Intérêt de l'adiponectine comme marqueur diagnostique du cancer du pancréas

Objectif. L objectif de notre étude était d évaluer l intérêt de l adiponectine en tant que marqueur diagnostique du cancer du pancréas en particulier chez les patients porteurs d un diabète, dont les principales caractéristiques ont été analysées. Méthode. Dans cette étude cas-témoin, tous les cas incidents de cancers du pancréas pris en charge dans un centre universitaire entre janvier 2006 et septembre 2007 ont été analysés. Une population contrôle de cas incidents de cancers colorectaux appariés sur l âge, le sexe et le stade tumoral a été sélectionnée sur la même période. En dehors des données démographiques, les variables étudiées étaient concentration sérique d adiponectine, l insulino-résistance (index HOMA > 3,5), la présence d un syndrome dysmétabolique (obésité, dyslipidémie, HTA), le pourcentage d amaigrissement et les données relatives à la tumeur. Le seuil d adiponectine optimal a été recherché par analyse des courbes ROC et mesure des aires sous la courbe. Les facteurs indépendants et significativement associés à une concentration sérique non abaissée d adiponectine d une part et au diabète associé au cancer du pancréas d autre part ont été recherchés par la méthode de régression logistique binaire en analyse multivariée. Résultats. Cinquante trois patients porteurs d un cancer du pancréas et 30 patients porteurs d un adénocarcinome colorectal ont été analysés. Un diabète était présent dans 18,2% des cas de cancer colorectal et 39,6% des cas de cancer du pancréas (p=0,037). La moyenne de l adiponectinémie était plus élevée dans le groupe cancer du pancréas (20,95% vs 15,98 ; p=0,03). Le seuil d adiponectine permettant le meilleur rapport sensibilité/spécificité a été calculé à 10 g/L (sensibilité 78% et spécificité 82%). En analyse multivariée après ajustement sur le sexe, l âge ( 20 mol/L) et l amaigrissement (> 10% du poids), les variables indépendamment liées à une concentration élevée d adiponectine (> 10 g/L) étaient : la présence d un cancer du pancréas (OR: 12,03, p=0,047), d un diabète (OR: 0,07, p=0,01) et d une insulino-résistance (OR: 0,42, p=0,05). Dans le groupe cancer du pancréas, parmi les patients diabétiques, le diabète était diagnostiqué dans 43,0% des cas dans les 3 ans précédant le diagnostic du cancer. Aucun patient non diabétique ne présentait d insulino-résistance contre 50% pour les patients diabétiques. En analyse multivariée, seule l obésité constituait un facteur indépendant expliquant le diabète dans le groupe cancer du pancréas (surpoids: OR=11,35, p=0,01 et obésité: OR=47,49, p 10 g/L) en cas de cancer du pancréas qu en cas de cancer colorectal. Nous montrons pour la première fois que l adiponectine pourrait constituer un marqueur diagnostique de cancer du pancréas. Le mécanisme du diabète pourrait passer, comme le suggère notre étude, par l induction d une insulinopénie, ce qui contraste avec le diabète de type 2 classique où l insulino-résistance est le mécanisme prépondérant et l adiponectine abaissée. Ces données doivent être confirmées sur de plus grands effectifs et pourraient avoir un intérêt dans le dépistage précoce du cancer du pancréas dans une population de patients présentant un diabète de novo et une concentration sérique d adiponectine non abaissée (> 10 g/L).GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

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International audienc

Liver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study

International audienc

Baseline Splenic Volume as a Prognostic Biomarker of FOLFIRI Efficacy and a Surrogate Marker of MDSC Accumulation in Metastatic Colorectal Carcinoma

International audienceBackground: Predictive biomarkers of response to chemotherapy plus antiangiogenic for metastatic colorectal cancer (mCRC) are lacking. The objective of this study was to test the prognostic role of splenomegaly on baseline CT scan. Methods: This study is a sub-study of PRODIGE-9 study, which included 488 mCRC patients treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab in first line. The association between splenic volume, and PFS and OS was evaluated by univariate and multivariable Cox analyses. The relation between circulating monocytic Myeloid derived suppressor cells (mMDSC) and splenomegaly was also determined. Results: Baseline splenic volume > 180 mL was associated with poor PFS (median PFS = 9.2 versus 11.1 months; log-rank p = 0.0125), but was not statistically associated with OS (median OS = 22.6 versus 28.5 months; log-rank p = 0.1643). The increase in splenic volume at 3 months had no impact on PFS (HR 0.928; log-rank p = 0.56) or on OS (HR 0.843; log-rank p = 0.21). Baseline splenic volume was positively correlated with the level of baseline circulating mMDSC (r = 0.48, p-value = 0.031). Conclusion: Baseline splenomegaly is a prognostic biomarker in patients with mCRC treated with FOLFIRI and bevacizumab, and a surrogate marker of MDSC accumulation

Structural and Socio-Spatial Determinants Influencing Care and Survival of Patients with a Pancreatic Adenocarcinoma: Results of the PANDAURA Cohort

Background and aims: Pancreatic cancer is highly lethal and often diagnosed at an advanced stage. This cohort study analyzes the impact of care pathways, delays, and socio-spatial determinants on pancreatic cancer patients’ diagnosis, treatment, and prognosis. Method: Patients with pancreatic adenocarcinoma newly diagnosed at all stages between January and June 2016 in the AuRA French region were included. The influence on survival of delays of care, healthcare centers’ expertise, and socio-spatial determinants was evaluated. Results: Here, 538 patients were included in 76 centers including 116 patients (21.8%) with resectable, 64 (12.0%) borderline-resectable, 147 (27.6%) locally-advanced tumors, and 205 (38.5%) with metastatic disease. A delay between first symptoms and CT scans did not statistically influence overall survival (OS). In resected patients, OS was significantly higher in centers with more than 20 surgeries (HR = 2.236 and HR5-20 surgeries/year = 1.215 versus centers with > 20 surgeries/year p = 0.0081). Regarding socio-spatial determinants, patients living in municipalities with greater access to a general practitioner (HR = 1.673, p = 0.0153) or with a population density below 795.1 people/km2 (HR = 1.881, p = 0.0057) were significantly more often resectable. Conclusion: This cohort study supports the pivotal role of general practitioner in cancer care and the importance of the centralization of pancreatic surgery to optimize pancreatic cancer patients’ care and outcomes. However, delays of care did not impact patient survival

Management of Patients with Pancreatic Ductal Adenocarcinoma in the Real-Life Setting: Lessons from the French National Hospital Database

Pancreatic ductal adenocarcinoma (PDAC) remains a major public health challenge, and faces disparities and delays in the diagnosis and access to care. Our purposes were to describe the medical path of PDAC patients in the real-life setting and evaluate the overall survival at 1 year. We used the national hospital discharge summaries database system to analyze the management of patients with newly diagnosed PDAC over the year 2016 in Auvergne-Rhône-Alpes region (AuRA) (France). A total of 1872 patients met inclusion criteria corresponding to an incidence of 22.6 per 100,000 person-year. Within the follow-up period, 353 (18.9%) were operated with a curative intent, 743 (39.7%) underwent chemo- and/or radiotherapy, and 776 (41.4%) did not receive any of these treatments. Less than half of patients were operated in a high-volume center, defined by more than 20 PDAC resections performed annually, mainly university hospitals. The 1-year survival rate was 47% in the overall population. This study highlights that a significant number of patients with PDAC are still operated in low-volume centers or do not receive any specific oncological treatment. A detailed analysis of the medical pathways is necessary in order to identify the medical and territorial determinants and their impact on the patient’s outcome

Perioperative Cetuximab with Cisplatin and 5-Fluorouracil in Esogastric Adenocarcinoma: A Phase II Study

Purpose: While perioperative chemotherapy provides a survival benefit over surgery alone in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, the results need to be improved. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin. Patients and Methods: Patients received six cycles of cetuximab, cisplatin, and simplified LV5FU2 before and after surgery. The primary objective was a combined evaluation of the tumor objective response (TOR), assessed by computed tomography, and the absence of major toxicities resulting in discontinuation of neoadjuvant chemotherapy (NCT) (45% and 90%, respectively). Results: From 2011 to 2013, 65 patients were enrolled. From 64 patients evaluable for the primary endpoint, 19 (29.7%) had a morphological TOR and 61 (95.3%) did not stop NCT prematurely due to major toxicity. Sixty patients (92.3%) underwent resection. Sixteen patients (/56 available, 28.5%) had histological responses (Mandard tumor regression grade ≤3). After a median follow-up of 44.5 months, median disease-free and overall survival were 24.4 [95% CI: 16.4-39.4] and 40.3 months [95% CI: 27.5-NA], respectively. Conclusion: Adding cetuximab to the NCT regimen in operable G/GEJ adenocarcinomas is safe, but did not show enough efficacy in the present study to meet the primary endpoint (NCT01360086)