Rullier A.,Bordeaux University Hospital Center |
Vendrely V.,Saint Andre Hospital |
Bioulac-Sage P.,Bordeaux University Hospital Center
American Journal of Surgical Pathology | Year: 2010
In locally advanced rectal adenocarcinoma, preoperative radiochemotherapy induces tumor response. The impact of pathologic tumor response on survival is still debated because of the numerous distinct tumor-response gradings available in the literature and the lack of standardized pathologic approach. The objective of this work was to study the impact of tumor response on survival, according to the 4 main tumor-response gradings available in the literature in locally advanced rectal adenocarcinoma after preoperative radiochemotherapy. From 1995 to 2004, 292 consecutive patients with cT3-T4 and/or N+ rectal adenocarcinoma were enrolled. Tumor response was evaluated according to ypTN-response gradings (downstaging: ypT0-2 N0 and complete pathologic response: ypT0 N0) and cellular-response gradings (ie, Mandard et als and Rodel et al's gradings). The impact of tumor-response gradings and of different clinicopathologic variables on 5-year disease-free and overall survival were studied by univariate and multivariate analyses. We found that all tumor-response gradings were associated with survival. However, multivariate analysis showed that downstaging was the only tumor-response grading that influenced survival independently. In the subgroup of stage II patients (n=99), we also observed no difference on both 5-year disease-free and overall survival between low and high responders according to cellular response. In conclusion, in our experience, downstaging is the only tumor-response grading that influenced survival independently in locally advanced rectal adenocarcinomas. Cellular-response gradings had no impact on survival even in stage II patients. © 2010 Lippincott Williams & Wilkins.
Chapman P.B.,Sloan Kettering Cancer Center |
Hauschild A.,University of Kiel |
Robert C.,CNRS Gustave Roussy Institute |
Haanen J.B.,Netherlands Cancer Institute |
And 23 more authors.
New England Journal of Medicine | Year: 2011
BACKGROUND: Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. METHODS: We conducted a phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of body-surface area intravenously every 3 weeks). Coprimary end points were rates of overall and progression-free survival. Secondary end points included the response rate, response duration, and safety. A final analysis was planned after 196 deaths and an interim analysis after 98 deaths. RESULTS: At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. CONCLUSIONS: Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann-La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.) Copyright © 2011 Massachusetts Medical Society.
McArthur G.A.,Peter MacCallum Cancer Center |
Chapman P.B.,Sloan Kettering Cancer Center |
Robert C.,CNRS Gustave Roussy Institute |
Larkin J.,Royal Marsden Hospital |
And 23 more authors.
The Lancet Oncology | Year: 2014
Background: In the BRIM-3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAFV600 mutation-positive melanoma. We present an extended follow-up analysis of the total population and in the BRAFV600E and BRAFV600K mutation subgroups. Methods: Patients older than 18 years, with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAFV600 mutations were eligible. Patients also had to have a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate haematological, hepatic, and renal function. Patients were randomly assigned by interactive voice recognition system to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg/m2 of body surface area intravenously every 3 weeks). Coprimary endpoints were overall survival and progression-free survival, analysed in the intention-to-treat population (n=675), with data censored at crossover. A sensitivity analysis was done. This trial is registered with ClinicalTrials.gov, NCT01006980. Findings: 675 eligible patients were enrolled from 104 centres in 12 countries between Jan 4, 2010, and Dec 16, 2010. 337 patients were randomly assigned to receive vemurafenib and 338 to receive dacarbazine. Median follow-up was 12·5 months (IQR 7·7-16·0) on vemurafenib and 9·5 months (3·1-14·7) on dacarbazine. 83 (25%) of the 338 patients initially randomly assigned to dacarbazine crossed over from dacarbazine to vemurafenib. Median overall survival was significantly longer in the vemurafenib group than in the dacarbazine group (13·6 months [95% CI 12·0-15·2] vs 9·7 months [7·9-12·8]; hazard ratio [HR] 0·70 [95% CI 0·57-0·87]; p=0·0008), as was median progression-free survival (6·9 months [95% CI 6·1-7·0] vs 1·6 months [1·6-2·1]; HR 0·38 [95% CI 0·32-0·46]; p<0·0001). For the 598 (91%) patients with BRAFV600E disease, median overall survival in the vemurafenib group was 13·3 months (95% CI 11·9-14·9) compared with 10·0 months (8·0-14·0) in the dacarbazine group (HR 0·75 [95% CI 0·60-0·93]; p=0·0085); median progression-free survival was 6·9 months (95% CI 6·2-7·0) and 1·6 months (1·6-2·1), respectively (HR 0·39 [95% CI 0·33-0·47]; p<0·0001). For the 57 (9%) patients with BRAFV600K disease, median overall survival in the vemurafenib group was 14·5 months (95% CI 11·2-not estimable) compared with 7·6 months (6·1-16·6) in the dacarbazine group (HR 0·43 [95% CI 0·21-0·90]; p=0·024); median progression-free survival was 5·9 months (95% CI 4·4-9·0) and 1·7 months (1·4-2·9), respectively (HR 0·30 [95% CI 0·16-0·56]; p<0·0001). The most frequent grade 3-4 events were cutaneous squamous-cell carcinoma (65 [19%] of 337 patients) and keratoacanthomas (34 [10%]), rash (30 [9%]), and abnormal liver function tests (38 [11%]) in the vemurafenib group and neutropenia (26 [9%] of 287 patients) in the dacarbazine group. Eight (2%) patients in the vemurafenib group and seven (2%) in the dacarbazine group had grade 5 events. Interpretation: Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAFV600E mutation and in patients with the less common BRAFV600K mutation. Funding: F Hoffmann-La Roche-Genentech. © 2014 Elsevier Ltd.
Balageas P.,Pellegrin Hospital |
Cornelis F.,Pellegrin Hospital |
Le Bras Y.,Pellegrin Hospital |
Hubrecht R.,Pellegrin Hospital |
And 4 more authors.
European Radiology | Year: 2013
Objectives: To evaluate survival and outcomes after percutaneous radiofrequency ablation (RFA) of malignant renal tumours in high-risk patients with long-term follow-up. Methods: Between 2002 and 2009, 62 patients (71 tumours), with a median age of 73.5 years (20-87), consecutively treated with RFA under ultrasound or computed tomography guidance for malignant renal tumours were retrospectively selected and prospectively followed until 2012, including 25 patients (40.3 %) with solitary kidney and 7 cystic cancers. Maximal tumour diameters were between 8 and 46 mm (median: 23 mm). Results: Radiofrequency ablation was technically possible for all patients. Mean follow-up was 38.8 months (range: 18-78 months). Primary and secondary technique effectiveness was 95.2 % and 98.4 % per patient respectively. The rates of local tumour progression and metastatic evolution were 3.2 % and 9.7 % per patient and were associated with tumour size >4 cm (P = 0.005). The disease-free survival rates were 88.3 % and 61.9 % at 3 and 5 years. No significant difference in glomerular filtration rates before and after the procedure was observed (P = 0.107). The major complications rate was 5.9 % per session with an increased risk in the case of central locations (P = 0.006). Conclusions: Percutaneous renal RFA appears to be safe and effective with useful nephron-sparing results. © 2013 European Society of Radiology.
Cornelis F.,Pellegrin Hospital |
Tricaud E.,Pellegrin Hospital |
Lasserre A.S.,Pellegrin Hospital |
Petitpierre F.,Pellegrin Hospital |
And 6 more authors.
European Radiology | Year: 2014
Objectives: To retrospectively evaluate the ability of multiparametric magnetic resonance (MR) imaging to differentiate renal tumours. Methods: MR images from 100 consecutive pathologically proven solid renal tumours without macroscopic fat [57 clear cell, 16 papillary and 7 chromophobe renal cell carcinomas (RCCs), 16 oncocytomas and 4 minimal fat angiomyolipomas (AMLs)] between 2009 and 2012 were evaluated. Two radiologists blinded to pathology results independently reviewed double-echo chemical shift, dynamic contrast-enhanced T1- and T2-weighted images and apparent diffusion coefficient (ADC) maps. Signal intensity index (SII), tumour-to-spleen SI ratio (TSR), ADC ratio, wash-in (WiI) and wash-out indices (WoI) between different phases were calculated. Results: There were significant differences between papillary RCCs and other renal tumours for arterial WiI (P<0.001), initial WoI (P=0.006) and ADC ratio (P<0.001); between chromophobe RCCs and oncocytomas for TSR (P=0.02), parenchymal WiI (P=0.03), late WiI (P=0.02), initial WoI (P=0.03) and late WoI (P=0.04); and between clear cell RCCs and oncocytomas for SII (P=0.01) and parenchymal WiI (P=0.01). Papillary RCCs were distinguished from other tumours (sensitivity 37.5 %, specificity 100 %) and oncocytomas from chromophobe RCCs (sensitivity 25 %, specificity 100 %) and clear cell RCCs (sensitivity 100 %, specificity 94.2 %). Conclusion: MR imaging provides criteria able to accurately distinguish papillary RCCs from other tumours and oncocytomas from chromophobe and clear cell RCCs. Key Points: • Multiparametric MR parameters accurately distinguish papillary RCCs with high specificity (100 %). • Oncocytomas can be distinguished from chromophobe RCCs with high specificity (100 %). • Oncocytomas can be distinguished from clear cell RCCs with high specificity (94.2 %). • In oncocytomatosis, imaging follow-up with such parameters analysis could be promoted. © 2014 European Society of Radiology.
Patel U.B.,Royal Marsden Hospital |
Brown G.,Royal Marsden Hospital |
Rutten H.,Catharina Hospital |
West N.,University of Leeds |
And 9 more authors.
Annals of Surgical Oncology | Year: 2012
Background: Magnetic resonance imaging (MRI) methods for chemoradiotherapy (CRT) response assessment of rectal cancer include posttreatment T staging (ymrT), tumor regression grading (mrTRG), volume reduction posttreatment, and modified RECIST measurement. We compared these methods in identifying good versus poor responders with the histopathological standards of T stage (ypT) and tumor regression grading (TRG). Methods: A total of 86 patients underwent CRT in a prospective phase II trial for MRI-defined locally advanced rectal cancer. Two readers independently assessed MRIs for ymrT, mrTRG, volume change, and RECIST. Parameters for each case were categorized as good or poor response and analyzed against ypT and TRG by univariate logistic regression. Results: A total of 83 patients had evaluable imaging, and 78 had final pathology (five did not undergo surgery). Of these, 34 patients had good response (ypT0-3a) and 44 had poor response (>ypT3a). Also, 27 patients had favorable pathologic TRG (predominant fibrosis) and 51 had unfavorable TRG (predominant tumor). Good mrTRG and ymr
Zerbib F.,Bordeaux University Hospital Center |
Zerbib F.,Saint Andre Hospital |
Des Varannes S.B.,University of Nantes |
Simon M.,Bordeaux University Hospital Center |
Galmiche J.P.,University of Nantes
Current Gastroenterology Reports | Year: 2012
Functional heartburn (FH) is a functional gastrointestinal disorder characterized by symptoms of heartburn not related to gastro-esophageal reflux. The absence of evidence of reflux-related symptoms relies on absence of esophagitis at endoscopy (including biopsies to exclude eosinophilic esophagitis), a normal esophageal acid exposure during esophageal pH-monitoring together with a negative symptom-reflux association analysis and an unsatisfactory response to proton pump inhibitor therapy. Addition of impedance measurement to pH-monitoring is likely to increase the number of patients with recognized reflux-related symptoms. The pathophysiology of functional heartburn remains largely unknown but involves disturbed esophageal perception and psychological factors such as depression, anxiety and somatization. The treatment of FH remains largely empirical and an individual approach is therefore recommended. The clinician should provide reassurance and refrain from performing too many invasive tests or therapeutic procedures. The use of pain modulators is recommended by most experts despite the lack of appropriate clinical trials to support it. © Springer Science+Business Media, LLC 2012.
Denost Q.,Saint Andre Hospital |
Denost Q.,University of Bordeaux Segalen |
Adam J.-P.,Saint Andre Hospital |
Adam J.-P.,University of Bordeaux Segalen |
And 8 more authors.
Annals of Surgery | Year: 2015
Objective: Oncologic and functional outcomes were compared between transanal and transabdominal specimen extraction after laparoscopic coloanal anastomosis for rectal cancer. Background: Laparoscopic coloanal anastomosis is an attractive new surgical option in patients with low rectal cancer because laparotomy is not necessary due to transanal specimen extraction. Risks of tumor spillage and fecal incontinence induced by transanal extraction are not known. Methods: Between 2000 and 2010, 220 patients with low rectal cancer underwent laparoscopic rectal excision with hand-sewn coloanal anastomosis. The rectal specimen was extracted transanally in 122 patients and transabdominally in 98 patients. End points were circumferential resection margin, mesorectal grade, local recurrence, survival, and functional outcome. Results: The mortality rate was 0.5% and surgical morbidity rate was 17%. The rate of positive circumferential resectionmargin was 9% and the mesorectum was graded complete in 79%, subcomplete in 12%, and incomplete in 9%. After a follow-up of 51 months (range, 1-151), the local recurrence rate was 4% and overall survival and disease-free survival rates were 83% and 70% at 5 years, respectively. The continence score was 6 (range, 0-20). There was no difference of mortality rate, morbidity rate, circumferential resection margin, mesorectal grade, local recurrence (4% vs 5%, P = 0.98), and disease-free survival rate (72% vs 68%, P = 0.63) between transanal and transabdominal extraction groups. Continence score was also similar (6 vs 6, P = 0.92). Conclusions: Transanal extraction of the rectal specimen did not compromise oncologic and functional outcome after laparoscopic surgery for low rectal cancer and seems as a safe option to preserve the abdominal wall. Copyright © 2014 by Lippincott Williams & Wilkins.
Gauthier Y.,Saint Andre Hospital |
Indian Journal of Dermatology, Venereology and Leprology | Year: 2012
Background: Medical treatments are ineffective in many patients and surgical methods have therefore been developed. Objective: A review of autologous non-cultured melanocyte grafting techniques is proposed to obtain a successful repigmentation of vitiligo macules. Methods: Initially in 1992, we had developed a simplified grafting method which was carried out in the following two steps: production of blisters on the depigmented lesions by freezing with liquid nitrogen and injection in each blister of a non-cultured suspension of epidermal cells. The cellular suspension was obtained from samples of skin of the hair scalp after trypsinization. This very simple technique could be used at the dermatologist's clinic. Since 1998 (Olsson MJ, Juhlin L), quite comparable but improved and more sophisticated techniques have been proposed for the surgical treatment of vitiligo. These techniques require a laboratory set up to perform the melanocyte transplantation. The donor zone was usually taken on the gluteal region. The time of trypsinization was reduced to 60 minutes at 37C and the centrifuged cellular suspension added with hyaluronic acid (Van Geel) was directly applied on a dermabraded or laser abraded vitiligo lesions. Results: Whatever the technique chosen, repigmentation was evident within 25 to 30 days. Coalescence of the pigmented areas was spontaneously observed or obtained after UVB radiation. It is obvious that the complete repigmentation occurred more rapidly with the recent techniques compared with the initial method, but the efficiency was quite similar. Conclusion: The use of non-cultured epidermal suspension appears to be an effective, safe, and simple method for treating patients with achromic areas lacking melanocytes.
Zerbib F.,University of Bordeaux 1 |
Zerbib F.,Saint Andre Hospital |
Roman S.,University of Lyon
Journal of Clinical Gastroenterology | Year: 2015
With the development of high-resolution manometry and specific metrics to characterize esophageal motility, the Chicago Classification has become the gold standard for the diagnosis of esophageal motor disorders. Major and significant disorders, that is, never observed in healthy subjects, are achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, absent peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is relevant to predict the response to endoscopic and surgical therapies as several studies suggest that, pneumatic dilation is less effective than Heller myotomy, in type III achalasia. Peroral endoscopic myotomy, initially developed in expert centers, is a promising technique for the treatment of achalasia. The medical therapeutic options for distal esophageal spasm and hypercontractile esophagus are smooth muscle relaxants and pain modulators. Intraesophageal injection of botulinum toxin might be an interesting option for treatment of these disorders but further studies are required to determine the optimal injection protocol and the best candidates based on manometric patterns. The treatment of hypotensive motility disorders is disappointing and relies mainly on dietary and lifestyle changes as no effective esophageal prokinetic is currently available. © 2015 Wolters Kluwer Health, Inc.