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Pancreatic Neoplasms: HELP
Articles by Alessandro Vanoli
Based on 15 articles published since 2010
(Why 15 articles?)
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Between 2010 and 2020, Alessandro Vanoli wrote the following 15 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review ACTH-secreting pancreatic neoplasms associated with Cushing syndrome: clinicopathologic study of 11 cases and review of the literature. 2015

Maragliano, Roberta / Vanoli, Alessandro / Albarello, Luca / Milione, Massimo / Basturk, Olca / Klimstra, David S / Wachtel, Antonio / Uccella, Silvia / Vicari, Emanuela / Milesi, Marina / Davì, Maria Vittoria / Scarpa, Aldo / Sessa, Fausto / Capella, Carlo / La Rosa, Stefano. ·*Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy ‡‡Department of Pathology, Ospedale di Circolo, Varese, Italy †Department of Molecular Medicine, University of Pavia, Pavia, Italy ‡Department of Pathology, San Raffaele Hospital, Milan, Italy §Department of Pathology, National Institute of Cancer, Milan, Italy #Department of Pathology, Multimedica, Milan, Italy **Department of Medicine, "G.B. Rossi" University Hospital, Verona, Italy ††ARC-NET Research Center and Department of Pathology and Diagnostics, University of Verona, Verona, Italy ∥Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY ¶Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru. ·Am J Surg Pathol · Pubmed #25353285.

ABSTRACT: Adrenocorticotropic hormone (ACTH)-secreting pancreatic neuroendocrine tumors (PanNETs), although rare, are responsible for about 15% of ectopic Cushing syndrome (CS). They represent a challenging entity because their preoperatory diagnosis is frequently difficult, and clear-cut morphologic criteria useful to differentiate them from other types of PanNETs have not been defined. Ectopic ACTH secretion associated with CS can also be rarely due to pancreatic acinar cell carcinoma (ACC) and pancreatoblastoma, rare tumor types with morphologic features sometimes overlapping those of PanNETs and, for this reason, representing a diagnostic challenge for pathologists. We herein describe the clinicopathologic and immunohistochemical features of 10 PanNETs and 1 ACC secreting ACTH and associated with CS together with an extensive review of the literature to give the reader a comprehensive overview on ACTH-producing pancreatic neoplasms. ACTH-secreting PanNETs are aggressive neoplasms with an immunohistochemical profile that partially overlaps that of pituitary corticotroph adenomas. They are generally large and well-differentiated neoplasms without distinctive histologic features but with signs of aggressiveness including vascular and perineural invasion. They are more frequent in female individuals with a mean age of 42 years. At 5 and 10 years after diagnosis, 35% and 16.2% of patients, respectively, were alive. ACTH-secreting ACCs and pancreatoblastomas are very aggressive pediatric tumors with a poor prognosis. Using an appropriate immunohistochemical panel including ACTH, β-endorphin, trypsin, and BCL10 it is possible to recognize ACTH-secreting PanNETs and to distinguish them from the very aggressive ACTH-secreting ACCs.

2 Clinical Trial Preoperative chemotherapy and carbon ions therapy for treatment of resectable and borderline resectable pancreatic adenocarcinoma: a prospective, phase II, multicentre, single-arm study. 2019

Vitolo, Viviana / Cobianchi, Lorenzo / Brugnatelli, Silvia / Barcellini, Amelia / Peloso, Andrea / Facoetti, Angelica / Vanoli, Alessandro / Delfanti, Sara / Preda, Lorenzo / Molinelli, Silvia / Klersy, Catherine / Fossati, Piero / Orecchia, Roberto / Valvo, Francesca. ·National Center of Oncological Hadrontherapy (Fondazione CNAO), Pavia, Italy. · General Surgery Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. · Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy. · Department of Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. · National Center of Oncological Hadrontherapy (Fondazione CNAO), Pavia, Italy. amelia.barcellini@cnao.it. · Hepatology and Transplantation Laboratory, Department of Surgery, Faculty of Medicine, University of Geneva, Geneva, Switzerland. · Divisions of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland. · Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. · Service of Clinical Epidemiology & Biometry, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. · MedAustron Ion Therapy Center, Wiener Neustadt, Austria. · European Institute of Oncology (IEO), Milan, Italy. ·BMC Cancer · Pubmed #31521134.

ABSTRACT: BACKGROUND: Pancreatic adenocarcinoma is a high-mortality neoplasm with a documented 5-years-overall survival around 5%. In the last decades, a real breakthrough in the treatment of the disease has not been achieved. Here we propose a prospective, phase II, multicentre, single-arm study aiming to assess the efficacy and the feasibility of a therapeutic protocol combining chemotherapy, carbon ion therapy and surgery for resectable and borderline resectable pancreatic adenocarcinoma. METHOD: The purpose of this trial (PIOPPO Protocol) is to assess the efficacy and the feasibility of 3 cycles of FOLFIRINOX neoadjuvant chemotherapy followed by a short-course of carbon ion radiotherapy (CIRT) for resectable or borderline resectable pancreatic adenocarcinoma patients. Primary outcome of this study is the assessment of local progression free survival (L-PFS). The calculation of sample size is based on the analysis of the primary endpoint "progression free survival" according to Fleming's Procedure. DISCUSSION: Very preliminary results provide initial evidence of the feasibility of the combined chemotherapy and CIRT in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer. Completion of the accrual and long term results are awaited to see if this combination of treatment is advisable and will provide the expected benefits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03822936 registered on January 2019.

3 Article Comparison of pathology sampling protocols for pancreatoduodenectomy specimens. 2019

Grillo, Federica / Ferro, Jacopo / Vanoli, Alessandro / Delfanti, Sara / Pitto, Francesca / Peñuela, Leonardo / Bianchi, Rita / Grami, Oneda / Fiocca, Roberto / Mastracci, Luca. ·Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy. federica.grillo@unige.it. · Ospedale Policlinico San Martino Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy. federica.grillo@unige.it. · Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy. · Unit of Anatomic Pathology, Department of Molecular Medicine, University of Pavia, Viale Camillo Golgi, 19, 27100, Pavia, Italy. · Anatomic Pathology, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100, Pavia, Italy. · Medical Oncology, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100, Pavia, Italy. · Ospedale Policlinico San Martino Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy. ·Virchows Arch · Pubmed #31802231.

ABSTRACT: Pancreatoduodenectomy is one of the most challenging surgical specimens for pathologists. Recently, two different, standardized protocols have been proposed: the axial slicing Leeds protocol (LP) and the bi-valving Adsay protocol (AP). Comparison between standardized and non-standardized protocols (NSP) was performed with emphasis on margin involvement and lymph node yield. Pancreatoduodenectomy cases were retrospectively recruited: 46 sampled with LP, 52 cases with AP and 46 cases with NSP. Clinico-pathologic data and rates of margin/surface involvement were collected and their prognostic influence on survival was assessed. Statistical differences between NSP and AP and LP were seen for nodal yield (p = 0.0001), N+ (p = 0.0001) and lymph node ratio - LNR (p < 0.0008) but not between AP and LP. Differences in R1/R0 status were statistically significant between NSP group (R1-15%) and both the LP (R1-73.9%) and AP (R1-70%) groups (p = 0.0001) but not between LP and AP groups. At univariate survival analysis, grade (p = 0.0023) and number of involved margins (p = 0.0096) in AP and "N-category" (p = 0.0057) "resection margin status" (p = 0.0094), "stage" (p = 0.0143), and "number of involved margins" (p = 0.00398) in LP were statistically significant, while no variable was significant in the NSP group. At multivariate analysis "N category," "resection margin status," "stage," "number of involved margins," and "LNR" retained significance for the LP group. These results show that both LP and AP perform better than non-standardized sampling making standardization mandatory in pancreatoduodenectomy cut up. Both AP and LP show strengths and weaknesses, and these may impact on the choice of protocol in different institutions.

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

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

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

5 Article c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers. 2018

La Rosa, Stefano / Bernasconi, Barbara / Vanoli, Alessandro / Sciarra, Amedeo / Notohara, Kenji / Albarello, Luca / Casnedi, Selenia / Billo, Paola / Zhang, Lizhi / Tibiletti, Maria Grazia / Sessa, Fausto. ·Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, 25 rue du Bugnon, 1011, Lausanne, Switzerland. stefano.larosa@chuv.ch. · Department of Medicine and Surgery, University of Insubria, Varese, Italy. · Department of Molecular Medicine, University of Pavia, Pavia, Italy. · Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, 25 rue du Bugnon, 1011, Lausanne, Switzerland. · Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan. · Pathology Unit, San Raffaele Scientific Institute, Milan, Italy. · Centre de Pathologie, Strasbourg, France. · Unit of Pathology, Ospedale Civile, Legnano, Italy. · Department of Pathology, Mayo Clinic, Rochester, MN, USA. · Department of Pathology, ASST-Sette Laghi, Varese, Italy. ·Virchows Arch · Pubmed #29721608.

ABSTRACT: The molecular alterations of pancreatic acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MANECs) are not completely understood, and the possible role of c-MYC amplification in tumor development, progression, and prognosis is not known. We have investigated c-MYC gene amplification in a series of 35 ACCs and 4 MANECs to evaluate its frequency and a possible prognostic role. Gene amplification was investigated using interphasic fluorescence in situ hybridization analysis simultaneously hybridizing c-MYC and the centromere of chromosome 8 probes. Protein expression was immunohistochemically investigated using a specific monoclonal anti-c-myc antibody. Twenty cases had clones with different polysomies of chromosome 8 in absence of c-MYC amplification, and 5 cases had one amplified clone and other clones with chromosome 8 polysomy, while the remaining 14 cases were diploid for chromosome 8 and lacked c-MYC amplification. All MANECs showed c-MYC amplification and/or polysomy which were observed in 54% pure ACCs. Six cases (15.3%) showed nuclear immunoreactivity for c-myc, but only 4/39 cases showed simultaneous c-MYC amplification/polysomy and nuclear protein expression. c-myc immunoreactivity as well as c-MYC amplification and/or chromosome 8 polysomy was not statistically associated with prognosis. Our study demonstrates that a subset of ACCs shows c-MYC alterations including gene amplification and chromosome 8 polysomy. Although they are not associated with a different prognostic signature, the fact that these alterations are present in all MANECs suggests a role in the acinar-neuroendocrine differentiation possibly involved in the pathogenesis of MANECs.

6 Article KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment? 2017

Grillo, Federica / Valle, Luca / Ferone, Diego / Albertelli, Manuela / Brisigotti, Maria Pia / Cittadini, Giuseppe / Vanoli, Alessandro / Fiocca, Roberto / Mastracci, Luca. ·Pathology Unit, Department of Surgical Science and Integrated Diagnostics (DISC), University of Genoa, Largo Rosanna Benzi, 10, Genoa, 16132, Italy. federica.grillo@unige.it. · Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, Genoa, 16132, Italy. federica.grillo@unige.it. · Pathology Unit, Department of Surgical Science and Integrated Diagnostics (DISC), University of Genoa, Largo Rosanna Benzi, 10, Genoa, 16132, Italy. · Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, Genoa, 16132, Italy. · Endocrinology, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Largo Rosanna Benzi, 10, Genoa, 16132, Italy. · Department of Radiology, Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, Genoa, 16132, Italy. · Unit of Pathology, Department of Molecular Medicine, University of Pavia, Via Forlanini 14, Pavia, 27100, Italy. ·Endocrine · Pubmed #28726181.

ABSTRACT: PURPOSE: Ki-67 heterogeneity can impact on gastroenteropancreatic neuroendocrine tumor grade assignment, especially when tissue is scarce. This work is aimed at devising adequacy criteria for grade assessment in biopsy specimens. METHOD: To analyze the impact of biopsy size on reliability, 360 virtual biopsies of different thickness and lengths were constructed. Furthermore, to estimate the mean amount of non-neoplastic tissue component present in biopsies, 28 real biopsies were collected, the non-neoplastic components (fibrosis and inflammation) quantified and the effective area of neoplastic tissue calculated for each biopsy. RESULTS: Heterogeneity of Ki-67 distribution, G2 tumors and biopsy size all play an important role in reducing the reliability of biopsy samples in Ki-67-based grade assignment. In particular in G2 cases, 59.9% of virtual biopsies downgraded the tumor and the smaller the biopsy, the more frequent downgrading occurs. In real biopsies the presence of non-neoplastic tissue reduced the available total area by a mean of 20%. CONCLUSIONS: By coupling the results from these two different approaches we show that both biopsy size and non-neoplastic component must be taken into account for biopsy adequacy. In particular, we can speculate that if the minimum biopsy area, necessary to confidently (80% concordance) grade gastro-entero-pancreatic neuroendocrine tumors on virtual biopsies ranges between 15 and 30 mm

7 Article Non-ampullary-duodenal carcinomas: clinicopathologic analysis of 47 cases and comparison with ampullary and pancreatic adenocarcinomas. 2017

Xue, Yue / Vanoli, Alessandro / Balci, Serdar / Reid, Michelle M / Saka, Burcu / Bagci, Pelin / Memis, Bahar / Choi, Hyejeong / Ohike, Nobuyike / Tajiri, Takuma / Muraki, Takashi / Quigley, Brian / El-Rayes, Bassel F / Shaib, Walid / Kooby, David / Sarmiento, Juan / Maithel, Shishir K / Knight, Jessica H / Goodman, Michael / Krasinskas, Alyssa M / Adsay, Volkan. ·Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. · Department of Molecular Medicine, San Matteo Hospital, University of Pavia, Pavia, Italy. · Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea. · Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan. · Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan. · Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA. · Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA. · Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA. ·Mod Pathol · Pubmed #27739441.

ABSTRACT: Literature on non-ampullary-duodenal carcinomas is limited. We analyzed 47 resected non-ampullary-duodenal carcinomas. Histologically, 78% were tubular-type adenocarcinomas mostly gastro-pancreatobiliary type and only 19% pure intestinal. Immunohistochemistry (n=38) revealed commonness of 'gastro-pancreatobiliary markers' (CK7 55, MUC1 50, MUC5AC 50, and MUC6 34%), whereas 'intestinal markers' were relatively less common (MUC2 36, CK20 42, and CDX2 44%). Squamous and mucinous differentiation were rare (in five each); previously, unrecognized adenocarcinoma patterns were noted (three microcystic/vacuolated, two cribriform, one of comedo-like, oncocytic papillary, and goblet-cell-carcinoid-like). An adenoma component common in ampullary-duodenal cancers was noted in only about a third. Most had plaque-like or ulcerating growth. Mismatch repair protein alterations were detected in 13% (all with plaque-like growth and pushing-border infiltration). When compared with ampullary (n=355) and pancreatic ductal (n=227) carcinomas, non-ampullary-duodenal carcinomas had intermediary pathologic features with mean invasive size of 2.9 cm (vs 1.9, and 3.3) and 59% nodal metastasis (vs 45, and 77%). Its survival (3-, 5-year rates of 57 and 57%) was similar to that of ampullary-duodenal carcinomas (59 and 52%; P=0.78), but was significantly better than the ampullary ductal (41 and 29%, P<0.001) and pancreatic (28 and 18%, P<0.001) carcinomas. In conclusion, non-ampullary-duodenal carcinomas are more histologically heterogeneous than previously appreciated. Their morphologic versatility (commonly showing gastro-pancreatobiliary lineage and hitherto unrecognized patterns), frequent plaque-like growth minus an adenoma component, and frequent expression of gastro-pancreatobiliary markers suggest that many non-ampullary-duodenal carcinomas may arise from Brunner glands or gastric metaplasia or heterotopic pancreatobiliary epithelium. The clinical behavior of non-ampullary-duodenal carcinoma is closer to that of ampullary-duodenal subset of ampullary carcinomas, but is significantly better than that of ampullary ductal and pancreatic cancers. The frequency of mismatch repair protein alterations suggest that routine testing should be considered, especially in the non-ampullary-duodenal carcinomas with plaque-like growth and pushing-border infiltration.

8 Article The Clinicopathologic Heterogeneity of Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: Morphological Differentiation and Proliferation Identify Different Prognostic Categories. 2017

Milione, Massimo / Maisonneuve, Patrick / Spada, Francesca / Pellegrinelli, Alessio / Spaggiari, Paola / Albarello, Luca / Pisa, Eleonora / Barberis, Massimo / Vanoli, Alessandro / Buzzoni, Roberto / Pusceddu, Sara / Concas, Laura / Sessa, Fausto / Solcia, Enrico / Capella, Carlo / Fazio, Nicola / La Rosa, Stefano. ·Anatomic Pathology, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy. ·Neuroendocrinology · Pubmed #26943788.

ABSTRACT: BACKGROUND/AIMS: Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) are defined as neuroendocrine neoplasms (NENs) with a Ki-67 index >20% according to the 2010 WHO classification. Some reports suggest that this category is heterogeneous. We retrospectively studied a series of 136 patients affected by grade 3 GEP-NECs with the aim to clarify the prognostic role of tumor morphological differentiation, proliferation, defect in mismatch repair proteins (MMRd), CD117 expression, and site of origin. The primary endpoint was the correlation between these parameters and the overall survival (OS). METHODS: Univariate and multivariable Cox proportional hazards regression analyses were used to assess the prognostic significance of various clinical and histopathologic features. RESULTS: With a median follow-up of 81 months, the median OS was 12.9 months. At multivariate analysis, morphological differentiation, Ki-67 index, MMRd, stage, and CD117 expression were independent prognostic markers in NECs. Three different prognostic categories of NECs were identified according to the degree of morphologic differentiation (well vs. poorly differentiated) and Ki-67 index (<55% vs. ≥55%). On this basis, median OS was 43.6 months in well-differentiated neoplasms with a Ki-67 index 20-55% (named type A), 24.5 months in poorly differentiated neoplasms with a Ki-67 index 20-55% (type B), and 5.3 months (p < 0.0001) in poorly differentiated neoplasms with a Ki-67 index ≥55% (type C). CONCLUSIONS: The present study suggests that GEP-NECs represent a heterogeneous group of neoplasms which can be better classified in different prognostic categories using both tumor morphology and Ki-67 index.

9 Article TP53 alterations in pancreatic acinar cell carcinoma: new insights into the molecular pathology of this rare cancer. 2016

La Rosa, Stefano / Bernasconi, Barbara / Frattini, Milo / Tibiletti, Maria Grazia / Molinari, Francesca / Furlan, Daniela / Sahnane, Nora / Vanoli, Alessandro / Albarello, Luca / Zhang, Lizhi / Notohara, Kenji / Casnedi, Selenia / Chenard, Marie-Pierre / Adsay, Volkan / Asioli, Sofia / Capella, Carlo / Sessa, Fausto. ·Department of Pathology, Ospedale di Circolo, viale Borri 57, 21100, Varese, Italy. stefano.larosa@ospedale.varese.it. · Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy. · Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland. · Department of Pathology, Ospedale di Circolo, viale Borri 57, 21100, Varese, Italy. · Department of Molecular Medicine, University of Pavia, Pavia, Italy. · Pathology Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. · Department of Pathology, Kurashiki Central Hospital, Kurashiki, Japan. · Centre de Pathologie, Strasbourg, France. · Department of Pathology, Hospital De Hautepierre, Strasbourg, France. · Department of Pathology, Emory University, Atlanta, GA, USA. · Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. ·Virchows Arch · Pubmed #26586531.

ABSTRACT: The molecular alterations of pancreatic acinar cell carcinomas (ACCs) are poorly understood and have been reported as being different from those in ductal adenocarcinomas. Loss of TP53 gene function in the pathogenesis of ACCs is controversial since contradictory findings have been published. A comprehensive analysis of the different possible genetic and epigenetic mechanisms leading to TP53 alteration in ACC has never been reported and hence the role of TP53 in the pathogenesis and/or progression of ACC remains unclear. We investigated TP53 alterations in 54 tumor samples from 44 patients, including primary and metastatic ACC, using sequencing analysis, methylation-specific multiplex ligation probe amplification, fluorescence in situ hybridization, and immunohistochemistry. TP53 mutations were found in 13 % of primary ACCs and in 31 % of metastases. Primary ACCs and metastases showed the same mutational profile, with the exception of one case, characterized by a wild-type sequence in the primary carcinoma and a mutation in the corresponding metastasis. FISH analysis revealed deletion of the TP53 region in 53 % of primary ACCs and in 50 % of metastases. Promoter hypermethylation was found in one case. The molecular alterations correlated well with the immunohistochemical findings. A statistically significant association was found between the combination of mutation of one allele and loss of the other allele of TP53 and worse survival.

10 Article Hepatoid carcinoma of the pancreas with lymphoid stroma: first description of the clinical, morphological, immunohistochemical, and molecular characteristics of an unusual pancreatic carcinoma. 2015

Vanoli, Alessandro / Argenti, Francesca / Vinci, Alessio / La Rosa, Stefano / Viglio, Alessandra / Riboni, Roberta / Necchi, Vittorio / Pugliese, Luigi / Sessa, Fausto / Pietrabissa, Andrea / Paulli, Marco. ·Department of Pathology, Fondazione IRCCS Policlinico San Matteo, and Department of Molecular Medicine, University of Pavia, Pavia, Italy, ale.vanol@virgilio.it. ·Virchows Arch · Pubmed #25989715.

ABSTRACT: We report a case of tumour in the head of the pancreas observed in a 57-year-old man with a history of worsening jaundice and elevated alpha-fetoprotein (AFP) serum level, who underwent Whipple pancreatoduodenectomy. Histologically, the tumour was predominantly composed of solid sheets of large eosinophilic cells with a prominent lymphoid infiltration without association neither with DNA microsatellite instability nor Epstein-Barr virus infection. The tumour was diffusely and strongly positive for hepatocyte paraffin-1 (Hep Par-1) and glypican-3 leading to the diagnosis of hepatoid carcinoma. Strong cytoplasmic staining for AFP was focally observed. Moreover, tumour cells showed countless cytoplasmic eosinophilic globules immunoreactive for the stress protein p62. A primary hepatocellular carcinoma of the liver was ruled out by careful clinical analysis. Hepatoid carcinoma is an extremely rare pancreatic neoplasm, and here, we describe the first case of such variant associated with lymphoid stroma. The characteristic histologic features and the immunophenotypic profile help in distinguishing this carcinoma from other pancreatic tumours, notably from medullary carcinoma.

11 Article APC alterations are frequently involved in the pathogenesis of acinar cell carcinoma of the pancreas, mainly through gene loss and promoter hypermethylation. 2014

Furlan, Daniela / Sahnane, Nora / Bernasconi, Barbara / Frattini, Milo / Tibiletti, Maria Grazia / Molinari, Francesca / Marando, Alessandro / Zhang, Lizhi / Vanoli, Alessandro / Casnedi, Selenia / Adsay, Volkan / Notohara, Kenji / Albarello, Luca / Asioli, Sofia / Sessa, Fausto / Capella, Carlo / La Rosa, Stefano. ·Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy. ·Virchows Arch · Pubmed #24590585.

ABSTRACT: Genetic and epigenetic alterations involved in the pathogenesis of pancreatic acinar cell carcinomas (ACCs) are poorly characterized, including the frequency and role of gene-specific hypermethylation, chromosome aberrations, and copy number alterations (CNAs). A subset of ACCs is known to show alterations in the APC/β-catenin pathway which includes mutations of APC gene. However, it is not known whether, in addition to mutation, loss of APC gene function can occur through alternative genetic and epigenetic mechanisms such as gene loss or promoter methylation. We investigated the global methylation profile of 34 tumor suppressor genes, CNAs of 52 chromosomal regions, and APC gene alterations (mutation, methylation, and loss) together with APC mRNA level in 45 ACCs and related peritumoral pancreatic tissues using methylation-specific multiplex ligation probe amplification (MS-MLPA), fluorescence in situ hybridization (FISH), mutation analysis, and reverse transcription-droplet digital PCR. ACCs did not show an extensive global gene hypermethylation profile. RASSF1 and APC were the only two genes frequently methylated. APC mutations were found in only 7 % of cases, while APC loss and methylation were more frequently observed (48 and 56 % of ACCs, respectively). APC mRNA low levels were found in 58 % of cases and correlated with CNAs. In conclusion, ACCs do not show extensive global gene hypermethylation. APC alterations are frequently involved in the pathogenesis of ACCs mainly through gene loss and promoter hypermethylation, along with reduction of APC mRNA levels.

12 Article Growth hormone-releasing hormone-producing pancreatic neuroendocrine tumor in a multiple endocrine neoplasia type 1 family with an uncommon phenotype. 2013

Sala, Elisa / Ferrante, Emanuele / Verrua, Elisa / Malchiodi, Elena / Mantovani, Giovanna / Filopanti, Marcello / Ferrero, Stefano / Pietrabissa, Andrea / Vanoli, Alessandro / La Rosa, Stefano / Zatelli, Maria C / Beck-Peccoz, Paolo / Verga, Uberta. ·Department of Clinical Sciences and Community Health, Endocrinology and Diabetology Unit, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. elisasala@yahoo.it ·Eur J Gastroenterol Hepatol · Pubmed #23542451.

ABSTRACT: The objective of this study was to describe a multiple endocrine neoplasia type 1 (MEN1) family characterized by primary hyperparathyroidism, in association with acromegaly because of ectopic growth hormone-releasing hormone (GHRH) secretion by a pancreatic neuroendocrine tumor in a young man and with a bronchial carcinoid in his mother. We investigate the clinical, radiological imaging, histopathologic findings, and therapy. An 18-year-old man successfully underwent subtotal parathyroidectomy for primary hyperparathyroidism. A subsequent genetic analysis showed a MEN1 gene mutation. Three years later, acromegaly because of ectopic GHRH secretion was diagnosed (pituitary MRI negative and elevated GHRH levels). A search for an ectopic tumor was unsuccessful and somatostatin analog therapy was started. Successively, scintigraphy with somatostatin analogs (68-Ga-DOTATOC-PET) showed three focal areas in the pancreatic tail. Distal pancreatectomy showed multiple pancreatic neuroendocrine tumors and hormonal status was normalized. Afterwards, the evaluation of the patient's mother, carrying the same mutation, indicated a primary hyperparathyroidism and a 4 cm lung mass. The patient underwent subtotal pneumonectomy and the histological analysis was consistent with the diagnosis of a typical bronchial carcinoid. In conclusion, an atypical phenotype may be recorded in MEN1 families, thus emphasizing the importance of the new imaging and surgical techniques in the diagnosis and treatment of such a rare disease.

13 Article The prognostic role of time to diagnosis and presenting symptoms in patients with pancreatic cancer. 2013

Gobbi, Paolo G / Bergonzi, Manuela / Comelli, Mario / Villano, Lara / Pozzoli, Donatella / Vanoli, Alessandro / Dionigi, Paolo. ·Internal Medicine and Gastroenterology, University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy. gobbipg@smatteo.pv.it ·Cancer Epidemiol · Pubmed #23369450.

ABSTRACT: BACKGROUND: The aim of this study was to investigate the prognostic role of diagnostic delay and clinical presentation (regarding pain, jaundice, and weight loss) in pancreatic carcinoma. METHODS: One hundred and seventy patients with pancreatic cancer were diagnosed and treated in the decade 2001-2010 (100 males and 70 females, with a mean age of 65.8 years [range, 36-91]). Patients were staged with spiral computed tomography and 75% were found to have advanced disease (28 stage III, 99 stage IV disease). Ductal adenocarcinoma was diagnosed in 147 cases, other subtypes of carcinoma in the remaining 23. Fifty patients were operated with radical intent, 19 had palliative surgery, 101 were considered inoperable because of advanced disease or heavy anesthesiologic risk; 31 of these inoperable patients underwent biliary decompression by insertion of an endoluminal or percutaneous stent. Gemcitabine-containing regimens were administered to 143 patients and radiotherapy was combined in 19. Overall and relative survival were the parameters studied. Multivariate analysis was performed by multiple regressions applied to proportional-hazards model. RESULTS: From all the clinical, pathological and therapeutical factors evaluated the statistically significant ones were time to diagnosis and surgery. Among symptoms pain was related to the shortest mean time to diagnosis, weight loss to the longest, with corresponding differences in survival. These differences of observed survival were substantially confirmed in terms of relative survival. CONCLUSIONS: The poor prognosis of pancreatic carcinoma seems to depend, in part, on diagnostic delay and this, in turn, is influenced by the type of presenting symptoms.

14 Article Clinicopathologic study of 62 acinar cell carcinomas of the pancreas: insights into the morphology and immunophenotype and search for prognostic markers. 2012

La Rosa, Stefano / Adsay, Volkan / Albarello, Luca / Asioli, Sofia / Casnedi, Selenia / Franzi, Francesca / Marando, Alessandro / Notohara, Kenji / Sessa, Fausto / Vanoli, Alessandro / Zhang, Lizhi / Capella, Carlo. ·Department of Pathology, Ospedale di Circolo, 21100 Varese, Italy. stefano.larosa@ospedale.varese.it ·Am J Surg Pathol · Pubmed #23026929.

ABSTRACT: Acinar cell carcinoma (ACC) of the pancreas is a very rare tumor that has various morphologic features, which may give rise to diagnostic difficulties. Because of its rarity, many clinicopathologic characteristics remain to be further elucidated, and prognostic factors are yet to be well established. With the aim of better characterizing this carcinoma and searching for prognostic indicators, we collected 62 ACCs and investigated the following parameters: site, size, local infiltration, node and distant metastases, architectural pattern, nuclear atypia, presence of necrosis, lymphovascular and perineural invasion, proliferation, BCL10, trypsin, carboxyl ester lipase, amylase, lipase, PDX1, cytokeratin 19 (CK19), CK7, p53, and β-catenin expression. Twelve cases showing >30% of endocrine cells were reclassified as mixed acinar-neuroendocrine carcinomas, whereas 1 tumor was reclassified as a mixed ductal-acinar carcinoma and was excluded from the statistical prognostic evaluations. BCL10 and trypsin were the most reliable immunohistochemical markers, whereas amylase and lipase were not. Surgery was statistically correlated with a better prognosis (P=0.0008). Among resected tumors there was no difference in survival between ACCs and mixed acinar-neuroendocrine carcinomas, and factors that significantly correlated with poor prognosis were size >6.5 cm (P=0.004), lymph node (P=0.0039) and distant (P=0.008) metastases, and UICC stage (P=0.009). Stage was the only independent prognostic factor at multivariable analysis, and the best prognostic discrimination was observed on grouping together stages I and II and grouping together stages III and IV, suggesting a simplification of the UICC staging for such cancers. In addition, vascular and perineural invasion and CK19 and p53 expression showed a trend for poor prognosis, not reaching statistical significance.

15 Minor Carbon ion radiotherapy and completion pancreatectomy. A feasible model to explore a new integrated approach? 2017

Cobianchi, Lorenzo / Fossati, Piero / Peloso, Andrea / Brugnatelli, Silvia / Vanoli, Alessandro / Valvo, Francesca / Orecchia, Roberto / Dionigi, Paolo. ·Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, General Surgery 1, Fondazione IRCCS Policlinico San Matteo, Italy. Electronic address: l.cobianchi@smatteo.pv.it. · Centro Nazionale Adroterapia Oncologica (CNAO), Pavia, Italy; Radiotherapy Division, IEO, Milan, Italy. · Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, General Surgery 1, Fondazione IRCCS Policlinico San Matteo, Italy. · Department of Onco-Hematology, Oncology Section, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. · Division of Pathology, Department of Molecular Medicine, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. · Centro Nazionale Adroterapia Oncologica (CNAO), Pavia, Italy. ·Pancreatology · Pubmed #28063781.

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