Publications by authors named "Christian Pfister"

107 Publications

Efficacy and safety of single- and repeated-selurampanel dosing for 2 weeks in patients with chronic subjective tinnitus: Results of a randomized, double-blind, placebo-controlled, cross-over, proof-of-concept phase IIa study.

Prog Brain Res 2021 20;260:423-440. Epub 2021 Jan 20.

Department of Psychiatry and Psychotherapy, Bezirksklinikum, University of Regensburg, Regensburg, Germany.

To evaluate efficacy and safety of BGG492 (selurampanel; an orally active, competitive AMPA glutamate receptor antagonist) in patients with moderate-to-catastrophic chronic subjective tinnitus. Study (NCT01302873) enrolled patients with subjective tinnitus based on THI severity grade 3, 4 or 5 (moderate, severe or catastrophic), and those with chronic (>6 and <36 months) tinnitus. Primary endpoints were clinical status of tinnitus using TBF-12 and tinnitus loudness using VAS after multiple dose 2-week BGG492 treatment. Safety was assessed by recording all adverse events (AEs). After a single dose of BGG492 VAS scores for tinnitus loudness (P=0.012) and tinnitus annoyance (P=0.004) were significantly reduced vs placebo. After 2 weeks treatment a significantly greater proportion of patients showed improvement of ≥4 points from baseline in TBF-12 (stringent responder definition) with BGG492 vs placebo (26.7% [n=23] vs 14% [n=12], respectively; odds ratio [OR] (90% CI):2.30 (1.10, 4.83); P=0.064), fulfilling proof-of-concept achievement criteria. No notable difference in proportion of responders to BGG492 vs placebo was observed as assessed using VAS (26.7% [n=23] vs 27.6% [n=24], respectively; OR (90% CI):0.94 (0.52, 1.67); P=0.848). Dizziness was the most frequently reported AE in 50% [n=21] and 31.5% [n=17] patients on BGG492 100 and 50mg TID, respectively vs 9.6% [n=9] on placebo. In conclusion, BGG492 showed reduction of both tinnitus loudness and annoyance after a single dose and reduction of tinnitus handicap after 2 weeks of treatment in patients with chronic subjective tinnitus, thereby supporting further clinical investigation of AMPA receptor antagonists with an improved benefit/risk ratio. A dose of 100mg TID BGG492 showed higher efficacy but somewhat lower tolerability compared to 50mg TID.
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http://dx.doi.org/10.1016/bs.pbr.2020.12.004DOI Listing
January 2021

Prognostic Impact of pT3 Subclassification in a Multicentre Cohort of Patients with Urothelial Carcinoma of the Renal Pelvicalyceal System Undergoing Radical Nephroureterectomy: A Propensity Score-weighted Analysis After Central Pathology Review.

Eur Urol Focus 2020 Oct 23. Epub 2020 Oct 23.

Sorbonne University, GRC 5 Predictive ONCO-URO, AP-HP, Urology, Pitie-Salpetriere Hospital, F-75013 PARIS, France. Electronic address:

Background: The current pathological tumour-node-metastasis (pTNM) classification for upper tract urothelial carcinoma (UTUC) does not include any risk stratification of pT3 renal pelvicalyceal tumours.

Objective: To assess the prognostic impact of pT3 subclassification in a multicentre cohort of patients with UTUC of the renal pelvicalyceal system undergoing radical nephroureterectomy (RNU).

Design, Setting, And Participants: Data from all consecutive patients treated with RNU for pT3 renal pelvicalyceal UTUC at 14 French centres from 1995 to 2013 were reviewed retrospectively.

Intervention: A central pathology review (CPR) was used to stratify pT3 patients into those with infiltration of the renal parenchyma on a microscopic level (pT3a) versus those with infiltration of the renal parenchyma visible on gross inspection of the resection specimen and/or invasion of peripelvic fat (pT3b).

Outcome Measurements And Statistical Analysis: Inverse probability weighting (IPW)-adjusted Cox regression analyses were used to compare recurrence-free survival (RFS) and cancer-specific survival (CSS) between pT3a and pT3b patients.

Results And Limitations: Overall, 202 patients were included and further stratified into pT3a (n = 98; 48.5%) and pT3b (n = 104; 51.5%) subgroups. Median time to follow-up in the weighted population was 68 (interquartile range, 50-95) mo. In IPW-adjusted Cox regression analyses, pT3b versus pT3a substage was associated with a significant adverse effect on RFS (hazard ratio [HR] = 2.02; 95% confidence interval [CI] = [1.36-3.01]; p < 0.001) and CSS (HR = 1.84; 95% CI = [1.20-2.82]; p = 0.005). The study is limited by its retrospective design.

Conclusions: Using IPW-adjusted analyses after the CPR, we observed that RNU patients with pT3b renal pelvicalyceal UTUC had adverse prognosis as compared with those with pT3a disease. As such, this subclassification could help refine the current pTNM system for UTUC.

Patient Summary: In this report, we looked at the prognostic interest of stratifying patients with pT3 renal pelvicalyceal upper tract urothelial carcinoma based on the extent of local invasion. We found that those with extensive infiltration (pT3b) had adverse prognosis as compared with those with limited infiltration (pT3a). This information could be provided on pathology reports to further guide clinical decision making.
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http://dx.doi.org/10.1016/j.euf.2020.10.004DOI Listing
October 2020

Comparison of the prognosis of primary vs. progressive muscle invasive bladder cancer after radical cystectomy: Results from a large multicenter study.

Urol Oncol 2021 Mar 16;39(3):195.e1-195.e6. Epub 2020 Nov 16.

Department of Urology, Rouen University Hospital, Rouen, France.

Purpose: To assess whether progressive and primary muscle invasive bladder cancer (MIBC) have different prognosis after radical cystectomy or not. To date only a few data are available on this topic with conflicting results. Further studies on large cohort are needed to clarify these outcomes that may influence bladder cancer management for these patients.

Material And Methods: A multicentre retrospective study was conducted on patient treated for MIBC at 5 centres between 2005 and 2015 by radical cystectomy. Patients' outcomes were compared between patients with primary MIBC vs. progressive MIBC subsequent to a history of non-muscle invasive bladder cancer (NMIBC).

Results: A total of 1197 patients were included. Median (IQ) age was 65 (58-72) years and median follow-up was 65 months. Baseline characteristics were similar between the groups as well as the Tumour pT stage, N status and positive surgical margins. Patients with progressive MIBC had worse overall survival (OS) (hazard ratio [HR] 1.36, [95%CI 1.10-1.76]; P = 0.004), cancer specific survival (CSS) (HR 1.41 [1.13-1.78]; P = 0.002), and recurrence-free survival (RFS) (HR 1.21 [1.01-1.49]; P = 0.05). Pathological stage ≥pT3, positive surgical margins, and positive lymph nodes status (pN+) were also found as predictors of OS, CSS, and RFS.

Conclusions: Our results suggest that patient having a progressive BC have a worse prognosis in terms of OS, PFS, and CSS than patient with primary disease. These 2 groups may require different management and patients with high risk NMIBC should be assessed properly to avoid progression and be offered early cystectomy.
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http://dx.doi.org/10.1016/j.urolonc.2020.09.006DOI Listing
March 2021

Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Secondary Endpoints: Chemotherapy Toxicity and Pathological Responses.

Eur Urol 2021 Feb 28;79(2):214-221. Epub 2020 Aug 28.

Department of Medical Oncology, Saint-Louis-APHP, Faculté de Paris, France.

Background: Perioperative chemotherapy (neoadjuvant or adjuvant) has been developed to increase overall survival for nonmetastatic muscle-invasive bladder cancer (MIBC). Retrospective studies or prospective phase II trials have been reported to use dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC). As dd-MVAC has shown higher response rates in metastatic disease, better efficacy is expected in the perioperative setting.

Objective: We designed a randomized phase III trial to compare the efficacy of dd-MVAC or GC in MIBC perioperative (neoadjuvant or adjuvant) setting.

Design, Setting And Participants: A total of 500 patients were randomized from February 2013 to March 2018 in 28 centers and received either six cycles of dd-MVAC every 2 wk or four cycles of GC every 3 wk.

Outcome Measurements And Statistical Analysis: The primary endpoint (progression-free survival at 3 yr) was not reported. We focused on secondary endpoints: chemotherapy toxicity and pathological responses.

Results And Limitations: In the neoadjuvant group, 218 patients received dd-MVAC and 219 received GC. Of the patients, 60% received six cycles in the dd-MVAC arm and 84% received four cycles in the GC arm; 199 (91%) and 198 (90%) patients underwent surgery, respectively. Complete pathological response (ypT0pN0) was observed in 84 (42%) and 71 (36%) patients, respectively (p=0.2). An organ-confined status (
Conclusions: The toxicity of dd-MVAC was manageable with more severe asthenia and GI side effects than that of GC in perioperative chemotherapy. A higher local control rate (complete pathological response, tumor downstaging, or organ confined) was observed in the dd-MVAC arm (p=0.021). However, such data have to be confirmed on progression-free survival, with primary endpoint data expected in mid-2021.

Patient Summary: The authors have designed a randomized phase III controlled study comparing the efficacy of gemcitabine and cisplatin, and dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) in patients for whom chemotherapy has been decided, before or after radical cystectomy. Higher toxicity regarding asthenia and gastrointestinal side effects along with a better bladder control rate were observed in the dd-MVAC arm. However, such data have to be confirmed on progression-free survival, with primary endpoint data expected in mid-2021.
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http://dx.doi.org/10.1016/j.eururo.2020.08.024DOI Listing
February 2021

Observation vs. early drainage for grade IV blunt renal trauma: a multicenter study.

World J Urol 2020 May 23. Epub 2020 May 23.

Urology, University of Rouen, Rouen, France.

Introduction: The aim of this study was to compare observation and early drainage by ureteral stenting in patients with blunt renal trauma and urinary extravasation.

Materials And Methods: A retrospective national multicenter study was performed including all patients admitted for renal trauma at 17 hospitals between 2005 and 2015. Patients presenting with a urinary extravasation on initial imaging were considered for inclusion. Patients were divided in two groups according to the initial approach: observation vs. early drainage by ureteral stent (within 48 h after admission). The primary endpoint was the persistence of urinary extravasation on follow-up imaging.

Results: Out of 1799 patients with renal trauma, 238 were included in the analysis (57 in the early drainage and 181 in the observation group). In the early drainage group, 29 patients had persistent urinary extravasation vs. 77 in the observation group (50.9% vs. 42.5%; p value = 0.27). The rates of secondary upper urinary tract drainage did not differ significantly between the early drainage group (26.4%) and the observation group (16%) (p = 0.14). There were no statistically significant differences between the two groups in terms of secondary nephrectomy (0% vs. 2.8%; p = 0.34), and death from trauma (0% vs. 1.8%; p = 0.99). In multivariate analysis, early drainage remained not statistically associated with persistence of urinary extravasation on follow-up imaging (OR = 1.35; p = 0.36) CONCLUSION: In this multicenter cohort, observation was not different from early drainage in terms of persistent urinary extravasation after grade IV blunt renal trauma. Further randomized controlled prospective trials are needed to confirm these findings.
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http://dx.doi.org/10.1007/s00345-020-03255-3DOI Listing
May 2020

Evolution of prostate cancer diagnosis: retrospective analysis of magnetic resonance imaging/ultrasound fusion guided biopsies protocol in routine practice and patients management.

Transl Androl Urol 2020 Apr;9(2):629-636

Department of Urology, Rouen University Hospital, Rouen, France.

Background: Magnetic resonance imaging (MRI) is today strongly recommended in prostate cancer (PCa) diagnosis. Therefore, MRI/ultrasound (MRI/US) fusion-guided biopsy is becoming the new standard patients management.

Methods: We report our experience during the last 4 years using this technique, with a protocol of 6 random cores (instead of the most used 12 cores protocol) associated to the target cores (2 to 3 per lesion). Our study involved 236 patients including real life routine practice: biopsy naïve patients (n=107), patients with previous negative standard prostate biopsies (n=67) and patients in PCa active surveillance (n=62). Finally, 76 patients have a robotic radical prostatectomy.

Results: Mean age of the population was 66 years. Median PSA was 8.5 ng/mL. Overall and significant cancer detection were respectively 66.6% and 38.5%, with a large difference considering biopsy history: 63.5% in biopsy naïve patient, 53.7% in patient with previous negative biopsies and 82.3% in patients under active surveillance. Targeted biopsies missed 28 cancers among 8 were significant and standard biopsies missed 33 cancers among 14 were significant. Moreover, concordance between biopsy samples and radical prostatectomy specimens was evaluated at 80%.

Conclusions: Comparing to literature data, similar results were observed in our retrospective study, even with reduced random cores, suggesting a real change in patients management in particular in active surveillance group with a reclassification rate of 56.4% using the Epstein criteria.
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http://dx.doi.org/10.21037/tau.2020.02.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215024PMC
April 2020

Design of a randomized controlled phase III study of dose dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as peri-operative chemotherapy for patients with locally advanced transitional cell cancer of the bladder. The French GETUG/AFU V05 VESPER trial.

Contemp Clin Trials Commun 2020 Mar 30;17:100536. Epub 2020 Jan 30.

Department of Medical Oncology, Saint-Louis, APHP, Paris, France.

The main objective of the French GETUG/AFU V05 VESPER randomized phase III study was to assess the efficacy of dd-MVAC and GC in term of progression-free survival in patients for whom chemotherapy has been decided, before or after surgery. A total of 500 patients have been randomized in 28 reference centers. Inclusion criteria were urothelial carcinoma without neuro-endocrine variant, disease defined by a T2, T3 or T4a N0 (pelvic lymph node ≤ 10 mm on CT scan) M0 staging for patients receiving neoadjuvant chemotherapy or pT3 or pT4 or pN+ and M0 for patients receiving adjuvant chemotherapy. Secondary endpoints include overall survival, safety, response rate. The peri-operative chemotherapy schedule was experimental arm dd-MVAC for a total of 6 cycles versus standard arm GC 4 cycles. The toxicity was evaluated according to NCI CTCAE (v 4.0). The progression-free survival rate will be estimated at 3 years by the Kaplan-Meier method. All the patients will be followed for 5 years. The last patient was randomized in March 2018 and the primary endpoint results are expected for mid-2021. As the dd-MVAC schedule is associated with higher response rates in metastatic disease, the real question today is to confirm such benefit in the peri-operative setting, taking also in consideration the chemotherapy toxicity. Tomorrow, the challenge may be the best chemotherapy and immunotherapy association, the authors hope that final Vesper Trial results will help to determine the gold standard chemotherapy.
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http://dx.doi.org/10.1016/j.conctc.2020.100536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025084PMC
March 2020

Clinical interest of PD-L1 immuno-histochemistry expression as a predictive factor of Bacillus Calmette Guerin (BCG) efficacy in refractory high-risk non-muscle-invasive bladder cancer (NMIBC).

World J Urol 2020 Jun 5;38(6):1517-1524. Epub 2019 Sep 5.

Department of Urology, Charles Nicolle Rouen University Hospital, 1 rue de Germont, 76031, Rouen Cedex, France.

Objective: To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC.

Materials And Methods: Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant.

Results: A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly (p = 0.97) more frequent in the TC PD-L1 ≥ 1% group (n = 7, 20.0%) than in the TC PD-L1-negative group (n = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p < 0.05), with increased expression of PD-L1 by IC after BCG therapy (p = 0.006).

Conclusion: No association was observed between immuno-histochemistry PD-L1 positivity and ER after BCG therapy. Nevertheless, the relationship between immune infiltrate and PD-L1 positivity confirmed the interest of assessing the immune infiltrate density to define tumor's profile.
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http://dx.doi.org/10.1007/s00345-019-02896-3DOI Listing
June 2020

Long survival of patients with metastatic clear cell renal cell carcinoma. Results of real life study of 344 patients.

Int J Cancer 2020 03 1;146(6):1643-1651. Epub 2019 Aug 1.

Institut de Cancérologie de l'Ouest, Angers, Nantes, France.

The treatment landscape in metastatic renal cell carcinoma has changed fundamentally over the last decade by the development of antiangiogenic agents, mammalian target of rapamycin inhibitors and immunotherapy. Outside of the context of a clinical trial, the treatments are used sequentially. We describe results under real-life conditions of a sequential treatment strategy, before the era of immunotherapy. All patients were treated according to their prognostic score (either Memorial Sloan Kettering Cancer Center or International Metastatic Renal Cell Carcinoma Database Consortium) for advanced renal cell carcinoma. A treatment strategy involving 1 to 4 lines was determined including a rechallenge criterion for the repeat use of a treatment class. Three hundred forty-four patients were included over 3 years. Overall survival was 57 months in patients with good or intermediate prognosis and 19 months in patients with poor prognosis. In the former group, the proportions of patients treated with 2 to 4 treatment lines were 70%, 38% and 16%, respectively. The best objective response rates for lines 1 to 4 were 46%, 36%, 16% and 17%, respectively. Grade III/IV toxicity did not appear to be cumulative. The recommended strategy was followed in 68% of patients. A large proportion of patients with good or intermediate prognosis who progress after two lines of treatment still have a performance status good enough to receive a systemic treatment, which justifies such a strategy. Overall survival of patients with good and intermediate prognosis was long, suggesting a benefit from the applied approach. These results might be used as selection criterion for the treatment of patients in the era of immune checkpoint inhibitors.
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http://dx.doi.org/10.1002/ijc.32578DOI Listing
March 2020

Refining the use of neoadjuvant chemotherapy in locally advanced bladder cancer: from conviction to optimization.

Transl Androl Urol 2018 Aug;7(4):757-759

Department of Urology, Centre Hospitalier Universitaire, Rouen University, Rouen, France.

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http://dx.doi.org/10.21037/tau.2018.06.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127548PMC
August 2018

The maximum detrusor pressure as a predictive factor of success after sphincterotomy in detrusor-sphincter dyssynergia.

Neurourol Urodyn 2018 11 11;37(8):2758-2762. Epub 2018 Sep 11.

Department of Urology, Charles Nicolle University Hospital, Rouen Cedex, France.

Aims: To evaluate the impact of the pre-operative maximum detrusor pressure (MDP) on efficacy outcomes after incontinentation by sphincterotomy or urethral stent placement in male patients with neurogenic detrusor-sphincter dyssynergia (DSD).

Methods: A retrospective study was performed in 41 male patients treated between 2006 and 2013 in a tertiary reference center. All patients had a neurogenic DSD confirmed by baseline urodynamic studies, and were unable or secondary failed to practice CISC. Success was defined as a post-void residual volume <150 mL. Influence of MDP on treatment efficacy was evaluated through a Mann-Whitney U-Test.

Results: Median (range) age was 39 years (20-69). Spinal cord injury was the main underlying condition. Twenty-six patients had a sphincteric stent placement (Memocath®, Bard, Covington) and 15 had surgical sphincterotomy. Treatment was successful in 31 patients (76%). Patients with immediate successful outcomes had a significantly higher mean preoperative MDP (59.6 vs 29.7 cmH O; P = 0.002). Patients with MDP over the threshold of 40 cmH O had a 90% success rate. These differences were maintained at 6 months, MDP being higher in the success group than in the failure group (59.5 vs 39.8 cmH O, respectively, P = 0.008). The technique used (stent placement or incision) had no impact on immediate or 6-month success rates.

Conclusions: Our results suggested that MDP is associated with treatment success rate after surgical management of DSD of neurogenic origin by sphincteric stent placement or surgical sphincterotomy. A threshold of 40 mH O is associated with higher success rates.
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http://dx.doi.org/10.1002/nau.23759DOI Listing
November 2018

First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury.

Neurorehabil Neural Repair 2018 06 5;32(6-7):578-589. Epub 2018 Jun 5.

12 Balgrist University Hospital, Zurich, Switzerland.

Background: Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery.

Objective: This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia.

Methods: Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks).

Results: ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining >10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia.

Conclusions: ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.
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http://dx.doi.org/10.1177/1545968318776371DOI Listing
June 2018

Clinical Relevance of Gene Copy Number Variation in Metastatic Clear Cell Renal Cell Carcinoma.

Clin Genitourin Cancer 2018 08 23;16(4):e795-e805. Epub 2018 Feb 23.

Normandie University, UNIROUEN, IRON Group, Rouen University Hospital, Rouen, France; Urologic Oncology Unit, Department of Urology, Rouen University Hospital, Rouen, France; Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen, France.

Background: Gene copy number variations (CNVs) have been reported to be frequent in renal cell carcinoma (RCC), with potential prognostic value for some. However, their clinical utility, especially to guide treatment of metastatic disease remains to be established. Our objectives were to assess CNVs on a panel of selected genes and determine their clinical relevance in patients who underwent treatment of metastatic RCC.

Patients And Methods: The genetic assessment was performed on frozen tissue samples of clear cell metastatic RCC using quantitative multiplex polymerase chain reaction of short fluorescent fragment method to detect CNVs on a panel of 14 genes of interest. The comparison of the electropherogram obtained from both tumor and normal renal adjacent tissue allowed for CNV identification. The clinical, biologic, and survival characteristics were assessed for their associations with the most frequent CNVs.

Results: Fifty patients with clear cell metastatic RCC were included. The CNV rate was 21.4%. The loss of CDKN2A and PLG was associated with a higher tumor stage (P < .05). The loss of PLG and ALDOB was associated with a higher Fuhrman grade (P < .05). The loss of ALDOB was also associated with a worse Heng prognostic score (95% vs. 66%; P = .029) and lower 24-month survival rate (18% vs. 58%; P = .012). The loss of both ALDOB and PLG was frequent (32%) and was associated with a higher tumor stage and grade (P < .05).

Conclusion: As expected, we showed that several CNVs were associated with clinical relevance, especially those located on CDKN2A, PLG, and ALDOB, in a homogeneous cohort of patients with clear cell metastatic RCC.
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http://dx.doi.org/10.1016/j.clgc.2018.02.013DOI Listing
August 2018

Ladies first: Female and male adult height in Switzerland, 1770-1930.

Econ Hum Biol 2018 05 16;29:76-87. Epub 2018 Feb 16.

Institute of Evolutionary Medicine, University of Zurich, Switzerland.

When investigating the well-being of a society, the living conditions of females are of special importance, not only due to the immediate impact for those directly involved, but also because of the potential intergenerational effects. Studying the dimorphism in the mean height helps to depict variation in the basic biological sex difference due to gender-related factors that potentially determine net nutrition. To expand knowledge of diachronic development in Swiss well-being conditions we investigate changes in the height of adult females born 1770-1930, and compare the series with data on contemporary males from the same sources: We employ a sample of N = 21'028 women and N = 21'329 men from passport-, convict-, maternity hospital-, and voluntary World War II army auxiliary records. The secular height trend is found both in males, from the 1870s/1880s, and in females starting with the 1840s/1850s birth cohorts. During the decades under study, mean height increased from 157 cm to 164 cm in female and 167 cm to 172 cm in male passport applicants, 154 cm to 159 cm in female and 167 cm to 169 cm in male convicts, 159 cm to 163 cm in female auxiliaries, and 155 cm to 159 cm in females giving birth in the maternity hospital of Basel. Because females seem to have started the secular trend in height earlier than their male contemporaries, the height dimorphism decreased during the second half of the 19th century. Differences between socio-economic status (SES) and data sources are found in both females and males: Women with low SES were significantly shorter than those of the other SES groups in all sources (on average 1.40 cm, p-values between 0.00 and 0.03). In men we found individuals of upper SES to be significantly taller (on average 1.96 cm, p-value = 0.00-0.10). Concerning differences between the sources, overall, passport applicants were the tallest for men as well as women; in females the individuals measured at the maternity hospital and in prison were the shortest. The variances across the datasets highlight the importance of considering different sources to depict average living conditions. Noteworthy is the finding that the diverse sources under study all show the same trajectory of increasing mean height over the course of the 19th century. In the long run, the improving net nutritional status of Swiss females may have been one of the contributors behind the general rise in well-being of the country's population from the later 19th century onwards.
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http://dx.doi.org/10.1016/j.ehb.2018.02.002DOI Listing
May 2018

Safety and efficacy of temsirolimus as second line treatment for patients with recurrent bladder cancer.

BMC Cancer 2018 02 17;18(1):194. Epub 2018 Feb 17.

INSERM U1194, Montpellier Cancer Research Institute, Montpellier, France.

Background: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. Metastatic patients have a poor prognosis with a median overall survival of 14 months. Until recently, vinflunine was the only second-line chemotherapy available for patients who relapse. Deregulation of the PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and suggested the use of mTOR as a target for the treatment of urothelial cancers.

Methods: This trial assessed the efficacy of temsirolimus in a homogenous cohort of patients with recurrent or metastatic bladder cancer following first-line chemotherapy. Efficacy was measured in terms of non-progression at two months according to the RECIST v1.1 criteria. Based on a two-stage optimal Simon's design, 15 non-progressions out of 51 evaluable patients were required to claim efficacy. Patients were treated at a weekly dose of 25 mg IV until progression, unacceptable toxicities or withdrawal.

Results: Among the 54 patients enrolled in the study between November 2009 and July 2014, 45 were assessable for the primary efficacy endpoint. A total of 22 (48.9%) non-progressions were observed at 2 months with 3 partial responses and 19 stable diseases. Remarkably, 4 patients were treated for more than 30 weeks. Fifty patients experienced at least a related grade1/2 (94%) and twenty-eight patients (52.8%) a related grade 3/4 adverse event. Eleven patients had to stop treatment for toxicity. This led to recruitment being halted by an independent data monitoring committee with regard to the risk-benefit balance and the fact that the primary objective was already met.

Conclusions: While the positivity of this trial indicates a potential benefit of temsirolimus for a subset of bladder cancer patients who are refractory to first line platinum-based chemotherapy, the risk of adverse events associated with the use of this mTOR inhibitor would need to be considered when such an option is envisaged in this frail population of patients. It also remains to identify patients who will benefit the most from this targeted therapy.

Trial Registration: ClinicalTrials.gov Identifier: NCT01827943 (trial registration date: October 29, 2012); Retrospectively registered.
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http://dx.doi.org/10.1186/s12885-018-4059-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816357PMC
February 2018

Metastatic chromophobe renal cell carcinoma treated with targeted therapies: A Renal Cross Channel Group study.

Eur J Cancer 2017 07 23;80:55-62. Epub 2017 May 23.

Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. Electronic address:

Background: Treatment of non-clear cell renal cell carcinoma (RCC) remains controversial despite several recent prospective studies of targeted therapies (TT). Often Vascular Endothelial growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) inhibitors are used, extrapolating the data from use of these agents in clear cell RCC.

Methods: We performed a retrospective data analysis within the Renal Cross Channel Group to determine metastatic chromophobe RCC (mChRCC) outcomes in the TT era. The end-points were overall response, overall survival (OS) and time to treatment failure (TTF). The two latter were estimated using the Kaplan-Meier method.

Results: 91 mChRCC patients from 26 centres were included. Median follow-up from the date of first metastasis was 6.1 years (range: 0-13.9). Median OS was 37.9 months (95% confidence interval [CI]: 21.4-46.8) from the diagnosis of metastatic disease. Among the 61 patients who received TT, 50 (82%) were treated with anti-angiogenic (AA) and 11 with mTOR inhibitors. Median TTF and OS in patients receiving a first line of AA was 8.7 months (95% CI: 5.2-10.9) and 22.9 months (95% CI: 17.8-49.2) versus 1.9 months (95% CI: 1.0-6.0) and 3.2 months (95% CI: 2.3-not evaluable) with mTOR inhibitors, respectively. A stratified log-rank test was used to compare AA and mTOR inhibitors TT, while controlling the effect of the International Metastatic RCC Database Consortium risk group and no significant difference between AA and mTOR inhibitors was observed for TTF (p = 0.26) or for OS (p = 0.55).

Conclusion: We report the largest retrospective cohort of patients with mChRCC treated with TT and no significant difference between AA and mTOR inhibitors was observed for TTF and OS.
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http://dx.doi.org/10.1016/j.ejca.2017.03.011DOI Listing
July 2017

Diagnostic performance of contrast-enhanced ultrasonography and magnetic resonance imaging for the assessment of complex renal cysts: A prospective study.

Int J Urol 2017 03 1;24(3):184-189. Epub 2017 Feb 1.

Urology Department, Rouen University Hospital, Rouen, France.

Objectives: To compare the diagnostic performance of computed tomography, magnetic resonance imaging and contrast enhanced ultrasonography for the assessment of complex renal cysts.

Methods: We carried out a prospective single-center study from January 2012 to December 2013. We included patients with Bosniak category 2F or 3 renal cysts found on computed tomography and reviewed by two expert radiologists. Magnetic resonance imaging and contrast-enhanced ultrasonography were then carried out. Patients with a Bosniak ≥3 cyst on magnetic resonance imaging, as well as those upgraded as appearing malignant on contrast-enhanced ultrasonography, were surgically managed. Imaging results were compared with histological data. For patients without surgery, imaging examinations were compared with follow-up data. For each imaging examination, diagnostic performance and Cohen's kappa coefficient were assessed.

Results: A total of 47 patients were included. The median follow up was 36 months (range 17-48 months). At initial computed tomography, cysts were classified as Bosniak 2F and Bosniak ≥3 in 34 and 13 patients, respectively. Magnetic resonance imaging found 13 Bosniak ≥3 cysts, and contrast-enhanced ultrasonography upgraded six more patients with cysts that appeared malignant. A total of 19 patients had surgery. Histological analysis reported 14 malignant tumors. No tumor progression was found in followed-up patients. Computed tomography showed poor sensitivity (36%) and specificity (76%; κ = 0.11). Magnetic resonance imaging showed 71% sensitivity and 91% specificity (κ = 0.64). Contrast-enhanced ultrasonography showed high sensitivity (100%) and specificity (97%), and a negative predictive value at 100% (κ = 0.95).

Conclusions: The present results suggested that contrast-enhanced ultrasonography could be useful in improving the assessment of complex renal cysts. Indeed, computed tomography accuracy might be limited in this indication requiring further investigations to determine the best treatment strategy.
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http://dx.doi.org/10.1111/iju.13289DOI Listing
March 2017

[Urothelial tumors in 2016: Are we at the dawn of a new diagnostic and therapeutic era?]

Ann Pathol 2016 Dec;36(6):369-370

Service d'urologie et de transplantation du rein, hôpital Charles-Nicolle, 1, rue de Germont, 76031 Rouen, France. Electronic address:

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http://dx.doi.org/10.1016/j.annpat.2016.11.001DOI Listing
December 2016

Final results of the phase III URO-BCG 4 multicenter study: efficacy and tolerance of one-third dose BCG maintenance in nonmuscle invasive bladder cancer.

Anticancer Drugs 2017 03;28(3):335-340

aUrology Department, Charles Nicolle University Hospital bInserm 1404, Onco-Urology Group, Clinical Investigation Center, Rouen cUrology Department, Nantes University Hospital, Nantes dUrology Department, Amiens University Hospital, Amiens eUrology Department, Lyon University Hospital, Lyon fUrology Department, Kremlin Bicêtre University Hospital, Paris gUrology Department, Toulouse University Hospital, Toulouse, France.

The objective of this study was to assess at 3 years bacillus Calmette-Guerin (BCG) maintenance treatment for NMIBC using one-third dose schedule and fewer instillations every 3 or 6 months. This was a phase III randomized study including patients with intermediate-risk or high-risk NMIBC, who received, after a full-dose induction schedule, three-weekly instillations of one-third dose BCG every 6 months (group I) and two-weekly instillations every 3 months (group II) during 3 years. We assessed oncological efficacy, BCG side effects, leukocyturia, and prostate-specific antigen. No tumor recurrence was reported at 36 months for 55 (82.09%) patients in group I versus 64 (90.14%) patients in group II (P=0.241). Muscle invasion was observed in six patients at 36 months (P=0.942). In terms of BCG toxicity, grade II and III local or systemic side effects were, respectively, reported in 8.7 and 23.9% of patients during the first year. Nevertheless, the adverse events (AEs) score at 36 months underlined a lower median value of 0.8 in group I versus 1.1 in group II (P=0.037). Furthermore, 9.9% major AEs occurred in group II versus 3% in group I (P=0.031). Leukocyturia and prostate-specific antigen level were not associated significantly with either tumor recurrence or muscle progression. We observed a significant difference in the AEs score at 36 months, suggesting less toxicity in patients who were treated with one-third dose of BCG for 3 consecutive weeks every 6 months.
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http://dx.doi.org/10.1097/CAD.0000000000000456DOI Listing
March 2017

Post-chemotherapy retroperitoneal teratoma in nonseminomatous germ cell tumors: Do predictive factors exist? Results from a national multicenter study.

J Surg Oncol 2016 Dec 18;114(8):992-996. Epub 2016 Nov 18.

Department of Urology, Hopital d'Instruction des Armees Begin, Saint Mandé, France.

Background And Objectives: To identify predictive preoperative factors of the presence of teratoma in retroperitoneal lymph node dissection specimens.

Methods: We performed a 20 years multicenter retrospective analysis of all patients who underwent retroperitoneal lymph node dissection for residual masses after chemotherapy (PC-RPLND). Patients had undergone PC-RPLND after chemotherapy for advanced testicular cancer. The histologic components of the primary tumor were compared with those of the residual masses using logistic regression.

Results: A total of 469 NSGCT patients underwent PC-RPLND (complete data available for 211). By PC-RPLND, necrosis was found in 84 cases, teratoma in 102 cases, and viable tumor in 25 cases. The univariate and multivariate analyses showed that teratoma (P = 0.001 and P = 0.002, respectively) and yolk sac tumor (P = 0.009 and P = 0.035, respectively) in orchiectomy specimens were statistically significant predictors of the presence of teratoma in retroperitoneal lymph nodes.

Conclusions: PC-RPLND is the standard treatment for any supracentimetric residual lesion. This procedure is associated with a high morbidity, and almost half patients are overtreated. The presence of teratoma and yolk sac tumor in the orchiectomy specimen were independent significant predictors of teratoma in retroperitoneal masses. J. Surg. Oncol. 2016;114:992-996. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jso.24464DOI Listing
December 2016

From Undernutrition to Overnutrition: The Evolution of Overweight and Obesity among Young Men in Switzerland since the 19th Century.

Obes Facts 2016 20;9(4):259-72. Epub 2016 Aug 20.

Institute of Evolutionary Medicine, University of Zurich, Zurich, Switzerland.

Objective: The global obesity epidemic continues, new approaches are needed to understand the causes. We analyzed data from an evolutionary perspective, stressing developmental plasticity.

Methods: We present diachronical height, weight, and BMI data for 702,902 Swiss male conscripts aged 18-20 years, a representative, standardized and unchanged data source.

Results: From 1875 to 1879, the height distribution was slightly left-skewed; 12.1% of the conscripts were underweight, overweight and obesity were rare. The BMI-to-height relationship was positive but not linear, and very short conscripts were particularly slim. Since the 1870s, Swiss conscripts became taller, a trend that markedly slowed in the 1990s. In contrast, weight increased in two distinct steps at the end of the 1980s and again after 2002. Since 2010, BMI did not increase but stabilized at a high level.

Conclusions: The body of young men adapted differently to varying living conditions over time: First, less investment in height and weight under conditions of undernutrition and food uncertainty; second, more investment in height under more stable nutritional conditions; third, development of obesity during conditions of plateaued height growth, overnutrition, and decreasing physical activity. This example contributes to the evaluation of hypotheses on human developmental plasticity.
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http://dx.doi.org/10.1159/000446966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644905PMC
September 2017

Clinical activity of sunitinib rechallenge in metastatic renal cell carcinoma-Results of the REchallenge with SUnitinib in MEtastatic RCC (RESUME) Study.

Eur J Cancer 2016 07 15;62:28-35. Epub 2016 May 15.

Medical Oncology, Hôpital Saint-André, CHU Bordeaux, Bordeaux, France.

Aim: To assess the efficacy and tolerability of sunitinib rechallenge in the third-line or later setting in patients with metastatic renal cell carcinoma (mRCC).

Patients And Methods: This observational study comprised 61 mRCC patients at 19 centres in France who received sunitinib rechallenge between January 2006 and May 2013. Patients received first-line sunitinib, ≥1 different targeted therapies, and then sunitinib rechallenge. Patient/disease characteristics, tolerability, treatment modalities, and outcomes of therapeutic lines were recorded. The primary end-point was progression-free survival (PFS) in sunitinib rechallenge.

Results: Analyses included 52 patients; median age was 59 years, 75% were male, and 98% had clear-cell mRCC and prior nephrectomy. At sunitinib rechallenge versus first-line, patients had poorer performance (Karnofsky performance status 90-100: 30% versus 81%) and Memorial Sloan Kettering Cancer Centre prognostic risk (poor risk: 18% versus 3%). Overall, 20%, 65%, 12%, and 4% received sunitinib rechallenge as third-, fourth-, fifth-, and sixth-line therapy, respectively, at 14.6 months (median) after stopping initial treatment. With first-line sunitinib and rechallenge, median PFS was 18.4 and 7.9 months, respectively; objective response rate was 54% and 15%. Two of eight rechallenge responders had not achieved first-line response. Median overall survival was 55.9 months. The sunitinib rechallenge safety profile was as expected, with no new adverse events reported.

Conclusions: Sunitinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients. Disease progression with first-line sunitinib may not be associated with complete or irreversible resistance to therapy.
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http://dx.doi.org/10.1016/j.ejca.2016.04.003DOI Listing
July 2016

Predictive Value of NRAMP1 and HGPX1 Gene Polymorphism for Maintenance BCG Response in Non-muscle-invasive Bladder Cancer.

Anticancer Res 2016 Apr;36(4):1737-43

Department of Urology, Rouen University Hospital, Rouen, France Clinical Investigation Center, Inserm 6204, Onco-Urology Group, Rouen, France

Aim: To assess the potential predictive value of natural resistance-associated macrophage protein 1 (NRAMP1) and human glutathione peroxidase 1 (hGPX1) polymorphism in non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin (BCG) instillation, we conducted an original ancillary multicenter study.

Patients And Methods: We evaluated patients included in the multicenter URO-BCG 4 trial, who received three weekly instillations of one-third dose BCG every 6 months (group I) or two weekly instillations every 3 months (group II) for 3 years. For clinical evaluation we also evaluated tumor recurrence and muscle progression. NRAMP1 and hGPX1 polymorphism analyses were performed on blood DNA. NRAMP1 exon 15 and hGPX1 exon 1c were amplified using Type-it Microsatellite PCR Kit® for multiplex polymerase chain reaction.

Results: From June 2004 to April 2010, 146 randomized patients were included in this retrospective study. Blood samples were obtained from 107 patients. With 36 months of follow-up, 13.6% of patients had a tumor recurrence and muscle-invasive progression was observed in 4.3% of patients. Concerning NRAMP1 D543N polymorphism, patients with allele A had no tumor recurrence or muscle-invasive progression. No significant difference was observed in gene polymorphism distribution between groups I and II. Moreover, we did not observe any significant association of gene polymorphisms, tumor recurrence or muscle-invasive progression, event time and disease-free survival.

Conclusion: Our results suggest that no significant difference was found for NRAMP1 and hGPX1 gene polymorphisms associated with recurrence time, muscle invasion frequency and disease-free survival, nevertheless, we observed that the NRAMP1 D543N GG genotype group had a shorter time to tumor recurrence.
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April 2016

Morbidity-mortality conference for adverse events associated with totally implanted venous access for cancer chemotherapy.

Support Care Cancer 2016 Apr 10;24(4):1857-63. Epub 2015 Oct 10.

Department of Epidemiology and Public Health, Rouen University Hospital, 1 rue de Germont, 76031, Rouen cedex, France.

Purpose: Although considered safer than central venous catheters for administration of cancer chemotherapy, totally implanted venous access (TIVA) is associated with adverse events that may impair prognosis and quality of life of patients receiving chemotherapy. Our aim was to assess the feasibility and interest of surveillance of cancer chemotherapy TIVA-adverse events (AE), associated with morbidity-mortality conferences (MMCs) on TIVA-AE.

Methods: We performed a prospective interventional study in two hospitals (a university hospital and a comprehensive care center). For each cancer chemotherapy care pathway within each hospital, we set up surveillance of TIVA-AE and MMC on these events. Patients included in surveillance were those with a TIVA either placed or used for chemotherapy cycles in one of the participating wards. Feasibility of MMC was assessed by the number of MMC meetings that actually took place and the number of participants at each meeting. The interest of MMC was assessed by the number of TIVA-AE identified and analyzed, and the number and type of improvement actions selected and actually implemented.

Results: We recorded 0.41 adverse events per 1000 TIVA-day. MMCs were implemented in all care pathways, with sustained pluriprofessional attendance throughout the survey; 39 improvement actions were identified during meetings, and 18 were actually implemented.

Conclusions: Surveillance of TIVA-AE associated with MMC is feasible and helps change practices. It could be useful for improving care of patients undergoing cancer chemotherapy.
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http://dx.doi.org/10.1007/s00520-015-2969-1DOI Listing
April 2016

RE: Marginal Donors in Renal Transplantation.

Transplant Proc 2015 Jul-Aug;47(6):2081-2

Department of Urology and Renal Transplantation, Rouen University Hospital, France. Electronic address:

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http://dx.doi.org/10.1016/j.transproceed.2015.07.006DOI Listing
February 2016

TP53 and FGFR3 Gene Mutation Assessment in Urine: Pilot Study for Bladder Cancer Diagnosis.

Anticancer Res 2015 Sep;35(9):4915-21

Department of Urology, Rouen University Hospital, Rouen, France Clinical Investigation Center, Inserm 6204, Urological Cancerology, Rouen, France

Aim: To assess, in a prospective clinical research study, a new non-invasive and reliable test to accurately detect tumor protein 53 (TP53) and fibroblast growth factor receptor-3 (FGFR3) mutations in cells in urine.

Materials And Methods: TP53 mutations were analyzed using the functional analysis of separated allele in yeast (FASAY) method, which allows functional analysis of the P53 protein, and FGFR3 mutations were assessed with the SNaPshot system, detecting the eight most frequent point-mutations of this gene. Chi-square test or Fisher's exact test were used to compare TP53 and FGFR3 mutations in the tumors according to tumor stage and grade.

Results: TP53 and FGFR3 mutations in bladder tumors increased and decreased respectively with increasing tumor stage and cellular grade (p<0.05 and p<0.001, respectively). A total of 103 tumor/urinary sediment couples were analyzed. TP53 or FGFR3 mutations were observed in 76 tumors. The sensitivity for the detection of this type of mutation in urine was 46%, the specificity was 81%, the positive predictive value was 94% and the negative predictive value was 37%.

Conclusion: Our original data confirmed the feasibility of TP53 and FGFR3 mutation detection in urine sediment. These measurements, together with urine cytology, may increase tumor detection. The sensitivity of the TP53/FGFR3 phenotype test in the urine was less than 50% and was not able to replace standard cystoscopy in the diagnosis of bladder tumors.
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September 2015

The subclassification of papillary renal cell carcinoma does not affect oncological outcomes after nephron sparing surgery.

World J Urol 2016 Mar 7;34(3):347-52. Epub 2015 Jul 7.

Cancerology Committee of the French Association of Urology (CCAFU), Paris, France.

Objectives: To evaluate the oncological outcomes of papillary renal cell carcinoma (pRCC) following nephron sparing surgery (NSS) and to determine whether the subclassification type of pRCC could be a prognostic factor for recurrence, progression, and specific death.

Materials And Methods: An international multicentre retrospective study involving 19 institutions and the French network for research on kidney cancer was conducted after IRB approval. We analyzed data of all patients with pRCC who were treated by NSS between 2004 and 2014.

Results: We included 486 patients. Tumors were type 1 pRCC in 369 (76 %) cases and type 2 pRCC in 117 (24 %) cases. After a mean follow-up of 35 (1-120) months, 8 (1.6 %) patients experienced a local recurrence, 12 (1.5 %) had a metastatic progression, 24 (4.9 %) died, and 7 (1.4 %) died from cancer. Patients with type I pRCC had more grade II (66.3 vs. 46.1 %; p < 0.001) and less grade III (20 vs. 41 %; p < 0.001) tumors. Three-year estimated cancer-free survival (CFS) rate for type 1 pRCC was 96.5 % and for type 2 pRCC was 95.1 % (p = 0.894), respectively. Three-year estimated cancer-specific survival rate for type 1 pRCC was 98.4 % and for type 2 pRCC was 97.3 % (p = 0.947), respectively. Tumor stage superior to pT1 was the only prognostic factor for CFS (HR 3.5; p = 0.03).

Conclusion: Histological subtyping of pRCC has no impact on oncologic outcomes after nephron sparing surgery. In this selected population of pRCC tumors, we found that tumor stage is the only prognostic factor for cancer-free survival.
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http://dx.doi.org/10.1007/s00345-015-1634-0DOI Listing
March 2016

A difficult decision: what should we do when malignant tumours are diagnosed in patients supported by left ventricular assist devices?

Eur J Cardiothorac Surg 2015 Sep 18;48(3):e30-6. Epub 2015 Jun 18.

Department of Thoracic and Cardiovascular Surgery, Rouen University Hospital Charles Nicolle, Rouen, France Department of Urology, Andrology and Renal Transplantation, Rouen University Hospital Charles Nicolle, Rouen, France Department of General and Thoracic Surgery, Rouen University Hospital Charles Nicolle, Rouen, France Unit of Vascular Haemostasis, Rouen University Hospital Charles Nicolle, Rouen, France INSERM U1096, Rouen University Hospital, Rouen, France.

Objectives: Left ventricular assist devices (LVADs) are used as a bridge to heart transplantation. During the preimplantation or pretransplantation screening, malignant tumours can be discovered. Owing to the lack of guidelines, the management is difficult. We describe our perioperative approach and the patients' outcomes.

Methods: Between 2006 and 2014, 55 patients underwent implantation of HeartMate II LVAD. Five were diagnosed with malignant tumours: 2 renal, 2 lung and 1 breast tumours. The renal tumours were diagnosed during the preimplantation screening. An LVAD was implanted in both followed by partial nephrectomies 8 and 9 months later. The lung cancers were diagnosed after device implantation, a left pulmonary segmentectomy and a right upper sleeve lobectomy were performed. The breast cancer was diagnosed few months after support and a tumourectomy with lymphadenectomy was performed.

Results: Tumour resection was performed successfully in all patients. Prior to surgery haemostasis, device and heart function were evaluated. During surgery, haemodynamics and anticoagulation were monitored. Reoperations were necessary to evacuate haemothorax after lobectomy and an abdominal haematoma post-nephrectomy. After discussion with oncologists, 3 patients were relisted for heart transplantation. Two were successfully transplanted 2 and 3 years after partial nephrectomy with an actual survival of 56 and 59 months after the cancer diagnosis. The follow-up revealed no cancer recurrences.

Conclusions: Malignant tumours during support with LVAD can be successfully resected. A multidisciplinary evaluation in these high-risk patients is mandatory. After careful evaluation, regaining the patient's heart transplant candidacy is possible.
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http://dx.doi.org/10.1093/ejcts/ezv203DOI Listing
September 2015

Nephrectomy improves overall survival in patients with metastatic renal cell carcinoma in cases of favorable MSKCC or ECOG prognostic features.

Urol Oncol 2015 Aug 16;33(8):339.e9-15. Epub 2015 Jun 16.

Department of Urology, Bicetre Hospital, Paris XI University, Le Kremlin Bicêtre, France.

Objectives: The role of cytoreductive nephrectomy (CN) in the treatment of patients harboring metastatic renal cell carcinoma (mRCC) has become controversial since the emergence of effective targeted therapies. The aim of our study was to compare the overall survival (OS) between CN and non-CN groups of patients presenting with mRCC in the era of targeted drugs and to assess these outcomes among the different Memorial Sloan-Kettering Cancer Center (MSKCC) and The Eastern Cooperative Oncology Group (ECOG) performance status subgroups.

Methods And Materials: A total of 351 patients with mRCC at diagnosis recruited from 18 tertiary care centers who had been treated with systemic treatment were included in this retrospective study. OS was assessed by the Kaplan-Meier method according to the completion of a CN. The population was subsequently stratified according to MSKCC and ECOG prognostic groups.

Results: Median OS in the entire cohort was 37.1 months. Median OS was significantly improved for patients who underwent CN (16.4 vs. 38.1 months, P<0.001). However, subgroup analysis demonstrated that OS improvement after CN was only significant among the patients with an ECOG score of 0 to 1 (16.7 vs. 43.3 months, P = 0.03) and the group of patients with good and intermediate MSKCC score (16.8 vs. 42.4 months, P = 0.02). On the contrary, this benefit was not significant for the patients with an ECOG score of 2 to 3 (8.0 vs. 12.6 months, P = 0.8) or the group with poor MSKCC score (5.2 vs. 5.2, P = 0.9).

Conclusions: CN improves OS in patients with mRCC. However, this effect does not seem to be significant for the patients in ECOG performance status groups of 2 to 3 or poor MSKCC prognostic group.
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http://dx.doi.org/10.1016/j.urolonc.2015.05.014DOI Listing
August 2015