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Pancreatic Neoplasms: HELP
Articles by Philippe Ruszniewski
Based on 78 articles published since 2010
(Why 78 articles?)
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Between 2010 and 2020, P. Ruszniewski wrote the following 78 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
26 Article Antisecretory Effects of Chimeric Somatostatin/Dopamine Receptor Ligands on Gastroenteropancreatic Neuroendocrine Tumors. 2017

Couvelard, Anne / Pélaprat, Didier / Dokmak, Safi / Sauvanet, Alain / Voisin, Thierry / Couvineau, Alain / Ruszniewski, Philippe. ·From the *Faculté de Médecine Xavier Bichat, INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Unity, Université Paris Diderot; †Université Paris Diderot; ‡Département de Pathologie Beaujon-Bichat, Hôpital Bichat, DHU UNITY, AP-HP, Paris; and §Département de Chirurgie Pancréatico-Biliaire and ∥Département de Gastroentérologie-Pancréatologie, Hôpital Beaujon, DHU UNITY, AP-HP, Clichy, France. ·Pancreas · Pubmed #28375946.

ABSTRACT: OBJECTIVES: The recent finding that gastroenteropancreatic neuroendocrine tumors expressed the dopaminergic D2 receptor in addition to somatostatin (sst) receptors suggested that multiple targeting approaches might decrease hormone hypersecretion more effectively than sst agonists alone. METHODS: To test this hypothesis, (i) we measured the expression of sst receptor type 2 (sst2 receptor) and D2 receptor in 11 gastroenteropancreatic neuroendocrine tumors and (ii) we compared the ability of lanreotide, cabergoline, their combination, and sst/D2 chimeric ligands to decrease chromogranin A (CgA), gastrin, or serotonin release in primary cultures derived from these tumors. RESULTS: Moderate to high positivity was observed for sst2 receptor and D2 receptor, the latter being more expressed in pancreatic tumors. Lanreotide decreased CgA secretion in all cultures, but only 3 tumors responded to cabergoline. No additivity was observed in lanreotide. BIM 23A781 decreased CgA release to the same extent as lanreotide, whereas the other chimeric ligands were less efficient. However, BIM 23A781 was 50 times less potent than lanreotide. Similar patterns were found for gastrin or serotonin. CONCLUSION: No improvement was brought by the sst/D2 combination or chimeric ligands. Factors that underlie these tissue-specific differences remain to be elucidated.

27 Article Neuroendocrine liver metastases: Vascular patterns on triple-phase MDCT are indicative of primary tumour location. 2017

Ronot, Maxime / Cuccioli, Francesco / Dioguardi Burgio, Marco / Vullierme, Marie-Pierre / Hentic, Olivia / Ruszniewski, Philippe / d'Assignies, Gaspard / Vilgrain, Valérie. ·Department of Radiology, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM U1149, centre de recherche biomédicale Bichat-Beaujon, CRB3, Paris, France. Electronic address: maxime.ronot@aphp.fr. · Department of Radiology, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France. · Department of Pancreatology, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France. · University Paris Diderot, Sorbonne Paris Cité, Paris, France; Department of Pancreatology, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France. · Department of Radiology, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM U1149, centre de recherche biomédicale Bichat-Beaujon, CRB3, Paris, France. ·Eur J Radiol · Pubmed #28267533.

ABSTRACT: PURPOSE: To re-evaluate and compare CT features of neuroendocrine liver metastases (NLM) from pancreatic (p) and enteric (e) gastroenteropancreatic (GEP) tumours. MATERIAL AND METHODS: From 2006-2013, all patients with proven GEP-neuroendocrine tumours (NETs) with at least one NLM, no previous treatment were included. On unenhanced, arterial and portal phases, NLMs were characterized as hypo-, iso- or hyperattenuating in consensus by 2 radiologists blinded to clinical data. Enhancement patterns (EP) corresponded to the combination of arterial/portal CT attenuation. RESULTS: 78 patients (43 men, 55%, mean 56±13 yo) and 559NLMs were analyzed. pNLMs were more frequently hypoattenuating on unenhanced CT than eNLMs (72% vs. 57%, p<0.001). 70% of the lesions were hypervascular with no significant difference between pNLMs and eNLMs (p=0.32). eNLMs were more frequently hypoattenuating on portal phase than pNLMs (88% vs. 56%, p<0.001). eNLMs were more frequently hyper/hypo than pNLMs (56% vs. 28%, p<0.001). pNLMs were more frequently hyper/iso than eNLMs (33% vs. 8%, p<0.001). Other NLMs showed various patterns, including hypo/hypo in 12%. CONCLUSION: Most NLMs of GEP tumours are hypervascular but the enhancement pattern on multiphasic CT depends on the primary tumour. These differences are helpful when the primary tumour has not been diagnosed.

28 Article MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors. 2016

Cros, J / Hentic, O / Rebours, V / Zappa, M / Gille, N / Theou-Anton, N / Vernerey, D / Maire, F / Lévy, P / Bedossa, P / Paradis, V / Hammel, P / Ruszniewski, P / Couvelard, A. ·Department of PathologyAP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France U1149 - University Paris DiderotParis, France. · Department of Gastroenterology and PancreatologyAP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France. · U1149 - University Paris DiderotParis, France Department of Gastroenterology and PancreatologyAP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France. · Department of RadiologyAP-HP, DHU UNITY, Beaujon Hospital, Clichy, France. · Department of PathologyAP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France. · Department of Somatic GeneticAP-HP, DHU UNITY, Bichat University Hospital, Paris, France. · Methodology and Quality of Life in Oncology Unit (EA 3181)University Hospital of Besançon, Besançon, France. · U1149 - University Paris DiderotParis, France Department of Digestive OncologyAP-HP, DHU UNITY, Beaujon University Hospital, Clichy, France. · U1149 - University Paris DiderotParis, France Department of PathologyAP-HP, DHU UNITY, Bichat University Hospital, Paris, France anne.couvelard@bch.aphp.fr. ·Endocr Relat Cancer · Pubmed #27353036.

ABSTRACT: Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

29 Article Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study. 2015

Thevenon, J / Bourredjem, A / Faivre, L / Cardot-Bauters, C / Calender, A / Le Bras, M / Giraud, S / Niccoli, P / Odou, M F / Borson-Chazot, F / Barlier, A / Lombard-Bohas, C / Clauser, E / Tabarin, A / Pasmant, E / Chabre, O / Castermans, E / Ruszniewski, P / Bertherat, J / Delemer, B / Christin-Maitre, S / Beckers, A / Guilhem, I / Rohmer, V / Goichot, B / Caron, P / Baudin, E / Chanson, P / Groussin, L / Du Boullay, H / Weryha, G / Lecomte, P / Schillo, F / Bihan, H / Archambeaud, F / Kerlan, V / Bourcigaux, N / Kuhn, J M / Vergès, B / Rodier, M / Renard, M / Sadoul, J L / Binquet, C / Goudet, P. ·CHU de DijonCentre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, University of Burgundy, EA4271 GAD, Dijon, FranceINSERMCIC1432, Dijon, FranceCentre Hospitalier Universitaire de DijonCentre d'Investigation Clinique, éssais cliniques/épidémiologie clinique, Dijon FranceCentre Hospitalier Régional et Universitaire de LilleService de Médecine interne et Endocrinologie, Clinique Marc Linquette, Lille, FranceHospices Civils de LyonHôpital E. Herriot, Génétique moléculaire et clinique, Lyon, FranceCentre Hospitalier Universitaire de NantesClinique d'Endocrinologie, Nantes, FranceAPHMservice d'Oncologie Médicale, Institut Paoli-Calmettes, Université Aix-Marseille, Marseille, FranceCHRU de LilleService d'Hormonologie, Métabolisme-Nutrition, Oncologie, Pôle de Biologie Pathologie Génétique, Université de Lille2, Lille, FranceHospices Civils de Lyon et Université LYON1Groupement hospitalier Est, Fédération d'Endocrinologie, Lyon, FranceAP-HMHôpital la Conception, Laboratoire de Biologie Moléculaire, Marseille, FranceAix-Marseille UniversityCRN2M UMR 7286-CNRS, Marseille, FranceHospices Civils de LyonHôpital E. Herriot, Service d'Oncologie, Lyon, FranceUniversité Paris-DescartesFaculté de Médecine Paris-Descartes-Paris-V, UMR-S970, Paris, FranceAPHPHôpital Cochin, Laboratoire d'Oncogénétique, Paris, FranceCentre Hospitalier Universitaire et Université de Bordeaux 2Service d'Endocrinologie,Hôpital du Haut Levêque, Pessac,FranceAPHPHôpital Cochin, Service de Biochimie et de Génétique Moléculaire,Paris, FranceCentre Hospitalier Universitaire de GrenobleService d'Endocrinologie, Diabète et Maladies métaboliques, Hôpital Michalon, Grenoble,FranceCentre Hospitalier Universitaire de LiègeDomaine Universitaire du Sart-Tilman, University of Liège, Laboratoire de génétique moléculaire, Liège, BelgiumAPHPHôpital Beaujon et Université Paris 7 Denis Diderot, Service de Gastroentérologie-pancréa ·Eur J Endocrinol · Pubmed #26392472.

ABSTRACT: BACKGROUND: MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. METHODS: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. RESULTS: Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs. CONCLUSION: The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.

30 Article Can pancreatic neuroendocrine tumour biopsy accurately determine pathological characteristics? 2015

Rebours, Vinciane / Cordova, Jacqueline / Couvelard, Anne / Fabre, Monique / Palazzo, Laurent / Vullierme, Marie Pierre / Hentic, Olivia / Sauvanet, Alain / Aubert, Alain / Bedossa, Pierre / Ruszniewski, Philippe. ·Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France; Inserm U773-CRB3, Paris-Diderot University, Paris, France. Electronic address: vinciane.rebours@bjn.aphp.fr. · Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France. · Inserm U773-CRB3, Paris-Diderot University, Paris, France; Pathology Department, Bichat Hospital, AP-HP, Paris-Diderot University, France. · Pathology Department, Institut Gustave Roussy, Villejuif, France. · Endoscopy and Gastroenterology Department, Clinique du Trocadéro, Paris, France. · Radiology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France. · Pancreatic Surgery Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France. · Pathology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France. · Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France; Inserm U773-CRB3, Paris-Diderot University, Paris, France. ·Dig Liver Dis · Pubmed #26169284.

ABSTRACT: BACKGROUND: Assessment of the pathological characteristics of pancreatic neuroendocrine tumours is crucial for appropriate management. We compared preoperative pathological data with surgical specimens for accuracy. METHODS: Surgical patients with pancreatic neuroendocrine tumours who underwent preoperative endoscopic ultrasound-guided fine needle aspiration of the primary tumour or biopsy of liver metastasis were retrospectively included. Tumour differentiation and the Ki67 proliferation index on biopsies were compared with pancreatic specimens. RESULTS: Fifty-seven patients were included. A preoperative biopsy of the primary tumour or of a liver metastasis was obtained in 48 and 9 patients respectively. Tumour differentiation was high in 98%, and poor in 2% on biopsy and high in 100% of surgical specimens. Ki67 index values were 0 (0-19) and 2 (0-15) on biopsy and surgical specimens (p=0.01). Correlation between preoperative and surgical findings was stronger for liver (r=0.62, p=0.001) than for pancreas (r=0.23, p=0.11). Correlation for pancreas varied according to the tumour pattern: solid (r=0.24, p=0.16), mixed (r=0.91, p=0.0036) or cystic (r=0.04, p=0.89). Tumour grade was different between pancreatic biopsies and surgical specimens, for grade 1 (63% vs 37%) and grade 2 (28% vs 72%), p=0.0007. CONCLUSIONS: Tumour grade assessment is accurate in biopsies of liver metastases of pancreatic neuroendocrine tumours, while pancreatic fine-needle aspiration biopsies are less accurate.

31 Article Metachronous hormonal syndromes in patients with pancreatic neuroendocrine tumors: a case-series study. 2015

de Mestier, Louis / Hentic, Olivia / Cros, Jérôme / Walter, Thomas / Roquin, Guillaume / Brixi, Hedia / Lombard-Bohas, Catherine / Hammel, Pascal / Diebold, Marie-Danièle / Couvelard, Anne / Ruszniewski, Philippe / Cadiot, Guillaume. · ·Ann Intern Med · Pubmed #25984844.

ABSTRACT: BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) may evolve and cause hormonal hypersecretion-related symptoms that were not present at the initial diagnosis, termed metachronous hormonal syndromes (MHSs). Their setting, characteristics, and outcomes are not well-described. OBJECTIVE: To describe MHSs in patients with sporadic PNETs. DESIGN: Retrospective, multicenter study. SETTING: 4 French referral centers. PATIENTS: Patients with PNETs who developed MHSs related to hypersecretion of insulin, gastrin, vasoactive intestinal peptide, or glucagon between January 2009 and January 2014. MEASUREMENTS: Tumor extension, biological markers, and treatments at initial PNET diagnosis and MHS onset. Pathologic specimens were evaluated centrally, including Ki-67 index and hormone immunolabeling. RESULTS: Of 435 patients with PNETs, 15 (3.4%) were identified as having MHSs involving the hypersecretion of insulin (5 patients), vasoactive intestinal peptide (5 patients), gastrin (2 patients), or glucagon (4 patients). Metachronous hormonal syndromes developed after a median of 55 months (range, 7 to 219) and in the context of PNET progression, stability, and tumor response in 8, 6, and 1 patients, respectively. The median Ki-67 index was 7% (range, 1% to 19%) at PNET diagnosis and 17.5% (range, 2.0% to 70.0%) at MHS onset. Immunolabeling of MHS-related peptides was retrospectively found in 8 of 14 of pathologic PNET specimens obtained before MHS diagnosis. Median survival after MHS onset was 28 months (range, 3 to 56). Seven patients with MHSs died during follow-up, all due to PNETs, including 4 patients with insulin-related MHSs. LIMITATION: Retrospective data collection and heterogeneity of pathologic specimen size and origin. CONCLUSION: Metachronous hormonal syndromes were identified more often in the context of PNET progression and increased Ki-67 indices. Patients with insulin-related MHSs may have decreased survival rates. PRIMARY FUNDING SOURCE: None.

32 Article Reappraisal of pancreatic enucleations: A single-center experience of 126 procedures. 2015

Faitot, Francois / Gaujoux, Sébastien / Barbier, Louise / Novaes, Marleny / Dokmak, Safi / Aussilhou, Béatrice / Couvelard, Anne / Rebours, Vinciane / Ruszniewski, Philippe / Belghiti, Jacques / Sauvanet, Alain. ·AP-HP, Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, DHU UNITY, Clichy, France. · AP-HP, Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, DHU UNITY, Clichy, France; Université Paris Diderot, Paris, France; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Biomédicale Bichat Beaujon, (CRB3)/INSERM U773, Clichy, France. · AP-HP, Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, DHU UNITY, Clichy, France; Université Paris Diderot, Paris, France. · AP-HP, Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, DHU UNITY, Clichy, France; Université Paris Diderot, Paris, France; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Biomédicale Bichat Beaujon, (CRB3)/INSERM U773, Clichy, France; AP-HP, Department of Pathology, Hôpital Beaujon, DHU UNITY, Clichy, France. · Université Paris Diderot, Paris, France; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Biomédicale Bichat Beaujon, (CRB3)/INSERM U773, Clichy, France; AP-HP, Department of Gastroenterology, Hôpital Beaujon, DHU UNITY, Clichy, France. · AP-HP, Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, DHU UNITY, Clichy, France; Université Paris Diderot, Paris, France; Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Biomédicale Bichat Beaujon, (CRB3)/INSERM U773, Clichy, France. Electronic address: alain.sauvanet@bjn.aphp.fr. ·Surgery · Pubmed #25956743.

ABSTRACT: BACKGROUND: Parenchyma-sparing pancreatectomies, especially enucleations, could avoid disappointing functional results associated with standard resections for benign/low-grade pancreatic neoplasms. This study aimed to assess short- and long-term outcomes in a large, single-center series of enucleations. METHODS: All 126 patients who underwent enucleation for benign/low-grade neoplasms between 1996 and 2011 were included retrospectively. RESULTS: Lesions were mainly incidentally diagnosed (71%), most often located in the head (46%), and with a median size of 20 mm. Enucleations were mainly performed for branch-duct intraductal papillary mucinous neoplasm (30%), nonfunctioning pancreatic neuroendocrine tumors (29%), and mucinous cystadenoma (21%). Overall mortality was 0.8% and morbidity 63%, mainly owing to pancreatic fistula (57%). Most were significant clinically, that is, grade B or C (41%), but managed conservatively (85%). Reoperation rate was 3%, mainly owing to hemorrhage. Postoperative de novo diabetes was 0.8%, and exocrine insufficiency never observed. The 1-, 3-, and 5-year recurrence-free survival were 100%, 98%, and 93%, respectively. CONCLUSION: Enucleation is associated with substantial morbidity, especially pancreatic fistula. Enucleations as an alternative to standard resection are best indicated for small, benign, and low-grade lesions located far from the main pancreatic duct. Enucleations should be proposed to young and fit patients able to tolerate postoperative morbidity and who could benefit from the excellent long-term results.

33 Article Laparoscopic pancreaticoduodenectomy should not be routine for resection of periampullary tumors. 2015

Dokmak, Safi / Ftériche, Fadhel Samir / Aussilhou, Béatrice / Bensafta, Yacine / Lévy, Philippe / Ruszniewski, Philippe / Belghiti, Jacques / Sauvanet, Alain. ·Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France. Electronic address: safi.dokmak@bjn.aphp.fr. · Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France. · Department of Gastroenterology, Beaujon Hospital, Clichy, France. ·J Am Coll Surg · Pubmed #25840531.

ABSTRACT: BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is a difficult procedure that has become increasingly popular. Nevertheless, comparative data on outcomes remain limited. Our aim was to compare the outcomes of LPD and open pancreaticoduodenectomy (OPD). STUDY DESIGN: Between April 2011 and April 2014, 46 LPD were performed and compared with 46 OPD, which theoretically can be done by the laparoscopic approach. Patients were also matched for demographic data, associated comorbidities, and underlying disease. Patient demographics and perioperative and postoperative outcomes were studied from our single center prospective database. RESULTS: Lower BMI (23 vs 27 kg/m(2), p < 0.001) and a soft pancreas (57% vs 47%, p = 0.38) were observed in patients with LPD, but there were no differences in associated comorbidities or underlying disease. Surgery lasted longer in the LPD group (342 vs 264 minutes, p < 0.001). One death occurred in the LPD group (2.1% vs 0%, p = 0.28) and severe morbidity was higher (28% vs 20%, p = 0.32) in LPD due to grade C pancreatic fistula (PF) (24% vs 6%, p = 0.007), bleeding (24% vs 7%, p = 0.02), and revision surgery (24% vs 11%, p = 0.09). Pathologic examination for malignant diseases did not identify any differences between the LPD and OPD as far as size (2.51 vs 2.82 cm, p = 0.27), number of harvested (20 vs 23, p = 0.62) or invaded (2.4 vs 2, p = 0.22) lymph nodes, or R0 resection (80% vs 80%; p = 1). Hospital stays were similar (25 vs 23 days, p = 0.59). There was no difference in outcomes between approaches in patients at a lower risk of PF. CONCLUSIONS: This study found that LPD is associated with higher morbidity, mainly due to more severe PF. Laparoscopic pancreaticoduodenectomy should be considered only in the subgroup of patients with a low risk of PF.

34 Article High c-Met expression in stage I-II pancreatic adenocarcinoma: proposal for an immunostaining scoring method and correlation with poor prognosis. 2015

Neuzillet, Cindy / Couvelard, Anne / Tijeras-Raballand, Annemilaï / de Mestier, Louis / de Gramont, Armand / Bédossa, Pierre / Paradis, Valérie / Sauvanet, Alain / Bachet, Jean-Baptiste / Ruszniewski, Philippe / Raymond, Eric / Hammel, Pascal / Cros, Jérôme. ·INSERM UMR1149. · Department of Digestive Oncology, Beaujon University Hospital, Clichy, France. · Paris 7 Denis Diderot University, Paris, France. · Department of Pathology, Bichat-Beaujon University Hospital, Paris-Clichy, France. · Department of Translational Research, AAREC Filia Research, Boulogne-Billancourt, France. · Department of Medical Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. · Department of Biliary and Pancreatic Surgery, Beaujon University Hospital, Clichy, France. · Department of Gastroenterology, Pitié-Salpêtrière University Hospital, Paris, France. · Department of Gastroenterology and Pancreatology, Beaujon University Hospital, Clichy, France. ·Histopathology · Pubmed #25809563.

ABSTRACT: AIMS: c-Met is an emerging biomarker in pancreatic ductal adenocarcinoma (PDAC); there is no consensus regarding the immunostaining scoring method for this marker. We aimed to assess the prognostic value of c-Met overexpression in resected PDAC, and to elaborate a robust and reproducible scoring method for c-Met immunostaining in this setting. METHODS AND RESULTS: c-Met immunostaining was graded according to the validated MetMab score, a classic visual scale combining surface and intensity (SI score), or a simplified score (high c-Met: ≥ 20% of tumour cells with strong membranous staining), in stage I-II PDAC. A computer-assisted classification method (Aperio software) was developed. Clinicopathological parameters were correlated with disease-free survival (DFS) and overall survival(OS). One hundred and forty-nine patients were analysed retrospectively in a two-step process. Thirty-seven samples (whole slides) were analysed as a pre-run test. Reproducibility values were optimal with the simplified score (kappa = 0.773); high c-Met expression (7/37) was associated with shorter DFS [hazard ratio (HR) 3.456, P = 0.0036] and OS (HR 4.257, P = 0.0004). c-Met expression was concordant on whole slides and tissue microarrays in 87.9% of samples, and quantifiable with a specific computer-assisted algorithm. In the whole cohort (n = 131), patients with c-Met(high) tumours (36/131) had significantly shorter DFS (9.3 versus 20.0 months, HR 2.165, P = 0.0005) and OS (18.2 versus 35.0 months, HR 1.832, P = 0.0098) in univariate and multivariate analysis. CONCLUSIONS: Simplified c-Met expression is an independent prognostic marker in stage I-II PDAC that may help to identify patients with a high risk of tumour relapse and poor survival.

35 Article Obesity and Fatty Pancreatic Infiltration Are Risk Factors for Pancreatic Precancerous Lesions (PanIN). 2015

Rebours, Vinciane / Gaujoux, Sébastien / d'Assignies, Gaspard / Sauvanet, Alain / Ruszniewski, Philippe / Lévy, Philippe / Paradis, Valérie / Bedossa, Pierre / Couvelard, Anne. ·Pancreatology Department, Beaujon Hospital, DHU Unity, AP-HP, Clichy, Paris-Diderot University, Paris, France. Inserm U773-CRB3, DHU Unity, Paris-Diderot University, Paris, France. vinciane.rebours@bjn.aphp.fr. · Inserm U773-CRB3, DHU Unity, Paris-Diderot University, Paris, France. Pancreatic Surgery Department, Beaujon Hospital, DHU Unity, AP-HP, Clichy, Paris-Diderot University, Paris, France. · Radiology Department, Beaujon Hospital, DHU Unity, AP-HP, Clichy, Paris-Diderot University, Paris, France. · Pancreatic Surgery Department, Beaujon Hospital, DHU Unity, AP-HP, Clichy, Paris-Diderot University, Paris, France. · Pancreatology Department, Beaujon Hospital, DHU Unity, AP-HP, Clichy, Paris-Diderot University, Paris, France. Inserm U773-CRB3, DHU Unity, Paris-Diderot University, Paris, France. · Pancreatology Department, Beaujon Hospital, DHU Unity, AP-HP, Clichy, Paris-Diderot University, Paris, France. · Inserm U773-CRB3, DHU Unity, Paris-Diderot University, Paris, France. Pathology Department, Beaujon Hospital, DHU Unity, AP-HP, Clichy, Paris-Diderot University, Paris, France. · Inserm U773-CRB3, DHU Unity, Paris-Diderot University, Paris, France. Pathology Department, Bichat Hospital, DHU Unity, AP-HP, Paris-Diderot University, Paris, France. ·Clin Cancer Res · Pubmed #25700304.

ABSTRACT: PURPOSE: The roles of intravisceral and subcutaneous fat are unknown, and the prevalence of precancerous lesions in obese patients was never evaluated. This study aims to assess the frequency and severity of pancreatic intraepithelial neoplasia (PanIN) and to correlate pathologic findings with metabolic abnormalities, type of fat, and fatty pancreatic infiltration. EXPERIMENTAL DESIGN: Normal pancreatic tissue from surgical specimens was analyzed. Fatty infiltration and fibrosis in intra- and extralobular locations and PanIN lesions were assessed. General characteristics were collected: body mass index (BMI), diabetes, and tobacco intake. Liver steatosis and subcutaneous and intravisceral fat were assessed by CT scan (ImageJ software). RESULTS: Of note, 110 patients were included [median age, 53.8 (17-85) years]. Arterial hypertension, diabetes, and tobacco intake were found in 19%, 9%, and 23%, respectively. Median BMI was 24 (16-37; BMI < 25: 45%, 25 ≤ 30: 24%, ≥30: 11%). Overall, PanIN lesions were found in 65% (type I, II, and III PanIN in 62%, 38%, and 1%, respectively). Fibrosis and fatty pancreas (intra- and extralobular locations) were found in 1% and 24% and in 30% and 51%, respectively. A correlation was observed between PanIN lesions and fatty pancreas [extralobular (0.01) and intralobular (<0.0001)], intralobular fibrosis (0.003), high BMI (P = 0.02), and subcutaneous (P = 0.02) and intravisceral fat (P = 0.02). The number of PanIN lesions was correlated with intravisceral fat (r = 0.22, P = 0.04), but not with subcutaneous fat (r = 0.14, P = 0.22). In multivariate analysis, PanIN lesions were associated with intralobular fibrosis [OR, 5.61; 95% confidence interval (CI), 1.18-42.99] and intralobular fat (OR, 17.86; 95% CI, 4.935-88.12). CONCLUSIONS: Obesity (especially android obesity) and pancreatic fatty infiltration are risk factors for pancreatic precancerous lesions.

36 Article MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d'étude des Tumeurs Endocrines. 2015

Goudet, P / Dalac, A / Le Bras, M / Cardot-Bauters, C / Niccoli, P / Lévy-Bohbot, N / du Boullay, H / Bertagna, X / Ruszniewski, P / Borson-Chazot, F / Vergès, B / Sadoul, J L / Ménégaux, F / Tabarin, A / Kühn, J M / d'Anella, P / Chabre, O / Christin-Maitre, S / Cadiot, G / Binquet, C / Delemer, B. ·Centre Hospitalier Universitaire de Dijon (P.G.), Endocrine Surgery, Dijon, France · INSERM U866, Dijon, France · University of Burgundy, Dijon, France · Service d'Endocrinologie et Maladies Métaboliques (A.D., N.L-B.), Centre Hospitalier Universitaire, Hôpital Robert Debré, Reims, France, Clinique d'Endocrinologie (M.L.), Centre Hospitalier Universitaire, Nantes, France · Service de Médecine Interne et Endocrinologie (C.C-B.), Clinique Marc Linquette, Centre Hospitalier Régional et Universitaire, Lille, France · Service d'Oncologie Médicale (P.N.), Institut Paoli-Calmettes, APHM, Université Aix-Marseille, Marseille, France · Service d'Endocrinologie (H.dB.), Centre Hospitalier de Chambéry, Chambéry, France · Département d'Endocrinologie (X.B.), Hôpital Cochin, Université Paris Descartes, Paris, France · Service de Gastroentérologie-Pancréatologie (P.R.), APHP, Hôpital Beaujon et Université Paris 7 Denis Diderot, Clichy, France · Fédération d'Endocrinologie (F.B-C.), Hospice Civils de Lyon et Université Lyon 1, Groupement Hospitalier Est. Lyon, France · Service d'Endocrinologie (B.V.), Diabète et Maladies Métaboliques, Centre Hospitalier Universitaire de Dijon, Hôpital du Bocage, Dijon, France · Département d'Endocrinologie (J.L.S.), Hopital de l'Archet, Nice, France · Service de Chirurgie Générale (F.M.), Viscérale et Endocrinienne, Groupement Hospitalier Universitaire Est, Hôpital de la Pitié, Paris, France · Service d'Endocrinologie (A.T.), Centre Hospitalier Universitaire, Hôpital du Haut Levêque, Pessac, France · Département d'Endocrinologie (J.M.K.), Hôpital Universitaire de Rouen. Rouen, France · Service d'Endocrinologie (P.dA.), Centre Hospitalier d'Avignon, Avignon, France · Service d'Endocrinologie (O.C.), Diabète et Maladies Métaboliques, Centre Hospitalier Universitaire de Grenoble, Hôpital Michalon, Grenoble, France · Service d'Endocrinologie (S.C-M.), Centre Hôpitalier Universitaire. Hôpital St-Antoine, Paris, France · Service d'Hép ·J Clin Endocrinol Metab · Pubmed #25594862.

ABSTRACT: CONTEXT: Multiple endocrine neoplasia Type-1 (MEN1) in young patients is only described by case reports. OBJECTIVE: To improve the knowledge of MEN1 natural history before 21 years old. METHODS: Obtain a description of the first symptoms occurring before 21 years old (clinical symptoms, biological or imaging abnormalities), surgical outcomes related to MEN1 Neuro Endocrine Tumors (NETs) occurring in a group of 160 patients extracted from the "Groupe d'étude des Tumeurs Endocrines" MEN1 cohort. RESULTS: The first symptoms were related to hyperparathyroidism in 122 cases (75%), pituitary adenoma in 55 cases (34%), nonsecreting pancreatic tumor (NSPT) in 14 cases (9%), insulinoma in 20 cases (12%), gastrinoma in three cases (2%), malignant adrenal tumors in 2 cases (1%), and malignant thymic-NET in one case (1%). Hyperparathyrodism was the first lesion in 90 cases (56%). The first symptoms occurred before 10 years old in 22 cases (14%) and before 5 years old in five cases (3%). Surgery was performed before age 21 in 66 patients (41%) with a total of 74 operations: pituitary adenoma (n = 9, 16%), hyperparathyroidism (n = 38, 31%), gastrinoma (n = 1, 33%), NSPT (n = 5, 36%), and all cases of insulinoma, adrenal tumors, and thymic-NET. One patient died before age 21 due to a thymic-NET. Overall, lesions were malignant in four cases. CONCLUSIONS: Various MEN1 lesions occurred frequently before 21 years old, but mainly after 10 years of age. Rare, aggressive tumors may develop at any age. Hyperparathyroidism was the most frequently encountered lesion but was not always the first biological or clinical abnormality to appear during the course of MEN1.

37 Article Endoscopic management of pancreatic fistula after enucleation of pancreatic tumors. 2015

Maire, Frédérique / Ponsot, Philippe / Debove, Clotilde / Dokmak, Safi / Ruszniewski, Philippe / Sauvanet, Alain. ·Service de Gastroentérologie-Pancréatologie, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92118, Clichy Cedex, France. frederique.maire@bjn.aphp.fr. · Service de Gastroentérologie-Pancréatologie, Hôpital Beaujon, AP-HP, 100 Boulevard du Général Leclerc, 92118, Clichy Cedex, France. · Service de Chirurgie Viscérale, Hôpital Beaujon, AP-HP, Clichy Cedex, France. · Paris-Diderot University, Paris, France. ·Surg Endosc · Pubmed #25515987.

ABSTRACT: INTRODUCTION: Pancreatic fistula (PF) are frequent after pancreatic surgical resection, and particularly after enucleation. Endoscopic treatment might be proposed for postoperative PF, but has never been evaluated after pancreatic enucleation. PATIENTS AND METHODS: From January 2000 to June 2012, 161 patients underwent pancreatic enucleation in our center. In case of PF in the postoperative period, conservative management (somatostatin analogs combined with enteral or parenteral nutrition and drainage) was proposed. If PF persisted after 20 days (output >50 cc/d), endoscopic treatment (pancreatic sphincterotomy and stent placement if evidence of main duct leakage) was proposed. Primary outcome was the delay of PF closure after endoscopic treatment. RESULTS: Ninety-one patients (56 %) developed postoperative PF. PF closed within 3 weeks with conservative management in 78 (86 %) patients. Endoscopic treatment was required in 7 (8 %) patients. Daily PF output was 240 (50-300) mL. Pancreatic sphincterotomy was performed in all patients. A pancreatic stent was inserted in 4 of 5 patients with main pancreatic duct leakage. One patient presented a stent migration requiring a second procedure. No complication of endoscopic treatment was reported. The closure of PF was obtained in all cases, after 13 (3-24) days. Pancreatic stents were removed after 2, 5, 5, and 8 months, respectively. Median postoperative follow-up was 46 (21-70) months. At study endpoint, two patients had small asymptomatic pancreatic collections, four had mild dilatation of main pancreatic duct upstream pancreatic duct leakage, and none developed exocrine pancreatic insufficiency, diabetes, or recurrence of pancreatic tumor. CONCLUSIONS: PF occurs in half patients after enucleation. Endoscopic treatment combining pancreatic sphincterotomy and stenting is safe and effective if conservative treatment fails, avoiding a complementary pancreatic resection.

38 Article Long-term Prognosis of Resected Pancreatic Neuroendocrine Tumors in von Hippel-Lindau Disease Is Favorable and Not Influenced by Small Tumors Left in Place. 2015

de Mestier, Louis / Gaujoux, Sébastien / Cros, Jérôme / Hentic, Olivia / Vullierme, Marie-Pierre / Couvelard, Anne / Cadiot, Guillaume / Sauvanet, Alain / Ruszniewski, Philippe / Richard, Stéphane / Hammel, Pascal. ·*Department of Gastroenterology and Pancreatology, Beaujon Hospital, Clichy, France; †Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré Hospital, Reims-Champagne-Ardennes University, Reims, France; ‡Department of Hepato-Pancreatico-Biliary Surgery, Beaujon Hospital, Clichy, France; §Denis-Diderot University, Paris, France; Departments of ¶Pathology, and ‖Radiology, Beaujon Hospital, Clichy, France; **Department of Pathology, Bichat Hospital, Paris, France; ††Expert National Center for Rare Cancers PREDIR, INCa/APHP, Bicêtre Hospital, Le Kremlin-Bicêtre, France; and ‡‡Oncogenetics EPHE Laboratory and INSERM U753, Faculty of Medicine Paris Sud, Le Kremlin-Bicêtre, France. ·Ann Surg · Pubmed #25185468.

ABSTRACT: BACKGROUND: Management of pancreatic neuroendocrine tumors (PNETs) associated with von Hippel-Lindau disease (VHL) is challenging because of the malignant potential and difficulty in predicting prognosis. OBJECTIVE: Compare the long-term outcome of resected VHL-PNET and sporadic PNET. METHODS: Data of all patients with VHL (n = 23) operated on for nonmetastatic PNET were reviewed. Patient characteristics and recurrence-free survival rates were compared with those in patients operated on for sporadic PNET, matched for tumor size, stage, and Ki-67 index. RESULTS: Patients in both groups had similar demographic characteristics, except that patients with VHL were younger (36 vs 56 years, P < 0.0001). Median tumor size was 30 mm. Median Ki-67 index was 3% and 4% in the VHL and sporadic groups (P = 0.95), respectively, and lymph node metastases were present in 43% and 30% of cases, respectively (P = 0.45). Sixteen (70%) patients with VHL had multiple PNET; lesions less than 15 mm were left in place in 11 patients. Median postoperative follow-up was 107 months (interquartile range, 57-124 months) and 71 months (interquartile range, 58-131 months) in the VHL and control groups, respectively. Median recurrence-free survival could not have been estimated in the VHL group due to the low number of events (hazard ratio, 5.6; 95% confidence interval, 1.4-22.6; P = 0.013). Five patients with VHL died (3 from VHL-related tumors including 1 from PNET), whereas only one control patient died due to unrelated causes. CONCLUSIONS: The long-term outcome of resected VHL-PNET is better than that of sporadic PNET. PNET less than 15 mm left in place did not progress. A parenchyma-sparing surgical strategy seems appropriate in patients with VHL-PNET, who may develop more life-threatening tumors of other organs.

39 Article Adenocarcinoma of the pancreas: Does prognosis depend on mode of lymph node invasion? 2014

Buc, E / Couvelard, A / Kwiatkowski, F / Dokmak, S / Ruszniewski, P / Hammel, P / Belghiti, J / Sauvanet, A. ·Department of Hepato-Pancreato-Biliary Surgery - Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, hôpital Beaujon, Clichy, France. Electronic address: ebuc@chu-clermontferrand.fr. · Department of Pathology, AP-HP, hôpital Beaujon, Clichy, France. · Department of Biostatistics, Centre Jean Perrin, Clermont-Ferrand, France. · Department of Hepato-Pancreato-Biliary Surgery - Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, hôpital Beaujon, Clichy, France. · Department of Gastroenterology, Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, hôpital Beaujon, Clichy, France. ·Eur J Surg Oncol · Pubmed #24923739.

ABSTRACT: BACKGROUND: Lymph node (LN) invasion in pancreatic ductal adenocarcinoma (PDAC) is the most important prognostic factor after surgical resection. The mechanisms of LN invasion include lymphatic spreading and/or direct extension from the main tumor. However, few studies have assessed the impact of these different patterns of invasion on prognosis. PATIENTS AND METHODS: Pathologic reports of pancreatic resections for PDAC from 1997 to 2007 were retrospectively analyzed. The mode of LN invasion was defined as follows: standard lymphatic metastases (S), contiguous from the main tumor (C) and standard with extracapsular invasion (EI). Clinical outcomes were compared according to the mode of invasion and the number of invaded LN. RESULTS: 306 patients were reviewed. Median age at resection was 61 years (range, 34-81). Eighty seven patients were N- (28.9%) and 214 were N+ (71.1%). Of the N+ patients, 195 (91.1%) were S+, 35 (16.3%) were C+, and 24 (12.3% of the S+ patients) were EI+. Median survival in N+ patients was lower than in N- patients (29 vs. 57 months, p < 0.001). In patients without standard involvement, C+ patients (n = 19) had worse survival than C- patients (n = 47) (34 vs. 57 months, p = 0.037). In S+ patients, C status was correlated with prognosis when the number of LN S+ was <2 (p = 0.07). EI status had no influence on prognosis. On multivariate analysis, only perineural invasion (p = 0.02) and LN ratio (p = 0.042) were independent prognostic factors. CONCLUSION: Direct invasion of LN by the tumor is predictive of reduced survival, but has little impact compared to standard LN involvement and perineural invasion.

40 Article Lessons from McCune-Albright syndrome-associated intraductal papillary mucinous neoplasms: : GNAS-activating mutations in pancreatic carcinogenesis. 2014

Parvanescu, Alina / Cros, Jérôme / Ronot, Maxime / Hentic, Olivia / Grybek, Virginie / Couvelard, Anne / Levy, Philippe / Chanson, Philippe / Ruszniewski, Philippe / Sauvanet, Alain / Gaujoux, Sebastien. ·Assistance Publique-Hôpitaux de Paris, Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Clichy, France2Institut National de la Santé et de la Recherche Médicale, Unité 773, Groupe Hospitalier Paris. · Institut National de la Santé et de la Recherche Médicale, Unité 773, Groupe Hospitalier Paris-Nord Val de Seine, Paris, France3Assistance Publique-Hôpitaux de Paris, Department of Pathology, Hôpital Beaujon, Clichy, France4Université Paris Diderot, Paris. · Université Paris Diderot, Paris, France5Assistance Publique-Hôpitaux de Paris, Department of Radiology, Hôpital Beaujon, Clichy, France. · Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Clichy, France. · Institut National de la Santé et de la Recherche Médicale, Unité 986, Groupe Hospitalier Paris-Sud, Le Kremlin-Bicêtre, France. · Institut National de la Santé et de la Recherche Médicale, Unité 773, Groupe Hospitalier Paris-Nord Val de Seine, Paris, France4Université Paris Diderot, Paris, France8Assistance Publique-Hôpitaux de Paris, Department of Pathology, Hôpital Bichat, Paris. · Université Paris Diderot, Paris, France6Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Clichy, France. · Université Paris-Sud 11, Unité Mixte de Recherche 693, Le Kremlin-Bicêtre, France10Assistance Publique-Hôpitaux de Paris, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Service d'Endocrinologie et des Maladies de la Reproduction. · Institut National de la Santé et de la Recherche Médicale, Unité 773, Groupe Hospitalier Paris-Nord Val de Seine, Paris, France4Université Paris Diderot, Paris, France6Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology, Hôpital Beaujon. · Assistance Publique-Hôpitaux de Paris, Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, Clichy, France4Université Paris Diderot, Paris, France. ·JAMA Surg · Pubmed #24898823.

ABSTRACT: GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in McCune-Albright syndrome, characterized by fibrous dysplasia, precocious puberty, and café au lait spots. Recently, IPMNs have been described as a McCune-Albright syndrome-associated tumor, present in about 15% of patients. The aim of the present work was to assess the prevalence of polyostotic fibrous dysplasia and McCune-Albright syndrome among patients operated on for presumptive sporadic IPMNs. All patients operated on for IPMNs between January 1, 2007, and December 31, 2012, with available imaging were retrospectively screened for polyostotic fibrous dysplasia based on their preoperative abdominal or thoracoabdominal spiral computed tomography images. Systematic screening of 272 patients operated on for IPMNs revealed 1 patient with axial and peripheral polyostotic fibrous dysplasia and café au lait spots on clinical examination suggestive of McCune-Albright syndrome. This patient had been operated on for an unusually large invasive colloid adenocarcinoma (pT3N0M0 R0) derived from an intestinal subtype GNAS-mutated IPMN. The patient underwent adjuvant chemotherapy with gemcitabine for 6 months and was alive without recurrence 6 years later. Besides providing additional evidence of a syndromic IPMN as a feature of McCune-Albright syndrome, this observation is further evidence of the functional oncogenic consequences of GNAS mutations in the pancreas.

41 Article CT and MR imaging of multilocular acinar cell cystadenoma: comparison with branch duct intraductal papillary mucinous neoplasia (IPMNs). 2014

Delavaud, Christophe / d'Assignies, Gaspard / Cros, Jérome / Ruszniewski, Philippe / Hammel, Pascal / Levy, Philippe / Couvelard, Anne / Sauvanet, Alain / Dokmak, Safi / Vilgrain, Valérie / Vullierme, Marie-Pierre. ·Service de Radiologie, Hôpital Beaujon, 100, Boulevard du Général Leclerc, 92118, Clichy Cedex, France, christophe.delavaud@hotmail.fr. ·Eur Radiol · Pubmed #24895037.

ABSTRACT: OBJECTIVES: To describe CT and MR imaging findings of acinar cell cystadenoma (ACC) of the pancreas and to compare them with those of branch duct intraductal papillary mucinous neoplasia (BD-IPMN) to identify distinctive elements. METHODS: Five patients with ACC and the 20 consecutive patients with histologically proven BD-IPMN were retrospectively included. Clinical and biological information was collected and histological data reviewed. CT and MR findings were analysed blinded to pathological diagnosis in order to identify imaging diagnostic criteria of ACC. RESULTS: Patients with ACC were symptomatic in all but one case and were younger than those with BD-IPMN (p = 0.006). Four radiological criteria allowed for differentiating ACC from IPMN: five or more cysts, clustered peripheral small cysts, presence of cyst calcifications and absence of communication with the main pancreatic duct (p < 0.05). Presence of at least two or three of these imaging criteria had a strong diagnostic value for ACC with a sensitivity of 100% and 80% and a specificity of 85% and 100%, respectively. CONCLUSIONS: Preoperative differential diagnosis between ACC and BD-IPMN can be achieved using a combination of four CT and/or MR imaging criteria. Recognition of ACC patients could change patient management and lead to more conservative treatment. KEY POINTS: Four imaging findings are associated with acinar cell cystadenoma (ACC). Imaging could achieve differential diagnosis between ACC and BD-IPMN. Diagnosis on imaging would change patient management and avoid surgical resection.

42 Article Reappraisal of central pancreatectomy a 12-year single-center experience. 2014

Goudard, Yvain / Gaujoux, Sebastien / Dokmak, Safi / Cros, Jérôme / Couvelard, Anne / Palazzo, Maxime / Ronot, Maxime / Vullierme, Marie-Pierre / Ruszniewski, Philippe / Belghiti, Jacques / Sauvanet, Alain. · ·JAMA Surg · Pubmed #24740703.

ABSTRACT: IMPORTANCE: Central pancreatectomy, as an alternative to standard resection for benign and low-grade pancreatic neoplasms, has been described in mainly small retrospective series. OBJECTIVE: To describe a large single-center experience with central pancreatectomy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective case series in a tertiary referral center included 100 consecutive patients undergoing central pancreatectomy with pancreaticogastrostomy from January 1, 2000, to March 1, 2012. MAIN OUTCOMES AND MEASURES: Surgical indications, postoperative morbidity, mortality, and long-term outcomes regarding pancreatic function and recurrence. RESULTS: Central pancreatectomies were performed mainly for neuroendocrine tumors (35%), intraductal papillary mucinous neoplasms (33%), solid pseudopapillary neoplasms(12%), and mucinous cystadenomas (6%). The postoperative mortality rate was 3% (due to pulmonary embolisms in 2 patients and hemorrhage after pancreatic fistula in 1 patient). Clavien-Dindo III or IV complications occurred in 15%of patients and were due mainly to pancreatic fistula, requiring 10 radiologic drainage procedures, 7 endoscopic procedures, and 6 reoperations overall. After a median follow-up of 36 months, the rates of new-onset exocrine and endocrine insufficiency were 6%and 2%, respectively. Overall, 7 lesions could be considered undertreated, including 3 node-negative R0 microinvasive intraductal papillary mucinous neoplasms (without recurrence at 27, 29, and 34 months) and 4 node-positive neuroendocrine tumors (with 1 hepatic recurrence at 66 months). Among the 25 patients with a doubtful preoperative diagnosis, 9 could be considered over treated (ie, operated on for benign non evolutive asymptomatic lesions). CONCLUSIONS AND RELEVANCE: Central pancreatectomy is associated with an excellent pancreatic function at the expense of a significant morbidity and a non-nil mortality rate,underestimated by the published literature. The procedure is best indicated for benign or low-grade lesions in young and fit patients who can sustain a significant postoperative morbidity and could benefit from the excellent long-term results.

43 Article In situ proteomic analysis by MALDI imaging identifies ubiquitin and thymosin-β4 as markers of malignant intraductal pancreatic mucinous neoplasms. 2014

Rebours, Vinciane / Le Faouder, Julie / Laouirem, Samira / Mebarki, Mounya / Albuquerque, Miguel / Camadro, Jean-Michel / Léger, Thibaut / Ruszniewski, Philippe / Lévy, Philippe / Paradis, Valérie / Bedossa, Pierre / Couvelard, Anne. ·Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France; Inserm U773-CRB3, Paris-Diderot University, Paris, France. Electronic address: vinciane.rebours@bjn.aphp.fr. · Inserm U773-CRB3, Paris-Diderot University, Paris, France. · Inserm U773-CRB3, Paris-Diderot University, Paris, France; Pathology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France. · Mass Spectrometry Facility, Jacques Monod Institute, UMR7592, Paris-Diderot University - CNRS, Paris, France; Molecular and Cellular Pathology Program, Jacques Monod Institute, UMR7592, Paris-Diderot University - CNRS, Paris, France. · Mass Spectrometry Facility, Jacques Monod Institute, UMR7592, Paris-Diderot University - CNRS, Paris, France. · Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France; Inserm U773-CRB3, Paris-Diderot University, Paris, France. · Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France. · Inserm U773-CRB3, Paris-Diderot University, Paris, France; Pathology Department, Bichat Hospital, AP-HP, Paris-Diderot University, France. ·Pancreatology · Pubmed #24650966.

ABSTRACT: PURPOSE: Intraductal pancreatic mucinous neoplasms (IPMN) are precancerous cystic lesions. The aim was to investigate the in situ IPMN proteome using MALDI (Matrix-Assisted Laser Desorption/Ionisation) imaging and to characterize biomarkers associated with the grade of dysplasia. EXPERIMENTAL DESIGN: Frozen human Branch duct -IPMN sections were selected according to dysplasia and proteomic analyses were performed by MALDI imaging to obtain mass spectra distribution. The most discriminating peaks were identified using tissue extraction and nanoLC-ESI-MS/MS. Identified peaks were validated in independent series of IPMN by immunochemistry on surgical specimens (tissue-microarrays (TMA), n = 45) and endoscopic ultrasound fine-needle aspiration (EUS FNA) samples (n = 25). RESULTS: BD-IPMN samples with low (n = 10) and high (n = 10) grades of dysplasia were analyzed. Differential spectra of proteins were found in the two groups with significantly different intensities (n = 15). The two peaks (intense in high grade IPMN) (m/z 8565 and 4747) were characterized as the monomeric ubiquitin (Mascot score = 319.22) and an acetylated fragment of thymosin-β4 (2-42) (Omssa score = 1.37 E-9). Validation on TMA and EUS FNA samples confirmed that ubiquitin was overexpressed in high grade dysplasia (p = 0.04 and p = 0.0004). Thymosin-β4 expression was confirmed on TMA by immunohistochemistry on high grade IPMN (p = 0.011). CONCLUSION: Ubiquitin and thymosin-β4 are overexpressed in IPMN with high grade dysplasia. Positive immunochemical staining on EUS-FNA material is a major argument in support of preventive resection.

44 Article Parenchyma-sparing pancreatectomy for presumed noninvasive intraductal papillary mucinous neoplasms of the pancreas. 2014

Sauvanet, Alain / Gaujoux, Sébastien / Blanc, Benjamin / Couvelard, Anne / Dokmak, Safi / Vullierme, Marie-Pierre / Ruszniewski, Philippe / Belghiti, Jacques / Lévy, Philippe. ·*Department of Hepato-Pancreato-Biliary Surgery-Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, Beaujon Hospital, Clichy, France †University Paris 7 Denis Diderot, Paris, France ‡Department Hospitalo-Universitaire UNITY (Addressing Unmet Needs for Innovation in HepaTology and GastroenterologY) §Department of Pathology ¶Department of Radiology ‖Department of Gastroenterology, Pôle des Maladies de l'Appareil Digestif, AP-HP, Beaujon Hospital, Clichy, France. ·Ann Surg · Pubmed #24646561.

ABSTRACT: OBJECTIVE: To assess the feasibility and outcomes of parenchyma-sparing pancreatectomy (PSP), including enucleation (EN), resection of uncinate process (RUP), and central pancreatectomy (CP), as an alternative to standard pancreatectomy for presumed noninvasive intraductal papillary and mucinous neoplasms (IPMNs). BACKGROUND: Pancreaticoduodenectomy and distal pancreatectomy are associated with significant perioperative morbidity, a substantial risk of pancreatic insufficiency, and may overtreat noninvasive IPMNs. METHODS: From 1999 to 2011, PSP was attempted in 91 patients with presumed noninvasive IPMNs, after complete preoperative work-up including computed tomography, magnetic resonance imaging, and endoscopic ultrasonography. Intraoperative frozen section examination was routinely performed to assess surgical margins and rule out invasive malignancy. Follow-up included clinical, biochemical, and radiological assessments. RESULTS: Overall PSP was achieved with a feasibility rate of 89% (n = 81), including 44 ENs, 5 RUPs, and 32 CPs. Postoperative mortality rate was 1.3% (n = 1), and overall morbidity was noteworthy (61%; n = 47). Definitive pathological examination confirmed IPMN diagnosis in 95% of patients (n = 77), all except 2 (3%), without invasive component. After a median follow-up of 50 months, both pancreatic endocrine/exocrine functions were preserved in 92% of patients. Ten-year progression-free survival was 76%, and reoperation for recurrence was required in 4% of patients (n = 3). CONCLUSIONS: In selected patients, PSP for presumed noninvasive IPMN in experienced hands is highly feasible and avoids inappropriate standard resections for IPMN-mimicking lesions. Early morbidity is greater than that after standard resections but counterbalanced by preservation of pancreatic endocrine/exocrine functions and a low rate of reoperation for tumor recurrence.

45 Article Pure laparoscopic middle pancreatectomy: single-center experience with 13 cases. 2014

Dokmak, Safi / Aussilhou, Béatrice / Ftériche, Fadhel Samir / Levy, Philippe / Ruszniewski, Philippe / Belghiti, Jacques / Sauvanet, Alain. ·Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, Clichy, France, safi.dokmak@bjn.aphp.fr. ·Surg Endosc · Pubmed #24380987.

ABSTRACT: BACKGROUND: Laparoscopic pancreatic surgery is performed with increasing frequency, but laparoscopic middle pancreatectomy (LMP) is rarely described. This study aimed retrospectively to describe the authors' unicentrically and prospectively collected data at a specialized center. METHODS: Since July 2011, 13 patients have undergone LMP. In this study, all their demographics and operative and postoperative data were studied from a prospectively maintained database. RESULTS: The study included eight women and five men with a mean age of 51 (range 27-75 years) and a body mass index of 26 kg/m(2) (range 22-32 kg/m(2)). The main indications were neuroendocrine tumor (n = 7), intraductal papillary mucinous neoplasia (n = 2), solid pseudopapillary tumor (n = 2), and other (n = 2). The median duration of surgery was 190 min (range 120-285 min), and the mean blood loss was 100 ml (range 50-800 ml). Only one conversion was performed (8 %). The postoperative outcomes showed no mortality. Clinically significant pancreatic fistula (B and C) were found in 30 % of the cases. Bleeding was observed in two patients (15 %) and reintervention in three patients (23 %). The median hospital stay was 24 days (range 14-53 days), with no readmissions. The long-term follow-up evaluation showed no endocrine insufficiency and only one endocrine insufficiency (8 %). CONCLUSIONS: LMP is a safe surgical procedure allowing a minimally invasive approach for low malignant-potential lesions and offering a postoperative outcome comparable with that of the open approach.

46 Article Sporadic nonfunctioning pancreatic neuroendocrine tumors: prognostic significance of incidental diagnosis. 2014

Birnbaum, David Jérémie / Gaujoux, Sébastien / Cherif, Rim / Dokmak, Safi / Fuks, David / Couvelard, Anne / Vullierme, Marie-Pierre / Ronot, Maxime / Ruszniewski, Philippe / Belghiti, Jacques / Sauvanet, Alain. ·Department of Hepato-Pancreato-Biliary Surgery - Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, hôpital Beaujon, Clichy, France. · Department of Hepato-Pancreato-Biliary Surgery - Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, hôpital Beaujon, Clichy, France; Université Paris Diderot, Paris, France; Centre de Recherche Biomédicale Bichat Beaujon (CRB3)/INSERM U773, Institut National de la Santé et de la Recherche Médicale, Paris, France. · Department of Hepato-Pancreato-Biliary Surgery - Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, hôpital Beaujon, Clichy, France; Université Paris Diderot, Paris, France. · Université Paris Diderot, Paris, France; Centre de Recherche Biomédicale Bichat Beaujon (CRB3)/INSERM U773, Institut National de la Santé et de la Recherche Médicale, Paris, France; Département of Pathology, AP-HP, hôpital Beaujon, Clichy, France. · Department of Radiology, AP-HP, hôpital Beaujon, Clichy, France. · Université Paris Diderot, Paris, France; Département of Pathology, AP-HP, hôpital Beaujon, Clichy, France; Department of Radiology, AP-HP, hôpital Beaujon, Clichy, France. · Université Paris Diderot, Paris, France; Centre de Recherche Biomédicale Bichat Beaujon (CRB3)/INSERM U773, Institut National de la Santé et de la Recherche Médicale, Paris, France; Department of Gastroenterology, Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, hôpital Beaujon, Clichy, France. · Department of Hepato-Pancreato-Biliary Surgery - Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, hôpital Beaujon, Clichy, France; Université Paris Diderot, Paris, France. Electronic address: alain.sauvanet@bjn.aphp.fr. ·Surgery · Pubmed #24238123.

ABSTRACT: BACKGROUND: Sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed as incidentalomas, and their resection is usually recommended. The prognostic significance of this diagnosis feature is poorly studied, and management of these tumors remains controversial. Clinical, pathologic characteristics and outcome of resected incidentally diagnosed NF-PNET (Inc) were compared with resected symptomatic NF-PNET (Symp) to better assess their biologic behavior and tailor their management. METHODS: From 1994 to 2010, 108 patients underwent resection for sporadic nonmetastatic NF-PNET. Diagnosis was considered as incidental in patients with no abdominal symptoms or symptoms unlikely to be related to tumor mass. Patients with Inc were compared with patients with Symp, regarding demographics, postoperative course, pathology, and disease-free survival (DFS). RESULTS: Of the 108 patients, 65 (61%) had incidentally diagnosed tumors. Pancreas-sparing pancreatectomies (enucleation/central pancreatectomy) were performed more frequently in Inc (62% vs 30%, P = .001). Inc tumors were more frequently <20 mm (65% vs 42%, P = .019), staged T1 (62% vs 33%, P = .0001), node negative (85% vs 60%; P = .005), and grade 1 (66% vs 33%, P = .0001). One postoperative death occurred in the Inc group, and postoperative morbidity was similar between the two groups (60% vs 65%, P = .59). DFS was substantially better in the Inc group (5-year DFS = 92% vs 82%, P = .0016). CONCLUSION: Incidentally diagnosed NF-PNETs are associated with less aggressive features compared with symptomatic lesions but cannot always be considered to be benign. Operative resection remains recommended for most. Incidentally diagnosed NF-PNET may be good candidates for pancreas-sparing pancreatectomies.

47 Article EGFR expression in pancreatic adenocarcinoma. Relationship to tumour morphology and cell adhesion proteins. 2014

Handra-Luca, Adriana / Hammel, Pascal / Sauvanet, Alain / Lesty, Claude / Ruszniewski, Philippe / Couvelard, Anne. ·Département d'Anatomie pathologique, APHP Hôpital Avicenne, , Bobigny, France. ·J Clin Pathol · Pubmed #24170210.

ABSTRACT: AIMS: We aimed to study epidermal growth factor receptor (EGFR) expression in surgically resected pancreatic ductal adenocarcinomas (PDACs) by immunohistochemistry and their relationship to clinicopathological features, cell proliferation and cell adhesion protein expression. METHODS: A total of 99 PDACs were analysed on tissue microarrays for EGFR, E-cadherin and β-catenin expression patterns in tumour cells. The percentage of cells expressing the three proteins (membrane, cytoplasm or nuclear pattern) and of Ki67-positive tumour cells was assessed. Tumour protein expression was studied with regard to clinicomorphological features, Ki67 index and for postsurgical survival. RESULTS: Membrane tumour EGFR correlated with histological poor differentiation (dedifferentiation), increased number of mitoses and severe tumour cell atypia (pleiomorphism) as well as with aberrant adhesion protein expression such as nuclear β-catenin and cytoplasmic E-cadherin. Cytoplasmic tumour E-cadherin correlated with an increased Ki67-positive tumour cell component, whereas nuclear E-cadherin correlated with a shorter postsurgical overall survival, as well as with tumour necrosis and an abundant clear cell component. CONCLUSIONS: In conclusion, the results of our study suggest a complex role for EGFR in PDAC carcinogenesis, tumour expression of this protein being associated with tumour dedifferentiation, mitotic activity or pleiomorphism, as well as with aberrant tumour cell adhesion protein expression.

48 Article Hepatobiliary and Pancreatic neoplasms in patients with McCune-Albright syndrome. 2014

Gaujoux, Sébastien / Salenave, Sylvie / Ronot, Maxime / Rangheard, Anne-Sophie / Cros, Jérôme / Belghiti, Jacques / Sauvanet, Alain / Ruszniewski, Philippe / Chanson, Philippe. ·Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Beaujon, Departments of Hepato-Pancreato-Biliary Surgery-Pôle des Maladies de l'Appareil Digestif (PMAD) (S.G., J.B., A.S.), Radiology (M.R.), Pathology (J.C.), and Gastroenterology-PMAD (P.R.), and Inserm Centre de Recherche Biomédicale Bichat Beaujon (CRB3) Unité 773 (S.G., M.R., J.C., J.B., A.S., P.R.), Clichy F-92110, France · Faculté de Médecine, Université Paris Diderot (S.G., M.R., J.C., J.B., A.S., P.R.), F-75010 Paris, France · AP-HP, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Service d'Endocrinologie et des Maladies de la Reproduction (S.S., P.C.) and Service de Radiologie (A.-S.R.), and Université Paris-Sud 11 (P.C.), Le Kremlin Bicêtre F-94275, France · and Inserm Unité 693 (P.C.), Faculté de Médecine Paris-Sud, F-94276 Le Kremlin-Bicêtre, France. ·J Clin Endocrinol Metab · Pubmed #24170100.

ABSTRACT: BACKGROUND: McCune-Albright syndrome (MAS), which includes polycystic fibrous dysplasia, precocious puberty, and café au lait spots, is a rare disorder caused by somatic activating mutations of the GNAS gene. GNAS mutations have also been implicated in various sporadic tumors, including hepatobiliary and pancreatic neoplasms. AIM: The aim of this study was to assess the prevalence of hepatobiliary and pancreatic neoplasms in patients with McCune-Albright syndrome. PATIENTS AND METHODS: Nineteen patients diagnosed between 1995 and 2012 with MAS in a tertiary referral center for rare growth disorders were screened with dedicated gadolinium-enhanced magnetic resonance imaging for hepatobiliary and pancreatic neoplasms between June 2011 and December 2012. RESULTS: Six (32%) of the 19 screened patients were found to have hepatic, pancreatic, or biliary lesions, excluding liver hemangiomas, liver cysts, and focal nodular hyperplasia. This includes pancreatic ductal lesions observed in 4 patients, including numerous branch-duct intraductal papillary mucinous neoplasms in 3 patients. Biliary lesions were observed in 1 patient, with a large choledochal cyst also involving the left biliary branch. Finally, multiple inflammatory/telangiectatic hepatic adenomas were observed in 2 patients, including 1 with proven somatic GNAS mutation. CONCLUSION: We describe the first observation of syndromic intraductal papillary mucinous neoplasms and the new association between MAS and pancreatic neoplasms, namely intraductal papillary mucinous neoplasms of the pancreas but also rare hepatobiliary neoplasms including liver adenomas and choledochal cysts. These findings strongly suggest that somatic activating GNAS mutations, possibly through cAMP pathway disorders, are involved in the tumorigenesis of hepatobiliary and pancreatic tissues originating from the foregut endoderm and have led us to use a routine screening by dedicated magnetic resonance imaging including both pancreatobiliary and liver sequences in patients with MAS.

49 Article Pancreatic intraepithelial neoplasia in patients with intraductal papillary mucinous neoplasms: the interest of endoscopic ultrasonography. 2013

Maire, Frédérique / Couvelard, Anne / Palazzo, Laurent / Aubert, Alain / Vullierme, Marie-Pierre / Rebours, Vinciane / Hammel, Pascal / Sauvanet, Alain / Levy, Philippe / Ruszniewski, Philippe. · ·Pancreas · Pubmed #24152960.

ABSTRACT: OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) are both precancerous lesions. Papillary mucinous neoplasms have been described in patients with IPMN, but their relationship is still poorly understood. The aims of this study were to look for PanIN lesions in patients operated on for IPMN and to search for correlations between endoscopic ultrasonography(EUS) features and pathologic findings. METHODS: Endoscopic ultrasonography was preoperatively performed in all patients with IPMN consecutively operated on in our center. Endoscopic ultrasonography features were prospectively compared with pathologic data from surgical specimen. RESULTS: Forty patients underwent resection for benign (52.5%) or malignant (47.5%) IPMN. Pancreatic intraepithelial neoplasia lesions were observed in 78% of cases (PanIN-3 in 19% of patients). PanIN-3 lesions were observed in 11% and 26% of patients with benign and malignant IPMN, respectively. Endoscopic ultrasonography changes(microcysts and/or hyperechoic foci) corresponded to PanIN lesions in 83% of cases. Endoscopic ultrasonography detected 69% of patients with PanIN lesions and 57% of those with panIN-3 lesions. CONCLUSIONS: Pancreatic intraepithelial neoplasia lesions are very frequently associated with IPMN, and 19% of patients with IPMN had PanIN-3 lesions. In two thirds of patients, EUS can detect minimal changes in the pancreas corresponding to PanIN lesions.

50 Article Observational study of natural history of small sporadic nonfunctioning pancreatic neuroendocrine tumors. 2013

Gaujoux, Sébastien / Partelli, Stefano / Maire, Frédérique / D'Onofrio, Mirko / Larroque, Béatrice / Tamburrino, Domenico / Sauvanet, Alain / Falconi, Massimo / Ruszniewski, Philippe. ·MD, Department of Hepatobiliary and Pancreatic Surgery, Hospital Beaujon, 100, Boulevard du Général Leclerc, 92110 Clichy, France. alain.sauvanet@bjn.aphp.fr. ·J Clin Endocrinol Metab · Pubmed #24057286.

ABSTRACT: CONTEXT: Asymptomatic sporadic nonfunctioning, well-differentiated pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed, and their management is controversial because of their overall good but heterogeneous prognosis. OBJECTIVE: The objective of the study was to assess the natural history of asymptomatic sporadic NF-PNETs smaller than 2 cm in size and the risk-benefit balance of nonoperative management. EXPERIMENTAL DESIGN: From January 2000 to June 2011, 46 patients with proven asymptomatic sporadic NF-PNETs smaller than 2 cm in size were followed up for at least 18 months with serial imaging in tertiary referral centers. RESULTS: Patients were mainly female (65%), with a median age of 60 years. Tumors were mainly located in the pancreatic head (52%), with a median lesion size of 13 mm (range 9-15). After a median follow-up of 34 months (range 24-52) and an average of four (range 3-6) serial imaging sessions, distant or nodal metastases appeared on the imaging in none of the patients. In six patients (13%), a 20% or greater increase in size was observed. Overall median tumor growth was 0.12 mm per year, and neither patients nor tumor characteristics were found to be significant predictors of tumor growth. Overall, eight patients (17%) underwent surgery after a median time from initial evaluation of 41 months (range 27-58); all resected lesions were European Neuroendocrine Tumor Society T stage 1 (n = 7) or 2 (n = 1), grade 1, node negative, with neither vascular nor peripancreatic fat invasion. CONCLUSIONS: In selected patients, nonoperative management of asymptomatic sporadic NF-PNETs smaller than 2 cm in size is safe. Larger and prospective multicentric studies with long-term follow-up are now needed to validate this wait-and-see policy.

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