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Pancreatic Neoplasms: HELP
Articles by Marc Giovannini
Based on 39 articles published since 2009
(Why 39 articles?)
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Between 2009 and 2019, Marc Giovannini wrote the following 39 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Pancreatic cancer screening: Still a delusion? 2017

Moutinho-Ribeiro, Pedro / Coelho, Rosa / Giovannini, Marc / Macedo, Guilherme. ·Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal; Faculty of Medicine, University of Porto, Portugal. Electronic address: pmoutinhoribeiro@gmail.com. · Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal. · Endoscopic Unit, Paoli-Calmettes Institute, Marseilles, France. · Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal; Faculty of Medicine, University of Porto, Portugal. ·Pancreatology · Pubmed #28739291.

ABSTRACT: Pancreatic adenocarcinoma represents the fourth most common cause of cancer mortality and death due to pancreatic cancer (PC) have increased since 2003. Its incidence has also raised about 30% in the past decade and it is expected to become the second cause of cancer mortality by 2020 in the USA. Most PC present with metastatic disease and improvements in treatment outcomes for this group have been disappointing. These observations support the idea that screening to identify patients at an earlier stage might be an important strategy in improving overall PC outcomes. Many protocols have been tested, nevertheless, by now there is no effective screening program. Given the overall low incidence of disease and the current lack of accurate, inexpensive and noninvasive screening tests, the consensus is that widespread population-based screening for PC in the general population or in patients with only one affected first-degree relative is neither practicable nor indicated in most countries. However, a different scenario is screening patients with higher risk for PC, most of them with hereditary conditions predisposing the development of this neoplasia. In fact, some guidelines are now available helping to select these individuals at risk and to screen them, in order to achieve early detection of PC.

2 Review Endoscopic ultrasonography: Transition towards the future of gastro-intestinal diseases. 2016

De Lisi, Stefania / Giovannini, Marc. ·Stefania De Lisi, Department of Gastroenterology, A.O. Fatebenefratelli e Oftalmico, 20121 Milan, Italy. ·World J Gastroenterol · Pubmed #26855537.

ABSTRACT: Endoscopic ultrasonography (EUS) is a technique with an established role in the diagnosis and staging of gastro-intestinal tumors. In recent years, the spread of new devices dedicated to tissue sampling has improved the diagnostic accuracy of EUS fine-needle aspiration. The development of EUS-guided drainage of the bilio-pancreatic region and abdominal fluid collections has allowed EUS to evolve into an interventional tool that can replace more invasive procedures. Emerging techniques applying EUS in pancreatic cancer treatment and in celiac neurolysis have been described. Recently, confocal laser endomicroscopy has been applied to EUS as a promising technique for the in vivo histological diagnosis of gastro-intestinal, bilio-pancreatic and lymph node lesions. In this state-of-the-art review, we report the most recent data from the literature regarding EUS devices, interventional EUS, EUS-guided confocal laser endomicroscopy and EUS pancreatic cancer treatment, and we also provide an overview of their principles, clinical applications and limitations.

3 Review International Association of Pancreatology (IAP)/European Pancreatic Club (EPC) consensus review of guidelines for the treatment of pancreatic cancer. 2016

Takaori, Kyoichi / Bassi, Claudio / Biankin, Andrew / Brunner, Thomas B / Cataldo, Ivana / Campbell, Fiona / Cunningham, David / Falconi, Massimo / Frampton, Adam E / Furuse, Junji / Giovannini, Marc / Jackson, Richard / Nakamura, Akira / Nealon, William / Neoptolemos, John P / Real, Francisco X / Scarpa, Aldo / Sclafani, Francesco / Windsor, John A / Yamaguchi, Koji / Wolfgang, Christopher / Johnson, Colin D / Anonymous480853. ·Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: takaori@kuhp.kyoto-u.ac.jp. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Academic Unit of Surgery, University of Glasgow, Glasgow, United Kingdom. · Department of Radiation Oncology, University Hospitals Freiburg, Germany. · Department of Pathology and Diagnostics, University of Verona, Verona, Italy. · Department of Pathology, Royal Liverpool University Hospital, Liverpool, United Kingdom. · Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom. · Pancreatic Surgery Unit, Università Vita e Salute, Milano, Italy. · HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom. · Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan. · Endoscopic Unit, Paoli-Calmettes Institute, Marseille, France. · NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom. · Department of Radiation Oncology and Image-applied Therapy, Kyoto University Hospital, Kyoto, Japan. · Division of General Surgery, Yale University, New Haven, CT, United States of America. · Epithelial Carcinogenesis Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. · Department of Surgery, University of Auckland, HBP/Upper GI Unit, Auckland City Hospital, Auckland, New Zealand. · Department of Advanced Treatment of Pancreatic Disease, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. · Department of Surgery, The Johns Hopkins University, Baltimore, MD, United States of America. · University Surgical Unit, Southampton General Hospital, Southampton, United Kingdom. ·Pancreatology · Pubmed #26699808.

ABSTRACT: BACKGROUND: Pancreatic cancer is one of the most devastating diseases with an extremely high mortality. Medical organizations and scientific societies have published a number of guidelines to address active treatment of pancreatic cancer. The aim of this consensus review was to identify where there is agreement or disagreement among the existing guidelines and to help define the gaps for future studies. METHODS: A panel of expert pancreatologists gathered at the 46th European Pancreatic Club Meeting combined with the 18th International Association of Pancreatology Meeting and collaborated on critical reviews of eight English language guidelines for the clinical management of pancreatic cancer. Clinical questions (CQs) of interest were proposed by specialists in each of nine areas. The recommendations for the CQs in existing guidelines, as well as the evidence on which these were based, were reviewed and compared. The evidence was graded as sufficient, mediocre or poor/absent. RESULTS: Only 4 of the 36 CQs, had sufficient evidence for agreement. There was also agreement in five additional CQs despite the lack of sufficient evidence. In 22 CQs, there was disagreement regardless of the presence or absence of evidence. There were five CQs that were not addressed adequately by existing guidelines. CONCLUSION: The existing guidelines provide both evidence- and consensus-based recommendations. There is also considerable disagreement about the recommendations in part due to the lack of high level evidence. Improving the clinical management of patients with pancreatic cancer, will require continuing efforts to undertake research that will provide sufficient evidence to allow agreement.

4 Review Pancreatic metastasis from osteosarcoma and Ewing sarcoma: literature review. 2013

Bertucci, François / Araujo, Julia / Giovannini, Marc. ·Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France. BERTUCCIF@ipc.unicancer.fr ·Scand J Gastroenterol · Pubmed #22861647.

ABSTRACT: OBJECTIVES: Pancreatic metastasis from osteosarcoma and Ewing sarcoma is extremely rare. Differential diagnosis with primary pancreatic carcinoma is crucial before any treatment, but may be very difficult. MATERIAL AND METHODS: We searched for and reviewed the cases reported in the English literature. RESULTS: Twelve cases were identified, including nine osteosarcoma patients and three Ewing sarcoma cases. The median time between the sarcoma diagnosis and that of pancreatic metastasis was 3 years. In most of the cases, the pancreatic relapse followed or was associated with relapse(s) in one or more sites. Two out of eight patients with available follow-up were alive without disease 6+ and 11+ months after complete surgical removal, whereas five patients died from disease. Histological diagnosis was obtained before surgery in only five cases using percutaneous Tru-Cut biopsy in three cases and endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) in the two most recent ones. CONCLUSIONS: Osteosarcoma or Ewing sarcoma metastasis should be included in the differential diagnosis of pancreatic solid lesion, particularly in patients with a primary tumor. In this context, EUS and EUS-FNAB are reliable methods for the pre-operative diagnosis and should thus be discussed before any therapeutic decision.

5 Review Contrast-enhanced and 3-dimensional endoscopic ultrasonography. 2010

Giovannini, Marc. ·Paoli-Calmettes Institute, 232 Boulevard Sainte Marguerite, 13273 Marseille Cedex 9, France. uemco@marseille.fnclcc.fr ·Gastroenterol Clin North Am · Pubmed #21093759.

ABSTRACT: Recent progress of the data processing applied to ultrasonographic (US) examination has made it possible to develop new software. The US workstation of the last generation thus incorporated in their center a computer allowing a precise treatment of the US image. This advancement has made it possible to work out new images such as 3-dimensional (3D) US, contrast harmonic US associated with the intravenous injection of contrast agents, and even more recently, elastography. These techniques, quite elaborate in percutaneous US at present, are to be adapted and evaluated with endoscopic US (EUS). The contribution of contrast agents of US to pancreatic EUS and then 3D EUS are successively approached in this article.

6 Review Contrast-enhanced endoscopic ultrasound and elastosonoendoscopy. 2009

Giovannini, Marc. ·Paoli-Calmettes Institute, Marseille, France. uemco@marseille.fnclcc.fr ·Best Pract Res Clin Gastroenterol · Pubmed #19744639.

ABSTRACT: Until recently, there was no contrast harmonic imaging technique available for EUS examination. Second-generation US contrast agents produce harmonic signals at lower acoustic powers and, therefore, are suitable for EUS imaging at low acoustic powers. CE-EUS could provide a contribution to the differential diagnosis between a primary pancreatic carcinoma, chronic pancreatitis and a pancreatic metastasis, and therefore can have a decisive influence on the selection of appropriate therapeutic strategies (follow-up, chemotherapy or surgery, for example). However, histology remains the standard in the differential diagnosis of pancreatic tumours. Regarding lymph nodes, CE-EUS cannot replace EUS-guided fine-needle aspiration. Elastography examines the elastic properties of tissues by applying a slight compression to the tissue and comparing an image obtained before and after this compression. EUS elastography is a new application in the field of endosonography and seems to be able to differentiate fibrous and benign tissue from malignant lesions. While our results are very encouraging, further research will be needed to further define the place of this new technique and should be aimed at further defining criteria for accurate elastography as well as subsequently assessing the technique using multiple operators in a blinded setting. EUS-guided sonoelastography has the potential for further guiding the diagnosis and therapy of gastrointestinal-related tumours.

7 Clinical Trial Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy in solid pancreatic masses. 2016

Giovannini, Marc / Caillol, Fabrice / Monges, Geneviève / Poizat, Flora / Lemaistre, Anne-Isabelle / Pujol, Bertrand / Lucidarme, Damien / Palazzo, Laurent / Napoléon, Bertrand. ·Department of Hepatogastroenterology, Institut Paoli Calmettes, Marseille, France. · Department of Biopathology, Institut Paoli Calmettes, Marseille, France. · Department of Biopathology, Centre Léon Bérard, Lyon, France. · Department of Gastroenterology, Ramsay Générale de Santé, Hôpital privé Jean Mermoz, Lyon, France. · Medicosurgical Department of Hepatogastroenterology, Hôpital Saint-Philibert, Lomme-lès-Lille, France. · Department of Gastroenterology, Clinique du Trocadéro, Paris, France. ·Endoscopy · Pubmed #27576181.

ABSTRACT: BACKGROUND AND STUDY AIMS: The differential diagnosis of solid pancreatic masses by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is currently suboptimal in centers that are not equipped with rapid on-site evaluation. Needle-based confocal laser endomicroscopy (nCLE) enables real-time in vivo microscopic imaging during endoscopy. This study aimed to describe nCLE interpretation criteria for the characterization of pancreatic masses, with histopathological correlation, and to perform the first validation of these criteria. PATIENTS AND METHODS: A total of 40 patients were evaluated by EUS-FNA combined with nCLE for the diagnosis of pancreatic masses. Final diagnosis was based on EUS-FNA histology and follow-up at 1 year. Five unblinded examiners defined nCLE criteria for adenocarcinoma, chronic pancreatitis, and neuroendocrine tumor (NET) using a set of video sequences from 14 patients with confirmed pathology (Step 1). These criteria were retrospectively validated by four independent, blinded examiners using sequences from 32 patients (Step 2). RESULTS: nCLE criteria were described for adenocarcinoma (dark cell aggregates, irregular vessels with leakages of fluorescein), chronic pancreatitis (residual regular glandular pancreatic structures), and NET (black cell aggregates surrounded by vessels and fibrotic areas). These criteria correlated with the histological features of the corresponding lesions. In the validation review, a conclusive nCLE result was obtained in 75 % of cases (96 % correct). Statistical evaluation provided promising results, with high specificity, and negative and positive predictive values for all types of pancreatic masses. CONCLUSION: Considering the low negative predictive value of EUS-FNA, nCLE could help to rule out malignancy after a previous inconclusive EUS-FNA. Larger studies are required to confirm these findings and to establish the role of nCLE in the diagnosis of pancreatic masses. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01563133).

8 Clinical Trial A novel approach to the diagnosis of pancreatic serous cystadenoma: needle-based confocal laser endomicroscopy. 2015

Napoléon, Bertrand / Lemaistre, Anne-Isabelle / Pujol, Bertrand / Caillol, Fabrice / Lucidarme, Damien / Bourdariat, Raphaël / Morellon-Mialhe, Blandine / Fumex, Fabien / Lefort, Christine / Lepilliez, Vincent / Palazzo, Laurent / Monges, Geneviève / Filoche, Bernard / Giovannini, Marc. ·Department of Gastroenterology, Hôpital privé Jean Mermoz, Générale de Santé, Lyon, France. · Department of Biopathology, Centre Léon Bérard, Lyon, France. · Department of Hepatogastroenterology, Institut Paoli Calmettes, Marseille, France. · Medicosurgical Department of Hepatogastroenterology, Saint-Philibert Hospital Centre, Lomme-lès-Lille, France. · Department of Digestive Surgery, Hôpital privé Jean Mermoz, Générale de Santé, Lyon, France. · Department of Gastroenterology, Clinique du Trocadéro, Paris, France. · Department of Biopathology, Institut Paoli Calmettes, Marseille, France. ·Endoscopy · Pubmed #25325684.

ABSTRACT: BACKGROUND AND STUDY AIMS: The differential diagnosis of solitary pancreatic cystic lesions is frequently difficult. Needle-based confocal laser endomicroscopy (nCLE) performed during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a new technology enabling real-time imaging of the internal structure of such cysts. The aim of this pilot study was to identify and validate new diagnostic criteria on nCLE for pancreatic cystic lesions. PATIENTS AND METHODS: A total of 31 patients with a solitary pancreatic cystic lesion of unknown diagnosis were prospectively included at three centers. EUS-FNA was combined with nCLE. The final diagnosis was based on either a stringent gold standard (surgical specimen and/or positive cytopathology) or a committee consensus. Six nonblinded investigators reviewed nCLE sequences from patients with the most stringent final diagnosis, and identified a single feature that was only present in serous cystadenoma (SCA). The findings were correlated with the pathology of archived specimens. After a training session, four blinded independent observers reviewed a separate independent video set, and the yield and interobserver agreement for the criterion were assessed. RESULTS: A superficial vascular network pattern visualized on nCLE was identified as the criterion. It corresponded on pathological specimen to a dense and subepithelial capillary vascularization only seen in SCA. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of this sign for the diagnosis of SCA were 87 %, 69 %, 100 %, 100 %, and 82 %, respectively. Interobserver agreement was substantial (κ = 0.77). CONCLUSION: This new nCLE criterion seems highly specific for the diagnosis of SCA. The visualization of this criterion could have a direct impact on the management of patients by avoiding unnecessary surgery or follow-up.Clinicaltrials.gov NCT01563133.

9 Clinical Trial Radiation plus docetaxel and cisplatin in locally advanced pancreatic carcinoma: a non-comparative randomized phase II trial. 2014

Ducreux, Michel / Giovannini, Marc / Baey, Charlotte / Llacer, Carmen / Bennouna, Jaafar / Adenis, Antoine / Peiffert, Didier / Mornex, Françoise / Abbas, Moncef / Boige, Valèrie / Pignon, Jean-Pierre / Conroy, Thierry / Cellier, Patrice / Juzyna, Beata / Viret, Frédéric. ·Gustave Roussy, Villejuif, France; Université Paris Sud, Le Kremlin Bicetre, France. Electronic address: michel.ducreux@gustaveroussy.fr. · Institut Paoli Calmettes, Marseille, France. · Gustave Roussy, Villejuif, France. · Institut du Cancer Montpellier - Val d'Aurelle, Montpellier, France. · Institut de Cancérologie de l'Ouest - René Gauducheau, Nantes, France. · Centre Oscar Lambret, Lille, France. · Institut de Cancérologie de Lorraine - Alexis Vautrin, Nancy, France. · Hôpital Lyon Sud, Lyon, France. · Institut de Cancérologie de l'Ouest - Paul Papin, Angers, France. · Unicancer, Paris, France. ·Dig Liver Dis · Pubmed #25027552.

ABSTRACT: BACKGROUND: We performed a randomized, non-comparative phase II study evaluating docetaxel in combination with either daily continuous (protracted IV) 5-fluorouracil or cisplatin administered weekly, concurrent to radiotherapy in the treatment of locally advanced pancreatic carcinoma. Results of the docetaxel plus cisplatin regimen are reported. METHODS: Forty chemotherapy-naive patients with locally advanced pancreatic carcinoma were randomly assigned to receive 5-fluorouracil and docetaxel or docetaxel 20mg/m(2) and cisplatin 20mg/m(2)/week, plus concurrent radiotherapy for 6 weeks. The radiation dose to the primary tumour was 54Gy in 30 fractions. The trial's primary endpoint was the 6-month crude non-progression rate. RESULTS: 51 patients from 7 centres were included in the docetaxel-cisplatin treatment group. Six-month non-progression rate was 39% (95% confidence interval: 26-53). Median overall survival was 9.6 months (95% confidence interval: 2.4-60.7); 6 complete and 8 partial responses were obtained. Six patients survived more than 2 years after their inclusion in the trial. Grade ≥3 toxicity was reported in 63% of patients; no treatment-related death occurred. Severe toxicities were mainly anorexia (22%), vomiting (20%) and fatigue (24%). CONCLUSIONS: Despite inadequate efficacy according to the main end point, this regimen gave a satisfactory rate of objective response (27%) with tolerable toxicity.

10 Clinical Trial Feasibility and yield of a novel 22-gauge histology EUS needle in patients with pancreatic masses: a multicenter prospective cohort study. 2013

Larghi, Alberto / Iglesias-Garcia, Julio / Poley, Jan-Werner / Monges, Geneviève / Petrone, Maria Chiara / Rindi, Guido / Abdulkader, Ihab / Arcidiacono, Paolo Giorgio / Costamagna, Guido / Biermann, Katharina / Bories, Erwan / Doglioni, Claudio / Dominguez-Muñoz, J Enrique / Hassan, Cesare / Bruno, Marco / Giovannini, Marc. ·Digestive Endoscopy Unit, Catholic University, Largo A. Gemelli 8, 00168, Rome, Italy, albertolarghi@yahoo.it. ·Surg Endosc · Pubmed #23644834.

ABSTRACT: BACKGROUND: The option of obtaining tissue samples for histological examination during endoscopic ultrasound (EUS) has theoretical and practical advantages over cytology alone. The aim of this study was to evaluate the feasibility, yield, and diagnostic accuracy of a new EUS 22-G fine-needle biopsy (FNB) device in patients with solid pancreatic masses in a multicenter, prospective study. METHODS: All consecutive patients who underwent EUS-guided fine-needle biopsy (EUS-FNB) using a newly developed 22-G FNB needle between September 2010 and October 2010 were enrolled in the study. The EUS-FNB technique was standardized among the participating endoscopists. Only a single needle pass was performed. RESULTS: A total of 61 patients (35 males, mean age 64.2 ± 12.4 years) with solid pancreatic masses with a mean size of 32.4 ± 8.5 mm (range 13-90 mm) participated. EUS-FNB was performed through the duodenum in 35 cases (57.4 %) and was technically feasible in all but one of the 61 (98.4 %) patients without complications. Tissue samples for histological examination were obtained from 55 patients (90.2 %) and were deemed adequate in 54 of the cases (88.5 %). The diagnoses established by EUS-FNB were adenocarcinoma (39 patients), neuroendocrine tumors (5), chronic focal pancreatitis (5), sarcoma (2), lymphoma (1), acinar cellular tumor (1), and pancreatic metastasis from renal cell carcinoma (1). In an intention-to-treat (ITT) analysis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the histologic diagnosis of a pancreatic mass were 87.5, 100, 100, 41.7, and 88.5 %, respectively. CONCLUSIONS: EUS-FNB was technically feasible in 98 % of patients with a solid pancreatic mass. A suitable sample for histological evaluation was obtained in 88.5 % of the cases after only one single needle pass. The apparently low negative predictive value is likely to be improved by increasing the number of needle passes.

11 Article A multicenter randomized trial comparing a 25-gauge EUS fine-needle aspiration device with a 20-gauge EUS fine-needle biopsy device. 2019

van Riet, Priscilla A / Larghi, Alberto / Attili, Fabia / Rindi, Guido / Nguyen, Nam Quoc / Ruszkiewicz, Andrew / Kitano, Masayuki / Chikugo, Takaaki / Aslanian, Harry / Farrell, James / Robert, Marie / Adeniran, Adebowale / Van Der Merwe, Schalk / Roskams, Tania / Chang, Kenneth / Lin, Fritz / Lee, John G / Arcidiacono, Paolo Giorgio / Petrone, Mariachiara / Doglioni, Claudio / Iglesias-Garcia, Julio / Abdulkader, Ihab / Giovannini, Marc / Bories, Erwan / Poizat, Flora / Santo, Erwin / Scapa, Erez / Marmor, Silvia / Bucobo, Juan Carlos / Buscaglia, Jonathan M / Heimann, Alan / Wu, Maoxin / Baldaque-Silva, Francisco / Moro, Carlos Fernández / Erler, Nicole S / Biermann, Katharina / Poley, Jan-Werner / Cahen, Djuna L / Bruno, Marco J. ·Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. · Department of Endoscopy, Catholic University Rome, Rome, Italy. · Department of Pathology, Catholic University Rome, Rome, Italy. · Department of Endoscopy, Royal Adelaide Hospital, Adelaide, Australia. · Department of Pathology, Royal Adelaide Hospital, Adelaide, Australia. · Department of Endoscopy, Kinki University, Osaka-Sayama, Japan. · Department of Pathology, Kinki University, Osaka-Sayama, Japan. · Department of Endoscopy, Yale University School of Medicine, New Haven, Connecticut, USA. · Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA. · Department of Endoscopy, University Hospital Leuven, Leuven, Belgium. · Department of Pathology, University Hospital Leuven, Leuven, Belgium. · Department of Endoscopy, University of California, Irvine, California, USA. · Department of Pathology, University of California, Irvine, California, USA. · Department of Endoscopy, Vita Salute San Raffaele University, Milan, Italy. · Department of Pathology, Vita Salute San Raffaele University, Milan, Italy. · Department of Endoscopy, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. · Department of Pathology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. · Department of Endoscopy, Institut Paoli-Calmettes, Marseilles, France. · Department of Pathology, Institut Paoli-Calmettes, Marseilles, France. · Department of Endoscopy, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Department of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Department of Endoscopy, Stony Brook University Hospital, Stony Brook, New York, USA. · Department of Pathology, Stony Brook University Hospital, Stony Brook, New York, USA. · Department of Upper GI Diseases, Unit of Gastrointestinal Endoscopy, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden. · Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, Sweden. · Department of Biostatistics, Erasmus MC University Medical Center Rotterdam, the Netherlands. · Department of Pathology, Erasmus MC University Medical Center Rotterdam, the Netherlands. ·Gastrointest Endosc · Pubmed #30367877.

ABSTRACT: BACKGROUND AND AIMS: Several studies have compared EUS-guided FNA with fine-needle biopsy (FNB), but none have proven superiority. We performed a multicenter randomized controlled trial to compare the performance of a commonly used 25-gauge FNA needle with a newly designed 20-gauge FNB needle. METHODS: Consecutive patients with a solid lesion were randomized in this international multicenter study between a 25-gauge FNA (EchoTip Ultra) or a 20-gauge FNB needle (ProCore). The primary endpoint was diagnostic accuracy for malignancy and the Bethesda classification (non-diagnostic, benign, atypical, malignant). Technical success, safety, and sample quality were also assessed. Multivariable and supplementary analyses were performed to adjust for confounders. RESULTS: A total of 608 patients were allocated to FNA (n = 306) or FNB (n = 302); 312 pancreatic lesions (51%), 147 lymph nodes (24%), and 149 other lesions (25%). Technical success rate was 100% for the 25-gauge FNA and 99% for the 20-gauge FNB needle (P = .043), with no differences in adverse events. The 20-gauge FNB needle outperformed 25-gauge FNA in terms of histologic yield (77% vs 44%, P < .001), accuracy for malignancy (87% vs 78%, P = .002) and Bethesda classification (82% vs 72%, P = .002). This was robust when corrected for indication, lesion size, number of passes, and presence of an on-site pathologist (odds ratio, 3.53; 95% confidence interval, 1.55-8.56; P = .004), and did not differ among centers (P = .836). CONCLUSION: The 20-gauge FNB needle outperformed the 25-gauge FNA needle in terms of histologic yield and diagnostic accuracy. This benefit was irrespective of the indication and was consistent among participating centers, supporting the general applicability of our findings. (Clinical trial registration number: NCT02167074.).

12 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.

13 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.

14 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.

15 Article Gene expression profiling of patient-derived pancreatic cancer xenografts predicts sensitivity to the BET bromodomain inhibitor JQ1: implications for individualized medicine efforts. 2017

Bian, Benjamin / Bigonnet, Martin / Gayet, Odile / Loncle, Celine / Maignan, Aurélie / Gilabert, Marine / Moutardier, Vincent / Garcia, Stephane / Turrini, Olivier / Delpero, Jean-Robert / Giovannini, Marc / Grandval, Philippe / Gasmi, Mohamed / Ouaissi, Mehdi / Secq, Veronique / Poizat, Flora / Nicolle, Rémy / Blum, Yuna / Marisa, Laetitia / Rubis, Marion / Raoul, Jean-Luc / Bradner, James E / Qi, Jun / Lomberk, Gwen / Urrutia, Raul / Saul, Andres / Dusetti, Nelson / Iovanna, Juan. ·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. · Hôpital Nord, Marseille, France. · CIC1409, AP-HM-Hôpital Nord, Aix-Marseille Université, Marseille, France. · Institut Paoli-Calmettes, Marseille, France. · Hôpital de la Timone, Marseille, France. · Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France. · Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. · Laboratory of Epigenetics and Chromatin Dynamics, Departments of Biochemistry and Molecular Biology and Medicine, Mayo Clinic, Rochester, MN, USA. · Centre Interdisciplinaire de Nanoscience de Marseille-CNRS UMR 7325, Parc Scientifique et Technologique de Luminy, Aix-Marseille Université, Marseille, 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 nelson.dusetti@inserm.fr juan.iovanna@inserm.fr. ·EMBO Mol Med · Pubmed #28275007.

ABSTRACT:

16 Article A pancreatic ductal adenocarcinoma subpopulation is sensitive to FK866, an inhibitor of NAMPT. 2016

Barraud, Marine / Garnier, Jonathan / Loncle, Celine / Gayet, Odile / Lequeue, Charlotte / Vasseur, Sophie / Bian, Benjamin / Duconseil, Pauline / Gilabert, Marine / Bigonnet, Martin / Maignan, Aurélie / Moutardier, Vincent / Garcia, Stephane / Turrini, Olivier / Delpero, Jean-Robert / Giovannini, Marc / Grandval, Philippe / Gasmi, Mohamed / Ouaissi, Mehdi / Secq, Veronique / Poizat, Flora / Guibert, Nicolas / Iovanna, Juan / Dusetti, Nelson. ·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, Marseille, France. · Hôpital Nord, Marseille, France. · CIC1409, AP-HM - Nord University Hospital, Aix-Marseille University, Marseille, France. · Institut Paoli-Calmettes, Marseille, France. · Hôpital de la Timone, Marseille, France. · Hospices Civils de Lyon, Lyon, France. ·Oncotarget · Pubmed #27462772.

ABSTRACT: Treating pancreatic cancer is extremely challenging due to multiple factors, including chemoresistance and poor disease prognosis. Chemoresistance can be explained by: the presence of a dense stromal barrier leading to a lower vascularized condition, therefore limiting drug delivery; the huge intra-tumoral heterogeneity; and the status of epithelial-to-mesenchymal transition. These factors are highly variable between patients making it difficult to predict responses to chemotherapy. Nicotinamide phosphoribosyl transferase (NAMPT) is the main enzyme responsible for recycling cytosolic NAD+ in hypoxic conditions. FK866 is a noncompetitive specific inhibitor of NAMPT, which has proven anti-tumoral effects, although a clinical advantage has still not been demonstrated. Here, we tested the effect of FK866 on pancreatic cancer-derived primary cell cultures (PCCs), both alone and in combination with three different drugs typically used against this cancer: gemcitabine, 5-Fluorouracil (5FU) and oxaliplatin. The aims of this study were to evaluate the benefit of drug combinations, define groups of sensitivity, and identify a potential biomarker for predicting treatment sensitivity. We performed cell viability tests in the presence of either FK866 alone or in combination with the drugs above-mentioned. We confirmed both inter- and intra-tumoral heterogeneity. Interestingly, only the in vitro effect of gemcitabine was influenced by the addition of FK866. We also found that NAMPT mRNA expression levels can predict the sensitivity of cells to FK866. Overall, our results suggest that patients with tumors sensitive to FK866 can be identified using NAMPT mRNA levels as a biomarker and could therefore benefit from a co-treatment of gemcitabine plus FK866.

17 Article Heterogeneity of metastatic pancreatic adenocarcinoma: Lung metastasis show better prognosis than liver metastasis-a case control study. 2016

Decoster, Claire / Gilabert, Marine / Autret, Aurélie / Turrini, Olivier / Oziel-Taieb, Sandrine / Poizat, Flora / Giovannini, Marc / Viens, Patrice / Iovanna, Juan / Raoul, Jean-Luc. ·Department of Medical Oncology, Paoli-Calmettes Institute, Marseille 13273, France. · Biostatistic Unit, Paoli-Calmettes Institute, Marseille 13273, France. · Department of Digestive Surgery, Paoli-Calmettes Institute, Marseille 13273, France. · Department of Pathology, Paoli-Calmettes Institute, Marseille 13273, France. · Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Marseille 13273, France. ·Oncotarget · Pubmed #27286454.

ABSTRACT: The prognosis of metastatic pancreatic ductal adenocarcinoma (PDAC) is grim, with a median overall survival of under 1 year. In our clinical practice, we observed a few cases of isolated lung metastases from PDAC with unusually long outcomes. We compared these cases in a case-control study of lung-only vs. liver-only metastases from PDAC.From our database, we found 37 cases of lung-only metastases and paired them with 37 cases of liver-only metastases by age, tumor location and treatment.The lung-only group differed significantly from the liver-only group with respect to the following parameters: female predominance, more metachronous cases, fewer nodules per patient, and smaller increases in tumor markers. Local invasion parameters (i.e., arterial or venous involvement) were not significantly different. The outcomes were significantly different, with a median overall survival from the occurrence of metastases of 20.8 vs. 9.1 months and a median progression-free survival of 11 vs. 3.5 months.In conclusion, this case-control study seemed to confirm that lung-only PDAC metastases have prognoses different from those of liver-only metastases. A better understanding of the mechanisms underlying these differences will help identify abnormalities associated with tumor aggressiveness.

18 Article Expression of Genes with Copy Number Alterations and Survival of Patients with Pancreatic Adenocarcinoma. 2016

Birnbaum, David J / Bertucci, François / Finetti, Pascal / Adélaïde, José / Giovannini, Marc / Turrini, Olivier / Delpero, Jean Robert / Raoul, Jean Luc / Chaffanet, Max / Moutardier, Vincent / Birnbaum, Daniel / Mamessier, Emilie. ·Department of Molecular Oncology UMR1068, Paoli-Calmettes Instituet, Marseille, France Department of Digestive Surgery, North Hospital, Marseille, France Aix-Marseille University, Marseille, France david.birnbaum10@gmail.com. · Department of Molecular Oncology UMR1068, Paoli-Calmettes Instituet, Marseille, France Aix-Marseille University, Marseille, France Department of Medical Oncology, Paoli-Calmettes Instituet, Marseille, France. · Department of Molecular Oncology UMR1068, Paoli-Calmettes Instituet, Marseille, France. · Department of Gastroenterology, Paoli-Calmettes Instituet, Marseille, France. · Aix-Marseille University, Marseille, France Department of Digestive and Oncologic Surgery, Marseille Research Center of Cancerology UMR1068, Paoli-Calmettes Instituet, Marseille, France. · Aix-Marseille University, Marseille, France Department of Medical Oncology, Paoli-Calmettes Instituet, Marseille, France. · Department of Digestive Surgery, North Hospital, Marseille, France Aix-Marseille University, Marseille, France. · Department of Molecular Oncology UMR1068, Paoli-Calmettes Instituet, Marseille, France Aix-Marseille University, Marseille, France. ·Cancer Genomics Proteomics · Pubmed #27107061.

ABSTRACT: BACKGROUND/AIM: Individual molecular information might improve management of pancreatic adenocarcinoma. To identify actionable genes, at the transcriptional level, we investigated candidate genes that we had previously identified using array-comparative genomic hybridization (aCGH). MATERIALS AND METHODS: We collected 10 public gene-expression datasets, gathering a total of 524 pancreatic samples (105 normal and 419 malignant tissues). Based on our previous aCGH analysis, we searched for genes differentially expressed between normal and malignant samples and genes associated with survival. RESULTS: Among genes amplified/gained by aCGH, 48% were overexpressed in malignant tissues. The majority of these genes were related to apoptosis, cell-cycle regulation and differentiation. Among genes located in areas of loss, 41% were underexpressed in malignant tissues; most of them were involved in ion transport, homeostasis maintenance and fatty acid metabolism. Survival analysis identified genes significantly related to shorter (n=17) or longer (n=29) survival. CONCLUSION: Some of these genes can be further investigated as potential prognostic markers.

19 Article Treatment of Pancreatic Adenocarcinoma in Elderly Patients over 75 Years of Age: A Retrospective Series of 129 Patients. 2016

Oziel-Taieb, Sandrine / Faure, Marjorie / Gilabert, Marine / Autret, Aurélie / Turrini, Olivier / Moureau-Zabotto, Laurence / Giovannini, Marc / Rousseau, Frederique / Raoul, Jean-Luc. ·Department of Medical Oncology, Paoli-Calmettes Institute, BP 156, 13273, Marseille, France. oziels@ipc.unicancer.fr. · Department of Medical Oncology, Paoli-Calmettes Institute, BP 156, 13273, Marseille, France. faurem@ipc.unicancer.fr. · Department of Medical Oncology, Paoli-Calmettes Institute, BP 156, 13273, Marseille, France. gilabertm@ipc.unicancer.fr. · Statistical Unit, Paoli-Calmettes Institute, BP 156, 13273, Marseille, France. autreta@ipc.unicancer.fr. · Department of Surgical Oncology, Paoli-Calmettes Institute, BP 156, 13273, Marseille, France. turrinio@ipc.unicancer.fr. · Department of Radiotherapy, Paoli-Calmettes Institute, BP 156, 13273, Marseille, France. moureaul@ipc.unicancer.fr. · Department of Interventional Endoscopy, Paoli-Calmettes Institute, BP 156, 13273, Marseille, France. giovanninim@ipc.unicancer.fr. · Department of Medical Oncology, Paoli-Calmettes Institute, BP 156, 13273, Marseille, France. rousseauf@ipc.unicancer.fr. · Department of Medical Oncology, Paoli-Calmettes Institute, BP 156, 13273, Marseille, France. raouljl@ipc.unicancer.fr. ·J Gastrointest Cancer · Pubmed #26545612.

ABSTRACT: PURPOSE: To better know the presentation and outcome of pancreatic adenocarcinoma in patients above 75 years of age. METHOD: Retrospective analysis of consecutive patients with a pancreatic adenocarcinoma seen in the Comprehensive Cancer Center of Marseille between January 2002 and January 2012 was used. RESULTS: During these 10 years, 129 patients older than 75 years of age were seen, 61 females and 68 males, median age 78. At diagnosis, the tumor was metastatic in 45%. First line treatments were: surgical resection in 22 cases, radio-chemotherapy in 20 cases (1 operated on later), systemic chemotherapy in 59 cases, and best supportive care alone in 28 cases. Resection was possible in 19 cases and was R0 in 17; post-operative mortality was 0%, and half received adjuvant chemotherapy. Median overall survival was 43 months with a 2-year overall survival of 64%. For locally advanced tumor, 16 received best supportive care and 33 a specific treatment (20 cases of radio-chemotherapy). Median overall survival was 9.1 months and 2-year overall, survival was 6.1%. Among the 58 metastatic patients, 79% received systemic chemotherapy (most by gemcitabine); tolerance was correct in half. Median overall survival was 4.7 months, with a 2-year overall survival of 5.3%. CONCLUSIONS: Surgery of pancreatic adenocarcinoma is feasible and safe in elderly patients with good outcomes. In advanced and metastatic patients, the outcome is poor despite a correct tolerance of systemic chemotherapy. Randomized trials specially designed for this population are urgently needed.

20 Article In vivo characterization of pancreatic cystic lesions by needle-based confocal laser endomicroscopy (nCLE): proposition of a comprehensive nCLE classification confirmed by an external retrospective evaluation. 2016

Napoleon, Bertrand / Lemaistre, Anne-Isabelle / Pujol, Bertrand / Caillol, Fabrice / Lucidarme, Damien / Bourdariat, Raphaël / Morellon-Mialhe, Blandine / Fumex, Fabien / Lefort, Christine / Lepilliez, Vincent / Palazzo, Laurent / Monges, Geneviève / Poizat, Flora / Giovannini, Marc. ·Department of Gastroenterology, Hôpital Privé Jean Mermoz, Générale de Santé, 4 rue Jacqueline Auriol, 69008, Lyon, France. bertrand.napoleon@dartybox.com. · Department of Biopathology, Centre Léon Bérard, Lyon, France. · Department of Gastroenterology, Hôpital Privé Jean Mermoz, Générale de Santé, 4 rue Jacqueline Auriol, 69008, Lyon, France. · Department of Hepato-gastroenterology, Institut Paoli Calmettes, Marseille, France. · Medico-surgical Department of Hepato-gastroenterology, Hôpital Saint-Philibert, Lomme-lès-Lille, France. · Department of Digestive Surgery, Hôpital Privé Jean Mermoz, Générale de Santé, Lyon, France. · Department of Gastroenterology, Clinique du Trocadéro, Paris, France. · Department of Biopathology, Institut Paoli Calmettes, Marseille, France. ·Surg Endosc · Pubmed #26428198.

ABSTRACT: BACKGROUND AND AIMS: The differential diagnosis of solitary pancreatic cystic lesions is sometimes difficult. Needle-based confocal laser endomicroscopy (nCLE) performed during endoscopic ultrasound-fine-needle aspiration (EUS-FNA) enables real-time imaging of the internal structure of such cysts. Criteria have already been described for serous cystadenoma and intraductal papillary mucinous neoplasm (IPMN). The aims of the study were to determine new nCLE criteria for the diagnosis of pancreatic cystic lesions, to propose a comprehensive nCLE classification for the characterization of those lesions, and to carry out a first external retrospective validation . METHODS: Thirty-three patients with a lone pancreatic cystic lesion were included (CONTACT 1 study). EUS-FNA was combined with nCLE. Diagnosis was based on either pathology result (Group 1, n = 20) or an adjudication committee consensus (Group 2, n = 13). Six investigators, unblinded, studied cases from Group 1 and identified nCLE criteria for mucinous cystic neoplasm (MCN), pseudocyst (PC), and cystic neuroendocrine neoplasm (NEN). Four external reviewers assessed, blinded, the yield and interobserver agreement for the newly identified (MCN, PC) and previously described (IPMN, SC) criteria in a subset of 31 cases. RESULTS: New nCLE criteria were described for MCN (thick gray line), PC (field of bright particles), and cystic NEN (black neoplastic cells clusters with white fibrous areas). These criteria correlated with the histological features of the corresponding lesions. In the retrospective validation, a conclusive nCLE result was obtained for 74 % of the cases (87 % "true" and 13 % "false" with respect to the final diagnosis). On this limited case series, the nCLE criteria showed a trend for high diagnostic specificity (>90 % for mucinous cysts, 100 % for non-mucinous cysts). CONCLUSIONS: Based on this newly completed atlas of interpretation criteria, nCLE could facilitate the diagnosis of pancreatic cystic lesion types.

21 Article Rapid on-site cytopathological examination (ROSE) performed by endosonagraphers and its improvement in the diagnosis of pancreatic solid lesions. 2015

Ganc, Ricardo Leite / Carbonari, Augusto Pincke Cruz / Colaiacovo, Rogério / Araujo, Júlia / Filippi, Sheila / Silva, Rodrigo Altenfender / Pacheco Junior, Adhemar Monteiro / Rossini, Lucio Giovanni Battista / Giovannini, Marc. ·Faculdade de Ciências Médicas, Santa Casa de São Paulo, Sao Paulo, SP, Brazil. · French Brazilian Centre of Endoscopic Ultrasound, Sao Paulo, SP, Brazil. · Endoscopy Department, Sirio-Libanes Hospital, Sao Paulo, SP, Brazil. · FCMSCSP, Sao Paulo, SP, Brazil. · Institut Paoli-Calmettes, Marseille, France. ·Acta Cir Bras · Pubmed #26270143.

ABSTRACT: PURPOSE: To evaluate the diagnosis improvement of EUS-FNA when using ROSE performed by the endosonographer. METHODS: A retrospective study was conducted. A total of 48 pancreatic solid masses EUS-FNA were divided into two groups according to the availability of on-site cytology (ROSE) - the first 24 patients (group A-without ROSE) and the latter 24 cases (group B-with ROSE). Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, complications and inadequacy rate of EUS-FNA were determined and compared. RESULTS: Among the 48 EUS-FNA, the overall performance was: sensitivity 82%; specificity 100%; positive predictive value (PPV) 100%; negative predictive value (NPV) 70% and accuracy 87%. The sensitivity of the Group A was 71%, versus 94% in-group B (p=0.61). Moreover, the negative predictive value was 58% versus 87% (p=0.72). The accuracy rate increased from 79% to 96% (p=0.67) in the ROSE group. The number of punctures was similar between the groups. No major complications were reported. CONCLUSION: Rapid on-site cytopathological examination, even when performed by the endosonographer, may improve the diagnostic performance in the diagnosis of solid pancreatic lesions, regardless of the slight increase in the number of punctures.

22 Article [Echo-endoscopic ultrasound and pancreatic cancer]. 2015

Giovannini, Marc. · ·Rev Prat · Pubmed #26016201.

ABSTRACT: -- No abstract --

23 Article Transcriptomic analysis predicts survival and sensitivity to anticancer drugs of patients with a pancreatic adenocarcinoma. 2015

Duconseil, Pauline / Gilabert, Marine / Gayet, Odile / Loncle, Celine / Moutardier, Vincent / Turrini, Olivier / Calvo, Ezequiel / Ewald, Jacques / Giovannini, Marc / Gasmi, Mohamed / Bories, Erwan / Barthet, Marc / Ouaissi, Mehdi / Goncalves, Anthony / Poizat, Flora / Raoul, Jean Luc / Secq, Veronique / Garcia, Stephane / Viens, Patrice / Iovanna, Juan / Dusetti, Nelson. ·Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France. · Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France; Department of Surgery, Hôpital Nord, Marseille, France. · Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France; Paoli-Calmettes Institute, Marseille, France. · Genomic Center, CHUL Research Centre, Quebec City, Quebec, Canada. · Paoli-Calmettes Institute, Marseille, France. · Department of Gastroenterology, Hôpital Nord, Marseille, France. · Department of Surgery, La Timone Hospital, Marseille, France. · Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France. Electronic address: juan.iovanna@inserm.fr. · Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France. Electronic address: nelson.dusetti@inserm.fr. ·Am J Pathol · Pubmed #25765988.

ABSTRACT: A major impediment to the effective treatment of patients with pancreatic ductal adenocarcinoma (PDAC) is the molecular heterogeneity of this disease, which is reflected in an equally diverse pattern of clinical outcome and in responses to therapies. We developed an efficient strategy in which PDAC samples from 17 consecutive patients were collected by endoscopic ultrasound-guided fine-needle aspiration or surgery and were preserved as breathing tumors by xenografting and as a primary culture of epithelial cells. Transcriptomic analysis was performed from breathing tumors by an Affymetrix approach. We observed significant heterogeneity in the RNA expression profile of tumors. However, the bioinformatic analysis of these data was able to discriminate between patients with long- and short-term survival corresponding to patients with moderately or poorly differentiated PDAC tumors, respectively. Primary culture of cells allowed us to analyze their relative sensitivity to anticancer drugs in vitro using a chemogram, similar to the antibiogram for microorganisms, establishing an individual profile of drug sensitivity. As expected, the response was patient dependent. We also found that transcriptomic analysis predicts the sensitivity of cells to the five anticancer drugs most frequently used to treat patients with PDAC. In conclusion, using this approach, we found that transcriptomic analysis could predict the sensitivity to anticancer drugs and the clinical outcome of patients with PDAC.

24 Article Interobserver agreement and accuracy of preoperative endoscopic ultrasound-guided biopsy for histological grading of pancreatic cancer. 2015

Larghi, Alberto / Correale, Loredana / Ricci, Riccardo / Abdulkader, Ihab / Monges, Geneviève / Iglesias-Garcia, Julio / Giovannini, Marc / Attili, Fabia / Vitale, Giovanna / Hassan, Cesare / Costamagna, Guido / Rindi, Guido. ·Digestive Endoscopy Unit, Università Cattolica del Sacro Cuore, Rome, Italy. · Department of Pathology, Università Cattolica del Sacro Cuore, Rome, Italy. · Department of Pathology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. · Department of Pathology, Paoli-Calmettes Institute, Marseilles, France. · Gastroenterology Department, Foundation for Research in Digestive Diseases (FIENAD), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. · Endoscopic Unit, Paoli-Calmettes Institute, Marseilles, France. ·Endoscopy · Pubmed #25521572.

ABSTRACT: BACKGROUND AND STUDY AIM: Poorly differentiated/high grade pancreatic ductal adenocarcinoma (PDAC) is associated with an early unfavorable outcome, and patients with these tumors may be candidates for neo-adjuvant treatment. Endoscopic ultrasound-guided pancreatic fine-needle biopsy (EUS-FNB) may, in theory, allow preoperative assessment of PDAC histological grading. The aim of the current study was to assess the interobserver agreement and accuracy of preoperative PDAC grading from EUS-FNB specimens. METHODS: Data from 42 postsurgical PDAC patients who had undergone preoperative EUS-FNB were retrieved. Four experienced pathologists independently reviewed the EUS-FNB slides and reported tumor grading (well, moderately, or poorly differentiated). Agreement among pathologists for grading of preoperative EUS-FNB samples was expressed by using Cohen's or Fleiss' kappa statistic, as appropriate. Postsurgical PDAC grading was used as the gold standard to assess the cumulative accuracy of EUS-FNB for the preoperative prediction of PDAC grading. RESULTS: The kappa values for PDAC grading on EUS-FNB specimens ranged from 0.09 to 0.41. The total agreement among the four pathologists was only fair (κ = 0.27; 95 % confidence interval [CI] 0.14 - 0.38). When tumor grades were grouped as well or moderately differentiated vs. poorly differentiated, kappa values ranged from 0.19 to 0.50, with only a fair overall agreement (κ = 0.27; 95 %CI 0.21 - 0.49). The accuracy of preoperative grading from EUS-FNB was 56 % (75/134 readings; 95 %CI 40 % - 65 %), with mean sensitivity and specificity to detect a high grade, poorly differentiated tumor of 41 % (95 %CI 19 % - 54 %) and 78 % (53/68 readings; 95 %CI 60 % - 99 %), respectively. CONCLUSIONS: Preoperative EUS-FNB-based histological grading of PDAC is unreliable, and current results do not support the use of this information in clinical practice. This appears to be due to suboptimal interobserver agreement among pathologists and an overall low accuracy in predicting postsurgical grading.

25 Article Probe-based confocal laser endomicroscopy in the pancreatic duct provides direct visualization of ductal structures and aids in clinical management. 2015

Kahaleh, Michel / Turner, Brian G / Bezak, Karl / Sharaiha, Reem Z / Sarkaria, Savreet / Lieberman, Michael / Jamal-Kabani, Armeen / Millman, Jennifer E / Sundararajan, Subha V / Chan, Ching / Mehta, Shivani / Widmer, Jessica L / Gaidhane, Monica / Giovannini, Marc. ·Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY, United States. Electronic address: mkahaleh@gmail.com. · Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY, United States. · Department of Gastroenterology, Paoli-Calmettes Institute, Marseille, France. ·Dig Liver Dis · Pubmed #25499063.

ABSTRACT: BACKGROUND: Confocal endomicroscopy provides real-time evaluation of various sites and has been used to provide detailed endomicroscopic imaging of the biliary tree. We aimed to evaluate the feasibility and utility of probe-based confocal laser endomicroscopy of the pancreatic duct as compared to cytologic and histologic results in patients with indeterminate pancreatic duct strictures. METHODS: Retrospective data on patients with indeterminate pancreatic strictures undergoing endoscopic retrograde cholangiopancreatography (ERCP) and confocal endomicroscopy were collected from two tertiary care centres. Real-time confocal endomicroscopy images were obtained during ERCP and immediate interpretation according to the Miami Classification was performed. RESULTS: 18 patients underwent confocal endomicroscopy for evaluation of pancreatic strictures from July 2011 to December 2012. Mean pancreatic duct size was 4.2mm (range 2.2-8mm). Eight cases were interpreted as benign, 4 as malignant, 4 suggestive of intraductal papillary mucinous neoplasms, and 2 appeared normal. Cytology/histopathology for 15/16 cases showed similar results to confocal endomicroscopy interpretation. Kappa coefficient of agreement between cyto/histopathology and confocal endomicroscopy was 0.8 (p=0.0001). Pancreatic confocal endomicroscopy changed management in four patients, changing the type of surgery from total pancreatectomy to whipple. CONCLUSIONS: Confocal endomicroscopy is effective in assisting with diagnosis of indeterminate pancreatic duct strictures as well as mapping of abnormal pancreatic ducts prior to surgery.

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