The inhibitory effects of pimozide, an antipsychotic drug, on voltage-gated K+ channels in rabbit coronary arterial smooth muscle cells.

Pimozide is an antipsychotic drug used to treat chronic psychosis, such as Tourette's syndrome. Despite its widespread clinical use, pimozide can cause unexpected adverse effects, including arrhythmias. However, the adverse effects of pimozide on vascular K+ channels have not yet been determined. Therefore, we investigated the effects of pimozide on voltage-gated K+ (Kv) channels in rabbit coronary arterial smooth muscle cells. Pimozide concentration-dependently inhibited the Kv currents with an IC50 value of 1.78 ± 0.17 µM and a Hill coefficient of 0.90 ± 0.05. The inhibitory effect on the Kv current by pimozide was highly voltage-dependent in the voltage range of Kv channel activation, and additive inhibition of the Kv current by pimozide was observed in the full activation voltage range. The decay rate of inactivation was significantly accelerated by pimozide. Pimozide shifted the inactivation curve to a more negative potential. The recovery time constant from inactivation increased in the presence of pimozide. Furthermore, pimozide-induced inhibition of the Kv current was augmented by applying train pulses. Although pretreatment with the Kv2.1 subtype inhibitor guangxitoxin and the Kv7 subtype inhibitor linopirdine did not alter the degree of pimozide-induced inhibition of the Kv currents, pretreatment with the Kv1.5 channel inhibitor DPO-1 reduced the inhibitory effects of pimozide on Kv currents. Pimozide induced membrane depolarization. We conclude that pimozide inhibits Kv currents in voltage-, time-, and use (state)-dependent manners. Furthermore, the major Kv channel target of pimozide is the Kv1.5 channel.

Safety of autologous bone marrow-derived mesenchymal stem cells in erectile dysfunction: an open-label phase 1 clinical trial.

BACKGROUND AIMS: The efficacy of phosphodiesterase type 5 inhibitors (PDE5Is), which are commonly used to treat erectile dysfunction (ED), is not satisfactory in patients with denervation of the cavernous nerve due to pelvic surgeries and diabetes mellitus (DM). Pre-clinical studies using bone marrow-derived mesenchymal stem cells (BMSCs) to treat ED have shown promising results. The authors conducted a phase 1 clinical trial with autologous BMSCs in patients with ED due to radical prostatectomy or DM. METHODS: Ten patients (five with post-prostatectomy ED and five with DM-associated ED) who could not perform sexual activity despite taking the maximum dose of a PDE5I were enrolled. The brief clinical trial protocol was registered with the US National Institutes of Health on ClinicalTrials.gov (NCT02344849). The primary outcome was the safety of stem cell therapy, and the secondary outcome was the improvement of erectile function. RESULTS: Of the 13 patients screened, 10 were registered in the clinical trial and received autologous BMSCs and nine completed the clinical trial. One patient with post-prostatectomy ED experienced two treatment-emergent adverse events (TEAEs) (pyrexia and back pain), and two patients with DM-associated ED experienced a total of five TEAEs (one case each of viral upper respiratory tract infection, prostatitis and pruritus and two cases of hyperglycemia). Of these patients, one with DM-associated ED experienced two serious TEAEs (two instances of hyperglycemia). All TEAEs were considered not to be related to autologous BMSC therapy. In addition, no clinical significance was identified related to other safety measures, such as laboratory tests and vital signs. The mean International Index of Erectile Function score increased significantly at 1 month versus baseline (24.9 versus 18.1, P = 0.0222). CONCLUSIONS: This phase 1 clinical trial confirmed the safety and potential efficacy of autologous BMSC therapy in patients with ED. The authors' results need to be confirmed by a phase 2 clinical trial.

The effects of tegaserod, a gastrokinetic agent, on voltage-gated K+ channels in rabbit coronary arterial smooth muscle cells.

Tegaserod, a gastroprokinetic agent, is used to treat irritable bowel syndrome. Despite its extensive clinical use, little is known about the effects of tegaserod on vascular ion channels, especially K+ channels. Therefore, we examined the effects of tegaserod on voltage-gated K+ (Kv) channels in rabbit coronary arterial smooth muscle cells using the whole-cell patch-clamp technique. Tegaserod inhibited Kv channels in a concentration-dependent manner with an IC50 value of 1.26 ± 0.31 µmol/L and Hill coefficient of 0.81 ± 0.10. Although tegaserod had no effect on the steady-state activation curves of the Kv channels, the steady-state inactivation curve was shifted toward a more negative potential. These results suggest that tegaserod inhibits Kv channels by influencing their voltage sensors. The recovery time constant of channel inactivation was extended in the presence of tegaserod. Furthermore, application of train steps (1 and 2 Hz) in the presence of tegaserod progressively increased the inhibition of Kv currents suggesting that tegaserod-induced Kv channel inhibition is use (state)-dependent. Pretreatment with a Kv1.5 subtype inhibitor suppressed the Kv current. However, additional application of tegaserod did not induce further inhibition. Pretreatment with a Kv2.1 or Kv7 inhibitor did not affect the inhibitory effect of tegaserod on Kv channels. Based on these results, we conclude that tegaserod inhibits vascular Kv channels in a concentration- and use (state)-dependent manner independent of its own functions. Furthermore, the major Kv channel target of tegaserod is the Kv1.5 subtype.

Diagnostic Performance of %[-2]proPSA and Prostate Health Index for Prostate Cancer: Prospective, Multi-institutional Study.

BACKGROUND: We evaluated the clinical performance of [-2]proPSA (p2PSA) and its derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) in Korean men. METHODS: A total of 246 men with total prostate-specific antigen (tPSA) ≥ 3.5 ng/mL who underwent their first prostate biopsy were included in this prospective, multicenter, observational study. Diagnostic accuracy of tPSA, free-to-total PSA ratio (%fPSA), p2PSA, %p2PSA, and the Beckman Coulter prostate health index (PHI) was assessed by receiver operating characteristic curve analyses and logistic regression analyses. RESULTS: Overall, PCa was detected in 125 (50.8%) subjects. In men with tPSA 3.5-10 ng/mL, the detection rate of PCa was 39.4% (61/155). In this group, PHI and %p2PSA were the most accurate predictors of PCa and significantly outperformed tPSA and %fPSA; area under the curve for tPSA, %fPSA, %p2PSA, and PHI was 0.56, 0.69, 0.74, and 0.76, respectively. PHI was also the strongest predictor of PCa with Gleason score ≥ 7. CONCLUSION: This study demonstrates the superior clinical performance of %p2PSA and PHI in predicting the presence and aggressiveness of PCa in Korean men. The %p2PSA and PHI appear to improve detection of PCa and provide prognostic information.

Ileal Augmentation Cystoplasty Combined with Ileal Ureter Replacement After Radical Treatment for Cervical Cancer.

BACKGROUND: This study reviewed the outcomes for patients who underwent simultaneous bladder and ureter reconstructive surgery using the ileum after radical treatment for cervical cancer. METHODS: The medical records of seven patients who underwent augmentation ileocystoplasty with ileal ureter replacement between September 2006 and May 2013 were reviewed. Data on indications for surgery, underlying urologic comorbidities, type of ureteral replacement, postoperative complications, and changes in renal function were obtained. RESULTS: The median age of the patients was 56 years. The primary tumor was cervical cancer in all the patients, and the majority of the patients (4/7, 57.1 %) were previously treated with radical hysterectomy plus radiotherapy. Ileal ureter replacement was performed on 11 renal units, and bilateral ileal ureter substitution was performed for four patients, with the largest ureteral defect being 15 cm. The median length of the ileum used for augmentation and ureter substitution was 30 cm (range 15-40 cm), and the median hospital stay was 23 days (range 18-47 days). The overall rate of major complications (grade ≥3) was 57.1 % (4 of 7 patients). The median preoperative and immediate postoperative serum creatinine levels were respectively 1.2 mg/dL and 0.9 mg/dL. During a mean follow-up duration of 38 months, none of the patients experienced deterioration of renal function after surgery. CONCLUSION: Ileal ureter substitution combined with augmentation ileocystoplasty is a useful surgical technique for bridging long ureteral defects caused by ureteric stenosis from surgery, radiotherapy, or both for pelvic tumors in contracted low-compliance bladders.

Bone marrow-derived mesenchymal stromal cell therapy in a rat model of cavernous nerve injury: Preclinical study for approval.

BACKGROUND AIMS: Although clinical studies using stem cells to treat erectile dysfunction have been performed or are ongoing, there is little consensus on the optimal protocol. We aimed to develop a protocol optimizing human bone marrow-derived mesenchymal stromal cell (hBMSC) therapy in a rat model of cavernous nerve injury. METHODS: We performed, in order, a dose-finding study, a toxicokinetic study of hBMSCs, and a study to determine the timing and number of cell injections. RESULTS: From the dose-finding study, 1 × 10(6) cells were selected as the dose per hBMSC injection. From the toxicokinetic study, 14 days was selected as the interval between repeat treatments. In the final study, the ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the control group than in the sham group (23.4% vs. 55.1%, P <0.001). An immediate single injection of hBMSCs significantly improved erectile function compared with the control group (39.8%, P = 0.035), whereas a delayed single injection showed improvement with a marginal trend (38.1%, P = 0.079). All histomorphometric changes were significantly more improved in the immediate or delayed single injection groups than in the control group. Repeat treatments did not provide any benefit for the recovery of erectile function and histomorphometric changes. CONCLUSIONS: Intracavernous injection of 1 × 10(6) hBMSCs results in a recovery of penile erection and histomorphometric changes in a rat model of cavernous nerve injury, even when treatment was delayed until 4 weeks after cavernous nerve injury.

Hand-assisted laparoscopic bladder cuff excision via the same hand port as that used for nephroureterectomy.

PURPOSE: The aim of this study was to report our technique of hand-assisted laparoscopic bladder cuff excision through the same hand port as that used for nephroureterectomy and evaluate its benefits and short-term oncologic outcomes. MATERIALS AND METHODS: We included 67 consecutive patients treated by a single surgeon between June 2011 and November 2014 with hand-assisted laparoscopic bladder cuff excision through the same hand port as that used for nephroureterectomy. We retrospectively analyzed procedure-related clinical data and short-term oncologic outcomes. RESULTS: The mean patient age was 66.2 ± 10.6 years. The mean follow-up period was 17.6 months (range 1-37 months). The mean operation time was 243.5 ± 60.4 min. There were no major accidents or open conversions. Forty-two patients (63 %) underwent immediate mitomycin C instillation without complications. There was one high-grade complication (prolonged lymphatic leakage) that required reoperation and multiple hospitalizations. Thirty patients (45 %) underwent regional lymph node dissection. The pathological stages included CIS in 2 (3 %), Ta/T1 in 32 (48 %), T2 in 6 (9 %), T3 in 27 (40 %), and N+ in 4 (6 %) cases. G1, G2, and G3 were seen in 3 (5 %), 21 (31 %), and 43 (64 %) patients, respectively. Eighteen patients (26 %) underwent postoperative adjuvant chemotherapy. Two patients died during the study period, and nine patients (13 %) had bladder recurrences. CONCLUSIONS: HAL bladder cuff excision through the same hand port used for nephroureterectomy is a feasible technique that is both amenable to oncologic principles and can reproduce the open surgical technique.

Nomogram Using Prostate Health Index for Predicting Prostate Cancer in the Gray Zone: Prospective, Multicenter Study.

PURPOSE: To create a nomogram that can predict the probability of prostate cancer using prostate health index (PHI) and clinical parameters of patients. And the optimal cut-off value of PHI for prostate cancer was also assessed. MATERIALS AND METHODS: A prospective, multi-center study was conducted. PHI was evaluated prior to biopsy in patients requiring prostate biopsy due to high prostate-specific antigen (PSA). Among screened 1,010 patients, 626 patients with clinically suspected prostate cancer with aged 40 to 85 years, and with PSA levels ranging from 2.5 to 10 ng/mL were analyzed. RESULTS: Among 626 patients, 38.82% (243/626) and 22.52% (141/626) were diagnosed with prostate cancer and clinically significant prostate cancer, respectively. In the PSA 2.5 to 4 ng/mL group, the areas under the curve (AUCs) of the nomograms for overall prostate cancer and clinically significant prostate cancer were 0.796 (0.727-0.866; p<0.001), and 0.697 (0.598-0.795; p=0.001), respectively. In the PSA 4 to 10 ng/mL group, the AUCs of nomograms for overall prostate cancer and clinically significant prostate cancer were 0.812 (0.783-0.842; p<0.001), and 0.839 (0.810-0.869; p<0.001), respectively. CONCLUSIONS: Even though external validations are necessary, a nomogram using PHI might improve the prediction of prostate cancer, reducing the need for prostate biopsies.

Prostate Cancer Presenting with Pruritus and Cholestasis.

Jaundice is a rare symptom of the paraneoplastic syndrome associated with prostate cancer. We report a case of metastatic prostate cancer that presented as jaundice. There was an absence of biliary obstruction and hepatic metastasis; therefore, the paraneoplastic syndrome was suggested as the etiology of cholestasis. Jaundice improved with the treatment of prostate cancer. In the literature, interleukin-6 has been suggested to be associated with paraneoplastic syndrome.

Atypical antipsychotic olanzapine inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells.

BACKGROUND: Olanzapine, an FDA-approved atypical antipsychotic, is widely used to treat schizophrenia and bipolar disorder. In this study, the inhibitory effect of olanzapine on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells was investigated. METHODS: Electrophysiological recordings were performed in freshly isolated coronary arterial smooth muscle cells. RESULTS: Olanzapine inhibited the Kv channels in a concentration-dependent manner with an IC50 value of 7.76 ± 1.80 µM and a Hill coefficient of 0.82 ± 0.09. Although olanzapine did not change the steady-state activation curve, it shifted the inactivation curve to a more negative potential, suggesting that it inhibited Kv currents by affecting the voltage sensor of the Kv channel. Application of 1 or 2 Hz train pulses did not affect the olanzapine-induced inhibition of Kv channels, suggesting that its effect on Kv channels occurs in a use (state)-independent manner. Pretreatment with DPO-1 (Kv1.5 subtype inhibitor) reduced the olanzapine-induced inhibition of Kv currents. In addition, pretreatment with guangxitoxin (Kv2.1 subtype inhibitor) and linopirdine (Kv7 subtype inhibitor) partially decreased the degree of Kv current inhibition. Olanzapine induced membrane depolarization. CONCLUSION: From these results, we suggest that olanzapine inhibits the Kv channels in a concentration-dependent, but state-independent, manner by affecting the gating properties of Kv channels. The primary Kv channel target of olanzapine is the Kv1.5 subtype.

The anti-diabetic drug alogliptin induces vasorelaxation via activation of Kv channels and SERCA pumps.

In the present study, we investigated the vasorelaxant effects of alogliptin, an oral antidiabetic drug in the dipeptidyl peptidase-4 (DPP-4) inhibitor class, using phenylephrine (Phe)-induced pre-contracted aortic rings. Alogliptin induced vasorelaxation in a dose-dependent manner. Pre-treatment with the voltage-dependent K+ (Kv) channel inhibitor 4-aminopyridine (4-AP) significantly decreased the vasorelaxant effect of alogliptin, whereas pre-treatment with the inwardly rectifying K+ (Kir) channel inhibitor Ba2+, ATP-sensitive K+ (KATP) channel inhibitor glibenclamide, and large-conductance Ca2+-activated K+ (BKCa) channel inhibitor paxilline did not alter the effects of alogliptin. Although pre-treatment with the Ca2+ channel inhibitor nifedipine did not affect the vasorelaxant effect of alogliptin, pre-treatment with the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin and cyclopiazonic acid effectively attenuated the vasorelaxant response of alogliptin. Neither cGMP/protein kinase G (PKG)-related signaling pathway inhibitors (guanylyl cyclase inhibitor ODQ and PKG inhibitor KT 5823) nor cAMP/protein kinase A (PKA)-related signaling pathway inhibitors (adenylyl cyclase inhibitor SQ 22536 and PKA inhibitor KT 5720) reduced the vasorelaxant effect of alogliptin. Similarly, the vasorelaxant effect of alogliptin was not changed by endothelium removal or pre-treatment with the nitric oxide (NO) synthase inhibitor L-NAME or the small- and intermediate-conductance Ca2+-activated K+ (SKCa and IKCa) channel inhibitors apamin and TRAM-34. Based on these results, we suggest that alogliptin induced vasorelaxation in rabbit aortic smooth muscle by activating Kv channels and the SERCA pump independent of other K+ channels, cGMP/PKG-related or cAMP/PKA-related signaling pathways, and the endothelium.

Preoperative prostate health index and %p2PSA as the significant biomarkers of postoperative pathological outcomes of prostate cancer in Korean males: A prospective multi-institutional study.

Purpose: To evaluate the clinical utility of percentage of serum prostate-specific antigen (proPSA) to free PSA (%p2PSA) and the prostate health index (PHI) for predicting aggressive pathological outcomes of radical prostatectomy (RP) in Korean males. Materials and Methods: This prospective observational multicenter study included 160 Korean males who consecutively underwent RP. The predictive utility of preoperative %p2PSA and PHI for predicting the following pathological outcomes of RP including pT3 disease, pathologic Gleason sum ≥7, and Gleason sum upgrading was investigated using multivariate and decision-curve analyses. Results: The PHI and %p2PSA levels were significantly higher in patients with pT3 disease, pathologic Gleason sum ≥7, and Gleason sum upgrading. On univariate analysis, PHI was an accurate predictor of pT3 disease, pathologic Gleason sum ≥7, and Gleason sum upgrading. Multivariate and decision curve analyses revealed that inclusion of PHI to a base multivariate model including total PSA, percentage free PSA, PSA density, percentage of positive biopsy core, biopsy Gleason sum, and clinical stage factors significantly increased its predictive accuracy; %p2PSA showed a similar result. However, PHI was a more valuable predictor of pathological outcomes of RP. Conclusions: This study revealed PHI and %p2PSA as preoperative biomarkers of pathological outcomes in Korean males who underwent RP for prostate cancer.

Establishment of NOAEL for intracavernous injections of human bone marrow-derived mesenchymal stem cells in rats.

Purpose: To assess the possible negative health effects of human bone marrow-derived mesenchymal stem cells (hBMSCs) on fertility and early embryonic development following intracavernous injections in rats. Materials and Methods: A total of 88 Crl:CD(SD) male and female rats were equally divided into 4 groups in a random manner: control group (normal saline), low-dose group (2×105 hBMSCs), moderate-dose group (1×106 hBMSCs), and high-dose group (2×106 hBMSCs). hBMSCs or normal saline was injected into the penis of the rats 3 times at 2-week-intervals prior to mating. We compared each group with respect to parameters of reproduction and histopathology. Results: For male rats, various degrees of flushing and swelling were observed at the penile injection site in all the groups, although the severity increased in a dose-dependent manner in the hBMSC injection groups. There were no statistically significant differences in mean body weights and food consumption among all the groups of both sexes. There were no statistically significant differences in reproductive parameters among all the groups of both sexes. The absolute and relative organ weights did not significantly differ among the groups. At the time of necropsy, no remarkable findings were observed in gross examinations in all groups. On histopathological analysis, minimal mononuclear cell infiltration was observed in the right epididymis of each rat in the moderate- and high-dose groups. Conclusions: The non-toxic amount of hBMSCs for male fertility and early embryogenesis in rats under the test conditions was determined to be 2×106 cells/head.

Hypoxic Preconditioned Mesenchymal Stromal Cell Therapy in a Rat Model of Renal Ischemia-reperfusion Injury: Development of Optimal Protocol to Potentiate Therapeutic Efficacy.

Although previous and ongoing clinical studies have used stromal cells during renal ischemia-reperfusion injury (IRI), there is little consensus regarding the optimal protocol. We aimed to optimize the protocol for hypoxic preconditioned human bone marrow-derived mesenchymal stromal cell (HP-hBMSC) therapy in a rat model of renal IRI. We determined the optimal injection route (renal arterial, renal parenchymal, and tail venous injection), dose (low-dose: 1×106, moderate-dose: 2×106, and high-dose: 4×106), and injection period (pre-, concurrent-, and post-IRI). During optimal injection route study, renal arterial injections significantly reduced the decreasing glomerular filtration rate (GFR), as compared to GFRs for the IRI control group, 2 and 4 days after IRI. Therapeutic effects and histological recoveries were the greatest in the group receiving renal arterial injections. During the dose finding study, high-dose injections significantly reduced the decreasing GFR, as compared to GFRs for the IRI control group, 3 days after IRI. Therapeutic effects and histological recoveries were the greatest in the high-dose injection group. While determining the optimal injection timing study, concurrent-IRI injection reduced elevated serum creatinine levels, as compared to those of the IRI control group, 1 day after IRI. Pre-IRI injection significantly reduced the decreasing GFR, as compared with GFRs for the IRI control group, 1 day after IRI. Therapeutic effects and histological recoveries were the greatest in the concurrent-IRI group. In conclusion, the concurrent-IRI administration of a high dose of HP-hBMSC via the renal artery leads to an optimal recovery of renal function after renal IRI.

Outcomes of patients with ureteral obstruction who achieved stent-free state following balloon dilatation.

OBJECTIVE: The aim of this study was to assess the therapeutic role of ureteral stent removal following balloon dilatation (BD) in patients with a stent implanted for unilateral ureteral obstruction and with normal contralateral renal function. MATERIALS AND METHODS: This retrospective cohort study consisted of 37 consecutive patients with unilateral ureteral obstruction whose stents were removed after BD. All patients satisfied the following criteria: normal contralateral renal function, no evidence of malignancy, and the patient was eager to obtain a stent-free state (SFS) without invasive treatment. The relative function of the affected kidney and total renal function before and after stent removal were analyzed using renal scans and estimated glomerular filtration rate (eGFR). A successful outcome was defined as SFS without pain or febrile urinary tract infection plus maintenance of eGFR. RESULTS: The mean age of all patients was 58.2 years. The mean follow-up periods before and after stent removals were 15.7 and 23.6 months, respectively. The most common underlying cause of ureteral obstruction was pelvic or abdominal surgery (51.4%). Of the 37 patients, 32 (86.5%) achieved successful SFS at last follow-up. Overall in the 37 patients, the eGFR (from 77.1 to 69.8 ml/min/1.73 m(2); p = 0.017) and relative renal function of the affected kidney (from 35.5 to 30.2%; p = 0.002) were significantly compromised. However, the reduction in total eGFR was not significant (p = 0.075) in the successful SFS group. CONCLUSION: The removal of a stent with BD is a viable option for achieving a successful SFS in patients with unilateral ureteral obstruction.

Changes of calcific density in pediatric patients with testicular microlithiasis.

PURPOSE: Testicular microlithiasis (TM) is a relatively rare clinical entity of controversial significance characterized by the existence of hydroxyapatite microliths located in the seminiferous tubules. The aim of this study was to observe the natural course of changes in the calcific density of pediatric TM. MATERIALS AND METHODS: We included a total of 23 TM patients undergoing scrotal ultrasound (US) on at least two occasions from July 1997 to August 2014. We retrospectively analyzed the patient characteristics, clinical manifestations, specific pathological features, and clinical outcomes. We measured the calcified area and compared the calcific density between the initial and final USs. RESULTS: The mean age at diagnosis was 11.3±4.6 years, and the follow-up period was 79.1±38.8 months (range, 25.4-152.9 months). During the follow-up period, no patients developed testicular cancer. Calcific density on US was increased in the last versus the initial US, but not to a statistically significant degree (3.74%±6.0% vs. 3.06%±4.38%, respectively, p=0.147). When we defined groups with increased and decreased calcification, we found that diffuse TM was categorized into the increased group to a greater degree than focal TM (10/20 vs. 4/23, respectively, p=0.049). In addition, five of eight cases of cryptorchidism (including two cases of bilateral cryptorchidism) were categorized in the increased calcification group. CONCLUSIONS: Diffuse TM and cryptorchidism tend to increase calcific density. Close observation is therefore recommended for cases of TM combined with cryptorchidism and cases of diffuse TM.

Complications after polymeric and metallic ureteral stent placements including three types of fistula.

PURPOSE: To report complications, including three types of fistula, intractable hematuria, and pain, which can develop after polymeric ureteral stent (PUS) or metallic ureteral stent placements and to evaluate the risk factors for these adverse events. PATIENTS AND METHODS: We reviewed seven patients referred to our trauma and reconstructive subdivision for complications that presented after placement of a PUS (two patients), double-layered, coated, self-expandable, mesh metallic stent (three patients), Memokath stent (one patient), or Resonance stent (one patient). We retrospectively reviewed their medical records and accessed the predisposing factors, mechanism of injury, diagnosis, and interventional and surgical management. RESULTS: The two patients with PUS presented with ureteroarterial fistula (UAF). Among patients with a self-expandable metallic mesh stents, UAF developed UAF in one patient, ureteroenteral fistula (UEF) developed in one patient, and ureterovaginal fistula (UVF) developed in one patient. There were five patients with fistula who had a history of pelvic surgery, radiation therapy, long-term ureteral stent, or high-pressure balloon dilation. Surgical procedures were needed to manage these problems, including nephrectomy in two patients and bypass surgery with ureter ligation in two patients. UAF was seen with massive gross hematuria that necessitated angiography. UEF required small bowel resection. The patient with UVF underwent multiple surgeries for recurrent fistula. Patients with a Memokath or Resonance stent presented with intractable flank pain and hematuria. These persons required a surgical or other procedure to remove the stents. CONCLUSIONS: UAF should be highly suspected in patients with long-term ureteral stents, especially if gross hematuria develops. The placement of a metallic ureteral stent using a high-pressure balloon should be performed cautiously, especially in patients with a history of pelvic surgery or radiation.

Kidney Laterality and the Safety of Hand-assisted Live Donor Nephrectomy: Review of 1000 Consecutive Cases at a Single Center.

OBJECTIVE: To determine the feasibility of performing right-sided, hand-assisted, laparoscopic donor nephrectomy (HALDN) and compare with the results of left-sided surgeries in both donors and recipients. METHODS: Between September 2006 and September 2013, 1000 consecutive patients underwent HALDN at our institution. Patient characteristics and the intraoperative or postoperative parameters of the donors and recipients were retrospectively evaluated. Preoperative data, including relative renal function, vascular anatomy, and parenchymal abnormalities, were evaluated to determine the reasons for harvesting the right kidney. Intraoperative and postoperative data, including pneumoperitoneum time, warm ischemia time, complications, chronic kidney disease stage, and graft function, were compared between donors and recipients who underwent right- and left-sided procurement. RESULTS: Mean follow-up period was 21 months in donor and 42 months in recipient. Right-sided HALDN was performed on 421 patients (42.1%). The most common reasons for selecting the right kidney was reduced right kidney function (53.4%) followed by multiple left renal arteries (34.2%). None of 1000 patients required conversion to open surgery or developed major complications. Serum creatinine concentrations and chronic kidney disease stage at the last follow-up examinations were similar in donors. There were no significant differences in graft function and ureter-related complications between right- and left-sided kidneys at the last follow-up examination. CONCLUSION: Right-side HALDN is a safe procedure. The donor side can be freely selected using HALDN to benefit both donors and recipients.

Comparative study of autologous stromal vascular fraction and adipose-derived stem cells for erectile function recovery in a rat model of cavernous nerve injury.

The abilities of intracavernous injection of autologous stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) to facilitate recovery of erectile function in a rat model of cavernous nerve (CN) injury were compared. Forty male Sprague-Dawley rats were randomly divided into four groups: sham and control groups (intracavernous injection of phosphate-buffered saline), SVF group (intracavernous injection of SVF), and ADSC group (intracavernous injection of ADSCs). Rats in the latter three groups underwent bilateral CN injury prior to injection. The evaluation of erectile function and histomorphometric studies were performed 4 weeks after injection. The ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the control group than in the sham group (0.18 vs. 0.56, p < .001). Intracavernous injection of SVF (0.36, p = .035) significantly improved erectile function compared with that in the control group, whereas the ADSC group (0.35, p = .052) showed marginally significant improvement. The smooth muscle/collagen ratio, smooth muscle content, number of neuronal nitric-oxide synthase-positive nerve fibers, and expression of von Willebrand factor were significantly higher in the SVF and ADSC groups than in the control group. Expression of endothelial nitric-oxide synthase was significantly increased in the SVF group. The increases in the smooth muscle/collagen ratio and von Willebrand factor expression were larger in the SVF group than in the ADSC group. Intracavernous injection of SVF or ADSCs was equally effective in recovering penile erection in a rat model of CN injury.