Involvement of NOTCH1-mediated Microglia Activation in Neuromodulation of Chronic Prostatitis-related Pain.

BACKGROUND/AIM: This study aimed to investigate the role of NOTCH receptor 1 (NOTCH1)-mediated activation of microglia in the L5-S2 spinal dorsal horn in chronic prostatitis pain. MATERIALS AND METHODS: Rats were divided into chronic prostatitis (CP) group and control group. Complete Freund's adjuvant was injected into the prostate, and prostate pathology and pain-related behavior were monitored to assess the successful establishment of the CP-related pain model. The dorsal horn of the L5-S2 spinal cord was collected for the detection of ionized calcium-binding adapter molecule 1 (IBA-1) and NOTCH1 expression by quantitative real time polymerase chain reaction and the detection of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) by enzyme-linked immunosorbent assay. Electrical excitability was assessed with whole-cell patch clamp. In addition, NOTCH1 receptor inhibitor or inhibitor of microglial cell activation was injected into the subarachnoid space, and the pro-inflammatory cytokines in the spinal cord were detected. RESULTS: In the CP group, the expression of NOTCH1, IBA-1, TNF-α and IL-1ß began to increase at 4 days, peaked at 12 days, and began to decline at 24 days, and it was significantly higher than in the control group (p<0.01). Inhibition of microglia or NOTCH1 receptor markedly reduced the content of TNF-α and IL-1ß in the spinal cord (p<0.05). At 4, 12 and 24 days, the amplitude and frequency of neuronal action potential increased and the threshold decreased markedly as compared to the control group (p<0.05), and spontaneous action potential was noted. CONCLUSION: NOTCH1 mediates the activation of microglia in the L5-S2 spinal cord, leading to the secretion of inflammatory factors and enhanced electrical excitability of neurons, which is related to persistent and refractory chronic prostatitis-related pain.

Differential Efficacy of Small Molecules Dynasore and Mdivi-1 for the Treatment of Dry Eye Epitheliopathy or as a Countermeasure for Nitrogen Mustard Exposure of the Ocular Surface.

The ocular surface comprises the wet mucosal epithelia of the cornea and conjunctiva, the associated glands, and the overlying tear film. Epitheliopathy is the common pathologic outcome when the ocular surface is subjected to oxidative stress. Whether different stresses act via the same or different mechanisms is not known. Dynasore and dyngo-4a, small molecules developed to inhibit the GTPase activity of classic dynamins DNM1, DNM2, and DNM3, but not mdivi-1, a specific inhibitor of DNM1L, protect corneal epithelial cells exposed to the oxidant tert-butyl hydroperoxide (tBHP). Here we report that, while dyngo-4a is the more potent inhibitor of endocytosis, dynasore is the better cytoprotectant. Dynasore also protects corneal epithelial cells against exposure to high salt in an in vitro model of dysfunctional tears in dry eye. We now validate this finding in vivo, demonstrating that dynasore protects against epitheliopathy in a mouse model of dry eye. Knockdown of classic dynamin DNM2 was also cytoprotective against tBHP exposure, suggesting that dynasore's effect is at least partially on target. Like tBHP and high salt, exposure of corneal epithelial cells to nitrogen mustard upregulated the unfolded protein response and inflammatory markers, but dynasore did not protect against nitrogen mustard exposure. In contrast, mdivi-1 was cytoprotective. Interestingly, mdivi-1 did not inhibit the nitrogen mustard-induced expression of inflammatory cytokines. We conclude that exposure to tBHP or nitrogen mustard, two different oxidative stress agents, cause corneal epitheliopathy via different pathologic pathways. SIGNIFICANCE STATEMENT: Results presented in this paper, for the first time, implicate the dynamin DNM2 in ocular surface epitheliopathy. The findings suggest that dynasore could serve as a new topical treatment for dry eye epitheliopathy and that mdivi-1 could serve as a medical countermeasure for epitheliopathy due to nitrogen mustard exposure, with potentially increased efficacy when combined with anti-inflammatory agents and/or UPR modulators.

Recombinant Human Clusterin Seals Damage to the Ocular Surface Barrier in a Mouse Model of Ophthalmic Preservative-Induced Epitheliopathy.

There is a significant unmet need for therapeutics to treat ocular surface barrier damage, also called epitheliopathy, due to dry eye and related diseases. We recently reported that the natural tear glycoprotein CLU (clusterin), a molecular chaperone and matrix metalloproteinase inhibitor, seals and heals epitheliopathy in mice subjected to desiccating stress in a model of aqueous-deficient/evaporative dry eye. Here we investigated CLU sealing using a second model with features of ophthalmic preservative-induced dry eye. The ocular surface was stressed by topical application of the ophthalmic preservative benzalkonium chloride (BAC). Then eyes were treated with CLU and sealing was evaluated immediately by quantification of clinical dye uptake. A commercial recombinant form of human CLU (rhCLU), as well as an rhCLU form produced in our laboratory, designed to be compatible with U.S. Food and Drug Administration guidelines on current Good Manufacturing Practices (cGMP), were as effective as natural plasma-derived human CLU (pCLU) in sealing the damaged ocular surface barrier. In contrast, two other proteins found in tears: TIMP1 and LCN1 (tear lipocalin), exhibited no sealing activity. The efficacy and selectivity of rhCLU for sealing of the damaged ocular surface epithelial barrier suggests that it could be of therapeutic value in treating BAC-induced epitheliopathy and related diseases.

Ecological Risk Assessment and Source Apportionment of Heavy Metals in the Soil of an Opencast Mine in Xinjiang.

To study the influence of open-pit coal mining on the surrounding soil environment and human health, this study selected the Hongshaquan coal mine in Xinjiang as the research area and took 31 soil samples from the dump and artificial forest of the mining area. The contents of seven heavy metals (As, Cd, Cr, Cu, Ni, Pb and Zn) in the soil were analyzed. The pollution index method, geoaccumulation index method (Igeo), potential ecological risk index method, health ecological risk assessment model and principal component analysis (PCA) were used to evaluate and analyze the heavy metal pollution, potential ecological risk and health ecological risk of the soil. The results showed that compared with the background value of soil in Xinjiang, except for Pb, other heavy metal elements were essentially pollution-free and belonged to the low ecological risk area. The health risk assessment model showed that Pb and As were the main pollution factors of noncarcinogenic risk, and that exposure to Ni, Pb and As had a lower carcinogenic risk. The PCA showed that Cu, Cr, Ni, Pb, As and Zn in the dump were from transportation and industrial activities, Cd was from natural resources, and Cr, Zn, Ni, Cd and Pb were from transportation in the artificial forest. Cu came from industrial sources and As from soil parent material. The dump was more seriously disturbed by human factors than by artificial forests. Our research provides a reference for heavy metal pollution and source analysis caused by mining.

Phytoplankton-Zooplankton Community Structure in Coal Mining Subsidence Lake.

Land subsidence from coal mining has shaped new artificial aquatic ecosystems, these subsidence lakes are known for their restricted ecological system, water pollution, and extreme habitat conditions. However, knowledge concerning the community structure of plankton in these types of water bodies is still limited. Therefore, both phytoplankton and zooplankton communities' abundance, distribution, and diversity, as well as relations of these communities to physicochemical water quality variables were analyzed, alongside the interaction between phytoplankton and zooplankton groups. The results indicate zooplankton abundance was 842.375 to 186,355.0 ind./L. Biomass ranged from 0.3408 to 10.0842 mg/L. Phytoplankton abundance varied between 0.541 × 106 cell/L and 52.340 × 106 cell/L while phytoplankton wet biomass ranged from 0.5123 to 5.6532 mg/L. Pearson correlation analysis revealed that both the zooplankton and phytoplankton total densities were significantly correlated with nutrients (TN, TP, PO43-) and CODcr; zooplankton abundance was significantly correlated with phytoplankton abundance. According to the biodiversity index of Shannon-Wiener, both phytoplankton and zooplankton revealed less biodiversity in the subsidence water region than in the Huihe river system and Xiangshun canal, with values ranging from 0.20 to 2.60 for phytoplankton and 1.18 to 2.45 for zooplankton; however, the phytoplankton community showed lower biodiversity index values compared to the zooplankton community. Overall, the knowledge gleaned from the study of plankton community structure and diversity represents a valuable approach for the evaluation of the ecological conditions within the subsidence lakes, which has significant repercussions for the management and protection of aquatic environments in mining areas.

Small-molecule antagonism of the interaction of the RAGE cytoplasmic domain with DIAPH1 reduces diabetic complications in mice.

The macro- and microvascular complications of type 1 and 2 diabetes lead to increased disease severity and mortality. The receptor for advanced glycation end products (RAGE) can bind AGEs and multiple proinflammatory ligands that accumulate in diabetic tissues. Preclinical studies indicate that RAGE antagonists have beneficial effects on numerous complications of diabetes. However, these antagonists target the extracellular domains of RAGE, which bind distinct RAGE ligands at diverse sites in the immunoglobulin-like variable domain and two constant domains. The cytoplasmic tail of RAGE (ctRAGE) binds to the formin, Diaphanous-1 (DIAPH1), and this interaction is important for RAGE signaling. To comprehensively capture the breadth of RAGE signaling, we developed small-molecule antagonists of ctRAGE-DIAPH1 interaction, termed RAGE229. We demonstrated that RAGE229 is effective in suppressing RAGE-DIAPH1 binding, Förster resonance energy transfer, and biological activities in cellular assays. Using solution nuclear magnetic resonance spectroscopy, we defined the molecular underpinnings of the interaction of RAGE229 with RAGE. Through in vivo experimentation, we showed that RAGE229 assuaged short- and long-term complications of diabetes in both male and female mice, without lowering blood glucose concentrations. Last, the treatment with RAGE229 reduced plasma concentrations of TNF-α, IL-6, and CCL2/JE-MCP1 in diabetic mice, in parallel with reduced pathological and functional indices of diabetes-like kidney disease. Targeting ctRAGE-DIAPH1 interaction with RAGE229 mitigated diabetic complications in rodents by attenuating inflammatory signaling.

A Renal Cell Carcinoma with Biallelic Somatic TSC2 Mutation: Clinical Study and Literature Review.

OBJECTIVE: To elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC). METHODS: Mutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted. RESULTS: Two novel somatic mutations of TSC2 in unilateral and solitary RCC samples from a 14-year-old female were identified. The pathological features suggest the tumor as a clear-cell renal cell carcinoma. In addition, immunohistochemistry revealed elevated levels of phosphorylated S6K1. Results from in vitro cellular experiments suggest that the mutant TSC2 proteins were quickly degraded and they failed to repress the phosphorylation of S6K1 and STAT3, which leads to constitutive activation of mTORC1 pathway and ultimately cause the development of RCC. CONCLUSION: Detecting TSC2 mutation in patients with early RCC onset would be beneficial and mTOR inhibitor could be a therapeutic option for TSC2 mutation-induced RCC.

Synthesis and pharmacological evaluation of novel epidermal growth factor receptor inhibitors against prostate tumor cells.

The aim of the present study was to investigate the activities of novel synthetic epidermal growth factor receptor (EGFR) inhibitors (ZINC05463076, ZINC2102846 and ZINC19901103) against prostate tumors, in vitro models and investigate the potential underlying mechanisms. A panel of prostate tumor cell lines (LNCaP, DU-145, PC-3 and LNCaP-AI cells) were used to evaluate antitumor activity of ZINC05463076, ZINC2102846, and ZINC19901103 in vitro. Cell growth and clonal formation were determined by MTT assay and Soft agar colony formation assay, respectively. An EGFR kinase assay following treatment of the compounds was performed by ELISA. Cell cycle-regulating proteins, including cyclin-dependent kinase (CDK)1, CKD2, CKD4 and inhibitory effects of these compounds on downstream signaling were analyzed by western blotting. Flow cytometry was performed to investigate apoptosis and cell cycle phases of the treated cells. It was revealed that all compounds synthesized in the present study demonstrated significant EGFR inhibition abilities, compared with approved EGFR inhibitor drug gefitinib. Treatment of LNCaP, DU-145, PC3 and LNCaP-AI cells with these compounds revealed cell proliferation inhibition and colony formation suppression dose-dependently in vitro. The agents impaired phosphorylation of EGFR and extracellular signal-regulated kinase 1/2 and suppressed their downstream signaling. In addition, these novel synthetic agents decreased the expression level of survivin, which may induce G1 cell cycle phase arrest and cell apoptosis in PCa cells subsequently. Collectively, ZINC05463076, ZINC2102846 and ZINC19901103 exhibited significant antitumor activity in human prostate tumors in vitro, by inhibiting EGFR and promoting apoptosis, which suggested a rationale for clinical development in prostate tumor therapy.

Head-to-Head Comparison of Modified Laparoscopic Pyeloplasty and Robot-Assisted Pyeloplasty for Ureteropelvic Junction Obstruction in China.

OBJECTIVE: To compare the outcomes of modified laparoscopic pyeloplasty (LP) and robot-assisted pyeloplasty (RLP) for ureteropelvic junction obstruction (UPJO) in China patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent modified LP and RLP using a transperitoneal laparoscopic approach at 2 different medical institutions between October 2009 and November 2017. RESULTS: Seventy-six patients underwent modified LP and 140 patients underwent RLP. No open conversion occurred. The mean operative time of RLP was shorter than that of modified LP (p = 0.042). For UPJO concomitant with renal calculi, there was no difference in operative time between 2 groups (p = 0.656). With RLP, the operative time for UPJO concomitant with horseshoe was shorter (p = 0.011). In terms of complication rate, there was no significant difference between 2 groups (p = 0.596). The postoperative hospital stay for modified LP was shorter than that for RLP (p < 0.05). The mean follow-up time for modified LP and RLP was 31.79 months and 10.85 months respectively (p < 0.05). The success rate was 96.05 and 97.86% for modified LP and RLP, respectively (p = 0.736). CONCLUSIONS: Modified LP and RLP are safe and efficient treatment for UPJO with similar success rates.

Treatment and outcomes of urethral recurrence after orthotopic neobladder replacement in patients with bladder cancer - practice in a single centre.

Objectives To report on the treatment of urethral recurrence after orthotopic urinary diversion at our institution. Methods We retrospectively reviewed clinical information of urethral recurrence in patients who underwent radical cystectomy and orthotopic urinary diversion between January 1998 and January 2013. Results Of 341 patients, 282 presented for follow-up (median follow-up: 56 months; range: 1-174 months). Eight patients developed local recurrence of urothelial cancer after radical cystectomy. The rate of urethral recurrence (1.4%) in female patients who underwent orthotopic urinary diversion was lower than in male patients (3.3%). The median (range) time to recurrence was 33 (6-120) months after radical cystectomy and orthotopic urinary diversion. Recurrences were treated by transurethral resection of tumour, urethrectomy, neobladder resection, revision of urinary diversion, adjuvant chemotherapy, or radiation therapy, based on individual circumstances. Survival analysis showed that 5-year cancer-specific survival was significantly higher in patients with urethral recurrence alone (83.3%), compared with patients with other recurrences, including pelvic/abdomen recurrence and distant metastasis (26.8%). Conclusions En bloc urethrectomy and revision of urinary diversion remain the principle surgical choices. Selection of transurethral tumour resection was based on tumour stage and was used in carefully chosen patients. Cancer-specific survival might depend on multidisciplinary therapy.

Notch3 overexpression enhances progression and chemoresistance of urothelial carcinoma.

Abnormal activation of Notch signaling is involved in the etiology of various diseases, including cancer, but the association between Notch3 expression in urothelial cancer and clinical outcome remains unclear, and the molecular mechanisms underlying Notch3 signaling activation are not well defined. In this study we examined 59 urothelial cancer patients and found that Notch3 was more highly expressed in human urothelial cancer tissues than in non-tumorous bladder tissue samples, with Notch3 overexpression being associated with poor clinical outcome. Notch3 knockdown resulted in decreased proliferation of urothelial cancer cells in vitro and decreased xenograft tumor growth in vivo. In addition, Notch3 knockdown rendered urothelial cancer cells more sensitive to cisplatin. Furthermore, suberoylanilide hydroxamic acid (SAHA, a histone deacetylase [HDAC] inhibitor) induced acetylation of NOTCH3, downregulated Notch 3, prevented urothelial cancer cell proliferation, and induced cell cycle arrest. Taken together, these data suggested that Notch 3 overexpression promotes growth and chemoresistance in urothelial cancer.

Downregulated XPA promotes carcinogenesis of bladder cancer via impairment of DNA repair.

Bladder cancer is the most common malignant tumor of urinary system, largely resulting from failure of repair of DNA damage to the environmental insults. The function of XPA in nucleotide excision repair pathway has been well documented. However, participation of XPA in the repair of DNA double-strand break remains unknown. Here, we reported that bladder cancer expressed low XPA levels compared to adjacent non-tumor bladder tissue, and this phenotype was closely associated with chromosomal aberrations. Moreover, downregulated XPA appeared to increase incidence of chromosome aberration. XPA reduction increased cell viability of a bladder cancer cell line RT4, while XPA re-expression decreased the cell viability of RT4 cells. Since high mutation frequency is the basis of mutations of oncogenes and anti-oncogenes, and may be the essence of bladder cancer susceptibility, our study suggests that downregulated XPA may promote carcinogenesis of bladder cancer via impairment of DNA repair.

Ginkgolide B Inhibits Human Bladder Cancer Cell Migration and Invasion Through MicroRNA-223-3p.

BACKGROUND/AIMS: Ginkgolide B (GB) is currently used as an anticancer drug for treatment of some malignant cancers. However, whether it may have therapeutic effects on bladder cancer remains unknown. Here, we studied the effects of GB on bladder cancer cells. METHODS: Bladder cells were treated with different doses of GB, and the effects on ZEB1 and microRNA-223-3p (miR-223-3p) were analyzed by RT-qPCR and/or Western blot. Prediction of a regulatory relationship between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. RESULTS: We found that GB dose-dependently decreased ZEB1 protein, but not mRNA, in bladder cancer cells, resulting in suppression of cell invasion. Moreover, in bladder cancer cells, GB dose-dependently decreased the levels of miR-223-3p, which suppressed the protein translation of ZEB1 through binding to 3'-UTR of ZEB1 mRNA. Overexpression of miR-223-3p decreased ZEB1 protein, while depletion of miR-223-3p increased ZEB1 protein in bladder cancer cells. CONCLUSION: GB inhibits bladder cancer cell invasiveness through suppressing ZEB1 protein translation via upregulating miR-223-3p.

Higher expression of XPF is a critical factor in intrinsic chemotherapy resistance of human renal cell carcinoma.

Human renal cancer is extremely resistant to chemotherapy and radiation therapy. This clinical characteristic reduces the efficacy of chemotherapeutic agents in the treatment of recurrence or metastasis following surgical resection. Understanding the mechanism of chemotherapy resistance in renal cell carcinoma remains a significant challenge. In this study, we have shown that varied level of XPF expression was organ-tissue specific by comparing human renal cancer, bladder cancer, testicular cancer and their normal tissue counterparts, respectively. The expression of XPF was significantly higher in renal cancer than in bladder cancer and testicular cancer and correlated with the clinical characteristic of their chemotherapeutics sensitivity. These novel findings proposed that the intrinsic chemoresistance of human renal cell carcinomas might be derived from the high level of XPF expression. In a panel of five cancer cell lines, decreasing cisplatin sensitivity correlated with increasing levels of XPF expression. Knockdown of XPF expression not only increased sensitivity of renal carcinoma cells to cisplatin treatment by affecting the DNA damage response, including DNA repair, cell cycle regulation and apoptosis, but also increased senescence of renal cancer cell. Furthermore, experiment in vivo confirmed that silenced XPF significantly increased the sensitivity and survival following treatment with cisplatin in xenograft mice bearing renal cell tumor. These findings firstly uncover a partial mechanism of intrinsic chemoresistance in renal cancer and may provide a new approach to break through the obstacle of intrinsic chemoresistance by targeting the XPF protein with a potential new inhibitor.

Small Molecule Inhibition of Ligand-Stimulated RAGE-DIAPH1 Signal Transduction.

The receptor for advanced glycation endproducts (RAGE) binds diverse ligands linked to chronic inflammation and disease. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. The cytoplasmic tail (ct) of RAGE is essential for RAGE ligand-mediated signal transduction and consequent modulation of gene expression and cellular properties. RAGE signaling requires interaction of ctRAGE with the intracellular effector, mammalian diaphanous 1 or DIAPH1. We screened a library of 58,000 small molecules and identified 13 small molecule competitive inhibitors of ctRAGE interaction with DIAPH1. These compounds, which exhibit in vitro and in vivo inhibition of RAGE-dependent molecular processes, present attractive molecular scaffolds for the development of therapeutics against RAGE-mediated diseases, such as those linked to diabetic complications, Alzheimer's disease, and chronic inflammation, and provide support for the feasibility of inhibition of protein-protein interaction (PPI).

A Novel Portable Foldable Laparoscopic Trainer for Surgical Education.

OBJECTIVES: Training in laparoscopic surgeries is difficult due to high cost and limited opportunity of commercially available laparoscopic training. Many "home-made" trainers were reported to solve this obstacle, but they were either cumbersome or high cost, or both. This study aimed to create an available and effective trainer to enable the trainees in developing laparoscopic skills anytime and anywhere. METHORDS: The laparoscopic trainer contains clamshell-like plastic plates and an electronic device with camera function, which could be supplied into a serious of laparoscopic procedures. The training procedure is detailed in this study. RESULTS: The creation of the portable and foldable trainer led to the development of "home-made" laparoscopic trainers. The integration of clamshell-like plastic plates and camera function device resulted in a trainer with low cost and enabled the trainees to practice skills in intermediate-fidelity environment. Additionally, the teaching effects show that the 3DV and 3DP models were significantly better than the traditional anatomical atlas. CONCLUSION: The trainer in this study was built to create a prototype of "home-made" trainer with flexible features and low cost. It can be considered as an alternate way of developing laparoscopic skills required in operation room.

Knockdown of ZFX suppresses renal carcinoma cell growth and induces apoptosis.

The ZFX (zinc finger protein, X-linked) gene located on the human X chromosome controls the self-renewal of embryonic and hematopoietic stem cells as a transcriptional regulator. Recently, studies have affirmed that ZFX is associated with several human cancers, including lymphoma, laryngeal squamous cell carcinoma, prostate cancer, and liver cancer, which suggests ZFX as a potential therapeutic target in cancer. However, the functional role of ZFX in human renal cancer remains unclear. Herein, we detected the expression of ZFX in 42 patients with renal cancer and found the expression of ZFX was specifically upregulated in cancer tissues at the mRNA and protein levels. Moreover, we employed lentivirus-mediated short hairpin RNA (shRNA) to knock down ZFX expression in two human renal cell carcinoma cell lines, 786-0 and ACHN. Functional analysis indicated that ZFX silencing significantly inhibited renal cell carcinoma cell proliferation and cell cycle progression, probably because of suppression of CDK4 and cyclin D1, and induced apoptosis via activation of Bax, Caspase 3, and PUMA in a p53-dependent manner. Our findings suggest that knockdown of ZFX by shRNA may be a potential therapeutic approach for the treatment of renal cancer.

Use of urostomy bags in the management of perioperative urine leakage after radical cystectomy.

BACKGROUND: Urine leakage is a common complication in patients with bladder cancer after radical cystectomy and neobladder reconstruction. OBJECTIVE: The aim of this study was to evaluate the clinical value of the use of urostomy bags in the management of urine leakage in patients with bladder cancer after radical cystectomy. METHODS: Urine leakage during the perioperative period was retrospectively analyzed in 483 patients with bladder cancer who underwent radical cystectomy from 2004 to 2010. Before 2008, all patients with urine leakages were treated by routine dressing changes (group A). After 2008, the leakages were managed with urostomy bags (group B). The perioperative quality of life (EQ-5D) and cost for urine leakage for both groups were compared in this controlled study. RESULTS: The average cost in management of preoperative urine leakage was significantly higher in group A than in group B as well as the patients with extravasations of urine or lymphoceles. Patients in group B had an overall better perioperative life quality compared with group A. In particular, the score for pain/discomfort was significantly higher in group A than in group B. CONCLUSIONS: The management of perioperative urine leakage with urostomy bags avoided constant body wetness and significantly increased the quality of life and reduced the special costs of urine leakage in patients with bladder cancer after cystectomy. IMPLICATIONS FOR PRACTICE: Early use of urostomy bag is a good choice for perioperative urine leakage in patients with bladder cancer after radical cystectomy and neobladder reconstruction.

Concomitant treatment of ureteropelvic junction obstruction and renal calculi with robotic laparoscopic surgery and rigid nephroscopy.

INTRODUCTION: The treatment of ureteropelvic junction obstruction (UPJO) and concomitant calculus poses a technically challenging situation. We present our experience with using rigid nephroscopy for renal calculi removal during robot-assisted pyeloplasy (RAP) for UPJO. TECHNICAL CONSIDERATIONS: From December 2010 to November 2012, 25 patients with UPJO had RAP at our institution; 9 of those had concurrent renal calculi, which were simultaneously treated with rigid nephroscopy. For stone extraction, a rigid ureteroscope was passed through an assistant trocar under laparoscopic vision directly into a previously created pyelotomy. The stones were extracted using a rigid grasper or stone basket through the rigid ureteroscope. For the removal of the stones within the upper and lower calyces, the rigid ureteroscope was introduced into the incised renal pelvis through robotic trocars if the "assistant trocar" route failed. Complete stone clearance was achieved in 8 of 9 patients. Residual calculi in 1 patient were removed with a single session of extracorporeal shock wave lithotripsy. At the mean follow-up of 10.2 months, no patients had obstruction or recurrent stones. The mean operative time was 187.1 minutes, which was 40.9 minutes longer than the mean operative time in patients without renal calculi. There was no significant difference in blood loss, hospital stay, complications, and success rates between patients with and without renal calculi. CONCLUSION: Our data suggest that the use of a concomitant rigid nephroscope and RAP is a safe and feasible option for the treatment of UPJO complicated with renal calculi.

Long-term evaluation of patients undergoing genitoplasty due to disorders of sex development: results from a 14-year follow-up.

PURPOSE: To summarize the experience in treating patients with genitoplasty due to disorders of sex development in China. METHODS: The operative procedures, gender of rearing, surgical outcome, and psychosocial and family adjustments of 262 patients were reviewed retrospectively. RESULTS: At initial diagnosis, the mean age was 14.3 ± 2.8 years (range: 2-38 years). There were 96 children, 133 adolescents, and 33 adults. Follow-up was done every 6 months. Patients with female sex assignment had no urinary incontinence or voiding difficulty. Five patients underwent the second surgery (3%); vaginal dilation was performed in 35 patients with postoperative vaginal stenosis; 12 patients (7.4%) were unsatisfactory with the outcome. For patients with male sex assignment, the median length of penis was 2.2 cm in prepubertal patients, 4.2 cm in pubertal patients, and 5.0 cm in adults; 39 patients developed postvoid dribbling (39%); 21 patients underwent a second surgery (21%); urethral dilation was done in 28 patients (28%) due to urethral stricture; 38 patients were unsatisfactory with the outcome (38%). In addition, 136 patients (83%) with female sex assignment and 54 (54%) with male sex assignment had favorable psychosocial adjustment. CONCLUSIONS: Patients with male sex assignment have more surgical complications and difficulties in psychosocial adjustment as compared to those with female sex assignment.