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Pancreatic Neoplasms: HELP
Articles by Gianfranco Delle Fave
Based on 6 articles published since 2009
(Why 6 articles?)
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Between 2009 and 2019, G. Delle Fave wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Risk of pancreatic malignancy and mortality in branch-duct IPMNs undergoing surveillance: A systematic review and meta-analysis. 2016

Crippa, Stefano / Capurso, Gabriele / Cammà, Calogero / Fave, Gianfranco Delle / Castillo, Carlos Fernández-Del / Falconi, Massimo. ·Division of Pancreatic Surgery, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Italy. · Gastroenterology Unit, Internal Medicine Department, University of Palermo, Palermo, Italy. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA. · Division of Pancreatic Surgery, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Dig Liver Dis · Pubmed #26965783.

ABSTRACT: BACKGROUND: Safety of non-operative management for low-risk branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) is debated. AIM: To perform a systematic review/meta-analysis to determine their risk of developing pancreatic malignancy and of pancreatic malignancy-related deaths. METHODS: A MEDLINE search was performed and methodology was based on PRISMA statement. Incidence rates of overall pancreatic malignancy, malignant BD-IPMN, IPMN-distinct PDAC, and of pancreatic malignancy-related death rates were calculated by dividing the total number of events by the total number of person-years (pyrs) of follow-up. Heterogeneity was determined by I(2) statistic. RESULTS: 20 studies including 2177 patients were included. Mean follow-up ranged from 29.3 to 76.7 months. Overall, 82 patients (3.7%) developed a pancreatic malignancy with a pooled estimate rate of 0.007/pyrs (I(2)=32.8%). The pooled estimate rate of malignant IPMN was 0.004/pyrs (I(2)=40.8%), and the pooled estimate rate of distinct PDAC 0.002/pyrs (I(2)=0%). The rate of death due to pancreatic malignancy during follow-up was 0.9%, with an overall pooled estimate rate of death of 0.002/pyrs (I(2)=0%). CONCLUSION: Non-operative management of low-risk BD-IPMN is safe, with a very low risk of malignant transformation of IPMN and of distinct PDAC. The rate of pancreatic malignancy-related mortality is low, particularly when compared with the mortality of pancreatic surgery.

2 Article Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study. 2019

Campa, Daniele / Matarazzi, Martina / Greenhalf, William / Bijlsma, Maarten / Saum, Kai-Uwe / Pasquali, Claudio / van Laarhoven, Hanneke / Szentesi, Andrea / Federici, Francesca / Vodicka, Pavel / Funel, Niccola / Pezzilli, Raffaele / Bueno-de-Mesquita, H Bas / Vodickova, Ludmila / Basso, Daniela / Obazee, Ofure / Hackert, Thilo / Soucek, Pavel / Cuk, Katarina / Kaiser, Jörg / Sperti, Cosimo / Lovecek, Martin / Capurso, Gabriele / Mohelnikova-Duchonova, Beatrice / Khaw, Kay-Tee / König, Anna-Katharina / Kupcinskas, Juozas / Kaaks, Rudolf / Bambi, Franco / Archibugi, Livia / Mambrini, Andrea / Cavestro, Giulia Martina / Landi, Stefano / Hegyi, Péter / Izbicki, Jakob R / Gioffreda, Domenica / Zambon, Carlo Federico / Tavano, Francesca / Talar-Wojnarowska, Renata / Jamroziak, Krzysztof / Key, Timothy J / Fave, Gianfranco Delle / Strobel, Oliver / Jonaitis, Laimas / Andriulli, Angelo / Lawlor, Rita T / Pirozzi, Felice / Katzke, Verena / Valsuani, Chiara / Vashist, Yogesh K / Brenner, Hermann / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Pancreatic and Digestive Endocrine Surgery - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · First Department of Medicine, University of Szeged, Szeged, Hungary. · Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. · Department of Surgery, Unit of Experimental Surgical Pathology, University of Pisa, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department for 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, The 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 Laboratory Medicine, University-Hospital of Padova, Padua, Italy. · Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Third Surgical Clinic - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University, Rome, Italy. · PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy. · Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. · University of Cambridge School of Clinical Medicine Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. · MTA-SZTE Momentum Translational Gastroenterology Research Group, Szeged, Hungary. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · ARC-NET, University and Hospital Trust of Verona, Verona, Italy. · Division of Abdominal Surgery, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Int J Cancer · Pubmed #30325019.

ABSTRACT: Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10

3 Article Alternative polyadenylation of ZEB1 promotes its translation during genotoxic stress in pancreatic cancer cells. 2017

Passacantilli, Ilaria / Panzeri, Valentina / Bielli, Pamela / Farini, Donatella / Pilozzi, Emanuela / Fave, Gianfranco Delle / Capurso, Gabriele / Sette, Claudio. ·Department of Biomedicine and Prevention, Section of Anatomy, University of Rome 'Tor Vergata', Rome, Italy. · Department of science medical/chirurgic and translational medicine, University of Rome 'Sapienza', Rome, Italy. · Laboratory of Neuroembryology, Fondazione Santa Lucia IRCCS, Rome, Italy. ·Cell Death Dis · Pubmed #29120411.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extremely poor prognosis. The standard chemotherapeutic drug, gemcitabine, does not offer significant improvements for PDAC management due to the rapid acquisition of drug resistance by patients. Recent evidence indicates that epithelial-to-mesenchymal transition (EMT) of PDAC cells is strictly associated to early metastasization and resistance to chemotherapy. However, it is not exactly clear how EMT is related to drug resistance or how chemotherapy influences EMT. Herein, we found that ZEB1 is the only EMT-related transcription factor that clearly segregates mesenchymal and epithelial PDAC cell lines. Gemcitabine treatment caused upregulation of ZEB1 protein through post-transcriptional mechanisms in mesenchymal PDAC cells within a context of global inhibition of protein synthesis. The increase in ZEB1 protein correlates with alternative polyadenylation of the transcript, leading to shortening of the 3' untranslated region (UTR) and deletion of binding sites for repressive microRNAs. Polysome profiling indicated that shorter ZEB1 transcripts are specifically retained on the polysomes of PDAC cells during genotoxic stress, while most mRNAs, including longer ZEB1 transcripts, are depleted. Thus, our findings uncover a novel layer of ZEB1 regulation through 3'-end shortening of its transcript and selective association with polysomes under genotoxic stress, strongly suggesting that PDAC cells rely on upregulation of ZEB1 protein expression to withstand hostile environments.

4 Article The Neutrophil/Lymphocyte Ratio at Diagnosis Is Significantly Associated with Survival in Metastatic Pancreatic Cancer Patients. 2017

Piciucchi, Matteo / Stigliano, Serena / Archibugi, Livia / Zerboni, Giulia / Signoretti, Marianna / Barucca, Viola / Valente, Roberto / Fave, Gianfranco Delle / Capurso, Gabriele. ·Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology,"Sapienza" University of Rome, 00189 Rome, Italy. matteopiciucchi@libero.it. · Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology,"Sapienza" University of Rome, 00189 Rome, Italy. seri_stigliano@yahoo.it. · Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology,"Sapienza" University of Rome, 00189 Rome, Italy. livia.archibugi@hotmail.it. · Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology,"Sapienza" University of Rome, 00189 Rome, Italy. giulia.zerboni@gmail.com. · Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology,"Sapienza" University of Rome, 00189 Rome, Italy. mariannasignoretti@gmail.com. · Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology,"Sapienza" University of Rome, 00189 Rome, Italy. viola.barucca@gmail.com. · Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology,"Sapienza" University of Rome, 00189 Rome, Italy. robbie.valente@gmail.com. · Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology,"Sapienza" University of Rome, 00189 Rome, Italy. gianfranco.dellefave@gmail.com. · Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology,"Sapienza" University of Rome, 00189 Rome, Italy. gabriele.capurso@gmail.com. ·Int J Mol Sci · Pubmed #28353661.

ABSTRACT: Different inflammation-based scores such as the neutrophil/lymphocyte ratio (NLR), the Odonera Prognostic Nutritional Index (PNI), the Glasgow Prognostic Score, the platelet/lymphocyte ratio, and the C-reactive protein/albumin ratio have been found to be significantly associated with pancreatic cancer (PDAC) prognosis. However, most studies have investigated patients undergoing surgery, and few of them have compared these scores. We aimed at evaluating the association between inflammatory-based scores and PDAC prognosis. In a single center cohort study, inflammatory-based scores were assessed at diagnosis and their prognostic relevance as well as that of clinic-pathological variables were evaluated through multiple logistic regression and survival probability analysis. In 206 patients, age, male sex, tumor size, presence of distant metastasis, access to chemotherapy, and an NLR > 5 but not other scores were associated with overall survival (OS) at multivariate analysis. Patients with an NLR < 5 had a median survival of 12 months compared to 4 months in those with an NLR > 5. In the 81 patients with distant metastasis at diagnosis, an NLR > 5 resulted in the only variable significantly associated with survival. Among patients with metastatic disease who received chemotherapy, the median survival was 3 months in patients with an NLR > 5 and 7 months in those with an NLR < 5. The NLR might drive therapeutic options in PDAC patients, especially in the setting of metastatic disease.

5 Article Active Surveillance Beyond 5 Years Is Required for Presumed Branch-Duct Intraductal Papillary Mucinous Neoplasms Undergoing Non-Operative Management. 2017

Crippa, Stefano / Pezzilli, Raffaele / Bissolati, Massimiliano / Capurso, Gabriele / Romano, Luigi / Brunori, Maria Paola / Calculli, Lucia / Tamburrino, Domenico / Piccioli, Alessandra / Ruffo, Giacomo / Fave, Gianfranco Delle / Falconi, Massimo. ·Department of Surgery, Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy. · Pancreas Translational &Clinical Research Center, Division of Pancreatic Surgery, Università Vita-Salute, San Raffaele Scientific Institute, Milan, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Division of Transplant Surgery, San Raffaele Scientific Institute, Milan, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, University Sapienza, Rome, Italy. · Department of Radiology, Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy. · Division of Gastroenterology, Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy. · Department of Radiology, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Surgery, Università Politecnica delle Marche, Ancona, Italy. ·Am J Gastroenterol · Pubmed #28244498.

ABSTRACT: OBJECTIVES: To evaluate the results of active surveillance beyond 5 years in patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WF) and high-risk stigmata (HRS) undergoing non-operative management. METHODS: Patients with a minimum follow-up of 5 years who underwent surveillance with at least yearly magnetic resonance imaging were included. New onset of and predictors of WF/HRS during follow-up as well as long-term survival were analyzed. RESULTS: In all, 144 patients were followed for a median of 84 months. At diagnosis multifocal BD-IPMNs were found in 53% of cases and mean size of the largest cyst was 15.5 mm. Changes during follow-up were observed in 69 patients (48%). New onset of WF/HRS were observed in 26 patients (18%) but the rate of HRS was only 4%. WF and HRS developed after a median follow-up of 71 and 77.5 months from diagnosis, respectively, and without previous changes in 19/26 patients. Independent predictors of WF/HRS development were size at diagnosis>15 mm, increase in number of lesions, main pancreatic duct growth rate ≥0.2 mm/year, cyst growth rate >1 mm/year. Overall, the rate of pancreatic invasive malignancy was 2% and the 12-year disease-specific survival was 98.6%. CONCLUSIONS: Long-term nonoperative management is safe for BD-IPMNs without WF and HRS. Discontinuation of surveillance cannot be recommended since one out of six patients developed WF/HRS far beyond 5 years of surveillance and without previous relevant modifications. An intensification of follow-up should be considered after 5 years.

6 Article Modulation of PKM alternative splicing by PTBP1 promotes gemcitabine resistance in pancreatic cancer cells. 2016

Calabretta, S / Bielli, P / Passacantilli, I / Pilozzi, E / Fendrich, V / Capurso, G / Fave, G Delle / Sette, C. ·Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy. · Department of Science Medical/Chirurgic and Translational Medicine, University of Rome La Sapienza, Rome, Italy. · Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy. · Department of Clinic and Molecular Medicine, University of Rome La Sapienza, Rome, Italy. · Department of Surgery, Philipps-University Marburg, Marburg, Germany. ·Oncogene · Pubmed #26234680.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and incurable disease. Poor prognosis is due to multiple reasons, including acquisition of resistance to gemcitabine, the first-line chemotherapeutic approach. Thus, there is a strong need for novel therapies, targeting more directly the molecular aberrations of this disease. We found that chronic exposure of PDAC cells to gemcitabine selected a subpopulation of cells that are drug-resistant (DR-PDAC cells). Importantly, alternative splicing (AS) of the pyruvate kinase gene (PKM) was differentially modulated in DR-PDAC cells, resulting in promotion of the cancer-related PKM2 isoform, whose high expression also correlated with shorter recurrence-free survival in PDAC patients. Switching PKM splicing by antisense oligonucleotides to favor the alternative PKM1 variant rescued sensitivity of DR-PDAC cells to gemcitabine and cisplatin, suggesting that PKM2 expression is required to withstand drug-induced genotoxic stress. Mechanistically, upregulation of the polypyrimidine-tract binding protein (PTBP1), a key modulator of PKM splicing, correlated with PKM2 expression in DR-PDAC cell lines. PTBP1 was recruited more efficiently to PKM pre-mRNA in DR- than in parental PDAC cells. Accordingly, knockdown of PTBP1 in DR-PDAC cells reduced its recruitment to the PKM pre-mRNA, promoted splicing of the PKM1 variant and abolished drug resistance. Thus, chronic exposure to gemcitabine leads to upregulation of PTBP1 and modulation of PKM AS in PDAC cells, conferring resistance to the drug. These findings point to PKM2 and PTBP1 as new potential therapeutic targets to improve response of PDAC to chemotherapy.