Matthieu Durand

Anatomical grades of nerve sparing: a risk-stratified approach to neural-hammock sparing during robot-assisted radical prostatectomy (RARP).

Whats known on the subject? and What does the study add?

Effect of a Risk-stratified Grade of Nerve-sparing Technique on Early Return of Continence After Robot-assisted Laparoscopic Radical Prostatectomy

BACKGROUND The impact of nerve sparing (NS) on urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RALP) has yet to be defined. OBJECTIVE To evaluate the effect of a risk-stratified grade of NS technique on early return of urinary continence. DESIGN, SETTING, AND PARTICIPANTS Data were collected from 1546 patients who underwent RALP by a single surgeon at a tertiary care center from December 2008 to October 2011. Patients were categorized preoperatively by a risk-stratified approach into risk grades 1-4, with risk grade 1 patients more likely to receive NS grade 1 or complete hammock preservation. This categorization was also conducted for risk grades 2-4, with grade 4 patients receiving a non-NS procedure. INTERVENTION Risk-stratified grading of NS RALP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariate and multivariate analysis identified predictors of early return of urinary continence, defined as no pad use at ≤ 12 wk postoperatively. RESULTS AND LIMITATIONS Early return of continence was achieved by 791 of 1417 men (55.8%); of those, 199 of 277 (71.8%) were in NS grade 1, 440 of 805 (54.7%) were in NS grade 2, 132 of 289 (45.7%) were in NS grade 3, and 20 of 46 (43.5%) were in NS grade 4 (p<0.001). On multivariate analysis, better NS grade was a significant independent predictor of early return of urinary continence when NS grade 1 was the reference variable compared with NS grade 2 (p<0.001; odds ratio [OR]: 0.46), NS grade 3 (p<0.001; OR: 0.35), and NS grade 4 (p=0.001; OR: 0.29). Lower preoperative International Prostate Symptom Score (p=0.001; OR: 0.97) and higher preoperative Sexual Health Inventory for Men score (p=0.002; OR: 1.03) were indicative of early return of urinary continence. Positive surgical margin rates were 7.2% (20 of 277) of grade 1 cases, 7.6% (61 of 805) of grade 2 cases, 7.6% (22 of 289) of grade 3 cases, and 17.4% (8 of 46) of grade 4 cases (p=0.111). Extraprostatic extension occurred in 6.1% (17 of 277) of NS grade 1 cases, 17.5% (141 of 805) of NS grade 2 cases, 42.5% (123 of 289) of NS grade 3 cases, and 63% (29 of 46) of NS grade 4 cases (p<0.001). Some limitations of the study are that the study was not randomized, grading of NS was subjective, and possible selection bias existed. CONCLUSIONS Our study reports a correlation between risk-stratified grade of NS technique and early return of urinary continence as patients with a lower grade (higher degree) of NS achieved an early return of urinary continence without compromising oncologic safety.

Obesity is associated with worse oncological outcomes in patients treated with radical cystectomy.

Little is known on the association between obesity and urothelial carcinoma of the bladder (UCB). Most studies have shown that higher body mass index (BMI) is associated with higher rates of perioperative complications. Only one study specifically investigated obesity and bladder cancer‐specific outcomes and reported no significant association between higher BMI and disease‐specific survival in patients with UCB treated with radical cystectomy. However, that study was limited by its small sample size and a high rate of preoperative therapies. In contrast to the only previous study evaluating the association of BMI with oncological outcomes in UCB, we found that obesity (BMI ≥30 kg/m2) was associated with features of biologically aggressive UCB and clinical outcomes after radical cystectomy and, even when adjusting for the effects of standard clinicopathological features, obesity remained an independent predictor of cancer recurrence, cancer‐specific mortality and overall mortality.

Role of magnetic resonance imaging in bladder cancer: current status and emerging techniques

Whats known on the subject? and What does the study add?

Improving time to continence after robot-assisted laparoscopic prostatectomy: augmentation of the total anatomic reconstruction technique by adding dynamic detrusor cuff trigonoplasty and suprapubic tube placement.

After robot-assisted laparoscopic prostatectomy, total anatomic reconstruction (TR) with the additions of a circumapical urethral dissection, a dynamic detrusor cuff trigonoplasty, and placement of a suprapubic catheter was performed in 49 patients from June to July 2012. Continence at 6 weeks after catheter removal was assessed for an initial group of 23 patients, and also at 2 weeks in an additional 26 patients who most recently had undergone surgery. Follow-up appointments and telephone interviews were used to assess pad use and continence. Of the initial 23 patients receiving the modified TR, 60.9% had 0 pad use at 6 weeks. By 2 weeks, 65.4% of the most recent 26 patients operated on achieved continence with 0-1 pad use. Preservation and reconstruction of the pelvic floor and supporting bladder structures leads to an earlier return of continence. These key steps need to be validated and confirmed in larger and randomized trials.

Real-time in vivo periprostatic nerve tracking using multiphoton microscopy in a rat survival surgery model: a promising pre-clinical study for enhanced nerve-sparing surgery.

To assess the ability of multiphoton microscopy (MPM) to visualise, differentiate and track periprostatic nerves in an in vivo rat model, mimicking real‐time imaging in humans during RP and to investigate the tissue toxicity and reproducibility of in vivo MPM on prostatic glands in the rat after imaging and final histological correlation study.

The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma

Background Clear-cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Although ccRCC is characterized by common recurrent genetic abnormalities, including inactivation of the von Hippel-Lindau (vhl) tumor suppressor gene resulting in stabilization of hypoxia-inducible factors (HIFs), the tumor aggressiveness and outcome of ccRCC is variable. New biomarkers are thus required to improve ccRCC diagnosis, prognosis and therapeutic options. This work aims to investigate the expression of HIF and proteins involved in metabolism and pH regulation. Their correlation to histoprognostic parameters and survival was analyzed. Methods ccRCC of 45 patients were analyzed. HIF-1α, HIF-2α, HAF, GLUT1, MCT1, MCT4, CAIX and CAXII expression was assessed by immunohistochemistry in a semi-quantitative and qualitative manner. The GLUT1, MCT1, MCT4, CAIX and CAXII mRNA levels were analyzed in an independent cohort of 43 patients. Results A significant correlation was observed between increased GLUT1, MCT1, CAXII protein expression and a high Fuhrman grade in ccRCC patients. Moreover, while HIF-1α, HIF-2α and HAF expression was heterogenous within tumors, we observed and confirmed that HIF-2α co-localized with HAF. We confirmed, in an independent cohort, that GLUT1, MCT1 and CAXII mRNA levels correlated with the Fuhrman grade. Moreover, we demonstrated that the high mRNA level of both MCT1 and GLUT1 correlated with poor prognosis. Conclusions This study demonstrates for the first time a link between the aggressiveness of high- Fuhrman grade ccRCC and metabolic reprogramming. It also confirms the role of HIF-2α and HAF in tumor invasiveness. Finally, these results demonstrate that MCT1 and GLUT1 are strong prognostic markers and promising therapeutic targets.

Sirtuin 7: a new marker of aggressiveness in prostate cancer

Predictive biomarkers for advanced prostate cancer (PCa) are still missing. The sirtuin 7 (SIRT7) has been linked to tumorogenesis but its role in prostate cancer is poorly documented. To determine if SIRT7 can be a biomarker for aggressive prostate cancer and plays a role in PCa aggressiveness. We analyzed the expression of SIRT7 by immunohistochemistry in 57 patients comparing healthy with adjacent cancer tissue. SIRT7 levels were significantly elevated in tumors and its expression was positively associated with the grade. We also demonstrated that the knock down of SIRT7 decreased the migration of DU145 and PC3 cells (two androgen-independent prostate cancer cell lines) whereas the overexpression of the native protein but not the mutated form increased the cell migration and the invasion of the poorly aggressive prostate cancer cell line LNCaP. Finally, we also showed that SIRT7 overexpression induced the resistance to docetaxel. Our results demonstrate that SIRT7 promotes prostate cancer cell aggressiveness and chemoresistance and suggest that SIRT7 is a good predictive biomarker of PCa aggressiveness.

Magnetic Resonance Microscopy May Enable Distinction Between Normal Histomorphological Features and Prostate Cancer in the Resected Prostate Gland.

To determine imaging protocol parameters for characterization of prostate tissue at histological length scales.

Update on the ICUD-SIU consultation on multi-parametric magnetic resonance imaging in localised prostate cancer

IntroductionProstate cancer (PCa) imaging is a rapidly evolving field. Dramatic improvements in prostate MRI during the last decade will probably change the accuracy of diagnosis. This chapter reviews recent current evidence about MRI diagnostic performance and impact on PCa management.Materials and methodsThe International Consultation on Urological Diseases nominated a committee to review the literature on prostate MRI. A search of the PubMed database was conducted to identify articles focussed on MP-MRI detection and staging protocols, reporting and scoring systems, the role of MP-MRI in diagnosing PCa prior to biopsy, in active surveillance, in focal therapy and in detecting local recurrence after treatment.ResultsDifferences in opinion were reported in the use of the strength of magnets [1.5 Tesla (T) vs. 3T] and coils. More agreement was found regarding the choice of pulse sequences; diffusion-weighted MRI (DW-MRI), dynamic contrast-enhanced MRI (DCE MRI), and/or MR spectroscopy imaging (MRSI) are recommended in addition to conventional T2-weighted anatomical sequences. In 2015, the Prostate Imaging Reporting and Data System (PI-RADS version 2) was described to standardize image acquisition and interpretation. MP-MRI improves detection of clinically significant PCa (csPCa) in the repeat biopsy setting or before the confirmatory biopsy in patients considering active surveillance. It is useful to guide focal treatment and to detect local recurrences after treatment. Its role in biopsy-naive patients or during the course of active surveillance remains debated.ConclusionMP-MRI is increasingly used to improve detection of csPCa and for the selection of a suitable therapeutic approach.