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Pancreatic Neoplasms: HELP
Articles by Jean Robert Delpero
Based on 63 articles published since 2010
(Why 63 articles?)
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Between 2010 and 2020, J-R Delpéro wrote the following 63 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials). 2014

Bonnetain, Franck / Bonsing, Bert / Conroy, Thierry / Dousseau, Adelaide / Glimelius, Bengt / Haustermans, Karin / Lacaine, François / Van Laethem, Jean Luc / Aparicio, Thomas / Aust, Daniela / Bassi, Claudio / Berger, Virginie / Chamorey, Emmanuel / Chibaudel, Benoist / Dahan, Laeticia / De Gramont, Aimery / Delpero, Jean Robert / Dervenis, Christos / Ducreux, Michel / Gal, Jocelyn / Gerber, Erich / Ghaneh, Paula / Hammel, Pascal / Hendlisz, Alain / Jooste, Valérie / Labianca, Roberto / Latouche, Aurelien / Lutz, Manfred / Macarulla, Teresa / Malka, David / Mauer, Muriel / Mitry, Emmanuel / Neoptolemos, John / Pessaux, Patrick / Sauvanet, Alain / Tabernero, Josep / Taieb, Julien / van Tienhoven, Geertjan / Gourgou-Bourgade, Sophie / Bellera, Carine / Mathoulin-Pélissier, Simone / Collette, Laurence. ·Methodology and Quality of Life Unit in Cancer, EA 3181, University Hospital of Besançon and CTD-INCa Gercor, UNICNCER GERICO, Besançon, France. Electronic address: franck.bonnetain@univ-fcomte.fr. · Leiden University Medical Center, Leiden, Netherlands. · Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France. · Bordeaux Segalen University & CHRU, Bordeaux, France. · Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden. · Department of Radiation Oncology, Leuven, Belgium. · Digestive Surgical Department, Tenon hospital, Paris, France. · Gastro Intestinal Cancer Unit Erasme Hospital Brussels, Belgium. · Gastroenterology Department, Avicenne Hospital, Paris 13, Bobigny, France. · Institute for Pathology, University Hospital Carl-Gustav-Carus, Dresden, Germany. · Surgical and Gastroenterological Department, Endocrine and Pancreatic Unit, Hospital of 'G.B.Rossi', University of Verona, Italy. · Institut de Cancérologie de l'Ouest - Centre Paul Papin Centre de Lutte Contre le Cancer (CLCC), Angers, France. · Biostatistics Unit, Centre Antoine Lacassagne, Nice, France. · Oncology Department, Hôpital Saint-Antoine & CTD-INCa GERCOR, Assistance Publique des Hôpitaux de Paris, UPMC Paris VI, Paris, France. · Gastroenterology Department, Hopital la Timone, Assitance publique des Hopitaux de Marseille, Marseille, France. · Department of Surgery, Institut Paoli Calmettes, Marseille, France. · Department of Surgery, Agia Olga Hospital, Athens, Greece. · Department of Gastroenterology, Institut Gustave Roussy, Villejuif, France. · Biostatistician, Biostatistics Unit, Centre Antoine Lacassagne, Nice, France. · Department of Radiotherapy, Institut fuer Radioonkologie, Vienna, Austria. · Department of Surgical Oncology, Royal Liverpool Hospital, United Kingdom. · Department of Gastroenterology, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France. · Digestive Oncology and Gastro-enterology Department, Jules Bordet Institute, Brussels, Belgium. · Digestive Cancer Registry, INSERM U866, Dijon, France. · Medical Oncology Unit, Ospedali Riuniti di Bergamo, Bergame, Italy. · Inserm, Centre for Research in Epidemiology and Population Health, U1018, Biostatistics Team, Villejuif, France. · Gastroenterology Department, Caritas Hospital, Saarbrücken, Germany. · Department of the Gastrointestinal Tumors and Phase I Unit, Vall d'Hebron University Hospital, Barcelona, Spain. · Statistics Department, EORTC, Brussels, Belgium. · Department of Medical Oncology, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France. · Division of Surgery and Oncology at the University of Liverpool and Royal Liverpool University Hospital, Liverpool, United Kingdom. · Department of Digestive Surgery, Universitu Hospital Strasbourg, France. · Department of Hepato-pancreatic and Biliary Surgery, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France. · Department of Hepato-gastroenterology and Digestive Oncology, Georges Pompidou European hospital, Paris, France. · Department of Radiation Oncology, Academisch Medisch Centrum, Amsterdam, The Netherlands. · Institut Du Cancer de Montpellier, Comprehensive Cancer Centre, and Data Center for Cancer Clinical Trials, CTD-INCa, Montpellier, France. · Clinical and Epidemiological Research Unit, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France; Data Center for Cancer Clinical Trials, CTD-INCa, Bordeaux, France; INSERM, Centre d'Investigation Clinique - Épidémiologie Clinique CIC-EC 7, F-33000 Bordeaux, France. ·Eur J Cancer · Pubmed #25256896.

ABSTRACT: BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

2 Review Optimizing the management of locally advanced pancreatic cancer with a focus on induction chemotherapy: Expert opinion based on a review of current evidence. 2019

Seufferlein, Thomas / Hammel, Pascal / Delpero, Jean Robert / Macarulla, Teresa / Pfeiffer, Per / Prager, Gerald W / Reni, Michele / Falconi, Massimo / Philip, Philip A / Van Cutsem, Eric. ·University Medical Center Ulm, Ulm, Germany. Electronic address: thomas.seufferlein@uniklinik-ulm.de. · Hôpital Beaujon (AP-HP), Clichy, and Université Paris VII-Denis Diderot, France. Electronic address: pascal.hammel@aphp.fr. · Aix Marseille Université, Marseille, France. Electronic address: delperojr@ipc.unicancer.fr. · Vall d'Hebron University Hospital, Barcelona, Spain. Electronic address: tmacarulla@vhio.net. · Odense University Hospital, Odense, Denmark. Electronic address: per.pfeiffer@rsyd.dk. · Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University Vienna, Austria. Electronic address: gerald.prager@meduniwien.ac.at. · Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: reni.michele@hsr.it. · Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. · Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA. Electronic address: philipp@karmanos.org. · Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium. Electronic address: eric.vancutsem@uzleuven.be. ·Cancer Treat Rev · Pubmed #31163334.

ABSTRACT: Surgical resection of pancreatic cancer offers a chance of cure, but currently only 15-20% of patients are diagnosed with resectable disease, while 30-40% are diagnosed with non-metastatic, unresectable locally advanced pancreatic cancer (LAPC). Treatment for LAPC usually involves systemic chemotherapy, with the aim of controlling disease progression, reducing symptoms and maintaining quality of life. In a small proportion of patients with LAPC, primary chemotherapy may successfully convert unresectable tumours to resectable tumours. In this setting, primary chemotherapy is termed 'induction therapy' rather than 'neoadjuvant'. There is currently a lack of data from randomized studies to thoroughly evaluate the benefits of induction chemotherapy in LAPC, but Phase II and retrospective data have shown improved survival and high R0 resection rates. New chemotherapy regimens such as nab-paclitaxel + gemcitabine and FOLFIRINOX have demonstrated improvement in overall survival for metastatic disease and shown promise as neoadjuvant treatment in patients with resectable and borderline resectable disease. Prospective trials are underway to evaluate these regimens further as induction therapy in LAPC and preliminary data indicate a beneficial effect of FOLFIRINOX in this setting. Further research into optimal induction schedules is needed, as well as guidance on the patients who are most suitable for induction therapy. In this expert opinion article, a panel of surgeons, medical oncologists and gastrointestinal oncologists review the available evidence on management strategies for LAPC and provide their recommendations for patient care, with a particular focus on the use of induction chemotherapy.

3 Review [Management of localized, locally advanced and metastatic pancreatic adenocarcinoma]. 2015

Delpero, Jean-Robert / Turrini, Olivier / Raoul, Jean-Luc. · ·Rev Prat · Pubmed #26016202.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy. The prognosis is extremely poor because PDAC is usually a systemic disease at diagnosis. All stages, the survival does not exceed 5% at 5 years. However 15% of PDAC can be resected and today a margin-negative resection followed by adjuvant chemotherapy remains the only potential for a prolonged survival. Postoperative mortality had significantly decreased and the benefit of postoperative adjuvant chemotherapy has been clearly shown. Substantial progress has been made in the field of palliative chemotherapy by introducing new chemotherapy regimens (FOLFIRINOX [folinic acid, 5-fluorouracil, irinotecan and oxaliplatin] and gemcitabine/nab-paclitaxel), when the patient's performance status allows the use of these drugs. The role of radiation therapy remains controversial.

4 Review [Pancreatic tumours]. 2014

Barbier, Louise / Delpero, Jean-Robert. · ·Rev Prat · Pubmed #25638877.

ABSTRACT: -- No abstract --

5 Clinical Trial Prognostic Value of Resection Margin Involvement After Pancreaticoduodenectomy for Ductal Adenocarcinoma: Updates From a French Prospective Multicenter Study. 2017

Delpero, Jean Robert / Jeune, Florence / Bachellier, Philippe / Regenet, Nicolas / Le Treut, Yves Patrice / Paye, Francois / Carrere, Nicolas / Sauvanet, Alain / Adham, Mustapha / Autret, Aurelie / Poizat, Flora / Turrini, Olivier / Boher, Jean Marie. ·*Department of Surgery, Paoli-Calmettes Institute, Marseille, France †Department of Surgery, La Pitié-Salpêtrière - Université Pierre and Marie Curie, Paris VI, France ‡Department of Surgery, Hautepierre Hospital, University of Strasbourg, Strasbourg, France §Department of Surgery, Hotel Dieu Hospital, University of Nantes, Nantes, France ¶Department of Surgery, Hospital de la Conception, University of Aix-Marseille, Marseille, France ||Department of Surgery, Saint Antoine Hospital, University of Paris VI, Paris, France **Department of Surgery, Purpan Hospital, University of Toulouse Hospital Centre, Toulouse, France ††Department of Surgery, Beaujon Hospital, University of Paris VII, Clichy, France ‡‡Groupement Hospitalier Edouard Herriot, Université Claude Bernard Lyon 1, France §§Department of Histopathology, Paoli-Calmettes Institute, Marseille, France ¶¶Department of Biostatistics, Paoli-Calmettes Institute, Aix Marseille Univeristy, INSERM, IRD, SESSTIM, Marseille, France. ·Ann Surg · Pubmed #28953554.

ABSTRACT: OBJECTIVE: The aim of the study was to assess the relevance of resection margin status for survival after resection of pancreatic-head ductal adenocarcinoma. SUMMARY BACKGROUND DATA: The definition and prognostic value of incomplete microscopic resection (R1) remain controversial. METHODS: Prognostic factors were analyzed in 147 patients included in a prospective multicenter study on the impact of tumor clearance evaluated using a standardized pathology protocol. RESULTS: Thirty patients received neoadjuvant treatment (NAT = 20%); 41 had venous resection (VR = 28%), and 70% received adjuvant chemotherapy. In-hospital mortality was 3% (5/147). Follow-up was 83 months. Tumor clearance was 0, <1.0, <1.5, and <2.0 mm in 35 (25%), 92 (65%), 95 (67%), and 109 (77%) patients, respectively. R0-resection rates decreased from 75% to 35% when changing the definition of R1 status from R1-direct invasion (0 mm) to R1 <1.0 mm. On univariate analysis, clearance <1.0 or <1.5 mm, pT stage, pN stage, LNR ≥0.2, tumor grade 3, and lymphovascular invasion were significantly associated with 5-year survival. On multivariate analysis, pN was the most powerful independent predictor (P = 0.004). Clearance <1.0 or <1.5 mm had borderline significance for the entire cohort, but was relevant in certain subgroups (upfront pancreatectomy (n = 117; P = 0.049); without VR or NAT (n = 87; P = 0.003); N+ without VR or NAT (n = 50; P = 0.004). No N0-patient had R1-0 mm. Additional independent risk predictors were (1) R1 <1.0 mm for the SMA-margin in specific subgroups (upfront pancreatectomy, N0 patients without NAT, N+ patients without NAT or VR; (2) R1-0 mm posterior-margin for the NAT group (P = 0.004). CONCLUSION: Tumor clearance <1.0 or <1.5 mm was an independent determinants of postresection survival in certain subgroups. To avoid misinterpretation, future trials should specify the clearance margin in millimeter. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00918853.

6 Clinical Trial BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. 2012

Gonçalves, A / Gilabert, M / François, E / Dahan, L / Perrier, H / Lamy, R / Re, D / Largillier, R / Gasmi, M / Tchiknavorian, X / Esterni, B / Genre, D / Moureau-Zabotto, L / Giovannini, M / Seitz, J-F / Delpero, J-R / Turrini, O / Viens, P / Raoul, J-L. ·Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France. goncalvesa@marseille.fnclcc.fr ·Ann Oncol · Pubmed #22771827.

ABSTRACT: BACKGROUND: Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways. A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer (APC) patients. The BAYPAN study was a multicentric, placebo-controlled, double-blind, randomized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC. PATIENTS AND METHODS: The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma, no prior therapy for advanced disease and a performance status of zero to two. The primary end point was progression-free survival (PFS). The patients received gemcitabine 1000 mg/m(2) i.v., weekly seven times followed by 1 rest week, then weekly three times every 4 weeks plus sorafenib 200 mg or placebo, two tablets p.o., twice daily continuously. RESULTS: Between December 2006 and September 2009, 104 patients were enrolled on the study (52 pts in each arm) and 102 patients were treated. The median and the 6-month PFS were 5.7 months and 48% for gemcitabine/placebo and 3.8 months and 33% for gemcitabine/sorafenib (P = 0.902, stratified log-rank test), respectively. The median overall survivals were 9.2 and 8 months, respectively (P = 0.231, log-rank test). The overall response rates were similar (19 and 23%, respectively). CONCLUSION: The addition of sorafenib to gemcitabine does not improve PFS in APC patients.

7 Clinical Trial Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study). 2011

Heinrich, Stefan / Pestalozzi, Bernhard / Lesurtel, Mickael / Berrevoet, Frederik / Laurent, Stéphanie / Delpero, Jean-Robert / Raoul, Jean-Luc / Bachellier, Phillippe / Dufour, Patrick / Moehler, Markus / Weber, Achim / Lang, Hauke / Rogiers, Xavier / Clavien, Pierre-Alain. ·Department of General and Abdominal Surgery, University Hospital of Mainz, Langenbeck-strasse 1, 55118 Mainz, Germany. ·BMC Cancer · Pubmed #21831266.

ABSTRACT: BACKGROUND: Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy. METHODS/DESIGN: This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m(2)) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and representative histological sections will be centrally reviewed by a dedicated pathologist. DISCUSSION: The NEOPAC study will determine the efficacy of neoadjuvant chemotherapy in pancreatic cancer for the first time and offers a unique potential for translational research. Furthermore, this trial will provide the unbiased overall survival of all patients undergoing surgery for resectable cancer of the pancreatic head. TRIAL REGISTRATION: clinicalTrials.gov NCT01314027.

8 Clinical Trial Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: New neoadjuvant regimen was safe and provided an interesting pathologic response. 2010

Turrini, O / Ychou, M / Moureau-Zabotto, L / Rouanet, P / Giovannini, M / Moutardier, V / Azria, D / Delpero, J-R / Viret, F. ·Department of Surgical Oncology, Institut Paoli-Calmettes and Université de la Méditerranée, Marseille, France. ·Eur J Surg Oncol · Pubmed #20828979.

ABSTRACT: PURPOSE: To assess the safety and efficacy of a new neoadjuvant chemoradiation (CRT) docetaxel-based regimen in patients with resectable adenocarcinoma of the pancreatic head or body. PATIENTS AND METHODS: 34 patients with histologically-confirmed resectable pancreatic adenocarcinoma were included in this prospective two-center phase II study. Radiotherapy was delivered at the dose of 45 Gy in 25 fractions of 1.8 Gy per fractions, 5 days/week, over 5 weeks. Docetaxel was administered as a 1-h intravenous (IV) infusion repeated every week during 5 weeks. The dose was 30 mg/m(2)/week. All patients were restaged after completion of CRT. RESULTS: Tumor progression was documented in 11 patients (32%), stable disease was documented in 20 patients (59%), and partial remission was documented in 3 patients (9%). 23 patients still with local disease at restaging underwent explorative laparotomy. Of this, 17 patients (50%) had a curative pancreaticoduodenectomy with lymphadenectomy. Morbidity and mortality rates were 29% and 0%, respectively. Three patients (17%) had complete histological responses and 5 patients had minimal residual disease. All resected patients (n = 17) underwent R0 resection. The median and five-year survival times for the resected patients were 32 months and 41%, respectively. Among the resected patients, ten (59%) died as a result of recurrent pancreatic cancer without local tumor bed recurrence. CONCLUSIONS: Neoadjuvant docetaxel-based chemoradiation is well-tolerated. Resected patients had a prolonged survival time. Further studies are needed to confirm our findings and determine the role of such a neoadjuvant approach.

9 Article Outcomes of patients with initially locally advanced pancreatic adenocarcinoma who did not benefit from resection: a prospective cohort study. 2020

Garnier, Jonathan / Ewald, Jacques / Marchese, Ugo / Gilabert, Marine / Launay, Simon / Moureau-Zabotto, Laurence / Poizat, Flora / Giovannini, Marc / Delpero, Jean-Robert / Turrini, Olivier. ·Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France. jonathan-garnier@hotmail.fr. · Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France. · Department of Oncology, Institut Paoli-Calmettes, Marseille, France. · Department of Radiotherapy, Institut Paoli-Calmettes, Marseille, France. · Department of Pathology, Institut Paoli-Calmettes, Marseille, France. · Department of Endoscopy, Institut Paoli-Calmettes, Marseille, France. · Department of Surgery, Aix-Marseille University, Institut Paoli-Calmettes, CRCM, Marseille, France. ·BMC Cancer · Pubmed #32164564.

ABSTRACT: BACKGROUND: The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings. METHODS: Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan-Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method. RESULTS: FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR) = 1.2, 95% confidence interval: 0.86-1.6, P = .03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0-1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR = 1.38, 95% confidence interval: 1-1.9, P < .01) and limited short-term treatment-related toxicity. CONCLUSIONS: The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.

10 Article Borderline or locally advanced pancreatic adenocarcinoma: A single center experience on the FOLFIRINOX induction regimen. 2020

Garnier, Jonathan / Ewald, Jacques / Marchese, Ugo / Gilabert, Marine / Moureau-Zabotto, Laurence / Giovannini, Marc / Poizat, Flora / Delpero, Jean-Robert / Turrini, Olivier. ·Department of Surgery, Institut Paoli-Calmettes, Marseille, France. Electronic address: garnierj@ipc.unicancer.fr. · Department of Surgery, Institut Paoli-Calmettes, Marseille, France. Electronic address: ewaldj@ipc.unicancer.fr. · Department of Surgery, Institut Paoli-Calmettes, Marseille, France. Electronic address: marcheseu@ipc.unicancer.fr. · Department of Oncology, Institut Paoli-Calmettes, Marseille, France. Electronic address: gilabertm@ipc.unicancer.fr. · Department of Radiotherapy, Institut Paoli-Calmettes, Marseille, France. Electronic address: moureaul@ipc.unicancer.fr. · Department of Endoscopy, Institut Paoli-Calmettes, Marseille, France. Electronic address: giovanninim@ipc.unicancer.fr. · Department of Pathology, Institut Paoli-Calmettes, Marseille, France. Electronic address: poizatf@ipc.unicancer.fr. · Department of Surgery, Institut Paoli-Calmettes, Marseille, France. Electronic address: delperojr@ipc.unicancer.fr. · Aix-Marseille University, Institut Paoli-Calmettes, Department of Surgery, CNRS, Inserm, CRCM, Marseille, France. Electronic address: turrinio@ipc.unicancer.fr. ·Eur J Surg Oncol · Pubmed #32146053.

ABSTRACT: INTRODUCTION: This study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice. MATERIAL AND METHODS: From 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment. RESULTS: The 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3-16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P < 0.001). In resected patients, the ASA 3 score (P < 0.01), venous resection (P < 0.01), hemorrhage (P < 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P < 0.001). CONCLUSIONS: Neoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.

11 Article Effect of clinical status on survival in patients with borderline or locally advanced pancreatic adenocarcinoma. 2019

Duconseil, Pauline / Garnier, Jonathan / Weets, Victoria / Ewald, Jacques / Marchese, Ugo / Gilabert, Marine / Moureau-Zabotto, Laurence / Poizat, Flora / Giovannini, Marc / Delpero, Jean-Robert / Turrini, Olivier. ·Department of Surgical Oncology, Institut Paoli Calmettes, Aix-Marseille University, CRCM, 232 Boulevard de Sainte Marguerite, Marseille, 13009, France. pauline.duconseil@gmail.com. · Department of Surgical Oncology, Institut Paoli Calmettes, Aix-Marseille University, CRCM, 232 Boulevard de Sainte Marguerite, Marseille, 13009, France. · Department of Oncology, Institut Paoli-Calmettes, Marseille, France. · Department of Radiotherapy, Institut Paoli-Calmettes, Marseille, France. · Department of Pathology, Institut Paoli-Calmettes, Marseille, France. · Department of Endoscopy, Institut Paoli-Calmettes, Marseille, France. ·World J Surg Oncol · Pubmed #31164144.

ABSTRACT: OBJECTIVE: To determine the effect of clinical status (weight variation and performance status [PS]) at diagnosis and during induction treatment on resectability and overall survival (OS) rates in patients with borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC). METHODS: From 2005 to 2017, 454 consecutive patients were diagnosed with LAPC or BRPC. We evaluated the PS (0-1 or 2-3), body mass index at diagnosis, and weight loss (WL) > 5% at initial staging and after induction treatment and separated continuous weight loss (CWL) from weight stabilization. RESULTS: A total of 294 patients (64.8%) presented with WL, and 57 patients (12.6%) presented with a PS of 2-3. At restaging, 60 patients (13.2%) presented with CWL. Independent factors that poorly influenced the OS were a PS of 2-3 at diagnosis (P < .01), CWL at restaging (P < .01), and absence of resection (P < .01). Factors independently impeding resection were LAPC (P < .01), PS > 1 at diagnosis (P < .01), and CWL (P = .01). In total, 142 patients (31.3%) underwent pancreatectomy. Independent factors that poorly influenced the OS in the resected group were PS > 0 at diagnosis (P = .01) and obesity (P < .01). For the 312 unresected cancer patients (68.7%), CWL (P < .01) was identified as an independent factor that poorly influenced the OS. CONCLUSION: Clinical parameters that are easy to measure and monitor are independent factors of poor prognosis. The variation of weight during the induction treatment, more than WL at diagnosis, significantly precluded resection and was an independent factor of shorter OS in unresected patients.

12 Article Psychological Outcomes and Quality of Life in Relation to Pancreatectomy: A Systematic Review. 2019

Lounis, Léna / Aurran-Schleinitz, Thérèse / Turrini, Olivier / Delpero, Jean-Robert / Bréjard, Vincent. ·Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France. ·Pancreas · Pubmed #30973462.

ABSTRACT: This review aimed to inventory and analyze previous studies regarding quality of life (QoL) and psychological outcomes in relation to pancreatectomy. PubMed and PsycInfo databases were reviewed using the Preferred Reporting Items for Systematic review and Meta-Analysis guidelines. Thirteen studies were selected, 9 of which focused on the QoL after surgery. Quality of life significantly improved 3 to 6 months after surgery. Regarding the postoperative experience, one study reported high fear of recurrence of cancer, whereas another emphasized various expressions of patient needs. One study explained how strategy and ability to adapt are not related to the type, the cause, nor the physical condition, but are mainly influenced by the age and the subjective experience of the patients. A last study showed that depression did not affect survival rate after surgery. Our systematic review found only few studies regarding the psychological condition after pancreatectomy and highlights the need to describe and characterize the patients' psychological characteristics in this setting.

13 Article How Does Chemoradiotherapy Following Induction FOLFIRINOX Improve the Results in Resected Borderline or Locally Advanced Pancreatic Adenocarcinoma? An AGEO-FRENCH Multicentric Cohort. 2019

Pietrasz, Daniel / Turrini, Olivier / Vendrely, Véronique / Simon, Jean-Marc / Hentic, Olivia / Coriat, Romain / Portales, Fabienne / Le Roy, Bertrand / Taieb, Julien / Regenet, Nicolas / Goere, Diane / Artru, Pascal / Vaillant, Jean-Christophe / Huguet, Florence / Laurent, Christophe / Sauvanet, Alain / Delpero, Jean-Robert / Bachet, Jean Baptiste / Sa Cunha, Antonio. ·Department of Hepato-Bilio-Pancreatic Surgery, Liver Transplant Center, Paul Brousse Hospital, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. daniel.pietrasz@wanadoo.fr. · Department of Digestive and Hepatobiliary Surgery, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC University, Paris 06, France. daniel.pietrasz@wanadoo.fr. · Surgical Oncology Department, Institut Paoli Calmette, Marseille, France. · Departement of Radiotherapy, Hopital Haut Lévêque, CHU de Bordeaux, Pessac, France. · Radiation Oncology, Pitié-Salpêtrière Hospital, Paris, France. · Pancreato-Gastroenterology Department, Beaujon Hospital, Clichy, France. · Gastroenterology Unit, Cochin Hospital, Paris, France. · Institut du Cancer de Montpellier, Montpellier, France. · CHU Estaing, Service de Chirurgie Digestive, Université Clermont Auvergne, Clermont-Ferrand, France. · Hepatogastroenterology and Digestive Oncology Department, Georges Pompidou Hospital, Paris, France. · Department of Digestive Surgery, Nantes Hospital, Nantes, France. · Surgical Oncology Department, Gustave Roussy, Villejuif, France. · Department of Gastroenterology, Hôpital Privé Jean Mermoz, Lyon, France. · Department of Digestive and Hepatobiliary Surgery, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC University, Paris 06, France. · Department of Radiation Oncology, Tenon Hospital, Hôpitaux Universitaires Est Parisien, Assistance Publique-Hôpitaux de Paris, Paris, France. · Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hôpital Haut Lévêque, CHU de Bordeaux, Pessac, France. · Department of Digestive Surgery and Transplantation, Beaujon Hospital, Clichy, France. · Gastroenterology and Digestive Oncology Department, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC University, Paris, France. · Department of Hepato-Bilio-Pancreatic Surgery, Liver Transplant Center, Paul Brousse Hospital, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. ·Ann Surg Oncol · Pubmed #30362063.

ABSTRACT: BACKGROUND: Patients with borderline (BR) or locally advanced (LA) pancreatic adenocarcinoma (PAC) are often treated with induction FOLFIRINOX (FLX). However, the role of additional preoperative chemoradiotherapy (CRT) is controversial. The aim of this study is to evaluate its impact in patients who underwent resection after induction FLX. PATIENTS AND METHODS: Retrospective analysis of prospective consecutive surgical BR or LA PAC patients after induction FLX in 23 French centers between November 2010 and December 2015, treated with or without preoperative additional CRT (FLX vs FLX + CRT groups). RESULTS: Two hundred three patients were included (106 BR, 97 LA PAC). Median number of FLX cycles was 6 (range 1-30); 50% (n = 102) of patients received additional CRT. Median duration between diagnosis and surgery was 5.4 and 8.7 months (P = 0.001) in the FLX and FLX + CRT group, respectively. The 90-day mortality, major complications, and pancreatic fistula rates were 4.4%, 17.7%, and 5.4%, respectively. After 45.1 months follow-up, overall survival (OS) and disease-free survival were 45.4 months and 16.2 months, respectively. Patients with additional CRT had higher R0 resection rate (89.2% vs 76.3%; P = 0.017), ypN0 rate (76.2% vs 48.5%; P < 0.001), and higher rate of pathologic major response (33.3% vs 12.9%; P = 0.001). In the FLX + CRT group, patients had lower rate of locoregional relapse (28.3% vs 50.7%; P = 0.004). Patients with additional CRT had longer OS than those receiving FLX alone (57.8 vs 35.5 months; P = 0.007). CONCLUSIONS: Pathological results and survival data argue for interest in additional CRT. Prospective studies on an intention-to-treat basis are needed to confirm these results.

14 Article Patients with resectable pancreatic adenocarcinoma: A 15-years single tertiary cancer center study of laparotomy findings, treatments and outcomes. 2018

Gilabert, Marine / Turrini, Olivier / Ewald, Jacques / Moureau-Zabotto, Laurence / Poizat, Flora / Raoul, Jean-Luc / Delpero, Jean-Robert. ·Department of Medical Oncology, Paoli-Calmettes Institute, 13232, Marseille Cedex 9, France. Electronic address: gilabertm@ipc.unicancer.fr. · Department of Digestive Surgery, Paoli-Calmettes Institute, 13232, Marseille Cedex 9, France. · Department of Radiotherapy, Paoli-Calmettes Institute, 13232, Marseille Cedex 9, France. · Department of Pathology, Paoli-Calmettes Institute, 13232, Marseille Cedex 9, France. · Department of Medical Oncology, Paoli-Calmettes Institute, 13232, Marseille Cedex 9, France. ·Surg Oncol · Pubmed #30449481.

ABSTRACT: BACKGROUND: To describe, in patients with resectable pancreatic ductal adenocarcinoma (PDAC), the laparotomy findings, treatments and outcomes before (period 1) and after 2010 (period 2). METHODS: From 2000 to 2015, patients newly diagnosed with resectable PDAC at Paoli-Calmettes Institute, France, were evaluated. Survival was examined using the Kaplan-Meier method, and statistical comparisons were conducted using log rank tests. RESULTS: Among 1175 patients diagnosed with pancreatic mass, 164 underwent laparotomy with an intention of pancreatic resection. Some of them did not undergo pancreatic resection due to peroperative discovery of advanced disease. For those who were finally resected (n = 119), there were fewer pancreaticoduodenectomies (p = 0.045), shorter operation times (p < 0.01), lower mortality rates (p = 0.02), more advanced-stage tumors (T3), more frequent perineural invasion and R1 resection in period 2. This group had a trend of better outcomes after 2010 (51 months vs. 36 months (p = 0.065)). CONCLUSION: Improvement in surgical procedures and postoperative management led to prolonged survival of those who underwent surgery for resectable pancreatic cancer since 2010, despite a higher frequency of advanced tumors at the diagnosis in our institution.

15 Article A pancreatic zone at higher risk of fistula after enucleation. 2018

Duconseil, Pauline / Marchese, Ugo / Ewald, Jacques / Giovannini, Marc / Mokart, Djamel / Delpero, Jean-Robert / Turrini, Olivier. ·Department of Surgery, Institut Paoli-Calmettes, Marseille, France. · Department of Endoscopy, Institut Paoli-Calmettes, Marseille, France. · Department of Intensive Care, Institut Paoli-Calmettes, Marseille, France. · Department of Surgery, Aix-Marseille University, Institut Paoli-Calmettes, CNRS, Inserm, CRCM, Marseille, France. oturrini@yahoo.fr. ·World J Surg Oncol · Pubmed #30157952.

ABSTRACT: BACKGROUND: To determine predictive factors of postoperative pancreatic fistula (POPF) in patients undergoing enucleation (EN). METHODS: From 2005 to 2017, 47 patients underwent EN and had magnetic resonance imaging available for precise analysis of tumor location. Three pancreatic zones were delimited by the right side of the portal vein and the main pancreatic head duct (zone #3 comprising the lower head parenchyma and the uncinate process). RESULTS: The mortality and morbidity rates were 0% and 62%, respectively. POPF occurred in 23 patients (49%) and was graded as B or C (severe) in 15 patients (32%). Four patients (8.5%) developed a postoperative hemorrhage, and 5 patients (11%) needed a reintervention. In univariate and multivariate analyses, the pancreatic zone was the unique predictive factor of overall (P = .048) or severe POPF (P = .05). We did not observe any difference in postoperative courses when comparing the EN achieved in zones #1 and #2. We noted a longer operative duration (P = .016), higher overall (P = .017) and severe POPF (P = .01) rates, and longer hospital stays (P = .04) when comparing the EN achieved in zone #3 versus that in zones #1 and #2. Patients who underwent EN in zone #3 had a relative risk of developing a severe POPF of 3.22 compared with patients who underwent EN in the two other pancreatic zones. CONCLUSION: Our study identifies the lower head parenchyma and the uncinate process as a high-risk zone of severe POPF after EN. Patients with planned EN in this zone could be selected and benefit from preoperative and/or intraoperative techniques to reduce the severe POPF rate.

16 Article Impact of adjuvant chemotherapy after pancreaticoduodenectomy for distal cholangiocarcinoma: a propensity score analysis from a French multicentric cohort. 2018

Bergeat, Damien / Turrini, Olivier / Courtin-Tanguy, Laetitia / Truant, Stéphanie / Darnis, Benjamin / Delpero, Jean Robert / Mabrut, Jean-Yves / Regenet, Nicolas / Sulpice, Laurent. ·Department of HPB and Digestive Surgery, Pontchaillou Hospital, CHU Rennes, Rennes, France. · Rennes 1 University, Rennes, France. · INRA, UR1341 ADNC, St Gilles, France. · Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France. · Department of Digestive Surgery and Transplantation, CHRU de Lille, Lille, France. · Department of General Surgery and Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, Lyon, France. · Department of Digestive Surgery, Nantes University Hospital, Nantes, France. · Department of HPB and Digestive Surgery, Pontchaillou Hospital, CHU Rennes, Rennes, France. laurent.sulpice@chu-rennes.fr. · Rennes 1 University, Rennes, France. laurent.sulpice@chu-rennes.fr. · UMR991 Liver Metabolism and Cancer, Inserm, Rennes, France. laurent.sulpice@chu-rennes.fr. ·Langenbecks Arch Surg · Pubmed #30112638.

ABSTRACT: BACKGROUND: The benefit of adjuvant chemotherapy (AC) after pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) remains controversial. The study aimed to evaluate the impact of AC after PD for DCC in a large multicentric cohort. METHODS: Patients from five French centers who underwent from PD for DCC between 2000 and 2015 and received AC (AC+ group) or surgery only (AC- group) were included in the analysis. Variables associated with AC administration were analyzed by univariate analysis. The Cox regression identified covariates associated with overall survival (OS) and disease-free survival (DFS). The AC+ cohort was matched to the AC- cohort (1:1) by a propensity score (PS) based on the likelihood of AC administration and independent factors associated with decreased OS and DFS. RESULTS: Of the 178 patients included, 56 (31.5%) received AC. In the whole cohort, no difference on OS and DFS between the AC+ and AC- groups was identified (P = 0.15 and P = 0.07, respectively). After PS matching, the AC+ group (n = 49) was comparable to the AC- group (n = 49) on factors associated with AC administration and on factors associated with a decreased survival in the large cohort. After matching, the medians of OS and DFS in the AC+ group and in the AC- group were comparable (26.27 vs 43.33 months, P = 0.34, and 15.47 vs. 14.70 months, P = 0.79, respectively). CONCLUSION: Our study did not demonstrate a survival benefit of adjuvant chemotherapy (mostly base on gemcitabine regimen) for DCC after PD even after propensity score matching. New trial specially designed for DCC is urgently needed to improve survival after surgical resection.

17 Article Total Pancreatectomy for Presumed Intraductal Papillary Mucinous Neoplasms: A Multicentric Study of the French Surgical Association (AFC). 2018

Poiraud, Charles / El Amrani, Mehdi / Barbier, Louise / Chiche, Laurence / Mabrut, Jean Yves / Bachellier, Philippe / Pruvot, François-René / Delpero, Jean-Robert / Tuech, Jean Jacques / Adham, Mustapha / Sauvanet, Alain / Turrini, Olivier / Truant, Stéphanie. ·Department of Digestive Surgery, Hôpital Claude Huriez, Lille, France. · University of Lille, Lille, France. · Department of Digestive Surgery, Hôpital Trousseau, Tours, France. · Department of Digestive Surgery, Hôpital Beaujon, Paris, France. · Department of Digestive Surgery, Maison du Haut-Lévêque, Bordeaux, France. · Department of Digestive Surgery, Hôpital de la Croix Rousse, Lyon, France. · Department of Digestive Surgery, Hopital de Hautepierre, Strasbourg, France. · Department of Digestive Surgery, Institut Paoli Calmettes, Marseille, France. · Department of Surgery, Hôpital Charles Nicolle, Rouen, France. · Department of Digestive Surgery, Hôpital Edouard-Herriot, Lyon, France. ·Ann Surg · Pubmed #30048327.

ABSTRACT: OBJECTIVE: The aim of the current study was to assess the short and long-term outcome of total pancreatectomy (TP) for IPMN based on the largest series to date. BACKGROUND: Literature data are scarce regarding TP for IPMN, though increasingly performed in this setting. METHODS: Data of 888 IPMN patients operated between 2004 and 2013 were collected in a multicentric retrospective AFC database. Ninety-three patients (10.5%) who had TP entered this study. Patient demographics, indications, intraoperative data, 3-month morbi-mortality (Clavien), and long-term outcome were analyzed. RESULTS: Most patients had mixed type IPMN (59%) and underwent upfront (56%) or intraoperatively-decided (33%) TP. Morbidity and mortality rates were 47.3% and 4.3%, respectively, with no lethal hypoglycemia; morbidity was higher for intraoperatively-decided TP. Misdiagnoses were frequent regarding main pancreatic duct involvement (12%), invasiveness (33%), or mural nodules (50%), resulting in 12 TPs (13%) performed for asymptomatic IPMN showing only low/moderate dysplasia (LMD). On histopathological examination, there were 54 (58%) invasive IPMN (mostly pT3/T4 (76%), N+ (60%), R0 (75%)), with a significantly worse 5-year survival (21.2%) compared to noninvasive group (85.7%; P < 0.0001). In the former, 24 (58.5%) developed recurrence showing mostly distant metastasis, within 2 years in 92%. CONCLUSION: This large series of TP for IPMN reported acceptable morbi-mortality rates with no long-term death from diabetes-related complication. Morphologic assessment was imperfectly reliable with 13% of TP done for LMD only. More than half of patients were operated at an invasive carcinoma stage with poor outcome. Conversely, long-term survival was excellent after TP for noninvasive IPMN.

18 Article Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes. 2018

Lomberk, Gwen / Blum, Yuna / Nicolle, Rémy / Nair, Asha / Gaonkar, Krutika Satish / Marisa, Laetitia / Mathison, Angela / Sun, Zhifu / Yan, Huihuang / Elarouci, Nabila / Armenoult, Lucile / Ayadi, Mira / Ordog, Tamas / Lee, Jeong-Heon / Oliver, Gavin / Klee, Eric / Moutardier, Vincent / Gayet, Odile / Bian, Benjamin / Duconseil, Pauline / Gilabert, Marine / Bigonnet, Martin / Garcia, Stephane / Turrini, Olivier / Delpero, Jean-Robert / Giovannini, Marc / Grandval, Philippe / Gasmi, Mohamed / Secq, Veronique / De Reyniès, Aurélien / Dusetti, Nelson / Iovanna, Juan / Urrutia, Raul. ·Division of Research, Department of Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin, 53226, USA. glomberk@mcw.edu. · Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 14 rue Corvisart, Paris, 75013, France. · Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA. · Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin, 53226, USA. · Epigenomics Program, Center for Individualized Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA. · Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. · Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, Marseille, 13288, France. · Hôpital Nord, Chemin des Bourrely, Marseille, 13015, France. · Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, Marseille, 13009, France. · Hôpital de la Timone, 264 rue Saint-Pierre, Marseille, 13385, France. · Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, Marseille, 13288, France. juan.iovanna@inserm.fr. · Division of Research, Department of Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin, 53226, USA. rurrutia@mcw.edu. · Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin, 53226, USA. rurrutia@mcw.edu. · Epigenomics Program, Center for Individualized Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA. rurrutia@mcw.edu. ·Nat Commun · Pubmed #29773832.

ABSTRACT: Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival. Moreover, we describe the state of promoters, enhancers, super-enhancers, euchromatic, and heterochromatic regions for each subtype. Further analyses indicate that the distinct epigenomic landscapes are regulated by different membrane-to-nucleus pathways. Inactivation of a basal-specific super-enhancer associated pathway reveals the existence of plasticity between subtypes. Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets.

19 Article Severe postoperative complications decrease overall and disease free survival in pancreatic ductal adenocarcinoma after pancreaticoduodenectomy. 2018

Lubrano, Jean / Bachelier, Philippe / Paye, François / Le Treut, Yves Patrice / Chiche, Laurence / Sa-Cunha, Antonio / Turrini, Olivier / Menahem, Benjamin / Launoy, Guy / Delpero, Jean-Robert. ·Department of Digestive Surgery, University Hospital of Caen, France; NORMANDIE UNIV, UNICAEN, INSERM, ANTICIPE, 14000, Caen, France. Electronic address: lubrano-j@chu-caen.fr. · Department of Digestive Surgery, University Hospital of Strasbourg, France. · Department of Digestive Surgery, Hospital Saint Antoine, Paris, France. · Department of Digestive Surgery, University Hospital of la Timone, Marseille, France. · Department of Digestive Surgery, University Hospital of Bordeaux, France. · Department of Digestive Surgery, Paul-Brousse Hospital, Paris, France. · Department of Digestive Surgery, Paoli-Calmette Institution, Marseille, France. · Department of Digestive Surgery, University Hospital of Caen, France; NORMANDIE UNIV, UNICAEN, INSERM, ANTICIPE, 14000, Caen, France. Electronic address: menahem-b@chu-caen.fr. · NORMANDIE UNIV, UNICAEN, INSERM, ANTICIPE, 14000, Caen, France. ·Eur J Surg Oncol · Pubmed #29685757.

ABSTRACT: BACKGROUND: Postoperative complications influence overall and disease free survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma is still a matter of debate and controversy. METHODS: The outcome of 942 consecutive patients, from the multicentric study of the French Association of Surgery, between January 2004 and December 2009 was analyzed. Perioperative data, including severe complications (grade III and above), were used in univariate and multivariate analysis to assess their influence on overall and disease free survival. Recurrence and its location were investigated as well. RESULTS: Median overall and disease free survival were 24 and 19 months respectively. Postoperative complications occurred in 444 patients (47%) with 18.3% of severe complications. On multivariate analysis, severe complications, positive lymph node status and R1-R2 resection were independent prognostic factors for both overall and disease free survival. The median overall survival decreased from 25 to 22 months (p = 0.005) and disease free survival from 21 to 16 months (p = 0.02) if severe complications occurred. Severe complications were independent prognostic factor of recurrence (p < 0.001). CONCLUSIONS: Severe complications significantly alter both overall and disease free survival and are an independent factor of recurrence.

20 Article How to Reliably Assess Nodal Status in Distal Pancreatectomy for Adenocarcinoma. 2018

Faron, Matthieu / Vuarnesson, Hélène / Boher, Jean-Marie / Bachellier, Philippe / Sauvanet, Alain / Sa Cunha, Antonio / Le Treut, Yves-Patrice / Mabrut, Jean-Yves / Delpero, Jean-Robert / Paye, François. · ·Pancreas · Pubmed #29351122.

ABSTRACT: OBJECTIVES: The optimal number of lymph nodes that need to be analyzed to reliably assess nodal status in distal pancreatectomy for adenocarcinoma is still unknown. METHODS: Two hundred seventy-eight patients who underwent distal pancreatectomy for adenocarcinoma were retrieved from a retrospective French nationwide database. The relations between the number of analyzed lymph nodes and the nodal status of the tumor were studied. The beta-binomial law was used to estimate the probability of being truly node negative depending on the number of analyzed lymph nodes. Cox proportional hazard model was used for the survival analysis. RESULTS: The median number of analyzed lymph nodes was 15. There was a positive correlation between the number of positive lymph nodes and the number of lymph nodes analyzed. The curve reached a plateau at approximately 25 lymph nodes. The beta binomial model demonstrated that an analysis of 21 negative lymph nodes shows a probability to be truly N0 at 95%. N+ status was associated with survival, but the number of lymph node analyzed was not. CONCLUSION: At least 21 lymph nodes should be analyzed to ensure a reliable assessment of the nodal status, but this number may be hard to reach in distal pancreatectomy.

21 Article How I do hanging manoeuvres to facilitate portal vein resection during pancreaticoduodenectomy for borderline tumours. 2018

Turrini, Olivier / Marchese, Ugo / Ewald, Jacques / Delpero, Jean-Robert. ·Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France. · Marseille University of Mediterranean, Marseille, France. ·ANZ J Surg · Pubmed #29194886.

ABSTRACT: -- No abstract --

22 Article Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas. 2018

Lupinacci, Renato M / Goloudina, Anastasia / Buhard, Olivier / Bachet, Jean-Baptiste / Maréchal, Raphaël / Demetter, Pieter / Cros, Jérôme / Bardier-Dupas, Armelle / Collura, Ada / Cervera, Pascale / Scriva, Aurélie / Dumont, Sylvie / Hammel, Pascal / Sauvanet, Alain / Louvet, Christophe / Delpéro, Jean-Robert / Paye, François / Vaillant, Jean-Christophe / André, Thierry / Closset, Jean / Emile, Jean-François / Van Laethem, Jean-Luc / Jonchère, Vincent / Abd Alsamad, Issam / Antoine, Martine / Rodenas, Anita / Fléjou, Jean-François / Dusetti, Nelson / Iovanna, Juan / Duval, Alex / Svrcek, Magali. ·INSERM, UMR S 938 - Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, Equipe labellisée par la Ligue Nationale contre le Cancer, F-75012, Paris, France; Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France; Groupe Hospitalier Diaconesses - Croix Saint-Simon, Service de Chirurgie Digestive, Viscérale et Endocrinienne, Paris, France. · INSERM, UMR S 938 - Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, Equipe labellisée par la Ligue Nationale contre le Cancer, F-75012, Paris, France; Inovarion F - 75013, Paris, France. · INSERM, UMR S 938 - Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, Equipe labellisée par la Ligue Nationale contre le Cancer, F-75012, Paris, France. · Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service d'Hépato-Gastro-Entérologie, Paris, France. · Department of Gastroenterology and Digestive Oncology, Erasme Hospital, Brussels, Belgium. · Department of Pathology, Erasme Hospital, Brussels, Belgium. · AP-HP, Service d'Anatomie et Cytologie Pathologiques, Hôpital Beaujon, Clichy, France; Université Paris Diderot - Paris 7, Paris, France. · AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service d'Anatomie et Cytologie Pathologiques, Paris, France. · INSERM, UMR S 938 - Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, Equipe labellisée par la Ligue Nationale contre le Cancer, F-75012, Paris, France; Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France. · INSERM, UMR S 938 - Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, Equipe labellisée par la Ligue Nationale contre le Cancer, F-75012, Paris, France; Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France; AP-HP, Hôpitaux Universitaires Est Parisien, Hôpital Saint-Antoine, Service d'Anatomie et Cytologie Pathologiques, Paris, France. · AP-HP, Hôpitaux Universitaires Est Parisien, Hôpital Saint-Antoine, Service d'Anatomie et Cytologie Pathologiques, Paris, France. · Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France. · Université Paris Diderot - Paris 7, Paris, France; AP-HP, Hôpital Beaujon, Department of Gastroenterology, Pôle des Maladies de l'Appareil Digestif (PMAD), Clichy, France. · Université Paris Diderot - Paris 7, Paris, France; AP-HP, Hôpital Beaujon, Department of Hepato-Pancreato-Biliary Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Clichy, France. · Department of Oncology, Institut Mutualiste Montsouris, Paris, France. · Department of Digestive Surgical Oncology, Paoli Calmettes Institute, Comprehensive Cancer Centre, Marseille, France. · Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France; AP-HP, Hôpitaux Universitaires Est Parisien, Hôpital Saint-Antoine, Service de Chirurgie Générale et Digestive, Paris, France. · Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Chirurgie Digestive et Hépato-bilio-pancréatique, Paris, France. · Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France; Department of Oncology, Hôpital Saint Antoine, Paris, France. · EA4340 and Service d'Anatomie et Cytologie Pathologiques, Hôpital Ambroise Paré, AP-HP and Versailles University, Boulogne, France. · Hôpital Intercommunal de Créteil, Service d'Anatomie et Cytologie Pathologiques, Créteil, France. · Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France; AP-HP, Hôpitaux Universitaires Est Parisien, Hôpital Tenon, Service d'Anatomie et Cytologie Pathologiques, Paris, France. · Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Parc Scientifique et Technologique de Luminy, Aix-Marseille Université and Institut Paoli-Calmettes, Marseille, France. · INSERM, UMR S 938 - Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, Equipe labellisée par la Ligue Nationale contre le Cancer, F-75012, Paris, France; Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France. Electronic address: alex.duval@inserm.fr. · INSERM, UMR S 938 - Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, Equipe labellisée par la Ligue Nationale contre le Cancer, F-75012, Paris, France; Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France; AP-HP, Hôpitaux Universitaires Est Parisien, Hôpital Saint-Antoine, Service d'Anatomie et Cytologie Pathologiques, Paris, France. Electronic address: magali.svrcek@aphp.fr. ·Gastroenterology · Pubmed #29158190.

ABSTRACT: Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors.

23 Article Predict pancreatic fistula after pancreaticoduodenectomy: ratio body thickness/main duct. 2018

Barbier, Louise / Mège, Diane / Reyre, Anthony / Moutardier, Vincent M / Ewald, Jacques A / Delpero, Jean-Robert. ·Oncological Surgery Department, Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France. · Digestive Surgery Department, Hôpital Timone, Aix-Marseille Université, Marseille, France. · Radiology Department, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France. · Digestive Surgery Department, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France. ·ANZ J Surg · Pubmed #28513069.

ABSTRACT: BACKGROUND: The occurrence of post-operative pancreatic fistula (POPF) after pancreaticoduodenectomy is a challenging issue. The aim was to identify variables on preoperative computed tomography (CT) scan, useful to predict clinically significant POPF (grades B-C) after pancreaticoduodenectomy. METHODS: Patients presented POPF after pancreaticoduodenectomy were included from two tertiary referral centres. B/W ratio was defined by ratio of pancreas body thickness (B) to main pancreatic duct (W). The predictive parameters of POPF on CT scan were assessed with a receiving operator characteristics (ROC) curve and intrinsic characteristics. RESULTS: Between 2010 and 2013, 186 patients who underwent pancreaticoduodenectomy were included. POPF occurred in 25% of them, and was clinically significant in 13%. After univariate analysis, endocrine tumours (P = 0.03), main pancreatic duct size (P < 0.01) and B/W ratio (P = 0.04) were significantly associated with POPF. ROC curve showed a greater area under curve for B/W ratio (0.68) than for main pancreatic duct size (0.33). A 3.8 threshold displayed 80 and 51% for sensibility and specificity, respectively, and a negative predictive value of 94%. A B/W ratio >3.8 increased the rates of post-operative haemorrhage (odds ratio = 4.3 (1.4-13.2), P = 0.01), and reintervention (odds ratio = 3.4 (1.2-9.6), P = 0.02). CONCLUSIONS: B/W ratio superior to 3.8 assessed on preoperative CT scan may be an easy tool to predict clinically significant POPF after pancreaticoduodenectomy.

24 Article Pancreatic Adenocarcinoma Therapeutic Targets Revealed by Tumor-Stroma Cross-Talk Analyses in Patient-Derived Xenografts. 2017

Nicolle, Rémy / Blum, Yuna / Marisa, Laetitia / Loncle, Celine / Gayet, Odile / Moutardier, Vincent / Turrini, Olivier / Giovannini, Marc / Bian, Benjamin / Bigonnet, Martin / Rubis, Marion / Elarouci, Nabila / Armenoult, Lucile / Ayadi, Mira / Duconseil, Pauline / Gasmi, Mohamed / Ouaissi, Mehdi / Maignan, Aurélie / Lomberk, Gwen / Boher, Jean-Marie / Ewald, Jacques / Bories, Erwan / Garnier, Jonathan / Goncalves, Anthony / Poizat, Flora / Raoul, Jean-Luc / Secq, Veronique / Garcia, Stephane / Grandval, Philippe / Barraud-Blanc, Marine / Norguet, Emmanuelle / Gilabert, Marine / Delpero, Jean-Robert / Roques, Julie / Calvo, Ezequiel / Guillaumond, Fabienne / Vasseur, Sophie / Urrutia, Raul / de Reyniès, Aurélien / Dusetti, Nelson / Iovanna, Juan. ·Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre le Cancer, Paris, France. Electronic address: remy.nicolle@ligue-cancer.net. · Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre le Cancer, Paris, France. · Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix Marseille Université, Marseille, France. · Hôpital Nord, Marseille, France; Aix Marseille Université, Marseille, France. · Aix Marseille Université, Marseille, France; Institut Paoli-Calmettes, Marseille, France. · Institut Paoli-Calmettes, Marseille, France. · Hôpital Nord, Marseille, France. · Division of Research, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · Aix Marseille Université, Marseille, France; Hôpital de la Timone, Marseille, France. · Hôpital de la Timone, Marseille, France. · Centre Génomique du Centre de Recherche du CHUL Research Center, Ville de Québec, QC, Canada. · Division of Research, Department of Surgery, Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix Marseille Université, Marseille, France. Electronic address: juan.iovanna@inserm.fr. ·Cell Rep · Pubmed #29186684.

ABSTRACT: Preclinical models based on patient-derived xenografts have remarkable specificity in distinguishing transformed human tumor cells from non-transformed murine stromal cells computationally. We obtained 29 pancreatic ductal adenocarcinoma (PDAC) xenografts from either resectable or non-resectable patients (surgery and endoscopic ultrasound-guided fine-needle aspirate, respectively). Extensive multiomic profiling revealed two subtypes with distinct clinical outcomes. These subtypes uncovered specific alterations in DNA methylation and transcription as well as in signaling pathways involved in tumor-stromal cross-talk. The analysis of these pathways indicates therapeutic opportunities for targeting both compartments and their interactions. In particular, we show that inhibiting NPC1L1 with Ezetimibe, a clinically available drug, might be an efficient approach for treating pancreatic cancers. These findings uncover the complex and diverse interplay between PDAC tumors and the stroma and demonstrate the pivotal role of xenografts for drug discovery and relevance to PDAC.

25 Article A 25-gene classifier predicts overall survival in resectable pancreatic cancer. 2017

Birnbaum, David J / Finetti, Pascal / Lopresti, Alexia / Gilabert, Marine / Poizat, Flora / Raoul, Jean-Luc / Delpero, Jean-Robert / Moutardier, Vincent / Birnbaum, Daniel / Mamessier, Emilie / Bertucci, François. ·Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm UMR1068, CNRS UMR725, Aix-Marseille Université, Marseille, France. · Département de Chirurgie Générale et Viscérale, AP-HM, Marseille, France. · Faculté de Médecine, Aix-Marseille Université, Marseille, France. · Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France. · Département d'Anatomopathologie, Institut Paoli-Calmettes, Marseille, France. · Département d'Oncologie Chirurgicale, Institut Paoli-Calmettes, Marseille, France. · Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Inserm UMR1068, CNRS UMR725, Aix-Marseille Université, Marseille, France. bertuccif@ipc.unicancer.fr. · Faculté de Médecine, Aix-Marseille Université, Marseille, France. bertuccif@ipc.unicancer.fr. · Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France. bertuccif@ipc.unicancer.fr. · Département d'Oncologie Moléculaire, Institut Paoli-Calmettes, 232 Bd. Ste-Marguerite, 13009, Marseille, France. bertuccif@ipc.unicancer.fr. ·BMC Med · Pubmed #28927421.

ABSTRACT: BACKGROUND: Pancreatic carcinoma is one of the most lethal human cancers. In patients with resectable tumors, surgery followed by adjuvant chemotherapy is the only curative treatment. However, the 5-year survival is 20%. Because of a strong metastatic propensity, neoadjuvant chemotherapy is being tested in randomized clinical trials. In this context, improving the selection of patients for immediate surgery or neoadjuvant chemotherapy is crucial, and high-throughput molecular analyses may help; the present study aims to address this. METHODS: Clinicopathological and gene expression data of 695 pancreatic carcinoma samples were collected from nine datasets and supervised analysis was applied to search for a gene expression signature predictive for overall survival (OS) in the 601 informative operated patients. The signature was identified in a learning set of patients and tested for its robustness in a large independent validation set. RESULTS: Supervised analysis identified 1400 genes differentially expressed between two selected patient groups in the learning set, namely 17 long-term survivors (LTS; ≥ 36 months after surgery) and 22 short-term survivors (STS; dead of disease between 2 and 6 months after surgery). From these, a 25-gene prognostic classifier was developed, which identified two classes ("STS-like" and "LTS-like") in the independent validation set (n = 562), with a 25% (95% CI 18-33) and 48% (95% CI 42-54) 2-year OS (P = 4.33 × 10 CONCLUSION: This study, the largest prognostic study of gene expression profiles in pancreatic carcinoma, reports a 25-gene signature associated with post-operative OS independently of classical factors and molecular subtypes. This classifier may help select patients with resectable disease for either immediate surgery (the LTS-like class) or neoadjuvant chemotherapy (the STS-like class). Its assessment in the current prospective trials of adjuvant and neoadjuvant chemotherapy trials is warranted, as well as the functional analysis of the classifier genes, which may provide new therapeutic targets.

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