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Pancreatic Neoplasms: HELP
Articles by Paola Capelli
Based on 57 articles published since 2009
(Why 57 articles?)
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Between 2009 and 2019, P. Capelli wrote the following 57 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Serous pancreatic neoplasia, data and review. 2017

Dietrich, Christoph F / Dong, Yi / Jenssen, Christian / Ciaravino, Valentina / Hocke, Michael / Wang, Wen-Ping / Burmester, Eike / Moeller, Kathleen / Atkinson, Nathan Ss / Capelli, Paola / D'Onofrio, Mirko. ·Christoph F Dietrich, Medizinische Klinik 2, Caritas-Krankenhaus Bad Mergentheim, 97980 Bad Mergentheim, Germany. ·World J Gastroenterol · Pubmed #28852316.

ABSTRACT: AIM: To describe the imaging features of serous neoplasms of the pancreas using ultrasound, endoscopic ultrasound, computed tomography and magnetic resonance imaging. METHODS: This multicenter international collaboration enhances a literature review to date, reporting features of 287 histologically confirmed cases of serous pancreatic cystic neoplasms (SPNs). RESULTS: Female predominance is seen with most SPNs presenting asymptomatically in the 5 CONCLUSION: The described ultrasound features can aid differentiation of SPN from other neoplastic lesions under most circumstances.

2 Review Pancreatic Ductal Adenocarcinoma and Its Variants. 2016

Luchini, Claudio / Capelli, Paola / Scarpa, Aldo. ·Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Piazzale Scuro, 10, Verona 37134, Italy; ARC-Net Research Center, University and Hospital Trust of Verona, Piazzale Scuro, 10, Verona 37134, Italy; Surgical Pathology Unit, Santa Chiara Hospital, Largo Medaglie D'oro, Trento 38122, Italy. Electronic address: claudio.luchini@katamail.com. · Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Piazzale Scuro, 10, Verona 37134, Italy. · Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Piazzale Scuro, 10, Verona 37134, Italy; ARC-Net Research Center, University and Hospital Trust of Verona, Piazzale Scuro, 10, Verona 37134, Italy. ·Surg Pathol Clin · Pubmed #27926359.

ABSTRACT: Pancreatic cancer represents the seventh leading cause of cancer death in the world, responsible for more than 300,000 deaths per year. The most common tumor type among pancreatic cancers is pancreatic ductal adenocarcinoma, an infiltrating neoplasm with glandular differentiation that is derived from pancreatic ductal tree. Here we present and discuss the most important macroscopic, microscopic, and immunohistochemical characteristics of this tumor, highlighting its key diagnostic features. Furthermore, we present the classic features of the most common variants of pancreatic ductal adenocarcinoma. Last, we summarize the prognostic landscape of this highly malignant tumor and its variants.

3 Review Extranodal extension in N1-adenocarcinoma of the pancreas and papilla of Vater: a systematic review and meta-analysis of its prognostic significance. 2016

Luchini, Claudio / Veronese, Nicola / Pea, Antonio / Sergi, Giuseppe / Manzato, Enzo / Nottegar, Alessia / Solmi, Marco / Capelli, Paola / Scarpa, Aldo. ·aDepartment of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona Departments of bMedicine (DIMED) cNeurosciences, University of Padua, Padua, Italy dDepartment of Surgery, Johns Hopkins University, Baltimore, Maryland, USA. ·Eur J Gastroenterol Hepatol · Pubmed #26566063.

ABSTRACT: The aim of the study was to investigate the prognostic role of extranodal extension (ENE) of lymph node metastasis in adenocarcinoma of the pancreas (PDAC) and papilla [cancer of the papilla of Vater (CPV)]. A PubMed and SCOPUS search from database inception until 5 January 2015 without language restrictions was conducted. Eligible were prospective studies reporting data on prognostic parameters in individuals with PDAC and/or CPV, comparing participants with the presence of ENE (ENE+) with those with intranodal extension (ENE-). Data were summarized using risk ratios for number of deaths/recurrences and hazard ratios for time-dependent risk related to ENE+, adjusted for potential confounders. ENE was found to be very common in these tumors (up to about 60% in both N1-PDAC and CPV), leading to a significant increased risk for all-cause mortality [risk ratio=1.20; 95% confidence interval (CI): 1.06-1.35, P=0.003, I(2)=44%; hazard ratio=1.415, 95% CI: 1.215-1.650, P<0.0001, I(2)=0%] and recurrence of disease (risk ratio=1.20, 95% CI: 1.03-1.40, P=0.02, I(2)=0%). On the basis of our results, in PDAC and CPV, ENE should be considered mandatorily from the gross sampling and pathology report to the oncologic staging and therapeutic approach.

4 Review Uncommon presentations of common pancreatic neoplasms: a pictorial essay. 2015

D'Onofrio, Mirko / De Robertis, Riccardo / Capelli, Paola / Tinazzi Martini, Paolo / Crosara, Stefano / Gobbo, Stefano / Butturini, Giovanni / Salvia, Roberto / Barbi, Emilio / Girelli, Roberto / Bassi, Claudio / Pederzoli, Paolo. ·Department of Radiology, G.B. Rossi Hospital, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy, mirko.donofrio@univr.it. ·Abdom Imaging · Pubmed #25772002.

ABSTRACT: Pancreatic neoplasms are a wide group of solid and cystic lesions with different and often characteristic imaging features, clinical presentations, and management. Among solid tumors, ductal adenocarcinoma is the most common: it arises from exocrine pancreas, comprises about 90% of all pancreatic neoplasms, and generally has a bad prognosis; its therapeutic management must be multidisciplinary, involving surgeons, oncologists, gastroenterologists, radiologists, and radiotherapists. The second most common solid pancreatic neoplasms are neuroendocrine tumors: they can be divided into functioning or non-functioning and present different degrees of malignancy. Cystic pancreatic neoplasms comprise serous neoplasms, which are almost always benign, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, which can vary from benign to frankly malignant lesions, and solid pseudopapillary tumors. Other pancreatic neoplasms, such as lymphoma, metastases, or pancreatoblastoma, are rarely seen in clinical practice and have different and sometimes controversial managements. Rare clinical presentations and imaging appearance of the most common pancreatic neoplasms, both solid and cystic, are more frequently seen and clinically relevant than rare pancreatic tumors; their pathologic and radiologic appearances must be known to improve their management. The purpose of this paper is to present some rare or uncommon clinical and radiological presentations of common pancreatic neoplasms providing examples of multi-modality imaging approach with pathologic correlations, thus describing the histopathological bases that can explain the peculiar imaging features, in order to avoid relevant misdiagnosis and to improve lesion management.

5 Review Pancreatic hepatoid carcinoma: a review of the literature. 2013

Marchegiani, Giovanni / Gareer, Haytham / Parisi, Alice / Capelli, Paola / Bassi, Claudio / Salvia, Roberto. ·Department of Surgery, Verona University Hospital, Verona, Italy. ·Dig Surg · Pubmed #24281319.

ABSTRACT: BACKGROUND: Hepatoid carcinomas (HCs) are extrahepatic neoplasms exhibiting features of hepatocellular tumors in terms of morphology and immunohistochemistry. They have been described in several organs, most notably in the stomach and ovary. They can present in pure forms or in association with other morphological aspects, such as endocrine tumors or ductal adenocarcinomas. The aim of this review is to describe aspects of hepatoid adenocarcinoma of the pancreas with regard to epidemiology, diagnosis, and treatment. METHODS: The PubMed database was searched for publications addressing hepatoid adenocarcinoma of the pancreas. We have searched for articles including the following keywords: 'pancreatic hepatoid carcinoma', 'ectopic liver cancer' and 'rare pancreas neoplasm' published to date. As references, we used case reports and review articles. RESULTS: Pancreatic forms of HCs are extremely uncommon: only 22 cases have been reported. CONCLUSIONS: The possibility of an HC of the pancreas should be considered in the differential diagnosis of an uncommon pathological mass of the pancreas. Treatment seems to be related to the association with other neoplasms, tumor extension at the time of diagnosis and the possibility to perform a radical resection. The common embryologic origin of the pancreas and liver, together with peculiar environmental factors, may explain the development of pancreatic HCs.

6 Review [Carcinoma of the exocrine pancreas: histology report]. 2013

Capella, C / Albarello, L / Capelli, P / Sessa, F / Zamboni, G / Anonymous1060764 / Anonymous1070764. ·Dipartimento di Scienze Chirurgiche e Morfologiche, Università dell'Insubria e Ospedale di Circolo, Varese. carlo.capella@uninsubria.it ·Pathologica · Pubmed #23858949.

ABSTRACT: -- No abstract --

7 Review Pathology - grading and staging of GEP-NETs. 2012

Capelli, Paola / Fassan, Matteo / Scarpa, Aldo. ·Department of Pathology and Diagnostics & ARC-NET Research Centre, University of Verona, Verona, Italy. paola.capelli@ospedaleuniverona.it ·Best Pract Res Clin Gastroenterol · Pubmed #23582914.

ABSTRACT: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) constitute a heterogeneous group of neoplasms. In the last few decades, due to a substantial rise in incidence and prevalence, GEP-NETs have been included among the most common tumours of the gastrointestinal tract. Diagnosis could be challenging and a significant number of patients present with metastatic or unresectable disease. The development of appropriate tools for standardised prognostic stratification and the introduction of effective target therapies have opened new horizons for planning tailored surgical or medical management and follow-up programs for these complex neoplasms. An overview on the GEP-NETs' diagnostic and prognostic criteria proposed by the recently published WHO classification and ENETS and UICC TNM staging systems is presented, focussing on their impact on the clinical and therapeutical approaches.

8 Review Nonneoplastic mimickers of pancreatic neoplasms. 2009

Zamboni, Giuseppe / Capelli, Paola / Scarpa, Aldo / Bogina, Giuseppe / Pesci, Anna / Brunello, Eleonora / Klöppel, Günter. ·Department of Pathology, University of Verona, Ospedale Sacro Cuore-Don Calabria, Via don Sempreboni 5, 37024 Negrar-Verona, Italy. giuseppe.zamboni@sacrocuore.it ·Arch Pathol Lab Med · Pubmed #19260749.

ABSTRACT: CONTEXT: A variety of nonneoplastic conditions may form pancreatic masses that mimic carcinoma. Approximately 5% to 10% of pancreatectomies performed with the clinical diagnosis of pancreatic cancer prove on microscopic evaluation to be pseudotumors. OBJECTIVES: To illustrate the clinical and pathologic characteristics of the 2 most frequent pseudotumoral inflammatory conditions, autoimmune pancreatitis and paraduodenal pancreatitis, and describe the criteria that may be useful in the differential diagnosis versus pancreatic carcinoma. DATA SOURCES: Recent literature and the authors' experience with the clinical and pathologic characteristics of autoimmune pancreatitis and paraduodenal pancreatitis. CONCLUSIONS: The knowledge of the clinical, radiologic, and pathologic findings in both autoimmune pancreatitis and paraduodenal pancreatitis is crucial in making the correct preoperative diagnosis. Autoimmune pancreatitis, which occurs in isolated or syndromic forms, is characterized by a distinctive fibroinflammatory process that can either be limited to the pancreas or extend to the biliary tree. Its correct preoperative identification on biopsy material with ancillary immunohistochemical detection of dense immunoglobulin G4-positive plasma cell infiltration is possible and crucial to prevent major surgery and to treat these patients with steroid therapy. Paraduodenal pancreatitis is a special form of chronic pancreatitis that affects young males with a history of alcohol abuse and predominantly involves the duodenal wall in the region of the minor papilla. Pathogenetically, the anatomical and/or functional obstruction of the papilla minor, resulting from an incomplete involution of the intraduodenal dorsal pancreas, associated with alcohol abuse represents the key factor. Endoscopic drainage of the papilla minor, with decompression of the intraduodenal and dorsal pancreas, might be considered in these patients.

9 Review Endocrine neoplasms of the pancreas: pathologic and genetic features. 2009

Capelli, Paola / Martignoni, Guido / Pedica, Federica / Falconi, Massimo / Antonello, Davide / Malpeli, Giorgio / Scarpa, Aldo. ·Department of Pathology, Section ofAnatomical Pathology, Policlinico G. B. Rossi, 37134 Verona, Italy. paola.capelli@azosp.vr.it ·Arch Pathol Lab Med · Pubmed #19260741.

ABSTRACT: CONTEXT: Pancreatic endocrine neoplasms (PENs) are diagnostically challenging tumors whose natural history is largely unknown. Histopathology allows the distinction of 2 categories: poorly differentiated high-grade carcinomas and well-differentiated neoplasms. The latter include more than 90% of PENs whose clinical behavior varies from indolent to malignant and cannot be predicted by their morphology. OBJECTIVES: To review the literature and report on additional primary material about the clinicopathologic features, classification, staging, grading, and genetic features of PENs. DATA SOURCES: Literature review of relevant articles indexed in PubMed (US National Library of Medicine) and primary material from the authors' institution. CONCLUSIONS: The diagnosis of PEN is generally easy, but unusual features may induce misdiagnosis. Immunohistochemistry solves the issue, provided that the possibility of a PEN has been considered. Morphology allows the distinction of poorly differentiated aggressive carcinomas from well-differentiated neoplasms. The World Health Organization classification criteria allow for the discernment of the latter into neoplasms and carcinomas with either benign or uncertain behavior. The recently proposed staging and grading systems hold great promise for permitting a stratification of carcinomas into clinically significant risk categories. To date, inactivation of the MEN1 gene remains the only ascertained genetic event involved in PEN genesis. It is inactivated in roughly one-third of PENs. The degree of genomic instability correlates with the aggressiveness of the neoplasm. Gene silencing by promoter methylation has been advocated, but a formal demonstration of the involvement of specific genes is still lacking. Expression profiling studies are furnishing valuable lists of mRNAs and noncoding RNAs that may advance further the research to discover novel markers and/or therapeutic targets.

10 Article CD200 expression is a feature of solid pseudopapillary neoplasms of the pancreas. 2019

Lawlor, Rita T / Daprà, Valentina / Girolami, Ilaria / Pea, Antonio / Pilati, Camilla / Nottegar, Alessia / Piccoli, Paola / Parolini, Claudia / Sperandio, Nicola / Capelli, Paola / Scarpa, Aldo / Luchini, Claudio. ·ARC-Net Research Center, University of Verona, Verona, Italy. · Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy. · Department of General and Visceral Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, Paris-Descartes University, Paris, France. · Department of Surgery, Section of Pathology, San Bortolo Hospital, Vicenza, Italy. · ARC-Net Research Center, University of Verona, Verona, Italy. aldo.scarpa@univr.it. · Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy. aldo.scarpa@univr.it. ·Virchows Arch · Pubmed #30132130.

ABSTRACT: CD200 has been recently indicated as a robust marker of well-differentiated neuroendocrine neoplasms. Here, we evaluate its role in differential diagnosis of solid pancreatic neoplasms. We immunostained for CD200 22 solid pseudopapillary neoplasms (SPNs), 8 acinar carcinomas (ACs), 2 pancreatoblastomas (PBs), 138 neuroendocrine tumors (PanNETs), and 48 ductal adenocarcinomas. All SPNs showed strong cytoplasmic and membranous staining for CD200, while only one case of AC had focal positivity. The two PBs showed focal CD200 positivity, mainly located in squamoid nests. The vast majority of PanNETs (96%) showed strong cytoplasmic and membranous staining for CD200, whereas all PDACs were negative. As both PanNETs and SPNs express CD200, it has no role in the differential diagnosis between these two entities.

11 Article CT Texture Analysis of Ductal Adenocarcinoma Downstaged After Chemotherapy. 2018

Ciaravino, Valentina / Cardobi, Nicolò / DE Robertis, Riccardo / Capelli, Paola / Melisi, Davide / Simionato, Francesca / Marchegiani, Giovanni / Salvia, Roberto / D'Onofrio, Mirko. ·Department of Radiology, G.B. Rossi Hospital - University of Verona, Verona, Italy. · Department of Radiology, Casa di Cura Dott. Pederzoli, Peschiera del Garda, Verona, Italy. · Department of Pathology, G.B. Rossi Hospital - University of Verona, Verona, Italy. · Department of Oncology, G.B. Rossi Hospital - University of Verona, Verona, Italy. · Department of Surgery, G.B. Rossi Hospital - University of Verona, Verona, Italy. · Department of Radiology, G.B. Rossi Hospital - University of Verona, Verona, Italy mirko.donofrio@univr.it. ·Anticancer Res · Pubmed #30061265.

ABSTRACT: BACKGROUND/AIM: Re-staging of ductal adenocarcinoma using computed tomography (CT) scan can be problematic so new imaging techniques and evaluation parameters are required. The aim of the study was to evaluate the added value of CT texture analysis in estimation of tissue changes in ductal adenocarcinoma downsized and resected after chemotherapy. MATERIALS AND METHODS: Patients with ductal adenocarcinoma downstaged after neoadjuvant treatment, and resected, were included. A pre- and post-treatment CT was obtained. In comparison, patients with disease progression were included for texture analysis evaluation at CT pre- and post-treatment. CT texture analysis results were compared. RESULTS: A total of 17 patients affected by un-resectable or borderline ductal adenocarcinoma reached the resectable stage after treatment. The comparison between Kurtosis pre- and Kurtosis post-treatment showed a statistically significant difference. On the contrary, in the comparison group composed of 14 patients with disease progression there was no statistical difference regarding this parameter. CONCLUSION: This evaluation may represent an added value in tumor tissue changes judgment and can be extremely useful to diagnose downstaging in those cases with no evident downsizing after chemotherapy.

12 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.

13 Article Can histogram analysis of MR images predict aggressiveness in pancreatic neuroendocrine tumors? 2018

De Robertis, Riccardo / Maris, Bogdan / Cardobi, Nicolò / Tinazzi Martini, Paolo / Gobbo, Stefano / Capelli, Paola / Ortolani, Silvia / Cingarlini, Sara / Paiella, Salvatore / Landoni, Luca / Butturini, Giovanni / Regi, Paolo / Scarpa, Aldo / Tortora, Giampaolo / D'Onofrio, Mirko. ·Department of Radiology, P. Pederzoli Hospital, Via Monte Baldo 24, 37019, Peschiera del Garda, Italy. riccardo.derobertis@hotmail.it. · Department of Computer Science, University of Verona, Strada le Grazie 15, 37134, Verona, Italy. · Department of Radiology, P. Pederzoli Hospital, Via Monte Baldo 24, 37019, Peschiera del Garda, Italy. · Department of Pathology, P. Pederzoli Hospital, Via Monte Baldo 24, 37019, Peschiera del Garda, Italy. · Department of Pathology, G.B. Rossi Hospital - University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. · Department of Oncology, P. Pederzoli Hospital, Via Monte Baldo 24, 37019, Peschiera del Garda, Italy. · Department of Oncology, G.B. Rossi Hospital - University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. · Department of Pancreatic Surgery, G.B. Rossi Hospital - University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. · Department of Pancreatic Surgery, P. Pederzoli Hospital, Via Monte Baldo 24, 37019, Peschiera del Garda, Italy. · Department of Radiology, G.B. Rossi Hospital - University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. ·Eur Radiol · Pubmed #29352378.

ABSTRACT: OBJECTIVES: To evaluate MRI derived whole-tumour histogram analysis parameters in predicting pancreatic neuroendocrine neoplasm (panNEN) grade and aggressiveness. METHODS: Pre-operative MR of 42 consecutive patients with panNEN >1 cm were retrospectively analysed. T1-/T2-weighted images and ADC maps were analysed. Histogram-derived parameters were compared to histopathological features using the Mann-Whitney U test. Diagnostic accuracy was assessed by ROC-AUC analysis; sensitivity and specificity were assessed for each histogram parameter. RESULTS: ADC CONCLUSIONS: Whole-tumour histogram analysis of ADC maps may be helpful in predicting tumour grade, vascular involvement, nodal and liver metastases in panNENs. ADC KEY POINTS: • Whole-tumour ADC histogram analysis can predict aggressiveness in pancreatic neuroendocrine neoplasms. • ADC entropy and kurtosis are higher in aggressive tumours. • ADC histogram analysis can quantify tumour diffusion heterogeneity. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information for prognostication.

14 Article Are Cystic Pancreatic Neuroendocrine Tumors an Indolent Entity Results from a Single-Center Surgical Series. 2018

Paiella, Salvatore / Marchegiani, Giovanni / Miotto, Marco / Malpaga, Anna / Impellizzeri, Harmony / Montagnini, Greta / Pollini, Tommaso / Nessi, Chiara / Butturini, Giovanni / Capelli, Paola / Posenato, Ilaria / Scarpa, Aldo / D'Onofrio, Mirko / De Robertis, Riccardo / Cingarlini, Sara / Boninsegna, Letizia / Bassi, Claudio / Salvia, Roberto / Landoni, Luca. · ·Neuroendocrinology · Pubmed #28586782.

ABSTRACT: INTRODUCTION: Cystic pancreatic neuroendocrine tumors (CPanNETs) represent an uncommon variant of pancreatic neuroendocrine tumors (PanNETs). Due to their rarity, there is a lack of knowledge with regard to clinical features and postoperative outcome. METHODS: The prospectively maintained surgical database of a high-volume institution was queried, and 46 resected CPanNETs were detected from 1988 to 2015. Clinical, demographic, and pathological features and survival outcomes of CPanNETs were described and matched with a population of 92 solid PanNETs (SPanNETs) for comparison. RESULTS: CPanNETs accounted for 7.8% of the overall number of resected PanNETs (46/587). CPanNETs were mostly sporadic (n = 42, 91%) and nonfunctioning (39%). Two functioning CPanNETs were detected (4.3%), and they were 2 gastrinomas. The median tumor diameter was 30 mm (range 10-120). All tumors were well differentiated, with 38 (82.6%) G1 and 8 (17.4%) G2 tumors. Overall, no CPanNET showed a Ki-67 >5%. A correct preoperative diagnosis of a CPanNET was made in half of the cases. After a median follow-up of >70 months, the 5- and 10-year overall survival of resected CPanNETs was 93.8 and 62.5%, respectively, compared to 92.7 and 84.6% for SPanNETs (p > 0.05). The 5- and 10-year disease-free survival rates were 94.5 and 88.2% for CPanNETs and 81.8 and 78.9% for SPanNETs, respectively (p > 0.05). CONCLUSION: In the setting of a surgical cohort, CPanNETs are rare, nonfunctional, and well-differentiated neoplasms. After surgical resection, they share the excellent outcome of their well-differentiated solid counterparts for both survival and recurrence.

15 Article Pancreatectomy with venous resection for pT3 head adenocarcinoma: Perioperative outcomes, recurrence pattern and prognostic implications of histologically confirmed vascular infiltration. 2017

Malleo, Giuseppe / Maggino, Laura / Marchegiani, Giovanni / Feriani, Giovanni / Esposito, Alessandro / Landoni, Luca / Casetti, Luca / Paiella, Salvatore / Baggio, Elda / Lipari, Giovanni / Capelli, Paola / Scarpa, Aldo / Bassi, Claudio / Salvia, Roberto. ·Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, The Pancreas Institute, University of Verona Hospital Trust, Italy. Electronic address: giuseppe.malleo@aovr.veneto.it. · Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, The Pancreas Institute, University of Verona Hospital Trust, Italy. · Unit of Vascular Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Italy. · Department of Pathology and Diagnostics, University of Verona Hospital Trust, Italy. · Department of Pathology and Diagnostics, University of Verona Hospital Trust, Italy; ARC-NET Research Center, University of Verona Hospital Trust, Italy. ·Pancreatology · Pubmed #28843714.

ABSTRACT: BACKGROUND: The outcomes of pancreatectomy with superior mesenteric vein (SMV) or portal vein (PV) resection have been mixed. This study investigated the morbidity and mortality profile after SMV-PV resection in comparison with standard pancreatectomy. Furthermore, we assessed whether tumors with histologically proven SMV-PV infiltration differ from other pT3 neoplasms in terms of recurrence pattern and survival. METHODS: All patients with a pT3 head adenocarcinoma resected from 2000 to 2013 were analyzed retrospectively. In the SMV-PV resection group, information on venous wall status was obtained through pathologic reports. Standard statistical methods were used for data analysis. RESULTS: The study population consisted of 651 patients, of whom 81 (12.4%) underwent synchronous SMV-PV resection. Venous resection was not associated with a higher rate of postoperative complications (60.5% versus 50.2%) and mortality (1.2% versus 1.1%) in comparison with standard pancreatectomy. Vascular infiltration was confirmed pathologically in 56/81 patients (69.1%). The median disease-specific survival of the entire population was 27 months (95% CI 24.6-29.3), with a 5-year survival rate of 20.5%. The median recurrence-free survival was 18 months (95% CI 15.0-20.9). On multivariate analysis, ASA score, preoperative pain, Ca 19-9 levels, tumor grade, R-status, lymph-vascular invasion, N-status, and adjuvant therapy resulted to be survival predictors. Similarly, Ca 19.9 levels, R-status, and N-status were predictors of recurrence. SMV-PV infiltration was not a significant prognostic factor. CONCLUSION: Morbidity and mortality rates of pancreatectomy with SMV-PV resection are comparable with standard pancreatectomy. Pancreatic head adenocarcinoma with histologically confirmed SMV-PV infiltration does not segregate prognostically from other pT3 tumors.

16 Article Solid non-functioning endocrine tumors of the pancreas: correlating computed tomography and pathology. 2017

Zamboni, Giulia A / Ambrosetti, Maria Chiara / Zivelonghi, Caterina / Lombardo, Fabio / Butturini, Giovanni / Cingarlini, Sara / Capelli, Paola / Pozzi Mucelli, Roberto. ·Istituto di Radiologia, DAI Patologia e Diagnostica, Policlinico GB Rossi, AOUI Verona, Verona, Italy. Electronic address: gzamboni@hotmail.com. · Istituto di Radiologia, DAI Patologia e Diagnostica, Policlinico GB Rossi, AOUI Verona, Verona, Italy. · Chirurgia Generale e Del Pancreas, DAI Chirurgia e Oncologia, Istituto Del Pancreas, Policlinico GB Rossi, AOUI Verona, Verona, Italy. · Oncologia Medica, DAI Chirurgia e Oncologia, Policlinico GB Rossi, AOUI Verona, Verona, Italy. · UOC Anatomia e Istologia Patologica, DAI Patologia e Diagnostica, Policlinico GB Rossi, AOUI Verona, Verona, Italy. ·HPB (Oxford) · Pubmed #28784262.

ABSTRACT: BACKGROUND: Since prognosis and treatment of pancreatic endocrine tumors (pNET) are based on tumor grade, contrast-enhanced multidetector computed tomography (MDCT) features of solid non-functioning pNETs were studied and correlated with pathology tumor grading. METHODS: MDCTs of diagnosed pNETs were reviewed retrospectively. Each tumor was analyzed for location, size, homogeneity, margins, arterial and venous phase enhancement, main pancreatic duct diameter, calcifications, vascular invasion, lymph-nodes enlargement, and liver metastases. RESULTS: Of 154 pNETs presenting between January 2000 and May 2016 with available histology from resected specimen or biopsy, there were 65 G1, 72 G2 and 17 G3 pNETs. Tumor diameter varied significantly between the three groups. Tumors >20 mm were more frequently malignant and non-homogeneous than smaller tumors. G1 tumors were more commonly hypervascular and G3 tumors more often non-hypervascular in the arterial phase. Arterial phase non-hyperdensity and tumor non-homogeneity had a higher rate of metastatic lesions. Vascular invasion correlated with presence of metastases and histological grade. G3 tumors were all >20 mm (p = 0.007), more often non-hypervascular in the arterial phase (p = 0.0025), and non-hyperdense in the venous phase (p = 0.009), and showed more often vascular invasion (p = 0.0198). CONCLUSION: CT correlated with tumor grade; differentiating low-grade and high-grade pNETs through routine CT imaging might improve patient management.

17 Article Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma. 2017

Luchini, Claudio / Pea, Antonio / Lionheart, Gemma / Mafficini, Andrea / Nottegar, Alessia / Veronese, Nicola / Chianchiano, Peter / Brosens, Lodewijk Aa / Noë, Michaël / Offerhaus, G Johan A / Yonescu, Raluca / Ning, Yi / Malleo, Giuseppe / Riva, Giulio / Piccoli, Paola / Cataldo, Ivana / Capelli, Paola / Zamboni, Giuseppe / Scarpa, Aldo / Wood, Laura D. ·Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · ARC-Net Research Center, University of Verona, Verona, Italy. · National Research Council, Neuroscience Institute, Aging Branch, Padua, Italy. · Institute for Clinical Research and Education in Medicine (IREM), Padua, Italy. · Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands. · Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy. · Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ·J Pathol · Pubmed #28722124.

ABSTRACT: Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. These results further support the classification of UCOGC as a PDAC variant and suggest that somatic mutations are not the determinants of the unique phenotype of UCOGC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

18 Article Comparison of imaging-based and pathological dimensions in pancreatic neuroendocrine tumors. 2017

Paiella, Salvatore / Impellizzeri, Harmony / Zanolin, Elisabetta / Marchegiani, Giovanni / Miotto, Marco / Malpaga, Anna / De Robertis, Riccardo / D'Onofrio, Mirko / Rusev, Borislav / Capelli, Paola / Cingarlini, Sara / Butturini, Giovanni / Davì, Maria Vittoria / Amodio, Antonio / Bassi, Claudio / Scarpa, Aldo / Salvia, Roberto / Landoni, Luca. ·Salvatore Paiella, Harmony Impellizzeri, Giovanni Marchegiani, Marco Miotto, Anna Malpaga, Claudio Bassi, Roberto Salvia, Luca Landoni, General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, 37134 Verona, Italy. ·World J Gastroenterol · Pubmed #28533666.

ABSTRACT: AIM: To establish the ability of magnetic resonance (MR) and computer tomography (CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors (PanNET) in a caseload of a tertiary referral center. METHODS: Patients submitted to surgery for PanNET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination (MR or CT scan) from January 2005 to December 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy. Bland-Altman (BA) and Mountain-Plot (MP) statistics were used to compare size measured by each modality with the pathology size. Passing-Bablok (PB) regression analysis was used to check the agreement between MR and CT. RESULTS: Our study population consisted of 292 patients. Seventy-nine (27.1%) were functioning PanNET. The mean biases were 0.17 ± 7.99 mm, 1 ± 8.51 mm and 0.23 ± 9 mm, 1.2 ± 9.8 mm for MR and CT, considering the overall population and the subgroup of non-functioning- PanNET, respectively. Limits of agreement (LOA) included the vast majority of observations, indicating a good agreement between imaging and pathology. The MP further confirmed this finding and showed that the two methods are unbiased with respect to each other. Considering ≤ 2 cm non-functioning-PanNET, no statistical significance was found in the size estimation rate of MR and CT ( CONCLUSION: MR and CT scan are accurate and interchangeable imaging techniques in predicting pathologic dimensions of PanNET.

19 Article Downstaging in Stage IV Pancreatic Cancer: A New Population Eligible for Surgery? 2017

Frigerio, Isabella / Regi, Paolo / Giardino, Alessandro / Scopelliti, Filippo / Girelli, Roberto / Bassi, Claudio / Gobbo, Stefano / Martini, Paolo Tinazzi / Capelli, Paola / D'Onofrio, Mirko / Malleo, Giuseppe / Maggino, Laura / Viviani, Elena / Butturini, Giovanni. ·HPB Surgical Unit, Pederzoli Hospital, Verona, Italy. isifrigerio@yahoo.com. · HPB Surgical Unit, Pederzoli Hospital, Verona, Italy. · General Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Pathology, Pederzoli Hospital, Verona, Italy. · Department of Radiology, Pederzoli Hospital, Verona, Italy. · Department of Radiology, G.B. Rossi Hospital, University of Verona, Verona, Italy. ·Ann Surg Oncol · Pubmed #28516291.

ABSTRACT: BACKGROUND: Recent papers consider surgery as an option for synchronous liver oligometastatic patients [metastatic pancreatic ductal adenocarcinoma (mPDAC)]. In this study, we present our series of resected mPDACs after neoadjuvant chemotherapy (nCT). PATIENTS AND METHODS: All patients resected after downstaging of mPDAC were included in this study. Downstaging criteria were disappearance of liver metastasis and a decrease in cancer antigen (CA) 19-9. The type and duration of nCT, last nCT surgery interval, histology, morbidity, and mortality were recorded, and overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: Overall, 24 of 535 patients (4.5%) observed with mPDAC were included. These patients received gemcitabine alone (5/24), gemcitabine + nanoparticle albumin-bound (nab)-paclitaxel (3/24), and FOLFIRINOX (16/24). Primary tumor size decreased from 31 to 19 mm (p < 0.001), and serum CA19-9 decreased from 596 to 18 U/mL (p < 0.001). In 14/24 patients, the tumor was located in the head. Median interval nCT surgery was 2 months, there were no mortalities, and the postoperative course was uneventful in 34% of cases. Grade B/C pancreatic fistula, postoperative bleeding, and sepsis occurred in 17/4, 4, and 12% of cases, respectively, and reoperation rate was 4%. R0 resection was achieved in 88% of cases, with 17% complete pathological response. Positive nodes were found in 9/24 patients with a median node ratio of 0.37, and OS and DFS was 56 and 27 months, respectively. CONCLUSIONS: Patients with mPDAC who were fully responsive to nCT may be cautiously considered for surgery, with potential benefit in survival compared with palliative chemotherapy alone. This is supported by results of our retrospective study, which is the largest ever reported.

20 Article Whole-genome landscape of pancreatic neuroendocrine tumours. 2017

Scarpa, Aldo / Chang, David K / Nones, Katia / Corbo, Vincenzo / Patch, Ann-Marie / Bailey, Peter / Lawlor, Rita T / Johns, Amber L / Miller, David K / Mafficini, Andrea / Rusev, Borislav / Scardoni, Maria / Antonello, Davide / Barbi, Stefano / Sikora, Katarzyna O / Cingarlini, Sara / Vicentini, Caterina / McKay, Skye / Quinn, Michael C J / Bruxner, Timothy J C / Christ, Angelika N / Harliwong, Ivon / Idrisoglu, Senel / McLean, Suzanne / Nourse, Craig / Nourbakhsh, Ehsan / Wilson, Peter J / Anderson, Matthew J / Fink, J Lynn / Newell, Felicity / Waddell, Nick / Holmes, Oliver / Kazakoff, Stephen H / Leonard, Conrad / Wood, Scott / Xu, Qinying / Nagaraj, Shivashankar Hiriyur / Amato, Eliana / Dalai, Irene / Bersani, Samantha / Cataldo, Ivana / Dei Tos, Angelo P / Capelli, Paola / Davì, Maria Vittoria / Landoni, Luca / Malpaga, Anna / Miotto, Marco / Whitehall, Vicki L J / Leggett, Barbara A / Harris, Janelle L / Harris, Jonathan / Jones, Marc D / Humphris, Jeremy / Chantrill, Lorraine A / Chin, Venessa / Nagrial, Adnan M / Pajic, Marina / Scarlett, Christopher J / Pinho, Andreia / Rooman, Ilse / Toon, Christopher / Wu, Jianmin / Pinese, Mark / Cowley, Mark / Barbour, Andrew / Mawson, Amanda / Humphrey, Emily S / Colvin, Emily K / Chou, Angela / Lovell, Jessica A / Jamieson, Nigel B / Duthie, Fraser / Gingras, Marie-Claude / Fisher, William E / Dagg, Rebecca A / Lau, Loretta M S / Lee, Michael / Pickett, Hilda A / Reddel, Roger R / Samra, Jaswinder S / Kench, James G / Merrett, Neil D / Epari, Krishna / Nguyen, Nam Q / Zeps, Nikolajs / Falconi, Massimo / Simbolo, Michele / Butturini, Giovanni / Van Buren, George / Partelli, Stefano / Fassan, Matteo / Anonymous7980896 / Khanna, Kum Kum / Gill, Anthony J / Wheeler, David A / Gibbs, Richard A / Musgrove, Elizabeth A / Bassi, Claudio / Tortora, Giampaolo / Pederzoli, Paolo / Pearson, John V / Waddell, Nicola / Biankin, Andrew V / Grimmond, Sean M. ·ARC-Net Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona 37134, Italy. · Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona 37134, Italy. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. · The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. · Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia. · South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia. · QIMR Berghofer Medical Research Institute, Herston Road, Brisbane 4006, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy. · Medical Oncology, University and Hospital Trust of Verona, Verona, Italy. · Department of Pathology, General Hospital of Treviso, Department of Medicine, University of Padua, Italy. · Department of Medicine, Section of Endocrinology, University and Hospital Trust of Verona, Verona, Italy. · The University of Queensland, School of Medicine, Brisbane 4006, Australia. · Pathology Queensland, Brisbane 4006, Australia. · Royal Brisbane and Women's Hospital, Department of Gastroenterology and Hepatology, Brisbane 4006, Australia. · Institute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. · School of Environmental &Life Sciences, University of Newcastle, Ourimbah, New South Wales 2258, Australia. · Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Centre for Cancer Bioinformatics, Peking University Cancer Hospital &Institute, Beijing 100142, China. · Department of Surgery, Princess Alexandra Hospital, Ipswich Rd, Woollongabba, Queensland 4102, Australia. · Department of Anatomical Pathology. St Vincent's Hospital, Sydney, New South Wales 2010, Australia. · Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G4 OSF, UK. · Department of Pathology, Queen Elizabeth University Hospital, Greater Glasgow &Clyde NHS, Glasgow G51 4TF, UK. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, MS226, Houston, Texas 77030-3411, USA. · Michael E. DeBakey Department of Surgery and The Elkins Pancreas Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030-3411, USA. · Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia. · Children's Medical Research Institute, The University of Sydney, Westmead, New South Wales 2145, Australia. · Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, New South Wales 2065, Australia. · University of Sydney. Sydney, New South Wales 2006, Australia. · Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia. · School of Medicine, Western Sydney University, Penrith, New South Wales 2175, Australia. · Department of Surgery, Fremantle Hospital, Alma Street, Fremantle, Western Australia 6160, Australia. · Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. · School of Surgery M507, University of Western Australia, 35 Stirling Highway, Nedlands, Western Australia 6009, Australia. · St John of God Pathology, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia. · Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital, Subiaco, Western Australia 6008, Australia. · University of Melbourne Centre for Cancer Research, University of Melbourne, Melbourne, 3010, Victoria, Australia. ·Nature · Pubmed #28199314.

ABSTRACT: The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 gene fusions), and telomere maintenance. In addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and HIF signalling.

21 Article Pancreatic neuroendocrine neoplasms: Magnetic resonance imaging features according to grade and stage. 2017

De Robertis, Riccardo / Cingarlini, Sara / Tinazzi Martini, Paolo / Ortolani, Silvia / Butturini, Giovanni / Landoni, Luca / Regi, Paolo / Girelli, Roberto / Capelli, Paola / Gobbo, Stefano / Tortora, Giampaolo / Scarpa, Aldo / Pederzoli, Paolo / D'Onofrio, Mirko. ·Riccardo De Robertis, Department of Radiology, Casa di Cura Pederzoli, 37019 Peschiera del Garda, Italy. ·World J Gastroenterol · Pubmed #28127201.

ABSTRACT: AIM: To describe magnetic resonance (MR) imaging features of pancreatic neuroendocrine neoplasms (PanNENs) according to their grade and tumor-nodes-metastases stage by comparing them to histopathology and to determine the accuracy of MR imaging features in predicting their biological behavior. METHODS: This study was approved by our institutional review board; requirement for informed patient consent was waived due to the retrospective nature of the study. Preoperative MR examinations of 55 PanNEN patients (29 men, 26 women; mean age of 57.6 years, range 21-83 years) performed between June 2013 and December 2015 were reviewed. Qualitative and quantitative features were compared between tumor grades and stages determined by histopathological analysis. RESULTS: Ill defined margins were more common in G2-3 and stage III-IV PanNENs than in G1 and low-stage tumors ( CONCLUSION: MR features of PanNENs vary according to their grade of differentiation and their stage at diagnosis and could predict the biological behavior of these tumors.

22 Article Role of Combined 68Ga-DOTATOC and 18F-FDG Positron Emission Tomography/Computed Tomography in the Diagnostic Workup of Pancreas Neuroendocrine Tumors: Implications for Managing Surgical Decisions. 2017

Cingarlini, Sara / Ortolani, Silvia / Salgarello, Matteo / Butturini, Giovanni / Malpaga, Anna / Malfatti, Veronica / DʼOnofrio, Mirko / Davì, Maria Vittoria / Vallerio, Paola / Ruzzenente, Andrea / Capelli, Paola / Citton, Elia / Grego, Elisabetta / Trentin, Chiara / De Robertis, Riccardo / Scarpa, Aldo / Bassi, Claudio / Tortora, Giampaolo. ·From the *Department of Oncology, Comprehensive Cancer Center, G.B. Rossi University Hospital of Verona; †Department of Nuclear Medicine, Sacro Cuore Don Calabria Hospital, Negrar; ‡Hepato-Biliary and Pancreas Unit, Pederzoli Hospital, Peschiera; Departments of §Pancreatic Surgery, ∥Radiology, ¶Internal Medicine, #Hepatobiliary Surgery, and **Pathology, Comprehensive Cancer Center, G.B. Rossi University Hospital of Verona, Verona, Italy. ·Pancreas · Pubmed #27906872.

ABSTRACT: OBJECTIVES: Ga-DOTATOC (Ga) positron emission tomography (PET)/computed tomography (CT) is recommended in the workup of pancreas neuroendocrine tumors (PanNETs); evidence suggests that F-FDG (F) PET/CT can also provide prognostic information. Aims of this study were to assess the role of combined Ga- and F-PET/CT in the evaluation of grade (G) 1-2 PanNETs and to test the correlation between F-PET/CT positivity and tumor grade. METHODS: Preoperative Ga- and F-PET/CT of 35 patients with surgically resected G1-2 PanNETs were evaluated. For grading, the 2010 World Health Organization Classification was used; an ancillary analysis with Ki67 cutoffs at 5% to 20% was conducted. Correlation between F-PET/CT positivity (SUVmax > 3.5) and grade was assessed. RESULTS: Of 35 PanNETs, 28.6% and 71.4% were G1 and G2 as per World Health Organization. Ga-PET/CT showed high sensitivity (94.3%) in detecting G1-2 PanNETs. F-PET/CT was positive in 20% and 76% G1 and G2 tumors (P = 0.002). F-PET/CT identified G2 PanNETs with high positive predictive value (PPV, 90.5%). F-PET/CT correlated with tumor grade also in the ancillary analysis (P = 0.009). CONCLUSIONS: The high sensitivity of Ga-PET/CT in NET detection is known. The high PPV of F-PET/CT in the identification of G2 forms suggests its potential role in PanNETs prognostication and risk stratification.

23 Article Oncocytic Intraductal Papillary Mucinous Neoplasms of the Pancreas: Imaging and Histopathological Findings. 2016

D'Onofrio, Mirko / De Robertis, Riccardo / Tinazzi Martini, Paolo / Capelli, Paola / Gobbo, Stefano / Morana, Giovanni / Demozzi, Emanuele / Marchegiani, Giovanni / Girelli, Roberto / Salvia, Roberto / Bassi, Claudio / Pederzoli, Paolo. ·From the *Department of Radiology, G.B. Rossi Hospital, University of Verona, Verona; †Department of Radiology, Casa di cura Pederzoli, Peschiera del Garda; ‡Department of Pathology, G.B. Rossi Hospital, University of Verona, Verona; §Department of Pathology, Casa di cura Pederzoli, Peschiera del Garda; ∥Department of Radiology, Ca' Foncello Hospital, Treviso; ¶Department of Surgery, G.B. Rossi Hospital, University of Verona, Verona; and #Department of Surgery, Casa di cura Pederzoli, Peschiera del Garda, Italy. ·Pancreas · Pubmed #27518461.

ABSTRACT: OBJECTIVES: To evaluate and correlate computed tomography/magnetic resonance findings and histopathologic features of oncocytic intraductal papillary mucinous neoplasms (O-IPMNs). METHODS: Computed tomography/magnetic resonance examinations and resection specimens of 16 O-IPMNs were retrospectively reviewed. Qualitative and quantitative imaging features were analyzed according to "worrisome features" and "high risk stigmata." Correlations between radiological and histopathological findings were evaluated using Fisher test. RESULTS: Most O-IPMNs (75%) presented as large mixed- or main duct-type lesions (mean size, 56.9 mm; range, 20-180); all branch-duct type lesions were larger than 3 cm. Ten lesions presented main pancreatic duct dilation of 10 mm or greater. Solid enhancing nodules were found in 10 cases. Two lesions presented foci of invasion at histopathologic analysis, the remaining presented high-grade dysplasia. Neither invasive carcinoma nor nodal metastases were found. No significant correlations were found between radiological predictors of malignancy and histopathological features. CONCLUSIONS: Oncocytic tumors are rare subtypes of pancreatic IPMN, whose imaging features are similar to other IPMN subtypes. Imaging predictors of malignancy as large size and huge solid internal nodules are frequently encountered in O-IPMNs; despite this, these features are not correlated with histopathological findings, being probably inapplicable to O-IPMNs.

24 Article Solid pseudopapillary tumors of the pancreas: Specific pathological features predict the likelihood of postoperative recurrence. 2016

Marchegiani, Giovanni / Andrianello, Stefano / Massignani, Marta / Malleo, Giuseppe / Maggino, Laura / Paiella, Salvatore / Ferrone, Cristina R / Luchini, Claudio / Scarpa, Aldo / Capelli, Paola / Mino-Kenudson, Mari / Lillemoe, Keith D / Bassi, Claudio / Castillo, Carlos Fernàndez-Del / Salvia, Roberto. ·Department of General and Pancreatic Surgery, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Department of General Surgery, Massachusetts General Hospital-Harvard Medical School, Boston, Massachusetts. · Department of Diagnostic and Public Health, ARC-Net Research Centre-University of Verona Hospital Trust, Verona, Italy. · Department of Pathology, Massachusetts General Hospital-Harvard Medical School, Boston, Massachusetts. · Department of General and Pancreatic Surgery, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. roberto.salvia@univr.it. ·J Surg Oncol · Pubmed #27471041.

ABSTRACT: BACKGROUND: Since their introduction in the WHO classification, the incidence of solid pseudopapillary tumors (SPTs) of the pancreas has progressively increased, mainly because of the widespread use of cross-sectional imaging. Few recent studies have analyzed the biological behavior of SPTs, but reliable data on long-term follow-up are needed. METHODS: Retrospective analysis of two Institutions with high caseload, The Department of General Surgery-Pancreas Institute, University of Verona Hospital Trust and the Department of General Surgery, Massachusetts General Hospital, Harvard Medical School, was carried out. Data from 131 consecutive resections for SPT performed during the last three decades were collected and analyzed. RESULTS: The majority of patients were female (86.3%) with a median age of 33 (7-68) years. The prevalent location was the pancreatic tail (33.5%). Applying the WHO criteria, 16 (12.2%) SPTs were considered malignant due to the presence of at least pancreatic parenchyma (9.9%), perineural (4.6%), and/or angiovascular invasion (2.3%). After a median of 62 months after surgery, only two patients had a recurrence (1.5%). Both of them fulfilled the WHO criteria for malignant SPT (vs. 10.7% of those who did not recur, P = 0.01), had an infiltrative growth pattern (vs. 10.8%, P = 0.01), pancreatic parenchyma invasion (vs. 9.7%, P = 0.01) and capsular invasion (vs. 4.9%, P = 0.004). CONCLUSION: Overall, SPTs are associated with excellent survival results after surgical resection. Disease recurrence is extremely rare, and might occur if the primary tumor presents with either pancreatic parenchyma or capsule invasion. J. Surg. Oncol. 2016;114:597-601. © 2016 Wiley Periodicals, Inc.

25 Article Genomic analyses identify molecular subtypes of pancreatic cancer. 2016

Bailey, Peter / Chang, David K / Nones, Katia / Johns, Amber L / Patch, Ann-Marie / Gingras, Marie-Claude / Miller, David K / Christ, Angelika N / Bruxner, Tim J C / Quinn, Michael C / Nourse, Craig / Murtaugh, L Charles / Harliwong, Ivon / Idrisoglu, Senel / Manning, Suzanne / Nourbakhsh, Ehsan / Wani, Shivangi / Fink, Lynn / Holmes, Oliver / Chin, Venessa / Anderson, Matthew J / Kazakoff, Stephen / Leonard, Conrad / Newell, Felicity / Waddell, Nick / Wood, Scott / Xu, Qinying / Wilson, Peter J / Cloonan, Nicole / Kassahn, Karin S / Taylor, Darrin / Quek, Kelly / Robertson, Alan / Pantano, Lorena / Mincarelli, Laura / Sanchez, Luis N / Evers, Lisa / Wu, Jianmin / Pinese, Mark / Cowley, Mark J / Jones, Marc D / Colvin, Emily K / Nagrial, Adnan M / Humphrey, Emily S / Chantrill, Lorraine A / Mawson, Amanda / Humphris, Jeremy / Chou, Angela / Pajic, Marina / Scarlett, Christopher J / Pinho, Andreia V / Giry-Laterriere, Marc / Rooman, Ilse / Samra, Jaswinder S / Kench, James G / Lovell, Jessica A / Merrett, Neil D / Toon, Christopher W / Epari, Krishna / Nguyen, Nam Q / Barbour, Andrew / Zeps, Nikolajs / Moran-Jones, Kim / Jamieson, Nigel B / Graham, Janet S / Duthie, Fraser / Oien, Karin / Hair, Jane / Grützmann, Robert / Maitra, Anirban / Iacobuzio-Donahue, Christine A / Wolfgang, Christopher L / Morgan, Richard A / Lawlor, Rita T / Corbo, Vincenzo / Bassi, Claudio / Rusev, Borislav / Capelli, Paola / Salvia, Roberto / Tortora, Giampaolo / Mukhopadhyay, Debabrata / Petersen, Gloria M / Anonymous91128 / Munzy, Donna M / Fisher, William E / Karim, Saadia A / Eshleman, James R / Hruban, Ralph H / Pilarsky, Christian / Morton, Jennifer P / Sansom, Owen J / Scarpa, Aldo / Musgrove, Elizabeth A / Bailey, Ulla-Maja Hagbo / Hofmann, Oliver / Sutherland, Robert L / Wheeler, David A / Gill, Anthony J / Gibbs, Richard A / Pearson, John V / Waddell, Nicola / Biankin, Andrew V / Grimmond, Sean M. ·Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. · The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. · Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia. · South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia. · QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. · Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA. · Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA. · Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA. · Genetic and Molecular Pathology, SA Pathology, Adelaide, South Australia 5000, Australia. · School of Biological Sciences, The University of Adelaide, Adelaide, South Australia 5000, Australia. · Harvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, USA. · Macarthur Cancer Therapy Centre, Campbelltown Hospital, New South Wales 2560, Australia. · Department of Pathology. 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ABSTRACT: Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

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