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Pancreatic Neoplasms: HELP
Articles by Patrick Maisonneuve
Based on 34 articles published since 2010
(Why 34 articles?)
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Between 2010 and 2020, P. Maisonneuve wrote the following 34 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Familial pancreatic cancer in Italy. Risk assessment, screening programs and clinical approach: a position paper from the Italian Registry. 2010

Del Chiaro, Marco / Zerbi, Alessandro / Capurso, Gabriele / Zamboni, Giuseppe / Maisonneuve, Patrick / Presciuttini, Silvano / Arcidiacono, Paolo Giorgio / Calculli, Lucia / Falconi, Massimo / Anonymous7420665. ·Division of General and Transplant Surgery, Pisa University Hospital, Via Paradisa 2, 56124 Cisanello, Pisa, Italy. m.delchiaro@ao-pisa.toscana.it ·Dig Liver Dis · Pubmed #20627831.

ABSTRACT: In Italy, pancreatic cancer is the fifth leading cause of tumor related death with about 7000 new cases per year and a mortality rate of 95%. In a recent prospective epidemiological study on the Italian population, a family history was found in about 10% of patients suffering from a ductal adenocarcinoma of the pancreas (PDAC). A position paper from the Italian Registry for Familial Pancreatic Cancer was made to manage these high-risk individuals. Even though in the majority of high-risk individuals a genetic test to identify familial predisposition is not available, a screening protocol seems to be reasonable for subjects who have a >10-fold greater risk for the development of PDAC. However this kind of screening should be included in clinical trials, performed in centers with high expertise in pancreatic disease, using the least aggressive diagnostic modalities.

2 Editorial Can we prevent pancreatic disease? 2014

Lowenfels, Albert B / Maisonneuve, Patrick. ·Departments of Surgery and Family and Community Medicine, New York Medical College, Valhalla, New York. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. ·Clin Gastroenterol Hepatol · Pubmed #24607697.

ABSTRACT: -- No abstract --

3 Review Epidemiology and burden of pancreatic cancer. 2019

Maisonneuve, Patrick. ·Unit of Clinical Epidemiology, IEO, European Institute of Oncology IRCCS, Milan, Italy. Electronic address: patrick.maisonneuve@ieo.it. ·Presse Med · Pubmed #30878335.

ABSTRACT: Pancreatic cancer, although infrequent, has a very poor prognosis, making it currently the fourth common causes of cancer mortality in most developed countries including the European Union (EU). Its incidence varies across regions, which suggests that lifestyle factors play an important role in its etiology, although part of the variation could be ascribed to difference in diagnostic and coding practices. Because pancreatic cancer is strongly age-dependent, increasing population longevity and ageing will lead to an increase of the global burden of pancreatic cancer. It was estimated that, by 2040, the total number of cases in the EU will increase by more than 30%. Pancreatic cancer is a multifactorial disease and many risk factors have been identified. Hereditary factors are responsible for less than 10% of the cases while tobacco smoking and excess body weight, the two most important potentially modifiable risk factors, are responsible for 10 to 30% of the cases, affording a unique opportunity for preventing one of our deadliest cancers.

4 Review Systemic therapies in patients with advanced well-differentiated pancreatic neuroendocrine tumors (PanNETs): When cytoreduction is the aim. A critical review with meta-analysis. 2018

Pozzari, Marta / Maisonneuve, Patrick / Spada, Francesca / Berruti, Alfredo / Amoroso, Vito / Cella, Chiara Alessandra / Laffi, Alice / Pellicori, Stefania / Bertani, Emilio / Fazio, Nicola. ·Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy. · Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy. · Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia at ASST Spedali Civili, Brescia, Italy. · Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. · Division of Gastrointestinal Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy. · Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy. Electronic address: nicola.fazio@ieo.it. ·Cancer Treat Rev · Pubmed #30352319.

ABSTRACT: INTRODUCTION: Cytoreduction is sometimes an important aim of systemic anti-tumor therapies in well-differentiated pancreatic neuroendocrine tumors (PanNETs). As there is not a gold standard treatment for these tumors in this field, we conducted a literature review in order to identify objective criteria for treatment choice. MATERIALS AND METHODS: We critically reviewed and performed a meta-analysis of all published clinical studies of systemic therapies in patients with well-differentiated unresectable PanNETs, selecting only those articles which reported tumor shrinkage (TS) with a waterfall plot (WP). Tumor downsizing of ≥10% was considered as objective response. RESULTS: We selected 17 out of 2758 studies, comprising 1118 patients with tumor response reported as WP. Proliferation index, tumor burden and anti-tumor therapies were heterogeneous. Chemotherapy alone (mainly, capecitabine/temozolomide) or in combination showed the best results, with ≥10% TS ranging from 65% to 93%. Peptide receptor radionuclide therapy combined with chemotherapy (Chemo-PRRT) and sunitinib appeared promising by inducing objective response in a significant proportion of patients (93% and 60%, respectively). Time to tumor response was reported in only two trials. No clear clinical and/or biological predictive factors emerged. CONCLUSION: Based on response criteria used in our retrospective analysis, systemic chemotherapy alone or in combination appeared to have the main cytoreductive impact. However no conclusions regarding either a specific regimen or combination can be drawn. Furthermore, tumor population selection and/or choice of regimen may have a significant influence. Further analysis should be also conducted to identify potential predictive biomarkers of responses, in order to design future prospective interventional clinical trials enrolling more homogenous populations of advanced well-differentiated PanNETs.

5 Review Systematic review and meta-analysis of prognostic role of splenic vessels infiltration in resectable pancreatic cancer. 2018

Crippa, Stefano / Cirocchi, Roberto / Maisonneuve, Patrick / Partelli, Stefano / Pergolini, Ilaria / Tamburrino, Domenico / Aleotti, Francesca / Reni, Michele / Falconi, Massimo. ·Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy. · Department of General and Oncologic Surgery, University of Perugia, St. Maria Hospital, Terni, Italy. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · Department of Surgery, Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy. · Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; Department of Oncology, San Raffaele Scientific Institute, Milan, Italy. · Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Eur J Surg Oncol · Pubmed #29183639.

ABSTRACT: BACKGROUND: Identification of factors associated with dismal survival after surgery in resectable pancreatic ductal adenocarcinoma is important to select patients for neoadjuvant treatment. The present meta-analysis aimed to compare the results of distal pancreatectomy for resectable adenocarcinoma of the pancreatic body-tail with and without splenic vessels infiltration. METHODS: A systematic search was performed of PubMed, Embase and the Cochrane Library in accordance with PRISMA guidelines. The inclusion criteria were studies including patients who underwent distal pancreatectomy for pancreatic cancer with or without splenic vessels infiltration. 5-year overall survival (OS) was the primary outcomes. Meta-analysis was carried out applying time-to-event method. RESULTS: Six articles with 423 patients were analysed. Patients with pathological splenic artery invasion had a worse survival compared with those without infiltration (Hazard ratio 1.76, 95% CI 1.36-2.28; P < 0.0001). A similar results was found when considering pathological splenic vessels infiltration, showing that survival was significantly poorer when splenic vein infiltration was present (Hazard ratio 1.51, 95% CI 1.19-1.93; P = 0.0009). CONCLUSIONS: This meta-analysis showed worse survival for patients with splenic vessels infiltration undergoing distal pancreatectomy for pancreatic cancer. Splenic vessels infiltration represents the stigmata of a more aggressive disease, although resectable.

6 Review Periodontal disease, edentulism, and pancreatic cancer: a meta-analysis. 2017

Maisonneuve, P / Amar, S / Lowenfels, A B. ·Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · Department of Chemistry & Biochemistry, Florida Atlantic University, Jupiter, FL, USA. · Department of Surgery and Department of Community and Preventive Medicine, New York Medical College, Valhalla, NY, USA. · Department of Family Medicine, New York Medical College, Valhalla, USA. ·Ann Oncol · Pubmed #28453689.

ABSTRACT: Background: Periodontal disease (PD), now our commonest infectious disorder leads to tooth loss, and has been linked to various systemic diseases, including various types of cancer. The aim of this study is to provide a systematic review and a meta-analysis of the relationship between PD, edentulism, and pancreatic cancer (PC). Patients and methods: From an initial review of 327 references we selected eight studies concerning periodontitis or edentulism with sufficient quantitative information to allow us to examine the risk of PC. We used relative risks (RRs), hazard ratios, or odds ratios to measure the association between periodontitis, edentulism, and PC. We employed random effects models to obtain summary risks, and we also provide measures of study differences and possible biases. Results: The summary RR for periodontitis and PC was 1.74 [95% confidence interval (CI) 1.41-2.15] and 1.54 for edentulism (95% CI 1.16-2.05). There was no evidence of heterogeneity for either variable, and no evidence of publication bias. The studies included reports from three continents, suggesting that the association is generalizable. Most of the studies were adjusted for variables thought to be associated with PC, such as gender, smoking, BMI, diabetes, and alcohol. Conclusions: Using meta-analysis, both periodontitis and edentulism appear to be associated with PC, even after adjusting for common risk factors. As yet, the mechanisms linking oral disease and PC are uncertain, but could be related to changes in the oral microbiome-an area of current research.

7 Review Increased incidence of extrapancreatic neoplasms in patients with IPMN: Fact or fiction? A critical systematic review. 2015

Pugliese, Luigi / Keskin, Muharrem / Maisonneuve, Patrick / D'Haese, Jan G / Marchegiani, Giovanni / Wenzel, Patrick / Del Chiaro, Marco / Ceyhan, Güralp O. ·Unit of General Surgery 2, Department of Surgery, IRCCS Policlinico San Matteo, Pavia, Italy. · Division of Gastroenterology, Department of Internal Medicine, Ege University, Izmir, Turkey. · Division of Epidemiology and Statistics, European Institute of Oncology, Milan, Italy. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy. · Department of Gastroenterology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Division of Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. Electronic address: gueralp.ceyhan@tum.de. ·Pancreatology · Pubmed #25841270.

ABSTRACT: BACKGROUND: To identify potential associations between intraductal papillary mucinous neoplasm of the pancreas (IPMN) and extrapancreatic neoplasms (EPN), a systematic review of the literature has been performed. METHODS: A systematic search of Medline/Pubmed was performed according to the PRISMA guidelines for reporting systematic reviews and meta-analysis for the following search terms: "extrapancreatic", "non pancreatic", "additional pancreatic", "additional primary" and alternatively matched with "neoplasms/tumours/cancers/malignancies/lesions". The results obtained specifically for IPMN were examined one by one by two independent investigators for further data selection and extraction. RESULTS: Fifteen studies were identified to be suitable and included for systematic review. Fourteen reported an elevated risk for extrapancreatic malignancy, particularly gastric and colon cancer, while the largest and only prospective study did not find any association. Most studies were retrospective with a weak level of evidence that was not substantially enhanced even by a recent multicentre case series. CONCLUSIONS: The available data on this clinically relevant question remain inconclusive. Due to lacking evidence on extrapancreatic neoplasms in IPMN patients, only a standard surveillance can be advised.

8 Review Diabetes, smoking, alcohol use, and family history of cancer as risk factors for pancreatic neuroendocrine tumors: a systematic review and meta-analysis. 2015

Haugvik, Sven-Petter / Hedenström, Per / Korsæth, Emilie / Valente, Roberto / Hayes, Alastair / Siuka, Darko / Maisonneuve, Patrick / Gladhaug, Ivar Prydz / Lindkvist, Björn / Capurso, Gabriele. ·Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway. ·Neuroendocrinology · Pubmed #25613442.

ABSTRACT: BACKGROUND AND AIMS: Risk factors for pancreatic neuroendocrine tumors (PNETs) are not well understood. The aim of this systematic review was to assess if diabetes mellitus, smoking, alcohol use, and family history of cancer are risk factors for PNETs. METHODS: MEDLINE and abstracts from the European and North American Neuroendocrine Tumor Societies (ENETS and NANETS) were searched for studies published until October 2013. Eligible studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Five studies evaluating 4 individual populations were included (study accrual period 2000-2011) into the meta-analysis, involving 827 cases (range 160-309 per study) and 2,407 controls (range 233-924 per study). All studies had a case-control design and described regional series. The pooled adjusted odds ratio was 2.74 (95% CI: 1.63-4.62; p < 0.01; I(2) = 60.4%) for history of diabetes, 1.21 (95% CI: 0.92-1.58; p = 0.18; I(2) = 45.8%) for ever smoking, 1.37 (95% CI: 0.99-1.91; p = 0.06; I(2) = 0.0%) for heavy smoking, 1.09 (95% CI: 0.64-1.85; p = 0.75; I(2) = 85.2%) for ever alcohol use, 2.72 (95% CI: 1.25-5.91; p = 0.01; I(2) = 57.8%) for heavy alcohol use, and 2.16 (95% CI: 1.64-2.85; p < 0.01; I(2) = 0.0%) for first-degree family history of cancer. CONCLUSIONS: Diabetes mellitus and first-degree family history of cancer are associated with an increased risk of sporadic PNET. There was also a trend for diagnosis of sporadic PNET associated with heavy smoking. Alcohol use may be a risk factor for PNET, but there was considerable heterogeneity in the meta-analysis. These results suggest the need for a larger, homogeneous, international study for the clarification of risk factors for the occurrence of PNET.

9 Review Risk factors for pancreatic cancer: a summary review of meta-analytical studies. 2015

Maisonneuve, Patrick / Lowenfels, Albert B. ·Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy and Departments of Surgery and of Family and Preventive Medicine, New York Medical College, Valhalla, NY, USA patrick.maisonneuve@ieo.it. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy and Departments of Surgery and of Family and Preventive Medicine, New York Medical College, Valhalla, NY, USA. ·Int J Epidemiol · Pubmed #25502106.

ABSTRACT: BACKGROUND: The aetiology of pancreatic cancer (PC) has been extensively studied and is the subject of numerous meta-analyses and pooled analyses. We have summarized results from these pooled and meta-analytical studies to estimate the fraction of PCs attributable to each of the identified risk factors. METHODS: Using a comprehensive strategy, we retrieved 117 meta-analytical or pooled reports dealing with the association between specific risk factors and PC risk. We combined estimates of relative risk and estimates of exposure to calculate the fraction of PCs caused or prevented by a particular exposure. RESULTS: Tobacco smoking ('strong' evidence) and Helicobacter pylori infection ('moderate' evidence) are the major risk factors associated with PC, with respective estimated population attributable fractions of 11-32% and 4-25%. The major protective factors are history of allergy ('strong' evidence) and increasing fruit or folate intake ('moderate' evidence), with respective population preventable fractions of 3-7% and 0-12%. CONCLUSIONS: We summarized results of 117 meta-analytical or pooled data reports dealing with 37 aetiological exposures, to obtain robust information about the suspected causes of PC. By combining these estimates with their prevalences in the population, we calculated population attributable or population preventable fractions. About two-thirds of the major risk factors associated with PC are potentially modifiable, affording a unique opportunity for preventing one of our deadliest cancers.

10 Review Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. 2012

Andriulli, Angelo / Festa, Virginia / Botteri, Edoardo / Valvano, Maria R / Koch, Maurizio / Bassi, Claudio / Maisonneuve, Patrick / Sebastiano, Pierluigi Di. ·Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo, Italy. ·Ann Surg Oncol · Pubmed #22012027.

ABSTRACT: BACKGROUND: Long-term prognosis for localized pancreatic cancer remains poor. We sought to assess the benefit of neoadjuvant/preoperative chemotherapy with or without radiotherapy. METHODS: Prospective studies where gemcitabine with or without radiotherapy was provided before surgery in patients with initially resectable or unresectable disease were reviewed by meta-analysis. Primary outcome was survival, and secondary outcomes were tumor response after therapy, toxicity, surgical exploration, and resection rates. RESULTS: Twenty independent studies with 707 participants were included, 366 with resectable lesions and 341 with unresectable lesions. Seven studies were phase I/II trials, 10 phase II, and 3 prospective cohort studies. Estimated 1- and 2-year survival probabilities after resection were 91.7% (95% confidence interval [CI] 75-100) and 67.2% (95% CI 38-87) for initially resectable patients, and 86.3% (95% CI 78-100) and 54.2% (95% CI 25-100) for initially unresectable patients. The complete/partial response rate was 12% (95% CI 4-23) and 27% (95% CI 18-38) in resectable and unresectable lesions, respectively. The rate of treatment-related grade 3-4 toxicity was 31% (95% CI 21-42). Of resectable patients evaluable after restaging, 91% (95% CI 83-97) underwent surgery, and 82% (95% CI 65-95) of explored patients underwent resection. R0 resections amounted to 89% (95% CI 83-94). Of unresectable patients evaluable after restaging, 39% (95% CI 28-50) underwent surgery, and 68% (95% CI 53-82) of explored patients were resected, with 60% (95% CI 50-71) R0 resections. CONCLUSIONS: Current analysis provides marginal support to the assumed benefits of neoadjuvant therapies for patients with resectable cancer, and indicates a potential advantage only for a minority of those with unresectable lesions.

11 Review Epidemiology of pancreatic cancer: an update. 2010

Maisonneuve, Patrick / Lowenfels, Albert B. ·Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. patrick.maisonneuve@ieo.it ·Dig Dis · Pubmed #21088417.

ABSTRACT: Pancreatic cancer, although infrequent, has a very poor prognosis, making it one of the 4 or 5 most common causes of cancer mortality in developed countries. Its incidence varies greatly across regions, which suggests that lifestyle factors such as diet, and environmental factors, such as vitamin D exposure, play a role. Because pancreatic cancer is strongly age-dependent, increasing population longevity and ageing will lead to an increase of the global burden of pancreatic cancer in the coming decades. Smoking is the most common known risk factor, causing 20-25% of all pancreatic tumors. Although a common cause of pancreatitis, heavy alcohol intake is associated only with a modest increased risk of pancreatic cancer. While viruses do not represent a major risk factor, people infected with Helicobacter pylori appeared to be at high risk of pancreatic cancer. Many factors associated with the metabolic syndrome, including overweight and obesity, impaired glucose tolerance, and long-standing diabetes also increase the risk disease, while atopic allergy and use of metformin as a treatment for diabetes have been associated with a reduced risk of pancreatic cancer. A family history of pancreatic cancer is associated with an increased risk of pancreatic cancer and it is estimated that 5-10% of patients with pancreatic cancer have an underlying germline disorder. Having a non-O blood group, another inherited characteristic, has also been steadily associated with an increased risk of pancreatic cancer. While many risk factors for pancreatic cancer are not modifiable, adopting a healthy lifestyle could substantially reduce pancreatic cancer risk.

12 Review ABO blood group and cancer. 2010

Iodice, Simona / Maisonneuve, Patrick / Botteri, Edoardo / Sandri, Maria Teresa / Lowenfels, Albert B. ·Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. simona.iodice@ieo.it ·Eur J Cancer · Pubmed #20833034.

ABSTRACT: BACKGROUND: ABO blood type has been associated with various malignancies, including pancreatic cancer. Our aim was to study this association using data from a hospital-based tumour registry. METHODS: From the tumour registry, we retrieved data from 15,359 cancer patients treated during 2000-2003 at the European Institute of Oncology (Milan, Italy), with defined ABO blood type. We performed a case-control analysis, comparing the distribution of ABO blood types of patients with each specific form of cancer against that of patients with other forms of cancer. We also reviewed the literature and performed a meta-analysis on the association between ABO blood group and pancreatic cancer. RESULTS: We observed a significantly lower frequency of blood type O in patients with exocrine pancreatic cancer compared to patients with other forms of cancer (29% versus 44%; P<0.001; odds ratio (OR), 0.53; 95% confidence intervals (CI), 0.33-0.83). This association was confirmed by the meta-analysis of seven prior studies (summary relative risk, 0.79; 95% CI, 0.70-0.90). No association was found for endocrine pancreatic cancer or for cancer originating in other organs. CONCLUSIONS: Our data suggest that the association between ABO blood group and cancer is limited to exocrine pancreas malignancy.

13 Review Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. 2010

Raimondi, Sara / Lowenfels, Albert B / Morselli-Labate, Antonio M / Maisonneuve, Patrick / Pezzilli, Raffaele. ·European Institute of Oncology, Milan, Italy. ·Best Pract Res Clin Gastroenterol · Pubmed #20510834.

ABSTRACT: Acute pancreatitis, chronic pancreatitis and pancreatic cancer are responsible for most of the burden of exocrine pancreatic disease. Glandular damage from recurrent bouts of acute pancreatitis can lead to irreversible changes characteristic of chronic pancreatitis. In recent decades accumulating evidence has defined longstanding pre-existing chronic pancreatitis as a strong risk factor for pancreatic cancer. The lag period between diagnosis of chronic pancreatitis and pancreatic cancer is usually one or two decades: pancreatitis appearing a year or two before the diagnosis of pancreatic cancer is often the result of tumour-related ductal obstruction. The risk of developing pancreatic cancer appears to be highest in rare types of pancreatitis with an early onset, such as hereditary pancreatitis and tropical pancreatitis. Even though there is a strong link between chronic pancreatitis and pancreatic cancer, over a 20 year period only around five percent of patients with chronic pancreatitis will develop pancreatic cancer. Until the development of more sophisticated screening procedures, screening is not recommended for patients with chronic pancreatitis.

14 Article Stromal Features of the Primary Tumor Are Not Prognostic in Genetically Engineered Mice of Pancreatic Cancer. 2019

Hasselluhn, Marie C / Klein, Lukas / Patzak, Melanie S / Buchholz, Sören M / Ströbel, Philipp / Ellenrieder, Volker / Maisonneuve, Patrick / Neesse, Albrecht. ·Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center, 37075 Göttingen, Germany. · Institute of Pathology, University Medical Center, 37075 Göttingen, Germany. · Division of Epidemiology and Biostatistics, IEO Istituto Europeo di Oncologia IRCCS, P.I. 08691440153 Milan, Italy. ·Cells · Pubmed #31878349.

ABSTRACT: The Kras

15 Article Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe. 2019

Javed, Muhammad Ahsan / Beyer, Georg / Le, Nha / Vinci, Alessio / Wong, Helen / Palmer, Daniel / Morgan, Robert D / Lamarca, Angela / Hubner, Richard A / Valle, Juan W / Alam, Salma / Chowdhury, Sumsur / Ma, Yuk Ting / Archibugi, Livia / Capurso, Gabriele / Maisonneuve, Patrick / Neesse, Albrecht / Sund, Malin / Schober, Marvin / Krug, Sebastian. ·NIHR Liverpool Pancreas Biomedical Research Unit, Institute of Translational Medicine, Royal Liverpool University Hospital, United Kingdom. · Department of Medicine A, University Medicine Greifswald, Greifswald, Germany; Medical Department II, University Hospital, LMU, Munich, Germany. · Gastroenterology Division, Second Internal Medicine Department, Semmelweis University, Budapest, Hungary. · University of Pavia, Department of Surgery, S. Matteo University Hospital Foundation, Pavia, Italy. · Department of Quality and Information Intelligence, The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom. · Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom. · Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom. · Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom; Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom. · Department of Hepatobiliary Oncology, New Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. · Digestive and Liver Disease Unit, S. Andrea Hospital, University Sapienza, Rome, Italy. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · University Medical Centre Göttingen, Department of Gastroenterology and Gastrointestinal Oncology, Göttingen, Germany. · University of Umea, Department of Surgical and Perioperative Sciences, Umea, Sweden. Electronic address: malin.sund@surgery.umu.se. · Department of Gastroenterology and Hepatology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. ·Pancreatology · Pubmed #30529068.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe. METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors. RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis. CONCLUSION: Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.

16 Article Ki-67 and presence of liver metastases identify different progression-risk classes in pancreatic neuroendocrine neoplasms (pNEN) undergoing resection. 2019

Milione, Massimo / Maisonneuve, Patrick / Pellegrinelli, Alessio / Spaggiari, Paola / Centonze, Giovanni / Coppa, Jorgelina / Delconte, Gabriele / Droz Dit Busset, Michele / Lanhazo, Oleksandra / Pruneri, Giancarlo / Mazzaferro, Vincenzo. ·Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. · Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy. · Department of Pathology, Cancer Center Humanitas Research Hospital, Rozzano Milan, Italy. · Surgery and Neuroendocrine Tumor Group, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. · Endoscopy, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. · Surgery and Neuroendocrine Tumor Group, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. Electronic address: michele.drozditbusset@istitutotumori.mi.it. · Department of Surgery, Transcarpathian Regional Hospital, Užhorod, Ukraine. · Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; University of Milan, School of Medicine, Italy. · Surgery and Neuroendocrine Tumor Group, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; University of Milan, School of Medicine, Italy. ·Eur J Surg Oncol · Pubmed #30366875.

ABSTRACT: In pancreatic neuroendocrine neoplasms (pNEN), size ≤2 cm and Ki-67 < 3% suggest indolent behavior, but no factor alone predicts prognosis. We investigated factors predictive of tumor progression in 80 pNENs surgically resected in a single Institution from 1995 to 2015. At multivariable analysis the only two independent variables related to PFS were Ki-67 (HR 2.97; 95%CI 1.26-7.02) and presence of synchronous liver metastases (HR 3.60; 95%CI 1.70-7.61). Using Ki-67 < 3% and M0 as reference, the HR for tumor progression was 3.21 (95%CI 1.18-8.74) for M0 patients with Ki-67 3-20%, 5.06 (2.29-11.2) for M1 patients with Ki-67 ≤ 20% and 24.3 (6.64-89.2) for those with Ki-67 > 20%. Tumor size (≤2 vs. >2 cm) was not a predictive factor at any analysis. Intra-class correlation of Ki-67 values on pre-surgical biopsies vs. surgical specimens was 0.99 and Ki-67 classes were correctly identified in 97% of biopsies. Ki-67 and presence of liver metastases are the major prognostic factors in pNEN and identify different progression risks regardless of tumor size. Pre-surgical pNEN biopsy for Ki-67 assessment should be included in the evaluation of patients with 1-2 cm tumors to help in the decision on whether to perform surgical resection.

17 Article Risk of malignancy in resected pancreatic mucinous cystic neoplasms. 2018

Keane, M G / Shamali, A / Nilsson, L N / Antila, A / Millastre Bocos, J / Marijinissen Van Zanten, M / Verdejo Gil, C / Maisonneuve, P / Vaalavuo, Y / Hoskins, T / Robinson, S / Ceyhan, G O / Abu Hilal, M / Pereira, S P / Laukkarinen, J / Del Chiaro, M. ·Institute for Liver and Digestive Health, University College London, London. · Department of Surgery, Southampton University Hospital, Southampton, UK. · Department of Surgery, Karolinska University Hospital, Stockholm, Sweden. · Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland. · Department of Gastroenterology, Miguel Servet University Hospital, Zaragoza, Spain. · Department of Pathology, Nijmegen University Hospital, Nijmegen, The Netherlands. · Department of Gastroenterology, Ciudad Real University Hospital, Ciudad Real, Spain. · European Institute of Oncology, Milan, Italy. · Department of Hepato-Pancreato-Biliary Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Surgical Clinic, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. ·Br J Surg · Pubmed #29488646.

ABSTRACT: BACKGROUND: Pancreatic mucinous cystic neoplasms (MCNs) are rare mucin-producing cystic tumours defined by the presence of ovarian-type stroma. MCNs have a malignant potential and thus surgery is frequently performed. The aim of this cohort study was to define better the criteria for surgical resection in patients with MCN. METHODS: This multicentre retrospective study included all resected MCNs between 2003 and 2015 in participating centres. Lesions without ovarian-type stroma were excluded. Patient characteristics, preoperative findings, histopathology findings and follow-up data were recorded. RESULTS: The study included 211 patients; their median age was 53 (range 18-82) years, and 202 (95·7 per cent) were women. Median preoperative tumour size was 55 (range 12-230) mm. Thirty-four of the 211 (16·1 per cent) were malignant, and high-grade dysplasia (HGD) was found in a further 13 (6·2 per cent). One-third of MCNs in men were associated with invasive cancer, compared with 15·3 per cent in women. Five cases of malignant transformation occurred in MCNs smaller than 4 cm. All cases of malignancy or HGD were associated with symptoms or features of concern on preoperative cross-sectional imaging. In multivariable analysis, raised carbohydrate antigen 19-9 (odds ratio (OR) 10·54, 95 per cent c.i. 2·85 to 218·23; P < 0·001), tumour size (OR 4·23, 3·02 to 11·03; P = 0·001), mural nodules (OR 3·55, 1·31 to 20·55; P = 0·002) and weight loss (OR 3·40, 2·34 to 12·34; P = 0·034) were independent factors predictive of malignant transformation. CONCLUSIONS: Small indeterminate MCNs with no symptoms or features of concern may safely be observed as they have a low risk of malignant transformation.

18 Article Exclusive and Combined Use of Statins and Aspirin and the Risk of Pancreatic Cancer: a Case-Control Study. 2017

Archibugi, Livia / Piciucchi, Matteo / Stigliano, Serena / Valente, Roberto / Zerboni, Giulia / Barucca, Viola / Milella, Michele / Maisonneuve, Patrick / Delle Fave, Gianfranco / Capurso, Gabriele. ·Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. · Medical Oncology Unit, Istituto Nazionale Tumori Regina Elena (IFO), Rome, Italy. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. gabriele.capurso@gmail.com. ·Sci Rep · Pubmed #29026148.

ABSTRACT: Data on the association between aspirin and statin use and Pancreatic Ductal AdenoCarcinoma (PDAC) risk are conflicting. These drugs are often co-prescribed, but no studies evaluated the potential combined or confounding effect of the two at the same time. We aimed to investigate the association between aspirin and statin exclusive and combined use and PDAC occurrence. Data on environmental factors, family and medical history were screened in a case-control study. PDAC cases were matched to controls for age and gender. Power calculation performed ahead. Odds ratios (OR) and 95% confidence intervals(CI) were obtained from multivariable logistic regression analysis. In 408 PDAC patients and 816 matched controls, overall statin (OR 0.61; 95%CI,0.43-0.88), but not aspirin use was associated to reduced PDAC risk. Compared to non-users, exclusive statin (OR 0.51; 95%CI,0.32-0.80) and exclusive aspirin users (OR 0.64; 95%CI,0.40-1.01) had reduced PDAC risk. Concomitant statin and aspirin use did not further reduce the risk compared with statin use alone and no interaction was evident. Statin protective association was dose-dependent, and consistent in most subgroups, being stronger in smokers, elderly, obese and non-diabetic patients. The present study suggests that statin use is associated to reduced PDAC risk, supporting a chemopreventive action of statins on PDAC.

19 Article Risk and protective factors for the occurrence of sporadic pancreatic endocrine neoplasms. 2017

Valente, Roberto / Hayes, Alastair J / Haugvik, Sven-Petter / Hedenström, Per / Siuka, Darko / Korsæth, Emilie / Kämmerer, Daniel / Robinson, Stuart M / Maisonneuve, Patrick / Delle Fave, Gianfranco / Lindkvist, Bjorn / Capurso, Gabriele. ·Digestive and Liver Disease UnitSant' Andrea Hospital, Sapienza University of Rome, Rome, Italy. · Department of General SurgeryRoyal Infirmary of Edinburgh, Edinburgh, UK. · Department of Hepato-Pancreato-Biliary SurgeryOslo University Hospital, Oslo, Norway. · Unit of GastroenterologyDepartment of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. · Department of GastroenterologyUniversity Medical Centre Ljubljana, Ljubljana, Slovenia. · Department of General and Visceral SurgeryZentralklinik Bad Berka, Bad Berka, Germany. · Department of Hepatopancreatobiliary and Transplantation SurgeryThe Freeman Hospital, Newcastle upon Tyne, UK. · Division of Epidemiology and BiostatisticsEuropean Institute of Oncology, Milan, Italy. · Digestive and Liver Disease UnitSant' Andrea Hospital, Sapienza University of Rome, Rome, Italy gabriele.capurso@gmail.com. ·Endocr Relat Cancer · Pubmed #28566532.

ABSTRACT: Pancreatic neuroendocrine neoplasms (PNENs) represent 10% of all pancreatic tumors by prevalence. Their incidence has reportedly increased over recent decades in parallel with that of pancreatic adenocarcinoma. PNENs are relatively rare, and of the few institutions that have published potential risk factors, findings have been heterogeneous. Our objective was to investigate the association between potential risk and protective factors for the occurrence of sporadic PNENs across a European population from several institutions. A multinational European case-control study was conducted to examine the association of selected environmental, family and medical exposure factors using a standardized questionnaire in face-to-face interviews. A ratio of 1:3 cases to controls were sex and age matched at each study site. Adjusted univariate and multivariate logistic regression analysis were performed for statistically significant factors. The following results were obtained: In 201 cases and 603 controls, non-recent onset diabetes (OR 2.09, CI 1.27-3.46) was associated with an increased occurrence of PNENs. The prevalence of non-recent onset diabetes was higher both in cases with metastatic disease (TNM stage III-IV) or advanced grade (G3) at the time of diagnosis. The use of metformin in combination with insulin was also associated with a more aggressive phenotype. Drinking coffee was more frequent in cases with localized disease at diagnosis. Our study concluded that non-recent onset diabetes was associated with an increased occurrence of PNENs and the combination of metformin and insulin was consistent with a more aggressive PNEN phenotype. In contrast to previous studies, smoking, alcohol and first-degree family history of cancer were not associated with PNEN occurrence.

20 Article 3rd St. Gallen EORTC Gastrointestinal Cancer Conference: Consensus recommendations on controversial issues in the primary treatment of pancreatic cancer. 2017

Lutz, Manfred P / Zalcberg, John R / Ducreux, Michel / Aust, Daniela / Bruno, Marco J / Büchler, Markus W / Delpero, Jean-Robert / Gloor, Beat / Glynne-Jones, Rob / Hartwig, Werner / Huguet, Florence / Laurent-Puig, Pierre / Lordick, Florian / Maisonneuve, Patrick / Mayerle, Julia / Martignoni, Marc / Neoptolemos, John / Rhim, Andrew D / Schmied, Bruno M / Seufferlein, Thomas / Werner, Jens / van Laethem, Jean-Luc / Otto, Florian. ·CaritasKlinikum St. Theresia, Saarbrücken, Germany. Electronic address: m.lutz@caritasklinikum.de. · Department of Epidemiology and Preventive Medicine, School of Public Health, Monash University, The Alfred Centre, Melbourne, Australia. · Institut Gustave Roussy, Villejuif, France. · Department of Pathology, Universitätsklinikum Carl Gustav Carus, Dresden, Germany. · Department of Gastroenterology & Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, The Netherlands. · Chirurgische Universitätsklinik, Heidelberg, Germany. · Department of Surgery, Institut Paoli Calmettes, Marseille, France. · Klinik für Viszerale und Transplantationschirurgie, Inselspital, Bern, Switzerland. · Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK. · Department of General, Visceral and Transplantation Surgery, Klinikum der Universität München, Munich, Germany. · Radiooncology Service, Hôpital Tenon (Hôpitaux Universitaires Est Parisien), Paris Cedex 20, France. · Université René Descartes, UFR Biomédicale des Saints-Pères, Paris, France. · University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Germany. · Istituto Europeo di Oncologia, Divisione di Epidemiologia e Biostatistica, Milan, Italy. · Klinik und Poliklinik für Innere Medizin A, Universitätsmedizin, Greifswald, Germany; Medizinische Klinik und Poliklinik II, Klinikum der Universität München, Munich, Germany. · Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, TU München, Munich, Germany. · Department of Surgery, Liverpool University, Liverpool, UK. · University of Michigan, Ann Arbor, MI, USA. · Klinik für Chirurgie, Kantonsspital St. Gallen, St. Gallen, Switzerland. · Department of Internal Medicine I, Ulm University, Ulm, Germany. · Hopital Erasme, Anderlecht, Belgium. · Tumor- und Brustzentrum ZeTuP, St. Gallen, Switzerland. ·Eur J Cancer · Pubmed #28460245.

ABSTRACT: The primary treatment of pancreatic cancer was the topic of the 3rd St. Gallen Conference 2016. A multidisciplinary panel reviewed the current evidence and discussed controversial issues in a moderated consensus session. Here we report on the key expert recommendations. It was generally accepted that radical surgical resection followed by adjuvant chemotherapy offers the only evidence-based treatment with a chance for cure. Initial staging should classify localised tumours as resectable or unresectable (i.e. locally advanced pancreatic cancer) although there remains a large grey-zone of potentially resectable disease between these two categories which has recently been named as borderline resectable, a concept which was generally accepted by the panel members. However, the definition of these borderline-resectable (BR) tumours varies between classifications due to their focus on either (i) technical hurdles (e.g. the feasibility of vascular resection) or (ii) oncological outcome (e.g. predicting the risk of a R1 resection and/or occult metastases). The resulting expert discussion focussed on imaging standards as well as the value of pretherapeutic laparoscopy. Indications for biliary drainage were seen especially before neoadjuvant therapy. Following standard resection, the panel unanimously voted for the use of adjuvant chemotherapy after R0 resection and considered it as a reasonable standard of care after R1 resection, even though the optimal pathologic evaluation and the definition of R0/R1 was the issue of an ongoing debate. The general concept of BR tumours was considered as a good basis to select patients for preoperative therapy, albeit its current impact on the therapeutic strategy was far less clear. Main focus of the conference was to discuss the limits of surgical resection and to identify ways to standardise procedures and to improve curative outcome, including adjuvant and perioperative treatment.

21 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.

22 Article Risk Factors for Early-Onset and Very-Early-Onset Pancreatic Adenocarcinoma: A Pancreatic Cancer Case-Control Consortium (PanC4) Analysis. 2016

McWilliams, Robert R / Maisonneuve, Patrick / Bamlet, William R / Petersen, Gloria M / Li, Donghui / Risch, Harvey A / Yu, Herbert / Fontham, Elizabeth T H / Luckett, Brian / Bosetti, Cristina / Negri, Eva / La Vecchia, Carlo / Talamini, Renato / Bueno de Mesquita, H Bas / Bracci, Paige / Gallinger, Steven / Neale, Rachel E / Lowenfels, Albert B. ·From the *Department of Oncology, Mayo Clinic, Rochester, MN; †Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy; ‡Division of Biostatistics, Mayo Clinic; §Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ∥Department of Gastrointestinal Medical Oncology, UT MD Anderson Cancer Center, Houston, TX; ¶Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT; #Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI; **Louisiana State University School of Public Health, New Orleans, LA; ††Tulane School of Public Health, New Orleans, LA; ‡‡Department of Epidemiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," and §§Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; ∥∥S.O.C. Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy; ¶¶National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; School of Public Health, Imperial College London, London, United Kingdom; ##Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA; ***Division of General Surgery, University of Toronto, Toronto, Ontario, Canada; †††Cancer and Population Studies Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia; and ‡‡‡Department of Surgery, Department of Family Medicine, New York Medical College, Valhalla, NY. ·Pancreas · Pubmed #26646264.

ABSTRACT: OBJECTIVES: While pancreatic cancer (PC) most often affects older adults, to date, there has been no comprehensive assessment of risk factors among PC patients younger than 60 years. METHODS: We defined early-onset PC (EOPC) and very-early-onset PC (VEOPC) as diagnosis of PC in patients younger than 60 and 45 years, respectively. We pooled data from 8 case-control studies, including 1954 patients with EOPC and 3278 age- and sex-matched control subjects. Logistic regression analysis was performed to identify associations with EOPC and VEOPC. RESULTS: Family history of PC, diabetes mellitus, smoking, obesity, and pancreatitis were associated with EOPC. Alcohol use equal to or greater than 26 g daily also was associated with increased risk of EOPC (odds ratio, 1.49; 95% confidence interval, 1.21-1.84), and there appeared to be a dose- and age-dependent effect of alcohol on risk. The point estimate for risk of VEOPC was an odds ratio of 2.18 (95% confidence interval, 1.17-4.09). CONCLUSIONS: The established risk factors for PC, including smoking, diabetes, family history of PC, and obesity, also apply to EOPC. Alcohol intake appeared to have an age-dependent effect; the strongest association was with VEOPC.

23 Article Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium. 2015

Waterhouse, M / Risch, H A / Bosetti, C / Anderson, K E / Petersen, G M / Bamlet, W R / Cotterchio, M / Cleary, S P / Ibiebele, T I / La Vecchia, C / Skinner, H G / Strayer, L / Bracci, P M / Maisonneuve, P / Bueno-de-Mesquita, H B / Zaton Ski, W / Lu, L / Yu, H / Janik-Koncewicz, K / Polesel, J / Serraino, D / Neale, R E / Anonymous2000830. ·Division of Population Health, QIMR Berghofer Medical Research Institute, Herston Centre for Research Excellence in Sun and Health, Queensland University of Technology, Kelvin Grove, Australia. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, USA. · Department of Epidemiology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy. · Division of Epidemiology and Community Health, University of Minnesota, Minneapolis. · Department of Health Sciences Research, Mayo Clinic, Rochester, USA. · Prevention and Cancer Control, Cancer Care Ontario, Toronto Dalla Lana School of Public Health, University of Toronto, Toronto. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto Department of Surgery, University of Toronto, Toronto, Canada. · Division of Population Health, QIMR Berghofer Medical Research Institute, Herston. · Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. · Truven Health Analytics, Durham. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · National Institute for Public Health and the Environment, Bilthoven Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK. · Department of Epidemiology, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. · Epidemiology Program, University of Hawaii Cancer Center, Honolulu, USA. · Division of Population Health, QIMR Berghofer Medical Research Institute, Herston Centre for Research Excellence in Sun and Health, Queensland University of Technology, Kelvin Grove, Australia rachel.neale@qimrberghofer.edu.au. ·Ann Oncol · Pubmed #25977560.

ABSTRACT: BACKGROUND: The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations. PATIENTS AND METHODS: We used data from nine case-control studies from the International Pancreatic Cancer Case-Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake. RESULTS: Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 × 10(-6), P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P = 2.4 × 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake. CONCLUSION: Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.

24 Article Association between pancreatic intraductal papillary mucinous neoplasms and extrapancreatic malignancies. 2015

Marchegiani, Giovanni / Malleo, Giuseppe / D'Haese, Jan G / Wenzel, Patrick / Keskin, Muharrem / Pugliese, Luigi / Borin, Alex / Benning, Valentina / Nilsson, Linda / Oruc, Nevin / Segersvard, Ralf / Friess, Helmut / Schmid, Roland / Löhr, Matthias / Maisonneuve, Patrick / Bassi, Claudio / Ceyhan, Güralp O / Salvia, Roberto / Del Chiaro, Marco. ·Unit of Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. Electronic address: giovanni.marchegiani@ospedaleuniverona.it. · Unit of Surgery B, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Department of Gastroenterology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Division of Gastroenterology, Department of Internal Medicine, Ege University, Izmir, Turkey. · Unit of General Surgery 2, Department of Surgery, IRCCS Policlinico San Matteo, Pavia, Italy. · Division of Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Division of Gastroenterology, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. ·Clin Gastroenterol Hepatol · Pubmed #25478920.

ABSTRACT: BACKGROUND & AIMS: The association between pancreatic intraductal papillary mucinous neoplasms (IPMNs) and extrapancreatic neoplasms (EPNs) is controversial. We performed a multicenter observational study to assess the incidence of EPNs after an IPMN diagnosis. METHODS: 1340 patients with IPMNs were evaluated from 2000 through 2013 at 4 academic institutions in Europe for development of EPN. To estimate the actual incidence of EPN, we excluded patients with an EPN previous or synchronous to the IPMN, and patients who had been followed for less than 12 months, resulting in a study population of 816 patients. The incidence of EPN was compared with sex-specific, age-adjusted European cancer statistics; the standardized incidence ratio (SIR), and the 5- and 10-year cumulative incidence rates were calculated. RESULTS: A total of 290/1340 patients had a history of EPN (prevalence of 21.6%). In this subgroup of patients, the IPMN was discovered incidentally in 241. Among the 816 patients included in the incidence analysis, 50 developed an EPN after a median time of 46 months from study enrollment. The incidence of any EPN was not greater in patients with than without IPMN with a SIR of 1.48 (95% confidence interval, 0.94-2.22) in males and of 1.39 (95% CI 0.90-2.05) in females. The 5- and 10-year cumulative incidence rates for development of EPN in patients with IPMN were 7.9% and 16.6% in men, and 3.4% and 23.1% in women. CONCLUSIONS: Patients with IPMN do not have a significantly higher incidence of EPNs than the general European population. It might not be necessary to screen patients with IPMN for EPN.

25 Article Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. 2014

Bosetti, C / Rosato, V / Li, D / Silverman, D / Petersen, G M / Bracci, P M / Neale, R E / Muscat, J / Anderson, K / Gallinger, S / Olson, S H / Miller, A B / Bas Bueno-de-Mesquita, H / Scelo, G / Janout, V / Holcatova, I / Lagiou, P / Serraino, D / Lucenteforte, E / Fabianova, E / Ghadirian, P / Baghurst, P A / Zatonski, W / Foretova, L / Fontham, E / Bamlet, W R / Holly, E A / Negri, E / Hassan, M / Prizment, A / Cotterchio, M / Cleary, S / Kurtz, R C / Maisonneuve, P / Trichopoulos, D / Polesel, J / Duell, E J / Boffetta, P / La Vecchia, C. ·Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy cristina.bosetti@marionegri.it. · Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy. · M.D. Anderson Cancer Center, University of Texas, Houston. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda. · Department of Health Sciences Research, Medicine and Medical Genetics, Mayo Clinic, Rochester. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA. · Queensland Institute of Medical Research, Brisbane, Australia. · Department of Public Health Sciences, Penn State University, Penn State. · Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, USA. · University Health Network, Department of Surgery, University of Toronto, Toronto, Canada. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA. · Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. · National Institute for Public Health and the Environment (RIVM), Bilthoven Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · International Agency for Research on Cancer (IARC), Lyon, France. · Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc. · Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Department of Epidemiology, Harvard School of Public Health, Boston, USA Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece. · Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, Aviano. · Department of Preclinical and Clinical Pharmacology Mario Aiazzi Mancini, Università degli Studi di Firenze, Florence, Italy. · Regional Authority of Public Health in Banská Bystrica, Banská Bystrica, Slovakia. · Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy M.D. Anderson Cancer Center, University of Texas, Houston Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda Department of Health Sciences Research, Medicine and Medical Genetics, Mayo Clinic, Rochester Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA Queensland Institute of Medical Research, Brisbane, Australia Department of Public Health Sciences, Penn State University, Penn State Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, USA University Health Network, Department of Surgery, University of Toronto, Toronto, Canada Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA Dalla Lana School of Public Health, University of Toronto, Toronto, Canada National Institute for Public Health and the Environment (RIVM), Bilthoven Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK International Agency for Research on Cancer (IARC), Lyon, France Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic Department of Epidemiology, Harvard School of Public Health, Boston, USA Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, Aviano Department of Preclinical and Clinical Pharmacology Mario Aiazzi Mancini, Università degli Studi di Firenze, Florence, Italy Regional Authority of Public Health in Banská Bystrica, Banská Bystrica, Slovakia Public Health, Women · Public Health, Women's and Children's Hospital, Adelaide, SA, Australia. · Cancer Center and Institute of Oncology, Warsaw, Poland. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Institute and MF MU, Brno, Czech Republic. · Louisiana State University School of Public Health, New Orleans, USA. · Dalla Lana School of Public Health, University of Toronto, Toronto, Canada Cancer Care Ontario, Toronto, Canada. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · Department of Epidemiology, Harvard School of Public Health, Boston, USA. · Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. · The Tisch Cancer Institute and Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, USA. · Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. ·Ann Oncol · Pubmed #25057164.

ABSTRACT: BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

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