Radiotherapy Induces Innate Immune Responses in Patients Treated for Prostate Cancers.

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.

Novel Paired Normal Prostate and Prostate Cancer Model Cell Systems Derived from African American Patients.

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.

Discovery of Metabolic Biomarkers Predicting Radiation Therapy Late Effects in Prostate Cancer 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.

Transobturator sling for post-prostatectomy incontinence: radiation's effect on efficacy/satisfaction.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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, p < 0.001), 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. CONCLUSIONS: 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.

Perioperative Outcomes of Robotic and Laparoscopic Simple Prostatectomy: A European-American Multi-institutional Analysis.

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 <8, maximum flow rate >15ml/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 100ml (range: 89-128). Median estimated blood loss was 200ml (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.

Use of "off the shelf" extracellular matrix graft materials for repair of testicular rupture: a novel technique.

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.

Multi-institutional outcomes and cost effectiveness of using alvimopan to lower gastrointestinal morbidity after cystectomy and urinary diversion.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: Times to first flatus (3.1 days versus 4.7 days, p < 0.01, 95% CI 0.96-2.24) and bowel movement (3.9 days versus 4.9 days, p < 0.01, 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, p < 0.01, 95% CI 0.70-2.10), regular diet (5.2 days versus 6.3 days, p < 0.01, 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%, p < 0.01). 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. CONCLUSION: 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.

Robotic-assisted prostatectomy and open radical retropubic prostatectomy for locally-advanced prostate cancer: multi-institution comparison of oncologic outcomes.

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.

Potency preservation following stereotactic body radiation therapy for prostate cancer.

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.

Predictors of Gleason score upgrading in a large African-American population.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.01) and percent of core involved with cancer (P < 0.01), increasing CAPRA score, and serum PSA were independent predictors of GSU on both uni- and multivariate regression analyses. African Americans had a 73 % increase in the incidence of GSU over other races. CONCLUSION: More than a quarter of low-risk prostate cancer patients were upgraded on final pathology in our series. Higher BMI, serum PSA, CAPRA score, percent of cores positive, and percent of cores involved were independent predictors of GSU. Individuals with those clinical parameters may harbor occult high-grade disease and should be carefully counseled on treatment decisions.

Stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer: the Georgetown University experience.

BACKGROUND: Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation which may be radiobiologically favorable to conventional low-dose fractions commonly used for prostate cancer radiotherapy. We report our early experience using SBRT for localized prostate cancer. METHODS: Patients treated with SBRT from June 2008 to May 2010 at Georgetown University Hospital for localized prostate carcinoma, with or without the use of androgen deprivation therapy (ADT), were included in this retrospective review of data that was prospectively collected in an institutional database. Treatment was delivered using the CyberKnife® with doses of 35 Gy or 36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were recorded and scored using the CTCAE v.3. Quality of life was assessed before and after treatment using the Short Form-12 Health Survey (SF-12), the American Urological Association Symptom Score (AUA) and Sexual Health Inventory for Men (SHIM) questionnaires. Late urinary symptom flare was defined as an AUA score ≥ 15 with an increase of ≥ 5 points above baseline six months after the completion of SBRT. RESULTS: One hundred patients (37 low-, 55 intermediate- and 8 high-risk according to the D'Amico classification) at a median age of 69 years (range, 48-90 years) received SBRT, with 11 patients receiving ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.2 ng/ml (range, 1.9-31.6 ng/ml) and the median follow-up was 2.3 years (range, 1.4-3.5 years). At 2 years, median PSA decreased to 0.49 ng/ml (range, 0.1-1.9 ng/ml). Benign PSA bounce occurred in 31% of patients. There was one biochemical failure in a high-risk patient, yielding a two-year actuarial biochemical relapse free survival of 99%. The 2-year actuarial incidence rates of GI and GU toxicity ≥ grade 2 were 1% and 31%, respectively. A median baseline AUA symptom score of 8 significantly increased to 11 at 1 month (p=0.001), however returned to baseline at 3 months (p=0.60). Twenty one percent of patients experienced a late transient urinary symptom flare in the first two years following treatment. Of patients who were sexually potent prior to treatment, 79% maintained potency at 2 years post-treatment. CONCLUSIONS: SBRT for clinically localized prostate cancer was well tolerated, with an early biochemical response similar to other radiation therapy treatments. Benign PSA bounces were common. Late GI and GU toxicity rates were comparable to conventionally fractionated radiation therapy and brachytherapy. Late urinary symptom flares were observed but the majority resolved with conservative management. A high percentage of men who were potent prior to treatment remained potent two years following treatment.

Robot-assisted simple prostatectomy: multi-institutional outcomes for glands larger than 100 grams.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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, p<0.001) and the maximum urine flow rate (preoperative vs postoperative 4.3 vs 19.1 mL/min, P<0.001). CONCLUSIONS: 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.

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer.

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.

Stone measurement by volumetric three-dimensional computed tomography for predicting the outcome after extracorporeal shock wave lithotripsy.

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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 (P < 0.001), 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 of <500 microL best predicted treatment success (P < 0.001) with 72% of patients with a stone volume of <500 microL having a successful outcome, vs only 27% with a stone volume of >500 microL. CONCLUSION: Our study suggests that stone volume is an optimal predictor of SF status after ESWL of solitary upper urinary tract calculi.

Practical approach to metabolic evaluation and treatment of the recurrent stone patient.

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.

Comparison of postoperative pain, convalescence, and patient satisfaction after laparoscopic and percutaneous ablation of small renal masses.

PURPOSE: To compare the convalescence and patient satisfaction between laparoscopic and percutaneous ablation for management of small renal masses. METHODS: 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. RESULTS: 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 (P<0.04), 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 (P<0.001), 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. CONCLUSION: Our study suggests that percutaneous ablation in carefully selected patients is associated with early convalescence compared with laparoscopic ablation.

Third prize: Effect of hydrocortisone on porcine ureteral contractility in vitro.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Hydrocortiosone effectively inhibits stretch-induced ureteral contractility of porcine ureter in an isolated in vitro assay.

Current practice patterns in the management of upper urinary tract calculi in the north central United States.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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 calculi <5 mm in size (92%). Although SWL continues to be the most commonly utilized therapy for renal (43%-92%) and proximal ureteral calculi <20 mm in size (29%-51%), and PCNL for renal calculi >20 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 calculi <5 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. CONCLUSION: 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.

Single center preliminary experience with hand-assisted laparoscopic resection of isolated renal cell carcinoma fossa recurrences.

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.

Current practice patterns in the use of ablation technology for the management of small renal masses at academic centers in the United States.

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.