Inhibition of endogenous hydrogen sulfide production in clear-cell renal cell carcinoma cell lines and xenografts restricts their growth, survival and angiogenic potential.

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H2S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism and angiogenesis. Using the H2S-specific probe MeRhoAz, it was found that H2S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H2S-producing enzymes could reduce the proliferation, metabolism and survival of ccRCC cell lines, as determined by live-cell imaging, XTT/ATP assay, and flow cytometry respectively. Using the chorioallantoic membrane angiogenesis model, it was found that systemic inhibition of endogenous H2S production was able to decrease vascularization of VHL-deficient ccRCC xenografts. Endogenous H2S production is an attractive new target in ccRCC due to its involvement in multiple aspects of disease.

Predicting biochemical response to clomiphene citrate in men with hypogonadism.

INTRODUCTION: Clomiphene citrate (CC) is as an effective treatment for men with hypogonadism (HG). Identifying the ideal candidate for this strategy has to date largely relied upon a patient's interest in preservation of testicular volume and spermatogenesis. AIM: This analysis was undertaken to define if predictors existed of robust elevation in serum testosterone (T) levels in response to CC. METHODS: Seventy-six men with a diagnosis of HG (two separate early morning total T levels <300 ng/dL) opting for CC therapy constituted the study population. Demographic, comorbidity data, and physical and laboratory characteristics were recorded. Laboratory tests were conducted 4 weeks after commencement and every 6 months thereafter. Multivariable analysis was conducted to define if predictors of biochemical response could be identified. Parameters included in the model were patient age, mean testicular volume, varicocele presence, and baseline total T, free T, and luteinizing hormone (LH) levels. MAIN OUTCOME MEASURE: Successful biochemical response to CC, defined as an increase of ≥200 ng/dL in total T level at ≥6 months after commencing CC, was the main outcome measure. RESULTS: Mean age was 46 ± 22 years. Mean pretreatment testicular volume was 16 ± 8 mL. Mean baseline T and LH levels were 179 ± 72 ng/dL and 7.2 ± 5.6 IU/mL, respectively. Mean total T on CC was 467 ± 190 ng/dL. Forty-seven patients (62%) met the responder definition, with a mean increase in total T levels of 302 ± 76 (204-464) ng/dL. In CC responders, the mean LH rise was 5.6 ± 3.1 IU/mL. On multivariable analysis, factors predictive of CC response included: mean testicular volume (adjusted [adj.] r = 0.32, P < 0.01), mean testicular volume ≥14 mL (hazard ratio [HR] 2.2, P < 0.01), LH level (adj. r = 0.48, P < 0.001), and LH level ≤6 IU/mL (HR 3.5, P < 0.001). CONCLUSION: These data indicate that two thirds of men with HG meet a robust responder definition and that pretreatment testicular volume and LH levels (in continuous and dichotomized fashions) are predictors of response.

Three-year outcomes of recovery of erectile function after open radical prostatectomy with sural nerve grafting.

INTRODUCTION: Optimal oncologic control of higher stage prostate cancers often requires sacrificing the neurovascular bundles (NVB) with subsequent postoperative erectile dysfunction (ED), which can be treated with interposition graft using sural nerve. AIMS: To examine the long term outcome of sural nerve grafting (SNG) during radical retropubic prostatectomy (RRP) performed by a single surgeon. METHODS: Sixty-six patients with clinically localized prostate cancer and preoperative International Index of Erectile Function (IIEF) score >20 who underwent RRP were included. NVB excision was performed if the risk of side-specific extra-capsular extension (ECE) was >25% on Ohori' nomogram. SNG was harvested by a plastic surgeon, contemporaneously as the urologic surgeon was performing RRP. IIEF questionnaire was used pre- and postoperatively and at follow-up. MAIN OUTCOME MEASURES: Postoperative IIEF score at three years of men undergoing RRP with SNG. Recovery of potency was defined as postoperative IIEF-EF domain score >22. RESULTS: There were 43 (65%) unilateral SNG and 23 (35%) bilateral SNG. Mean surgical time was 164 minutes (71 to 221 minutes).The mean preoperative IIEF score was 23.4+1.6. With a mean follow-up of 35 months, 19 (28.8%) patients had IIEF score >22. The IIEF-EF scores for those who had unilateral SNG and bilateral SNG were 12.9+4.9 and 14.8+5.3 respectively. History of diabetes (P=0.001) and age (P=0.007) negatively correlated with recovery of EF. 60% patients used PDE5i and showed a significantly higher EF recovery (43% vs. 17%, P=0.009). CONCLUSIONS: SNG can potentially improve EF recovery for potent men with higher stage prostate cancer undergoing RP. The contemporaneous, multidisciplinary approach provides a good quality graft and expedited the procedure without interrupting the work-flow.

Exploring the association between erectile rigidity and treatment adherence with sildenafil.

INTRODUCTION: Erection hardness has been shown to correlate with increased self-confidence, sexual satisfaction, and improvement in psychosocial factors such as sexual and overall relationship. It is estimated that one-third of men using phosphodiesterase type 5 inhibitors (PDE5) cease use of medication after one prescription and one-half cease use by 6 months. AIM: This study was undertaken to explore the link between erection hardness and treatment adherence. METHODS: Men presenting with erectile dysfunction (ED) who were candidates for PDE5 therapy constituted the study population. They were assessed at the baseline regarding their erectile function (EF) and rigidity using autoquestionnaires. Patients then received regular follow-up using the same assessment tools and were also asked about continued use of PDE5. The final patient assessment was conducted at a time point no sooner than 12 months after commencing PDE5. Multivariable analysis was conducted to define predictors of continued PDE5 use. MAIN OUTCOME MEASURES: Patients were assessed using the International Index of Erectile Function (IIEF) questionnaire and the Erection Hardness Score (EHS). Adherence was defined as continued use of PDE5 at least once per month. RESULTS: One hundred eighty-six men were analyzed. The mean age and the duration of ED were 61 ± 22 and 2.2 ± 2.9 years, respectively. Sixty-three percent were married or partnered. The mean partner age was 52 ± 8 years. Of the 186 patients, 32% had one vascular comorbidity, 34% had two vascular comorbidities, 26% had three vascular comorbidities, and 6% had ≥ 4 vascular comorbidities. All patients were treated with sildenafil and were sexually active. The mean time to end-of-treatment (EOT) interview and repeat completion of questionnaires was 17 ± 4 months. At the baseline, 26% were EHS 3 (mild ED), 42% were EHS 2 (moderate ED), and 32% were EHS 1 (severe ED). The mean baseline EF domain score was 14 ± 10, and at the EOT, it was 22 ± 5 (P < 0.01). At the follow-up interview, 4% were EHS 1, 12% were EHS 2, 28% were EHS 3, and 56% were EHS 4. Overall, 67% of the men continued to use PDE5 at follow-up. The distribution of patients continuing to use PDE5 after commencement was 15% of those achieving EHS 1, 30% for EHS 2, 66% for EHS 3, and 82% for EHS 4. Based on logistic regression analysis, the factors predictive of continued PDE5 use were being partnered, partner age, frequency of sexual activity, a shift of ≥ 2 points on the EHS, and reaching level 4 on the EHS scale. CONCLUSION: There is an excellent relationship between erection hardness and adherence to PDE5 treatment. Driving men to greater erectile rigidity appears to translate into lower dropout rates.

Androgen deprivation therapy before radical prostatectomy is associated with poorer postoperative erectile function outcomes.

UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Erectile dysfunction is a recognized complication of radical prostatectomy. Androgen deprivation therapy adversely impacts sexual function. Our study shows that the preoperative use of androgen deprivation therapy significantly reduces erectile function recovery after radical prostatectomy. The underneath pathophysiological mechanisms for this to occur are reviewed. OBJECTIVE: To define the impact of androgen deprivation therapy (ADT), undergone before radical prostatectomy (RP), on erectile function (EF) recovery. MATERIAL AND METHODS: A total of 38 consecutive patients presenting to a sexual medicine clinic after undergoing RP who had received ADT before RP (ADT+ group) were compared with a contemporary, age and comorbidity-matched cohort of 94 patients who did not receive ADT (ADT- group) before undergoing RP. Medical records were reviewed for demographics, comorbidity profiles and duration of ADT exposure. All the patients underwent Doppler penile ultrasonography within 6 months of RP and were administered the International Index of Erectile Function (IIEF) questionnaire. All the patients underwent evaluation of EF recovery. We analysed the incidence of venous leak (VL), mean IIEF EF domain score and proportion of men with EF domain scores ≥ 24 at 18 months after RP. RESULTS: The mean age, comorbidity profiles, median Gleason score, median pre-treatment PSA level, and mean time to evaluation after RP were similar between the two groups. The median duration of ADT exposure in the ADT+ group was 3 months. The incidence of VL within 6 months of surgery was 60% for the ADT+ and 20% for the ADT- group (P < 0.001). Likewise, the IIEF EF domain scores and proportion of men with EF domain scores ≥ 24 at 18 months were significantly lower in the ADT+ group, even when controlled for nerve-sparing status. CONCLUSION: Our data suggest that preoperative use of ADT adversely impacts EF outcomes and should therefore be avoided in the absence of robust data suggesting any oncological benefit.

Nodal counts during pelvic lymph node dissection for prostate cancer: an objective indicator of quality under the influence of very subjective factors.

UNLABELLED: Study Type--Therapy (case series). Level of Evidence 4. What's known on the subject? And what does the study add? In lymph node dissections for cancer, the more extended the dissection, the higher the number of lymph nodes removed. In addition, the higher the number of nodes retrieved, the better the staging. This leads many investigators to set a threshold of a minimal number of nodes below which the dissection is considered inadequate. Although the minimal threshold concept is generally good, it is not based on very objective data. a number of factors might influence the final number of nodes removed: (i) the surgeon and the surgical technique; (ii) the pathologists and tissue processing technique; (iii) the patient; and (iv) the audit effect and feedback to the surgeons about the number of nodes removed. OBJECTIVE: • To examine the number of lymph nodes removed over time for men undergoing a standard pelvic lymph node dissection (PLND) during radical prostatectomy. PATIENTS AND METHODS: • In total, 2119 consecutive patients with clinically localized prostate cancer were scheduled for non-salvage radical prostatectomy between February 2005 and September 2009. • All patients underwent PLND, including the external iliac, hypogastric and obturator fossa nodal groups. • We tested whether the number of lymph nodes increased over time by including the date of each patient's surgery into a linear regression model using nonlinear terms. RESULTS: • From 2008 onward, there appears to be a large increase in the number of nodes removed. • Date of surgery was a significant predictor of the number of nodes removed (P < 0.001). • The anatomical template of dissection, the specimen submission and pathological assessment were reportedly unchanged. • The nodal yield increase in the later part of the study coincides with an increase in the academic interest in PLND and nodal metastasis in prostate cancer at the institutional level and worldwide. CONCLUSIONS: • Without any intentional change in surgical technique or pathological processing, the number of lymph nodes removed in our radical prostatectomy experience increased. • This change coincided with an increased academic interest in the subject and highlights the positive feedback effect. • The change also raises concerns about unaccounted for confounding factors that could affect multi-institutional datasets and surgical clinical trials.

Renal cell carcinoma (RCC) arising in native kidneys of dialyzed and transplant patients: are they different entities?

UNLABELLED: What's known on the subject? and What does the study add? Patients with end-stage renal disease (ESRD) have an increased risk of developing RCC in their native kidneys. The prevalence of RCC is 3-4% in cases of ESRD in dialyzed and/or transplanted patients, which corresponds to a rate 100-times higher than that in the general population. This is the first study, to our knowledge, comparing the characteristics of kidney cancer in the ESRD population according to their dialysis or transplantation status at the time of diagnosis. The differences in stage and survival we observed may be due to differences in surveillance strategies between transplanted and not transplanted patients, nevertheless, the differences in pathological subtypes suggest they could also be due to differences in the tumorigenesis process. OBJECTIVE: • To compare clinical, pathological and outcome features of renal cell carcinomas (RCCs) arising in patients with chronic renal failure (CRF) with or without renal transplantation. PATIENTS AND METHODS: • In all, 24 French University Departments of Urology and Kidney Transplantation participated in this retrospective study comparing RCCs arising in patients with CRF according to their dialysis or transplantation status at the time of diagnosis. • Information about age, sex, symptoms, duration of CRF, mode and duration of dialysis, renal transplantation, tumour staging and grading, histological subtype and outcome were recorded in a unique database. • Qualitative and quantitative variables were compared by using chi-square and Student statistical analysis. Survival was assessed by Kaplan-Meier and Cox methods. RESULTS: • Data on 303 RCC cases diagnosed between 1985 and 2009 were identified in 206 men (76.3%) and 64 women (23.7%). • Transplanted and not transplanted patients accounted for 213 (70.3%) and 90 cases (29.7%), respectively. • In transplant recipients, RCC was diagnosed at a younger age [mean (sd) 53 (11) vs 61 (14) years, P < 0.001), the mean tumour size was smaller [3.4 (2.3) vs 4.2 (3.1) cm, P= 0.02), pT1a stage (75 vs 60%, P= 0.009) and papillary histological subtype (44 vs 22%, P < 0.001) were more frequent than in their dialysis-only counterparts. • Nodal (1 vs 6%, P= 0.03) and distant metastases rates (0 vs 5%, P < 0.001) were significantly increased in patients who had not had a transplant. However, Fürhman grading, symptoms, tumour multifocality or bilaterality, presence of acquired cystic kidney disease, were not significantly different between the groups. • Estimated 5-year survival rates were 97% and 77% for transplanted and not transplanted patients, respectively (P < 0.001). In univariate analysis, presence of symptoms (P= 0.008), poor performance status (P= 0.04), large tumour size, advanced TNM stage (P < 0.001), high Führman grade (P= 0.005) and absence of transplantation (P < 0.001) were all adverse prognostic factors. In multivariate analysis, only T stage remained an independent predictor for cancer-related death (P < 0.001). CONCLUSION: • RCC arising in native kidneys of transplant patients seems to exhibit many favourable clinical, pathological and outcome features compared with those diagnosed in dialysis-only patients. Further research is needed to determine whether it is due to particular molecular pathways or to biases in relation to mode of diagnosis.

Pilot study of salvage laparoscopic prostatectomy for the treatment of recurrent prostate cancer.

OBJECTIVE: • To evaluate feasibility, safety and oncological efficacy of salvage laparoscopic radical prostatectomy for pathology-proven biochemical recurrence after primary radiation therapy or cryotherapy for prostate cancer. MATERIALS AND METHODS: • This retrospective pilot study examined 15 patients from 2004 to 2010 with biochemical recurrence after external beam radiation therapy (N= 8), brachytherapy (N= 6) or cryotherapy (N= 1). • Patients were treated with salvage laparoscopic radical prostatectomy (11 conventional, four robotic-assisted) with bilateral pelvic dissection. RESULTS: • Median duration of surgery was 235 min. None of the following occurred: conversion to open surgery, transfusion, urethrovesical stenosis or perioperative or postoperative mortality. One patient presented with a rectal injury, repaired using uninterrupted sutures and a colostomy. One patient had anastomotic leak treated with prolonged Foley catheterization. • Pathological stage was pT2a in three, pT2b in three, pT3a in four, pT3b in three and pT4 in two patients; two patients had nodal metastasis. Within an 8-month median follow-up, 11 patients were disease-free and three had persistent postoperative prostate-specific antigen (PSA) elevation; the remaining patient experienced PSA recurrence after 21 months. • Seven patients achieved continence (no pads) by 8.4 months (median), one patient manifested severe incontinence corrected by implanting an artificial sphincter, and seven patients with a 12.6-month mean follow-up continued to need one or two pads per day. • Erectile dysfunction was present in five patients before surgery and in 14 patients after surgery. CONCLUSION: • Salvage laparoscopic radical prostatectomy seems to offer a safe therapeutic alternative for patients failing primary radiation or cryotherapy. However, larger studies with longer-term data are required.

Heading Towards a Possible Rebirth of the Induced Renal Cell Carcinoma Models?

: Introduction: Animal models are interesting tools to improve our knowledge of the pathophysiological processes underlying kidney cancer development. Recent advances have been made in the understanding of the genetic founding events underlying clear cell renal carcinoma. The aim of this paper was to review and discuss the characteristics of all the induced animal models of renal carcinogenesis that have been described in the scientific literature to date and to see if and how they could regain some use in the light of the latest discoveries. Methods: The authors reviewed all the papers available in PubMed regarding induced animal models of renal carcinogenesis. From this perspective, the keywords "induced", "animal model", and "renal cancer" were used in PubMed's search engine. Another search was done using the keywords "induced", "animal model", and "kidney cancer". PRISMA recommendations were used to develop the literature review. Results: Seventy-eight studies were included in this review. Results were presented depending on the mechanisms used to induce carcinogenesis in each model: induction by carcinogens, hormones, viral induction, or induction by other agents. Discussion focused on the possibility to rethink these different induced animal models and use them to answer new research questions. Conclusion: Many induced animal models have been developed in the past to study renal cancer. While these models seemed unable to yield new knowledge, the latest advances in the understanding of the genetics behind renal carcinogenesis could well bring the models back to the forefront.

Animal models of spontaneous renal carcinoma: A possible rebirth?

Introduction and Objectives The animal models for renal carcinogenesis have allowed researchers to better understand the physiopathological, genetic, molecular, and immunological mechanisms underlying the development of human renal cancers from the induction of precancerous lesions to the metastatic process. Our study aimed to review and discuss the characteristics of all the spontaneous animal models of renal carcinogenesis described in scientific literature to date and see how they could address future challenges in the field of personalized medicine. Methods and Materials We reviewed all the papers on PubMed which focus on spontaneous animal models of renal carcinogenesis. To do so, we used the keywords "spontaneous" AND "animal model" AND "renal cancer" in the PubMed search engine. We also conducted a search using the keywords "spontaneous" AND "animal model" AND "kidney cancer." PRISMA recommendations were used for the literature review. Results A total of 213 publications were found on PubMed with the keywords "spontaneous" AND "animal model" AND "kidney cancer." 219 publications were found on PubMed with the keywords "spontaneous" AND "animal model" AND "renal cancer." After pooling these 2 searches and removing the duplicate publications, 233 publications remained. Among these, 220 full-text articles were assessed for eligibility; 160 were removed because they were irrelevant to our topic, and the remaining 60 studies were included in our qualitative synthesis. Conclusions Many spontaneous animal models have been developed to study renal cancer. So far, these models have enabled the understanding of pathophysiological mechanisms underlying renal cancer. Though less appropriate than patient xenografts from the perspective of personalized medicine, we believe animal models can help medical professionals better understand the hows and whys of the genetic events underlying the intratumoral heterogeneity and spatial distribution of metastatic subclones.

Targeting the VEGF pathway in metastatic bladder cancer.

INTRODUCTION: Bladder cancer represents 7% of all new cancers diagnosed in the USA in 2015. Furthermore, the mortality of metastatic bladder cancer has not decreased substantially in the last four decades. Angiogenesis is known to play a major role in the pathogenesis of bladder cancer. AREAS COVERED: The following article provides an overview of the first results of agents targeting the VEGF pathway in the treatment of metastatic bladder cancer. EXPERT OPINION: Despite a few clinical trials providing preliminary encouraging results, the overall outcomes of the first published trials have been rather disappointing. In some instances, especially the case of trials which have investigated the use of new targeted agents as a single agent, no significant improvement in outcomes was seen, or was not sustained. In other cases, such as with combination trials, intolerable adverse effects have compromised the trials, due to overlapping toxicity between the targeted agent and chemotherapeutic agent(s). Further trials are warranted possibly combining different targeted agents or the use of sequential therapy. A better selection of the patient population may also be a key factor to improve patient outcomes, as many predictive factors of response seem to have already been identified.

Dovitinib: rationale, preclinical and early clinical data in urothelial carcinoma of the bladder.

INTRODUCTION: Bladder cancer (BC) is the third and fifth cancer in men in terms of incidence and mortality in the US. Overexpression and mutations of fibroblast growth factor receptor 3 (FGFR3) are frequently found in BC and can represent a very interesting therapeutic target. Different FGFR3-targeted strategies have been investigated through in vitro and in vivo settings, including FGFR3 tyrosine kinase inhibitors such as dovitinib . AREAS COVERED: The authors review the data that provide a scientific rationale for FGFR3-targeted therapy in BC. They also provide an evaluation of the currently available in vitro and in vivo data on the use of dovitinib in BC patients. EXPERT OPINION: The development and progression of BC rely on a very complex signaling network that involves many different receptors aside from FGFR3 and VEGFR2. The involved signaling network can also be very different from one BC to the other, and can also evolve through time in the same patient. Inhibiting only one single target may thus not be sufficient to achieve a complete downstream oncogenic signaling blockage. Additionally, in vitro data on the use of neutralizing monoclonal antibodies targeting FGFR3 show that it can be a more efficient strategy to reach the same goal, with the potential advantage of less toxicity.

Long-term outcomes of patients with lymph node metastasis treated with radical prostatectomy without adjuvant androgen-deprivation therapy.

BACKGROUND: The presence of lymph node metastasis (LNM) at radical prostatectomy (RP) is associated with poor outcome, and optimal treatment remains undefined. An understanding of the natural history of node-positive prostate cancer (PCa) and identifying prognostic factors is needed. OBJECTIVE: To assess outcomes for patients with LNM treated with RP and lymph node dissection (LND) alone. DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from a consecutive cohort of 369 men with LNM treated at a single institution from 1988 to 2010. INTERVENTION: RP and extended LND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary aim was to model overall survival, PCa-specific survival, metastasis-free progression, and freedom from biochemical recurrence (BCR). We used univariate Cox proportional hazard regression models for survival outcomes. Multivariable Cox proportional hazard regression models were used for freedom from metastasis and freedom from BCR, with prostate-specific antigen, Gleason score, extraprostatic extension, seminal vesical invasion, surgical margin status, and number of positive nodes as predictors. RESULTS AND LIMITATIONS: Sixty-four patients with LNM died, 37 from disease. Seventy patients developed metastasis, and 201 experienced BCR. The predicted 10-yr overall survival and cancer-specific survival were 60% (95% confidence interval [CI], 49-69) and 72% (95% CI, 61-80), respectively. The 10-yr probability of freedom from distant metastasis and freedom from BCR were 65% (95% CI, 56-73) and 28% (95% CI, 21-36), respectively. Higher pathologic Gleason score (>7 compared with ≤ 7; hazard ratio [HR]: 2.23; 95% CI, 1.64-3.04; p < 0.0001) and three or more positive lymph nodes (HR: 2.61; 95% CI, 1.81-3.76; p < 0.0001) were significantly associated with increased risk of BCR on multivariable analysis. The retrospective nature and single-center source of data are study limitations. CONCLUSIONS: A considerable subset of men with LNM remained free of disease 10 yr after RP and extended LND alone. Patients with pathologic Gleason score <8 and low nodal metastatic burden represent a favorable group. Our data confirm prior findings and support a plea for risk subclassification for patients with LNM.

Pudendal schwannoma: A case report and literature review.

Schwannomas are benign nerve sheath tumours most often associated with the cranial nerves and the peripheral nerve system of the neck and extremities. Pelvic schwannomas are rare, with only about 25 cases reported. We report the case of a 34-year-old man referred for worsening pain of 10 years duration involving the right testicle and right penile shaft. Magnetic resonance imaging discovered a well-circumscribed pelvic tumour of 3.2 × 2.8 × 3.2 cm. Considering the possible complications involved in exposing the pudendal nerve during surgical resection, we performed an extensive literature search to aid preoperative planning. The most commonly described surgical approach for pelvic schwannomas has been open median laparotomy with transperitoneal dissection. To our knowledge, pudendal schwannomas have never been described in the literature. However, after considering the location and characteristics of the tumour, we chose laparoscopy because it offers the advantages of better visualization of anatomical structures with minimal invasiveness and faster recovery. At the 3-week follow-up, the patient described a significant decrease in pain and normal neurological and urological examinations.

Impact of androgen deprivation therapy on sexual function.

Many patients with prostate cancer for whom androgen deprivation therapy (ADT) is indicated are young and desire to remain sexually active. In such patients, the side effects of androgen therapy on sexual function can be a source of serious reduction in overall quality of life. Providing the appropriate treatment options in this patient population is therefore essential. Nevertheless, treating such patients is challenging and an understanding of the underlying mechanisms of sexual physiology and pathophysiology is crucial to optimal patient care. In this paper, we reviewed what was known regarding the effects of ADT on sexual function in animal models and we also provided a detailed review on the effects of ADT on sexual health in humans and its treatment.

NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

OBJECTIVE: To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer. MATERIALS AND METHODS: From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses. RESULTS: The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P <.0001). The median disease-free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004). CONCLUSION: Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors.

Penile rehabilitation after prostate cancer treatment: outcomes and practical algorithm.

The number of patients diagnosed with prostate cancer was estimated to be 192,000 in 2009 according to the American Cancer Society. The prevalence of reported erectile dysfunction after radical prostatectomy has significant variance. Among the studies in which the nerve-sparing status was described, erectile function recovery adequate for sexual intercourse was achieved in 50% of patients. This article reviews the animal and human studies in this field and provides a useful penile rehabilitation algorithm.

Hip subluxation associated with Pipkin II fracture: an injury to look for before reduction.

Fractures of the femoral head are rare. They usually occur in association with a posterior hip dislocation secondary to a high-energy trauma (motor vehicle accident). We report a case of Pipkin II fracture associated with an irreducible hip subluxation. Clinical signs are poor unlike in posterior hip subluxation. CT scan is important to evaluate the traumatism. The Hardinge approach is relevant in this context of irreducible hip subluxation. The clinical, diagnostic, and therapeutic particularities of this lesion type are discussed.