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Karlin L.,Hopital Lyon Sud | Macro M.,Hopital Cote de Nacre | Garderet L.,HOpital Saint Antoine | Arnulf B.,Hopital Saint Louis | And 6 more authors.
Blood | Year: 2015

The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) can be safely administered to patients with end-stage relapsed/refractory multiple myeloma (RRMM). However, we observed a shorter median progression-free survival (PFS) and overall survival (OS) in these patients when characterized with adverse cytogenetics (deletion 17p and translocation [4;14]) in the Intergroupe Francophone Myélome (IFM) 2009-02 trial. We then sought to determine whether MM with adverse cytogenetics would benefit more from Pom-Dex if exposed earlier in the multicenter IFM 2010-02 trial. The intention-to-treat population included 50 patients, with a median age of 63 years (38% were ≥65 years). Interestingly, there was a striking difference in time to progression (TTP), duration of response, and overall response rate (ORR) according to the presence of del(17p) compared with t(4;14) (TTP, 7.3 vs 2.8 months; duration of response, 8.3 vs 2.4 months; and ORR, 32% vs 15%). OS was prolonged after Pom-Dex, particularly in t(4;14), given the short TTP, suggesting that patients were rescued at relapse with further lines of therapy. Pom-Dex, a doublet immunomodulatory drug-based regimen, is active and well tolerated in adverse cytogenetic patients with early RRMM, particularly in those with del(17p), who are characterized by a high and rapid development of a refractoriness state and known for their poor prognosis. Future studies will determine the underlying mechanisms of Pom-Dex activity in del(17p). © 2015 by The American Society of Hematology.

Fuks D.,University of Picardy | Regimbeau J.M.,University of Picardy | Le Treut Y.-P.,Hopital Conception | Raventos A.,Hospital Sant Pau | And 2 more authors.
World Journal of Surgery | Year: 2011

Background: Incidental gallbladder cancer (GBC) is frequently discovered on the specimen when cholecystectomy for a benign disease is performed. The objective of the present study was to assess the management of incidental GBC patients in a French registry. Methods: Data on patients with GBC treated between 1998 and 2008 were retrospectively collated in a French, multicenter database. Results: The registry contained 218 patients with incidental GBC (67 men and 151 women; median age = 64 years; age range = 31-88). One hundred forty-eight (68%) patients underwent re-resection after a median time interval of 48 days (range = 2-245). The most common complete procedure (66% of cases) was 4b + 5 segmentectomy with lymphadenectomy but not bile duct resection. Port-site excision was performed in 54 patients. The mortality and morbidity rates were 3 and 37%, respectively. Resection of the common bile duct (43%) increased postoperative complications (60 vs. 23%, p = 0.0001). Local residual tumor was found in 83 (56%) patients; it was significantly correlated with the T stage and influenced long-term survival. R0 was obtained in 143 (97%) patients and port-site invasion was histologically confirmed in one patient (1.8%). After a median follow-up period of 34 months, the 1-, 3-, and 5-year survival rates for the 148 patients with re-resection were 76, 54, and 41%, respectively. Re-resection significantly increased survival in patients with T2 (p = 0.0001) and T3 (p = 0.04) disease. Resection of the common bile duct increased neither R0 resection nor overall survival (p = 0.06). Conclusion: This study validates the concept of re-resection in T2 and T3 GBC. Bile duct resection increases postoperative morbidity but does not improve survival. There is currently a modification in the surgical management of incidental GBC, with minor liver resection and no common bile duct resection. © 2011 Société Internationale de Chirurgie.

Fraisse A.,Hopital de la Timone | Filippo S.D.,Hopital Louis Pradel | Maragnes P.,Hopital Cote de Nacre | Beghetti M.,Childrens Hospital | And 4 more authors.
Archives of Cardiovascular Diseases Supplements | Year: 2010

Justification: There is few data describing pulmonary arterial hypertension in children. Objectives: The objective was to describe the epidemiology and management of pulmonary arterial hypertension (PAH) in children, as well as its effects on the quality of life and its consequences, excluding patients with persistent pulmonary hypertension of the newborn and those with pulmonary arterial hypertension due to congenital heart disease. Methods: This multicenter non interventional study included children with pulmonary arterial hypertension who were prospectively followed for two years in 21 French centres. The WHO functional classification, the 6-minute walk distance, the quality of life (CHQ-PF50 questionnaire), the hemodynamics parameters and echodoppler performed were evaluated. Results: Fifty children with a mean age of 8.9 ± 5.4 years were included from May 2005 to June 2006. The prevalence of pulmonary arterial hypertension was estimated at 3.7 cases per million. The patients had the following types of pulmonary arterial hypertension: idiopathic (60%), familial (10%), associated with congenital heart disease that was not the cause of the pulmonary hypertension (24%), associated with a connective-tissue disease (4%) or with portal hypertension (2%). During follow-up there was an increase in the number of drugs prescribed specifically for pulmonary arterial hypertension (44% patients versus 22% at inclusion). The clinical status, 6-minute walk test and quality of life of the majority of patients remained stable. The survival at one and at two years was estimated at 86% [95% confidence interval (76, 96)] and 82% [95% confidence interval (71, 93)]. Conclusions: The majority of cases of pulmonary arterial hypertension in children are idiopathic / familial. A specific group of pulmonary arterial hypertension occurring with congenital heart disease has been identified and resembles idiopathic pulmonary arterial hypertension. The use of specific treatments for PAH may contribute to the stability of the disease and to better survival. © 2010 Elsevier Masson SAS.

Fraisse A.,Hopital de la Timone | Di Filippo S.,Hopital Louis Pradel | Maragnes P.,Hopital Cote de Nacre | Beghetti M.,Childrens Hospital | And 4 more authors.
Archives of Cardiovascular Diseases | Year: 2010

Background. - Limited data are available describing paediatric pulmonary arterial hypertension. Aims. - To characterize the epidemiology, management and impact on quality of life and outcome of paediatric pulmonary arterial hypertension, excluding persistent pulmonary hypertension of the newborn and pulmonary arterial hypertension caused by congenital heart disease. Methods. - In this multicentre study, children with pulmonary arterial hypertension were included and followed prospectively for two years at 21 referral centres in France. WHO functional class, 6-minute walk distance and quality of life (CHQ-PF50 questionnaire) were evaluated. Results. - Fifty children were included with a mean age of 8.9±5.4 years from May 2005 until June 2006. The estimated prevalence for pulmonary arterial hypertension was 3.7 cases/million. Patients had idiopathic pulmonary arterial hypertension (60%), familial pulmonary arterial hypertension (10%), pulmonary arterial hypertension associated with, but not caused by, congenital heart disease (24%), pulmonary arterial hypertension associated with connective tissue disease (4%) or portal hypertension (2%). During follow-up, the combination of pulmonary arterial hypertension-specific therapies was increasingly prescribed (44% patients versus 22% at inclusion). Patients remained stable regarding clinical status, 6-minute walk distance and quality of life. Survival estimates after one and two years were 86% (95% Cl 76, 96) and 82% (95% Cl 71, 93), respectively. Conclusions. - In children, idiopathic/familial pulmonary arterial hypertension accounts for the majority of cases. A specific pulmonary arterial hypertension group in conjunction with congenital heart disease can be identified that resembles patients with idiopathic pulmonary arterial hypertension. Combined pulmonary arterial hypertension-specific therapies may have contributed to disease stability and favourable survival. © 2010 Elsevier Masson SAS. All rights reserved.

Le Treut Y.P.,Aix - Marseille University | Gregoire E.,Aix - Marseille University | Klempnauer J.,Medizinische Hochschule | Jouve E.,Aix - Marseille University | And 12 more authors.
Annals of Surgery | Year: 2013

OBJECTIVE: The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period. BACKGROUND: LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases. METHODS: This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1-149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures. RESULTS: Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT. CONCLUSIONS: LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear. Copyright © 2013 by Lippincott Williams & Wilkins.

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