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INTRODUCTION AND OBJECTIVE:Pathogenic/likely pathogenic (P/LP) germline genetic variants occur in ∼10-15% of all prostate cancer (PCa) patients. However, complicated and restrictive testing guideli...

10500 Background: Approximately 10-15% of prostate cancer (PCa) patients (pts) have a pathogenic germline variant (PGV). Identification of a PGV has important implications affecting decisions regarding cancer screening, treatment selection, and family cascade testing. There exists limited data documenting real world recommendations post germline genetic testing (GGT). This study was designed to collect clinician reported outcomes from PCa pts who underwent GGT. Methods: An IRB-approved, nationwide, prospective registry recruited unselected PCa pts from 15 community and academic urology practices. Pts underwent an 84-gene panel test, with clinical outcomes collected via clinician-completed case report forms > 1-month post GGT. Statistical significance was determined by two-tailed Fisher’s exact test. Results: 982 predominantly white (75.9%), non-metastatic (80.7%) males with PCa were recruited; 56.9% met National Comprehensive Cancer Network (NCCN) GGT criteria. Average age was 65.3 years at PCa diagnosis. PGVs, most commonly CHEK2 (17) and BRCA2 (10), were identified in 100 (10.2%) pts; 34 (34%) of these did not meet NCCN GGT criteria. Among PGV positive pts, 241 recommendations were made (Table). They were more likely to have changes to treatment (p < 0.0001), follow up (p < 0.0001) and cascade testing recommendations (p < 0.0001) than those with negative/variant of uncertain significance (VUS) results. There were no significant differences in changes to treatment (p = 0.4471) or follow up (p = 0.861) for pts who met NCCN criteria versus those who did not. 7 pts with PGVs received targeted therapy or were referred to a clinical trial. 5 pts with VUS results were also referred to a clinical trial. Among these 12 pts, 6 (50%, 2 CHEK2 PGV, 1 ATM PGV, 1 VUS each ATM, BLM, CHEK2) did not meet NCCN GGT criteria. Referral to a genetic counselor was the most common follow up recommendation for those with PGV (38 patients, 38%) and VUS results (66, 13.7%). The most commonly reported impact to health outcomes for those with negative results was knowledge/reassurance (38, 7.88%). Conclusions: This study showed that GGT did influence PCa pts care. Appropriately, pts with PGVs received a greater number of recommendations for relatives, changes to follow up and treatment. [Table: see text]

10504 Background: Pathogenic/likely pathogenic (P/LP) germline genetic variants are estimated to occur in 10-15% of all prostate cancer (PCa) patients. However, genetic testing for PCa patients is underutilized, partially due to complicated and restrictive testing guidelines developed at a time when the cost of testing was high. We conducted a study based in community urology clinics to determine the incidence of P/LP variants in PCa patients who met and did not meet the NCCN 2019 PCa germline genetic testing criteria. Methods: An IRB-approved, multicenter, prospective registry was initiated with 15 community and academic urologists nationwide. Eligibility criteria included patients with a PCa diagnosis unselected for personal or family history, stage or histology who had not been previously tested. Consecutive patients ages 18-90 were consented and underwent an 84-gene germline panel test. HIPAA-compliant electronic case report forms distributed to clinician collected information on patient diagnoses, NCCN testing criteria, and results-based recommendations. Results: To date, 640 enrolled patients have genetic testing results available. Overall, 69 (10.8%) patients had 72 P/LP variants detected, 15% of which were in BRCA1/2. Of the 532 patients for whom we have clinician-reported data, 293 (55%) met NCCN criteria and 239 (45%) did not. Median age was 70 (range 44-90). Overall, 11.1% (59/532) of patients with clinician-reported data had a P/LP variant. 36 (12.3%) of patients who met NCCN criteria and 23 (9.6%) of patients who did not meet criteria had a P/LP variant. The difference in P/LP rate between the two groups was not statistically significant (p=0.33). If only a conservative 12-gene PCa panel was considered, P/LP yield was 5.5% (29/532), with 8 (28%) of these patients missed by guidelines. Stratification by self-reported ethnicity was: 76% White/Caucasian (52 patients w/ P/LP), 18% Black/African American (2 patients w/ P/LP), and

Primary hyperparathyroidism is a common cause of hypercalcemia with resulting hypercalciuria and a subset of these patients with primary hyperparathyroidism present with urolithiasis. We evaluated the metabolic stone profile in patients presenting for parathyroid surgery and determined whether there were differences between those with and without a history of urinary stones.A total of 60 patients with primary hyperparathyroidism presenting for parathyroid surgery were prospectively enrolled in the study, of whom 54 completed a preoperative 24-hour urine collection. Of these 54 patients 27 completed an additional postoperative 24-hour urine collection. We compared preoperative metabolic urinary profiles and serum calcium in patients with primary hyperparathyroidism with and without a history of urolithiasis. In addition, we compared changes in urine metabolic profiles that occurred after successful parathyroid surgery.There were no significant differences in preoperative 24-hour urine metabolic profiles or serum calcium between patients who had primary hyperparathyroidism with and without a history of urolithiasis. Compared to preoperative levels after successful parathyroid surgery there were significant decreases in serum calcium (10.8 to 9.3 mg/dl, p0.001), urinary calcium (319 to 156 mg per day, p0.01) calcium oxalate supersaturation (8.6 to 5.7, p = 0.016) and calcium phosphate supersaturation (1.6 to 0.9, p = 0.002) in the 27 patients who completed a postoperative 24-hour urine collection.Other etiological factors must exist that cause some patients with primary hyperparathyroidism to form stones, while most never have stones despite profound hypercalcemia and hypercalciuria. Routine 24-hour urine evaluation cannot predict which patients with primary hyperparathyroidism will have kidney stones.

The introduction of the da Vinci Surgical System to perform complex reconstructive procedures, such as repair of ureteropelvic junction obstruction, has helped to overcome some of the technical challenges associated with laparoscopy. We review our large multi-institutional experience with long-term followup of robotic dismembered pyeloplasty.A total of 140 patients from 3 university medical centers underwent robotic dismembered pyeloplasty. An institutional review board approved retrospective chart review was performed to collect demographic, preoperative, operative and postoperative data. Patients were analyzed as an entire cohort and then divided into various subgroups.Of the cases 117 (84.6%) were primary repairs and 23 (16.4%) were secondary repairs. There were 13 (9.3%) patients who underwent concomitant stone extraction and 5 (3.6%) procedures were performed on patients with solitary kidneys. A crossing vessel was found in 77 (55%) patients. Mean operative time was 217 minutes (range 80 to 510), estimated blood loss was 59.4 ml (range 10 to 600), mean length of hospital stay 2.1 days (range 0.75 to 7) and mean followup was 29 months (range 3 to 63). Radiographic resolution of obstruction on first postoperative diuretic renal scan or excretory urogram was noted in 134 patients (95.7%). There was a 7.1% major complication rate and a 2.9% minor complication rate. No statistically significant differences were found in any parameters among patients from the various cohorts.To our knowledge this review represents the largest multi-institutional experience of robotic dismembered pyeloplasty with long-term followup. Robotic pyeloplasty appears to be safe, durable and efficacious for primary and secondary ureteropelvic junction obstruction with or without concomitant stone extraction, and for patients with a solitary kidney.

Objectives Stone disease is a rare complication after renal transplantation, and the management of these stones can be difficult. In many cases, the best modality to treat stones in transplanted kidneys/ureters is with a percutaneous approach. The goal of this study was to review our series of percutaneous nephrolithotomy (PNL) to evaluate the success rates and present the key technical points to achieve a successful outcome. Methods We retrospectively reviewed our series of PNL from January 1997 to December 2007 and identified 15 patients who had had PNL performed in a transplanted kidney. We evaluated multiple perioperative variables and how the patients' urolithiasis presented. We also collected intraoperative data. Results A total of 15 patients underwent successful PNL in a transplanted kidney. In all patients, but 3, access into an anterior, upper pole calix was achieved, and access was obtained with ultrasound guidance alone or a combination of ultrasound guidance and fluoroscopy. Ten patients had a pre-existing nephrostomy tube, and this was used in all but 1 patient. Of the 15 patients, 8 (53%) were treated with percutaneous flexible nephroscopy/ureteroscopy, and 7 had tracts dilated to 30F to perform rigid PNL. All patients were rendered stone free at the end of the procedure, no complications developed, and no patient required a blood transfusion. Conclusions Nephrolithiasis in a transplanted kidney can be challenging to diagnose and to treat. PNL is most often the best modality to render patients stone free.

Objectives We have previously reported on the disparity in the clinicopathologic features of prostate cancer between black and white patients at our equal-access institution during the 1990s. The goal of this study was to determine whether the worse clinicopathologic features of prostate cancer in black patients have persisted in the 2000s. Methods We examined 362 men (224 black and 138 white) treated with radical prostatectomy at the Veterans Affairs Medical Center in New York. We compared the clinicopathologic variables between 227 patients treated during the 1990s (group 1) and 135 treated in the 2000s (group 2). Results In group 1, black patients were significantly younger ( P P = 0.001), Gleason score ( P = 0.005), and stage ( P = 0.03) than white patients. In group 2, black patients continued to have significantly greater PSA levels ( P = 0.04) and Gleason scores ( P = 0.005) than white patients. Comparing only the black patients, those in group 2 had significantly lower PSA levels ( P P = 0.03), but had worse Gleason scores ( P = 0.03) than those in group 1. On multivariate analysis, black patients were significantly more likely to have a worse Gleason score ( P = 0.005) than white patients. Conclusions Our data have demonstrated a narrowing of the differences in pathologic stage between black and white patients in the 2000s. However, black men have continued to have worse Gleason scores and greater PSA levels than white patients. These findings suggest that there may be different patterns of molecular alterations in black men that may contribute to the poor tumor differentiation. Additional research is underway to better characterize these underlying molecular mechanisms.

Purpose: Body mass index (BMI) has been shown to influence the outcome of various surgical procedures. The purpose of this study is to assess the relationship between BMI, gender, and the distribution of subcutaneous and perirenal fat. Methods: A retrospective review was performed for 123 patients who underwent radical or partial nephrectomy. Preoperative CT scans were reviewed by two independent observers. Subcutaneous fat was measured at three locations and perirenal fat was measured at six locations. Statistical analysis was performed using the Student's t test and the Pearson's correlation coefficient. Results: Mean anterior subcutaneous fat was significantly greater in females than in males (2.54 vs. 1.78 cm, p < 0.001) as was mean right posterolateral subcutaneous fat (2.78 vs. 2.21 cm, p = 0.03). With regard to perirenal fat, men were greater than women for all perirenal locations around the left kidney. For the right kidney, men were greater than women for four out of six perirenal positions. In both men and women, BMI was strongly correlated with subcutaneous fat. However, BMI was weakly correlated with perirenal fat. Conclusions: Women exceed men in subcutaneous fat, while men exceed women in perirenal fat. Obese patients are very likely to have large amounts of subcutaneous fat, but will not necessarily have proportionally increased fat around their kidneys when compared to the patients with lower BMI. These differences may have important implications for surgical approaches to the kidney. © 2010 Springer-Verlag.

Mesh erosion into the urinary bladder resulting in a bladder calculus is an uncommon, but significant, complication of herniorrhaphy. We present the operative and radiographic images of a 76-year-old woman who presented with inguinal drainage, urgency, frequency, recurrent urinary tract infections, and a large bladder calculus 3 years after femoral herniorrhaphy. Open cystolithotomy revealed the herniorrhaphy mesh had eroded into the bladder, causing the draining inguinal fistula tract and bladder calculi. Repeat herniorrhaphy without mesh and calculi extraction were performed without incident.

Intracorporeal suturing can be challenging, especially in the case of laparoscopic partial nephrectomy. During these procedures, suturing must reapproximate renal tissue to achieve hemostasis but not tear through tissue. We present a new device, the ANPA Suturelock, which can be adjusted to increase or decrease suture tension, optimizing tissue apposition.Two participants (one experienced laparoscopist, one junior resident) completed the protocol. A laparoscopic trainer was used to secure 2-0 polyglactin suture ends in rubber foam using five of each of the following: Traditional laparoscopic suture knots (one surgeon's knot and two square knots), square-to-slip knots, Weston extracorporeal knots, ANPA Suturelock, Lapra-Ty devices, Hem-O-Lock clips, and titanium clips. Tensile strength of each knot and knot substitute was measured using an Instron machine (Instron, Norwood, MA). Time to secure the two suture ends was measured for ANPA Suturelock and laparoscopic surgeon's knot. Statistical analysis was performed using the Student t test.Mean tensile strength of the three knot-tying methods was 53.0 newtons (N) while that of the four knot substitute devices was 8.3 N (P0.001). Each of the three individual knot-tying methods had significantly greater tensile strength than any of the knot substitutes (P0.001 for all). Of the knot-tying methods, the surgeon's knot was the strongest (mean tensile strength 63.2 N) and was significantly stronger than square-to-slip and Weston extracorporeal knots (39.1 N and 48.4 N, respectively, P0.05 for both). Of the knot substitutes, ANPA Suturelock (mean tensile strength 14.7 N) was significantly stronger than Lapra-Ty (6.1 N), Hem-O-Lock (5.4 N), and titanium clip (3.0 N) (P0.01 for all). When compared with a laparoscopic surgeon's knot, the time to securing the ANPA Suturelock was significantly quicker for a third year resident (106 sec vs 38 sec, P0.001) and an experienced laparoscopist (75 sec vs 23 sec, P = 0.02).The tensile strengths of traditional knot-tying techniques were greater than that of any knot substitute device. The ANPA Suturelock provided the greatest tensile strength of any knot substitute. The time to secure a knot using the ANPA device was also significantly quicker than tying a standard surgeon's knot.

Histone deacetetylases (HDACs) are a group of corepressors of transcriptional activators and their levels of expression are potentially dysregulated in prostate cancer. Certain inhibitors of histone deacetylases show anti-tumor activity in prostate cancer cell lines. Here, we systemically studied the expression of HDACs in human prostate cancer and the suppression of prostate cancer growth and invasion by HDAC inhibitor SAHA. HDAC1-5 showed increased expression using a combination of DNA microarray, in-situ hybridization, and immunohistochemistry in benign and malignant human prostate tissue as well as RT-PCR and Western blot analysis on various PCa cell lines. Importantly, HDAC inhibitor SAHA suppressed, in particular, prostate cancer cell growth and invasion determined using cell proliferation and Matrigel invasion assays. The findings of this study show that the expression of HDACs and their associated corepressors are increased in prostate cancer in humans and HDAC inhibitor SAHA could serve as a potential therapeutic agent in prostate cancer in addition to anti-androgens.

Bladder neck closure (BNC) is a procedure that, although not performed frequently, can be very beneficial for an appropriately selected patient. T he t raditional role of BNC w as in the female patient with a neurogenic bladder, destroyed bladder neck, and patulous urethra from longterm indwelling catheter drainage (1, 2, 3, 4). Other options for urethral reconstruction using vagina or bowel have been reported, but are very complex, and attempts to create a patent and continent outlet are often unsuccessful (5). Other indications for the procedure have included bladder neck destruction from pelvic trauma, labor and delivery complications, and multiple failed surgical interventions to treat incontinence or urethrovaginal fistulas (6). Bladder neck closure can be combined with other procedures such as creation of a continent catheterizable stoma both separately or in combination with augmentation cystoplasty for patients with small capacity bladders or refractory detrusor overactivity (6, 7, 8). If the patient is unwilling or unable to perform intermittent catheterization, urinary drainage can be managed with a suprapubic tube or an ileovesicostomy (9). In early reports, BNC was often unsuccessful, but refinements in patient selection and surgical technique have significantly improved patient outcomes (13).

Reconstructive surgery of the upper urinary tract can be complicated. During the last 2 decades minimally invasive techniques have emerged as viable options for these complex procedures. We reviewed our experience with robotic surgery for upper urinary tract reconstruction.Between May 2002 and December 2006, a single surgeon performed certain robotic reconstructions on the upper urinary tract in 26 males and 37 females (65 renal units), including dismembered pyeloplasty, dismembered pyeloplasty with stone extraction, ureteroureterostomy, ureterolysis with omental wrap, ureterocalicostomy, ureteral reimplantation and upper pole nephroureterectomy. We compared demographic, preoperative, intraoperative and postoperative data on patients undergoing these various procedures.Across all cases mean blood loss was 125 cc, mean operative time was 244.8 minutes and mean length of stay was 2.8 days. The rate of radiographic and symptomatic improvement was 97.3% and 100%, respectively. We observed 2 major complications during a mean followup of 18.7 months.Our data illustrate that robotics can be successfully and safely used for virtually any type of upper urinary tract reconstruction. Robotic techniques are a viable option for upper urinary tract reconstruction.

Orthopedic and hand surgery implants for internal fixation of fractures have evolved substantially over the past 50 years. Newer metal compositions have been used, and new standards have been applied to older alloys, resulting in modern implants with unique physical properties and better clinical performances. Conventional wisdom has long dictated that implanting different metals should be avoided, but few guidelines exist regarding the safety of using in proximity implant systems of dissimilar metals. To better characterize the landscape of internal fixation implant metallurgy, we have compiled the recommendations and conclusions of the currently available and pertinent literature.

OBJECTIVE To compare the surgical outcomes of elderly patients with renal masses treated with laparoscopic partial nephrectomy (LPN) or laparoscopic cryoablation (LCA). PATIENTS AND METHODS All 15 patients who had LCA at the authors’ institution between May 2003 and July 2005 were included, and compared with a matched cohort of 15 patients selected by patient age and tumour size, from a pre-existing database of 104 patients who had LPN from July 2002 to July 2005. The two groups were compared for gender, number of comorbidities, American Society of Anesthesiologists status (ASA), body mass index (BMI), baseline renal function and haematocrit, location and size of lesion, length of stay, operative time, estimated blood loss (EBL), transfusion rate, number and type of complications, conversion rate, and postoperative renal function and haematocrit. RESULTS The two groups were similar in age, sex, BMI, ASA, baseline renal function, haematocrit, size and side of tumour, the percentage of exophytic tumours, and the likelihood of more than one comorbidity. Surgical outcomes between the groups were also relatively similar. The length of stay, creatinine and haematocrit levels after surgery did not differ between the groups. The LPN group had a significantly longer operation (248 vs 152 min, P

We recently demonstrated that EGFR protein overexpression is more common in African American (AA) prostate cancer patients compared to Caucasian patients. We further examine EGFR dysregulation by determining EGFR mutation status in the tyrosine kinase (TK) domain in prostate cancer patients of different ethnicity. Normal and tumor DNA from 89 radical prostatectomy cases were studied for mutations in the EGFR TK domain using genomic DNA sequencing. We identified 4 novel missense mutations in exons 19, 20 and 21 of EGFR TK domain: 3 in Koreans and 1 in Caucasian but none in AA. We also identified 5 distinct synonymous DNA sequence changes, which did not alter the encoded amino acid, in exons 20 and 21 in 31/89 (35%) patients. Interestingly, these synonymous sequence changes were not observed in normal DNA in 7(23%) patients, indicating the presence of de novo somatic mutation to a new synonymous sequence. Our data reveal that EGFR missense mutation in the TK domain occurs in localized prostate cancer. Our data also demonstrate the presence of somatic mutation to a new synonymous sequence in a subset of patients. Larger population-based studies are required to define the association between EGFR mutations and the ethnic background of patients.

Aims To propose a urodynamic protocol to comprehensively assess all parameters of post prostatectomy incontinence (PPI). Methods Sixty men with a history of PPI after radical prostatectomy prospectively underwent a standardized video urodynamics protocol. A 7F urethral catheter was used for standard cystometry, abdominal leak point pressure (ALPP), and pressure flow measurements. The International Continence Society nomogram classified obstruction and further classification of obstruction was based on fluoro voiding cystourethrography and non-invasive flow rates (free Qmax). Results Twenty-four (40%) men had detrusor overactivity with 8 (13%) also having detrusor overactivity incontinence. Only one patient had impaired compliance. All men had urodynamic stress incontinence, but 21 (35%) men demonstrated it only after removal of the urethral catheter. For men leaking with and without the urethral catheter, the respective ALPP was significantly different, 86.3 and 67 cmH2O, respectively (P = 0.002). The men who leaked only in the absence of the urethral catheter had significantly higher ALPP measurements, P

The risk of developing a malignancy as a complication of solid organ transplantation and chronic immunosuppression has been reported. We report on the first lung transplant recipient to develop transitional cell carcinoma of the bladder and carcinoid of the small intestine after transplantation. The patient eventually required radical cystectomy with ileal conduit diversion because of the aggressive nature of the tumor. The surgical and infectious complications are discussed and the published data reviewed. We conclude that chronic immunosuppression may have contributed to the development of bladder carcinoma in this patient and that similar cases should be aggressively treated.