Marc Bienz

Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia Using the 180 Watt System: Multicenter Study of the Impact of Prostate Size on Safety and Outcomes

PURPOSE We evaluated photoselective vaporization of the prostate using the GreenLight™ XPS™ 180 W system for benign prostatic hyperplasia treatment in a large multi-institutional cohort at 2 years. We particularly examined safety, outcomes and the re-treatment rate in larger prostates, defined as a prostate volume of 80 cc or greater, to assess the potential of photoselective vaporization of the prostate as a size independent procedure. MATERIALS AND METHODS A total of 1,196 patients were treated at 6 international centers in Canada, the United States, France and England. All parameters were collected retrospectively, including complications, I-PSS, maximum urinary flow rate, post-void residual urine, prostate volume, prostate specific antigen and the endoscopic re-intervention rate. Subgroup stratified comparative analysis was performed according to preoperative prostate volume less than 80 vs 80 cc or greater on transrectal ultrasound. RESULTS Median prostate size was 50 cc in 387 patients and 108 cc in 741 in the prostate volume groups less than 80 and 80 cc or greater, respectively. The rate of conversion to transurethral prostate resection was significantly higher in the 80 cc or greater group than in the less than 80 cc group (8.4% vs 0.6%, p <0.01). I-PSS, quality of life score, maximum urinary flow rate and post-void residual urine were significantly improved compared to baseline at 6, 12 and 24 months of followup without significant differences between the prostate size groups. The re-treatment rate at 2 years reported in 5 of 411 patients was associated with the delivery of decreased energy density (2.1 vs 4.4 kJ/cc) in the group without re-treatment. CONCLUSIONS Photoselective vaporization of the prostate using the XPS 180 W system is safe and efficacious, providing durable improvement in functional outcomes at 2 years independent of prostate size when treated with sufficient energy.

Predictors of early continence following robot-assisted radical prostatectomy

INTRODUCTION Functional outcomes after robot-assisted radical prostatectomy (RARP) greatly influence patient quality of life. Data regarding predictors of early continence, especially 1 month following RARP, are limited. Previous reports mainly address immediate or 3-month postoperative continence rates. We examine preoperative predictors of pad-free continence recovery at the first follow-up visit 1 month after RARP. METHODS Between January 2007 and January 2013, preoperative and follow-up data were prospectively collected for 327 RARP patients operated on by 2 fellowship-trained surgeons (AEH and KCZ). Patient and operative characteristics included age, body mass index (BMI), staging, preoperative prostate-specific antigen (PSA), prostate weight, International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM) score and type of nerve-sparing performed. Continence was defined by 0-pad usage at 1 month follow-up. Univariate and multivariate logistic regression models were used to assess for predictors of early continence. RESULTS Overall, 44% of patients were pad-free 1 month post-RARP. In multivariate regression analysis, age (odds ratio [OR] 0.946, confidence interval [CI] 95%: 0.91, 0.98) and IPSS (OR: 0.953, CI 95%: 0.92, 0.99) were independent predictors of urinary continence 1 month following RARP. Other variables (BMI, staging, preoperative PSA, SHIM score, prostate weight and type of nerve-sparing) were not statistically significant predictors of early continence. Limitations of this study include missing data for comorbidities, patient use of pelvic floor exercises and patient maximal activity. Moreover, patient-reported continence using a 0-pad usage definition represents a semiquantitative and subjective measurement. CONCLUSION In a broad population of patients who underwent RARP at our institution, 44% of patients were pad-free at 1 month. Age and IPSS were independent predictors of early continence after surgery. Men of advanced age and those with significant lower urinary tract symptoms prior to RARP should be counselled on the increased risk of urinary incontinence in the early stages.

Androgen-deprivation therapy and bone loss in prostate cancer patients: a clinical review

Androgen-deprivation therapy (ADT) has become a standard of care in the management of advanced prostate cancer or as an adjunct therapy. However, ADT is associated with a well-known deleterious effect on bone health, resulting in a decrease in bone-mass density (BMD) and increased risk for fracture. With the longer life expectancy of prostate cancer patients, improvement of the quality of life has become increasingly important. Therefore, adequate screening, prevention and treatment of BMD loss is paramount. Zoledronic acid and denosumab have shown promising results in recent studies, which has led to the Food and Drug Administration approval of these treatment options in various settings throughout the course of the disease, including the prevention of ADT-associated bone loss. This review focuses on the various parameters that impact BMD loss in men initiating ADT, on the specific effect of ADT on bone health and on various lifestyle modifications and treatment options such as bisphosphonates, osteoclast-targeted therapy and selective estrogen-receptor modulators that have shown promising results in recent studies.

Management of bone metastases in prostate cancer: a review.

Purpose of reviewBone metastases in the advanced stages of prostate cancer have a detrimental effect on the quality of life, resulting in skeletal-related events and pain and place a significant burden on healthcare resources. Improvements in prostate cancer treatment have led to a longer survival of patients. Therefore, quality of life is of growing interest and importance. Successful management and prevention of the complications of bone metastasis in those patients remains, however, clinically challenging. Recent findingsRecently, radium-223 was approved as a treatment for bone metastasis in patients with prostate cancer, joining zoledronic acid, denosumab and other radiopharmaceuticals in the clinical armamentarium. Radium-223 has shown to improve overall survival in patients with bone metastasis. SummaryThis review focuses on the recent landmark studies on zoledronic acid, denosumab and radium-223 for patients with metastatic prostate cancer and gives a comprehensive overview of their mechanism of action, efficacy, dosage and safety profile.

Comparison of Fracture Risk Assessment Tool Score to Bone Mineral Density for Estimating Fracture Risk in Patients With Advanced Prostate Cancer on Androgen Deprivation Therapy

OBJECTIVE To estimate the risk of fracture (Fracture Risk Assessment Tool [FRAX] algorithm) because of the development of osteoporosis in prostate cancer patients undergoing androgen deprivation therapy (ADT) for patients who would otherwise not have been identified for treatment by the T score. METHODS This study includes men undergoing ADT for prostate cancer at our urology group. Clinical data were collected via chart review. Subjects were evaluated for fracture risk using country specific (for the United States of America) World Health Organizations FRAX. The FRAX calculations were then compared to fracture risk as determined by T score, for a subset of our cohort that received dual-energy X-ray absorptiometry. RESULTS Our cohort consisted of 613 patients on ADT, 94 of which had a dual-energy X-ray absorptiometry scan. The FRAX algorithm identified 61.6% patients requiring therapy without bone mass density (BMD), 46.8% with BMD, and 19.14% with T score alone. In addition, positive correlation was found between FRAX with and without BMD as well as T score and FRAX with BMD and without BMD. CONCLUSION Our data indicate that many patients who were not found at significant risk for fracture with T score were in fact found to be at risk with the FRAX calculation. The largest proportion of patients was found to be at risk through the FRAX calculation without BMD, followed by FRAX with BMD, followed by T score alone. The utility of FRAX is beneficial in identifying patients that may benefit from effective bone-tropic treatment modalities.

Microcirculatory response during on-pump versus off-pump coronary artery bypass graft surgery.

Objectives: The use of cardiopulmonary bypass (CPB) during coronary artery bypass graft surgery (CABG) is associated with a systemic inflammatory response, resulting in altered microcirculation. The aim of this study was to evaluate whether beating heart surgery can preserve the microcirculation. Methods: Sublingual microcirculation was characterized by a Sidestream Darkfield Imaging Microscope during off-pump (OPCABG) and on-pump (ONCABG) surgery. Microcirculatory parameters were evaluated during eight precise perioperative time points. Results: The quality of the microcirculation decreased during early ONCABG. OPCABG resulted in a significantly better microcirculation compared to ONCABG for three of six parameters during surgery. However, by the end of surgery and postoperatively, the microcirculatory parameters were no different between the groups. Conclusions: While the results do not show a marked preservation of the microcirculation during and after OPCABG compared to ONCABG, they coincide with the body temperature fluctuations of each group during and after surgery. Our work suggests that active warming could impact the microcirculation parameters.

IκB-Kinase-epsilon (IKKε) over-expression promotes the growth of prostate cancer through the C/EBP-β dependent activation of IL-6 gene expression

The inflammatory cytokine IL-6 has been shown to induce the nuclear translocation of androgen receptors in prostate cancer cells and to activate the androgen receptors in a ligand-independent manner, suggesting it may contribute to the development of a castrate-resistant phenotype. Elevated IL-6 serum levels have also been associated with metastasis-related morbidity in prostate cancer patients. We have previously established that over-expression of I-kappa-B-kinase-epsilon (IKKε also named IKKi or IκBKε) in hormone-sensitive prostate cancer cell lines induces IL-6 secretion. We have also reported that prostate cancer cell lines lacking androgen receptor expression exhibit high constitutive IKKε expression and IL-6 secretion. In the present study, we validated the impact of IKKε depletion on the in vitro proliferation of castrate-resistant prostate cancer cells, and characterized how IKKε depletion affects tumor growth and IL-6 tumor secretion in vivo through a mouse xenograft-based approach. We observed a significant growth delay in IKKε-silenced PC-3 cells injected in SCID mice fed with a doxycycline-supplemented diet in comparison with mice fed with a normal diet. We also found a decrease in IL-6 secretion levels that strongly correlated with tumor growth inhibition. Finally, using constructs with various IL-6-mutated promoters, we demonstrated that IKKε over-expression induces a NF-κB-independent stimulation of the IL-6 gene promoter through the activation and nuclear accumulation of the transcription factor C/EBP-β. Our study demonstrates the pro-proliferative role of the oncogene IKKε in castrate-resistant prostate cancer cell lines, involving the phosphorylation and nuclear translocation of C/EBP-β that initiates IL-6 gene expression.

Factors predicting prolonged operative time for individual surgical steps of robot-assisted radical prostatectomy (RARP): A single surgeon’s experience

INTRODUCTION We evaluated the average time required to complete individual steps of robotic-assisted radical prostatectomy (RARP) by an expert RARP surgeon. The intent is to help establish a time-based benchmark to aim for during apprenticeship. In addition, we aimed to evaluate preoperative patient factors, which could prolong the operative time of these individual steps. METHODS We retrospectively identified 247 patients who underwent RARP, performed by an experienced robotic surgeon at our institution. Baseline patient characteristics and the duration of each step were recorded. Multivariate analysis was performed to predict factors of prolonged individual steps. RESULTS In multivariable analysis, obesity was a significant predictor of prolonged operative time of: docking (odds ratio [OR] 1.96), urethral division (OR 3.13), and vesico-urethral anastomosis (VUA) (OR 2.63). Prostate volume was also a significant predictor of longer operative time in dorsal vein complex ligation (OR 1.02), bladder neck division (OR 1.03), pedicle control (OR 1.04), urethral division (OR 1.02), and VUA (OR 1.03). A prolonged bladder neck division was predicted by the presence of a median lobe (OR 5.03). Only obesity (OR 2.56) and prostate volume (OR 1.04) were predictors of a longer overall operative time. CONCLUSIONS Obesity and prostate volume are powerful predictors of longer overall operative time. Furthermore, both can predict prolonged time of several individual RARP steps. The presence of a median lobe is a strong predictor of a longer bladder neck division. These factors should be taken into consideration during RARP training.

Uroflow Stop Test and Potency Recovery: A Surrogate for Pelvic Floor Integrity Post Robotic-Assisted Radical Prostatectomy?

OBJECTIVE To study the relation between uroflow Stop Test and early recovery of potency following robot-assisted radical prostatectomy (RARP). We recently showed that the ability to completely stop urine flow during voiding, measured objectively by uroflowmetry at the time of catheter removal (uroflow Stop Test) can predict early urinary continence recovery following RARP. MATERIALS AND METHODS In this prospective observational cohort, data were collected on 108 patients operated by a single surgeon (AEH). Eighty patients had a positive uroflow Stop Test (group one) and 28 had a negative Stop Test (group two). Patients were followed for a minimum of 2 years. Covariates included age, body mass index, international prostate symptom score and sexual health inventory for men scores, prostate-specific antigen, tumor stage, prostate volume, nerve sparing status, and estimated blood loss. RESULTS Preoperative characteristics were comparable between both groups except nerve sparing and prostate-specific antigen which were statistically higher in group one (P <.05). Early 3- and 6-months recovery of erectile function was significantly higher in group one. Potency rates in group one and two at 1, 3, 6, 9, 12, 18, and 24 months were 25% vs 14.3% (P = .241), 54.5% vs 18.5% (P = .001), 55.4% vs 18.5% (P = .001), 56.4% vs 36% (P = .084), 66.6% vs 50% (P = .141), 65.5% vs 56% (P = .404) and 73.2% vs 57.7% (P = .160) respectively. Uroflow Stop Test was independent predictor of early potency recovery on multivariate regression analysis at 6 months [odds ratio 6.042 (confidence interval 95% 1.496-24.413) P = .012]. CONCLUSION Uroflow Stop Test is simple and can help predict early potency recovery following RARP.

Prevalence and risk factors of contralateral extraprostatic extension in men undergoing radical prostatectomy for unilateral disease at biopsy: A global multi-institutional experience

INTRODUCTION We assessed the incidence of contralateral prostate cancer (cPCa), contralateral EPE (cEPE) and contralateral positive surgical margins (cPSM) in patients diagnosed preoperatively with unilateral prostate cancer and evaluated risk factors predictive of contralateral disease extension. METHODS The occurrence of cPCa, cEPE and cPSM and the side-specific nerve-sparing technique performed were collected postoperatively from 327 men diagnosed with unilateral prostate cancer at biopsy. Parameters, such as the localization, proportion, and percentage of cancer in positive cores, were prospectively collected. RESULTS Overall, 50.5% of patients had bilateral disease, and were at higher risk when associated with a positive biopsy core at the apex (p = 0.016). The overall incidence of ipsilateral EPE and cEPE were 21.4% and 3.4%, respectively (p < 0.001). Compared to cPCa, ipsilateral disease was at an almost 4-fold higher risk of extending out of the prostate (p < 0.001). None of the criteria tested were identified as useful predictors for cEPE. The low incidence of cEPE in our cohort could limit our ability to detect significance. The overall incidence of ipsilateral PSM and cPSM were 15.3% and 5.8%, respectively (p < 0.001). More aggressive nerve-sparing was not associated with a higher incidence of PSM. Prostate sides selected for more aggressive nerve-sparing were associated with younger patients (p < 0.001), a smaller prostate (p = 0.006), and a lower percentage of cancer in biopsy material (p = 0.008). CONCLUSION Although the risk of cPCa is high in patients diagnosed with unilateral prostate cancer at biopsy, the risk of cEPE and cPSM is low, yet not insignificant. Contralateral aggressive nerve-sparing should be used with caution and should not compromise oncological outcome.