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E U R O P E A N U R O L O G Y 6 0 ( 2 0 1 1 ) 3 6 6 – 3 7 3
avai lable at www.sciencedirect .com
journal homepage: www.europeanurology.com
Kidney Cancer
Renal Cell Carcinoma (RCC) in Patients With End-Stage Renal
Disease Exhibits Many Favourable Clinical, Pathologic, and
Outcome Features Compared With RCC in the General Population
Yann Neuzillet a,*, Xavier Tillou b, Romain Mathieu c, Jean-Alexandre Long d, Marc Gigante e,Philippe Paparel f, Laura Poissonnier g, Herve Baumert h, Bernard Escudier i, Herve Lang j,Nathalie Rioux-Leclercq k, Pierre Bigot l, Jean-Christophe Bernhard m, Laurence Albiges i,Laurence Bastien n, Jacques Petit b, Fabien Saint b, Franck Bruyere o, Jean-Michel Boutin o,Nicolas Brichart o, Georges Karam p, Julien Branchereau p, Jean-Marie Ferriere m,Herve Wallerand m, Sebastien Barbet m, Hicham Elkentaoui m, Jacques Hubert q, Benoit Feuillu q,Pierre-Etienne Theveniaud q, Arnauld Villers r, Laurent Zini r, Aurelien Descazeaux s,Morgan Roupret t, Benoit Barrou t, Karim Fehri t, Thierry Lebret a, Jacques Tostain e,Jean-Etienne Terrier e, Nicolas Terrier d, Lucille Martin u, Fabrice Dugardin v, Ismael Galliot v,Frederic Staerman w, Marie-Dominique Azemar w, Jacques Irani x, Baptiste Tisserand x,Marc-Olivier Timsit y, Federico Sallusto z, Pascal Rischmann z, Laurent Guy A, Antoine Valeri B,Charles Deruelle B, Abdel-Rahmene Azzouzi l, Denis Chautard l, Arnaud Mejean y,Laurent Salomon n, Jerome Rigaud p, Christian Pfister v, Michel Soulie z, Francois Kleinclauss u,Lionel Badet g, Jean-Jacques Patard C, the members of the Comite de Transplantationde l’Association Francaise d’Urologie, the Comite de Cancerologie de l’AssociationFrancaise d’Urologie
a Department of Urology, Foch Hospital, Suresnes, Franceb Department of Urology, Amiens University Hospital, Amiens, Francec Department of Urology, Pontchaillou University Hospital, Rennes, Franced Department of Urology, Michallon University Hospital, Grenoble, Francee Department of Urology, Saint-Etienne University Hospital, Saint Etienne, Francef Department of Urology, Lyon University Hospital, Pierre-Benite, Franceg Department of Urology, Edouard Herriot University Hospital, Lyon, Franceh Department of Urology, Saint Joseph Hospital, Paris, Francei Department of Oncology, Gustave Roussy Institute, Villejuif, Francej Department of Urology, Strasbourg University Hospital, Strasbourg, Francek Department of Pathology, Pontchaillou University Hospital, Rennes, Francel Department of Urology, Angers University Hospital, Angers, Francem Department of Urology, Pellegrin University Hospital, Bordeaux, Francen Department of Urology, Henri Mondor University Hospital, Creteil, Franceo Department of Urology, Bretonneau University Hospital, Tours, Francep Department of Urology, Hotel Dieu University Hospital, Nantes, Franceq Department of Urology, Brabois University Hospital, Nancy, Francer Department of Urology, Claude Huriez University Hospital, Lille, France
* Corresponding author. Hospital Foch, Department of Urology, 40, rue Worth, 92150 Suresnes,France. Tel. +33 1 46 25 21 75.E-mail address: y.neuzillet@hopital-foch.org (Y. Neuzillet).
0302-2838/$ – see back matter # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2011.02.035
E U R O P E A N U R O L O G Y 6 0 ( 2 0 1 1 ) 3 6 6 – 3 7 3 367
s Department of Urology, Dupuytren University Hospital, Limoges, Francet Department of Urology, La Pitie University Hospital, Paris, Franceu Department of Urology, Saint Jacques University Hospital, Besancon, Francev Department of Urology, Charles Nicolle University Hospital, Rouen, Francew Department of Urology, Robert Debre University Hospital, Reims, Francex Department of Urology, La Miletrie University Hospital, Poitiers, Francey Department of Urology, Necker University Hospital, Paris, Francez Department of Urology, Rangueil University Hospital, Toulouse, FranceA Department of Urology, Gabriel Montpied University Hospital, Clermont-Ferrand, FranceB Department of Urology, La Cavale Blanche University Hospital, Brest, FranceC Department of Urology, Bicetre Hodpital, Paris XI University, France
Article info
Article history:Accepted February 20, 2011Published online ahead ofprint on March 2, 2011
Keywords:
End-stage renal disease
Pathology
Prognosis
Renal cell carcinoma
Transplantation
Abstract
Background: Patients with end-stage renal disease (ESRD) are at risk of developing
renal tumours.
Objective: Compare clinical, pathologic, and outcome features of renal cell carci-
nomas (RCCs) in ESRD patients and in patients from the general population.
Design, setting, and participants: Twenty-four French university departments of
urology participated in this retrospective study.
Intervention: All patients were treated according to current European Association
of Urology guidelines.
Measurements: Age, sex, symptoms, tumour staging and grading, histologic sub-
type, and outcome were recorded in a unique database. Categoric and continuous
variables were compared by using chi-square and student statistical analyses.
Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods.
Results and limitations: The study included 1250 RCC patients: 303 with ESRD and
947 from the general population. In the ESRD patients, age at diagnosis was younger
(55 � 12 yr vs 62 � 12 yr); mean tumour size was smaller (3.7 � 2.6 cm vs
7.3 � 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary
tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs
37%) and advanced T categories (�3) were more rare (10% vs 42%). Consistently, nodal
invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in
ESRD patients. After a median follow-up of 33 mo (range: 1–299 mo), 13 ESRD patients
(4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate
analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage,
high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse
predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained
independent CSS predictors in multivariate analysis. The limitation of this study is
related to the retrospective design.
Conclusions: RCC arising in native kidneys of ESRD patients seems to exhibit many
favourable clinical, pathologic, and outcome features compared with those diag-
nosed in patients from the general population.sociation of Urology. Published by Elsevier B.V. All rights reserved.
# 2011 European As1. Introduction
Renal cell carcinoma (RCC) is the third most common
urologic cancer. In specific populations, the risk of developing
RCC is increased due to genetic predispositions such as von
Hippel-Lindau (VHL) or Bourneville’s tuberous sclerosis
diseases [1]. Acquired cystic kidney disease (ACKD), which
is commonly associated with end-stage renal disease (ESRD),
also has been reported as a condition predisposing patients to
an increased risk of RCC [2]. However, data from the literature
are limited to a few small and noncomparative RCC series in
dialysed patients [3–8] and in renal transplant patients
[9–16]. These studies have individually suggested specific
clinical, pathologic, or outcome features for ESRD native renal
tumours. Moudouni et al, for example, have demonstrated in
10 transplant recipients that incidental diagnosis and
papillary RCC subtype accounted for two-thirds and 50% of
native kidney RCC cases, respectively [14]. Similarly,
Schwartz et al in a series with 25 transplant patients
suggested that low-stage, incidentally diagnosed, and papil-
lary RCCs were predominant in this population and that
ACKD played a predisposing role [10].
E U R O P E A N U R O L O G Y 6 0 ( 2 0 1 1 ) 3 6 6 – 3 7 3368
It seemed justified to conduct a multicentre, compre-
hensive analysis of RCC cases occurring in ESRD and/or
kidney transplant patient populations and to compare
patients’ epidemiologic, pathologic, and outcome features
with those of patients in the general population with
sporadic RCC tumours.
2. Materials and methods
2.1. Data collection and patient management
This retrospective study included data from 24 academic centres in France.
After approval by institutional review boards at all centres, patients with
RCCs arising in the context of ESRD (defined as chronic renal failure treated
by dialysis or transplantation) and/or who underwent a renal transplan-
tation were identified at each centre. The following variables were
recorded: age, sex, symptoms at diagnosis, Eastern Cooperative Oncology
Group performance status (ECOG PS), duration of exposure to ESRD,
presence of ACKD (defined by more than five cysts on each native kidney
assessed by computed tomography [CT] or ultrasound imaging [2]), mode
and duration of dialysis, renal transplantation, tumour staging and
grading, histologic subtype, renal transplant, cancer-specific survival
(CSS), and overall survival. For ESRD patients, surgical treatment of
localised RCC was radical nephrectomy. For the general population, radical
nephrectomy or nephron-sparing surgery was performed according to
tumour characteristics, centre preferences, and current European
Association of Urology guidelines when appropriate. In ESRD patients,
monitoring of native kidneys included one annual CT or ultrasound
imaging analysis. In case of RCCs arising in transplant recipients, it was the
general policy of most centres in recent years to switch to a regimen based
on mammalian target of rapamycin.
Exclusion criteria were RCCs diagnosed before ESRD, histologically
proven transitional cell carcinoma of the upper urinary tract for 2
patients, and missing data for 13 patients. This cohort was compared
with a no-ESRD control group operated in France during the same period
(1985–2009) and identified from a multicentre surgical database.
2.2. Tumour classification
Tumour stage was determined according to the 2002 TNM classification
[17]. Histologic subtype was recorded according to the 2004 World
Health Organisation classification [18]. Tumours were graded according
to the Fuhrman grading scheme by pathologists at each institution [19].
2.3. Statistical methods
Variables of interest in both groups were compared by using chi-square
(or Fisher) and t tests for categoric and continuous variables,
respectively. The Kaplan-Meier method and the Cox proportional
hazards model were used for uni- and multivariate analysis, with
RCC-specific survival as an end point. In univariate analysis, a p value of
0.05 was used to select explanatory variables for multivariate analysis.
Results were given as hazard ratios and 95% confidence intervals. A
p value <0.05 was considered significant. All tests were carried out with
SPSS v.16 (IBM Corp., Somers, NY, USA).
3. Results
3.1. Characteristics of the renal cell carcinoma study
population
The study included 1250 patients with renal tumours. The
ESRD cohort was composed of 303 cases that were
identified in 206 men (76.3%) and 64 women (23.7%).
Transplant and nontransplant patients accounted for 213
cases (70.3%) and 90 cases (29.7%), respectively. ACKD
was found in 83 ESRD patients (30.7%). Mean age at
ESRD diagnosis was 44 � 16 yr. Mean delay between ESRD
diagnosis and beginning of replacement therapy was 46 � 39
mo. Forty-one patients (15.2%) were treated with haemodia-
lysis, and 229 patients (84.8%) were treated with peritoneal
dialysis. Renal transplantation was performed after 71 � 64
mo of haemodialysis. Mean delay between start of haemo-
dialysis and RCC diagnosis in nontransplant ESRD patients was
65 � 60 mo. Total duration of exposure to ESRD before RCC
diagnosis was 104� 96 mo. Tumours were discovered
incidentally in 264 cases (87%), including 5 cases by pathologic
examination.
The control group was composed of 947 RCC cases in 586
men (61.9%) and 361 women (38.1%). Median follow-up for
the entire population and for ESRD and non-ESRD groups
were 33 mo (range: 1–299), 36 mo (range: 1–277), and 38
mo (range: 1–299) ( p > 0.05), respectively. At the end of
follow-up, 274 patients (21.9%) had died from cancer.
3.2. Comparison of renal cell carcinoma groups with and
without end-stage renal disease
In the ESRD group, RCC occurred in younger patients
(55 � 12 yr vs 62 � 12 yr; p < 0.0001) and more often in male
patients (3.2 men vs 1.6 women; p < 0.0001). Tumours were
more frequently discovered incidentally in the ESRD group
(87% vs 44%; p < 0.0001), and local symptoms (12% vs 31%;
p < 0.0001) or systemic symptoms (0% vs 24%; p < 0.0001)
were more rare in the ESRD group. Good ECOG PS was more
frequent in the ESRD group (76% vs 63%; p < 0.0001).
Mean RCC tumour size was smaller in the ESRD group
(3.7 � 2.6 cm vs 7.3� 3.8 cm; p < 0.0001), and rate of ad-
vanced T category (�3) was decreased in the ESRD group (10%
vs 42%; p < 0.0001). Moreover, nodal invasion (3% vs 12%;
p < 0.0001) and metastatic disease (2% vs 15%; p < 0.0001)
were rare in ESRD patients. Clear cell histology was less
frequent (59% vs 88%; p < 0.0001) and papillary RCC rate was
higher (37% vs 7%; p < 0.0001) in the ESRD group than in the
general RCC population. Finally, low Fuhrman grade tumours
were frequently associated with ESRD ( p < 0.0001). Main
comparison data are summarised in Table 1.
3.3. Predictive factors for survival in uni- and multivariate
analyses
Cancer-specific mortality rate was decreased (4.3% vs
27.6%; p < 0.0001) in ESRD patients. RCC-specific survival
time was longer in ESRD patients than in non-ESRD patients
(log-rank test, p < 0.0001; Fig. 1). Five-year survival rates
were 90.1% and 69.0% in ESRD and non-ESRD patients,
respectively ( p < 0.0001). This survival advantage for ESRD
patients remained even after stratifying for histologic
subtype (Fig. 2a and 2b).
In univariate analysis, histologic subtype ( p = 0.006),
symptoms at diagnosis, poor performance status (PS),
advanced TNM stage, high Fuhrman grade, large tumour
Table 1 – Comparison of clinical, pathologic, and outcome features of end-stage renal disease (ESRD) and non-ESRD renal cell carcinomapatients
Variables ESRD RCC patientsn = 303
Non-ESRD RCC patients,n = 947
p value
Age at diagnosis, yr, mean � SD 55 � 12 62 � 12 <0.0001
Male gender, no. (%) 231 (76.5) 586 (61.9) <0.0001
Incidental diagnosis, no. (%) 264 (87) 417 (44) <0.0001
Local symptoms at diagnosis, no. (%) 39 (13) 303 (32) <0.0001
Systemic symptoms at diagnosis, no. (%) 0 227 (24) <0.0001
Good ECOG PS (= 0), no. (%) 230 (76) 597 (63) <0.0001
Tumour size, cm, mean � SD 3.7 � 2.6 7.3 � 3.8 <0.0001
Papillary histology, no. (%) 112 (37) 66 (7) <0.0001
Clear cell histology, no. (%) 179 (59) 843 (89) <0.0001
Fuhrman grade �2, no. (%) 206 (68) 398 (42) <0.0001
T category �2, no. (%) 273 (90) 549 (58) <0.0001
N category �1, no. (%) 9 (3) 114 (12) <0.0001
M category = 1, no. (%) 6 (2) 142 (15) <0.0001
Death from cancer, no. (%) 13 (4.3) 261 (27.6) <0.0001
ECOG PS = Eastern Cooperative Oncology Group performance status; RCC = renal cell carcinoma; SD = standard deviation.
[()TD$FIG]
Fig. 1 – Comparison of renal cell carcinoma (RCC)–specific survival time for end-stage renal disease (ESRD) and non-ESRD patients.
E U R O P E A N U R O L O G Y 6 0 ( 2 0 1 1 ) 3 6 6 – 3 7 3 369
size, and non-ESRD diagnosis context were all adverse
predictors for survival ( p < 0.0001) (Table 2). However,
only symptoms at diagnosis, PS, TNM stage, and Fuhrman
grade remained independent CSS predictors in multivariate
analysis (Table 3).
4. Discussion
It is now well established from epidemiologic data that ESRD
is a predisposing environment for native kidney RCC
development. Our study confirms that RCC arising in native
kidneys of ESRD patients exhibits many favourable features.
In the present series, asymptomatic, small, low-stage, and
low-grade tumours were more frequent in ESRD patients
than in the general RCC population. Moudouni et al. [14],
Ianhez et al. [13], and Neuzillet et al. [12] reported a grade
distribution similar to that observed in the general popula-
tion, whereas in other series, low-grade tumours were
predominant [10,11]. Our study, which represents the largest
series of RCC in ESRD patients, confirms the predominance of
low-grade tumours in ESRD-associated tumours.
Similarly, we noticed a very small proportion of tumours
with nodal (3%) or metastatic (2%) disease. Consistently, in
previously published studies, the incidence of distant
metastases in transplant and dialysed patients was 0–10%
[11,13] and 0–12.5% [6,7], respectively. This may be due
[()TD$FIG]
Fig. 2 – Comparison of renal cell carcinoma (RCC)–specific survival time stratified by histologic subtype (a) for clear cell RCCs arising in end-stage renaldisease (ESRD) and non-ESRD patients and (b) for papillary RCCs arising in ESRD and non-ESRD patients.
E U R O P E A N U R O L O G Y 6 0 ( 2 0 1 1 ) 3 6 6 – 3 7 3370
either to the constitutional low aggressiveness of ESRD
tumours, related in part to their favourable histologic
phenotype, or to early diagnosis of renal tumours in the
ESRD setting. In our series, the incidental RCC diagnosis rate
was in 87% compared with 44% in the general population.
Such a high rate (75–100%) of incidental diagnosis had
already been reported [3,12]. We also reported more
pronounced incidence for the male gender among ESRD
patients than in the general RCC population. We hypothesise
that this finding may be related to the epidemiology of ESRD
[20]. Even though patients suffered from chronic kidney
failure, PS was clearly more favourable in the ESRD RCC
population.
The more specific difference between ESRD and
sporadic RCCs is histologic profile. Clear cell carcinomas
were less frequent (59% vs 89%) and, in parallel, papillary
carcinomas were more frequent (37%) than in the general
population (7%). In previous ESRD RCC series, the
Table 2 – Prognostic factors in 1250 renal cell carcinoma patientsincluding 303 end-stage renal disease cases in univariate analysis
Variables p value HR (95% CI)
Histologic subtype
(clear cell vs non–clear
cell RCC)
0.006 2.08 (1.37–3.14)
Tumour size >6 cm <0.0001 4.14 (3.13–5.47)
Symptoms at diagnosis <0.0001 8.25 (5.83–11.68)
ECOG PS �1 <0.0001 3.94 (3.15–4.92)
T category �3 <0.0001 7.15 (5.42–9.44)
N category �1 <0.0001 3.22 (2.66–3.91)
M category = 1 <0.0001 8.22 (6.36–10.62)
Fuhrman grade �3 <0.0001 4.65 (3.44–6.28)
Non-ESRD RCC <0.0001 4.74 (2.71–8.29)
CI = confidence interval; ECOG PS = Eastern Cooperative Oncology Group
performance status; ESRD = end-stage renal disease; HR = hazard ratio;
RCC = renal cell carcinoma.
Table 3 – Prognostic factors in 1250 renal cell carcinoma patientsincluding 303 end-stage renal disease cases in multivariateanalysis
Variables p value HR (95% CI)
T category �3 <0.0001 2.4 (1.8–3.3)
N category �1 0.004 1.4 (1.7–2.3)
M category = 1 <0.0001 3.0 (2.3–4.0)
ECOG PS �1 <0.0001 1.8 (1.4–2.4)
Presence of symptoms
at diagnosis
<0.0001 2.7 (1.8–4.0)
Fuhrman grade �3 <0.0001 1.8 (1.3–2.5)
ESRD tumours 0.58 NA
CI = confidence interval; ECOG PS = Eastern Cooperative Oncology Group
performance status; ESRD = end-stage renal disease; HR = hazard ratio.
E U R O P E A N U R O L O G Y 6 0 ( 2 0 1 1 ) 3 6 6 – 3 7 3 371
frequency of papillary RCC ranged from 23% to 50%
[12,14]. This finding is not likely to be explained by the
mode of diagnosis of ESRD RCC tumours. It suggests,
together with the presence of AKCD, that molecular
pathways distinct from the VHL/hypoxia-inducible factor/
vascular endothelial growth factor pathways are involved
in such tumours.
We demonstrated that the presence of ESRD, besides
usual prognostic factors such as TNM stage, tumour size,
Fuhrman grade, PS, and histologic subtype, was a favour-
able prognostic factor in univariate analysis. However, it
disappeared together with histologic subtype in multivari-
ate analysis. This finding means that the general favourable
outcome of ESRD RCC tumours is explained at least in part
by the mode of diagnosis of such tumours. This is consistent
again with published data reporting that incidental
diagnosis was more frequent in the ESRD setting
[3,12,21]. Notably, several studies have shown that
patients with ESRD, especially those with kidney trans-
plant, were more likely to have an abdominal imaging
examination [22,23]. The transplant–nontransplant ratio
that we observed in our series certainly favours this latter
hypothesis.
ESRD RCC is a unique model for identifying molecular
pathways leading to renal carcinogenesis; however, the
extent to which basic science information that can be
derived from this model is useful for understanding
conventional clear cell or papillary RCC is not clear. Up to
now, ACKD has been the main hypothesis for explaining the
epidemiology of RCC in ESRD patients. ACKD incidence
increases with dialysis time reaching 90% after 5–10 yr [2].
In this study, patients were transplanted after 71 � 64 mo of
haemodialysis, and mean duration of haemodialysis in
nontransplant patients was 65 � 60 mo. The incidence of
ACKD observed in this study was in accordance with these
durations. Cheuk et al suggested that in atypical epithelial
proliferations associated with ACKD, some chromosomal
aberrations, including chromosome 7 gains, may represent
early neoplastic lesions [24]. Hori et al have shown that
oxidative stress was more intense in ESRD RCCs than in
sporadic cases [25]. However, the intimate molecular
mechanisms leading to ACKD in the context of ESRD are
largely hypothetical and further malignant transformation is
even less understood. Moreover, the papillary–clear cell
histology ratio in the ESRD setting has not been explained
sufficiently to date. Recently, Pan et al performed immuno-
histochemical and molecular genetic analyses in 11 tumours,
including nine ACKD-associated RCCs, from three patients
with ACKD [26]. Based on immunohistochemical and molec-
ular analysis, tumours did not correspond to any usual form of
renal cortical epithelial neoplasm. Among 14 ESRD RCC cases,
Inoue et al found VHL gene mutation in three of eight clear cell
carcinomas and in no ACKD-associated RCCs [27]. A particular
clinical setting, a specific histologic profile, and certain
immunophenotypic and genetic characteristics support the
concept of ACKD-associated RCC as a unique neoplasm [26].
Ikeda et al showed that cell proliferation was less active in the
ACKD-associated RCC than in sporadic cases [28]. Finally, some
specific molecular pathways have been mentioned, including
hepatocyte growth factor, activated B-cell lymphoma 2, and c-
met for explaining renal cyst formation and subsequent tumour
transformation [29]. In summary, there are arguments for
supporting specific oncogenesis mechanisms in ESRD RCC
tumours; however, these arguments are inconclusive and need
further examination.
We acknowledge some limitations of our study that are
inherent in any retrospective study. For example, the
exhaustive identification of RCC cases in our ESRD popula-
tion may be questioned. Some RCC cases possibly could
have been managed in departments of urology distinct from
the transplantation centre. For logistical reasons, no central
pathology review has been performed. Consequently, new
entities that have been recently identified in ESRD have not
been taken into account [4,30]. Moreover, we were not able
to provide information about transformation of ACKD cysts
into RCCs and whether or not RCC was observed outside
cystic lesions. Finally, no molecular analysis has been
conducted from our specimens to date.
5. Conclusions
This study is the first comparing a large series of RCCs in
ESRD patients with those arising in the general population
and shows that these cancers are more often asymptomatic,
E U R O P E A N U R O L O G Y 6 0 ( 2 0 1 1 ) 3 6 6 – 3 7 3372
of lower stage and grade, and thus have a better prognosis.
The extent to which a relatively indolent outcome is due
only to the mode of diagnosis and not to specific ESRD-
related molecular pathways is still to be determined. The
more important frequency of papillary tumours in this
model also deserves further basic science investigation.
Author contributions: Yann Neuzillet had full access to all the data in the
study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Neuzillet, Patard, Badet.
Acquisition of data: Neuzillet, Tillou, Mathieu, Long, Gigante, Paparel,
Poissonnier, Bigot, Bastien, Brichart, Branchereau, Elkentaoui, Theveniaud,
Descazeaux, Fehri, Terrier, Martin, Galliot, Azemar, Tisserand, Timsit,
Sallusto, Guy, Deruelle.
Analysis and interpretation of data: Neuzillet.
Drafting of the manuscript: Neuzillet.
Critical revision of the manuscript for important intellectual content: Patard.
Statistical analysis: Neuzillet, Patard.
Obtaining funding: None.
Administrative, technical, or material support: Baumert, Escudier, Lang,
Rioux-Leclercq, Bernhard, Albiges, Petit, Saint, Bruyere, Boutin, Karam,
Ferriere, Wallerand, Barbet, Hubert, Feuillu, Villers, Zini, Descazeaux,
Roupret, Barrou, Lebret, Tostain, Terrier, Dugardin, Staerman, Irani,
Timsit, Sallusto, Rischmann, Guy, Valeri, Azzouzi, Chautard, Mejean,
Salomon, Rigaud, Pfister, Soulie, Kleinclauss, Badet, Patard.
Supervision: Baumert, Escudier, Lang, Rioux-Leclercq, Bernhard, Albiges,
Petit, Saint, Bruyere, Boutin, Karam, Ferriere, Wallerand, Barbet, Hubert,
Feuillu, Villers, Zini, Descazeaux, Roupret, Barrou, Lebret, Tostain, Terrier,
Dugardin, Staerman, Irani, Timsit, Sallusto, Rischmann, Guy, Valeri,
Azzouzi, Chautard, Mejean, Salomon, Rigaud, Pfister, Soulie, Kleinclauss,
Badet, Patard.
Other (specify): None.
Financial disclosures: I certify that all conflicts of interest, including
specific financial interests and relationships and affiliations relevant to the
subject matter or materials discussed in the manuscript (eg, employment/
affiliation, grants or funding, consultancies, honoraria, stock ownership or
options, expert testimony, royalties, or patents filed, received, or pending),
are the following: None.
Funding/Support and role of the sponsor: None.
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