nodal metastasis and vascular invasion may be considered cured by surgery. After 5 years without recurrence, follow-up should focus on excluding the development of liver metastases.

19 Article The Evolution of Surgical Strategies for Pancreatic Neuroendocrine Tumors (Pan-NENs): Time-trend and Outcome Analysis From 587 Consecutive Resections at a High-volume Institution. 2019

Landoni, Luca / Marchegiani, Giovanni / Pollini, Tommaso / Cingarlini, Sara / D'Onofrio, Mirko / Capelli, Paola / De Robertis, Riccardo / Davì, Maria V / Amodio, Antonio / Impellizzeri, Harmony / Malpaga, Anna / Miotto, Marco / Boninsegna, Letizia / Crepaz, Lorenzo / Nessi, Chiara / Zingaretti, Caterina C / Paiella, Salvatore / Esposito, Alessandro / Casetti, Luca / Malleo, Giuseppe / Tuveri, Massimiliano / Butturini, Giovanni / Salvia, Roberto / Scarpa, Aldo / Falconi, Massimo / Bassi, Claudio. ·General and Pancreatic Surgery Department, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Department of Oncology, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Department of Radiology, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Department of Pathology, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Department of Radiology, Pederzoli Hospital, Peschiera del Garda, Verona, Italy. · Department of Medicine, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Division of Surgery, Ospedale "Sacro Cuore-Don Calabria", Negrar (VR), Italy. · Department of Surgery, Pederzoli Hospital, Peschiera del Garda, Verona, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. ·Ann Surg · Pubmed #29189384.

ABSTRACT: OBJECTIVE: The objective of the present analysis is 2-fold: first, to define the evolution of time trends on the surgical approach to pancreatic neuroendocrine neoplasms (Pan-NENs); second, to perform a complete analysis of the predictors of oncologic outcome. BACKGROUND: Reflecting their rarity and heterogeneity, Pan-NENs represent a clinical dilemma. In particular, there is a scarcity of data regarding their long-term follow-up after surgical resection. METHODS: From the Institutional Pan-NEN database, 587 resected cases from 1990 to 2015 were extracted. The time span was arbitrarily divided into 3 discrete clusters enabling a balanced comparison between patient groups. Analyses for predictors of recurrence and survival were performed, together with conditional survival analyses. RESULTS: Among the 587 resected Pan-NENs, 75% were nonfunctioning tumors, and 5% were syndrome-associated tumors. The mean age was 54 years (±14 years), and 51% of the patients were female. The median tumor size was 20 mm (range 4 to 140), 62% were G1, 32% were G2, and 4% were G3 tumors. Time trends analysis revealed that the number of resected Pan-NENs constantly increased, while the size (from 25 to 20 mm) and G1 proportion (from 65% to 49%) decreased during the study period. After a mean follow-up of 75 months, recurrence analysis revealed that nonfunctioning tumors, tumor grade, N1 status, and vascular invasion were all independent predictors of recurrence. Regardless of size, G1 nonfunctioning tumors with no nodal involvement and vascular invasion had a negligible risk of recurrence at 5 years. CONCLUSIONS: Pan-NENs have been increasingly diagnosed and resected during the last 3 decades, revealing reliable predictors of outcome. Functioning and nodal status, tumor grade, and vascular invasion accurately predict survival and recurrence with resulting implications for patient follow-up.

20 Article International Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients With Resected Pancreatic Cancer. 2018

van Roessel, Stijn / Kasumova, Gyulnara G / Verheij, Joanne / Najarian, Robert M / Maggino, Laura / de Pastena, Matteo / Malleo, Giuseppe / Marchegiani, Giovanni / Salvia, Roberto / Ng, Sing Chau / de Geus, Susanna W / Lof, Sanne / Giovinazzo, Francesco / van Dam, Jacob L / Kent, Tara S / Busch, Olivier R / van Eijck, Casper H / Koerkamp, Bas Groot / Abu Hilal, Mohammed / Bassi, Claudio / Tseng, Jennifer F / Besselink, Marc G. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. · Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. · Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. · Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. · Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy. · Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts. · Department of Surgery, Southampton University Hospital National Health Service Foundation Trust, Southampton, United Kingdom. · Department of Surgery, Erasmus MC, Rotterdam, the Netherlands. ·JAMA Surg · Pubmed #30285076.

ABSTRACT: Importance: The recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation. Objective: To validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018. Exposures: Patients were retrospectively staged according to the seventh and eighth editions of the TNM staging system. Main Outcomes and Measures: Prognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics. Results: A total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For patients who were node negative, the T stage was not associated with prognostication of survival in either edition. In the eighth edition, the N stage was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9% in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57) for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition. Conclusions and Relevance: The eighth edition of the TNM staging system demonstrated a more equal distribution among stages and a modestly increased prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma compared with the seventh edition. The revised T stage remains poorly associated with survival, whereas the revised N stage is highly prognostic.

21 Article Importance of main pancreatic duct dilatation in IPMN undergoing surveillance. 2018

Marchegiani, G / Andrianello, S / Morbin, G / Secchettin, E / D'Onofrio, M / De Robertis, R / Malleo, G / Bassi, C / Salvia, R. ·Department of Surgery and Oncology, General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Radiology, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Radiology, Casa di Cura Pederzoli, Peschiera del Garda, Italy. ·Br J Surg · Pubmed #30106195.

ABSTRACT: BACKGROUND: The association between risk of pancreatic cancer and a dilated main pancreatic duct (MPD) in intraductal papillary mucinous neoplasm (IPMN) is debated. The aim of this study was to assess the role of MPD size in predicting pancreatic cancer in resected IPMNs and those kept under surveillance. METHODS: All patients with IPMN referred to the Pancreas Institute, University of Verona Hospital Trust, from 2006 to 2016 were included. The primary endpoint was the occurrence of malignancy detected at surgery or during follow-up. RESULTS: The final cohort consisted of 1688 patients with a median follow-up of 60 months. Main pancreatic duct dilatation was associated with other features of malignancy in both the resected and surveillance groups. In patients who underwent resection, only a MPD of at least 10 mm was an independent predictor of malignancy. In patients kept under surveillance, MPD dilatation was not associated with malignancy. Fifteen of 71 patients (21 per cent) with malignancy in the resection cohort had a dilated MPD alone, whereas only one of 30 (3 per cent) under surveillance with MPD dilatation alone developed malignancy. Patients with a dilated MPD and other worrisome features had an increased 5-year cumulative incidence of malignancy compared with those with a non-dilated duct (11 versus 1·2 per cent; P < 0·001); however, the risk of malignancy was not significantly increased in patients with a dilated MPD alone (4 versus 1·2 per cent; P = 0·448). CONCLUSION: In patients under surveillance, a dilated MPD alone was not associated with an increased incidence of malignancy in IPMN.

22 Article PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implications. 2018

Luchini, Claudio / Cros, Jerome / Pea, Antonio / Pilati, Camilla / Veronese, Nicola / Rusev, Borislav / Capelli, Paola / Mafficini, Andrea / Nottegar, Alessia / Brosens, Lodewijk A A / Noë, Michaël / Offerhaus, G Johan A / Chianchiano, Peter / Riva, Giulio / Piccoli, Paola / Parolini, Claudia / Malleo, Giuseppe / Lawlor, Rita T / Corbo, Vincenzo / Sperandio, Nicola / Barbareschi, Mattia / Fassan, Matteo / Cheng, Liang / Wood, Laura D / Scarpa, Aldo. ·Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy. · Department of Pathology, Beaujon Hospital, 92110 Clichy, France; Paris-Diderot School of Medicine, Inflammation Research Center, 75013 Paris, France. · Department of Surgery, University and Hospital Trust of Verona, 37134 Verona, Italy. · Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, Paris-Descartes University, 75006 Paris, France. · National Institute of Gastroenterology-Research Hospital, IRCCS "S. de Bellis," 70013, Castellana Grotte, Bari, Italy. · ARC-Net Research Center, University of Verona, 37134 Verona, Italy. · Department of Surgery, Section of Pathology, San Bortolo Hospital, 36100 Vicenza, Italy. · Department of Pathology, University Medical Center Utrecht, 3508 Utrecht, The Netherlands; Department of Pathology, Radboud University Medical Center, 6500, HB, Nijmegen, The Netherlands. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA. · Department of Pathology, University Medical Center Utrecht, 3508 Utrecht, The Netherlands. · Surgical Pathology Unit, Santa Chiara Hospital, 38122 Trento, Italy. · Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA; Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA. Electronic address: ldwood@jhmi.edu. · Department of Diagnostics and Public Health, Section of Pathology, University of Verona, 37134 Verona, Italy; ARC-Net Research Center, University of Verona, 37134 Verona, Italy. Electronic address: aldo.scarpa@univr.it. ·Hum Pathol · Pubmed #30031096.

ABSTRACT: Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has a striking genetic similarity to PDAC but a significantly improved overall survival. We hypothesize that this difference could be due to the immune response to the tumor, and as such, we investigated the expression of PD-1, PD-L1, and CD163 in a series of UCOGC. To this aim, 27 pancreatic UCOGCs (11 pure and 16 PDAC-associated), 5 extrapancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas were immunostained using antibodies against PD-1, PD-L1, and CD163. In pancreatic UCOGCs, PD-L1 was expressed in neoplastic cells of 17 (63%) of 27 cases, more often in cases with an associated PDAC (P = .04). Expression of PD-L1 was associated with poor prognosis, confirmed by multivariate analysis: patients with PD-L1-positive UCOGCs had a risk of all-cause mortality that was 3 times higher than did patients with PD-L1-negative UCOGCs (hazard ratio, 3.397; 95% confidence interval, 1.023-18.375; P = .034). PD-L1 expression on tumor cells was also associated with aberrant P53 expression (P = .035). PD-1 was expressed on rare lymphocytes in 12 UCOGCs (44.4%), mainly located at the tumor periphery. CD163 was expressed on histiocytes, with a diffuse and strong staining pattern in all UCOGCs. Extrapancreatic tumors with osteoclast-like giant cells showed very similar staining patterns for the same proteins. Anaplastic carcinomas have some similarities to UCOGCs, but PD-L1 has no prognostic roles. Our results may have important implications for immunotherapeutic strategies in UCOGCs; these tumors may also represent a model for future therapeutic approaches against PDAC.

23 Article Impact of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: An analysis of 1500 consecutive cases. 2018

De Pastena, Matteo / Marchegiani, Giovanni / Paiella, Salvatore / Malleo, Giuseppe / Ciprani, Debora / Gasparini, Clizia / Secchettin, Erica / Salvia, Roberto / Gabbrielli, Armando / Bassi, Claudio. ·General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. ·Dig Endosc · Pubmed #29943483.

ABSTRACT: BACKGROUND AND AIM: Implications of preoperative biliary drain on morbidity and mortality after pancreatoduodenectomy are still controversial. The present study aims to assess the impact of preoperative biliary drain on postoperative outcome and to define optimal serum bilirubin cut-off to recommend biliary drainage in patients undergoing pancreatoduodenectomy. METHODS: All consecutive pancreatoduodenectomies carried out at Verona Hospital from 2005 to 2016 were retrospectively analyzed. The study population was divided into three groups: preoperative biliary drained (Stented Group), preoperative jaundice without drainage (Jaundiced Group) and the control group of non-jaundiced, non-stented patients (Control Group). RESULTS: A total of 1500 patients were included. Seven hundred and fourteen patients (47.6%) received biliary drain (stented group), 258 (17.2%) patients did not (jaundiced group) and 528 (35.2%) patients represented the (control group). Major complications and mortality rates did not differ between groups. Conversely, the risk of developing surgical site infections doubled in the stented group (18.1%) (OR = 2.1, 95% CI = 1.5-2.8). In jaundiced patients, a preoperative bilirubin value greater than 7.5 mg/dL (128 μmol/L) accurately predicted the likelihood of postoperative complications. CONCLUSION: Preoperative biliary drain does not increase major complications and mortality rates after pancreatoduodenectomy, but it is associated with higher surgical site infection rates. In jaundiced patients, a bilirubin value greater than 7.5 mg/dL (128 μmol/L) should indicate biliary drainage.

24 Article The role of age in pancreatic intraductal papillary mucinous neoplasms of the pancreas: Same risk of death but different implications for management. 2018

Marchegiani, Giovanni / Andrianello, Stefano / Perri, Giampaolo / Pollini, Tommaso / Caravati, Andrea / Secchettin, Erica / Malleo, Giuseppe / Bassi, Claudio / Salvia, Roberto. ·Department of General and Pancreatic Surgery - The Pancreas Institute, University of Verona Hospital Trust, Italy. · Department of General and Pancreatic Surgery - The Pancreas Institute, University of Verona Hospital Trust, Italy. Electronic address: roberto.salvia@univr.it. ·Dig Liver Dis · Pubmed #29941281.

ABSTRACT: BACKGROUND: Current guidelines do not address the role of age in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. AIM: To evaluate whether clinical features and risk for malignancy are affected by patient's age at diagnosis. METHODS: In total, 2189 IPMNs, both surgically resected or surveilled, were dichotomized according to a 50-year-old cutoff and compared in terms of pathological features, cumulative risk of developing high-risk stigmata (HRS), overall survival (OS) and disease-specific survival (DSS). RESULTS: Patients <50 years had more frequent abdominal pain (38.5 vs. 22.4%; p < 0.01) and acute pancreatitis (20.4 vs. 9.3%; p < 0.01) at presentation. Patients ≥50 years old had more multifocal IPMNs (50 vs. 36.9%; p < 0.01), HRS (8.5% vs. 4.3%; p = 0.04) and invasive IPMNs (26.6% vs. 17.3%; p = 0.03) when resected. Moreover, patients ≥50 years old had a significantly higher cumulative risk of developing HRS over time, and a significantly lower OS, but similar DSS when compared with those <50 years old. CONCLUSIONS: IPMNs diagnosed in older patients are more likely to progress to HRS despite the fact that cancer-related death is not affected by age. The follow-up schedule should not be adjusted according to age, but one should take into account that IPMNs in younger individuals have more time to progress toward malignancy.

25 Article EUS-guided Radiofrequency Ablation (EUS-RFA) of Solid Pancreatic Neoplasm Using an 18-gauge Needle Electrode: Feasibility, Safety, and Technical Success. 2018

Crinò, Stefano Francesco / D'Onofrio, Mirko / Bernardoni, Laura / Frulloni, Luca / Iannelli, Michele / Malleo, Giuseppe / Paiella, Salvatore / Larghi, Alberto / Gabbrielli, Armando. ·Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy. stefanocrino@hotmail.com or stefanofrancesco.crino@aovr.veneto.it. · Department of Radiology, G.B. Rossi University Hospital, Verona, Italy. · Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy. · Department of Pancreatic Surgery, The Pancreas Institute, G.B. Rossi University Hospital, Verona,Italy. · Digestive Endoscopy Unit, Catholic University, Rome, Italy. ·J Gastrointestin Liver Dis · Pubmed #29557417.

ABSTRACT: BACKGROUND AND AIMS: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising technique for the treatment of pancreatic neoplasm. We evaluated the feasibility, safety, and technical success of pancreatic EUS-RFA performed in a single center. METHODS: 9 consecutive patients (8 with pancreatic adenocarcinoma and 1 with renal cancer metastasis) were referred for EUS-RFA between November 2016 and July 2017. EUS-RFA was performed using 18-gauge internally cooled electrode with a 5 or 10 mm exposed tip. Feasibility, technical success or early and late adverse events were assessed. RESULTS: One patient was excluded because of a large necrotic portion. EUS-RFA was feasible in all the other 8 (100%) cases. An ablated area inside the tumor was achieved in all treated patients. No early or late major adverse event was observed after a mean follow-up of 6 months. Three patients experienced mild post-procedural abdominal pain. CONCLUSIONS: EUS-RFA seems a feasible, safe, and effective procedure for pancreatic neoplasms. Its role in the treatment and management of pancreatic masses must be further investigated.

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