Urology - Articles in Press

Non-contrast Computed Tomography After Percutaneous Nephrolithotomy: Findings and Clinical Significance - Corrected Proof

2012-02-06

Objective: To describe the post-percutaneous nephrolithotomy (PNL) non–contrast-enhanced computed tomography (NCCT) findings and assessed their clinical significance. NCCT evaluates stone clearance after PNL and also reveals procedure-related changes. Methods: One hundred consecutive patients who underwent PNL were evaluated by NCCT one day post-procedure. Two radiologists analyzed the type and severity of the NCCT findings, which were then statistically analyzed in relation to the patient's clinical course. Results: The patients' mean age was 54 years (range 18–82) and the mean maximal stone diameter was 37 mm (range 15–70). The median operative time was 110 minutes for an immediate stone-free rate of 83%, changing to 94% (P = .073) after a second-look PNL in 11 patients. The post-PNL NCCT findings were hydronephrosis (70%), atelectasis (54%), ipsilateral pleural effusion (52%), paracolic gutter fluid (44%), perinephric hematoma (40%), perinephric fluid (32%), ureteronephrosis (31%), renal swelling (23%), contralateral pleural effusion (22%), residual fragments (RFs) (17%), subcapsular hematoma (10%), and flank hematoma (6%). Univariate analysis revealed a significant association with clinical variables for all NCCT findings except for atelectasis, ureteronephrosis, contralateral pleural effusion, RFs, and flank hematoma. In multivariate analysis, only perinephric fluid (P = .007) and ipsilateral pleural effusion (P = .034) were associated with longer hospitalization, and perinephric fluid with longer recovery (P = .004). The complication rate was 12%, but none were linked with the radiological findings. Conclusion: This work describes the post-PNL NCCT findings and their clinical significance. Perinephric fluid and ipsilateral pleural effusion were found to independently predict longer hospitalization and recovery time.

Long-term Outcomes of Percutaneous Nephrolithotomy in Patients With Chronic Kidney Disease: A Single-center Experience - Corrected Proof

2012-02-06

Objective: To present our long-term follow-up data from patients with kidney stones and chronic kidney disease to identify the factors that could help predict the likelihood of long-term deterioration in renal function. Methods: From January 2002 to July 2010, we performed 1117 percutaneous nephrolithotomy (PNL) procedures in 1051 patients. We retrospectively analyzed 69 PNL procedures for 67 patients (47 men and 20 women) in whom the estimated glomerular filtration rate (eGFR) was <60 mL/min/1.73 m2. Two outcomes were measured. The percentage of change in the eGFR was measured comparing the preoperative and postoperative values. A 5% change in renal function was arbitrarily chosen to divide the population into 3 groups: group 1, an eGFR change of ≤5%; group 2, an eGFR increase of >5%; and group 3, an eGFR decrease of <5%. The second outcome measure was the presence of chronic kidney disease progressing in the first and consecutive years. Results: The mean patient age was 57 ± 14.1 years. The complication rate was 23.1% using the Clavien classification. The mean follow-up time was 45.7 ± 17.08 months. The mean eGFR before and after PNL was 37.9 ± 14.05 and 45.1 ± 16.8, respectively. Diabetes mellitus (odds ratio 15.82, P = .036) and urinary infection (odds ratio 10.6, P = .04) were predictive of renal function deterioration at 1 year on multivariate analysis. Conclusion: PNL in patients with chronic kidney disease is safe and results in renal function preservation for a 5-year period. Diabetes mellitus and urinary infection were independent predictive of renal function impairment. Therefore, patients with diabetes mellitus and urinary tract infection should be followed up carefully and informed about hazardous potential of those diseases.

Editorial Comment - Corrected Proof

Boris Gershman, Brian H. Eisner — 2012-02-06

This study presents a retrospective analysis of the changes in renal function after percutaneous nephrolithotomy (PCNL) performed at a large-volume facility in patients with pre-existing renal impairment. The authors observed a significant increase in Modification of Diet in Renal Disease-estimated glomerular filtration rate (GFR) for up to a 3-year period after surgery compared with the perioperative values. Perhaps the more important observation is the absence of renal deterioration after PCNL in patients with compromised renal function. The GFR appears to have remained stable for 1-5 years after surgery, even in this patient cohort with moderate-to-severe pre-existing chronic kidney disease (CKD) and risk factors for additional decline (eg, hypertension, recurrent infection). This is an important observation, because it suggests PCNL itself does not appear to increase the risk of renal deterioration in the intermediate term.

Para-meatus Skin Incision With Long Channel Technique for Midshaft Hypospadias Repair Without Penile Curvature - Corrected Proof

Cheng Su, Tianyou Yang, Zhichong Zhang, Yeqing Xu, Qifeng Liang — 2012-02-06

Objective: To report a new surgical technique for midshaft hypospadias repair without penile curvature. Methods: From September 2007 to October 2010, 21 patients, aged 13 months to 8.9 years, underwent single-stage hypospadias repair by 1 surgeon. The skin incision was created around the meatus, and a long channel beneath the urethral plate was created through the incision to the apex of the glans. The inner preputial flaps were tubularized into a neourethra, which was then transposed to the ventral channel through a ventrolateral tunnel beneath Buck's fascia. Most of the neourethra was covered by the intact soft tissue of the distal ventral penis. The proximal portion of the neourethra was covered by Buck's and dartos fascia around the skin incision, and the skin incision was closed longitudinally. The length of the urethral defect and channel and the postoperative complications were collected and analyzed. Results: A total of 21 patients underwent single-staged hypospadias repair. The average length of the channel was 30 mm (range 25-35). The average length of the neourethra was 35 mm (range 30 to 40). The mean operative time was 60 minutes (range 50-70). The mean hospital stay was 12 days (range 10-14). With an average follow-up of 20 months (range 6-37), no postoperative complication was detected. Conclusion: This technique provides excellent short-term results for midshaft hypospadias without penile curvature and is a safe and simple solution.

Efficacy of Gabapentin for Prevention of Postoperative Catheter-related Bladder Discomfort in Patients Undergoing Transurethral Resection of Bladder Tumor - Corrected Proof

Indu Bala, Neerja Bharti, Vinod K. Chaubey, Arup K. Mandal — 2012-02-06

Objective: To evaluate the effect of 600 mg and 1200 mg oral gabapentin pretreatment for the prevention of postoperative catheter-related bladder discomfort (CRBD) in patients undergoing catheterization after transurethral resection of bladder tumor (TURBT). Materials and Methods: One hundred adult patients undergoing elective TURBT under spinal anesthesia were randomly allocated into 3 groups. Group I patients received placebo, group II patients received 600 mg gabapentin, and group III patients received 1200 mg gabapentin 1 hour before surgery. Lumber subarachnoid block was administered with 2.5 mL 0.5% hyperbaric bupivacaine. The patients were observed for the incidence and severity of CRBD in the postoperative period. Results: The incidence of CRBD was 90% in group I, 66% in group II, and 26% in group III. The incidence of bladder discomfort was significantly low in group III at all time points compared with group I and at 4, 6, 12, and 24 hours compared with group II. The severity of CRBD was also less in group II and III patients compared with group I. Fifteen patients in group I developed moderate discomfort, whereas 1 patient in group II and none in group III. None of the patient receiving gabapentin had severe discomfort. The duration and level of sensory and motor block was comparable among groups. One patient in group II and 2 patients in group III were complained of dizziness in postoperative period. Conclusion: Gabapentin 1200 mg administered before surgery is more effective than gabapentin 600 mg in decreasing the incidence of postoperative CRBD.

Long-term Outcomes After Primary Failures of Artificial Urinary Sphincter Implantation - Corrected Proof

Rou Wang, Edward J. McGuire, Chang He, Gary J. Faerber, Jerilyn M. Latini — 2012-02-06

Objectives: To assess our institutional outcomes after primary artificial urinary sphincter (AUS) failures. Methods: From 1985 to 2010, a total of 149 patients underwent 318 primary and additional AUS procedures. We classified additional procedures as revisions, replacements, or explantations. Results: At a median of 52 months (range, 6-250 months), 53% of patients had required at least 1 additional procedure beyond their initial implantation. These included 106 (63%) revisions, 42 (24.9%) explantations, and 21 (12.4%) replacements. The most common revision was reservoir upsizing (37/106). Reasons for first revision included recurrent incontinence (56.7%), mechanical malfunction (22%), and infection or erosion (18.6%). Explantations were performed primarily for infection and erosion (64.3%). Median time to first revision was 20.1 months (range, 0.1-173 months) after implantation, with a median of 9.5 months (range, 1-102 months) between revisions. Explantation occurred at a median of 22 months (range, 1-221 months) after implant, and subsequent replacement at a median of 33.6 months (range, 2-138 months). At 5 years, 28/83 (33.7%) patients had undergone no additional procedures. Patients with previous radiation were more likely to experience infection (P = .03; OR 3.99; 95% CI 1.03-15.42). Patients with previous myocardial infarction were more likely to experience erosion (P = .04; OR 2.29; 95% CI 1.05-5.02), and obese patients were more likely to experience mechanical malfunction (P = .04; OR 2.62; 95% CI 1.07-6.4). Conclusions: More than half of patients with an AUS will require additional procedures, most likely revision. Radiation, previous myocardial infarction, and obesity are linked to complications. Median time to first revision or explantation is slightly less than 2 years, indicating that long-term follow-up is required after initial implantation.

Radiofrequency Ablation of Incidental Benign Small Renal Mass: Outcomes and Follow-up Protocol - Corrected Proof

2012-02-06

Objective: To review our 10-year experience with radiofrequency ablation, focusing on the outcomes for the incidental benign renal tumor. Tumor ablation is an alternative minimally invasive approach for the treatment of small renal masses (SRMs), with published series appropriately emphasizing the outcomes for the renal cell carcinoma subset of treated tumors. However, just as with partial nephrectomy, approximately 20% of SRMs are benign. The intermediate- to long-term outcome of the incidentally ablated benign tumor and its appropriate follow-up protocol is unknown. Methods: All SRMs treated with temperature-based radiofrequency ablation from 2001 to 2011 were reviewed. Of a total of 280 enhancing SRMs biopsied at radiofrequency ablation, 47 were confirmed as benign tumors. Ablation success was defined as the lack of enhancement on the initial postablation axial imaging. Recurrence was defined as tumor growth and enhancement on follow-up axial imaging. Results: Of the 47 benign tumors, 32 were treated percutaneously and 15 laparoscopically. The histologic biopsy finding was angiomyolipoma in 10 and oncocytoma in 37. The median tumor size was 2 cm (range 1-3.6), and the mean follow-up was 45 months. No recurrences developed, and all lesions required only 1 treatment session. The median pre- and postoperative glomerular filtration rate was 77 mL/min/1.73 m2 (range 39-137) and 68 mL/min/1.73 m2 (range 36-137). The present study was limited by its retrospective nature and small sample population. Conclusion: Radiofrequency ablation of SRMs <3.5 cm found to be benign on concurrent biopsy can be efficaciously treated with a single treatment session. Long-term follow-up imaging might not be required if successful ablation is determined at the initial post-treatment cross-sectional imaging study.

The Augmented Nontransected Anastomotic Urethroplasty for the Treatment of Bulbar Urethral Strictures - Corrected Proof

Blayne K. Welk, Ron T. Kodama — 2012-02-06

Objective: The augmented anastomotic urethroplasty (AAU) combines resection of a urethral stricture and an onlay graft. The augmented nontransected anastomotic urethroplasty (ANTA) is a modification of the AAU and involves complete stricture excision without transecting the spongiosum. Materials and Methods: This is a retrospective cohort study comparing ANTA with dorsal onlay buccal grafting (DOBG) for bulbar urethral strictures. Medical records between 2005 and 2010 were reviewed. A cross-sectional questionnaire was used to assess long-term outcomes. Medians and interquartile ranges are reported. Results: Forty-four men (23 DOBG, 21 ANTA) with a median follow-up of 2.3 years (range 1.2-3.8) were identified. There were no significant differences between ANTA patients and DOBG patients in terms of age, previous treatment, stricture location, or postoperative follow-up. There was no significant difference between groups in the use of bilateral buccal grafts (P = .416); median buccal length harvested was significantly less in the ANTA group (4.5 cm [range 4.0-5.0]) vs the DOBG group (5.0 cm [range 5.0-8.0], P = .047). Response rate to the cross-sectional survey was 59%. Five patients reported postoperative donor site complications, and there were no significant differences between the ANTA and DOBG groups. Overall success was 93% and not statistically different between groups (log rank test, P = .548). One ANTA patient and 2 DOBG patients required posturethroplasty treatment. Conclusions: The ANTA has results similar to DOBG and appears to be a viable option in the treatment of bulbar urethral strictures. This technique allows the surgeon to avoid urethral transection, to reconfigure the width of the urethral plate, and to use a smaller buccal graft.

Clinical Analysis of Management of Pediatric Testicular Germ Cell Tumors - Corrected Proof

2012-02-03

Abstract: Objective: To analyze our experiences of pediatric testicular tumors and investigate the management of pediatric testicular germ cell tumors. Pediatric testicular tumors are rare and the treatment of them has not been well defined. Methods: Children treated for primary testicular tumors between January 1998 and July 2010 were retrospectively analyzed. For yolk sac tumor, the difference of survival rates between patients with and without retroperitoneal lymph node dissection (RPLND) was calculated. Results: Eighty-seven cases met our criteria and 78 were germ cell tumors, including 40 cases with yolk sac tumor. Patients were 3–128 months old (median 19), and 53 patients were diagnosed at younger than 2 years of age. For germ cell tumors, serum α-fetoprotein and β-human chorionic gonadotropin were elevated in 48 and 7 patients, respectively, including 38 and 2 in those with yolk sac tumor. RPLND and chemotherapy were performed in 13 and 19 patients, respectively, and surveillance was performed in 50 patients. With median follow-up of 50 months, 6 patients had recurrence, 4 patients died, and the others achieved complete remission. For stage I yolk sac tumor, the difference of survival rates between patients with and without RPLND was not significant (P = .808). Conclusion: Yolk sac tumor is the most common type of pediatric testicular tumor. For stage I yolk sac tumor, radical inguinal orchiectomy is effective, salvage chemotherapy is promising, and RPLND may not be necessary.

Delayed Presentation of Posterior Urethral Valves in Discordant Twins - Corrected Proof

Matthew S. Christman, Stephen A. Zderic, Thomas F. Kolon — 2012-02-03

Concordant and discordant presentations of posterior urethral valves (PUV) in twins have been described. Twin gestation may complicate the diagnosis of PUV based on prenatal evaluation. A case series of 2 sets of twin births is presented, each of which was discordant for the diagnosis of PUV. A delay in diagnosis occurred in both cases, despite prenatal ultrasound abnormalities. This delay could result from failed sensitivity of prenatal ultrasound or from postnatal evaluation of the incorrect twin. Caution must be exercised during follow-up of abnormalities identified on prenatal ultrasound in diseases in which there are no external distinguishing characteristics.

Optimal Surgical Margin in Nephron-sparing Surgery for T1b Renal Cell Carcinoma - Corrected Proof

Xu-sheng Chen, Zhen-ting Zhang, Jun Du, Xin-chun Bi, Guang Sun, Xin Yao — 2012-02-03

Objective: To determine the optimal surgical margins in nephron-sparing surgery (NSS) for T1b renal cell carcinomas (RCC). Materials and methods: We retrospectively assessed 87 T1b RCC specimens after radical nephrectomy through whole-kidney continuous sections, with 92 T1a RCCs included as controls. The completeness of pseudocapsule (PS) and extra-PS lesions and multifocality were microscopically examined, as was the greatest distance between extra-PS lesions and primary tumors. Results: The rates of incomplete PS (34% [30/87] vs 18% [17/92], P = .015) and positive cancer lesions beyond the PS (39% [34/87] vs 25% [23/92], P = .043) were significantly higher in the T1b than in the T1a group. All extra-PS lesions were located within 3.0 mm of the primary tumor. Multifocal tumors were found in 6% (5/87) of patients with T1b and 5% (5/92) of patients with T1a tumors (P = .928). Conclusion: These results indicate that 4 mm may be the optimal surgical margin for NSS for patients with T1b RCC because all extra-PS lesions were located within 3 mm of the primary tumors.

Ureteropyelostomy Using the Native Ureter for the Management of Ureteric Obstruction or Symptomatic Reflux Following Renal Transplantation - Corrected Proof

Kevinjit Sandhu, Jonathan Masters, Yaron Ehrlich — 2012-02-03

Objective: To evaluate the outcome of ureteropyelostomy using the native ureter for the management of ureteric obstruction or symptomatic reflux after renal transplantation. Materials and methods: This is a single-center retrospective review of consecutive patients who underwent ureteropyelostomy after renal transplantation between the years 2000 and 2009. Ureteropyelostomy was performed using the ipsilateral native ureter. The native kidney was not removed. Patients' baseline characteristics, preceding interventions, and postprocedural outcomes were analyzed. Results: Ten patients underwent ureteropyelostomy after renal transplantation. All had initial Lich Gregoir ureterovesical anastomosis. Reasons for the reconstructive surgery were transplant ureteric stenosis in 8 patients or vesicoureteric reflux causing recurrent graft pyelonephritis in 2 patients. Median follow-up was 53 months (range 24-76). Postoperative complications included 3 patients who had transient anastomotic obstruction after removal of the double pigtail stent. They were managed with short-term ureteric restenting or nephrostomy tube insertion. In addition, 2 patients required delayed ipsilateral native nephrectomy because of infection. At last follow-up, all grafts remained unobstructed and free of infections. Conclusion: Ureteropyelostomy using the native ureter for the management of transplant ureteric obstruction or symptomatic reflux is safe and provides good long-term preservation of graft function in selected patients.

Ultrafine Structure of the Hydroxyapatite Amorphous Phase in Noninfectious Phosphate Renal Calculi - Corrected Proof

Markéta Zelenková, Otakar Sohnel, Felix Grases — 2012-01-31

Objective: We aimed to establish detailed morphology of the structureless amorphous hydroxyapatite (HAP) phase to improve our understanding of the formation mechanism of these concretions. Noninfectious phosphate renal calculi composed mainly of HAP consist of inorganic material in the form of spherules, in a seemingly structureless and amorphous phase and organic matter. Methods: Several cross-sections of a fraction of phosphate renal stone composed solely of the amorphous HAP phase were examined with atomic force microscope. Both 2- and 3-dimensional images of their structure and nanoscale elastic modulus maps were obtained. Results: The amorphous hap phase consists of 2 distinctly different morphologic forms of hydroxyapatite: separate and/or intergrown columnar crystals, and spherical agglomerates with diameters in the range 150-300 nm consisting of spherulites approximately 10 nm in diameter. The columnar crystals are irregularly disseminated in the stone interior, which is porous because of cavities with depths in excess of 100 nm. Organic matter is almost evenly distributed throughout the stone interior. Conclusion: Based on the observed calculus structure, the following mechanism of formation of the noninfectious phosphate calculi is suggested: Spherulites formed via the perikinetic aggregation of Posner's clusters present in urine supersaturated with respect to hydroxyapatite aggregate into spherical agglomerates that, after reaching a certain size, are retained in cavities with poor urodynamics, gradually settle, and become incorporated into developing concretion. The columnar crystals are probably nucleated on the detritus of organic origin embedded in the hydroxyapatite structureless phase.

Ritonavir Interacts With Bortezomib to Enhance Protein Ubiquitination and Histone Acetylation Synergistically in Renal Cancer Cells - Corrected Proof

Akinori Sato, Takako Asano, Keiichi Ito, Tomohiko Asano — 2012-01-31

Objective: To investigate the combined effects of the HIV protease inhibitor ritonavir and proteasome inhibitor bortezomib on renal cancer cells. Ritonavir induces endoplasmic reticulum (ER) stress and we hypothesized that inhibiting proteasome activity under ER stress would further inhibit cancer cell growth by enhancing protein ubiquitination. Methods: The effectiveness of the combination of ritonavir and bortezomib on renal cancer cells (Caki-1, ACHN, 786-O, 769-P) was assessed by MTS assay, colony formation assay, cell cycle analysis, and annexin-V assay. In vivo efficacy was evaluated using mice subcutaneous tumor models. Induction of ER stress, protein ubiquitination, histone acetylation, and changes in the expression of histone deacetylase (HDAC) were evaluated by Western blotting. Results: Ritonavir in combination with bortezomib induced apoptosis and inhibited renal cancer growth synergistically at clinically feasible concentrations. In subcutaneous tumor models using Caki-1 cells, 10-day treatment with the combination was well tolerated and inhibited tumor growth significantly. Ritonavir induced ER stress and the combination enhanced protein ubiquitination synergistically. The combination was also found to induce histone acetylation by suppressing the HDAC expression. Conclusion: The combination of ritonavir and bortezomib inhibits renal cancer growth synergistically. The effectiveness of the combination is caused by protein ubiquitination and histone acetylation. Our results provide a rationale for investigating the combination in patients with renal cancer.

Honokiol Attenuates Torsion/Detorsion-induced Testicular Injury in Rat Testis by Way of Suppressing Endoplasmic Reticulum Stress-related Apoptosis - Corrected Proof

2012-01-30

Objective: To investigate the protective effect of honokiol, a phytochemical used in traditional medicine, on testicular injury after torsion/detorsion (T/D) in a rat model. Testicular torsion is a medical emergency that can cause impairment of semen quality and permanent testicular atrophy or loss. Methods: Male Wistar rats were randomized to each time point of each group (n = 6/time point/group). After 2 hours of torsion, the testes were counter-rotated to the natural position. The rats in each group underwent a sham operation, T/D, or T/D with honokiol treatment (5 mg/kg and 10 mg/kg intraperitoneally, immediately before detorsion). Bilateral orchiectomy was performed at 6 and 24 hours and 3 months after detorsion. The testes were examined histologically. Apoptosis and endoplasmic reticulum stress were detected by Western blot. Results: Histologic examination revealed that testicular T/D induced acute injury after 6 and 24 hours, and spermatogenesis was decreased at 3 months of follow-up. At 24 hours after T/D, increases were found in the activation of apoptosis-related molecules [poly (ADP-ribose) polymerase and caspases 3 and 7], and the expression levels of endoplasmic reticulum stress-associated molecules (phosphorylated-eukaryotic translation initiation factor 2 subunit α and CCAAT/enhancer-binding protein homologous protein). These increases were significantly reversed with honokiol treatment. Furthermore, honokiol effectively reversed the inhibition of spermatogenesis in testes treated with T/D for 3 months. Conclusion: The results of our study have shown that the endoplasmic reticulum stress-related apoptotic pathway is involved in testicular injury after testicular T/D. It remains to be determined whether alterations in this pathway would have a protective affect against reperfusion damage.

Effect of Combined Locally Delivered Growth Factors and Systemic Sildenafil Citrate on Microrecanalization in Biodegradable Conduit for Vas Deferens Reconstruction - Corrected Proof

2012-01-30

Objective: To investigate the effect of the combination of locally delivered growth factors and oral sildenafil citrate on cross-conduit microrecanalization. Methods: A total of 42 rats were divided into 7 groups. Of the 42 rats, 6 underwent bilateral vasectomy and bilateral end-to-end vasovasostomy and 12 underwent bilateral vasectomy. Of the latter 12, 6 received sildenafil citrate orally (10 mg/kg/d) for 24 weeks and 6 received placebo. A total of 24 rats underwent bilateral vasectomy and bilateral reconstruction with implantation of a 5-mm biodegradable conduit that bridged the 2 vasal ends. Of the 24 rats with conduits, 12 also had 250 pg of transforming growth factor-β and 12.5 pg of platelet-derived growth factor-β sustained release nanoparticles placed in immediate proximity to the conduit. The remaining 12 rats with conduits (6 without growth factors and 6 with growth factors) also received sildenafil citrate orally (10 mg/kg/d) for 24 weeks; the others received placebo. The reconstructed segments were harvested for histologic examination at 24 weeks. Results: Five of 6 primary vasovasostomy and no vasectomy-only rats sired litters. Significantly more microcanals per conduit were observed in rats receiving sildenafil citrate: without growth factors, 3.9 vs. 0 canals/conduit (P < 0.001); with growth factors, 5.5 vs. 0.25 canals/conduit (P < 0.001). The rats receiving sildenafil citrate with growth factors showed a trend toward more microcanals per conduit than the rats receiving sildenafil citrate without growth factors (5.5 vs 3.9; P = .10). Rats receiving growth factors but no sildenafil citrate did not produce more canals than the rats receiving neither growth factor nor sildenafil citrate (0.25 vs 0; P = NS). Conclusion: Orally administered sildenafil citrate enhances formation of microcanalization after postvasectomy reconstruction using a biodegradable conduit in a rat model. Locally delivered growth factors appear to increase the number of microcanals.

Undescended Testis in Inguinal Canal Detected Incidentally on Fluorodeoxyglucose PET/CT Imaging - Corrected Proof

Pelin Ozcan Kara, Bugra Kaya, Gonca Kara Gedik, Oktay Sari, Erhan Varoglu — 2012-01-16

Abstract: The differential diagnosis at the inguinal region is very important for hypermetabolic foci because of the possibility of metastasis at this level in cancer patients ongoing PET imaging for detection of metastases. It is important to distinguish this activity from other possible malignant and benign conditions such as lymph node activity, testicular cancer, metastatic disease activity, inflammation and urine skin contamination artefact (1). A 66-year-old male patient with operated colon cancer and liver metastasis was referred for PET/CT examination for re-staging because of suspicious metastases. Findings of PET/CT imaging with undescended testis detected incidentally was presented.

Is There Any Role for Urodynamic Study in Children with High-grade Vesicoureteral Reflux? - Corrected Proof

Hossein Karami, Abdollah Razi, Mohammad Mohsen Mazloomfard, Babak Javanmard — 2012-01-13

Objective: To determine the clinical symptoms and urodynamic characteristics among children with primary high-grade vesicoureteral reflux (VUR). Materials and Methods: We prospectively studied clinical symptoms and urodynamic parameters in 147 consecutive patients ≤12 years old with idiopathic high-grade VUR referred to our hospital. Results: Of 147 patients with high-grade VUR, 139 cases with mean age of 5.3 years met our inclusion criteria (88.5% females, 11.5% males). The most common symptom was recurrent urinary tract infection (57%) and urgency (59%) followed by enuresis (31.6%) and frequency (26.6%). Normal urodynamic findings were observed in 23% of patients. Overactive bladder (74%), high-end filling pressure (72.7%), low-compliance bladder (56%), and low bladder capacity (51%) were the most common urodynamic reports in this study. Other urodynamic findings were underactive bladder (1.5%), hypersensitive bladder (1.5%), hyposensitive bladder (3%), and high capacity bladder (2.2%). Conclusion: Proper management of VUR is very important because of its harmful potential effects on kidney function in children. With regard to the issue that most children with grade III and higher VUR had overactive bladder, high-end filling pressure, and other urodynamic disorders in their urodynamic study, it seems that these urodynamic disorders could be the basic cause of reflux.

Long-term Outcomes of Open Radical Retropubic Prostatectomy for Clinically Localized Prostate Cancer in the Prostate-specific Antigen Era - Corrected Proof

2012-01-13

Objective: To determine long-term oncological outcomes and complication rates for patients with clinically organ confined prostate adenocarcinoma (PCa) treated with open radical retropubic prostatectomy and pelvic lymph node dissection (RRP/PLND) in the prostate-specific antigen (PSA) era. Methods: Outcomes data were obtained from a prospectively maintained prostate cancer database. Patients with cT1/cT2 PCa undergoing RRP/PLND without neoadjuvant therapy between July 1988 and June 2008 were included. Kaplan–Meier and Cox proportional regression models were used to evaluate factors influencing biochemical recurrence, clinical recurrence, and overall survival (OS). Results: A total of 2487 patients met inclusion criteria, and median follow-up was 7.2 years (range 1-21 years). Of the patients, 49.7% were low risk, 33.2% intermediate risk, and 16.1% high risk by D'Amico criteria, and 6% were LN+. The 10-year biochemical recurrence–free survival (BCRFS) for low-, intermediate-, and high-risk patients was 92%, 83%, and 76%, respectively (P < .001), and 10 year OS was 91%, 83%, and 74%, respectively (P < .001). BCRFS at 10 years was 76% and 88% for patients with positive and negative margins, respectively (P < .001). Of the 2487 patients, 11% developed BCR, and 3.7% experienced CR, with 9 local recurrences. The overall complication rate was 2.3%, and the cancer specific mortality rate was 2%. Conclusion: D'Amico risk group, margin status, and LN status are significantly correlated with outcomes in patients undergoing RRP/PLND for clinically localized PCa. Local recurrence and death from prostate cancer are rare in patients undergoing open RRP/PLND for clinically organ confined disease in the PSA era.

Pressure Transmission Through Ureteric Stents: a Novel in Vivo Human Study - Corrected Proof

Wael M. Sameh, Ahmed Abulfotooh Eid — 2012-01-13

Objective: To document, in an in vivo study, the pressure transmission from the urinary bladder to the upper tract through ureteric stents in human patients. Stents have acquired special importance in the urological armamentarium. Flank pain and hydronephrosis are associated with stenting in 50% and 18% of cases, respectively. Pressure transmission from urinary bladder to the upper tract through the stent is the logical explanation for loin pain and hydronephrosis. Methods: This study was conducted in a prospective manner. We did not select patients or modify their management; instead, we studied patients who, during the course of urological management of some upper tract disease, are left with both a ureteric stent and a nephrostomy tube. Twenty patients fulfilled our criteria. After written consent, a pressure–flow study was done monitoring pressure changes in the renal pelvis during different phases of bladder filling in sitting and recumbent positions. Results: Pressure–flow curves showed almost equal transmission of pressure from the bladder to the renal pelvis throughout all phases of bladder filling and emptying. Any voluntary and involuntary rise of pressure in the bladder was instantly and almost equally transmitted to the renal pelvis. A subgroup of patients with infravesical obstruction resulting from benign prostatic hyperplasia also showed equal transmission of the elevated intravesical pressure during voiding to the renal pelvis. Conclusion: Pressure from the lower urinary tract is transmitted to the upper tract through the stent, posing a threat to the renal parenchyma and function. Stent placement, when indicated, should be used for the shortest period possible, in sterile urine.

The Effect of Extralumenal Safety Wires on Ureteral Injury and Insertion Force of Ureteral Access Sheaths: Evaluation Using an Ex Vivo Porcine Model - Corrected Proof

2012-01-13

Objective: To evaluate the effect that a safety wire (SW) had on insertion force and direct ureteral trauma using ureteral access sheaths (UAS) in an ex vivo porcine model. Material and Methods: UASs were advance into 20 fresh ex vivo porcine kidney-ureters, either with or without SWs. The average and max force of insertion were recorded. Retrograde saline injection was used to identify the presence of lacerations. Results: For SW vs no SW, the mean insertion force (1.79 vs 0.67, P = .0003, respectively) and max insertion force (2.29 kg vs 1.00, P = .0007) was greater in the SW group. There were 9 lacerations, 6 of which were partial and 3 complete. Of the partial injuries, 2 were in the no SW group and 4 were in the SW group. Of the complete lacerations, 2 occurred in the no SW group and 1 in the SW group. However, there was no significant difference in the total number of lacerations (P = 1.00), the number of partial lacerations (P = .628), or the number of complete lacerations (P = 1.00) between the 2 groups. Conclusions: The use of an SW significantly increases the force required to insert a UAS; however, it does not appear to affect the force or the degree of ureteral injury.

Role of Spinal Cord in Regulating Mouse Kidney: A Virally Mediated Trans-synaptic Tracing Study - Corrected Proof

2012-01-13

Objective: To determine the spinal innervation and neuronal connections is important for studying renal metabolic responses. Materials and Methods: In this study, the spinal cords of 10 adult male C57BL/6J strain mice were mapped retrograde using injections of pseudorabies virus (PRV)-614. The virus, injected into the kidney, was specifically transported to the spinal cord. Results: At 5 days after injection of the PRV-614, PRV-614–positive cells were found in the intermediolateral cell column, the intercalates nucleus, or the central autonomic nucleus of spinal cord segments T4-L1, and most PRV-614–labeled cells were found in the T9 segment. Conclusion: Our results revealed neuroanatomical circuits between kidney and the spinal intermediolateral cell column neurons.

Durability of Antireflux Effect of Ureteral Reimplantation for Primary Vesicoureteral Reflux: Findings on Long-term Cystography - Corrected Proof

2012-01-13

Objective: To evaluate the long-term durability of successful ureteral reimplantation (UR) for vesicoureteral reflux (VUR) through a review of late cystography (LC) findings. Materials and Methods: We performed a retrospective chart review of all children with primary VUR who underwent successful open UR (grade 0 VUR into the reimplanted ureter[s] on initial cystogram) at our institution from January 1990 to December 2002. We identified successful UR patients who underwent LC ≥1 year after UR and reviewed the results for the presence of recurrent VUR into the reimplanted ureter(s). Results: Seven-hundred ninety-four patients underwent successful open UR for primary VUR, of whom 60 (7.6%) had a subsequent LC. Preoperative VUR grade was ≤II in 20 (34.5%) and ≥III in 38 (65.5%). Median age at UR was 3.5 years (IQR 1.3–6.2 years); 51 (85%) were female. UR was intravesical in 45 (75%) and bilateral in 19 (32%). LC was performed at a median of 38.7 months after UR (IQR 19.6–66.1 months). Indication for LC was febrile urinary tract infection (UTI) in 16 (27%), nonfebrile UTIs in 15 (25%), follow-up of contralateral VUR in 16 (27%), and other clinical indications in 13 (21%). The recurrence rate was 0%; of the 79 reimplanted ureters, 100% (95% CI 95.4–100) had no VUR (grade 0). Conclusion: Among children who underwent successful open UR for primary VUR, there was no VUR recurrence on extended follow-up. This suggests that the late durability of open antireflux surgery is excellent.

Histologic Inflammatory Changes on the Prostatic Gland Due to Immunosuppression for Kidney Transplantation - Corrected Proof

2012-01-13

Objective: To determine the incidence of type IV prostatitis in patients with kidney transplantation receiving an immunosuppression regimen and to compare it with that of a nonimmunosuppressed control group. Methods: We retrospectively reviewed 216 electronic charts of patients who had undergone surgical treatment for benign prostatic hyperplasia from August 2000 to January 2006. Of the 216 patients, 183 did not receive immunosuppressive therapy and were included in the control group (group 1). The other 33 patients had undergone kidney transplantation and were included in the study group (group 2). The patient data were accessed for age at surgery, International Prostate Symptom Score, prostate volume, preoperative serum prostate-specific antigen level, history of acute urinary retention, and surgical approach (open vs transurethral resection of prostate). Histologic findings from the surgical specimens were also recorded. Results: The mean age at surgery, mean serum prostate-specific antigen level, mean prostate volume, and mean International Prostate Symptom Score were not significantly different between both groups. However, histologic evidence of chronic prostatitis was obtained in 145 surgical specimens (78%) from group 1 and in just 3 specimens from group 2 (9%; P < .001). Moreover, nonimmunosuppressed patients had a 38.2 times greater risk of presenting with prostatitis than did the immunosuppressed patients. Conclusion: Imunnosuppresion therapy in kidney transplantation has a protective factor in the prostatitis incidence.

Pure Mini-laparoscopic Transperitoneal Pyeloplasty in an Adult Population: Feasibility, Safety, and Functional Results After One Year of Follow-up - Corrected Proof

2012-01-13

Objective: To report the results of mini-laparoscopic pyeloplasty (mLP) in an adult population. The feasibility of pure mLP has been previously reported in children. Material and methods: From April 2009 to February 2010, 10 patients with ureteropelvic junction obstruction (UPJO) were enrolled in this prospective study and underwent pure mLP (using only 3-mm instruments) according to the Anderson-Hynes technique. Inclusion criteria were: age >18 years, body mass index <25, primary UPJO, and no previous surgery on the affected kidney or a history of major abdominal surgery. Demographic and perioperative data, as well as 1-, 3-, 6-, and 12-month follow-up data were collected. Results: The mean operative time was 134 minutes, and blood loss was negligible. All procedures but one were completed using only 3.9-mm ports and 3-mm instruments. No perioperative complications occurred, and no patients had computed tomography evidence of hydronephrosis at 6 months after surgery. No functional obstructions were visualized with renal scintigraphy at 12 months after surgery. All patients were satisfied with the intervention and with their cosmetic results, as assessed by the Patient Scar Assessment Questionnaire and Scoring System. Conclusions: The results of our study suggest that pure mLP in an adult population is feasible and seems to be safe and effective in the treatment of UPJO. Furthermore, the patients tolerated the procedure well and appreciated its excellent cosmetic results. Further studies are required to determine the true advantages of mLP over standard laparoscopy.

Biomechanical Properties of Human Pelvic Organs - Corrected Proof

2012-01-13

Objective: To comparatively define the biomechanical characteristics of the pelvic organs (the vagina, bladder, and rectum), which are crucial for the maintenance of pelvic support. Despite minimal fundamental studies, meshes are increasingly implanted into the vesicovaginal and rectovaginal spaces to replace disrupted native tissues and to treat pelvic organ prolapse. However, the mechanical characteristics of these materials have not yet been compared with those of the “functional unit,” the vagina, bladder, and rectum. Methods: Samples from 5 fresh female cadavers without prolapse were collected. Uniaxial tension tests under monotonic and cyclic loading were performed and the stress-strain curves obtained. Results: The biomechanical properties of the vaginal, bladder, and rectal tissues differed significantly. We were able to demonstrate a nonlinear relationship between the stress and strain and a visco-hyperelastic behavior with a Mullins effect of damage of the tissues examined. Comparable rigidity was found between the investigated tissues at low strains; however, at large strain levels, marked differences could be observed. The vagina was much more rigid and less extendible than the rectal tissue, which, in turn, was more rigid than the bladder tissue. The anterior and posterior vagina revealed a different stiffness, and the bladder tissue was anisotropic at large strain levels. Conclusion: Our results underline the pivotal role of the vaginal tissue for the maintenance of pelvic support. The observed differences with respect to tissue rigidity should have pronounced effects on the physiologic organ function, pointing to the necessity of a differentiated view on using the same prosthetic material for different anatomic locations.

Pre- and Postoperative Urodynamic Findings in Patients After a Bulbourethral Composite Suspension with Intraoperative Urodynamically Controlled Sling Tension Adjustment for Postprostatectomy Incontinence - Corrected Proof

2012-01-13

Objectives: To compare pre- and postoperative urodynamic findings in patients with a bulbourethral composite suspension and intraoperative urodynamically controlled sling tension adjustment. Methods and Patients: All data were prospectively collected from 10 patients (mean age 66 years) who successfully underwent bulbourethral composite suspension for moderate to severe postprostatectomy incontinence. Patients were evaluated preoperatively and 3–6 months postoperatively by urodynamic measurements, including urethra pressure profiles (UPPs) and pressure flow studies (PFSs). Clinical outcome was evaluated by patient-reported pad use and questionnaires (ICIQ-UI SF and I-QOL). Intraoperatively sling tension was adjusted under repeated urodynamic measurements of abdominal leak point pressure. Data were evaluated using the Kruskal–Wallis Wilcoxon test. Results: Sling implantation was successful in all patients. Pre- to postoperative pad use decreased significantly (P < .005). Five patients were pad-free, 3 used 1 pad, and 2 used 2 pads per day. Continence and quality of life improved significantly (ICIQ-UI SF: pre-op 17 vs post-op 4.9; I-QOL: pre-op 66 vs post-op 91; P < .05 for both). Urodynamic parameters during the filling phase remained unchanged. UPPs revealed a significant increase of the maximal urethral closure pressure (pre-op 40 cm H2O vs post-op 58 cm H2O) and functional length (pre-op 31 mm vs post-op 40 mm; P < .05 for both). Postoperatively, urodynamic maximal flow rates were slightly reduced from 16 mL/s to 12 mL/s (P = .4). PFSs revealed an unobstructed voiding in all patients. Conclusions: According to the present evaluation, a bulbourethral composite suspension with intraoperative urodynamically controlled sling tension adjustment improves continence without causing prolonged clinically or urodynamically significant voiding obstruction.

Understanding Variation in Primary Prostate Cancer Treatment Within the Veterans Health Administration - Corrected Proof

2012-01-13

Objective: To examine the variation in prostate cancer treatment in the Veterans Health Administration (VHA)—a national, integrated delivery system. We also compared the care for older men in the VHA with that in fee-for-service Medicare. Methods: We used data from the Veterans Affairs Central Cancer Registry linked with administrative data and Surveillance, Epidemiology, and End Results-Medicare data to identify men with local or regional prostate cancer diagnosed during 2001 to 2004. We used multinomial logistic and hierarchical regression models to examine the patient, tumor, and facility characteristics associated with treatment in the VHA and, among older patients, used propensity score methods to compare primary therapy between the VHA and fee-for-service Medicare. Results: The rates of radical prostatectomy and radiotherapy varied substantially across VHA facilities. Among the VHA patients, older age, black race/ethnicity, and greater comorbidity were associated with receiving neither radical prostatectomy nor radiotherapy. Facilities with more black patients with prostate cancer had lower rates of radical prostatectomy, and those with less availability of external beam radiotherapy had lower radiotherapy rates. The adjusted rates of radiotherapy (39.7% vs 52.0%) and radical prostatectomy (12.1% vs 15.8%) were lower and the rates of receiving neither treatment greater (48.2% vs 32.2%) in the VHA versus fee-for-service Medicare (P < .001). Conclusions: In the VHA, the treatment rates varied substantially across facilities, and black men received less aggressive prostate cancer treatment than white men, suggesting factors other than patient preferences influence the treatment decisions. Also, primary prostate cancer therapy for older men is less aggressive in the VHA than in fee-for-service Medicare.

Relationship Between Procalcitonin Levels and Presence of Vesicoureteral Reflux During First Febrile Urinary Tract Infection in Children - Corrected Proof

Ilke Ozahi Ipek, Rabia Gonul Sezer, Evrim Senkal Kınay, Abdulkadir Bozaykut — 2012-01-13

Objective: To investigate the association between the procalcitonin (PCT) level during the first febrile urinary tract infection (UTI) in children and the presence of vesicoureteral reflux (VUR). VUR-associated UTI is among the primary causes of chronic renal failure in Turkey. Methods: From March 2008 to November 2009, patients admitted with their first febrile UTI were included in the present prospective hospital-based study. The serum concentrations of C-reactive protein, complete blood count, and PCT were measured. All patients underwent renal ultrasonography and voiding cystourethrography. Results: Of the 66 patients who were diagnosed with UTI, 18 had VUR. The geometric mean of the PCT levels was significantly greater in the children with VUR than in those without (P = .006). After logistic regression adjustment, the association between the PCT levels and the presence of VUR remained significant (odds ratio 5.08, 95% confidence interval [CI] 1.43-18.02). A PCT level >0.56 ng/mL had 66.7% sensitivity (95% CI 41-86.6) and 77.1% specificity (95% CI 62.7-88) for diagnosing VUR. The area under the receiver operating characteristic curve for PCT was 0.715 (95% CI, 0.56-0.86, P = .007), and the area under the curve for C-reactive protein was 0.723 (95% CI 0.58-0.86, P = .006). Conclusion: A PCT-guided strategy could help in detecting patients with VUR. Large cohort studies are needed to define an accurate cutoff value for children who are at risk of VUR, which increases the risk of renal damage and subsequent scarring.

Unilateral Exophthalmos Revealing Metastatic Prostate Cancer - Corrected Proof

2012-01-13

Prostate cancer, when metastatic, typically involves the axial skeleton. Sphenoidal metastasis is uncommon. We report a rare case of a 75-year-old man who presented with isolated unilateral exophthalmos. Digital rectal examination and serum prostate-specific antigen level were suggestive of metastatic prostate cancer. The prostate biopsy and imaging findings confirmed the source of the exophthalmos as a sphenoidal metastasis of an aggressive prostate adenocarcinoma.

Müllerian Remnant Malignancy - Corrected Proof

Adrien Phalen, Ardavan Akhavan, Simon J. Hall — 2012-01-13

Mixed gonadal dysgenesis is a disorder of sexual differentiation, characterized by mosaicism, ambiguous external genitalia, and both Wolffian and Müllerian internal genitalia. These patients are at a known increased risk of germ cell cancer, specifically gonadoblastoma; however, in this report we describe a case of adenocarcinoma of a remnant Müllerian structure.

Long-term Results of Small Intestinal Submucosa Graft in Bulbar Urethral Reconstruction - Corrected Proof

2012-01-13

Objective: To retrospectively report the long-term results of the use of a small intestinal submucosa (SIS) graft in bulbar urethral repair. Methods: From 2003 to 2007, 25 men (mean age 40.5 years) with bulbar strictures underwent patch graft urethroplasty using SIS placed on the dorsal or ventral or dorsal plus ventral surface of the urethra. The mean follow-up period was 71 months (range 52-100). The clinical outcome was considered a failure when any postoperative instrumentation, including dilation, was needed. Results: Of the 25 cases, 19 (76%) were successful and 6 (24%) were failures. No postoperative complications were related to the use of heterologous graft material, such as infection or rejection. The failure rate was 14% for strictures <4 cm and 100% for strictures >4 cm. Conclusion: At long-term follow-up, in bulbar stricture repair, SIS grafts showed similar results to penile skin grafts but were less effective than buccal mucosa grafts. The use of SIS as graft material should not be the first choice but represents an alternative option for patients with bulbar strictures that are not long and who refuse the harvesting or are not ideal candidates for buccal mucosa or penile skin grafts. Larger series of patients with longer follow-up are needed before widespread use can be advocated.

Factors Influencing Urologist Treatment Preference in Surgical Management of Stone Disease - Corrected Proof

M. Adam Childs, Laureano J. Rangel, James E. Lingeman, Amy E. Krambeck — 2012-01-13

Objective: To assess the surgeon factors influencing the surgical treatment decisions for symptomatic stone disease. The factors influencing the selection of shock wave lithotripsy (SWL), ureteroscopy, or percutaneous nephrolithotomy to treat symptomatic stone disease are not well studied. Methods: Electronic surveys were sent to urologists with American Medical Association membership. Information on training, practice, and ideal treatment of common stone scenarios was obtained and statistically analyzed. Results: In November 2009, 600 surveys were sent and 180 were completed. High-volume SWL practices (>100 cases annually) were more common in community practice (P < .01), and high-volume ureteroscopy and percutaneous nephrolithotomy practices were more common in academic practice (P = .03). Community practice was associated with SWL selection for proximal urolithiasis and upper pole nephrolithiasis (P < .005). An increasing time since urologic training was associated with SWL selection for proximal urolithiasis and upper pole nephrolithiasis (P < .01). Urologists reporting shock wave lithotriptor ownership were 3-4 times more likely to select SWL for urolithiasis or nephrolithiasis compared with urologists who did not own a lithotripter (P < .01). Routine concern for stent pain and rigid ureteroscope preference (vs flexible) were associated with SWL selection (P < .03). Conclusion: Surgeon factors significantly affected urolithiasis treatment selection. SWL was associated with community urology practice, increasing time since training, shock wave lithotriptor ownership, concern for stent pain, and ureteroscope preference.

Expression of TRAIL, DR4, and DR5 in Bladder Cancer: Correlation With Response to Adjuvant Therapy and Implications of Prognosis - Corrected Proof

2012-01-12

Objectives: To explore the interrelationship of human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptors DR4 and DR5 expressions level with patient prognosis and the response to adjuvant therapy in bladder cancer, the synergism function that is between chemotherapy and TRAIL on apoptosis induction in tumor cells. Methods: The expression of TRAIL, DR4, and DR5 was studied using immunohistochemistry of paraffin-embedded tumor specimens from 229 bladder cancer patients who had undergone transurethral resection. Results: Cytoplasmic TRAIL, DR4, and DR5 expressions were detected in 35%, 75.1%, and 74.2% of bladder cancer patients, respectively. Patients with bladder cancer with either high DR4 or DR5 expression had a significantly longer postoperative recurrence-free rate than those with low expression of both during the 10-year follow-up. Multivariate analysis revealed that the expression of DR4 (P < .001), DR5 (P < .001) and epirubicin therapy (P = .034) were independent prognostic indicators of bladder cancer. Furthermore, epirubicin therapy significantly improved recurrence-free rate for the patients with DR4-high (P = .006) or DR5-high (P = .042) tumor. Conclusions: The results of the present study have shown for the first time that a combination of DR4 and DR5 expression have significant value in predicting the prognosis of bladder cancer. In addition, patients with high expression of both DR4 and DR5 might benefit from epirubicin therapy.

Pharmacological Effect of TRK-380, a Novel Selective Human β3-Adrenoceptor Agonist, on Mammalian Detrusor Strips - Corrected Proof

2011-12-26

Objective: To clarify the potential of TRK-380 as a drug for overactive bladder in humans by evaluating the agonistic activities for human β-adrenergic receptors (β-ARs) and the relaxing effects on isolated detrusor strips. Methods: The agonistic activities for human β-ARs were evaluated in SK-N-MC cells (for human β3-ARs) and Chinese hamster ovary cells expressing human β1- or human β2-ARs using the cyclic adenosine monophosphate accumulation assay. The relaxing effects on the resting tension in isolated detrusor strips from humans, monkeys, dogs, and rats and on carbachol- or KCl-induced contractions in human detrusor strips were evaluated. Results: In the cyclic adenosine monophosphate accumulation assay, the agonistic activity of TRK-380 for human β3-ARs was potent and equivalent to that of the potent nonselective β-AR agonist isoproterenol and superior to that of selective β3-AR agonists, such as BRL-37344 and CL316,243. TRK-380 showed no agonistic activity for human β1-ARs and a weak agonistic effect on human β2-ARs. In isolated detrusor strips, the concentration-dependent relaxing effects of TRK-380 on the resting tension were equivalent to those of isoproterenol in humans, monkeys, and dogs but weaker than the effects in rats. The selective β3-AR antagonist SR59230A shifted the concentration-response curve in a concentration-dependent manner to TRK-380 for the resting tension of human detrusor strips to the right. TRK-380 had a concentration-dependent relaxing effect on the contractile responses to carbachol and KCl in human detrusor strips. Conclusion: TRK-380 was a potent and selective human β3-AR agonist, and the isolated human detrusor relaxation was mainly mediated by activation of the β3-AR. Consequently, TRK-380 might be a promising compound for the treatment of overactive bladder.

Label Retaining and Stem Cell Marker Expression in the Developing Rat Urinary Bladder - Corrected Proof

2011-12-26

Objective: To identify potential stem cells in urinary bladder by label-retaining cell (LRC) strategy and immunostaining for putative stem cell markers. Methods: Newborn rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine (EdU) and their bladders harvested at 4 different time points afterward. The bladders were processed for EdU staining and immunofluorescence staining for stem cell markers Lgr5, CD34, SSEA-1, and c-kit. EdU-positive cells were counted and colocalization with stem cell markers determined. Results: At day 1 post-EdU injection, 1804.0 ± 227.7 bladder cells were labeled in each cross-section. As time increased, fewer bladders remained labeled, dropping to 236.5 ± 53.0 cells per field. In the 1-day bladders, 27.5% ± 4.9% of the epithelial cells were labeled as compared to 12.1% ± 2.8% in the detrusor. The labeling rates in these 2 tissue compartments gradually equalized, reaching at approximately 5.5% in the 8-week samples. Distribution of LRC was random, without preferential labeling of basal cells. Lgr5 and SSEA-1 were detectable in the urothelium, and CD34 and c-kit in the lamina propria and detrusor. Approximately 30%-40% of c-kit–positive cells were EdU positive. Conclusion: Labeling of bladder cells by EdU occurred randomly, and label retaining was not associated with expression of Lgr5, CD34, or SSEA-1. The strong association between label retaining and c-kit expression appears to relate to interstitial cells of Cajal, not stem cells.

Prospective Long-term Analysis of Nerve-sparing Extravesical Robotic-assisted Laparoscopic Ureteral Reimplantation - Corrected Proof

2011-12-26

Objective: To prospectively review our experience with extravesical robotic-assisted laparoscopic ureteral reimplantation to determine whether postoperative voiding dysfunction can be avoided with pelvic plexus visualization and to assess the efficacy of this approach for the treatment of vesicoureteral reflux (VUR). Methods: We prospectively followed 150 patients who underwent bilateral extravesical robotic-assisted laparoscopic ureteral reimplantation by a single surgeon at an academic institution. Each patient was followed for a 2-year period. All 150 patients had primary VUR of grade 3 or greater bilaterally, with 127 having parenchymal defects found on renal scans. All patients were toilet trained before surgical intervention. The operation was performed with an extravesical transperitoneal approach with robotic assistance using the daVinci Surgical System. All patients underwent voiding cystourethrography at 3 months postoperatively to document the resolution of VUR. Voiding dysfunction was assessed in each patient by uroflow, postvoid residual urine volume, and a validated questionnaire. Results: The operative success rate was 99.3% for VUR resolution on voiding cystourethrography. One patient with bilateral grade 5 VUR that was downgraded to unilateral grade 2 VUR was considered to have treatment failure. This patient ultimately underwent subsequent subureteral injection therapy after an episode of pyelonephritis. No patient experienced de novo voiding dysfunction. Conclusion: Bilateral nerve-sparing robotic-assisted extravesical reimplantation has the same success rate as the traditional open approaches, with minimal morbidity and no voiding complications in our series.

Expression and alpha1-Adrenoceptor Regulation of Caldesmon in Human Prostate Smooth Muscle - Corrected Proof

2011-12-26

Objective: To investigate expression and α1-adrenergic regulation of caldesmon in the human prostate. Caldesmon is an important mediator and regulator of contraction in different smooth muscle types. However, this has not been investigated in the prostate to date. The activity of caldesmon may be tightly regulated by serine-789 phosphorylation. Materials and Methods: Prostate tissue was obtained from patients undergoing radical prostatectomy. Caldesmon expression was studied by Western blot analysis and immunohistochemistry. The adrenergic regulation of caldesmon phosphorylation was investigated by Western blot analyses with a site- and phosphospecific antibody. Results: Caldesmon expression was detectable by Western blot analysis in all investigated samples of human prostates (n = 8 patients). Immunoreactivity after staining with a caldesmon antibody was strong in smooth muscle cells, but not observed in glandular or epithelial cells (n = 5 patients). In double fluorescence staining, caldesmon co-localized with α1A-adrenoceptors and α-smooth muscle actin (n = 6 patients). Stimulation of prostate tissue with noradrenaline (30 μM, n = 6 patients) or the α1-adrenergic agonist phenylephrine (10 μM, n = 6 patients) resulted in progressive phosphorylation of caldesmon at serine-789. Noradrenaline-induced caldesmon phosphorylation was 1.5 ± 0.2-fold after 5 minutes (P<.04 vs basal phosphorylation), and 1.6 ± 0.2-fold after 10 minutes (P<.04). Phenylephrine-induced caldesmon phosphorylation was 1.7 ± 0.2-fold after 10 minutes (P<.02 vs basal phosphorylation), and 2.4 ± 0.6-fold after 20 minutes (P<.05). Conclusions: Caldesmon is an effector of α1-adrenoceptors in the human prostate. Caldesmon activation may be of importance for α1-adrenergic prostate contraction, and during therapy with α1-blockers.

Effect of Small Interfering RNA Targeting Hypoxia-inducible Factor-1α on Radiosensitivity of PC3 Cell Line - Corrected Proof

2011-12-23

Objective: To evaluate the effect of silencing hypoxia-inducible factor-1α (HIF-1α) expression by small interfering RNA (siRNA) on the radiosensitivity of the PC3 cell line. Methods: The expression of HIF-1α in PC3, a p53-null and androgen-independent prostate cancer cell line, was knocked down by siRNA. Irradiation was performed at 48 hours after transfection. The cells were divided into 3 groups: the PC3 group, control group (transfected with scramble siRNA), and HIF-1α silence group. HIF-1α expression was determined using real-time polymerase chain reaction and Western immunoblotting. A clonogenic assay and the cell counting kit-8 assay were performed to determine the radiosensitivity. Flow cytometry was used to assess apoptosis and cell cycle distribution. Results: HIF-1α siRNA downregulated HIF-1α expression in PC3 cells on the mRNA level and protein level, and its silencing effect on mRNA level was evident at 24-72 hours. The HIF-1α silence group had a low final slope of exponential part of a radiation survival curve, survival fraction of 2 Gy, quasi-threshold dose, and extrapolation number, and the sensitizing enhancement ratio was 1.24. The cell counting kit-8 assay showed decreased cellular viability (24 hours, F = 139.74, P < .01; 48 hours, F = 495.49, P < .01; 72 hours, F = 426.89, P < .01; 96 hours, F = 471.11, P < .01) in the HIF-1α silence group. Silencing HIF-1α also induced more apoptosis (PC3, 17.9% ± 1.65%; control group, 18.6% ± 1.37%; HIF-1α silence group, 29.1% ± 2.16%; F = 169.9, P < .01) and cell cycle arrest at the S, G2/M phase. Conclusion: The suppression of HIF-1α in PC3 cells sensitizes the PC3 cells to irradiation. We have shown that HIF-1α inhibition attenuates repair of postradiation injury, with an increase in both interphase death and reproductive death after irradiation, apoptotic potential, and cell cycle arrest at the proliferative phase.

Anorchia Masked by Septo-optic Dysplasia - Corrected Proof

Kelly MacArthur, Durwood E. Neal, Amie M. VanMorlan — 2011-12-23

Hypogonadism affecting the male pediatric population is uncommon, with that attributed to multiple unrelated etiologies being exceedingly rare. We report a case of septo-optic dysplasia, an atypical cause of delayed puberty, with subsequent workup unveiling 2 coexistent conditions: hypogonadotropic hypogonadism and anorchia. Primary and secondary etiologies must be considered in patients with undescended testes. Thorough evaluation is mandatory to ensure proper diagnosis and care, because Occam's razor can, on unique occasions, be double-edged.

Safety and Efficacy of Ultrasound-guided Percutaneous Nephrolithotomy for Treatment of Urinary Stone Disease in Children - Corrected Proof

2011-12-23

Objective: To present the feasibility and efficacy of ultrasound-guided percutaneous nephrolithotomy for the treatment of urinary stone disease in children. Methods: The medical records and files of 17 patients with renal stones (17 renal units) who were aged ≤16 years who had undergone ultrasound-guided percutaneous nephrolithotomy from 2008 to 2010 were retrospectively reviewed and analyzed. Ultrasonography was used for guidance in all patients in every step of the procedure. Fluoroscopy was used to aid in tract dilation in the initial cases of the series and to evaluate for stone clearance in all cases. The operative and postoperative findings were assessed. Results: The average age of the patients was 8.8 ± 2.86 years (range 5-15). The mean stone size was calculated as 337.4 ± 52.9 mm2 (range 260-446). The mean operative time was 67.9 ± 14.58 minutes (range 45-95). Fever, urine leakage, and bleeding requiring blood transfusion were observed in 3, 1, and 1 patient, respectively. The fluoroscopic screening time was limited to 17.76 ± 15.5 seconds (range 1-54). Neighboring organ injuries were not observed. The overall success rate improved from 82.35% to 100% with additional treatment modalities (shock wave lithotripsy in 2 and ureteroscopy in 1). Conclusion: Percutaneous nephrolithotomy can be safely performed with ultrasound guidance in children, providing the advantages of less radiation exposure, no adjacent organ injury, and similar success and complication rates compared with fluoroscopic guidance.

Can We Avoid Percutaneous Nephrolithotomy in High-risk Elderly Patients Using the Charlson Comorbidity Index? - Corrected Proof

2011-12-23

Objective: To determine whether Charlson comorbidity index (CCI) predicts the postoperative complications after percutaneous nephrolithotomy (PCNL) and could be a plausible option to avoid surgery and its potential risks in elderly patients with significant comorbidites. Methods: The data from 283 elderly patients (age ≥60 years) who underwent PCNL in 4 large referral hospitals were reviewed in the present multicenter study. For each patient, we evaluated pre-existing comorbidities and calculated the CCI score. The patients were classified to 3 CCI score categories (0, 1, ≥2) and compared regarding the stone-free and complications rates. Results: The mean patient age was 64.7, 65.6, and 67.7 years in the 3 groups. The stone-free rate after primary PCNL was 85.7% in group 1, 86.1% in group 2, and 75.0% in group 3. These rates increased to 90.8%, 95.4%, and 83.9% after a second intervention (P = .049). The overall postoperative complication rate was 38.8%. The most common complication was hemorrhage necessitating blood transfusion in 34 patients (12%), and we found an increased risk of hemorrhage associated with the CCI score (P = .011). Life-threatening medical complications developed in 7.6% of the patients in group 1, 12% of the patients in group 2, and 28.6% of the patients in group 3 (P = .001). A multivariate logistic regression analysis showed that a high CCI score, bleeding, and operative time had significant influence on the postoperative medical complication in this population. Conclusion: Conservative management of asymptomatic large kidney stones appears to be a safe alternative to PCNL in elderly patients with significant comorbidites.

Is It Transitional Cell Carcinoma or Renal Cell Carcinoma on Computed Tomography Image? - Corrected Proof

Young Beom Jeong, Hyung Jin Kim — 2011-12-23

We report on a 58-year-old female patient with renal cell carcinoma simulating transitional cell carcinoma on computed tomography. The computed tomography scan showed an enhancing 2.5-cm left renal pelvic mass without renal parenchymal mass. Urinalysis revealed microscopic hematuria. Cystoscopy and urine cytology was negative for transitional cell carcinoma. Laparoscopic nephroureterectomy was done under the preoperative diagnosis of localized transitional cell carcinoma of the renal pelvis according to the computed tomography findings. The histologic result, however, was a clear cell renal cell carcinoma.

Early Allograft Calcifications After Kidney Transplantation - Corrected Proof

2011-12-20

Early allograft calcifications after kidney transplantation (KT) have already been reported, but the clinical implications of this finding are not clear thus far. Patient-related factors such as age, gender, underlying renal disease, and dialytic modality, seem to be irrelevant. It has been postulated that factors promoting the development of metastatic calcifications, including elevated calcium phosphate product and severe secondary hyperparathyroidism, could play a causal role. Here we report a case of a KT patient who developed early kidney calcifications which were associated with severe allograft dysfunction.

High-Grade Prostatic Adenocarcinoma Present in a Single Biopsy Core as Associated With Increased Extraprostatic Extension, Seminal Vesicle Invasion, and Positive Surgical Margins at Prostatectomy - Corrected Proof

2011-12-14

Objective: To evaluate the pathologic outcome of prostate-specific antigen-screened patients with high-grade (Gleason score ≥ 8) prostate cancer limited to 1 biopsy core, without clinical evidence of disease. Methods: Ninety-two patients with only 1 biopsy core with cancer and treated by radical prostatectomy were divided into 4 groups according to the biopsy Gleason score: 3 + 3 = 6 (23 cases), 3 + 4 = 7 (25 cases), 4 + 3 = 7 (20 cases), and ≥8 (24 cases). Results: Cases with Gleason score ≥8 showed a significantly higher proportion of extraprostatic extension (50%), positive surgical margins (21%), and seminal vesicle invasion (12%) when compared with the other groups. Patients with Gleason score ≥8 in the biopsy had a 25-fold increased in the odds ratio for extraprostatic extension in the prostatectomy. The incidence of extraprostatic extension was higher in those with prostatic cancer involving ≥50% of one core (88%) compared with cases involving <50% (32%). Conclusion: In patients with prostate cancer limited to 1 biopsy core, the presence of Gleason score ≥8 significantly increased the incidence of extraprostatic extension, positive surgical margins, and seminal vesicle invasion. The odds ratio was substantially higher in patients with ≥50% of Gleason ≥8 in the biopsy core. These data might be taken into account for proper clinical management of this set of patients.

Systematic Evaluation of Hybrid Guidewires: Shaft Stiffness, Lubricity, and Tip Configuration - Corrected Proof

Carl Sarkissian, Emily Korman, Kari Hendlin, Manoj Monga — 2011-12-14

Objective: To conduct a comparison of physical and mechanical properties for 5 commonly used guidewires to assess advantages of wires for specific applications. Methods: Tests on guidewires (0.035” diameter; straight, flexible tip) included tip bending, shaft buckling, lubricity, and tip puncture measurements. Guidewires included 2 hybrid wires: the U-Nite (Bard Urological, Covington, GA) and the Sensor (Boston Scientific, Natick, MA). Our aim was to compare the stiffness of these hybrid wires with the standard Amplatz SuperStiff (Boston Scientific). Our second aim was to compare the hydrophilic tip of the hybrid wires with 2 traditional hydrophilic guidewires: the NiCore (Bard Urological) and RadiFocus glidewire (Boston Scientific). Results: The Amplatz SuperStiff had a significantly stiffer shaft than either hybrid wire, with a buckling force of 1.81 ± 0.91 N compared with the Sensor (0.80 ± 0.29 N, P = .0002) and the U-Nite (0.77 ± 0.29 N, P < .0001). The Boston Scientific guidewire tips were less stiff than the Bard guidewires, requiring up to 48% less force to bend when encountering resistance (P < .0001). The U-Nite had the highest lubricity (0.09 ± 0.03 N, P < .0001) and roundest tip of all the guidewires tested. The RadiFocus required the greatest puncture force (1.80 ± 0.27 N, P < .0001) of all the guidewires tested. Conclusion: Hybrid wires offer a combination of a stiffer shaft and hydrophilic tip. The Amplatz SuperStiff remains the stiffest wire and as such is best suited for placement of ureteral access sheaths or larger stents. The Boston Scientific wires require less force to “bend” around a point of obstruction compared with the Bard wires. The Boston Scientific RadiFocus requires the greatest force to puncture aluminum foil.

Experience with the Diagnosis and Management of Symptomatic Ureteric Stones During Pregnancy - Corrected Proof

2011-12-14

Objective: To present our experience to describe diagnosis and management of symptomatic ureteric stones during pregnancy. Materials and Methods: Thirty-six pregnant women with symptomatic ureteric stones were evaluated in this study. The diagnosis was done by history, physical examination, symptoms, signs, ultrasonography, or ureteroscopy if needed. Initially, conservative management was performed on all patients. When conservative treatment failed, temporizing therapies (double-J stenting or percutaneous nephrostomy [PCN]) and (ureteroscopic lithotripsy) URSL were performed on the patients. Results: In 25 (69.4%) of the patients, ureteric stones was diagnosed on US. In the other 11 (30.6%) of the patients, definitive diagnosis was done by ureteroscopy in 5, and 6 of them passed their stones spontaneously. Conservative management was successful in 24 of 36 (66.6%) the patients. Temporizing therapies and URSL were required in 12 of 36 (33.4%) patients. A double-J stent was successfully placed in only 3 (8.3%) of the patients, and URSL was performed in 9 (25%). In 1 (2.7%) patient, PCN was performed because of persistent renal colic, fever, and pyonephrosis. In this patient, URSL was performed after symptoms and signs resolved, and then the percutaneous tube was removed. Conclusion: If ultrasonogrpahy fails, ureteroscopy may be an alternative approach for definitive diagnosis. When conservative approach fails, URSL may be a good alternative approach for definitive treatment.

Effects of Drinking Water Quality on Urinary Parameters in Men With and Without Urinary Tract Stones - Corrected Proof

Majid Mirzazadeh, Mina Ghadimi Nouran, Kyle A. Richards, Mariam Zare — 2011-12-14

Objective: There is some controversy regarding the impact of water hardness on stone risk. Our study addresses this issue in a controlled setting. Material and Methods: Fifteen stone-former (SF) and 14 non–stone-former (NSF) males participated in this study in 3 intervals of 2 days each. Subjects collected a 24-hour urine sample while consuming a self-selected diet. They were then administered controlled diets. During the first 2 days, patients consumed water of minimal hardness (WMH), followed by tap water (TW) with moderate hardness on days 3 and 4, and mineral water (MW) on the final 2 days. Calcium (Ca), phosphorus, uric acid, oxalate, citrate, magnesium (Mg), sodium, potassium, and creatinine (Cr) content were measured in 24-hour urine samples on days 2, 4, and 6. Results: Differences in water hardness and analytes were statistically significant among the different water types (P < .05). Urinary output in both groups increased during intervention with all 3 varieties of water (P < .05). Specific gravity of urine decreased in both groups drinking WMH and TW (P < .05) but not with MW. Mg/g Cr level was higher in NSF at baseline (P < .01), WMH (P < .05), and TW (P < .05). With the increase in drinking water hardness, Ca/g Cr ratio increased in SF but not in NSF (P < .05). Conclusions: NSF had significantly higher urinary Mg/g Cr excretion rate before intervention than SF (P < .01). Increasing drinking water hardness while controlling for all other factors increased Ca/g Cr ratio in SF, rendering them at least theoretically more inclined to stone formation.

Clinical Features and Testicular Morphology in Patients with Kallmann Syndrome - Corrected Proof

2011-12-14

Kallmann syndrome (KS) is a genetic disorder characterized by the simultaneous occurrence of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. Here, we present 3 cases of KS with detailed description. In Case 1, testicular morphology was examined by testicular biopsy, and Leydig cells were examined by immunohistochemistry using antibodies against Ad4BP/SF1. Contrary to our predictions, the present study revealed the presence of Leydig cells in the testis. Testicular morphology in the patients with KS is more varied than expected, and further investigation is required to elucidate hormonal effects on normal testicular development.

Prostate Cryoablation in Patients with Multiple-component Inflatable Penile Prostheses - Corrected Proof

Bruce B. Garber, Ashley H. Tapscott — 2011-12-14

Objective: To evaluate and assess any inflatable penile prosthesis (IPP)-related complications in patients with organ-confined prostate cancer treated definitively with third-generation, ultrasound-guided prostate cryoablation. material and methods: From November 2003 to October 2010, we identified 100 consecutive patients with clinically organ-confined prostate cancer who were treated with targeted cryoablation as primary or salvage therapy by a single surgeon. Review of these patients revealed 13 who had previously been diagnosed with organic erectile dysfunction and had been implanted with a multiple-component IPP by the same surgeon. To assess IPP complications related to the cryoablation procedure, we retrospectively reviewed events occurring within a 6-month postoperative follow-up period. Results: For the entire series, the patient ages ranged from 42-84 years (mean 68). Of the 13 patients with IPPs, no device-related complication (eg, IPP infection, erosion, or malfunction) was found. No patient required IPP revision or removal. Conclusion: Patients with organ-confined prostate cancer who also have a multiple-component IPP may safely undergo ultrasound-guided prostate cryoablation as definitive therapy. Cryoprobe and thermocouple placement must be carried out carefully, using ultrasound guidance. To avoid IPP reservoir injury, suprapubic tube placement should be avoided.