Abdel Rahmène Azzouzi

Association between estrogen and androgen receptor genes and prostate cancer risk

OBJECTIVE Prostate cancer (PC) is one of the principal causes of death among men. Steroid hormones are involved in normal prostate growth and carcinogenesis. The purpose of our study was to investigate the effects on PC risk of polymorphisms from three steroid hormone receptor genes: the androgen (AR), and the alpha (ESR1) and beta (ESR2) estrogen receptors. DESIGN AND METHODS The study was performed on a Caucasian population of 1045 PC patients and 814 controls. Using a logistic regression model, the different alleles and genotypes from those polymorphisms were analyzed according to case/control status, the tumor aggressiveness, and the age at onset. RESULTS A significant association between PC risk and the pooled 4/5, 5/6, and 6/6 genotypes of the GGGA repeat located in the first intron of ESR1 (odds ratio (OR)=3.00, 95% CI=1.32-6.82, P=0.008) was observed. When we stratified the cases, this association was confined to patients with a Gleason score of 2-4 (OR=8.34, 95% CI=2.91-23.91, P<0.0001) or late onset PC (OR=2.91, 95% CI=1.22-6.93, P=0.016). An association between a short AR CAG repeat (less than 17 repeats) was also observed among patients with late onset PC (OR=2.34, 95% CI=1.15-4.76, P=0.019). CONCLUSIONS These findings suggest that the GGGA repeat from ESR1 and the CAG repeat from AR may be associated with risk of late onset PC.

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

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.

Identification and validation of TGFBI as a promising prognosis marker of clear cell renal cell carcinoma

OBJECTIVE To identify prognostic biomarkers in clear cell renal cell carcinoma (ccRCC) using a proteomic approach. MATERIAL AND METHODS We performed a comparative proteomic profiling of ccRCC and normal renal tissues from 9 different human specimens. We assessed differential protein expression by iTRAQ (isobaric tagging reagent for absolute quantify) labeling with regard to tumor aggressiveness according to the stage, size, grade, and necrosis (SSIGN) score and confirmed our results using Western blot (9 patients) and immunohistochemistry (135 patients) analysis. RESULTS After proteomic analysis, 928 constitutive proteins were identified. Among these proteins, 346 had a modified expression in tumor compared with that of normal tissue. Pathway and integrated analyses indicated the presence of an up-regulation of the pentose phosphate pathway in aggressive tumors. In total, 14 proteins were excreted and could potentially become biomarkers. Overexpression of transforming growth factor, beta-induced (TGFBI) in ccRCC was confirmed using Western blot and immunohistochemistry analysis. A significant association was found between the presence of TGFBI expression with tumor category T3-4 (P<0.0001), Fuhrman grades III and IV (P<0.0001), tumor size>4cm (P<0.0001), presence of tumor necrosis (P<0.0001), nodal involvement (n = 0.009), metastasis (P = 0.012), SSIGN score≥5 (P<0.0001), cancer progression (P<0.0001), and cancer-specific death (P<0.0001). Cancer-specific survival was significantly better for patients with no cytoplasmic TGFBI expression (1-, 3-, 5-y cancer-specific survival of 94.7%, 87.8%, and 73.4% vs. 92.9%, 71.2%, and 49.8%, respectively; P<0.0001). CONCLUSION We identified 346 proteins involved in renal carcinogenesis and confirmed the presence of a metabolic shift in aggressive tumors. TGFBI was overexpressed in tumors with high SSIGN scores and was significantly associated with oncologic outcomes.

Impact of lower pole calculi in patients undergoing retrograde intrarenal surgery.

OBJECTIVE To assess if the presence of a lower pole stone (LPS) decreases the stone-free (SF) rate following retrograde intrarenal surgery (RIRS). The second purpose was to assess the result of RIRS for LPS and to identify predictors of SF status. PATIENTS AND METHODS We retrospectively analyzed 205 procedures in 162 patients with renal stones treated by RIRS between January 2010 and January 2013 at a single institute. The SF status was defined as no residual fragments. Independent-sample t-tests and Chi-square tests were used for comparisons of means and proportions, respectively, between patients with or without LPS. Logistic regression models were used to assess prognostic factors influencing SF status in cases of LPS. RESULTS LPS were present in 89 (54.9%) patients. There were no differences between patients with or without LPS regarding the mean operative time (p=0.77), the surgeons experience (p=0.522), the length of hospital stay (p=0.269), and the SF rate (p=0.224). SF status after RIRS in patients with or without LPS was 74.1% and 78% (p=0.224), respectively. In the case of LPS, the presence of multiple stones and a history of percutaneous nephrolithotomy (PCNL) were predictive factors for occurrence of residual fragments in univariate analysis (p=0.037 and p=0.015). In multivariable analysis, only the presence of multiple stones remained as a predictive factor (p=0.027; HR=3.2), whereas a trend was observed when there was a history of PCNL (p=0.07; HR=3). CONCLUSION The presence of a LPS does not alter the SF rate of RIRS even in cases of early experience. RIRS for LPS appears to be an effective technique, but special attention should be given to patients with multiple stones and/or a history of PCNL.

Overall mortality after radical nephrectomy in patients aged over 80 years with renal cancer : A retrospective study on preoperative prognostic factors

Objectives:  To evaluate the overall survival postnephrectomy for renal cancer for patients aged over 80 years, and to identify preoperative prognostic factors that might influence therapeutic strategies.

The role of surgery for metastatic renal cell carcinoma in the era of targeted therapies

PurposeWith the emergence of targeted therapies, the indications of cytoreductive nephrectomy have to be redefined. This review article presents the evidence data guiding our current indications of surgery in the management of metastatic renal cell carcinoma (mRCC) in the era of targeted therapies.MethodsA nonsystematic review of the electronic databases PubMed and MEDLINE from 1980 to 2012 was performed and limited to English language.ResultsTwo studies based on immunotherapy (EORTC 30947 and SWOG 8949) were at the origins of the recommendations on initial nephrectomy for patients with mRCC. Since the introduction of angiogenesis inhibitors, there is still no high-level evidence from prospective studies assessing the indication of surgery for mRCC. However, surgery still has its importance in the management of primary tumors and metastasis with the objective of an optimal balance between morbidity, quality of life, and survival. The treatment sequence between surgery and targeted therapies is still to be established and two randomized prospective studies were then specifically designed and are currently recruiting.ConclusionsPreliminary evidence data from retrospective series seem to be in favor of a benefit of surgery for patients with good and intermediate prognosis. However, patients’ inclusions in current prospective studies are highly recommended to clearly precise nephrectomy’s indications.

Thrombose partielle du corps caverneux. Faut-il rechercher systématiquement une anomalie de la coagulation ?

Resume Les auteurs rapportent un cas de thrombose partielle d’un corps caverneux, dont le diagnostic a ete confirme par l’imagerie IRM. Chez ce patient, un neuroleptique avait ete prescrit quelques jours avant la thrombose et le bilan de coagulation a mis en evidence une resistance a la proteine C. Un traitement conservateur associant heparine de bas poids moleculaire et aspirine a ete institue. Trois mois apres, la symptomatologie douloureuse avait disparu alors qu’une image sequellaire de thrombose persistait a l’IRM. L’etiologie de la thrombose du corps caverneux, cas rare, reste inconnue. Le traitement neuroleptique est incrimine. A partir de leur observation, les auteurs soulignent l’interet de realiser systematiquement un bilan de thrombose.

Partial nephrectomy after selective embolization of tumor vessels in a hybrid operating room: A new approach of zero ischemia in renal surgery

It is established that partial nephrectomy is the standard of care for tumors confined to the kidney. Achieving a partial nephrectomy without renal ischemia and limiting operative bleeding is the subject of numerous researches. Since 2010, hybrid operating rooms have been used to perform both interventional radiology and surgical procedures at the same place and time. We used this latest technology to treat 3 patients with localized kidney tumors. The tumors were of moderate complexity and all were treated after immediate hyperselective embolization by laparoscopic surgery without dissection and clamping of the renal pedicle. The embolization of tumor vessels could be performed using image‐stitching software. After embolization, operative time was 50, 70 and 80 minutes and blood loss was less than 100 ml for each case. Postoperative control 3D arteriography confirmed the respect of the vascularization of the healthy renal parenchyma. No postoperative complications occurred. Combined approach including hyperselective embolization and partial nephrectomy in the same time in a dedicated operating room is a new approach of zero ischemia during partial nephrectomy which reduces the difficulty of the surgery, limits injury to the kidney and increases patient safety. J. Surg. Oncol. 2016;113:135–137.

Impact de l'obésité sur le PSA lors du dépistage du cancer de la prostate

Resume But L’obesite est associee a des modifications seriques des taux d’androgenes et d’oestrogenes qui pourraient moduler le metabolisme prostatique. L’objectif de ce travail etait de rechercher un lien entre le taux de PSA et le degre d’obesite sur une population candidate au depistage du cancer de la prostate afin de determiner si une adaptation du taux de PSA avant biopsie devrait etre exploree. Materiel Lors d’une campagne de depistage dans un arrondissement francais, les resultats d’un PSA serique et de l’index de masse corporelle (IMC) etait disponible chez 541 hommes. Ces hommes etaient repartis dans 4 groupes de corpulence : Normal (IMC Resultats Le PSA moyen pour chaque groupe diminuait de maniere inversement proportionnelle a l’IMC, avec un taux moyen de 3.7, 2.9, 2.6 et 1.5 pour les groupes Normal, Surpoids, Obesite I et Obesite II+III respectivement. Il existait une difference significative entre ces groupes (p = 0.03). Il existait egalement une correlation inverse entre IMC et PSA (r = 0.1, p = 0.01). Conclusion Dans une population soumise au depistage, le PSA est d’autant plus faible que l’IMC est grand. Une adaptation du seuil de depistage du PSA selon l’IMC devrait etre exploree.

Correlation between prostate volume and single nucleotide polymorphisms implicated in the steroid pathway

ObjectivesA few preliminary studies have suggested a link between some genetics variants and benign prostatic hyperplasia (BPH). Our goal was to study the link between a set of single nucleotide polymorphisms (SNPs) implicated in the steroid pathway and accurate measurement of prostate volume in a cohort of men who underwent radical prostatectomy.MethodsClinical and pathological data including prostate weight were obtained from 611 Caucasian patients with small volume, localized prostate cancer treated by radical prostatectomy. Patients were genotyped for 90 SNPs located inside or nearby genes implicated in the steroid pathway (Sequenom iPLEX). Correlation between prostate weight and genotypes from each SNP was studied by analysis of covariance, adjusted on age and tumor stage. A Bonferroni correction was applied, and the SNPs implicated were then incorporated in a multivariable model.Results and limitationsSeven SNPs located in or nearby genes implicated in steroid hormone metabolism were significantly associated with prostate volume: HSD17B2 (rs1119933), ESR2 (rs8006145), SULT2B1 (rs279451), NQO1 (rs2917670), ESR1 (rs1569788), GSTP1 (rs1138272), and CYP19A1 (rs17523880). Significant association was maintained after multivariate analysis for four SNPs, indicating their independent association with prostate volume. The power of the association of each SNP with prostate volume was comparable to the effect of age. The strongest associations were found with variants in ESR1, ESR2, HSD17B2, and CYP19A1 genes, indicating a potential role of the estrogen signaling pathway in genesis of BPH.ConclusionsOur results are in favor of an implication of estrogen biotransformation and signaling pathways in the pathophysiology of BPH.