Overall survival and oncological outcomes after partial nephrectomy and radical nephrectomy for cT2a renal tumors: A collaborative international study from the French kidney cancer research network UroCCR.

BACKGROUND: Partial nephrectomy (PN) is recommended as first-line treatment for cT1 stage kidney tumors because of a better renal function and probably a better overall survival than radical nephrectomy (RN). For larger tumors, PN has a controversial position due to lack of evidence showing good cancer control. The aim of this study was to compare the results of PN and RN in cT2a stage on overall survival and oncological results. METHOD: A retrospective international multicenter study was conducted in the frame of the French kidney cancer research network (UroCCR). We considered all patients aged≥18 years who underwent surgical treatment for localized renal cell carcinoma (RCC) stage cT2a (7.1-10cm) between 2000 and 2014. Cox and Fine-Gray models were performed to analyze overall survival (OS), cancer specific survival (CSS) and cancer-free survival (CFS). Comparison between PN and RN was realized after an adjustment by propensity score considering predefined confounding factors: age, sex, tumor size, pT stage of the TNM classification, histological type, ISUP grade, ASA score. RESULTS: A total of 267 patients were included. OS at 3 and 5 years was 93.6% and 78.7% after PN and 88.0% and 76.2% after RN, respectively. CSS at 3 and 5 years was 95.4% and 80.2% after PN and 91.0% and 85.0% after RN. No significant difference between groups was found after propensity score adjustment for OS (HR 0.87, 95% CI: 0.37-2.05, P=0.75), CSS (HR 0.52, 95% CI: 0.18-1.54, P=0.24) and CFS (HR 1.02, 95% CI: 0.50-2.09, P=0.96). CONCLUSION: PN seems equivalent to RN for OS, CSS and CFS in cT2a stage kidney tumors. The risk of recurrence is probably more related to prognostic factors than the surgical technique. The decision to perform a PN should depend on technical feasibility rather than tumor size, both to imperative and elective situation. LEVEL OF EVIDENCE: 4.

Preliminary results of a new tool to evaluate cavernous body fibrosis following radical prostatectomy: penile elastography.

Development of cavernous tissue fibrosis due to neurovascular bundle damage during radical prostatectomy has been shown in many trials with invasive methods. In this study, we evaluated the changes in cavernous tissue elasticity by elastography in patients who underwent radical prostatectomy with or without neurovascular bundle preservation. Data from 65 patients underwent open retropubic radical prostatectomy between April 2014 and December 2015 was collected prospectively. Patients were grouped with respect to nerve-sparing status (non-, unilateral, and bilateral nerve sparing). International Index of Erectile Function scores, penile lengths, and elasticity scores were recorded at preoperative and postoperative follow-up visits (at 3rd and 6th months). The primary endpoint of the study was to evaluate the changes of the elasticity scores in all groups. Elasticity scores were measured with real-time elastography by a single experienced radiologist. Mean age, baseline total testosterone level, IIEF-5 score, elasticity scores of the cavernous body, and penile length were comparable in all groups. At postoperative 3rd and 6th months, statistically significant higher (in favor for fibrosis) mean cavernous body elasticity scores (p = 0.0001), lower mean IIEF-5 scores (p = 0.0001), and shorter penile lengths (p < 0.05) were observed in non-nerve-sparing group compared to other groups while there were no statistically significant differences between unilateral and bilateral nerve-sparing groups. Very strong negative correlation was detected between IIEF-5 and elasticity scores (p = 0.0001). According to our results, preservation of the neurovascular bundle in at least one side mediates lower elasticity scores, better International Index of Erectile Function scores, and penile lengths. Preliminary results of the penile elastography studies are promising for prediction of erectile functions and cavernous tissue fibrosis.

Can the effect of adhesion barriers and/or intravesical balloon inflation improve bladder autoaugmentation outcomes in a rabbit model?

INTRODUCTION: Bladder augmentation is used for the treatment of bladder dysfunction in order to minimize intravesical pressure and increase bladder capacity. However, less-invasive procedures, such as autoaugmentation, have been proposed due to several complications that have occurred using bowel and gastric segments. The technique of autoaugmentation involves wide excision of the detrusor by leaving the bladder mucosa intact and has shown increased bladder capacity and compliance. An additional step to keep the achieved surface area of this non-contractible bladder segment and, thus, bladder capacity, was reported by using an intravesical balloon to prevent shrinkage of the surgically achieved diverticulum during autoaugmentation. On the other hand, adhesion barriers (AB) with absorbable hydrogel, which can spare tissue and organ plans, are used to prevent postsurgical adhesions. The efficacy of sprayable AB has been demonstrated in animal models and it is now mostly used in laparoscopic surgeries. OBJECTIVE: The present study aimed to compare the efficacy of AB and/or intravesical balloon insertion, which might potentially improve the urodynamic and histopathological outcomes of autoaugmentation in a rabbit model. METHODS: A total of 25 New Zealand rabbits were included in the study. Following the surgical reduction to form a low-capacity bladder model (35-40% of the initial volume), standard detrusorotomy was performed in all groups except the sham group. Group 2 had only autoaugmentation as the control group. The bladders in Group 3 were supported with an intravesical balloon. An Adhesion Barrier System (CUI Tissue Expander) was used for all bladders in Group 4, without balloon inflation. In Group 5, both intravesical balloon inflation and adhesion barrier application were performed following autoaugmentation. Urodynamic evaluations were performed at day 0 before reduction, day 0 after reduction, and the 90th postoperative day. Capacity and compliance measurements were noted. Bladders were histopathologically evaluated. Expression of CD31 (microvessel density) and fibrosis were noted. RESULTS: Autoaugmentation does not result in a reliable increase in bladder capacity and compliance when compared to a sham group. Urodynamic measurements were similar in balloon-inflated groups (Group 3 and Group 5), showing a statistically significant improvement. Sprayable AB system alone revealed a slight, but not statistically significant, increase (Table). No significant differences between all five groups were detected regarding microvessel density (CD31 expression) and fibrosis. DISCUSSION: In the present study, the intravesical balloon application (IVBA) efficiency was investigated alone and in combination with AB. The main basis of this study were the previous findings, which demonstrated prevention or decrease in the contraction of diverticula by IVBA. The role of AB alone or within a combination was also evaluated. Adhesion barriers are mostly used in laparoscopic gynecologic and colorectal operations. They decrease the postoperative adhesions by forming a physical barrier. In the present study, it was thought that AB might reduce postoperative adhesions and enhance the outcome of autoaugmentation. One of the most important outcomes was the inconsistency of fibrosis density with final bladder capacity and compliance values; this finding did not support the role of fibrosis prevention with IVBA. The present study had some limitations: the partial cystectomy method, which was used to form a low-compliance bladder, is a different clinical condition to neurogenic bladder, and a rectal catheter was not used during urodynamic evaluation. General anesthesia and muscle relaxant were performed during urodynamy and abdominal contractions were not seen. CONCLUSION: Bladder autoaugmentation in a rabbit model, followed by intravesical balloon inflation offers improvement in bladder capacity and compliance. The use of sprayable adhesion barrier hydrogel technology may facilitate tissue healing and result in it being easier to maintain the success achieved by surgery when only supported with an intravesical balloon.

SLC30A8 nonsynonymous variant is associated with recovery following exercise and skeletal muscle size and strength.

Genome-wide association studies have identified thousands of variants that are associated with numerous phenotypes. One such variant, rs13266634, a nonsynonymous single nucleotide polymorphism in the solute carrier family 30 (zinc transporter) member eight gene, is associated with a 53% increase in the risk of developing type 2 diabetes (T2D). We hypothesized that individuals with the protective allele against T2D would show a positive response to short-term and long-term resistance exercise. Two cohorts of young adults-the Eccentric Muscle Damage (EMD; n = 156) cohort and the Functional Single Nucleotide Polymorphisms Associated with Muscle Size and Strength Study (FAMuSS; n = 874)-were tested for association of the rs13266634 variant with measures of skeletal muscle response to resistance exercise. Our results were sexually dimorphic in both cohorts. Men in the EMD study with two copies of the protective allele showed less post-exercise bout strength loss, less soreness, and lower creatine kinase values. In addition, men in the FAMuSS, homozygous for the protective allele, showed higher pre-exercise strength and larger arm skeletal muscle volume, but did not show a significant difference in skeletal muscle hypertrophy or strength with resistance training.

The 1p13.3 LDL (C)-associated locus shows large effect sizes in young populations.

Genome-wide association studies (GWASs) have identified polymorphic loci associated with coronary artery disease (CAD) risk factors (i.e. serum lipids) in adult populations (42-69 y). We hypothesized that younger populations would show a greater relative genetic component due to fewer confounding variables. We examined the influence of 20 GWAS loci associated with serum lipids and insulin metabolism, in a university student cohort (n = 548; mean age = 24 y), and replicated statistically associated results in a second study cohort of primary school students (n = 810, mean age = 11.5 y). Nineteen loci showed no relationship with studied risk factors in young adults. However, the ancestral allele of the rs646776 (SORT1) locus was strongly associated with increased LDL (C) in young adults [TT: 97.6 ± 1.0 mg/dL (n = 345) versus CT/CC: 87.3 ± 1.0 mg/dL (n = 203); p = 3 × 10(x6)] and children [TT: 94.0 ± 1.3 mg/dL (n = 551) versus CT/CC: 84.7 ± 1.4 mg/dL (n = 259); p = 4 × 10(x6)]. This locus is responsible for 3.6% of population variance in young adults and 2.5% of population variance in children. The effect size of the SORT1 locus is considerably higher in young populations (2.5-4.1%) compared with older subjects (1%).

CCL2 and CCR2 variants are associated with skeletal muscle strength and change in strength with resistance training.

Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation. The present study hypothesizes that genetic variations in CCL2 and its receptor (CCR2) may help explain muscle trait variability. College-aged subjects [n = 874, Functional Single-Nucleotide Polymorphisms Associated With Muscle Size and Strength (FAMUSS) cohort] underwent a 12-wk supervised strength-training program for the upper arm muscles. Muscle size (via MR imaging) and elbow flexion strength (1 repetition maximum and isometric) measurements were taken before and after training. The study participants were then genotyped for 11 genetic variants in CCL2 and five variants in CCR2. Variants in the CCL2 and CCR2 genes show strong associations with several pretraining muscle strength traits, indicating that inflammatory genes in skeletal muscle contribute to the polygenic system that determines muscle phenotypes. These associations extend across both sexes, and several of these genetic variants have been shown to influence gene regulation.