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Pancreatic Neoplasms: HELP
Articles by Jean-Yves Scoazec
Based on 41 articles published since 2010
(Why 41 articles?)
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Between 2010 and 2020, J-Y Scoazec wrote the following 41 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Malignant insulinoma: recommendations for characterisation and treatment. 2013

Baudin, Eric / Caron, Philippe / Lombard-Bohas, Catherine / Tabarin, Antoine / Mitry, Emmanuel / Reznick, Yves / Taieb, David / Pattou, François / Goudet, Pierre / Vezzosi, Delphine / Scoazec, Jean-Yves / Cadiot, Guillaume / Borson-Chazot, Françoise / Do Cao, Christine / Anonymous2980768 / Anonymous2990768. ·Service de médecine nucléaire et d'oncologie endocrinienne, institut Gustave-Roussy, 94800 Villejuif, France. ·Ann Endocrinol (Paris) · Pubmed #23993836.

ABSTRACT: -- No abstract --

2 Guideline Pathology. 2013

Scoazec, Jean-Yves / Couvelard, Anne / Leteurtre, Emmanuelle / Terris, Benoît / Anonymous2710761. ·Laboratoire d'anatomie et de cytologie pathologiques, groupement hospitalier Édouard-Herriot, bâtiment 10, 5, place d'Arsonval, 69437 Lyon, France. jean-yves.scoazec@chu-lyon.fr ·Ann Endocrinol (Paris) · Pubmed #23768679.

ABSTRACT: -- No abstract --

3 Review Imaging of neuroendocrine tumors of the pancreas. 2016

Dromain, C / Déandréis, D / Scoazec, J-Y / Goere, D / Ducreux, M / Baudin, E / Tselikas, L. ·Service de radiodiagnostic et radiologie interventionnelle, bureau CIBM 09-084, rue Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: Clarisse.Dromain@chuv.ch. · Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Anapathology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Surgery department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. · Oncology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France. ·Diagn Interv Imaging · Pubmed #27876341.

ABSTRACT: Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous disease. PNET can be functioning or non-functioning with different clinical presentations and different prognosis based on WHO and pTNM classifications. The role of imaging includes the localization of small functioning tumor, differentiation of these tumors from adenocarcinoma, identification of signs of malignancy and evaluation of extent. PNETs have a broad spectrum of appearance. On CT and MRI, most of functioning PNETs are well defined small tumors with intense and homogeneous enhancement on arterial and portal phases. However, some PNETs with a more fibrous content may have a more delayed enhancement that is best depicted on the delayed phase. Other PNETs can present as purely cystic, complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are larger with less intense and more heterogeneous enhancement. Functional imaging is useful for disease staging, to detect disease recurrence or the primary but also to select patient candidate for peptide receptor radiometabolic treatment. Somatostatin receptor scintigraphy (SRS) (Octreoscan

4 Review Cystic and ductal tumors of the pancreas: diagnosis and management. 2013

Scoazec, J Y / Vullierme, M P / Barthet, M / Gonzalez, J M / Sauvanet, A. ·Anatomie pathologique et centre de recherche en cancérologie de Lyon, Inserm U1052/CNRS UMR5286, hospices civils de Lyon, hôpital Edouard-Herriot, 69437 Lyon cedex 03, France. ·J Visc Surg · Pubmed #23518192.

ABSTRACT: Incidentally discovered cystic tumors of the pancreas (CTP) are an increasingly frequent entity. It is essential to differentiate lesions whose malignant potential is either nil or negligible (pseudocyst, serous cystadenoma, simple cysts) from lesions with intermediate malignant potential (intraductal papillary mucinous tumor of the pancreas [IPMN] involving the secondary ducts, cystic endocrine tumor) or those with high malignant potential (mucinous cystadenoma, solid pseudopapillary tumors and IPMN involving the main pancreatic duct). The approach to defining malignant potential is based on diagnostic CT scan, magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS), often complemented by EUS-guided cyst puncture for biochemical and cytological analysis of cyst fluid. Surgery for diagnostic purposes should be avoided because of its significant morbidity. For pseudocysts, simple cysts and serous cystadenomas, abstention is the general rule. Resection, preserving as much pancreatic parenchyma as possible, is the rule for IPMN involving the main pancreatic duct, mucinous cystadenomas, solid and pseudopapillary tumors, and cystic endocrine tumors. Resection is rarely indicated at the outset for IPMN involving secondary pancreatic ducts; morphologic observation is the general rule and preventive excision may be indicated secondarily. Good collaboration between surgeons, radiologists and endosonographists is necessary for optimal management of CTP.

5 Review Intervention in gastro-enteropancreatic neuroendocrine tumours. 2012

Baudin, Eric / Planchard, David / Scoazec, Jean-Yves / Guigay, Joël / Dromain, Clarisse / Hadoux, Julien / Debaere, Thierry / Elias, Dominique / Ducreux, Michel. ·Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France. baudin@igr.fr ·Best Pract Res Clin Gastroenterol · Pubmed #23582924.

ABSTRACT: Neuroendocrine tumours require dedicated interventions to control their capacity to secrete hormones but also, antitumour growth strategies. Recommendations for early interventions in NET include the management of hormone-related symptoms and poorly differentiated neuroendocrine carcinomas. In contrast, prognostic heterogeneity is a key feature of well differentiated NET that complexified the antitumour strategy whatever the stage in this subgroup of tumour. In this review, timely therapeutic interventions to control hormone-related symptoms and tumour growth in GEP NET patients are discussed. The necessity of controlling hormone-related symptoms as the first step of any strategy affects also the tumour growth control strategy. In the absence of cure at the metastatic stage, progresses are expected in the recognition of well differentiated NET subgroups that display either excellent or poor prognosis.

6 Review [Histologic assessment of treatment effect of preoperative chemoradiation in patients presenting with resectable pancreatic adenocarcinoma]. 2011

Le Scodan, R / Mornex, F / Partensky, C / Mercier, C / Valette, P-J / Ychou, M / Bibeau, F / Scoazec, J-Y. ·Département de Radiothérapie, Centre René-Huguenin, 35 rue Dailly, 92210 Saint-Cloud, France. ·Cancer Radiother · Pubmed #21084206.

ABSTRACT: PURPOSE: Several phase II studies have shown the feasibility of neoadjuvant chemoradiation regimens for resectable localized pancreatic adenocarcinoma. However, there is to date no completed phase III study to validate this approach and treatment effects evaluation still remains an active area of investigation. From the mature results of the SFRO-FFCD 9704 trial, we explored the antitumoral effect of a 5-fluoro-uracil and cisplatin-based preoperative chemoradiation regimen, with a special highlight on the histopathological response and performed a literature review. PATIENTS AND METHODS: Treatment consisted of concurrent radiotherapy (50 Gy within five weeks) and chemotherapy with 5-fluoro-uracil (300 mg/m(2)/day, five days/week, weeks 1-5) and cisplatin (20mg/m(2)/day, days 1-5 and 29-33), followed by surgical resection of the pancreatic tumour in patients without progression. RESULTS: In all, 41 patients were enrolled, 26 patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. A total of 13 of 26 specimens (50%) presented a major pathologic response (≥ 80% of severely degenerative cancer cells), with one complete pathologic response. The local recurrence and two-year survival rates were 4 and 32%, respectively, for the 26 operated patients. CONCLUSION: Our results suggest that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Evaluation of histopathological response to neoadjuvant chemoradiation may serve as a surrogate marker for treatment efficacy and further research is needed to determine new prognostic and predictive factors of treatment response.

7 Clinical Trial Evaluating bevacizumab in combination with FOLFIRI after the failure of platinum-etoposide regimen in patients with advanced poorly differentiated neuroendocrine carcinoma: The PRODIGE 41-BEVANEC randomized phase II study. 2018

Walter, Thomas / Malka, David / Hentic, Olivia / Lombard-Bohas, Catherine / Le Malicot, Karine / Smith, Denis / Ferru, Aurélie / Assenat, Eric / Cadiot, Guillaume / Lievre, Astrid / Kurtz, Jean-Emmanuel / Dahan, Laetitia / Dubreuil, Olivier / Hautefeuille, Vincent / Lepere, Céline / Gangloff, Alice / Elhajbi, Farid / Coriat, Romain / Roquin, Guillaume / Bouarioua, Nadia / Granger, Victoire / Scoazec, Jean-Yves / Lepage, Côme. ·Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. Electronic address: thomas.walter@chu-lyon.fr. · Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France. · Gastroenterology-Pancreatology Department, Beaujon Hospital, PMAD, Clichy, France. · Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. · Fédération Francophone de Cancérologie Digestive, Dijon, France. · Hepatogastroenterology and Digestive Oncology Department, Haut-Lévèque, University Hospital of Bordeaux, Pessac, France. · Pôle régional de cancérologie, University Hospital of Poitiers, Poitiers, France. · Medical Oncology Department, University Hospital St Eloi, Montpellier, France. · Department of Hepatogastroenterology and Digestive Oncology, Robert Debré Hospital, University Hospital of Reims, Reims, France. · Service des maladies de l'appareil digestif, University Hospital of Pontchaillou, Rennes, France. · Oncology Department, Nouvel Hospital Civil, University Hospital of Strasbourg, Strasbourg, France. · Digestive Oncology Department, University Hospital Timone, Marseille, France. · Hepatogastroenterology and Digestive Oncology Department, Pitié Salpêtrière Hospital, Paris, France. · Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France. · European Georges Pompidou Hospital, Paris, France. · Gastroenterology Department, University Hospital of Rouen, Rouen, France. · Oncology Department, Oscar Lambret Center, Lille, France. · Gastroenterology Department, Cochin Hospital, Paris, France. · Gastroenterology & Digestive Oncology, University Hospital of Angers, Angers, France. · Service de gastroentérologie et oncologie digestive, hôpital Nord, Saint Priest en Jarez, France. · Hepatogastroenterology Department, Michallon Hospital, University Hospital of Grenoble, Grenoble, France. · Gustave Roussy Cancer Campus, Department of Surgical and Molecular Pathology, Villejuif Cedex, France; Université Paris Saclay, Université Paris Sud XI, Faculté de Médecine de Bicêtre, Le Kremlin-Bicêtre, France. · Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France; Gastroenterology & Digestive Oncology, University Hospital Le Bocage, Dijon, France. ·Dig Liver Dis · Pubmed #29258812.

ABSTRACT: INTRODUCTION: Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment. AIM: PRODIGE 41-BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC. MATERIALS AND METHODS: The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy. RESULTS: A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response. CONCLUSION: The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017.

8 Clinical Trial Evaluating lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours. 2017

Lepage, Côme / Dahan, Laetitia / Bouarioua, Nadia / Toumpanakis, Christos / Legoux, Jean-Louis / Le Malicot, Karine / Guimbaud, Rosine / Smith, Denis / Tougeron, David / Lievre, Astrid / Cadiot, Guillaume / Di Fiore, Frédéric / Bouhier-Leporrier, Karine / Hentic, Olivia / Faroux, Roger / Pavel, Marianne / Borbath, Ivan / Valle, Juan W / Rinke, Anja / Scoazec, Jean-Yves / Ducreux, Michel / Walter, Thomas. ·Department of Digestive Oncology, Burgundy Franche-Conté University, University hospital Dijon, Dijon, France; Burgundy Franche-Conté University, EPICAD, INSERM LNC UMR1231, Dijon, France; French Federation of Digestive Oncology (FFCD), INSERM LNC UMR1231 EPICAD, Dijon, France. Electronic address: come.lepage@u-bourgogne.fr. · Department of Digestive Oncology, Aix-Marseille University - Assistance Publique Hôpitaux de Marseille, Marseille, France. · Department of Gastroenterology and Digestive Oncology, Saint Etienne, France. · Royal Free Hospital, Neuroendocrine Tumour Unit, Londres, Grande-Bretagne, UK. · Regional Hospital of Orleans, Orleans, France. · French Federation of Digestive Oncology (FFCD), INSERM LNC UMR1231 EPICAD, Dijon, France. · Hôpital Rangueil, Toulouse, France. · Hôpital Haut Lévêque, Service d'hépato-gastroentérologie, Pessac, France. · Hôpital de la Milétrie, Poitiers, France. · CHU de Rennes-Hôpital Pontchaillou, Rennes, France. · Hôpital Robert Debré, Reims, France. · CHU Charles Nicolle, Rouen, France. · CHU Côte de Nacre, Caen, France. · Hôpital Beaujon, Clichy, France. · CH Les Oudairies, La Roche sur Yon, France. · Charite Campus Virchow Kinikum, Berlin, Germany. · Cliniques universitaires Saint-Luc, Bruxelles, Belgium. · University of Manchester, Division of Cancer Sciences/The Christie NHS Foundation Trust, Manchester, UK. · University Hospital Marburg, Marburg, Germany. · Pathology Department, Gustave Roussy, Villejuif, France. · Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France; Faculté de Médecine, Paris Sud University Le Kremlin Bicêtre, France. · Edouard Herriot Hospital, Department of Gastroenterology, Hospices Civils de Lyon, Lyon, France. ·Dig Liver Dis · Pubmed #28292641.

ABSTRACT: INTRODUCTION: Patients with metastatic or locally advanced, non-resectable, grade 1 or 2 well-differentiated duodeno-pancreatic (WDDP) NETs are treated following European guidelines. Patients (Pts) with aggressive disease, i.e. progressive and/or symptomatic metastases and/or with significant hepatic invasion (>30-50%), and/or bone metastases, anti-tumour therapy should receive systemic combination of chemotherapy once disease control is obtained. AIM(S): The aim is to stop chemotherapy until progression. REMINET is an academic randomized, double-blind, placebo-controlled, phase II/III study designed to evaluate lanreotide (LAN) as maintenance treatment after L1 chemotherapy in G1-G2 WDDP NET. MATERIALS AND METHODS: Main eligibility criteria: adults pts with a metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 1 or 2 WDDP NETs and documented control disease after L1 therapy at least 4 weeks prior to randomization. RESULTS: 222 patients will be randomly assigned in a 1:1 ratio to receive 120mg LAN or placebo, every 28 days, until disease progression or unacceptable toxicity. The aim of the phase II part is to demonstrate a 6-months PFS >45% in LAN arm. Secondary endpoints are PFS according to central review, overall survival, safety and quality of life. A bio-bank of frozen blood will be constituted. CONCLUSION: The study is currently open in France, Germany, Belgium, United Kingdom and Ireland. A total of 25 patients are randomized (NCT02288377).

9 Clinical Trial Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial)--a phase II non-randomised trial. 2014

Ducreux, Michel / Dahan, Laetitia / Smith, Denis / O'Toole, Dermot / Lepère, Céline / Dromain, Clarisse / Vilgrain, Valérie / Baudin, Eric / Lombard-Bohas, Catherine / Scoazec, Jean-Yves / Seitz, Jean-François / Bitoun, Laurence / Koné, Sébastien / Mitry, Emmanuel. ·Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France; Faculté de Médecine, Paris Sud Uiversty Le Kremlin Bicêtre, France. Electronic address: Michel.DUCREUX@igr.fr. · Gastrointestinal Oncology Department, La Timone Hospital, Aix-Marseille Université, Marseille, France. Electronic address: laetitia.dahan@mail.hp-hm.fr. · Medical Oncology Department, Saint-André Hospital, Bordeaux, France. Electronic address: denis.smith@chu-bordeaux.fr. · Clinical Medicine and Gastroenterology Department, St James's Hospital and Trinity College, Dublin, Ireland. Electronic address: OTOOLED1@tcd.ie. · Medical Oncology Department, Georges Pompidou European Hospital, Paris, France. Electronic address: celine.lepere@egp.aphp.fr. · Radio Diagnostic Department, Gustave Roussy Institute, Villejuif, France. Electronic address: dromain@igr.fr. · Radiology Department, Beaujon Hospital, Clichy, France. Electronic address: valerie.vilgrain@bjn.aphp.fr. · Nuclear Medicine and Endocrine Oncology Department, Gustave Roussy Institute, Villejuif, France. Electronic address: Eric.BAUDIN@igr.fr. · Medical Oncology Department, Edouard Herriot Hospital, Lyon, France. Electronic address: catherine.lombard-bohas@chu-lyon.fr. · Pathology Department, Edouard Herriot Hospital, Lyon, France. Electronic address: jy.scoazec@gmail.com. · Gastrointestinal Oncology Department, La Timone Hospital, Aix-Marseille Université, Marseille, France. Electronic address: Jean-francois.SEITZ@ap-hm.fr. · Clinial Operating Department, Roche Laboratories, Boulogne-Billancourt, France. Electronic address: laurence.bitoun@roche.com. · Oncology Department, Roche Laboratories, Boulogne-Billancourt, France. Electronic address: sebastien.kone@roche.com. · Medical Oncology Department, Curie Institute, Paris, France. Electronic address: emmanuel.mitry@curie.net. ·Eur J Cancer · Pubmed #25454412.

ABSTRACT: AIM OF THE STUDY: Neuroendocrine tumours are highly vascular neoplasms known to overexpress vascular endothelial growth factor (VEGF) and its receptor. Bevacizumab, an inhibitor of VEGF, was assessed in combination with chemotherapy in pancreatic neuroendocrine tumour (P-NET). PATIENTS AND METHODS: BETTER was a multicentre, open-label, non-randomised, two-group phase II trial. Patients with progressive metastatic, well-differentiated P-NET received a minimum of 6 month treatment of bevacizumab at 7.5 mg/kg IV on d1 q3w with 5-FU at 400 mg/m2/day and streptozocin at 500 mg/m2/day IV from d1 to d5 every 42 days. The primary end-point was progression-free survival (PFS); secondary end-points were overall survival (OS), overall response rate, safety and quality of life. RESULTS: A total of 34 patients were included. Median age was 55 years, 65% of patients were men, 97% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and 97% had a Ki-67 proliferative index of <15%. After a maximum of 24 month follow-up per patient, the median PFS assessed by investigators was 23.7 months [95% confidence interval (CI): 13.1; not reached], 19 (56%) patients had a partial response and 15 (44%) had stable disease as best response. OS rate at 24 months was 88%. The most frequently reported grade 3-4 adverse events were hypertension (21% patients), abdominal pain (12%) and thromboembolic events (9%). CONCLUSION: Bevacizumab with 5-FU/streptozocin in the treatment of pancreatic NETs seems to be feasible with a PFS of 23.7 months, which deserves further attention. No unexpected toxicity was observed.

10 Clinical Trial 18F-FLT and 18F-FDG positron emission tomography for the imaging of advanced well-differentiated gastro-entero-pancreatic endocrine tumours. 2011

Giammarile, Francesco / Billotey, Claire / Lombard-Bohas, Catherine / Le Bars, Didier / Bournaud, Claire / Masson, Sandrine / Walter, Thomas / Houzard, Claire / Scoazec, Jean-Yves / Hervieu, Valérie / Vuillez, Jean-Philippe / Cornu, Catherine / Janier, Marc / Borson-Chazot, Françoise. ·Nuclear Medicine Department, Hospices Civils de Lyon, Lyon-Sud Hospital, France. francesco.giammarile@chu-lyon.fr ·Nucl Med Commun · Pubmed #21076344.

ABSTRACT: PURPOSE: Gastro-entero-pancreatic (GEP) endocrine tumours are a heterogenous group of tumours of variable localization and prognosis. It has been suggested that positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) may have a prognostic value and help to identify patients at risk of progression. [18F]fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) has been recently developed as a PET proliferation tracer. At present, there are no studies investigating its role in GEP. The aim of this prospective study was to assess the value of 18F-FLT-PET for the evaluation of GEP. MATERIALS AND METHODS: Ten patients with biopsy-proven locally advanced or metastasized, well-differentiated GEP neuroendocrine tumours were prospectively enrolled and scheduled for 18F-FDG and 18F-FLT-PET. Images were compared with other conventional diagnostic procedures, namely computed tomography, ultrasound, somatostatin receptor scintigraphy and with clinical and diagnostic follow-up. RESULTS: Evaluation criteria were interpreted in terms of assumed presence of tumoral tissue. According to the patient's status, FDG was positive in five out of the seven patients with stable disease and in two out of the three patients with progressive disease. No positive case was identified by 18F-FLT in either the primary or the metastatic tumour site, whatever the status of patients, and this was probably a reflection of the slow proliferation rate of tumours. CONCLUSION: These preliminary data suggest that 18F-FLT-PET is not a suitable tracer for the evaluation of advanced well-differentiated GEP tumours. FDG showed good diagnostic performance but does not help to identify patients at risk of progression.

11 Clinical Trial Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study. 2010

Napoleon, B / Alvarez-Sanchez, M V / Gincoul, R / Pujol, B / Lefort, C / Lepilliez, V / Labadie, M / Souquet, J C / Queneau, P E / Scoazec, J Y / Chayvialle, J A / Ponchon, T. ·Department of Gastroenterology, Hôpital Privé Jean Mermoz, Lyon, France. dr.napoleon@wanadoo.fr ·Endoscopy · Pubmed #20593334.

ABSTRACT: BACKGROUND AND STUDY AIMS: Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques. This prospective study aimed to evaluate the accuracy of a new procedure, imaging the microcirculation pattern of the pancreas by contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) with a new Olympus prototype echo endoscope. PATIENTS AND METHODS: 35 patients presenting with solid pancreatic lesions were prospectively enrolled. All patients had conventional B mode and power Doppler EUS. After an intravenous bolus injection of 2.4 ml of a second-generation ultrasound contrast agent (SonoVue) CEH-EUS was then performed with a new Olympus prototype echo endoscope (xGF-UCT 180). The microvascular pattern was compared with the final diagnosis based on the pathological examination of specimens from surgery or EUS-guided fine-needle aspiration (EUS-FNA) or on follow-up for at least 12 months. RESULTS: The final diagnoses were: 18 adenocarcinomas, 9 neuroendocrine tumors, 7 chronic pancreatitis, and 1 stromal tumor. Power Doppler failed to display microcirculation, whereas harmonic imaging demonstrated it in all cases. Out of 18 lesions with a hypointense signal on CEH-EUS, 16 were adenocarcinomas. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of hypointensity for diagnosing pancreatic adenocarcinoma were 89 %, 88 %, 88 %, 89 %, and 88.5 %, compared with corresponding values of 72 %, 100 %, 77 %, 100 %, and 86 % for EUS-FNA. Of five adenocarcinomas with false-negative results at EUS-FNA, four had a hypointense echo signal at CEH-EUS. CONCLUSIONS: CEH-EUS with the new Olympus prototype device successfully visualizes the microvascular pattern in pancreatic solid lesions, and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

12 Article O6-methylguanine-DNA methyltransferase (MGMT) status in neuroendocrine tumors: a randomized phase II study (MGMT-NET). 2019

Lemelin, Annie / Barritault, Marc / Hervieu, Valérie / Payen, Léa / Péron, Julien / Couvelard, Anne / Cros, Jérome / Scoazec, Jean-Yves / Bin, Sylvie / Villeneuve, Laurent / Lombard-Bohas, Catherine / Walter, Thomas / Anonymous5440981. ·Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. · Departement of Molecular Biology, Multi-Site Pathology Institute of the Hospices Civils de Lyon-East Site, GHE University Hospital, Bron, France. · Institute of Multi-Site Pathology of the HCL-Est Site, GHE University Hospital, Bron, France. · CIRCAN (CIRculating CANcer) Platform, GHS University Hospital, Pierre-Benite, France. · Department of Biostatistics, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, France. · Department of Pathology, Bichat Hospital, Paris, France. · Department of Pathology, Beaujon University Hospital, Clichy, France. · Gustave Roussy Cancer Campus, Department of Surgical and Molecular Pathology, Villejuif, France. · Pole Information Médical Recherche, Clinical Research Department, Lyon, France. · Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. Electronic address: Thomas.walter@chu-lyon.fr. ·Dig Liver Dis · Pubmed #30824408.

ABSTRACT: INTRODUCTION: Neuroendocrine tumors (NETs) are rare, but their incidence is rising. Alkylating agents (ALKY), temozolomide and streptozotocin, are the main chemotherapies used for advanced pancreatic NETs. According to retrospective data, O6-methylguanine-DNA methyltransferase (MGMT) status appears to be a predictive factor of the response to ALKY. AIMS: The main objective is to evaluate the value of tumor MGMT promoter (pMGMT) methylation in the prediction of the objective response (OR) at 3 months in patients treated with ALKY. Secondly, we will evaluate the value of MGMT immunohistochemistry and the efficacy of treatment with ALKY vs. oxaliplatin-based chemotherapy (Ox). MATERIALS AND METHODS: A national, prospective, open-label, randomized, controlled and multicenter trial was designed. Main inclusion criteria are: adult patients with well-differentiated advanced duodeno-pancreatic, lung, or unknown primitive NETs with a validated indication for chemotherapy. pMGMT methylation will be assessed by pyrosequencing, but an ancillary study will compare this technique with others ones including MGMT immunohistochemistry. RESULTS: A total of 104 patients will be randomly assigned (1:1 for unmethylated or 2:1 for methylated pMGMT NETs) to either the ALKY arm or to the Ox arm. CONCLUSION: Recruitment started on October 16, 2018 (NCT03217097) and will be open in 21 centers in France.

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

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

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

14 Article Combinatorial Treatment with mTOR Inhibitors and Streptozotocin Leads to Synergistic 2018

Bollard, Julien / Patte, Céline / Massoma, Patrick / Goddard, Isabelle / Gadot, Nicolas / Benslama, Noura / Hervieu, Valérie / Ferraro-Peyret, Carole / Cordier-Bussat, Martine / Scoazec, Jean-Yves / Roche, Colette / Walter, Thomas / Vercherat, Cécile. ·Groupe des tumeurs neuroendocrines, Département de Recherche Translationnelle et Innovation, Centre Léon Bérard, Lyon, France. · INSERM U1052/CNRS UMR5286/Université de Lyon, Lyon1 UMR-S1052, Centre de Recherche en Cancérologie, Lyon, France. · Plateforme Anatomopathologie-Recherche, Département de Recherche Translationnelle et Innovation, Centre Léon Bérard, Lyon, France. · Service Central d'Anatomie et Cytologie Pathologiques, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France. · Université de Lyon, Université Claude Bernard Lyon 1, Villeurbanne cedex, France. · Service de pathologie morphologique et moléculaire, Département de biologie et pathologie médicales; AMMICa, Inserm US23/CNRS UMS3655, Gustave Roussy Cancer Campus, Villejuif, France. · Faculté de Médecine de Bicêtre, Université Paris Sud, Université Paris Saclay, Le Kremlin-Bicêtre, France. · Service d'hépatogastroentérologie et d'oncologie digestive, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France. · Groupe des tumeurs neuroendocrines, Département de Recherche Translationnelle et Innovation, Centre Léon Bérard, Lyon, France. cecile.vercherat@inserm.fr. ·Mol Cancer Ther · Pubmed #29051320.

ABSTRACT: Streptozotocin-based chemotherapy is the first-line chemotherapy recommended for advanced pancreatic neuroendocrine tumors (pNETs), whereas targeted therapies, including mTOR inhibitors, are available in second-line treatment. Unfortunately, objective response rates to both treatments are limited. Because mTOR pathway activation, commonly observed in pNETs, has been reported as one of the major mechanisms accounting for chemoresistance, we investigated the potential benefit of mTOR inhibition combined with streptozotocin treatment in a subset of pNETs, namely insulinomas. To evaluate the potential of mTOR inhibition in combination with streptozotocin, we selected four different inhibitors acting at various levels of the pathway (everolimus: inhibition of mTORC1; MK-2206: inhibition of AKT; BKM120: inhibition of PI3K, mTORC1, and mTORC2; and BEZ235: inhibition of mTORC1 and mTORC2). Effects on cell viability and apoptosis were assessed in insulinoma cell lines INS-1E (rat) and MIN6 (mouse)

15 Article Chemotherapy for Well-Differentiated Pancreatic Neuroendocrine Tumours with a Ki-67 Index ≥10%: Is There a More Effective Antitumour Regimen? A Retrospective Multicentre Study of the French Group of Endocrine Tumours (GTE). 2018

Roquin, Guillaume / Baudin, Eric / Lombard-Bohas, Catherine / Cadiot, Guillaume / Dominguez, Sophie / Guimbaud, Rosine / Niccoli, Patricia / Legoux, Jean-Louis / Mitry, Emmanuel / Rohmer, Vincent / Ruszniewski, Philippe / Walter, Thomas / Ducreux, Michel / Couvelard, Anne / Scoazec, Jean-Yves / Ramond-Roquin, Aline / Caroli-Bosc, François-Xavier / Hentic, Olivia. ·Department of Hepatogastroenterology and Digestive Oncology, CHU Angers, Angers University, LUNAM University, Angers, France. ·Neuroendocrinology · Pubmed #28152531.

ABSTRACT: BACKGROUND: The best chemotherapy regimen for well- differentiated pancreatic neuroendocrine tumours (pNETs) with a Ki-67 index ≥10% is still debated. We evaluated the antitumour efficacy of various first-line chemotherapy regimens (streptozocin based, platinum based, or dacarbazine/temozolomide based) in this situation. METHODS: In this retrospective multicentre study of the French Group of Endocrine Tumours (GTE), we recruited consecutive patients with advanced well-differentiated pNETs and a Ki-67 index ≥10% receiving chemotherapy between 2000 and 2012. The primary endpoint was progression-free survival (PFS) according to RECIST. RESULTS: Seventy-four patients (42 men, median age 55.5 years) were enrolled from 10 centres. Fifty-one patients (69%) had grade 2 NET and 61 (82%) were stage IV. Median overall survival was 36.3 months. Forty-four patients (59%) received streptozocin-based, 18 (24%) platinum-based, and 12 (16%) dacarbazine/temozolomide-based chemotherapy regimens. These 3 groups were similar regarding age, functioning tumours, grade, the number of metastatic sites, and surgery for primary tumours, but not regarding surgery for metastases and time since diagnosis. Grade 3 NET (HR 2.15, 95% CI: 1.18-3.92, p = 0.012) and age above 55 years (HR 1.84, 95% CI: 1.06-3.18, p = 0.030) were associated with shorter median PFS in the multivariate analyses. Compared to streptozocin-based chemotherapy, no difference was found in terms of PFS for the platinum-based or for the dacarbazine/temozolomide-based chemotherapy regimen: median PFS was 7.2, 7.5, and 7.2 months, respectively (p = 0.51). CONCLUSIONS: Patients with intermediate or highly proliferative well-differentiated pNETs may benefit from 1 of the 3 chemotherapy regimens. Increased age and grade 3 were associated with shorter median PFS. Randomised studies searching for response predictors and the best efficacy-tolerance ratio are required to personalise the strategy.

16 Article [Classification of pancreatic neuroendocrine tumours: Changes made in the 2017 WHO classification of tumours of endocrine organs and perspectives for the future]. 2017

Scoazec, Jean-Yves / Couvelard, Anne / Anonymous7520927. ·Département de biologie et pathologie médicales, Gustave-Roussy Cancer Campus, 114, rue Edouard-Vaillant, 94805 Villejuif cedex, France; Faculté de médecine de Bicêtre, université Paris Sud, 94270 Le Kremlin-Bicêtre, France. Electronic address: jean-yves.scoazec@gustaveroussy.fr. · DHU Unity, département de pathologie, hôpital Bichat, Assistance publique-Hôpitaux de Paris, 75018 Paris, France; Faculté de médecine Bichat, université Paris Diderot, 75018 Paris, France. ·Ann Pathol · Pubmed #29169836.

ABSTRACT: The WHO classification of the tumors of endocrine organs, published in July 2017, has introduced significant changes in the classification of pancreatic neuroendocrine tumors, the previous version of which has appeared in 2010, within the WHO classification of the tumors of the digestive system. The main change is the introduction of a new category of well-differentiated neoplasms, neuroendocrine tumors G3, in addition to the previous categories of neuroendocrine tumors G1 and G2. The differential diagnosis between neuroendocrine tumors G3 (well-differentiated) and neuroendocrine carcinomas (poorly-differentiated) might be difficult; the authors of the WHO classification therefore suggest the use of a number of immunohistochemical markers to facilitate the distinction between the two entities. The other changes are: (a) the modification of the threshold between neuroendocrine tumors G1 and G2, now set at 3%; (b) the terminology used for mixed tumors: the previous term mixed adeno-neuroendocrine carcinoma (MANEC) is substituted by the term mixed neuroendocrine-non neuroendocrine neoplasm (MiNEN). Finally, the recommendations for Ki-67 index evaluation are actualized. Even if these changes only concern, stricto sensu, the neuroendocrine tumors of pancreatic location, they will probably be applied, de facto, for all digestive neuroendocrine tumors. The revision of the histological classification of pancreatic neuroendocrine tumors coincides with the revision of their UICC TNM staging; significant changes have been made in the criteria for T3 and T4 stages. Our professional practices have to take into account all these modifications.

17 Article Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma. 2017

Ali, Abir Salwa / Grönberg, Malin / Federspiel, Birgitte / Scoazec, Jean-Yves / Hjortland, Geir Olav / Grønbæk, Henning / Ladekarl, Morten / Langer, Seppo W / Welin, Staffan / Vestermark, Lene Weber / Arola, Johanna / Österlund, Pia / Knigge, Ulrich / Sorbye, Halfdan / Grimelius, Lars / Janson, Eva Tiensuu. ·Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden. · Department of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. · Department of Biopathology, Institut Gustave Roussy, Villejuif, France. · Department of Oncology, Oslo University, Oslo, Norway. · Department of Hepatology & Gastroenterology, Aarhus university Hospital, Aarhus, Denmark. · Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. · Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. · Department of Oncology, Odense University Hospital, Odense, Denmark. · Pathology, HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. · Department of Oncology, Helsinki University Hospital and Helsinki University, Helsinki Finland. · Department of Oncology, Tampere University Hospital, Tampere, Finland. · Department of Surgery C and Endocrinology PE, Rigshospitalet, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark. · Department of Oncology, Haukeland University Hospital and Department of Clinical Science, University of Bergen, Bergen, Norway. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. ·PLoS One · Pubmed #29112960.

ABSTRACT: BACKGROUND: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance of immunoreactive p53 protein in GEP-NEC. MATERIALS AND METHODS: Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate and differentiation were re-evaluated. All specimens were immunostained for p53 protein using a commercially available monoclonal antibody. Kaplan-Meier curves and cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS). RESULTS: All tumor tissues were immunoreactive for either one or both neuroendocrine biomarkers (chromogranin A and synaptophysin) and Ki67 index was >20% in all cases. p53 immunoreactivity was only shown in 39% of the cases and was not found to be a prognostic marker for the whole cohort. However, p53 immunoreactivity was correlated with shorter PFS in patients with colorectal tumors (HR = 2.1, p = 0.03) in a univariate analysis as well as to poorer PFS (HR = 2.6, p = 0.03) and OS (HR = 3.4, p = 0.02) in patients with colorectal tumors with distant metastases, a correlation which remained significant in the multivariate analyses. CONCLUSION: In this cohort of GEP-NEC patients, p53 expression could not be correlated with clinical outcome. However, in patients with colorectal NECs, p53 expression was correlated with shorter PFS and OS. Further studies are needed to establish the role of immunoreactive p53 as a prognostic marker for GEP-NEC patients.

18 Article Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort. 2017

Walter, T / Tougeron, D / Baudin, E / Le Malicot, K / Lecomte, T / Malka, D / Hentic, O / Manfredi, S / Bonnet, I / Guimbaud, R / Coriat, R / Lepère, C / Desauw, C / Thirot-Bidault, A / Dahan, L / Roquin, G / Aparicio, T / Legoux, J-L / Lombard-Bohas, C / Scoazec, J-Y / Lepage, C / Cadiot, G / Anonymous2580906. ·University Hospital, Lyon, France. Electronic address: thomas.walter@chu-lyon.fr. · University Hospital, Poitiers, France. · Gustave Roussy Institute, Villejuif, France. · FFCD, Dijon, France. · Trousseau Hospital, Tours, France. · Beaujon Hospital, Clichy, France. · University Hospital, Rennes, France. · Valenciennes Hospital, Valenciennes, France. · University Hospital, Toulouse, France. · Cochin Hospital, University Paris Descartes, Paris, France. · Georges Pompidou European Hospital, University Paris-V, Paris, France. · University Hospital, Lille, France. · Hôpitalde Bicêtre, Le Kremlin Bicêtre, France. · La Timone Hospital, Marseille, France. · University Hospital, Angers, France. · Avicenne Hospital, Bobigny, France. · Hôpital de la Source, Orléans, France. · University Hospital, Lyon, France. · FFCD, Dijon, France; University Hospital, Dijon, France. · University Hospital, Reims, France. ·Eur J Cancer · Pubmed #28501762.

ABSTRACT: BACKGROUND: Diagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC. PATIENTS AND METHODS: All patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded. RESULTS: 253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0-1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20-100). Median overall survival was 15.6 (13.6-17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE>2 upper limit of normal [ULN]; HR = 3.2), CgA>2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72). CONCLUSIONS: We report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.

19 Article Treatment of metastatic pancreatic neuroendocrine tumors: relevance of ENETS 2016 guidelines. 2017

Foulfoin, Margaux / Graillot, Emmanuelle / Adham, Mustapha / Rousset, Pascal / Forestier, Julien / Hervieu, Valérie / Robinson, Philip / Scoazec, Jean-Yves / Lombard-Bohas, Catherine / Walter, Thomas. ·Hospices Civils de LyonHôpital Edouard Herriot, Service de Gastroentérologie et d'Oncologie Médicale, Lyon, France. · University of LyonUniversité Lyon 1, Lyon, France. · Hospices Civils de LyonHôpital Edouard Herriot, Service de chirurgie, Lyon, France. · Hospices Civils de LyonHôpital Edouard Herriot, Service de radiologie, Lyon, France. · Hospices Civils de LyonHôpital Edouard Herriot, Service Central d'Anatomie et Cytologie Pathologiques, Lyon, France. · Hospices Civils de LyonDRCI, Lyon, France. · Hospices Civils de LyonHôpital Edouard Herriot, Service de Gastroentérologie et d'Oncologie Médicale, Lyon, France thomas.walter@chu-lyon.fr. ·Endocr Relat Cancer · Pubmed #27965277.

ABSTRACT: The choice of first-line treatment for metastatic pancreatic neuroendocrine tumors (mP-NET) is mainly based on prognostic factors. ENETS-2016 guidelines stratified treatment according to 3 groups: Group 1, patients in whom all lesions could be removed; Group 2, patients with Ki67 <10%, low tumor burden, no symptoms and stable disease, for whom a watch-and-wait strategy or somatostatin analogs are proposed; Group 3, symptomatic patients or with Ki67 >10% or significant tumor burden or progressive disease, for whom a systemic chemotherapy is proposed. This retrospective study aimed to determine patient distribution, characteristics and outcome among these 3 groups. Patients with mP-NET diagnosis from 2004 to 2016 were categorized into the three groups. Prognosis was calculated using the Kaplan-Meier method. All treatments were recorded, and consistency with ENETS guidelines was explored. 104 patients were analyzed: 64% synchronous mP-NET, 80% grade 2 tumors and median overall survival (OS) of 104 (95% CI: 65-143) months. There were 15 patients in ENETS Group 1, 16 in Group 2 and 73 in Group 3. Median OS was not reached in Groups 1 and 2 and was 64 months (35-93) in Group 3. High liver tumor volume, high-grade tumor and progressive disease were associated with worse OS in multivariate analysis. The first-line treatment was in accordance with guidelines in 82%. 77% percent of deceased patients received less than 4 lines of treatment. Most patients are in Group 3 and do not receive all available treatments. Thus, trials are warranted to improve first-line chemotherapy. Alternative treatments may be considered for less aggressive disease.

20 Article Professional Practices and Diagnostic Issues in Neuroendocrine Tumour Pathology: Results of a Prospective One-Year Survey among French Pathologists (the PRONET Study). 2017

Scoazec, Jean-Yves / Couvelard, Anne / Monges, Geneviève / Guyétant, Serge / Bisot-Locard, Segolène / Parot, Xavier / Lepage, Côme / Anonymous7470875. ·Département de Biologie et Pathologie Médicales, Gustave Roussy Cancer Campus, Villejuif, France. ·Neuroendocrinology · Pubmed #27442514.

ABSTRACT: INTRODUCTION: Many changes have recently occurred in the practice of neuroendocrine tumour (NET) pathology. We therefore aimed to evaluate how pathologists have adapted their daily practice to the most recent international guidelines for diagnostic and prognostic evaluation. PROCEDURES: A 12-month prospective study (PRONET) was carried out among French pathologists between August 2010 and July 2011. Data were collected using an anonymous electronic case report form. OBSERVATIONS: Five hundred laboratories were invited, 149 accepted to participate, 80 were active and 59 provided eligible cases. A total of 1,340 cases were collected. The primary tumour was gastroenteropancreatic in 58.1% of cases and thoracic in 18.1%; it was from another site in 9.7%; 12.3% of cases were metastases of unknown origin. Pathological diagnosis was made from the examination of surgical samples in 58.1% of cases, biopsy specimens in 33.5%, endoscopic resections in 3.1% and cytological preparations in 4.2%. For the demonstration of the neuroendocrine nature of the tumour, chromogranin A and synaptophysin were tested in, respectively, 97.1 and 82.8% of cases. The differentiation status was definitely provided in 95.7% of cases. Mitotic count was attempted in 80.1% of cases and Ki67 index in 80.7%. In gastroenteropancreatic (GEP)-NETs, histological grading was available in 95.9% of the cases. WHO classification was available or feasible in 94.1% of GEP-NETs and 93.8% of thoracic NETs. TNM staging was performed according to International Union against Cancer in 74.8% of GEP-NETs and according to European Neuroendocrine Tumour Society in 55.6%. CONCLUSIONS: The PRONET study shows that the current recommendations and diagnostic procedures are satisfactorily respected by most pathologists in daily practice.

21 Article Not All Patients with a Pancreatic Neuroendocrine Tumour Will Benefit from All Approved or Recommended Therapeutic Options: A Real-Life Retrospective Study. 2017

Berdelou, Amandine / Boige, Valérie / Arfi-Rouche, Julia / Malka, David / Ederhy, Stéphane / Izzedine, Hassan / Leboulleux, Sophie / Chougnet, Cécile N / Burtin, Pascal / De Baere, Thierry / Laplanche, Agnès / Elias, Dominique / Schlumberger, Martin / Scoazec, Jean-Yves / Ducreux, Michel / Baudin, Eric. ·Department of Nuclear Medicine and Endocrine Tumours, Gustave Roussy, Université Paris XI, Villejuif, France. ·Neuroendocrinology · Pubmed #27225439.

ABSTRACT: BACKGROUND: At least nine therapeutic options are recommended or approved for pancreatic neuroendocrine tumour (pNET). The primary endpoint of this study was to determine the number of therapeutic lines given before death. Secondary endpoints were to determine toxic events as a function of number of therapeutic lines and of time. METHODS: Patients with pNET treated between 1998 and 2010 at our centre were characterised. All therapeutic lines were recorded as well as tumour- or toxic-related deaths. Persistent treatment-related toxicity (PTRT) was defined as: chronic kidney disease, anaemia, thrombocytopenia, neutropenia, severe liver failure, cardiac failure and recurrent sepsis, precluding at least one other therapeutic option or second cancers. RESULTS: Ninety-two patients were analysed. The median follow-up was 7 years. The 1-, 2- and 5-year overall survival rates were 90, 81 and 51%, respectively. After 3 and 5 therapeutic lines, 23 and 50% of patients had died, respectively. After 3 and 5 lines, the frequency of toxic events was 8 and 24%, respectively. Overall, 17 toxic events were observed including 6 treatment-related deaths and 11 PTRT. After 1, 2 and 5 years of treatment, the frequency of toxic events was 6, 9 and 16%, respectively. CONCLUSION: Tumour- and toxic-related deaths as well as PTRT may preclude access to all therapeutic options in patients with pNET. Optimised risk benefit sequence should be investigated.

22 Article Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors. 2015

Bonnavion, Rémy / Teinturier, Romain / Jaafar, Rami / Ripoche, Doriane / Leteurtre, Emmanuelle / Chen, Yuan-Jia / Rehfeld, Jens F / Lepinasse, Florian / Hervieu, Valérie / Pattou, François / Vantyghem, Marie-Christine / Scoazec, Jean-Yves / Bertolino, Philippe / Zhang, Chang Xian. ·INSERM U1052, Lyon, France CNRS UMR5286, Lyon, France Université de Lyon, Lyon, France. · Institut de Pathologie, CHRU de Lille, Lille, France Université Lille 2, INSERM UMR 859, Lille, France. · Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China. · Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. · Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Anatomie Pathologique, Lyon, France. · INSERM U1052, Lyon, France CNRS UMR5286, Lyon, France Université de Lyon, Lyon, France Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Anatomie Pathologique, Lyon, France. · Université Lille 2, INSERM UMR 859, Lille, France CHRU Lille, Endocrine Surgery, Lille, France. · Université Lille 2, INSERM UMR 859, Lille, France CHRU Lille, Endocrinology, Lille, France. · INSERM U1052, Lyon, France CNRS UMR5286, Lyon, France Université de Lyon, Lyon, France Sino-French Life Science and Genomic Center, Ruijin Hospital, Shanghai, China chang.zhang@lyon.unicancer.fr. ·Mol Cell Biol · Pubmed #26169832.

ABSTRACT: The cells of origin of pancreatic gastrinomas remain an enigma, since no gastrin-expressing cells are found in the normal adult pancreas. It was proposed that the cellular origin of pancreatic gastrinomas may come from either the pancreatic cells themselves or gastrin-expressing cells which have migrated from the duodenum. In the current study, we further characterized previously described transient pancreatic gastrin-expressing cells using cell lineage tracing in a pan-pancreatic progenitor and a pancreatic endocrine progenitor model. We provide evidence showing that pancreatic gastrin-expressing cells, found from embryonic day 12.5 until postnatal day 7, are derived from pancreatic Ptf1a(+) and neurogenin 3-expressing (Ngn3(+)) progenitors. Importantly, the majority of them coexpress glucagon, with 4% coexpressing insulin, indicating that they are a temporary subpopulation of both alpha and beta cells. Interestingly, Men1 disruption in both Ngn3 progenitors and beta and alpha cells resulted in the development of pancreatic gastrin-expressing tumors, suggesting that the latter developed from islet cells. Finally, we detected gastrin expression using three human cohorts with pancreatic endocrine tumors (pNETs) that have not been diagnosed as gastrinomas (in 9/34 pNETs from 6/14 patients with multiple endocrine neoplasia type 1, in 5/35 sporadic nonfunctioning pNETs, and in 2/20 sporadic insulinomas), consistent with observations made in mouse models. Our work provides insight into the histogenesis of pancreatic gastrin-expressing tumors.

23 Article O6-Methylguanine-DNA methyltransferase status in neuroendocrine tumours: prognostic relevance and association with response to alkylating agents. 2015

Walter, T / van Brakel, B / Vercherat, C / Hervieu, V / Forestier, J / Chayvialle, J-A / Molin, Y / Lombard-Bohas, C / Joly, M-O / Scoazec, J-Y. ·1] Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'oncologie Digestive, 69437 Lyon, France [2] INSERM, UMR 1052, Lyon Cancer Research Center, Faculté Laennec, 69372 Lyon, France [3] Université de Lyon, Université Claude Bernard Lyon 1, 69622 Villeurbanne, France. · Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'oncologie Digestive, 69437 Lyon, France. · INSERM, UMR 1052, Lyon Cancer Research Center, Faculté Laennec, 69372 Lyon, France. · 1] INSERM, UMR 1052, Lyon Cancer Research Center, Faculté Laennec, 69372 Lyon, France [2] Université de Lyon, Université Claude Bernard Lyon 1, 69622 Villeurbanne, France [3] Hospices Civils de Lyon, Hôpital Edouard Herriot, Service Central d'Anatomie et Cytologie Pathologiques, 69437 Lyon, France. · 1] INSERM, UMR 1052, Lyon Cancer Research Center, Faculté Laennec, 69372 Lyon, France [2] Université de Lyon, Université Claude Bernard Lyon 1, 69622 Villeurbanne, France [3] Hospices Civils de Lyon, Hôpital Edouard Herriot, Hépatogastroentérologie, 69437 Lyon, France. ·Br J Cancer · Pubmed #25584486.

ABSTRACT: BACKGROUND: O(6)-Methylguanine-DNA methyltransferase (MGMT) loss of expression has been suggested to be predictive of response to temozolomide in neuroendocrine tumours (NETs), but so far, only limited data are available. We evaluated the prognostic and predictive value of MGMT status, assessed by two molecular methods and immunohistochemistry, in a large series of NETs of different origins. METHODS: A total of 107 patients, including 53 treated by alkylants (temozolomide, dacarbazine or streptozotocin), were retrospectively studied. In each case, we used methyl-specific PCR (MS-PCR) and pyrosequencing for evaluation of promoter methylation and immunohistochemistry for evaluation of protein status. RESULTS: MGMT promoter methylation was detected in 12 out of 99 (12%) interpretable cases by MS-PCR and in 24 out of 99 (24%) by pyrosequencing. O(6)-Methylguanine-DNA methyltransferase loss of expression was observed in 29 out of 89 (33%) interpretable cases. Status of MGMT was not correlated with overall survival (OS) from diagnosis. Progression-free survival and OS from first alkylant use (temozolomide, dacarbazine and streptozotocin) were higher in patients with MGMT protein loss (respectively, 20.2 vs 7.6 months, P<0.001 and 105 vs 34 months, P=0.006) or MGMT promoter methylation assessed by pyrosequencing (respectively, 26.4 vs 10.8 months, P=0.002 and 77 vs 43 months, P=0.026). CONCLUSIONS: Our results suggest that MGMT status is associated with response to alkylant-based chemotherapy in NETs.

24 Article [Malignant insulinoma: recommendations for workup and treatment]. 2014

Baudin, Eric / Caron, Philippe / Lombard-Bohas, Catherine / Tabarin, Antoine / Mitry, Emmanuel / Reznick, Yves / Taieb, David / Pattou, François / Goudet, Pierre / Vezzosi, Delphine / Scoazec, Jean-Yves / Cadiot, Guillaume / Borson-Chazot, Françoise / Do Cao, Christine / Anonymous1780795. ·Institut Gustave-Roussy, service de médecine nucléaire et d'oncologie endocrinienne, 94805 Villejuif cedex, France. Electronic address: eric.baudin@igr.fr. · CHU Rangueil-Larrey, pôle cardiovasculaire et métabolique, service d'endocrinologie et maladies métaboliques, 31059 Toulouse cedex 9, France. · Hôpital Édouard-Herriot, Fédération des spécialités digestives, 69003 Lyon, France. · Hôpital Haut-Lévêque, service d'endocrinologie, 33600 Pessac, France. · Institut Curie, hôpital René-Huguenin, service d'onco-gastroentérologie, 92210 Saint-Cloud, France. · CHU Côte-de-Nacre, unité fonctionnelle d'endocrinologie et maladies métaboliques, 14033 Caen cedex, France. · CHU de la Timone, service central de biophysique et de médecine nucléaire, 13005 Marseille, France. · Hôpital Claude-Huriez, service de chirurgie endocrinienne, 59000 Lille, France. · CHU de Dijon, service de chirurgie générale et endocrinienne, 21000 Dijon, France. · Institut Gustave-Roussy, service de biologie et de pathologie médicales, 94805 Villejuif cedex, France. · Hôpital Robert-Debré, service d'hépato-gastro-entérologie et de cancérologie digestive, 51100 Reims, France. · Hospices Civils de Lyon, Fédération d'endocrinologie du pole Est, Fédération d'endocrinologie et centre de médecine nucléaire, 69500 Lyon, France. · Hôpital Claude-Huriez, service d'endocrinologie et de maladies métaboliques, 59000 Lille, France. ·Presse Med · Pubmed #24857257.

ABSTRACT: Insulinoma are malignant in 4 to 14 % of cases. Their rarity and the sparse data available in the literature have limited publication of specific guidelines for their management. The following review aim to provide up-to-date recommendations on initial evaluation including pathologic grading, measures to control hypoglycemia, antitumor strategies and long term follow-up. Will be discussed in detail respective indications of surgery, diazoxide, somatostatin analogs, everolimus, sunitinib, liver directed treatments including arterial embolization, chemotherapy and radiometabolic therapy. A Medline search using terms "insulinoma", "neuroendocrine pancreatic tumors", "islet cell carcinoma", "malignant insulinoma" was performed limiting the selection to English language articles and adult age cases, along with cross referencing.

25 Article [Gastroenteropancreatic neuroendocrine tumors: what must the pathologist know and do in 2014?]. 2014

Scoazec, Jean-Yves / Couvelard, Anne / Anonymous1490788. ·Service central d'anatomie et cytologie pathologiques, hôpital Édouard-Herriot, 3, place d'Arsonval, 69437 Lyon cedex 03, France. Electronic address: jean-yves.scoazec@chu-lyon.fr. · Service central d'anatomie et cytologie pathologiques, hôpital Bichat Claude Bernard, 75018 Paris, France. ·Ann Pathol · Pubmed #24630636.

ABSTRACT: The diagnostic management of a possible case of gastroenteropancreatic neuroendocrine tumor has much changed in the last 10 years. It is now made of four successive steps. The first step is the positive diagnosis, i.e. the definitive identification of the neuroendocrine nature of the tumor: it relies on morphological and immunohistochemical arguments; several national and international recommendations have now clarified the immunohistochemical arguments necessary for, and sufficient to make a diagnosis of gastroenteropancreatic neuroendocrine tumor. The second step is the determination of the grade, essential for the evaluation of the risk of progression: it relies on the determination of the proliferative capacities, according to the proposals of the European NeuroEndocrine Tumor Society (ENETS), later adopted by WHO in 2010. The third step is the histoprognostic classification, which must use a standardized terminology: it is required to use the specific classification proposed in 2010 by WHO in the framework of the revision of the classifications of digestive tumors. The last step is staging, which relies on the use of one of the existing TNM classifications, that, official, proposed by UICC/AJCC or that proposed by ENETS. The minimal informations, which must be present in the pathological report have been stated by the Société Française de Pathologie, at the request of the French National Cancer Institute.

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