Sainte-Foy-lès-Lyon, France
Sainte-Foy-lès-Lyon, France

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Polkowski M.,Center of Oncology of Poland | Larghi A.,Catholic University of the Sacred Heart | Weynand B.,Catholic University of Louvain | Giovannini M.,Paoli Calmettes Institute | And 2 more authors.
Endoscopy | Year: 2012

This article is the second of a two-part publication that expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) about endoscopic ultrasound (EUS)-guided sampling, including EUS-guided fine needle aspiration (EUS-FNA) and EUS-guided Trucut biopsy. The first part (the Clinical Guideline) focused on the results obtained with EUS-guided sampling, and the role of this technique in patient management, and made recommendations on circumstances that warrant its use. The current Technical Guideline discusses issues related to learning, techniques, and complications of EUS-guided sampling, and to processing of specimens. Technical issues related to maximizing the diagnostic yield (e.g., rapid on-site cytopathological evaluation, needle diameter, microcore isolation for histopathological examination, and adequate number of needle passes) are discussed and recommendations are made for various settings, including solid and cystic pancreatic lesions, submucosal tumors, and lymph nodes. The target readership for the Clinical Guideline mostly includes gastroenterologists, oncologists, internists, and surgeons while the Technical Guideline should be most useful to endoscopists who perform EUS-guided sampling. A two-page executive summary of evidence statements and recommendations is provided. © Georg Thieme Verlag KG Stuttgart New York.


Tournigand C.,University Paris Est Creteil | Chibaudel B.,Institute Hospitalier Franco Britannique | Samson B.,Hopital Charles Lemoyne | Scheithauer W.,Universitatsklinik For Innere Medizin I | And 15 more authors.
The Lancet Oncology | Year: 2015

Background: The combination of an anti-VEGF or an anti-EGFR-targeted monoclonal antibody with chemotherapy has shown clinical activity in patients with metastatic colorectal cancer. However, combining both anti-VEGF and anti-EGFR antibodies with chemotherapy in first-line treatment resulted in adverse outcomes. We assessed whether the combination of erlotinib, an EGFR tyrosine kinase inhibitor, with bevacizumab could increase the efficacy of maintenance therapy in patients with unresectable metastatic colorectal cancer. Methods: This randomised, open-label, phase 3 study was undertaken in 49 centres in France, Austria, and Canada. Eligible patients were aged 18-80 years with histologically confirmed, unresectable metastatic colorectal cancer, WHO performance status 0-2, had received no previous therapy for metastatic disease, and had adequate organ function. Patients without disease progression after bevacizumab-based induction therapy were randomly assigned (1:1) by a minimisation technique to bevacizumab (7·5 mg/kg every 3 weeks) or bevacizumab plus erlotinib (150 mg once daily) as maintenance therapy until progression. All patients were stratified by centre, baseline performance status, age, and number of metastatic sites. The primary endpoint was progression-free survival on maintenance therapy analysed by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00265824. Findings: Between Jan 1, 2007, and Oct 13, 2011, 700 eligible patients were enrolled; following induction treatment, patients without disease progression were randomly assigned to bevacizumab (n=228) or bevacizumab plus erlotinib (n=224). At the final analysis, median follow-up was 51·0 months (IQR 36·0-60·0) in the bevacizumab group and 48·3 months (31·5-61·0) in the bevacizumab plus erlotinib group. In the primary analysis (after 231 progression-free survival events), median progression-free survival from randomisation was 5·1 months (95% CI 4·1-5·9) in the bevacizumab plus erlotinib group compared with 6·0 months (4·6-7·9) in the bevacizumab group (stratified hazard ratio [HR] 0·79 [95% CI 0·60-1·06]; p=0·11; unstratified HR 0·76 [0·59-0·99]; p=0·043). In the final analysis, median progression-free survival from randomisation was 5·4 months (95% CI 4·3-6·2) in the bevacizumab plus erlotinib group compared with 4·9 months (4·1-5·7) in the bevacizumab group (stratified HR 0·81 [95% CI 0·66-1·01], p=0·059; unstratified HR 0·78 [0·68-0·96], p=0·019). At the final analysis, median overall survival from maintenance was 24·9 months (95% CI 21·4-28·9) in the bevacizumab plus erlotinib group and 22·1 months (19·6-26·7) in the bevacizumab group (stratified HR 0·79 [95% CI 0·63-0·99], p=0·036; unstratified HR 0·79 [0·64-0·98], p=0·035). The most frequent grade 3-4 adverse events were skin rash (47 [21%] of 220 patients in the bevacizumab plus erlotinib group vs none of 224 patients in the bevacizumab alone group), diarrhoea (21 [10%] vs two [<1%]), and asthenia (12 [5%] vs two [<1%]). Interpretation: Maintenance bevacizumab plus erlotinib might be a new non-chemotherapy-based maintenance option for the first-line treatment of patients with unresectable metastatic colorectal cancer after bevacizumab-based induction therapy. Funding: GERCOR and F Hoffmann-La Roche. © 2015 Elsevier Ltd.


Plouin-Gaudon I.,Center Hospitalier Of Valence | Bossard D.,Hopital Prive Jean Mermoz | Ayari-Khalfallah S.,Hopital Femme Mere Enfant | Froehlich P.,Hopital Femme Mere Enfant
Archives of Otolaryngology - Head and Neck Surgery | Year: 2010

Objective: To evaluate the efficiency of diffusion-weighted magnetic resonance imaging (MRI) and highresolution computed tomographic (CT) scan coregistration in predicting and adequately locating primary or recurrent cholesteatoma in children. Design: Prospective study. Setting: Tertiary care university hospital. Patients: Ten patients aged 2 to 17 years (mean age, 8.5 years) with cholesteatoma of the middle ear, some of which were previously treated, were included for follow-up with systematic CT scanning and MRI between 2007 and 2008. Interventions: Computed tomographic scanning was performed on a Siemens Somaton 128 (0.5/0.2-mm slices reformatted in 0.5/0.3-mm images). Fine cuts were obtained parallel and perpendicular to the lateral semicircular canal in each ear (100x100-mm field of view). Magnetic resonance imaging was undertaken on a Siemens Avanto 1.5T unit, with a protocol adapted for young children. Diffusion-weighted imaging was acquired using a single-shot turbo spin-echo mode. To allow for diagnosis and localization of the cholesteatoma, CT and diffusion-weighted MRIs were fused for each case. Results: In 10 children, fusion technique allowed for correct diagnosis and precise localization (hypotympanum, epitympanum, mastoid recess, and attical space) as confirmed by subsequent standard surgery (positive predictive value, 100%). In 3 cases, the surgical approach was adequately determined from the fusion results. Lesion sizes on the CT-MRI fusion corresponded with perioperative findings. Conclusions: Recent developments in imaging techniques have made diffusion-weighted MRI more effective for detecting recurrent cholesteatoma. The major drawback of this technique, however, has been its poor anatomical and spatial discrimination. Fusion imaging using high-resolution CT and diffusion-weighted MRI appears to be a promising technique for both the diagnosis and precise localization of cholesteatomas. It provides useful information for surgical planning and, furthermore, is easy to use in pediatric cases. ©2010 American Medical Association. All rights reserved.


Alvarez-Sanchez M.V.,Hopital Prive Jean Mermoz | Jenssen C.,Krankenhaus Markisch Oderland | Faiss S.,Asklepios Klinik Barmbek | Napoleon B.,Hopital Prive Jean Mermoz
Surgical Endoscopy and Other Interventional Techniques | Year: 2014

Background: In recent years, endoscopic ultrasonography (EUS)-guided techniques have been developed as alternatives to surgical, radiologic, or conventional endoscopic approaches for the treatment or palliation of several digestive diseases. The use of EUS guidance allows the therapeutic area to be targeting more precisely, with a possible clinical benefit and less morbidity. Nevertheless, the risks persist and must be taken into consideration. This review gives an overview of the complications observed with the most established procedures of therapeutic EUS. Methods: The PubMed and Embase databases were used to search English language articles on interventional EUS. The studies considered for inclusion were those reporting on complications of EUS-guided celiac plexus block (EUS-CPB), EUS-guided celiac plexus neurolysis (EUS-CPN), drainage of fluid pancreatic and pelvic collections, and EUS-guided biliary and pancreatic drainage (EUS-BD and EUS-PD). Variations in methodology and design in most studies made a thorough statistical analysis difficult. Instead, a frequency analysis of complications and a critical discussion were performed. Results: Although EUS-guided celiac plexus injection causes mainly mild and transient complications, growing experience shows that EUS-CPN is not as benign a procedure as previously thought. Most of the major complications have been observed in patients with chronic pancreatitis. The findings show that EUS-guided drainage of fluid collections is a safe procedure. Complications occur more often after the drainage of pancreatic abscesses and necrosis. Although the heterogeneity of studies dealing with pancreatobiliary drainage makes the evaluation of risks after these procedures difficult, complications after EUS-BD and EUS-PD are relatively frequent and can be severe. The technical complexity and the lack of specifically designed devices may account for their complication rates. Conclusions: Clinicians can consider EUS-guided celiac injection and EUS-guided drainage of fluid collections to be safe alternatives to surgical and radiologic interventions. Well-designed prospective trials are needed to assess the risks of EUS-BD and EUS-PD accurately before they are broadly advocated after a failed endoscopic retrograde cholangiopancreatography (ERCP). © 2013 Springer Science+Business Media.


Plouin-Gaudon I.,Center Hospitalier Of Valence | Bossard D.,Hopital Prive Jean Mermoz | Fuchsmann C.,University of Lyon | Ayari-Khalfallah S.,University of Lyon | Froehlich P.,University of Lyon
International Journal of Pediatric Otorhinolaryngology | Year: 2010

Objective: To compare the efficiency of diffusion-weighted MR imaging (MRI) vs. high resolution CT in predicting recurrent or residual cholesteatoma in children who underwent prior middle ear surgery. Design: Prospective study. Setting: Tertiary care university hospital. Patients: Seventeen patients (4 with 2 recurrences) aged 5-17 years (mean 11.4) previously surgically treated for a cholesteatoma of the middle ear, were included for follow-up with systematic CT scan and MRI, between 2005 and 2007. Methodology: CT scan was performed on a Siemens Somaton 64 (0.5/0.2 mm slices reformatted in 0.5/0.3 mm images), parallel and perpendicular to the lateral semi-circular canal for each ear (100 mm × 100 mm FOV). MRI was undertaken on a Siemens Avanto 1.5 T unit, with an adapted protocol for young children. Diagnosis of recurrent cholesteatoma was based on the evidence of a hyperintense image at B1000 on diffusion-weighted images. Results of CT scan and MRI were compared with operative diagnosis. Results: Nine patients had a positive MRI, among which 8 had cholesteatoma confirmed during revision surgery. In the 12 negative MRI cases, 5 were positive on revision surgery. None of these lesions was over 3 mm. Two of them were diagnosed on the CT scan. CT scan alone had a positive predictive value of 75%, and a negative predictive value of 58%. Conclusion: Diffusion-weighted MRI is associated with a high positive predictive value for the detection of recurrent cholesteatoma. CT scan remains the first choice imaging technique. In case of doubtful CT scan, diffusion-weighted MRI could confirm a recurrence or, when negative, avoid second-look surgery. © 2009 Elsevier Ireland Ltd. All rights reserved.


Jenssen C.,Krankenhaus Markisch Oderland GmbH | Alvarez-Sanchez M.V.,Hopital Prive Jean Mermoz | Napoleon B.,Hopital Prive Jean Mermoz | Faiss S.,Asklepios Klinik Barmbek
World Journal of Gastroenterology | Year: 2012

Endoscopic ultrasonography (EUS) has gained wide acceptance as an important, minimally invasive diagnostic tool in gastroenterology, pulmonology, visceral surgery and oncology. This review focuses on data regarding risks and complications of non-interventional diagnostic EUS and EUS-guided fine-needle biopsy (EUSFNB). Measures to improve the safety of EUS und EUSFNB will be discussed. Due to the specific mechanical properties of echoendoscopes in EUS, there is a low but noteworthy risk of perforation. To minimize this risk, endoscopists should be familiar with the specific features of their equipment and their patients' specific anatomical situations (e.g., tumor stenosis, diverticula). Most diagnostic EUS complications occur during EUSFNB. Pain, acute pancreatitis, infection and bleeding are the primary adverse effects, occurring in 1% to 2% of patients. Only a few cases of needle tract seeding and peritoneal dissemination have been reported. The mortality associated with EUS and EUS-FNB is 0.02%. The risks associated with EUS-FNB are affected by endoscopist experience and target lesion. EUS-FNB of cystic lesions is associated with an increased risk of infection and hemorrhage. Peri-interventional antibiotics are recommended to prevent cyst infection. Adequate education and training, as well consideration of contraindications, are essential to minimize the risks of EUS and EUS-FNB. Restricting EUS-FNB only to patients in whom the cytopathological results may be expected to change the course of management is the best way of reducing the number of complications. © 2012 Baishideng.


Ortholan C.,University of Nice Sophia Antipolis | Romestaing P.,Hopital Prive Jean Mermoz | Chapet O.,University of Lyon | Gerard J.P.,University of Nice Sophia Antipolis
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To investigate, in rectal cancer, the benefit of a neoadjuvant radiation dose escalation with endocavitary contact radiotherapy (CXRT) in addition to external beam radiotherapy (EBRT). This article provides an update of the Lyon R96-02 Phase III trial. Methods and Materials: A total of 88 patients with T2 to T3 carcinoma of the lower rectum were randomly assigned to neoadjuvant EBRT 39 Gy in 13 fractions (43 patients) vs. the same EBRT with CXRT boost, 85 Gy in three fractions (45 patients). Median follow-up was 132 months. Results: The 10-year cumulated rate of permanent colostomy (CRPC) was 63% in the EBRT group vs. 29% in the EBRT+CXRT group (p < 0.001). The 10-year rate of local recurrence was 15% vs. 10% (p = 0.69); 10-year disease-free survival was 54% vs. 53% (p = 0.99); and 10-year overall survival was 56% vs. 55% (p = 0.85). Data of clinical response (CR) were available for 78 patients (36 in the EBRT group and 42 in the EBRT+CXRT group): 12 patients were in complete CR (1 patient vs. 11 patients), 53 patients had a CR ≥50% (24 patients vs. 29 patients), and 13 patients had a CR <50% (11 patients vs. 2 patients) (p < 0.001). Of the 65 patients with CR ≥50%, 9 had an organ preservation procedure (meaning no rectal resection) taking advantage of major CR. The 10-year CRPC was 17% for patients with complete CR, 42% for patients with CR ≥50%, and 77% for patients with CR <50% (p = 0.014). Conclusion: In cancer of the lower rectum, CXRT increases the complete CR, turning in a significantly higher rate of long-term permanent sphincter and organ preservation. © 2012 Elsevier Inc. All rights reserved.


Alvarez-Sanchez M.-V.,Hopital Prive Jean Mermoz | Alvarez-Sanchez M.-V.,Complejo Hospitalario Of Pontevedra | Napoleon B.,Hopital Prive Jean Mermoz
World Journal of Gastroenterology | Year: 2014

Over the last decade, the development of stabilised microbubble contrast agents and improvements in available ultrasonic equipment, such as harmonic imaging, have enabled us to display microbubble enhancements on a greyscale with optimal contrast and spatial resolution. Recent technological advances made contrast harmonic technology available for endoscopic ultrasound (EUS) for the first time in 2008. Thus, the evaluation of microcirculation is now feasible with EUS, prompting the evolution of contrast-enhanced EUS from vascular imaging to images of the perfused tissue. Although the relevant experience is still preliminary, several reports have highlighted contrast-enhanced harmonic EUS (CHEUS) as a promising noninvasive method to visualise and characterise lesions and to differentiate benign from malignant focal lesions. Even if histology remains the gold standard, the combination of CH-EUS and EUS fine needle aspiration (EUS-FNA) can not only render EUS more accurate but may also assist physicians in making decisions when EUS-FNA is inconclusive, increasing the yield of EUS-FNA by guiding the puncture with simultaneous imaging of the vascularity. The development of CH-EUS has also opened up exciting possibilities in other research areas, including monitoring responses to anticancer chemotherapy or to ethanolinduced pancreatic tissue ablation, anticancer therapies based on ultrasound-triggered drug and gene delivery, and therapeutic adjuvants by contrast ultrasound-induced apoptosis. Contrast harmonic imaging is gaining popularity because of its efficacy, simplicity and noninvasive nature, and many expectations are currently resting on this technique. If its potential is confirmed in the near future, contrast harmonic imaging will become a standard practice in EUS. © 2014 Baishideng Publishing Group Inc. All rights reserved.


Achalasia is an esophageal motility disorder defined by the absence of propagated contractions (aperistalsis) in the body of the esophagus and failure of relaxation of the lower esophageal sphincter. Thanks to high resolution manometry and study of the esophageal pressure topography, three subtypes, according to the classification of Chicago, have a direct interest in the choice of treatment to use: type I of achalasia presents the same result with pneumatic dilatation (81%) and surgery (85%); type II of achalasia presents the best result with pneumatic dilatation (100%); type III of achalasia called "spastic", which is the more resistant, have the best result with Heller-Dor myotomy (86%). More recently appeared the peroral endoscopic myotomy, which remains to study in France, but with the preliminary results, this technic could become the treatment of choice for achalasia, particularly in the type III which is the most resistant. © Springer-Verlag 2013.


Napoleon B.,Hopital Prive Jean Mermoz
Acta Endoscopica | Year: 2010

Ultrasound contrast agents in combination with contrast-specific scanning techniques have opened up exciting possibilities of further improving the diagnostic capability of endoscopic ultrasonography (EUS). The main field of application is characterization of focal lesions. Pancreatic tumors are the targets studied most, but a lot of other applications will no doubt be developed. Among all the latest technological evolutions, it is certainly the most promising for development of EUS in the future. © Springer-Verlag France 2010.

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