Jaspreet Parihar

Safety of Robot-Assisted Radical Prostatectomy with Pneumoperitoneum of 20 mm Hg: A Study of 751 Patients

BACKGROUND AND PURPOSE Early studies describing robot-assisted radical prostatectomy (RARP) reported the use of pneumoperitoneum at a pressure of 15 mm Hg. While higher insufflation pressures (20 mm Hg) may reduce venous oozing and improve visualization, the safety of this method has not been confirmed. This study evaluates the short-term perioperative outcomes of patients undergoing RARP with insufflation pressures of 20 mm Hg. PATIENTS AND METHODS A single-surgeon, prospectively maintained database of patients undergoing RARP was retrospectively analyzed. Patients who underwent RARP with a pneumoperitoneum pressure of 15 and 20 mm Hg for the entire procedure were analyzed. Preoperative and postoperative hemoglobin levels and estimated glomerular filtration rate (eGFR) were compared. Complications, operative time, and estimated blood loss were also examined. RESULTS The number of patients in the experimental (20 mm Hg) and control (15 mm Hg) groups were 550 and 201, respectively. The groups were well matched with respect to age and operative time. The experimental group had a significantly smaller decrease in mean hemoglobin levels after surgery (-1.18 vs-2.13 mg/dL, P<0.0001). There was no significant difference in the eGFR on the first day after surgery (postoperative day [POD]1) (88.4 vs 85.0 mL/min/1.73m(2), P=0.11) or in the change in eGFR from preoperative to POD1 levels (-0.49 vs 1.54 mL/min/1.73m(2), P=0.18). The complication rate in the experimental group was 8.55% vs 8.46% in the control group. CONCLUSION Pneumoperitoneum using a pressure of 20 mm Hg for RARP is safe and has no significant short-term effects on renal function and hemoglobin. Increased insufflation pressure was not associated with a higher complication rate.

Novel Cystine Ester Mimics for the Treatment of Cystinuria-induced Urolithiasis in a Knockout Mouse Model

OBJECTIVE To assess the effectiveness of l-cystine dimethyl ester (CDME), an inhibitor of cystine crystal growth, for the treatment of cystine urolithiasis in an Slc3a1 knockout mouse model of cystinuria. MATERIALS AND METHODS CDME (200 μg per mouse) or water was delivered by gavage daily for 4 weeks. Higher doses by gavage or in the water supply were administered to assess organ toxicity. Urinary amino acids and cystine stones were analyzed to assess drug efficacy using several analytical methods. RESULTS Treatment with CDME led to a significant decrease in stone size compared with that of the water group (P = .0002), but the number of stones was greater (P = .005). The change in stone size distribution between the 2 groups was evident by micro computed tomography. Overall, cystine excretion in urine was the same between the 2 groups (P = .23), indicating that CDME did not interfere with cystine metabolism. Scanning electron microscopy analysis of cystine stones from the CDME group demonstrated a change in crystal habit, with numerous small crystals. l-cysteine methyl ester was detected by ultra-performance liquid chromatography-mass spectrometer in stones from the CDME group only, indicating that a CDME metabolite was incorporated into the crystal structure. No pathologic changes were observed at the doses tested. CONCLUSION These data demonstrate that CDME promotes formation of small stones but does not prevent stone formation, consistent with the hypothesis that CDME inhibits cystine crystal growth. Combined with the lack of observed adverse effects, our findings support the use of CDME as a viable treatment for cystine urolithiasis.

Bladder neck contracture–incidence and management following contemporary robot assisted radical prostatectomy technique

Purpose: Bladder neck contracture (BNC) is a well-recognized complication following robot-assisted radical prostatectomy (RARP) for treatment of localized prostate cancer with a reported incidence of up to 1.4%. In this series, we report our institutional experience and management results. Methods: A prospectively collected database of patients who underwent RARP by a single surgeon from 2006 to 2012 was reviewed. Watertight bladder neck to urethral anastomosis was performed over 18-French foley catheter. BNC was diagnosed by flexible cystoscopy in patients who developed symptoms of bladder outlet obstruction. Subsequently, these patients underwent cold knife bladder neck incisions. Patients then followed a strict self regimen of clean intermittent catheterization (CIC). We identify the patient demographics, incidence of BNC, associated risk factors and success of subsequent management. Results: Total of 930 patients who underwent RARP for localized prostate cancer was identified. BNC was identified in 15 patients, 1.6% incidence. Mean patient age and preoperative prostate-specific antigen was 58.8 years old and 7.83 ng/mL (range, 2.5–14.55 ng/mL) respectively. Mean estimated blood loss was 361±193 mL (range, 50–650 mL). Follow-up was mean of 23.4 months. Average time to BNC diagnosis was 5.5 months. In three patients, a foreign body was identified at bladder neck. On multivariate analysis, estimated blood loss was significantly associated with development of BNC. All patients underwent cystoscopy and bladder neck incision with a 3-month CIC regimen. Out of 15 index patients, none had a BNC recurrence over the follow-up period. Conclusions: BNC was identified in 1.6% of patients in our series following RARP. Intraoperative blood loss was a significant risk factor for BNC. In 20% of BNC patients a migrated foreign body was noted at vesicourethral anastomosis. Primary management of patients with BNC following RARP should be bladder neck incision and self CIC regimen.

Regional Cost Variations of Robot-Assisted Radical Prostatectomy Compared With Open Radical Prostatectomy

INTRODUCTION The purpose of the study was to evaluate the cost differences between robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) in various census regions of the United States because RARP has been reported to be more expensive than ORP with significant regional cost variations in radical prostatectomy (RP) cost across the United States. PATIENTS AND METHODS International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with prostate cancer who underwent RARP or ORP from the Nationwide Inpatient Sample (NIS) database from 2009 to 2011. Hospital costs were compared using the Wilcoxon rank sum test and multivariable linear regression analysis adjusting for age, sex, race, comorbidities, and hospital characteristics. RESULTS From the NIS database, 24,636 RARP and 13,590 ORP procedures were identified and evaluated. The lowest cost overall was in the South; the highest cost RARP was in the West and for ORP in the Northeast. In multivariable analysis, adjusted according to patient and hospital characteristics, RARP was 43.3% more costly in the Midwest, 37.2% more costly in the South, and 39.1% more costly in the West (P < .0001 for all). In contrast, the cost for RARP in the Northeast was 12.8% less than for ORP (P < .0001). CONCLUSION Cost for RP significantly varies within the nation and in most regions it is significantly greater for RARP than for ORP. ORP in the Northeast is more costly than RARP. Further research is needed to delineate the reason for these differences and to optimize the cost of RP.

α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria

Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutritional supplement α-lipoic acid inhibits cystine stone formation in the Slc3a1−/− mouse model of cystinuria by increasing the solubility of urinary cystine. These findings identify a novel therapeutic strategy for the clinical treatment of cystinuria.

Risk of complications and urinary incontinence following cytoreductive prostatectomy: A multi-institutional study

Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer (PCa). Urinary incontinence was defined as the use of any pad. CRP had longer operative times (200 min vs 140 min, P < 0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared to the control group. However, both overall (8.82% vs 5.85%) and major complication rates (4.41% vs 2.17%) were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI: 1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01-1.36; P = 0.034). In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.

MP12-12 ?-LIPOIC ACID SUPPRESSES CYSTINE STONE FORMATION IN A GENETIC MOUSE MODEL OF CYSTINURIA

Pathogenic allele frequency, carrier rate and affected rate were calculated and estimated based on Hardy-Weinberg equilibrium. RESULTS: In 1KG, non-related healthy individuals (n1⁄42504) carry SLC3A1 and SLC7A9 variants in 1705 and 1287 loci, respectively. In HGMD, there are 110 pathogenic SLC3A1 mutations, and 85 for SLC7A9. These variants include missense mutations, nonsense mutations, insertions, deletions, and complex substitutions. Among 2504 non-related, healthy individuals in 1KG, there are 26 people who carry 9 different SLC3A1 mutations, while 12 people carry 5 different SLC7A9 mutations. There were no homozygotes, compound heterozygotes, multiple variants in cis or trans, double homozygotes, or double heterozygotes. Therefore, disease-causing alleles have a frequency of 0.52% for SLC3A1, and 0.24% for SLC7A9.Type A cysteine stone has a carrier rate of 1 in 96 individuals and affected rate of 1 in 37,100 individuals. For type B, carrier and affected rates would be 1 in 209 and 1 in 174,167, respectively. The combined (type A + type B) carrier rate for cysteine stones is 1 in 66, with an overall affected rate of 1 in 30,585. CONCLUSIONS: The prevalence of cystine stone type A and type B estimated from a genetic approach is lower than the prevalence of observed of phenotypes (1 in 30,585 v.s. 1 in 7,000). Possible explanations include undiscovered mutations, undiscovered genes, a different inheritance model, selection advantages over the pathogenic variant, or founder effect. Further studies and investigations are required.

Second-Line Hormonal for Castrate-Resistant Prostate Cancer

Abstract Initial systemic therapy with androgen deprivation has been the mainstay treatment of hormone-sensitive prostate cancer. Despite an initial response of 18–24 months, disease progression is usually the norm. When this castrate-resistant prostate cancer emerges, secondary hormonal manipulations have long been shown to demonstrate a therapeutic response. This chapter reviews the second-line hormonal therapies available to such patients. This includes the use of first-generation antiandrogens, such as flutamide, bicalutamide, and nilutamide, as well as the newer second-generation antiandrogens that include enzalutamide and ARN-509. Current concepts of antiandrogen withdrawal and the associated response rates are discussed. Traditional second-line treatment options with estrogens, cyproterone, megestrol, ketoconazole, aminoglutethimide, and corticosteroids are also presented. Finally, the role of extragonadal androgen suppression with abiraterone acetate is examined. With newer and emerging treatments, the concept of second-line hormonal manipulation is evolving and holds a tremendous therapeutic potential for men with prostate cancer.

Urodynamics in Male Lower Urinary Tract Symptoms

Lower urinary tract symptoms (LUTS) in men are due to bladder dysfunction or bladder outlet disorders such as benign prostatic enlargement and bladder neck or urethral sphincter dysfunction. Men with lower urinary tract symptoms prefer shared problem-solving and decision making during treatment planning. Urodynamic studies (UDS) in male LUTS (MLUTS) are useful for both diagnosis and prognosis. UDS help both the clinician and the patient in shared decision making regarding treatment of these men. The AUA/SUFU guidelines and EAU guidelines are helpful in cost-effective selection of patients with MLUTS for urodynamic evaluation. UDS are indicated in the subset of patients with MLUTS being considered for invasive and potentially morbid therapy. Uroflowmetry and post-void residual (PVR) volume measurement by bladder ultrasound scan are good screening tests in MLUTS. Urodynamic evidence of bladder outlet obstruction has been correlated with better outcomes following invasive therapy.