Orsetti B.,French Institute of Health and Medical Research |
Orsetti B.,Institut Universitaire de France |
Orsetti B.,Institute regional du Cancer Montpellier |
Selves J.,University Hospital of Purpan |
And 20 more authors.
BMC Cancer | Year: 2014
Background: It remains presently unclear whether disease progression in colorectal carcinoma (CRC), from early, to invasive and metastatic forms, is associated to a gradual increase in genetic instability and to a scheme of sequentially occurring Copy Number Alterations (CNAs).Methods: In this work we set to determine the existence of such links between CRC progression and genetic instability and searched for associations with patient outcome. To this aim we analyzed a set of 162 Chromosomal Instable (CIN) CRCs comprising 131 primary carcinomas evenly distributed through stage 1 to 4, 31 metastases and 14 adenomas by array-CGH. CNA profiles were established according to disease stage and compared. We, also, asked whether the level of genomic instability was correlated to disease outcome in stage 2 and 3 CRCs. Two metrics of chromosomal instability were used; (i) Global Genomic Index (GGI), corresponding to the fraction of the genome involved in CNA, (ii) number of breakpoints (nbBP).Results: Stage 1, 2, 3 and 4 tumors did not differ significantly at the level of their CNA profiles precluding the conventional definition of a progression scheme based on increasing levels of genetic instability. Combining GGI and nbBP,we classified genomic profiles into 5 groups presenting distinct patterns of chromosomal instability and defined two risk classes of tumors, showing strong differences in outcome and hazard risk (RFS: p = 0.012, HR = 3; OS: p < 0.001, HR = 9.7). While tumors of the high risk group were characterized by frequent fractional CNAs, low risk tumors presented predominantly whole chromosomal arm CNAs. Searching for CNAs correlating with negative outcome we found that losses at 16p13.3 and 19q13.3 observed in 10% (7/72) of stage 2-3 tumors showed strong association with early relapse (p < 0.001) and death (p < 0.007, p < 0.016). Both events showed frequent co-occurrence (p < 1x10-8) and could, therefore, mark for stage 2-3 CRC susceptible to negative outcome.Conclusions: Our data show that CRC disease progression from stage 1 to stage 4 is not paralleled by increased levels of genetic instability. However, they suggest that stage 2-3 CRC with elevated genetic instability and particularly profiles with fractional CNA represent a subset of aggressive tumors. © 2014 Orsetti et al.; licensee BioMed Central Ltd.
PubMed | Montpellier University, Hopital Timone, University of Nantes, Bordeaux University Hospital Center and 10 more.
Type: | Journal: Multiple sclerosis (Houndmills, Basingstoke, England) | Year: 2016
To evaluate the effectiveness and tolerance of mycophenolate mofetil (MMF) as a first-line treatment in neuromyelitis optica spectrum disorder (NMOSD).In all, 67 NMOSD patients treated by MMF as first-line therapy, from the NOMADMUS cohort were included. A total of 65 fulfilled 2015 NMOSD criteria, and 5 were myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) positive. Effectiveness was evaluated on percentage of patients continuing MMF, percentage of patients free of relapse, pre- and post-treatment change in the annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS).Among 67 patients, 40 (59.7%) continued treatment till last follow-up. A total of 33 (49.3%) were relapse-free. The median ARR decreased from one pre-treatment to zero post-treatment. Of 53 patients with complete EDSS data, the score improved or stabilized in 44 (83%; p<0.05). Effectiveness was observed in aquaporin-4 (AQP4)-IgG (57.8% continued treatment, 46.7% relapse-free), MOG-IgG (3/5 continued treatment, 4/5 relapse-free), and seronegative NMOSD (64.7% continued treatment, 61.3% relapse-free). In 16 patients with associated steroids, 13 (81.2%) continued MMF till last follow-up versus 15 of 28 (53.6%) in the non-steroid group. Nine patients discontinued treatment for tolerability purpose.MMF showed effectiveness and good tolerability as a first-line therapy in NMOSD, whatever the AQP4-IgG status. Concomitant use of oral steroids at start could limit the risk of treatment failure.
PubMed | Paul Brousse Hospital, Center Hospitalo University, Hopital Huriez, Hospital Fernando Foncesca and 9 more.
Type: Clinical Trial, Phase II | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016
Systemic chemotherapy typically converts previously unresectable liver metastases (LM) from colorectal cancer to curative intent resection in 15% of patients. This European multicenter phase II trial tested whether hepatic artery infusion (HAI) with triplet chemotherapy and systemic cetuximab could increase this rate to 30% in previously treated patients.Participants had unresectable LM from wt KRAS colorectal cancer. Main non-inclusion criteria were advanced extra hepatic disease, prior HAI and grade 3 neuropathy. Irinotecan (180 mg/m(2)), oxaliplatin (85 mg/m(2)) and 5-fluorouracil (2800 mg/m(2)) were delivered via an implanted HAI access port and combined with i.v. cetuximab (500 mg/m(2)) every 14 days. Multidisciplinary decisions to resect LM were taken after every three courses. The rate of macroscopic complete resections (R0 + R1) of LM, progression-free survival (PFS) and overall survival (OS) were computed according to intent to treat.The patient population consisted of 42 men and 22 women, aged 33-76 years, with a median of 10 LM involving a median of six segments. Up to 3 extrahepatic lesions of <1 cm were found in 41% of the patients. A median of six courses was delivered. The primary end point was met, with R0-R1 hepatectomy for 19 of the 64 previously treated patients, 29.7% (95% confidence interval 18.5-40.9). Grade 3-4 neutropenia (42.6%), abdominal pain (26.2%), fatigue (18%) and diarrhea (16.4%) were frequent. Objective response rate was 40.6% (28.6-52.3). Median PFS and OS reached 9.3 (7.8-10.9) and 25.5 months (18.8-32.1) respectively. Those with R0-R1 hepatectomy had a median OS of 35.2 months (32.6-37.8), with 37.4% (23.6-51.2) alive at 4 years.The coordination of liver-specific intensive chemotherapy and surgery had a high curative intent potential that deserves upfront randomized testing.EUDRACT 2007-004632-24, NCT00852228.
Woisard-Bassols V.,30030 University Hospital of Rangueil Larrey |
Alshehri S.,University Hospital of Rangueil Larrey |
Simonetta-Moreau M.,University Hospital of Purpan
European Archives of Oto-Rhino-Laryngology | Year: 2013
This prospective, open study was carried out in order to assess changes in the swallowing and dietary status after injection of Botulinum toxin A (BoNT-A) into the upper esophageal sphincter (UES) in a series of patients with cricopharyngeus (CP) muscle dysfunction associated with pharyngo-laryngeal weakness during at least 1 year follow-up after treatment. Patients who had a cricopharyngeus (CP) muscle dysfunction associated with pharyngo-laryngeal weakness and who were at risk for aspiration were included in the study. The upper border of the cricoid cartilage was identified and the CP muscle localized using a standard electromyogram (EMG). The dose of BoNT-A was determined depending on the results of EMG performed just before the injection. Outcomes were assessed by the penetration-aspiration scale (PAS), the level of residue in the pyriform sinus and the National Institute of Health-Swallow Safety Scale (NIH-SSS) on a video fluoroscopic swallowing (VFSS) assessment, the patient's subjective impressions of their ability to swallow by the Deglutition Handicap Index (DHI), and changes in dietary status by the Functional Oral Intake Scale. Eleven patients underwent the complete assessment of swallowing function at 1, 3, 6, and 12 months. After the first set of treatment, seven patients had a good response and four did not respond. A significant decrease in the PAS score (p = 0.03), the amount of residue (p = 0.04) and the NIH-SSS score (p = 0.03) was observed 3 months after the injection in comparison with the first VFSS before the treatment. A relapse of dysphagia occurred in 3 out of the 11 treated patients; at 3 and 4 months for 2 patients with a Wallenberg syndrome, and at 11 months for a patient with cranial nerve paralysis after a surgery for a glomus tumor. Two of them underwent a second injection. One patient had a good response and remained stable for at least 1 year. The second did not respond either to the second injection or to a myotomy of the cricopharyngeal muscle. The third one is waiting for further surgery (myotomy). Therefore, at the end of the study and after a follow-up of at least 12 months, 5 patients out of the 11 enrolled had a good result. Percutaneous injection of BoNT-A into the UES can be a useful solution to improve cricopharyngeal dysfunction, despite the underlying pharyngo-laryngeal weakness. © 2012 Springer-Verlag.
Muscari F.,Toulouse University Hospital Center |
Muscari F.,French Institute of Health and Medical Research |
Foppa B.,Toulouse University Hospital Center |
Carrere N.,University Hospital of Purpan |
And 3 more authors.
World Journal of Surgery | Year: 2011
Background: The aim of this study was to estimate the survival rates and define risk factors for tumor recurrence after resection surgery for single hepatocellular carcinomas (HCCs) ≥ 5 cm (on preoperative imaging) that developed on compensated cirrhosis. Methods: A retrospective review studied patients treated by surgical resection. Overall survival (OS), disease-free survival (DFS), recurrence rates, and risk factors were studied for all patients. Results: A total of 49 patients were treated by resection. The 5-year OS and DFS rates were 52 and 41%, respectively, after 2000. Three independent risk factors were found for OS and DFS: macroscopic vascular invasion, satellite nodules, R1 resection. In the absence of these three factors, the 5-year OS was 59%. Recurrence rates were 63%. Delayed recurrence was significantly related to the 5-year OS. One factor was correlated with early recurrence: the presence of satellite nodules; and one factor was correlated with late recurrence: hepatitis C virus infection. Conclusions: R0 resection for HCC on compensated cirrhosis may offer good long-term survival in the absence of satellites nodules and macrovascular invasion. Thus, a "first approach" resection is proposed with the possibility of "salvage transplantation." In other cases, resection may be a bridge to transplantation ("transplantation de principe"). © 2011 Société Internationale de Chirurgie.
Michelozzi C.,University of Milan |
Michelozzi C.,University Hospital of Purpan |
Januel A.C.,University Hospital of Purpan |
Cuvinciuc V.,University of Geneva |
And 6 more authors.
Journal of NeuroInterventional Surgery | Year: 2016
Object To report the morbidity and long term results in the treatment of paragangliomas by transarterial embolization with ethylene vinyl alcohol (Onyx), either as preoperative or palliative treatment. Methods Between September 2005 and 2012, 18 jugulotympanic, 7 vagal, and 4 carotid body paragangliomas (CBPs) underwent Onyx embolization, accordingly to our head and neck multidisciplinary team's decision. CBPs were embolized preoperatively. Jugulotympanic and vagal paragangliomas underwent surgery when feasible, otherwise palliative embolization was carried out alone, or in combination with radiotherapy or tympanic surgery in the case of skull base or tympanic extension. Treatment results, and clinical and MRI follow-up data were recorded. Results In all cases, devascularization of at least 60% of the initial tumor blush was obtained; 6 patients underwent two embolizations. Post-embolization, 8 patients presented with cranial nerve palsy, with partial or complete regression at follow-up (mean 31 months, range 3-86 months), except for 2 vagal and 1 hypoglossal palsy. 10 patients were embolized preoperatively; 70% were cured after surgery and 30% showed residual tumor. 19 patients received palliative embolization, of whom 5 underwent radiotherapy and 3 received tympanic surgery post-embolization. Long term follow-up of palliative embolization resulted in tumor volume stability (75%) or extension in intracranial or tympanic compartments. Onyx embolization of CBPs resulted in more difficult surgical dissection in 2 of 4 cases. Conclusions Onyx embolization is a valuable alternative to surgery in the treatment of jugulotympanic and vagal paragangliomas; tympanic surgery or radiosurgery of the skull base should be considered in selected cases. Preoperative Onyx embolization of CBPs is not recommended.
Schneider T.,University of Hamburg |
Mahraun T.,University of Hamburg |
Schroeder J.,University of Hamburg |
Frolich A.,University of Hamburg |
And 8 more authors.
Clinical Neuroradiology | Year: 2016
Purpose: The presence of intraparenchymal hyperattenuations (IPH) on flat-panel computed tomography (FP-CT) after endovascular recanalization in stroke patients is a common phenomenon. They are thought to occur in ischemic areas with breakdown of the blood-brain barrier but previous studies that investigated a mutual interaction are scarce. We aimed to assess the relationship of IPH localization with prethrombectomy diffusion-weighted imaging (DWI) lesions. Methods: This retrospective multicenter study included 27 acute stroke patients who underwent DWI prior to FP-CT following mechanical thrombectomy. After software-based coregistration of DWI and FP-CT, lesion volumetry was conducted and overlapping was analyzed. Results: Two different patterns were observed: IPH corresponding to the DWI lesion and IPH exceeding the DWI lesion. The latter showed demarcated infarction of DWI exceeding IPH at 24 h. No major hemorrhage following IPH was observed. Most IPH were manifested within the basal ganglia and insular cortex. Conclusion: The IPH primarily appeared within the initial ischemic core and secondarily within the penumbral tissue that progressed to infarction. The IPH represent the minimum final infarct volume, which may help in periinterventional decision making. © 2016 Springer-Verlag Berlin Heidelberg
Gouin F.,Nantes University Hospital Center |
Gouin F.,University of Nantes |
Rochwerger A.R.,University Hospital Of La Conception |
Di Marco A.,University of Strasbourg |
And 4 more authors.
European Journal of Cancer | Year: 2014
Background: Giant cell tumours (GCT) of bone are benign neoplasms associated with a high rate of local recurrence after extensive intra-lesional curettage. Recently, understanding of the biological molecular availability of strong anti-osteoclastic drugs has suggested their potential value in reducing local recurrences after curettage. Through a phase II clinical trial, we investigated the effect of a short treatment with zoledronic acid (ZOL) after intra-lesional curettage of GCT, as well as local recurrence and tolerance of the treatment. Methods and patients: Twenty-four patients were enrolled in a multicentre, phase 2 study. The patients were treated with extensive intra-lesional curettage followed by five courses of ZOL (4. mg IV every 3. weeks).The clinical and biological tolerance of each patient was assessed. Patients were reviewed clinically and by X-ray every 6. months until the end of the study (36. months). Results: Eighteen out of 20 patients reported side-effects with ZOL, mainly grade 1 and 2 effects. The local recurrence rate was 15%; three patients had a recurrence, one at 4. months (huge GCT of the sacrum), one at 24. months (patient who discontinued the treatment after the first course of ZOL), and one after the observational period, at 58. months. Finally, local relapse-free survival was 82. ±. 9% at 60. months. Conclusion: Short adjuvant treatments with ZOL after extensive intra-lesional curettage of GCT were associated with a low rate of recurrence but did not prevent local recurrence in this study. No serious general adverse effects were observed. More studies are needed to evaluate the potential benefit of medical bisphosphonate injections combined with intra-lesional curettage in the treatment of GCTB. © 2014 Elsevier Ltd.
Faguer S.,Toulouse University Hospital Center |
Faguer S.,French Institute of Health and Medical Research |
Faguer S.,University Paul Sabatier |
Chassaing N.,University Paul Sabatier |
And 17 more authors.
European Journal of Medical Genetics | Year: 2011
Chromosomal imbalance of the 17q12 region (which includes the HNF1B transcription factor) has recently emerged as a frequent condition. 17q12 deletion was found in patients with various renal abnormalities, diabetes mellitus (MODY type 5), genital tract or liver test abnormalities, while 17q12 duplication was identified in a subset of patients with autism, mental retardation, epilepsy and/or schizophrenia but no renal disorder. We report here two first-degree relatives carrying a 17q12 duplication and harboring various renal abnormalities (bilateral hypoplastic kidneys with vesico-ureteric reflux or multicystic dysplatic kidney with contralateral hyperechogenic kidney). Esophageal atresia (EA) type C was identified at birth in one patient while none had neurological disorder. Because EA has already been identified in patients with 17q12 duplication or HNF1B point mutation, we screened HNF1B (QMPSF and direct sequencing) in nine additional patients with EA and renal abnormalities but failed to identify any pathogenic variant. This is the second report of HNF1B mutation associated with EA. Moreover, we showed herein, that renal malformations may be part of the 17q12 duplication syndrome. © 2011 Elsevier Masson SAS.
PubMed | Friedrich - Alexander - University, Erlangen - Nuremberg, University Hospital of Purpan, Goethe University Frankfurt, University of Hamburg and Montpellier University
Type: | Journal: Clinical neuroradiology | Year: 2016
The presence of intraparenchymal hyperattenuations (IPH) on flat-panel computed tomography (FP-CT) after endovascular recanalization in stroke patients is acommon phenomenon. They are thought to occur in ischemic areas with breakdown of the blood-brain barrier but previous studies that investigated amutual interaction are scarce. We aimed to assess the relationship of IPH localization with prethrombectomy diffusion-weighted imaging (DWI) lesions.This retrospective multicenter study included 27 acute stroke patients who underwent DWI prior to FP-CT following mechanical thrombectomy. After software-based coregistration of DWI and FP-CT, lesion volumetry was conducted and overlapping was analyzed.Two different patterns were observed: IPH corresponding to the DWI lesion and IPH exceeding the DWI lesion. The latter showed demarcated infarction of DWI exceeding IPH at 24h. No major hemorrhage following IPH was observed. Most IPH were manifested within the basal ganglia and insular cortex.The IPH primarily appeared within the initial ischemic core and secondarily within the penumbral tissue that progressed to infarction. The IPH represent the minimum final infarct volume, which may help in periinterventional decision making.