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Prostate cancer is the most frequently diagnosed solid malignancy in men. African American (AA) men are at greater risk for developing prostate cancer, and experience higher mortality rates, as compared with Caucasian American men. However, mechanistic studies to understand this health disparity have been limited by the lack of relevant in vitro and in vivo models. There is an urgent need for preclinical cellular models to investigate molecular mechanisms underlying prostate cancer in AA men. We collected clinical specimens from radical prostatectomies of AA patients and established 10 paired tumor-derived and normal epithelial cell cultures from the same donors, which were further cultivated to extend the growth under “conditional reprogramming.” Clinical and cellular annotations characterized these model cells as intermediate risk and predominantly diploid. Immunocytochemical analyses demonstrated variable expression levels of luminal (CK8) and basal (CK5, p63) markers in both normal and tumor cells. However, expression levels of TOPK, c-MYC, and N-MYC were markedly increased only in tumor cells. To determine cell utility for drug testing, we examined viability of cells following exposure to the antiandrogen (bicalutamide) and two PARP inhibitors (olaparib and niraparib) and observed decreased viability of tumor-derived cells as compared with viability of normal prostate-derived cells. Significance: Cells derived from prostatectomies of AA patients conferred a bimodal cellular phenotype, recapitulating clinical prostate cellular complexity in this model cell system. Comparisons of viability responses of tumor derived to normal epithelial cells offer the potential for screening therapeutic drugs. Therefore, these paired prostate epithelial cell cultures provide an in vitro model system suitable for studies of molecular mechanisms in health disparities.

Purpose:Radiotherapy is a curative therapeutic modality used to treat cancers as a single agent or in combination with surgery and chemotherapy. Advanced radiotherapy technologies enable treatment with large fractions and highly conformal radiation doses to effect free-radical damage to cellular DNA leading to cell-cycle arrest, cell death, and innate immune response (IIR) stimulation.Experimental Design:To understand systemic clinical responses after radiation exposure, proteomic and metabolomic analyses were performed on plasma obtained from patients with cancer at intervals after prostate stereotactic body radiotherapy. Pathway and multivariate analyses were used to delineate molecular alterations following radiotherapy and its correlation with clinical outcomes.Results:DNA damage response increased within the first hour after treatment and returned to baseline by 1 month. IIR signaling also increased within 1 hour of treatment but persisted for up to 3 months thereafter. Furthermore, robust IIR and metabolite elevations, consistent with an early proinflammatory M1-mediated innate immune activation, were observed in patients in remission, whereas patients experiencing prostate serum antigen–determined disease progression demonstrated less robust immune responses and M2-mediated metabolite elevations.Conclusions:To our knowledge, these data are the first report of longitudinal proteomic and metabolomic molecular responses in patients after radiotherapy for cancers. The data supports innate immune activation as a critical clinical response of patients receiving radiotherapy for prostate cancer. Furthermore, we propose that the observed IIR may be generalized to the treatment of other cancer types, potentially informing multidisciplinary therapeutic strategies for cancer treatment.

Table S1. Clinical characterization of prostate cancer patients.

Figure S3: Immunocytochemistry analysis of normal (N) and tumor (T)- derived paired cell cultures of AP4 and AP10. Normal and tumor cells from AP4 and AP10 were stained with indicated antibodies. DAPI (bottom in blue) stained the nucleus. CK8, HMW CK, and TOPK were mainly located in the cytoplasm.

Material and methods of cell culture and CRC protocol

Prostate cancer is the most frequently diagnosed solid malignancy in men. African American (AA) men are at greater risk for developing prostate cancer, and experience higher mortality rates, as compared with Caucasian American men. However, mechanistic studies to understand this health disparity have been limited by the lack of relevant in vitro and in vivo models. There is an urgent need for preclinical cellular models to investigate molecular mechanisms underlying prostate cancer in AA men. We collected clinical specimens from radical prostatectomies of AA patients and established 10 paired tumor-derived and normal epithelial cell cultures from the same donors, which were further cultivated to extend the growth under “conditional reprogramming.” Clinical and cellular annotations characterized these model cells as intermediate risk and predominantly diploid. Immunocytochemical analyses demonstrated variable expression levels of luminal (CK8) and basal (CK5, p63) markers in both normal and tumor cells. However, expression levels of TOPK, c-MYC, and N-MYC were markedly increased only in tumor cells. To determine cell utility for drug testing, we examined viability of cells following exposure to the antiandrogen (bicalutamide) and two PARP inhibitors (olaparib and niraparib) and observed decreased viability of tumor-derived cells as compared with viability of normal prostate-derived cells.Significance:Cells derived from prostatectomies of AA patients conferred a bimodal cellular phenotype, recapitulating clinical prostate cellular complexity in this model cell system. Comparisons of viability responses of tumor derived to normal epithelial cells offer the potential for screening therapeutic drugs. Therefore, these paired prostate epithelial cell cultures provide an in vitro model system suitable for studies of molecular mechanisms in health disparities.

Test statistics comparing each post-RT time point to baseline (pre) in the GU cohort.

Heatmap visualization of significantly dysregulated metabolites following RT.

Patients presenting with prostate cancers undergo clinical staging evaluations to determine the extent of disease to guide therapeutic recommendations. Management options may include watchful waiting, surgery, or radiation therapy. Thus, initial risk stratification of prostate cancer patients is important for achieving optimal therapeutic results or cancer cure and preservation of quality of life. Predictive biomarkers for risks of complications or late effects of treatment are needed to inform clinical decisions for treatment selection. Here, we analyzed pre-treatment plasma metabolites in a cohort of prostate cancer patients (N = 99) treated with Stereotactic Body Radiation Therapy (SBRT) at Medstar-Georgetown University Hospital in a longitudinal, quality-of-life study to determine if individuals experiencing radiation toxicities can be identified by a molecular profile in plasma prior to treatment. We used a multiple reaction mass spectrometry-based molecular phenotyping of clinically annotated plasma samples in a retrospective outcome analysis to identify candidate biomarker panels correlating with adverse clinical outcomes following radiation therapy. We describe the discovery of candidate biomarkers, based on small molecule metabolite panels, showing high correlations (AUCs ≥ 95%) with radiation toxicities, suitable for validation studies in an expanded cohort of patients.

Patients presenting with prostate cancers undergo clinical staging evaluations to determine the extent of disease to guide therapeutic recommendations. Management options may include watchful waiting, surgery, or radiation therapy. Thus, initial risk stratification of prostate cancer patients is important for achieving optimal therapeutic results or cancer cure and preservation of quality of life. Predictive biomarkers for risks of complications or late effects of treatment are needed to inform clinical decisions for treatment selection. Here, we analyzed pre-treatment plasma metabolites in a cohort of prostate cancer patients (N = 99) treated with Stereotactic Body Radiation Therapy (SBRT) at Medstar-Georgetown University Hospital in a longitudinal, quality-of-life study to determine if individuals experiencing radiation toxicities can be identified by a molecular profile in plasma prior to treatment. We used a multiple reaction mass spectrometry-based molecular phenotyping of clinically annotated plasma samples in a retrospective outcome analysis to identify candidate biomarker panels correlating with adverse clinical outcomes following radiation therapy. We describe the discovery of candidate biomarkers, based on small molecule metabolite panels, showing high correlations (AUCs ≥ 95%) with radiation toxicities, suitable for validation studies in an expanded cohort of patients.

We review our experience with the AdVance sling in patients with post- prostatectomy incontinence, comparing the role that adjuvant radiation therapy plays in sling success and patient satisfaction at short and long term follow ups.Men who underwent AdVance sling placement for post-prostatectomy incontinence from 2007 to present were identified using Current Procedural Terminology (CPT) codes. Manual chart review was performed. Level of incontinence was assessed using Expanded Prostate Cancer Index Composite (EPIC) and pads per day (PPD) use. Satisfaction was assessed by willingness to recommend the procedure to a friend. Outcomes in men who received radiation were compared to radiation-naïve men.Fifty-two men underwent AdVance sling placement. Eighteen men received adjuvant radiation. Thirty-six men were available for short term (19.4 months) and 16 men for long term (61.5 months) follow up. Overall, significant improvement was seen in post-sling EPIC score (24.6, p0.001), EPIC incontinence score (39.1, p.001), and pad use (3.2 PPD to 1.4 PPD, p.001). Greater improvement in EPIC scores and PPD use was seen in radiation-free men. Irradiated men were less satisfied with the procedure at both short and long term follow up. Diminished efficacy and satisfaction occurred at extended follow up for both groups but was more pronounced with radiation.The majority of patients undergoing the AdVance sling procedure for post-prostatectomy urinary incontinence saw a significant reduction in pad use, and were overall satisfied in both radiated and non-radiated groups at short and long term follow up. However, improvements were greater in the non-radiated groups and diminished with time.

Gleason score from biopsy specimens is important for prostate cancer (PCa) risk stratification and influences treatment decisions. Gleason score upgrading (GSU) between biopsy and surgical pathology specimens has been reported as high as 50 % and presents a challenge in counseling low-risk patients. While recent studies have investigated predictors of GSU, populations in these studies have been largely Caucasian. We report our analysis of predictors of GSU in a large urban African-American population. A total of 959 patients with D’Amico low-risk prostate cancer underwent radical prostatectomy at Georgetown University or Washington Hospital Center between January 2005 and July 2012. Race, age, PSA, body mass index (BMI), cancer of the prostate risk assessment (CAPRA) score, and transrectal ultrasound (TRUS) biopsy characteristics (percent of biopsy cores showing adenocarcinoma, highest percent of biopsy core involved with cancer, and measured TRUS prostate volume) were analyzed with both univariate and multivariate analyses to identify significant predictors of GSU while controlling for clinical parameters. Of the 959 cases, 288 (30.0 %) were upgraded on final pathologic specimen with approximately 38 % (133/355) of African-American patients experiencing GSU. BMI (P = 0.02), percent positive biopsy cores (P

Purpose Robotic-assisted laparoscopic prostatectomy (RALP) offers reportedly comparable oncologic outcomes for localized disease compared with open radical retropubic prostatectomy (ORRP). However, the oncologic efficacy of RALP in locally-advanced prostate cancer (PCa) is less clear. We report and compare our experience with RALP and ORRP in men with locally advanced PCa. Methods Patients with locally advanced PCa (stage T3 or greater) were identified in both robotic and open cohorts. Clinicopathologic features including age, clinical stage, prostate-specific antigen, surgical margins, and Gleason score were reviewed. We further examined the incidence of positive surgical margins, the effect of the surgical learning curve on margins, and the need for adjuvant therapy. Results From 1997 to 2010, 1,011 patients underwent RALP and 415 patients were identified who underwent radical retropubic prostatectomy (RRP) across four institutions. 140 patients in the RALP group and 95 in the RRP group had locally advanced PCa on final pathology. The overall robotic positive margin rate 47.1% compared with 51.4% in the RRP group. A trend towards a lower positive margin rate was seen after 300 cases in the RALP group, with 66.7% positive margin rate in the first 300 cases compared with 41.8% in the latter 700 cases. In addition, a lower incidence of biochemical recurrence was also noted in the latter cases (30.6% vs. 9.5%). Conclusions Up to 2 out of 3 men undergoing RALP for locally-advanced PCa had positive margins during our initial experience. However, with increasing surgeon experience the overall positive margin rate decreased significantly and was comparable to the positive margin rate for patients with locally advanced disease undergoing ORRP over four academic institutions. We also noted a lower incidence of biochemical recurrence with increasing RALP experience, suggesting better oncologic outcomes with higher volume. Given this data, RALP has comparable oncologic outcomes compared to ORRP, especially with higher volume surgeons.

To compare the convalescence and patient satisfaction between laparoscopic and percutaneous ablation for management of small renal masses.We performed a telephone survey comparing convalescence and operative satisfaction of patients who underwent laparoscopic and percutaneous ablation between October 2000 and June 2006 at our institution. A retrospective chart review was performed to compare perioperative and postoperative convalescence parameters.A total of 93 patients underwent ablation of 103 small renal masses at our institution. Laparoscopic cryoablation was performed in 58 patients, percutaneous cryoablation in 20, and percutaneous radiofrequency ablation in 15 patients. Mean patient age was 66 years (range 24-86 years), median ASA (American society of Anesthesiologists) score was 3, and mean body mass index (BMI) was 30 kg/mm(2). There was no significant difference in the mean age, BMI, and median ASA scores between the groups. The mean diameter of the treated mass was slightly larger in the laparoscopic ablation group (2.6 cm) compared with masses in the percutaneous cryoablation (2.2 cm, P=0.027) and percutaneous radiofrequency ablation (2.2 cm, P=0.042) groups. All procedures were performed under general anesthesia. Compared with laparoscopic cryoablation, percutaneous cryoablation was associated with fewer probes used per lesion (P0.04), shorter mean anesthesia time (P=0.001), shorter mean hospital stay (P=0.007), early return to nonstrenuous activity (P=0.007), and shorter time to complete recovery (P = 0.05). Similarly, compared with laparoscopic cryoablation, percutaneous radiofrequency ablation was associated shorter mean anesthesia time (P0.001), early return to nonstrenuous activity (P=0.009), early return to strenuous activity (P=0.007), early return to strenuous activity (P=0.04), and early return to work (P=0.05). There was no difference in the percent of patients who had a preablation biopsy, the median opioid analgesic requirement, and patient satisfaction measured on a 0 to 5 scale between various groups.Our study suggests that percutaneous ablation in carefully selected patients is associated with early convalescence compared with laparoscopic ablation.

To determine the current practice patterns in the management of upper urinary tract calculi in a large group of urologists in the north central United States.An email survey was sent to 790 practicing members of the North Central Section of the American Urological Association. The survey consisted of questions pertaining to practice and training background, and case scenarios with treatment options for upper urinary tract calculi of different sizes at various locations. The responses were then statistically analyzed to determine practice trends.Seven urologists did not fill out the survey, as they did not manage patients with stone disease. The overall response rate was 23% (167/783). Although more than 75% of urologists were trained to perform extracorporeal shockwave lithotripsy (SWL), ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL) during their residency, only 61% and 17% were trained to perform open stone surgery (OSS) and medical expulsive therapy (MET), respectively. Twelve percent of respondents were fellowship trained in endourology. Observation was most commonly recommended for asymptomatic renal calculi5 mm in size (92%). Although SWL continues to be the most commonly utilized therapy for renal (43%-92%) and proximal ureteral calculi20 mm in size (29%-51%), and PCNL for renal calculi20 mm in size (72%-92%), many urologists (48%) favored PCNL for lower pole calculi 10 to 20 mm in size. Use of URS was mostly favored for distal (44%-90%) and proximal ureteral calculi (23%-46%), while MET was recommended for small ureteral calculi5 mm in size (25%-32%). Fellowship-trained endourologists, academic urologists, and urologists in practice for less than 5 years were more likely to utilize URS, PCNL, and MET, and less likely to utilize SWL for urinary calculi.The results of this survey suggest that practice patterns for treatment of stone disease match the treatment approach recommended in the published literature. This information can be further utilized for assessment of guidelines for the treatment of stone disease.

To compare tip temperatures of the vibrating blades of the newer-generation Harmonic Ace device and the older-generation Ultracision Harmonic Scalpel LCS-K5.Comparison of two different harmonic scalpel blades was performed by applying them to 3-mm strips of raw chicken breast at room temperature and measuring the temperature of the tip of the vibrating blade at 0.5-second intervals using a thermocouple. Following activation, the tip was allowed to passively cool to 30 degrees C each time before reactivation. Each device was tested at power settings of 3 and 5 after activation for 1 to 5 seconds. All measurements were performed 5 times.Compared to the older-generation Ultracision Harmonic Scalpel LCS-K5, the newer-generation Harmonic Ace was associated with higher tip temperatures at power level 5 at all times of activation (1-5 seconds), and at power level 3 at longer times of activation (3-5 seconds). The Harmonic Ace also takes longer to reach peak temperatures and can maintain blade hyperthermia for a longer period after activation for more than 3 seconds at power levels 3 and 5.The newer-generation Harmonic Ace may be potentially more effective in tissue dissection, but is associated with greater increases in peak temperatures and longer blade hyperthermia periods compared to the older-generation Ultracision Harmonic Scalpel LCS-K5. The difference is greater after longer periods of activation, and this may have more potential for collateral damage, particularly to nerves and bowel.

Objectives To determine the current practice patterns in the use of ablation technology for the management of small renal masses at academic centers in the United States. Methods An email survey was sent to 112 academic urologists subspecializing in minimally invasive management of renal cancer. The survey consisted of 13 questions and 4 clinical scenarios pertaining to the use of ablation technology. The responses were then tabulated and analyzed to determine practice trends. Results The overall response rate was 62%. Ablation was offered by 93% of the academic urology centers and cryoablation was more frequently used (79%) than radiofrequency ablation (55%). Lack of sufficient efficacy data was the most prevalent reason (80%) for not offering ablation. The maximum size limit for offering ablation was 4 cm by 55% and 3 cm by 34% of the respondents. A collaborative approach using both radiologist and urologist was most commonly used (51%). Most urologists (68%) used both laparoscopic and percutaneous technique, depending on the tumor and adjacent organ location. Intraoperative ultrasound was universally used during the laparoscopic technique and was usually performed by the urologist (95%). Computed tomographic scan was the most frequently used imaging modality for percutaneous ablation (78%) and for surveillance of recurrent disease (81%). In a younger, healthy patient, most urologists recommend extirpative approach for the management of a small renal mass, whereas laparoscopic-assisted ablation was most commonly recommended for an elderly patient with comorbidities. Conclusions Our survey suggests that laparoscopic and percutaneous ablation is offered by the majority of academic centers for carefully selected patients.

Objective To evaluate long-term outcomes between various methods of augmentation cystoplasty. Methods A retrospective analysis was performed of patients undergoing seromuscular colocystoplasty lined with urothelium (SCLU, n = 26), and their outcomes compared to a similar population of patients in the same institution who had received traditional forms of bladder augmentation (colocystoplasty and ileocystoplasty, n = 32). Measurements included efficacy of the procedure in increasing bladder capacity and achieving urinary continence, and the need of subsequent surgery for complications. Results There was no statistically significant difference in achieved bladder capacity, subjective urinary continence and the rates of subsequent surgery for stones, vesicoureteral reflux, augment failure, bladder neck continence and catheterizable channel. None of the patients in the SCLU group had spontaneous perforation or small bowel obstruction. Conclusion Patients with SCLU are at decreased risk for bowel obstruction and spontaneous perforation, but are not devoid of other long-term complications including bladder stones, vesicoureteral reflux and augment failure. Most of the risks and benefits of augmentation cystoplasty performed using ileum, colon, or SCLU appear similar.

OBJECTIVE To report our 5-year experience with laparoscopic and percutaneous cryoablation (LCA and PCA) for managing small renal masses. PATIENTS AND METHODS We retrospectively analysed patients undergoing LCA and PCA between October 2000 and March 2006 at our institution. After approval from the Institutional Review Board, charts were reviewed retrospectively for variables during and after CA, and for clinical outcomes, the latter including the efficacy of the procedure in achieving overall, cancer-specific and recurrence-free survival. RESULTS In all, 78 patients had CA of 88 small renal masses, by LCA in 58 and PCA in 20. The median American Society of Anesthesiology score was 3 and the mean body mass index was 30 kg/m2. All procedures were done under general anaesthesia, with a mean anaesthesia time of 220 min. The mean tumour size was 2.6 cm and the mean hospital stay was 2.1 days. At a mean follow-up of 19 months, the overall, cancer-specific and recurrence-free survival rates were 88.5%, 100% and 98.7%, respectively. Four patients required a repeat treatment due to persistent disease and one had progression to locally advanced disease. Five patients had complications during CA and seven had complications afterward. CONCLUSION This study suggests that CA is a safe, minimally invasive treatment option for patients with small renal masses, at the intermediate-term follow-up.

Background: Laparoscopic and robotic simple prostatectomy (SP) have been introduced with the aim of reducing the morbidity of the standard open technique. Objective: To report a large multi-institutional series of minimally invasive SP (MISP). Design, setting, and participants: Consecutive cases of MISP done for the treatment of bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPE) between 2000 and 2014 at 23 participating institutions in the Americas and Europe were included in this retrospective analysis. Intervention: Laparoscopic or robotic SP. Outcome measurements and statistical analysis: Demographic data and main perioperative outcomes were gathered and analyzed. A multivariable analysis was conducted to identify factors associated with a favorable trifecta outcome, arbitrarily defined as a combination of the following postoperative events: International Prostate Symptom Score 15 ml/s, and no perioperative complications. Results and limitations: Overall, 1330 consecutive cases were analyzed, including 487 robotic (36.6%) and 843 laparoscopic (63.4%) SP cases. Median overall prostate volume was 100 ml (range: 89-128). Median estimated blood loss was 200 ml (range: 150-300). An intraoperative transfusion was required in 3.5% of cases, an intraoperative complication was recorded in 2.2% of cases, and the conversion rate was 3%. Median length of stay was 4 d (range: 3-5). On pathology, prostate cancer was found in 4% of cases. Overall postoperative complication rate was 10.6%, mostly of low grade. At a median follow-up of 12 mo, a significant improvement was observed for subjective and objective indicators of BOO. Trifecta outcome was not significantly influenced by the type of procedure (robotic vs laparoscopic; p = 0.136; odds ratio [OR]: 1.6; 95% confidence interval [CI], 0.8-2.9), whereas operative time (p = 0.01; OR: 0.9; 95% CI, 0.9-1.0) and estimated blood loss ( p = 0.03; OR: 0.9; 95% CI, 0.9-1.0) were the only two significant factors. Retrospective study design, lack of a control arm, and limited follow-up represent major limitations of the present analysis. Conclusions: This study provides the largest outcome analysis reported for MISP for BOO/BPE. These findings confirm that SP can be safely and effectively performed in a minimally invasive fashion in a variety of healthcare settings in which specific surgical expertise and technology is available. MISP can be considered a viable surgical treatment in cases of large prostatic adenomas. The use of robotic technology for this indication can be considered in centers that have a robotic program in place for other urologic indications. Patient summary: Analysis of a large data set from multiple institutions shows that surgical removal of symptomatic large prostatic adenomas can be carried out with good outcomes by using robot-assisted laparoscopy.

Radical cystectomy is associated with significant morbidity and cost, with rates of gastrointestinal complications as high as 30%. Alvimopan is a mu opioid receptor antagonist that has been shown in randomized-control trials to accelerate gastrointestinal recovery in patients undergoing bowel resection with primary anastamosis. We report our experience with gastrointestinal recovery for patients undergoing cystectomy with urinary diversion treated with alvimopan and cost benefit associated.Between January 2008 and October 2012, 80 patients underwent radical cystectomy with urinary diversion at two institutions. Forty-two patients in our study did not receive alvimopan preoperatively. Thirty-eight patients received perioperative alvimopan and were without postoperative nasogastric decompression. Return of bowel function, initiation of diet, and gastrointestinal complications and estimated cost of hospitalization were evaluated.Times to first flatus (3.1 days versus 4.7 days, p0.01, 95% CI 0.96-2.24) and bowel movement (3.9 days versus 4.9 days, p0.01, 95% CI 0.45-1.55) were significantly shorter in those patients who received alvimopan. Additionally, the initiation of clear liquid diet (4.1 days versus 5.5 days, p0.01, 95% CI 0.70-2.10), regular diet (5.2 days versus 6.3 days, p0.01, 95% CI 0.39-1.81) and hospital discharge (6.1 days versus 7.7 days, p = 0.04, 95% CI 0.01-3.21) were accelerated in the alvimopan cohort. There were no incidences of prolonged ileus in patients who received perioperative alvimopan (0% versus 26.2%, p0.01). With an approximate average cost of alvimopan administration $825 per hospitalization, the average cost benefit of administration over control was $1515 per hospitalization. The cost benefit was mainly a result of a shorter inpatient hospitalization and lack of gastrointestinal morbidity which accumulated a majority of the difference.In our experience, the use of alvimopan perioperatively significantly accelerates the rate of gastrointestinal recovery and hospital discharge, eliminates the need for nasogastric tube decompression, and reduces the incidence of post-operative ileus in patients following radical cystectomy and urinary diversion.

Objective To describe a new technique for repairing traumatic testicular ruptures using readily available graft material. Materials and Methods Surgical management of testicular rupture is often associated with loss of testicular parenchyma because of tissue debridement and concerns of pressure-related ischemia. We present our experience with 3 cases using a novel technique using extracellular matrix graft materials for the reconstruction of tunica albuginea in patients with testicular rupture. We describe a case using bovine pericardium (Neovasc Inc, Richmond, British Columbia) and 2 cases using cadaveric dermis (Coloplast Inc, Minneapolis, MN) to repair complex testicular defects without debridement of extruded testicular parenchyma. Results No postoperative complications occurred in any of the patients. Long-term follow-up at 18 months for one patient revealed good cosmetic results, with radiographic findings confirming testicular integrity and flow. Conclusion The use of graft material in the repair of testicular rupture helps prevent the loss of testicular parenchyma through a tension-free closure leading to excellent cosmetic and radiographic outcomes.

Background Erectile dysfunction after prostate radiation therapy remains an ongoing challenge and critical quality of life issue. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT impotency would be higher than conventional radiation therapy approaches. This study sought to evaluate potency preservation and sexual function following SBRT for prostate cancer. Methods Between February 2008 and March 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. Potency was defined as the ability to have an erection firm enough for intercourse with or without sexual aids while sexual activity was defined as the ability to have an erection firm enough for masturbation and foreplay. Patients who received androgen deprivation therapy (ADT) were excluded from this study. Ninety-seven hormone-naïve men were identified as being potent at the initiation of therapy and were included in this review. All patients were treated to 35–36.25 Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Prostate specific antigen (PSA) and total testosterone levels were obtained pre-treatment, every 3 months for the first year and every 6 months for the subsequent year. Sexual function was assessed with the Sexual Health Inventory for Men (SHIM), the Expanded Prostate Index Composite (EPIC)-26 and Utilization of Sexual Medication/Device questionnaires at baseline and all follow-up visits. Results Ninety-seven men (43 low-, 50 intermediate- and 4 high-risk) at a median age of 68 years (range, 48–82 years) received SBRT. The median pre-treatment PSA was 5.9 ng/ml and the minimum follow-up was 24 months. The median pre-treatment total serum testosterone level was 11.4 nmol/L (range, 4.4-27.9 nmol/L). The median baseline SHIM was 22 and 36% of patients utilized sexual aids prior to treatment. Although potency rates declined following treatment: 100% (baseline); 68% (6 months); 62% (12 months); 57% (18 months) and 54.4% (24 months), 78% of previously potent patients had erections sufficient for sexual activity at 24 months post-treatment. Overall sexual aid utilization increased from 36% at baseline to 49% at 24 months. Average EPIC sexual scores showed a slow decline over the first two years following treatment: 77.6 (baseline); 68.7 (6 months); 63.2 (12 months); 61.9 (18 months); 59.3 (24 months). All sexual functions including orgasm declined with time. Prior to treatment, 13.4% of men felt their sexual function was a moderate to big problem which increased to 26.7% two years post treatment. Post-treatment testosterone levels gradually decreased with a median value at two year follow-up of 10.7 nmol/L. However, the average EPIC hormonal scores did not illustrate a statistically significant difference two years post-treatment. Review of the radiation doses to the penile bulb in this study, a potential marker of post-treatment sexual function, revealed that the dose was relatively low and at these low doses the percentage of the penile bulb receiving 29.5 Gy did not correlate with the development of ED. Conclusions Men undergoing SBRT monotherapy for prostate cancer report sexual outcomes comparable to those reported for conventional radiation modalities within the first 24 months after treatment. Longer follow-up is required to confirm the durability of these findings.

Purpose: Robot-assisted laparoscopic simple prostatectomy (RALSP) is a feasible option in men with markedly enlarged prostates (over 100 g) and urinary obstruction.1 Since January 2011, we have modified our surgical method in hope of further enhancing the perioperative outcomes related to RALSP. Herein, we report our initial experience utilizing a circumferential urinary reconstruction technique. Methods: A total of nine patients underwent RALSP with a surgical modification for symptomatic benign prostatic hypertrophy (BPH) in 2011. All, but one patient, were in complete urinary retention preoperatively. All RALSP were performed via the suprapubic approach. Upon removal of the obstructing prostate adenomas, a circumferential anastomosis was completed by advancing and approximating the bladder neck to the prostate urethral stump with 8 to 10 interrupted 2-0 vicryl suture, similar to that of the urethral vesical anastomosis during robotic radical prostatectomy. Six patients who underwent a standard...

INTRODUCTION AND OBJECTIVES: Gleason score from biopsy specimens is important for prostate cancer risk stratification and influences treatment decisions. Gleason score upgrading (GSU) between biopsy and surgical pathology specimens has been reported as high as 50% and presents a challenge in counseling low-risk patients. While recent studies have investigated predictors of GSU, populations in these studies have been largely Caucasian. We report our analysis of predictors of GSU in a large urban African-American population across two institutions. METHODS: A total of 959 patients with DAEAmico low risk prostate cancer underwent radical prostatectomy at our institution between January 2005 and July 2012. Race, age, PSA, body mass index, CAPRA score and TRUS biopsy characteristics (number of reported biopsy cores showing adenocarcinoma, highest percent of biopsy core positive for adenocarcinoma, and measured TRUS prostate volume) were analyzed with both univariate and multivariate analysis to identify significant predictors of GSU while controlling for clinical parameters. RESULTS: Of the 959 cases, 288 (30.0%) were upgraded on final pathologic specimen, while the remaining 671 had the same Gleason sum as the preoperative biopsy. (Table 1) Our patient population consisted of 40.0% African-Americans and 42.0 of the AfricanAmerican population showed GSU. Mean Gleason score for those who were upgraded was 7.24. Upon univariate and multivariate analysis, BMI, total positive biopsy cores, percent of core involved with cancer, CAPRA score, and smaller prostate volume were statistically significant in the upgraded cohort. Patients who upgraded tended to be of higher BMI and of African-American descent in our analysis. Transrectal biopsies of these patients showed smaller prostate volumes but higher cores positive with high % disease per core. CONCLUSIONS: More than a quarter of low-risk prostate cancer patients were upgraded on final pathology in our series. Higher BMI and CAPRA score, smaller prostate volume and total number of cores and percent of cores involved were independent predictors of GSU. Individuals, especially African-Americans, with those clinical parameters may harbor occult high-grade disease and should be carefully counseled on treatment decisions.

Introduction: Calyceal diverticula are cystic dilations within a renal collecting system and are prone to urinary stasis, stone formation, and recurrent infection.1 Management of calyceal ...

To present our experience with robot-assisted simple prostatectomy in patients with large gland adenoma (100 g) that would not be amenable to transurethral treatments.From August 2009 to May 2011, 13 robot-assisted simple suprapubic prostatectomies were performed in patients with symptomatic large gland (100 g) prostatomegaly on transrectal ultrasonography (mean 163 cc). Essential aspects of our technique include a transverse cystotomy just proximal to the prostatovesical junction and use of a robotic tenotomy grasper to aid in adenoma dissection.Mean operative time was 179 minutes (range 90-270 min), and mean estimated blood loss was 219 mL (range 50-500 mL). Mean hospital stay was 2.7 days (range 1-8 d), and the mean urethral catheterization time was 8.8 days (range 5-14 d). None of the patients needed blood transfusion. One patient had an intraoperative urinary leak after bladder closure that was managed with prolonged urethral catheterization (14 d). Histopathologic analysis confirmed benign prostatic hyperplasia (BPH) in all patients, and mean specimen weight on pathologic examination was 127 g (range 100-165 g). Mean follow-up duration was 7.2 months with all patients having a minimum of a 4-month follow-up. Significant improvements were noted in the International Prostate Symptom Score (preoperative vs postoperative 18.1 vs 5.3, p0.001) and the maximum urine flow rate (preoperative vs postoperative 4.3 vs 19.1 mL/min, P0.001).Minimally invasive robot-assisted simple prostatectomy is technically feasible in patients with large volume (100 g) BPH and is associated with significant improvements in obstructive urinary symptoms. Surgeons with robotic expertise may consider using this approach for treatment of their patients with large volume BPH.

Background The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism. Methods Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires. Results All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment. Conclusions Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.

Nephron sparing surgery (NSS) is accepted as the treatment of choice in patients with solitary kidney, bilateral renal masses, and in patients with renal insufficiency (1,2). In patients with renal tumors less than 4 cm and a normal contralateral kidney, NSS has been shown to have a decreased incidence of long-term renal insufficiency (2). It has also been associated with an improved quality of life (3,4). Open partial nephrectomy (OPN) is the gold standard treatment for NSS. Laparoscopic partial nephrectomy (LPN) has recently been popularized by Gill and associates (5). Although LPN has been shown to have good oncologic outcomes at an intermediate follow-up (6); it requires advanced laparoscopic skills and has associated perioperative morbidity (7,8). A recent large multicenter retrospective study compared the perioperative outcomes between open and laparoscopic partial nephrectomy (9). LPN was associated with shorter operative time, decreased operative blood loss, and shorter hospital stay. Although, the incidence of intraoperative complications was comparable in the two groups LPN was associated with longer ischemia time, more postoperative complications (particularly urological), and an increased number of subsequent procedures. Overall 25.2% of patients undergoing LPN had a postoperative complication compared to 19.8% who underwent OPN. After 3 months, renal functional outcomes for laparoscopic and open partial nephrectomy were similar.

To evaluate the efficacy of stone volume measured using a three-dimensional (3D) reconstruction of preoperative non-contrast computed tomography (NCCT) as an independent predictor of success after extracorporeal shock wave lithotripsy (ESWL) of upper urinary tract calculi.We evaluated preoperative NCCT in 94 patients who had ESWL for solitary upper urinary tract calculi of 4-20 mm in diameter. Axial images were used to measure the skin-to-stone distance (SSD), Hounsfield Unit (HU) density and axial stone diameter. Stone volume was calculated on a volume-rendered 3D image for each stone. Maximum stone length was determined by comparative measurements of each stone in coronal, sagittal and axial planes, and was also measured on a plain abdominal film before ESWL. For ESWL we used the DoliS lithotripter (Dornier Medical Systems, Marrietta, GA, USA). A plain film at 6 weeks was used to categorize patients as stone-free (SF) or with residual stone.In all, 58 (62%) patients were SF and 36 (38%) had RS; the mean stone volume was significantly different between these groups (274 vs 464 microL, P = 0.002). Logistic regression analysis showed that stone volume was the strongest predictor of SF status (P0.001), compared to peak HU (P = 0.015), mean HU (P = 0.04) and axial stone diameter (P = 0.006). The body mass index, SSD and maximum stone length on NCCT or a plain film did not predict success. A stone volume of500 microL best predicted treatment success (P0.001) with 72% of patients with a stone volume of500 microL having a successful outcome, vs only 27% with a stone volume of500 microL.Our study suggests that stone volume is an optimal predictor of SF status after ESWL of solitary upper urinary tract calculi.

Although significant progress has been made during the last 3 decades in the minimally invasive surgical management of stone disease, the medical prevention of urolithiasis still remains challenging as much less progress has been achieved during the same time period. The purpose of this article is to provide the practicing urologist with practical guidelines for the metabolic evaluation and management of the recurrent stone patient. The recommendations are based on the latest available information regarding the pathogenesis, medical treatment options, and decision-making rationale when managing these challenging patients.

Corticosteroids have been commonly used in medical expulsive therapy for obstructing ureteral calculi. The exact mechanism of action responsible for facilitation of stone expulsion is unknown, but it is attributed to the anti-inflammatory properties of corticosteroids. Corticosteroids inhibit the production of phospholipase A2 and cyclooxygenase-2, both of which are involved in prostaglandin synthesis. We sought to determine if hydrocortisone inhibits ureteral contractility directly by assessing its action in an isolated in vitro contractility assay.Porcine ureters were attached to force displacement transducers and suspended in organ tissue baths containing aerated Krebs buffer. Tissues were equilibrated for 1 hour, and a spontaneous contractility rate was established. After equilibration, tissues were incubated with a 10-fold concentration curve of hydrocortisone (1 nM-10 microM) for 90 minutes, and compared with indomethacin (1 microM) and dimethyl sulfoxide (DMSO) 0.1% as positive and negative controls of contraction, respectively. Contractility rates were recorded on a polygraph and analyzed for changes over exposure time during the course of the experiment.Hydrocortisone inhibited ureteral contractility in a concentration dependent trend. After 90 minutes of treatment, 100 nM, 1 microM, and 10 microM all produced a statistically significant decrease in ureteral contractility rates relative to DMSO controls. The average percent decrease was 43.7% by 100 nM, 66.9% by 1 microM, and 66% by 10 microM hydrocortisone. This decrease in ureteral contractility continued to be significant at 120 minutes. In addition, 10 microM and 1 microM hydrocortisone treatment caused a similar reduction in contractility to indomethacin at 120 minutes.Hydrocortiosone effectively inhibits stretch-induced ureteral contractility of porcine ureter in an isolated in vitro assay.

The introduction of minimally invasive surgery for radical retropubic prostatectomy has increased the incidence of recognition of accessory pudendal arteries. Early identification and preservation of these vessels is paramount for optimal functional outcomes. In this article, we describe our robotic surgical technique for identification and preservation of both lateral and apical accessory pudendal arteries. The illuminated, magnified surgical field, the pneumoperitoneum which minimizes venous bleeding, and the ability to acutely angle the robotic instruments assists in the preservation of these arteries. Although anatomy precludes the preservation of all accessory pudendal arteries, adopting a strategic approach to robotic dissection allows accessory pudendal arteries to be successfully spared in most cases.

Objectives Solitary metastasis to the renal fossa after radical nephrectomy for renal cell carcinoma is uncommon. We report the first series on hand-assisted laparoscopic excision for renal cell carcinoma fossa recurrences. Methods We performed a retrospective review of patients who underwent hand-assisted laparoscopic excision of renal cell carcinoma fossa recurrence. Patients with distant metastasis or local lymph node or adrenal metastasis were excluded from analysis. We collected data on patient and tumor characteristics, nephrectomy and fossa mass excision procedures, and postoperative outcomes. Results Between 2001 and 2007, 5 patients underwent laparoscopic resection of a renal fossa recurrence. Mean time to recurrence after radical nephrectomy was 23 months (range, 5 to 46 months) and mean size of the renal fossa mass was 6 cm (range, 4.2 to 9.5 cm). The average operative time was 232 minutes (range, 150 to 300 minutes) and average estimated blood loss was 175 mL (range, 25 to 400 mL). One patient required conversion to open surgery. There were no postoperative complications and mean hospital stay was 4 days. With mean follow-up of 43 months, the cancer-specific and disease-free survival rates were 60% and 20%, respectively. Of the 4 patients who underwent complete resection, 2 died from metastatic disease at 13 and 56 months, 1 continues to have progressive metastatic disease at 69 months, and 1 remains free of any clinical evidence of metastatic disease or recurrence at 37 months. One patient who underwent incomplete resection as a result of inferior vena cava invasion continues to have progressive local and distant metastatic disease at 40-month follow-up. Conclusions Hand-assisted laparoscopic excision of renal fossa recurrence after radical nephrectomy appears to be safe and effective for carefully selected patients.

The incidence of Peyronie's disease is up to 7% in some series. While there are numerous nonsurgical methods of treatment, they do not have a high rate of success. Nesbit plication was once the accepted surgery for Peyronie's disease. Tunical lengthening procedures became popular because they avoided penile shortening caused by the Nesbit procedure. More urologists now perform plaque incision or excision, followed by grafting with different materials. Small intestinal submucosa offered promise as an ideal graft material. It is available off the shelf as 1 or 4-ply graft material. In several studies it appeared to function as a collagen based scaffold with graft incorporation in host tissue.A single reconstructive urologist performed plaque incision and small intestinal submucosa grafting in 4 cases of Peyronie's disease using the same surgical technique.Although early results were positive, we have achieved less than satisfactory results with this material. The penis was straight in the immediate postoperative period but there was recurrent curvature in 3 of the 4 patients, of whom 2 had recurrence within 4 months of the procedure.We observed disappointing results with small intestinal submucosa for Peyronie's disease surgery with a high percent of recurrent curvature. Further studies are needed to determine if 1 or 4-ply small intestinal submucosa is an ideal graft material for the tunica albuginea.

Arteriovenous malformations (AVMs) of the scrotum are rare vascular lesions. To our knowledge we report the first case of recurrent scrotal AVM. CASE REPORT A 67-year-old American Indian male with a history of scrotal AVM diagnosed and treated at our institution with preoperative embolization followed by hemiscrotectomy was disease-free for 12 years. Recently a chronic nonhealing ulcer developed on the right hemiscrotum. The patient presented elsewhere on 2 occasions in shock secondary to severe arterial bleeding from the ulcer requiring prompt resuscitation.

We report an unusual case of a 2-year-old child with a psoas abscess fistulizing to the bladder, managed by non-surgical therapy including urethral catheter drainage, percutaneous abscess drainage and intravenous antibiotics.

To evaluate the intermediate-term outcomes of hand-assisted laparoscopic radical nephrectomy (HALRN) for clinically organ-confined renal cell carcinoma (RCC).We retrospectively reviewed patients who had HALRN for clinically organ-confined RCC at the University of Wisconsin from 1996 to 2003. All patients with pathologically confirmed RCC and withor=3 years of follow-up were included in a retrospective chart review of variables before, during and after HALRN, as well as the clinical outcomes.In all, 75 patients had HALRN in the study period; their mean age was 59 years, body mass index 29 kg/m(2), operative duration 227 min, estimated blood loss 130 mL, and none required conversion to open nephrectomy. The median time to first oral intake was 2.5 days and the median hospital stay 4 days. On pathological examination the mean tumour size was 5.8 cm; 70% were pT1, 26% pT2 and 4% pT3; 82% were clear cell, 9% papillary, 8% chromophobe and 1% collecting duct carcinoma. Of the 65 patients who had a follow-up ofor=36 months (mean 46, range 36-117), the 3- and 5-year disease-free survival rate was 93.4% and 90.2%, respectively; the 3- and 5-year cancer-specific survival rate was 96.5% and 94.4%, respectively.Our study suggests that HALRN is a safe and minimally invasive treatment for managing clinically organ-confined RCC, with good intermediate-term oncological outcomes.

Intracavernous self-injection of pharmacologic agents is an effective method of treatment of erectile dysfunction. Intracorporeal needle breakage is a rare complication of intracavernosal self-injection. We report an unusual case of multiple retained needles in a 44-year-old man who presented with penile edema after intracavernous self-injection complicated by needle breakage. The patient was treated with nonoperative therapy and observed on a course of antibiotics to which he responded favorably. He continued to have good erectile function. We also present a review of the reported data and recommend a treatment strategy for the management of retained intracorporeal needles.