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Pancreatic Neoplasms: HELP
Articles by Sergio Pedrazzoli
Based on 23 articles published since 2010
(Why 23 articles?)
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Between 2010 and 2020, S. Pedrazzoli wrote the following 23 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Outcome of pancreaticoduodenectomy in octogenarians: Single institution's experience and review of the literature. 2015

Beltrame, V / Gruppo, M / Pastorelli, D / Pedrazzoli, S / Merigliano, S / Sperti, C. ·Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, via Giustiniani 2, 35128 Padua, Italy. · Department of Oncology, Veneto Institute of Oncology, IOV, via Gattamelata 64, 35128 Padua, Italy. · Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, via Giustiniani 2, 35128 Padua, Italy. Electronic address: csperti@libero.it. ·J Visc Surg · Pubmed #26117303.

ABSTRACT: INTRODUCTION: Pancreatic and perampullary neoplasms in patients aged 80 or older trouble the surgeons because of the risk of surgical treatment. We have reviewed our experience and literature's reports of pancreaticoduodenectomy in octogenarians, evaluating early results and long-term survival in pancreatic cancer group. METHODS: Three hundred eighty-five patients who underwent pancreaticoduodenectomy for neoplasms from 1998 to 2011 were included in the study, and were divided in two groups: group 1, patients younger than 80 years of age, and group 2, patients 80 years of age and older. Operative morbidity, mortality, disease-free and long-term survival were analysed. English literature was systematically searched for pancreatic resection's outcome in octogenarians. RESULTS: There were 385 pancreaticoduodenectomies: 362 patients were in group 1 and 23 patients in group 2. There was no significant difference regarding gender, and pathologic findings between the two groups. Complications' rate (40 vs. 43%), mortality rate (4% vs. 0%), and overall median survival for pancreatic cancer patients were not statistically different in the two groups (median 21 vs. 19 months). Literature's review showed 14 reports of pancreatic resection in octogenarians. Most of the studies (particularly in centres with high-volume pancreatic surgery) showed that outcome after pancreatectomy was not different in octogenarians or in younger patients. CONCLUSION: Pancreaticoduodenectomy is an acceptable option for elderly patients. Age alone should not be considered a contraindication to major pancreatic resection, but a careful preoperative evaluation and an accurate postoperative management are mandatory.

2 Review Extent of lymphadenectomy to associate with pancreaticoduodenectomy in patients with pancreatic head cancer for better tumor staging. 2015

Pedrazzoli, Sergio. ·University of Padua, Via Crescini, 39, 35126 Padova, Italy. Electronic address: sergio.pedrazzoli@unipd.it. ·Cancer Treat Rev · Pubmed #26045226.

ABSTRACT: OBJECTIVES: To define the extent of lymphadenectomy to associate with surgery for pancreatic head cancer. BACKGROUND: Pancreaticoduodenectomy with extended lymphadenectomy fails to prolong patient survival. METHODS: Prospective randomized and nonrandomized controlled trials (RCTs and NRCTs), meta-analyses, retrospective reviews, consensus conferences and pre- and intraoperative diagnoses of lymph node (LN) metastases were retrieved. Standard and extended lymphadenectomies were reviewed, including their effects on postoperative complications, mortality rate and long-term survival. The minimum total number of LN examined (TNLE) for adequate tumor staging, and the incidence of metastasis to each LN station were also considered. A pros and cons analysis was performed on the removal of each LN station. RESULTS: Eleven retrospective studies (2514 patients), five prospective NRCTs (545 patients), and five prospective RCTs (586 patients) described different lymphadenectomies, which obtained similar long-term results. Five meta-analyses showed they did not influence long-term survival. However, N status is an important component of tumor staging. The recommended minimum TNLE is 15. The percent incidence of metastasis to each LN station was calculated considering at least 385 and up to 3725 patients. Preoperative imaging and intraoperative exploration frequently fail to identify metastatic nodes. A pros and cons analysis suggests that lymph node status is better established removing the following LN stations: 6, 8a-p, 12a-b-c, 13a-b, 14a-b-c-d, 16b1, 17a-b. Metastasis to 16b1 LNs significantly worsens prognosis. Their removal and frozen section examination, before proceeding with resection, may contraindicate resection. CONCLUSION: A standard lymphadenectomy demands an adequate TNLE and removal of the LN stations metastasizing more frequently, without increasing the surgical risk.

3 Review Leiomyosarcoma of the Pancreas with Liver Metastases as a Paradigm of Multimodality Treatment: Case Report and Review of the Literature. 2012

Moletta, Lucia / Sperti, Cosimo / Beltrame, Valentina / Gruppo, Mario / Blandamura, Stella / Pasquali, Claudio / Pedrazzoli, Sergio. ·Department of Surgical, Oncological, and Gastroenterological Sciences, 4th Surgical Clinic, University of Padua, via Giustiniani 2, 35128, Padova, Italy. · Department of Surgical, Oncological, and Gastroenterological Sciences, 4th Surgical Clinic, University of Padua, via Giustiniani 2, 35128, Padova, Italy. csperti@libero.it. · Clinica Chirurgica Geriatrica, University of Padua, Padova, Italy. · Department of Pathology, University of Padua, Padova, Italy. ·J Gastrointest Cancer · Pubmed #22733567.

ABSTRACT: -- No abstract --

4 Review Pancreatic resection for metastatic melanoma. Case report and review of the literature. 2011

Sperti, Cosimo / Polizzi, Maria Laura / Beltrame, Valentina / Moro, Margherita / Pedrazzoli, Sergio. ·Department of Medical and Surgical Sciences, 4th Surgical Clinic, University of Padua, Padova, Italy. csperti@libero.it ·J Gastrointest Cancer · Pubmed #20524082.

ABSTRACT: INTRODUCTION: Pancreatic metastasis from several malignancies are increasingly encountered in clinical practice, and the usefulness of surgical resection has been suggested for certain neoplasms. Isolated pancreatic metastasis from malignant melanoma is a rare occurrence, and the role of surgery as an adjunct to systemic therapy for melanoma metastatic to a solitary or multiple sites is still debated. CASE REPORT: We report a patient with melanoma of unknown primary site metastatic simultaneously to the lung and pancreas 3 years after axillary lymph node dissection. Distal pancreatectomy with splenectomy and video thoracoscopic assisted resection of pulmonary metastasis were performed. The postoperative course was uneventful, but 6 months after surgery, the patient experienced single pulmonary recurrence. During chemotherapy with different drugs, pulmonary lesion remained stable for 1 year, and no abdominal recurrence occurred. After then, the size of the lesion progressively increased and a second metastasis occurred in the lung. Five months later, brain metastases occurred, and the patients died 24 months after surgery. Sixteen pancreatic resections for metastatic malignant melanoma, reported with adequate clinical details, were also retrieved from the literature. CONCLUSION: In spite of the very limited experience, it appears that surgical resection is only a palliative procedure, because long-term survival is a rare event. However, considering the lack of effective systemic therapy, surgery may be considered as a part of an aggressive multidisciplinary approach in selected cases with malignant melanoma metastatic to single or multiple visceral sites.

5 Article PDAC-derived exosomes enrich the microenvironment in MDSCs in a 2017

Basso, Daniela / Gnatta, Elisa / Padoan, Andrea / Fogar, Paola / Furlanello, Sara / Aita, Ada / Bozzato, Dania / Zambon, Carlo-Federico / Arrigoni, Giorgio / Frasson, Chiara / Franchin, Cinzia / Moz, Stefania / Brefort, Thomas / Laufer, Thomas / Navaglia, Filippo / Pedrazzoli, Sergio / Basso, Giuseppe / Plebani, Mario. ·Department of Medicine - DIMED, University of Padova, Padova, Italy. · Department of Biomedical Sciences, University of Padova, Padova, Italy. · Proteomic Center, University of Padova, Padova, Italy. · Department of Woman and Child Health, Oncohematology Laboratory, University of Padova, Padova, Italy. · Eurofins Medigenomix GmbH, Ebersberg, Germany. · Comprehensive Biomarker Center GmbH (Recently re-named to Hummingbird Diagnostics GmbH), Heidelberg, Germany. · Association Wirsung Onlus, Padova, Italy. ·Oncotarget · Pubmed #29156694.

ABSTRACT: Tumor genetics and escape from immune surveillance concur in the poor prognosis of PDAC. In this study an experimental model was set up to verify whether CONCLUSION: PDAC-derived Exo from cells with

6 Article SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival. 2017

Mohelnikova-Duchonova, Beatrice / Strouhal, Ondrej / Hughes, David J / Holcatova, Ivana / Oliverius, Martin / Kala, Zdenek / Campa, Daniele / Rizzato, Cosmeri / Canzian, Federico / Pezzilli, Raffaele / Talar-Wojnarowska, Renata / Malecka-Panas, Ewa / Sperti, Cosimo / Federico Zambon, Carlo / Pedrazzoli, Sergio / Fogar, Paola / Milanetto, Anna Caterina / Capurso, Gabriele / Delle Fave, Gianfranco / Valente, Roberto / Gazouli, Maria / Malleo, Giuseppe / Teresa Lawlor, Rita / Strobel, Oliver / Hackert, Thilo / Giese, Nathalia / Vodicka, Pavel / Vodickova, Ludmila / Landi, Stefano / Tavano, Francesca / Gioffreda, Domenica / Piepoli, Ada / Pazienza, Valerio / Mambrini, Andrea / Pedata, Mariangela / Cantore, Maurizio / Bambi, Franco / Ermini, Stefano / Funel, Niccola / Lemstrova, Radmila / Soucek, Pavel. ·Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic. · Department of Physiology &Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland. · Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Department of Transplantation Surgery, Institute of Clinical and Experimental Medicine, Prague, Czech Republic. · Department of Surgery, The University Hospital and Faculty of Medicine, Brno Bohunice, Czech Republic. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Biology, University of Pisa, Pisa, Italy. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. · Department of Digestive Diseases, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Surgery, Oncology and Gastroenterology -DiSCOG, University of Padova, Italy. · Department of Medicine - DIMED, University of Padova, Italy. · Clinica Chirurgica 4, University of Padova, Italy. · Department of Laboratory Medicine, University-Hospital of Padova, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. · Department of Surgery and Oncology, University and Hospital Trust of Verona, Verona, Italy. · ARC-NET Applied research on Cancer Centre, University and Hospital Trust of Verona, Verona, Italy. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic and First Faculty of Medicine, Charles University in Prague, Czech Republic. · Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Oncology, Azienda USL 1 Massa Carrara, Massa Carrara, Italy. · Blood Transfusion Service, Children's Hospital Meyer, Azienda Ospedaliero Universitaria, Florence, Italy. ·Sci Rep · Pubmed #28272475.

ABSTRACT: Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated with overall survival of pancreatic cancer patients. This study tested whether genetic variability in SLC22A3 associates with pancreatic cancer risk and prognosis. Twenty four single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene sequence and regulatory elements were selected for analysis. Of these, 22 were successfully evaluated in the discovery phase while six significant or suggestive variants entered the validation phase, comprising a total study number of 1,518 cases and 3,908 controls. In the discovery phase, rs2504938, rs9364554, and rs2457571 SNPs were significantly associated with pancreatic cancer risk. Moreover, rs7758229 associated with the presence of distant metastases, while rs512077 and rs2504956 correlated with overall survival of patients. Although replicated, the association for rs9364554 did not pass multiple testing corrections in the validation phase. Contrary to the discovery stage, rs2504938 associated with survival in the validation cohort, which was more pronounced in stage IV patients. In conclusion, common variation in the SLC22A3 gene is unlikely to significantly contribute to pancreatic cancer risk. The rs2504938 SNP in SLC22A3 significantly associates with an unfavorable prognosis of pancreatic cancer patients. Further investigation of this SNP effect on the molecular and clinical phenotype is warranted.

7 Article SMAD4 loss enables EGF, TGFβ1 and S100A8/A9 induced activation of critical pathways to invasion in human pancreatic adenocarcinoma cells. 2016

Moz, Stefania / Basso, Daniela / Bozzato, Dania / Galozzi, Paola / Navaglia, Filippo / Negm, Ola H / Arrigoni, Giorgio / Zambon, Carlo-Federico / Padoan, Andrea / Tighe, Paddy / Todd, Ian / Franchin, Cinzia / Pedrazzoli, Sergio / Punzi, Leonardo / Plebani, Mario. ·University of Padova, Laboratory Medicine, Department of Medicine - DIMED, Padova, Italy. · University of Padova, Rheumatology Unit, Department of Medicine - DIMED, Padova, Italy. · University of Nottingham, School of Life Sciences, Queen's Medical Centre, Nottingham, UK. · Mansoura University, Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura City, Egypt. · University of Padova, Department of Biomedical Sciences, Padova, Italy. · Proteomics Center, University of Padova and Azienda Ospedaliera di Padova, Padova, Italy. · Associazione Wirsung-onlus, Padova, Italy. ·Oncotarget · Pubmed #27655713.

ABSTRACT: Epidermal Growth Factor (EGF) receptor overexpression, KRAS, TP53, CDKN2A and SMAD4 mutations characterize pancreatic ductal adenocarcinoma. This mutational landscape might influence cancer cells response to EGF, Transforming Growth Factor β1 (TGFβ1) and stromal inflammatory calcium binding proteins S100A8/A9. We investigated whether chronic exposure to EGF modifies in a SMAD4-dependent manner pancreatic cancer cell signalling, proliferation and invasion in response to EGF, TGFβ1 and S100A8/A9. BxPC3, homozigously deleted (HD) for SMAD4, and BxPC3-SMAD4+ cells were or not stimulated with EGF (100 ng/mL) for three days. EGF pre-treated and non pretreated cells were stimulated with a single dose of EGF (100 ng/mL), TGFβ1 (0,02 ng/mL), S100A8/A9 (10 nM). Signalling pathways (Reverse Phase Protein Array and western blot), cell migration (Matrigel) and cell proliferation (XTT) were evaluated. SMAD4 HD constitutively activated ERK and Wnt/β-catenin, while inhibiting PI3K/AKT pathways. These effects were antagonized by chronic EGF, which increased p-BAD (anti-apoptotic) in response to combined TGFβ1 and S100A8/A9 stimulation. SMAD4 HD underlied the inhibition of NF-κB and PI3K/AKT in response to TGFβ1 and S100A8/A9, which also induced cell migration. Chronic EGF exposure enhanced cell migration of both BxPC3 and BxPC3-SMAD4+, rendering the cells less sensitive to the other inflammatory stimuli. In conclusion, SMAD4 HD is associated with the constitutive activation of the ERK and Wnt/β-catenin signalling pathways, and favors the EGF-induced activation of multiple signalling pathways critical to cancer proliferation and invasion. TGFβ1 and S100A8/A9 mainly inhibit NF-κB and PI3K/AKT pathways and, when combined, sinergize with EGF in enhancing anti-apoptotic p-BAD in a SMAD4-dependent manner.

8 Article Blood expression of matrix metalloproteinases 8 and 9 and of their inducers S100A8 and S100A9 supports diagnosis and prognosis of PDAC-associated diabetes mellitus. 2016

Moz, Stefania / Basso, Daniela / Padoan, Andrea / Bozzato, Dania / Fogar, Paola / Zambon, Carlo-Federico / Pelloso, Michela / Sperti, Cosimo / Vigili de Kreutzenberg, Saula / Pasquali, Claudio / Pedrazzoli, Sergio / Avogaro, Angelo / Plebani, Mario. ·Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy. · Department of Laboratory Medicine, University Hospital of Padova, via Giustiniani 2, 35128 Padova, Italy. Electronic address: daniela.basso@sanita.padova.it. · Department of Laboratory Medicine, University Hospital of Padova, via Giustiniani 2, 35128 Padova, Italy. · Department of Surgical, Oncological and GastroenterologicalSciences - DISCOG, University of Padova, via Giustiniani 2, 35128 Padova, Italy. · Associazione Wirsung-onlus, via Giustiniani 2, 35128 Padova, Italy. · Department of Medicine - DIMED, University of Padova, via Giustiniani 2, 35128 Padova, Italy; Department of Laboratory Medicine, University Hospital of Padova, via Giustiniani 2, 35128 Padova, Italy. ·Clin Chim Acta · Pubmed #26923392.

ABSTRACT: BACKGROUND: Based on the knowledge that matrix metalloproteinases (MMPs) and S100A8/A9 synergistically work in causing PDAC-associated type 2 diabetes mellitus (T2DM), we verified whether tissue and blood MMP8, MMP9, S100A8 and S100A9 expression might help in distinguishing PDAC among diabetics. METHODS: Relative quantification of MMP8, MMP9, S100A8 and S100A9 mRNA was performed in tissues obtained from 8 PDAC, 4 chronic pancreatitis (ChrPa), 4 non-PDAC tumors and in PBMCs obtained from 30 controls, 43 T2DM, 41 ChrPa, 91 PDAC and 33 pancreatic-biliary tract tumors. RESULTS: T2DM was observed in PDAC (66%), in pancreatic-biliary tract tumors (64%) and in ChrPa (70%). In diabetics, with or without PDAC, MMP9 tissue expression was increased (p<0.05). Both MMPs increased in PDAC and MMP9 increased also in pancreatic-biliary tract tumors PBMCs. In diabetics, MMP9 was independently associated with PDAC (p=0.025), but failed to enhance CA 19-9 discriminant efficacy. A highly reduced S100A9 expression, found in 7 PDAC, was significantly correlated with a reduced overall survival (p=0.015). CONCLUSIONS: An increased expression of tissue and blood MMP9 reflects the presence of PDAC-associated diabetes mellitus. This finding fits with the hypothesized role of MMPs as part of the complex network linking cancer to diabetes.

9 Article TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. 2015

Campa, Daniele / Rizzato, Cosmeri / Stolzenberg-Solomon, Rachael / Pacetti, Paola / Vodicka, Pavel / Cleary, Sean P / Capurso, Gabriele / Bueno-de-Mesquita, H B As / Werner, Jens / Gazouli, Maria / Butterbach, Katja / Ivanauskas, Audrius / Giese, Nathalia / Petersen, Gloria M / Fogar, Paola / Wang, Zhaoming / Bassi, Claudio / Ryska, Miroslav / Theodoropoulos, George E / Kooperberg, Charles / Li, Donghui / Greenhalf, William / Pasquali, Claudio / Hackert, Thilo / Fuchs, Charles S / Mohelnikova-Duchonova, Beatrice / Sperti, Cosimo / Funel, Niccola / Dieffenbach, Aida Karina / Wareham, Nicholas J / Buring, Julie / Holcátová, Ivana / Costello, Eithne / Zambon, Carlo-Federico / Kupcinskas, Juozas / Risch, Harvey A / Kraft, Peter / Bracci, Paige M / Pezzilli, Raffaele / Olson, Sara H / Sesso, Howard D / Hartge, Patricia / Strobel, Oliver / Małecka-Panas, Ewa / Visvanathan, Kala / Arslan, Alan A / Pedrazzoli, Sergio / Souček, Pavel / Gioffreda, Domenica / Key, Timothy J / Talar-Wojnarowska, Renata / Scarpa, Aldo / Mambrini, Andrea / Jacobs, Eric J / Jamroziak, Krzysztof / Klein, Alison / Tavano, Francesca / Bambi, Franco / Landi, Stefano / Austin, Melissa A / Vodickova, Ludmila / Brenner, Hermann / Chanock, Stephen J / Delle Fave, Gianfranco / Piepoli, Ada / Cantore, Maurizio / Zheng, Wei / Wolpin, Brian M / Amundadottir, Laufey T / Canzian, Federico. ·Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. · Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic. · Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department of Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN. · Department of Laboratory Medicine, University Hospital of Padua, Padua, Italy. · Surgical and Oncological Department, Pancreas Institute - University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, Second Faculty of Medicine, Charles University in Prague and Central Military Hospital, Prague, Czech Republic. · 1st Department of Propaedeutic Surgery, School of Medicine, University of Athens, Athens, Greece. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA. · Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX. · National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Department of Surgery, Gastroenterology and Oncology (DISCOG), University of Padua, Padua, Italy. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. · Department of Oncology, Palacky University Medical School and Teaching Hospital in Olomouc, Olomouc, Czech Republic. · Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy. · German Cancer Consortium (DKTK), Heidelberg, Germany. · MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. · Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. · Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Department of Medicine - DIMED, University of Padua, Padua, Italy. · Department of Epidemiology and Public Health, Yale School of Public Health, New Haven, CT. · Department of Epidemiology, Harvard School of Public Health, Boston, MA. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. · Division of Epidemiology, Departments of Obstetrics and Gynecology, Environmental Medicine, and Population Health, New York University School of Medicine, New York, NY. · Surgical Clinic 4, University of Padua, Padua, Italy. · Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo Della Sofferenza,", San Giovanni Rotondo, Italy. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Epidemiology Research Program, American Cancer Society, Atlanta, GA. · Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD. · Blood Transfusion Service, Azienda Ospedaliero Universitaria Meyer, Florence, Italy. · Department of Biology, University of Pisa, Pisa, Italy. · Department of Epidemiology, University of Washington, Seattle, WA. · Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN. ·Int J Cancer · Pubmed #25940397.

ABSTRACT: A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.

10 Article Pancreatic secondary lesions from renal cell carcinoma. 2014

Moletta, Lucia / Milanetto, Anna Caterina / Vincenzi, Valter / Alaggio, Rita / Pedrazzoli, Sergio / Pasquali, Claudio. ·4th Surgical Clinic, University of Padua, Padua, Italy. ·World J Surg · Pubmed #24962493.

ABSTRACT: BACKGROUND: Metastatic lesions to the pancreas are uncommon. The most frequent metastases are from renal cell carcinoma (RCC). We analyzed the clinical features and survival of patients with pancreatic metastasis from renal cell carcinoma. METHODS: We retrospectively reviewed the clinical records of patients with pancreatic metastases from RCC, observed in our department from January 2004 to March 2010. Follow-up continued to September 2013. RESULTS: In the study period 13 patients with a diagnosis of metastasis from RCC were observed in our clinic, and among them 9 pancreatic resections were performed (2 pancreaticoduodenectomy, 1 duodenum-preserving pancreatic head resection, 1 central pancreatectomy, and 5 distal pancreatectomy). Four patients did not undergo a pancreatic resection: two refused surgery, one had an endoscopic biliary stent for jaundice placed and then underwent a surgical biliary bypass, and the fourth patient was too advanced and had only an endoscopic biliary stent. The mean follow-up was 56 months (range 5-115, median 53), with one nonresected patient lost in follow-up after 38 months. Among the other 12 patients, 4 died: two for progression of disease 5 and 20 months respectively after our observation. The mean (±SEM) disease-free survival of seven resected patients with curative intent was 40 ± 11 months (median 34). CONCLUSIONS: Pancreatic metastases from RCC are often asymptomatic. They generally present slow growth and an indolent behavior. Surgery is the treatment of choice in those patients with only pancreatic involvement, achieving long-term survival and disease-free survival.

11 Article Inflammation and pancreatic cancer: molecular and functional interactions between S100A8, S100A9, NT-S100A8 and TGFβ1. 2014

Basso, Daniela / Bozzato, Dania / Padoan, Andrea / Moz, Stefania / Zambon, Carlo-Federico / Fogar, Paola / Greco, Eliana / Scorzeto, Michele / Simonato, Francesca / Navaglia, Filippo / Fassan, Matteo / Pelloso, Michela / Dupont, Sirio / Pedrazzoli, Sergio / Fassina, Ambrogio / Plebani, Mario. ·Department of Laboratory Medicine, University-Hospital of Padova, Via Giustiniani 2, 35128 Padova, Italy. daniela.basso@sanita.padova.it. ·Cell Commun Signal · Pubmed #24670043.

ABSTRACT: BACKGROUND: In order to gain further insight on the crosstalk between pancreatic cancer (PDAC) and stromal cells, we investigated interactions occurring between TGFβ1 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC-associated S100A8 derived peptide, in cell signaling, intracellular calcium (Cai2+) and epithelial to mesenchymal transition (EMT). NF-κB, Akt and mTOR pathways, Cai2+ and EMT were studied in well (Capan1 and BxPC3) and poorly differentiated (Panc1 and MiaPaCa2) cell lines. RESULTS: NT-S100A8, one of the low molecular weight N-terminal peptides from S100A8 to be released by PDAC-derived proteases, shared many effects on NF-κB, Akt and mTOR signaling with S100A8, but mainly with TGFβ1. The chief effects of S100A8, S100A9 and NT-S100A8 were to inhibit NF-κB and stimulate mTOR; the molecules inhibited Akt in Smad4-expressing, while stimulated Akt in Smad4 negative cells. By restoring Smad4 expression in BxPC3 and silencing it in MiaPaCa2, S100A8 and NT-S100A8 were shown to inhibit NF-κB and Akt in the presence of an intact TGFβ1 canonical signaling pathway. TGFβ1 counteracted S100A8, S100A9 and NT-S100A8 effects in Smad4 expressing, not in Smad4 negative cells, while it synergized with NT-S100A8 in altering Cai2+ and stimulating PDAC cell growth. The effects of TGFβ1 on both EMT (increased Twist and decreased N-Cadherin expression) and Cai2+ were antagonized by S100A9, which formed heterodimers with TGFβ1 (MALDI-TOF/MS and co-immuno-precipitation). CONCLUSIONS: The effects of S100A8 and S100A9 on PDAC cell signaling appear to be cell-type and context dependent. NT-S100A8 mimics the effects of TGFβ1 on cell signaling, and the formation of complexes between TGFβ1 with S100A9 appears to be the molecular mechanism underlying the reciprocal antagonism of these molecules on cell signaling, Cai2+ and EMT.

12 Article Pancreatic tumors and immature immunosuppressive myeloid cells in blood and spleen: role of inhibitory co-stimulatory molecules PDL1 and CTLA4. An in vivo and in vitro study. 2013

Basso, Daniela / Fogar, Paola / Falconi, Massimo / Fadi, Elisa / Sperti, Cosimo / Frasson, Chiara / Greco, Eliana / Tamburrino, Domenico / Teolato, Sara / Moz, Stefania / Bozzato, Dania / Pelloso, Michela / Padoan, Andrea / De Franchis, Giuseppe / Gnatta, Elisa / Facco, Monica / Zambon, Carlo-Federico / Navaglia, Filippo / Pasquali, Claudio / Basso, Giuseppe / Semenzato, Gianpietro / Pedrazzoli, Sergio / Pederzoli, Paolo / Plebani, Mario. ·Department of Medicine, University of Padova, Padova, Italy. daniela.basso@sanita.padova.it ·PLoS One · Pubmed #23359812.

ABSTRACT: BACKGROUND: Blood and spleen expansion of immature myeloid cells (IMCs) might compromise the immune response to cancer. We studied in vivo circulating and splenic T lymphocyte and IMC subsets in patients with benign and malignant pancreatic diseases. We ascertained in vitro whether pancreatic adenocarcinoma (PDAC)-associated IMC subsets are induced by tumor-derived soluble factors and whether they are immunosuppressive focusing on the inhibitory co-stimulatory molecules PDL1 and CTLA4. METHODOLOGY AND PRINCIPAL FINDINGS: 103 pancreatic and/or splenic surgical patients were enrolled including 52 PDAC, 10 borderline and 10 neuroendocrine tumors (NETs). Lymphocytes and IMCs were analysed by flow cytometry in blood, in spleen and in three PDAC cell conditioned (CM) or non conditioned PBMC. PDL1 and CTLA4 were studied in 30 splenic samples, in control and conditioned PBMC. IMCs were FACS sorted and co-coltured with allogenic T lymphocytes. In PDAC a reduction was found in circulating CD8(+) lymphocytes (p = 0.004) and dendritic cells (p = 0.01), which were reduced in vitro by one PDAC CM (Capan1; p = 0.03). Blood myeloid derived suppressive cells (MDSCs) CD33(+)CD14(-)HLA-DR(-) were increased in PDAC (p = 0.022) and were induced in vitro by BxPC3 CM. Splenic dendritic cells had a higher PDL1 expression (p = 0.007), while CD33(+)CD14(+)HLA-DR(-) IMCs had a lower CTLA4 expression (p = 0.029) in PDAC patients. In vitro S100A8/A9 complex, one of the possible inflammatory mediators of immune suppression in PDAC, induced PDL1 (p = 0.018) and reduced CTLA4 expression (p = 0.028) among IMCs. IMCs not expressing CTLA4 were demonstrated to be immune suppressive. CONCLUSION: In PDAC circulating dendritic and cytotoxic T cells are reduced, while MDSCs are increased and this might favour tumoral growth and progression. The reduced CTLA4 expression found among splenic IMCs of PDAC patients was demonstrated to characterize an immune suppressive phenotype and to be consequent to the direct exposure of myeloid cells to pancreatic cancer derived products, S100A8/A9 complex in particular.

13 Article Usefulness of MALDI-TOF/MS identification of low-MW fragments in sera for the differential diagnosis of pancreatic cancer. 2013

Padoan, Andrea / Seraglia, Roberta / Basso, Daniela / Fogar, Paola / Sperti, Cosimo / Moz, Stefania / Greco, Eliana / Marchet, Alberto / de Manzoni, Giovanni / Zambon, Carlo-Federico / Navaglia, Filippo / Cristadoro, Luigi / Di Chiara, Alda / Nitti, Donato / Pedrazzoli, Sergio / Pavanello, Girolamo / Plebani, Mario. ·Department of Laboratory Medicine, University of Padova, Italy. ·Pancreas · Pubmed #23271396.

ABSTRACT: OBJECTIVES: To identify new biomarkers of pancreatic cancer (PaCa), we performed MALDI-TOF/MS analysis of sera from 22 controls, 51 PaCa, 37 chronic pancreatitis, 24 type II diabetes mellitus (DM), 29 gastric cancer (GC), and 24 chronic gastritis (CG). METHODS: Sera were purified by Sep-Pak C18 before MALDI-TOF/MS Anchorchip analysis. RESULTS: Features present in at least 5% of all spectra were selected (n = 160, m/z range, 1200-5000). At univariate analysis, 2 features (m/z 2049 and 2305) correlated with PaCa, 3 (m/z 1449, 1605, and 2006) with DM. No feature characterized gastric cancer or chronic gastritis. Ten-fold cross-validation binary recursive partitioning trees were obtained for patients' classification. The tree (CA 19-9, age, m/z 2006, 2599, 2753, and 4997), built considering only patients with diabetes, allowed a distinction between DM [area under the receiver operating characteristic curve (AUC), 0.997], chronic pancreatitis (AUC, 0.968), and PaCa (AUC, 0.980), with an overall correct classification rate of 89%. The tree including CA 19-9, 1550, and 2937 m/z features, achieved an AUC of 0.970 in distinguishing localized from advanced PaCa. MALDI-TOF-TOF analysis revealed the 1550 feature as a fragment of Apo-A1, which was determined as whole protein and demonstrated to be closely correlated with PaCa. CONCLUSIONS: The findings made demonstrate a role for serum peptides identified using MALDI-TOF/MS for addressing PaCa diagnosis.

14 Article Genetic susceptibility to pancreatic cancer and its functional characterisation: the PANcreatic Disease ReseArch (PANDoRA) consortium. 2013

Campa, Daniele / Rizzato, Cosmeri / Capurso, Gabriele / Giese, Nathalia / Funel, Niccola / Greenhalf, William / Soucek, Pavel / Gazouli, Maria / Pezzilli, Raffaele / Pasquali, Claudio / Talar-Wojnarowska, Renata / Cantore, Maurizio / Andriulli, Angelo / Scarpa, Aldo / Jamroziak, Krzysztof / Delle Fave, Gianfranco / Costello, Eithne / Khaw, Kay-Tee / Heller, Anette / Key, Tim J / Theodoropoulos, George / Malecka-Panas, Ewa / Mambrini, Andrea / Bambi, Franco / Landi, Stefano / Pedrazzoli, Sergio / Bassi, Claudio / Pacetti, Paola / Piepoli, Ada / Tavano, Francesca / di Sebastiano, Pierluigi / Vodickova, Ludmila / Basso, Daniela / Plebani, Mario / Fogar, Paola / Büchler, Markus W / Bugert, Peter / Vodicka, Pavel / Boggi, Ugo / Neoptolemos, John P / Werner, Jens / Canzian, Federico. ·German Cancer Research Center (DKFZ), Heidelberg, Germany. d.campa@dkfz.de ·Dig Liver Dis · Pubmed #23206934.

ABSTRACT: Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n=86), chronic pancreatitis (n=272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going.

15 Article Comparison of International Consensus Guidelines versus 18-FDG PET in detecting malignancy of intraductal papillary mucinous neoplasms of the pancreas. 2011

Pedrazzoli, Sergio / Sperti, Cosimo / Pasquali, Claudio / Bissoli, Sergio / Chierichetti, Franca. ·IV Surgical Clinic, Department of Medical and Surgical Sciences, University of Padua, Padova, Italy. sergio.pedrazzoli@unipd-it ·Ann Surg · Pubmed #22076067.

ABSTRACT: OBJECTIVE: To assess the reliability of the International Consensus Guidelines (ICG) and 18-fluorodeoxyglucose positron emission tomography (PET) in distinguishing benign from malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. BACKGROUND: Since 2006 the ICG have been used to choose immediate surgery or surveillance for IPMN patients, but their low specificity increases the number of benign IPMNs that undergo resective surgery. PET has proved highly sensitive and specific in detecting malignancy in cystic neoplasms of the pancreas, including IPMNs. METHODS: Patients suspected with IPMNs of the pancreas seen at our Department from January 1989 to July 2010 were identified and classified as cases of main duct, mixed type and branch type IPMN. The indication for resection or surveillance was verified a posteriori for all patients according to the ICG. PET was considered positive for a Standardized Uptake Value ≥2.5. Surveillance included clinical examination, laboratory tests, CA 19-9 serum levels, and computed tomography and/or magnetic resonance and magnetic resonance cholangiopancreatography every 6 months for 2 years and yearly thereafter. Endoscopic ultrasound was rarely performed. PET was repeated in clinically or radiologically suspect cases, or if tumor markers increased. RESULTS: Sixty-one main duct or mixed type and 101-branch type IPMNs were included in the study. A histological diagnosis was available for 81 of 162 patients, missing for 1 locally advanced IPMN, whereas 62 patients are under surveillance and it proved impossible to contact 18. Conservative surgery was performed in 16 of 68 patients with benign IPMNs. The sensitivity, specificity, positive and negative predictive value, and accuracy of the ICG in detecting malignancy were 93.2, 22.2, 59.4, 72.7, and 61.2, whereas for PET they were 83.3, 100, 100, 84.6, and 91.3. CONCLUSIONS: PET is more accurate than the ICG in distinguishing benign from malignant (invasive and noninvasive) IPMNs. Prophylactic IPMN resection in young patients fit for surgery should be guided by the ICG, whereas PET should be performed in older patients, cases at increased surgical risk, or when the feasibility of parenchyma-sparing surgery demands a reliable preoperative exclusion of malignancy.

16 Article Pancreatic cancer alters human CD4+ T lymphocyte function: a piece in the immune evasion puzzle. 2011

Fogar, Paola / Basso, Daniela / Fadi, Elisa / Greco, Eliana / Pantano, Giorgia / Padoan, Andrea / Bozzato, Dania / Facco, Monica / Sanzari, Maria Colomba / Teolato, Sara / Zambon, Carlo-Federico / Navaglia, Filippo / Semenzato, Gianpietro / Pedrazzoli, Sergio / Plebani, Mario. ·Department of Laboratory Medicine, University of Padova, Padova, Italy. ·Pancreas · Pubmed #21792088.

ABSTRACT: OBJECTIVES: To verify whether the dysregulation of CD4 T cells concurs in worsening the outcome of pancreatic cancer, we compared the effects of pancreatic cancer and other gastrointestinal cancer cell-conditioned media on the (1) proliferation, migration, and differentiation of CD4 T cells and (2) expansion of CD4 memory (CD45RO), naive (CD45RA), activated (CD69), and regulatory (CD25) subsets. METHODS: After culture of CD4 T cells in control, pancreatic (BxPC3, Capan1, MiaPaCa2), or gastrointestinal cancer (AGS, HepG2, HT29) cell-conditioned media, we evaluated proliferation, migration, interferon γ (IFNγ) production, and CD45RA, CD45RO, CD69, and CD25 membrane expression in control and conditioned CD4 T cells. RESULTS: Only pancreatic cancer-conditioned media (1) inhibited CD4 T-cell proliferation (P < 0.001) and migration under human stromal cell-derived factor-α chemotaxis (P < 0.001) and (2) induced CD4 T-cell IFNγ production (P < 0.05) and the expansion of the CD69-positive subset (P < 0.001) with respect to the control, with no changes being found in the CD45RA, CD45RO, and CD25 subsets. CONCLUSIONS: The in vitro findings achieved in the present study demonstrate that pancreatic cancer cells inhibit CD4 T-cell proliferation and migration, induce IFNγ production, and favor a CD69 subset expansion, suggesting that CD4 T cells play an important role in pancreatic cancer immune evasion.

17 Article Altered intracellular calcium fluxes in pancreatic cancer induced diabetes mellitus: Relevance of the S100A8 N-terminal peptide (NT-S100A8). 2011

Basso, Daniela / Greco, Eliana / Padoan, Andrea / Fogar, Paola / Scorzeto, Michele / Fadi, Elisa / Bozzato, Dania / Moz, Stefania / Navaglia, Filippo / Zambon, Carlo-Federico / Seraglia, Roberta / De Carlo, Eugenio / Valerio, Anna / Reggiani, Carlo / Pedrazzoli, Sergio / Plebani, Mario. ·Department of Laboratory Medicine, University of Padua, Padua, Italy. ·J Cell Physiol · Pubmed #20717964.

ABSTRACT: After isolating NT-S100A8 from pancreatic cancer (PC) tissue of diabetic patients, we verified whether this peptide alters PC cell growth and invasion and/or insulin release and [Ca(2+)](i) oscillations of insulin secreting cells and/or insulin signaling. BxPC3, Capan1, MiaPaCa2, Panc1 (PC cell lines) cell growth, and invasion were assessed in the absence or presence of 50, 200, and 500 nM NT-S100A8. In NT-S100A8 stimulated β-TC6 (insulinoma cell line) culture medium, insulin and [Ca(2+)] were measured at 2, 3, 5, 10, 15, 30, and 60 min, and [Ca(2+)](i) oscillations were monitored (epifluorescence) for 3 min. Five hundred nanomolars NT-S100A8 stimulated BxPC3 cell growth only and dose dependently reduced MiaPaCa2 and Panc1 invasion. Five hundred nanomolars NT-S100A8 induced a rapid insulin release and enhanced β-TC6 [Ca(2+)](i) oscillations after both one (F = 6.05, P < 0.01) and 2 min (F = 7.42, P < 0.01). In the presence of NT-S100A8, [Ca(2+)] in β-TC6 culture medium significantly decreased with respect to control cells (F = 6.3, P < 0.01). NT-S100A8 did not counteract insulin induced phosphorylation of the insulin receptor, Akt and IκB-α, but it independently activated Akt and NF-κB signaling in PC cells. In conclusion, NT-S100A8 exerts a mild effect on PC cell growth, while it reduces PC cell invasion, possibly by Akt and NF-κB signaling, NT-S100A8 enhances [Ca(2+)](i) oscillations and insulin release, probably by inducing Ca(2+) influx from the extracellular space, but it does not interfere with insulin signaling.

18 Article Distal pancreatectomy for body-tail pancreatic cancer: is there a role for celiac axis resection? 2010

Sperti, Cosimo / Berselli, Mattia / Pedrazzoli, Sergio. ·IV Surgical Clinic, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy. ·Pancreatology · Pubmed #20720451.

ABSTRACT: BACKGROUND/AIMS: Body-tail pancreatic cancer is an aggressive disease with a low resectability rate and a poor prognosis. Celiac axis invasion usually contraindicates resection. The aim of this study was to analyze the feasibility of distal pancreatectomy (DP) with celiac axis resection (DP-CAR) for locally advanced body-tail pancreatic cancer. METHODS: All DPs performed between January 1989 and December 2007 were considered. DP and DP-CAR were reviewed for pre-, intra- and postoperative data. An extensive, detailed literature review on DP and DP-CAR was also performed. RESULTS: DP was performed in 49 of our patients, and 745 cases were retrieved from the literature. The overall morbidity and mortality rates were 32.0 and 3.0%, respectively. We performed DP-CAR in 5 patients with no mortality but 80% morbidity. A further 90 patients were retrieved from the literature. Arterial reconstruction was needed in 1/5 of our patients and in 13/90 of patients in the literature. Collaterals from superior mesenteric artery maintained adequate hepatic artery blood flow in the remaining 81 patients. The overall morbidity and mortality rates were 40.6 and 2.1%, respectively. The median survival ranged between 4.5 and 25 months after DP and was 13 months after DP-CAR. CONCLUSIONS: DP-CAR improves resectability without increasing the mortality rate. The complication rate after DP-CAR was higher than after DP, but still within the range of extended DP. DP-CAR should be considered for the inclusion among the 'extended' procedures for the treatment of body-tail pancreatic cancers invading the celiac axis. and IAP.

19 Article Analogs of vitamin E epitomized by alpha-tocopheryl succinate for pancreatic cancer treatment: in vitro results induce caution for in vivo applications. 2010

Greco, Eliana / Basso, Daniela / Fadi, Elisa / Padoan, Andrea / Fogar, Paola / Zambon, Carlo-Federico / Navaglia, Filippo / Bozzato, Dania / Moz, Stefania / Pedrazzoli, Sergio / Plebani, Mario. ·Department of Laboratory Medicine, University of Padova, Padova, Italy. ·Pancreas · Pubmed #20562578.

ABSTRACT: OBJECTIVES: alpha-Tocopheryl succinate (alpha-TOS) is thought to be toxic only for cancer cells. We ascertained in vitro alpha-TOS effects on pancreatic cancer (PC) and normal cell growth and verified whether the combination of nontoxic alpha-TOS and 5-fluorouracil (5-FU) doses causes cancer cell death and whether alpha-TOS effects are mediated by the proapoptotic proteins Bax/Bak and/or SMAD4/DPC4 status. METHODS: Five PC cell lines, myoblasts, normal monocytes, wild-type (WT) and Bax/Bak double knockout mouse embryonic fibroblast (MEF) cells, and permanently SMAD4/DPC4-transfected PSN1 cells were cultured in 1% and 10% fetal calf serums (FCSs), without or with alpha-TOS (5-500 micromol/L). Nontoxic 5-FU (0.0001 mmol/L) and alpha-TOS alone or in combination were also evaluated. RESULTS: Only PSN1 PC cell line, which had SMAD4/DPC4 homozygous deletion, was sensitive to nontoxic alpha-TOS doses (5 micromol/L in 1% FCS and 50 micromol/L in 10% FCS). A 20-micromol/L alpha-TOS inhibited MEF-WT, not MEF-double knockout growth. Only PSN1 cells were sensitive to nontoxic 5-FU and alpha-TOS combination. SMAD4/DPC4 transfection restored PSN1 resistance to the effects of combined 5-FU and alpha-TOS effects. CONCLUSIONS: Only a minority of PC cells are sensitive to the antiproliferative effects of alpha-TOS, any sensitivity appearing to be correlated with SMAD4/DPC4 homozygous deletion and Bax/Bak expression.

20 Article Middle-preserving pancreatectomy: an interesting procedure for pancreas-sparing resection. 2010

Sperti, Cosimo / Polizzi, Maria Laura / Moro, Margherita / Beltrame, Valentina / Pedrazzoli, Sergio. ·Department of Medical and Surgical Sciences, University of Padua, Padua, Italy. csperti@libero.it ·JOP · Pubmed #20442523.

ABSTRACT: CONTEXT: Total pancreatectomy is the treatment of choice for multicentric diseases involving the head and the body-tail of the pancreas. Middle-preserving pancreatectomy is a recently reported alternative procedure when the pancreatic body is spared from disease. We report on the successful preservation of the pancreatic body in a patient harboring a multicentric intraductal papillary mucinous neoplasia (IPMN). CASE REPORT: A multicentric IPMN was diagnosed in a 59-year-old man. A standard pylorus preserving pancreaticoduodenectomy was performed, followed by a spleen-preserving distal pancreatectomy. The splenic vessels were carefully preserved. The residual 5 cm of the pancreatic body were anastomosed to the jejunum after verifying that the resection line on both sides was negative at frozen section examination. The postoperative course was complicated by transient peritoneal bleeding managed with angiographic embolization of the splenic artery. A borderline mixed type IPMN of the head and chronic pancreatitis of the tail were found at pathological examination. Eleven months after surgery, the patient is well and disease free; glycemic control is achieved by diet. CONCLUSION: A middle-preserving pancreatectomy can be performed safely for multicentric IPMNs involving the head and the body-tail of the gland. It can prevent problems with the glycemic control that usually follows total pancreatectomy.

21 Minor Adenosquamous carcinoma of the papilla of Vater: A phenotypic heterogeneity characterized by a common molecular landscape. 2018

Milanetto, Anna Caterina / Valbona, Liço / Alaggio, Rita / Munari, Giada / Pedrazzoli, Sergio / Fassan, Matteo / Pasquali, Claudio. ·Department of Surgery, Oncology and Gastroenterology (DiSCoG), Clinica Chirurgica I, University of Padua, Italy. · Department of Medicine, Surgical Pathology Unit, University of Padua, Italy. · Clinica Chirurgica IV, University of Padua, Italy. ·Pathol Int · Pubmed #30417956.

ABSTRACT: -- No abstract --

22 Minor Accuracy of CA 19-9 and radiologic imaging in detecting recurrence after resection for pancreatic cancer. 2013

Sperti, Cosimo / Beltrame, Valentina / Bissoli, Sergio / Pedrazzoli, Sergio. ·Third Surgical Clinic, Department of Surgery, Oncology and Gastroenterology, University of Padua. Padua, Italy. csperti@libero.it. ·JOP · Pubmed #24216562.

ABSTRACT: -- No abstract --

23 Minor Parenchyma-sparing resection for pancreatic neoplasms. 2010

Pedrazzoli, Sergio / Canton, Alen Silvio / Sperti, Cosimo / Pasquali, Claudio. · ·J Hepatobiliary Pancreat Sci · Pubmed #20454911.

ABSTRACT: -- No abstract --