Mutational heterogeneity between different regional tumour grades of clear cell renal cell carcinoma.

Only a limited number of studies have explored the possible associations between tumour grade and mutated genes in clear cell renal cell carcinoma (ccRCC), and we set out to investigate this further using a multiple sampling and next generation sequencing (NGS) approach in a series of ccRCCs. Multiple regions were sampled from formalin-fixated paraffin-embedded ccRCC tumour blocks from seven patients. In 27 samples from six patients, we performed targeted NGS using a custom 42-gene panel based on the most frequently mutated genes in ccRCC reported in public databases. In four samples from the seventh patient, we performed whole exome sequencing (WES) and array comparative genomic hybridisation for detection of copy number variants (CNVs). Mutated genes and the tumour grades of the samples in which they had been identified were compared both within and between all individual tumours. CNVs were compared across all samples from patient 7. We identified clear genetic heterogeneity within and across tumours, but VHL mutations were seen in all patients. Looking across all samples, we identified eleven genes that were only mutated in samples with one particular tumour grade. However, these genes were never mutated in all samples with that tumour grade. Increasing chromosomal instability corresponded with increasing tumour grade, but we observed minimal association between tumour grade and total mutational load in the WES data. Our study confirms the genetic heterogeneity and tumour grade heterogeneity of ccRCC. Although a relatively small number of samples was analysed, genes were identified that could potentially be specific, though insensitive, markers of higher ccRCC tumour grades.

Meta-analysis of Optimal Management of Lower Pole Stone of 10 - 20 mm: Flexible Ureteroscopy (FURS) versus Extracorporeal Shock Wave Lithotripsy (ESWL) versus Percutaneus Nephrolithotomy (PCNL).

BACKGROUND: the optimal management of lower calyceal stones is still controversial, because no single method is suitable for the removal of all lower calyceal stones. Minimally invasive procedures such as extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL) and flexible ureteroscopy (fURS) are the therapeutic methods for lower calyceal stones. The aim of this study was to identify the optimal management of 10-20 mm lower pole stones. METHODS: a meta-analysis of cohort studies published before July 2016 was performed from Medline and Cochrane databases. Management of 10-20 mm lower pole stone treated by fURS, ESWL and PCNL with follow-up of residual stones in 1-3 months after procedure were include and urinary stone in other location and size were excluded. A fixed-effects model with Mantzel-Haenzel method was used to calculate the pooled Risk Ratio (RRs) and 95% Confidence Interval (CIs). We assessed the heterogeneity by calculating the I2 statistic. All analyses were performed with Review manager 5.3. RESULTS: we analized 8 cohort studies. The stone free rate from 958 patients (271 PCNL, 174 fURS and 513 ESWL), 3 months after operation, was 90.8% (246/271) after PCNL; 75.3% (131/174) after fURS; and 64.7% (332/513) after ESWL. Base on stone free rate in 10-20 mm lower pole stone following management, PCNL is better than fURS (overall RR was 1.32 (95% CI 1.13 - 1.55); p<0.001 and I2=57%) and ESWL (overall risk ratio 1.42 (95% CI 1.30 - 1.55); p=<0.001 and I2 = 85%). But, if we compare between fURS and ESWL, fURS is better than ESWL base on stone free rate in 10-20 mm lower pole stone management with overall RR 1.16 (95% CI 1.04 - 1.30; p=0.01 and I2=40%). CONCLUSION: percutaneus nephrolithotomy provided a higher stone free rate than fURS and ESWL. This meta-analysis may help urologist in making decision of intervention in 10-20 mm lower pole stone management.

Tamsulosin and Sodium Diclofenac as an Effective Therapy to Reduce Pain After Ureteral Stent Removal: A Prospective, Double Blinded Randomized Placebo Controlled Trial.

PURPOSE: This study was conducted to determine the effects of tamsulosin and diclofenac sodium use on patients' pain perception after ureteral stents removal. MATERIALS AND METHODS: This study was a randomized control trial with double-blinded design. Eighty patients who underwent ureteral stent removal surgery at Kardinah Hospital during January to March 2017 were divided into four groups. The following medications were administered for two days, (A) placebo tid, or (B) diclofenac sodium 50 mg bid, or (C) tamsulosin 0.2 mg sid, or (D) combination of tamsulosin and diclofenac sodium. Analgesic effects were assessed with the Visual Analog Scale (VAS). Relationships among variables were assessed using one-way ANOVA and post hoc tests. RESULTS: The surgical procedure for ureteral stent removal consisted of 48 (60%) male and 32 (40%) female. The average age of group A, B, C, and D were 51.0, 51.9, 47.6, and 47.3 years, and the average stent dwell time was 6.3 weeks. VAS values of the entire experimental group were lower than the control group on the first day until the second day after the stent removal (p < 0.05). In the experimental group, there was no difference between group B and C (p > 0.05). Group D showed better analgesic effects than group B and C (p <0.05). No severe side effects were observed. CONCLUSION: The result shows that combination therapy of diclofenac sodium and tamsulosin is better in reducing the pain after ureteral stent removal compared to the admission of a single placebo, tamsulosin, or diclofenac sodium therapy.

Urine miR-21-5p and miR-200c-3p as potential non-invasive biomarkers in patients with prostate cancer.

OBJECTIVE: To evaluate the miR-21-5p and miR-200c-3p expressions in the urine of patients with prostate cancer (PCa) and to investigate their potential as biomarkers. MATERIAL AND METHODS: The urine samples collected from 80 patients, including 20 patients diagnosed with benign prostate hyperplasia (BPH) and 60 patients diagnosed with PCa, were examined. The exosome isolation was performed using the miRCURY exosome isolation kit (Exiqon, Denmark), total RNA was extracted using the miRCURY RNA Isolation Kit-Biofluid kit (Exiqon, Denmark), and complementary DNA (cDNA) was synthesized using the Universal cDNA Synthesis kit (Exiqon, Denmark). A quantitative polymerase chain reaction (qPCR) analysis of gene expression was performed using the qPCR CFX 96 Thermocycler (Bio-Rad). All the procedures followed the manufacturer's recommendations. RESULTS: The overexpressions of miR-21 in the non-metastatic PCa and metastatic PCa group compared to the BPH group were statistically significant with a p-value of 0.001 and 0.018, respectively. The non-metastatic PCa compared to the metastatic PCa group was also statistically significant with a p-value of 0.037. The under expressions of miR-200c in the non-metastatic PCa and metastatic PCa group compared to the BPH group are statistically significant with a p-value of 0.001 and 0.001, respectively. CONCLUSION: The overexpressions of miR-21 found in this study could be a potential non-invasive diagnostic tool for patients with PCa. Despite the significant results in our study, the use of micro-RNA in urine samples may vary due to epigenetic variation. Further studies with larger populations are required to investigate the role of miR-21 and miR-200c as biomarkers in PCa.

Increased tumor-associated macrophages in the prostate cancer microenvironment predicted patients' survival and responses to androgen deprivation therapies in Indonesian patients cohort.

BACKGROUND: Tumor-associated macrophages (TAMs) and microvessel density (MVD) play an essential role for tumor progression in prostate cancer (PCa). In this study, we evaluated the association between TAMs, the infiltration with tumor angiogenesis and the response to androgen deprivation therapies (ADTs) in PCa to evaluate TAM infiltration as a predictive factor for PCa survival. MATERIALS AND METHODS: Fifty-four specimens were collected and stained with CD 68 antibody to investigated TAM infiltration in tumor. Von Willebrand factor was stained to evaluate MVD around the cancer foci. We assessed the association between patient's age, preoperative serum prostate-specific antigen, pathologic Gleason sum (GS), TAM infiltration, MVD, and the response to ADT for 5 years after PCa diagnosis. RESULTS: The median TAM was observed in 28 (6-76)/high power field (x400). Increasing TAM correlated with increasing tumor angiogenesis (P < 0.001, r = 0.61), and the response to ADT was significantly better in patients with fewer TAMs (<28) than in patients with higher TAMs (>28) (P = 0.003). TAM infiltration was significantly higher in those with higher serum prostate-specific antigen, higher GS, and metastasis. Multivariate analysis showed that GS, ADT type, and MVD number were significant prognostic factors for response to ADT in PCa (P < 0.0001). An increased infiltration of TAM [hazards ratio (HR) = 4.47; 95% confidence interval (CI): 1.97-10.15], MVD (HR = 2.66; 95% CI: 1.27-5.61), metastatic status (HR = 2.29; 95% CI: 0.14-0.60), and prostate volume (HR = 2.19; 95% CI: 1.27-3.12) significantly correlated with shorter survival in PCa patients by univariate analysis (P < 0.05). Multivariate analyses revealed that TAM and metastatic status significantly correlated with poor overall survival. CONCLUSIONS: TAM infiltration is associated with response to ADT and increased tumor angiogenesis in PCa. GS, ADT type, and MVD in PCa specimens are useful predictive factors for poor response to ADT. Increasing TAM and positive metastatic status were prognostic factors for a poorer survival in PCa patients.

Lumbrokinase effects on pro- and anti-apoptotic gene expression in Wistar rats with testicular torsion.

BACKGROUND: Testicular reperfusion is believed to be the mechanism by which testicular injury occurs in the ischemic testis. This study was performed to determine the therapeutic efficacy of lumbrokinase for treating ischemia-reperfusion (IR) injury-induced bilateral testicular torsion. METHODS: Twenty-four male rats were equally divided into the following groups: torsion only (T), torsion plus lumbrokinase (TL), torsion-detorsion only (TD) and torsion-detorsion plus lumbrokinase (TDL) groups. The right testicle in each groups sample was rotated 720° for 4 h, followed by orchiectomy. The rats in the TD (TD and TDL) groups additionally underwent detorsion for 1 h after the initial rotation. Testicular tissues were collected for measuring anti-apoptotic B-cell lymphoma-2 (BCL-2) and pro-apoptotic BCL-2-associated X protein (BAX) gene expression levels using real-time polymerase chain reaction. RESULTS: Pro- and anti-apoptotic gene expression levels were increased in the TD groups. Lumbrokinase was significantly effective in lowering BAX expression levels, particularly those in the TDL group compared with those in the TD group (P<0.05). Lumbrokinase did not significant change BCL-2 expression levels. CONCLUSION: The administration of lumbrokinase before orchiectomy can protect against IR-induced testicular damage by reducing pro-apoptotic gene expression levels.

Laparoscopic repair of vesicovaginal fistulae with a transperitoneal approach at Universitas Gadjah Mada Urological Institute: a case report.

BACKGROUND: A vesicovaginal fistula is an abnormal fistulous tract extending between the bladder and the vagina that allows the continuous involuntary discharge of urine into the vaginal vault. In addition, the sequelae from these fistulae have a profound effect on the patients in view of their physical, psychological, and social dimensions. The treatment of vesicovaginal fistula is surgical in most cases and the choice of the repair technique is controversial. We evaluated the benefits of a laparoscopic approach in a patient with vesicovaginal fistulae. Here, we present our first experience using a simplified laparoscopic approach technique to repair vesicovaginal fistulae in our country. CASE PRESENTATION: A 46-year-old Javanese woman presented with urinary incontinence following an abdominal hysterectomy 3 months earlier and received laparoscopic repair. A cystoscopy was performed to confirm the fistula orifice and a stent was inserted into the fistula tract from her bladder to her vagina. A tamponade was inserted into her vagina up to the vaginal apex, to be able to identify the vagina. She had adhesions; therefore, adhesiolysis was performed using a combination of sharp and blunt dissection to expose the vaginal stump and the superior aspect of her bladder. A simple cystotomy was performed and extended to include the fistulae site, and then the defect was repaired by using a running stitch. A second layer of closure was performed in an imbricating fashion with the same suture. The vagina defect was not closed separately but covered with an omental flap. This procedure takes approximately 2.5 hours; estimated blood loss was minimal and there were no intraoperative complications. She had no recurrent symptoms 6 months after surgery. CONCLUSION: Our case report concludes that the simplified laparoscopic approach to vesicovaginal fistulae is a viable option for successful repair and that it reduces the size of bladder opening, causes minimal bleeding, and gives successful relief.

Association between tumor-associated macrophages and microvessel density on prostate cancer progression.

BACKGROUND: To evaluate tumor-associated macrophages (TAMs) infiltration and microvessel density as possible prognostic factors related to prostate cancer (PCa) progression. METHODS: Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 and microvessel density (MVD) using von Willebrand factor (vWF) from 25 specimens with high-grade prostatic intraepithelial neoplasia (HGPIN) and 25 specimens with PCa after transurethral resection of the prostate (TURP). Six microscopic (×200) fields were selected for TAM counting and six microscopic (×100) fields were selected for MVD counting around the cancer foci. Association between age, preoperative prostate-specific antigen (PSA), pathologic Gleason sum (GS), TAM, MVD, extracapsular extension, and metastasis were assessed using Pearson/Spearman, Student t test/Mann-Whitney U test and one-way analysis of variance/Kruskal-Wallis test. RESULTS: The mean of age, PSA, TAMs, and MVD were 69.1 ± 9.9, 67.1 ± 92.4, 26.2 ± 11.9, and 31.4 ± 14.0, respectively, from 50 specimens with PCa and HGPIN. Increasing TAMs number was not correlated with increasing MVD number and there was no significant mean difference statistically (P > 0.05) in TAMs and MVD although the mean of TAMs number was higher in PCa versus HGPIN but significant in PSA level (P < 0.001). In PCa specimens, age, PSA, TAMs, and MVD number were higher in patients with metastatic and extracapsular extension, but not significant statistically (P > 0.005). There was no correlation between TAMs and MVD (P > 0.001). CONCLUSIONS: TAMs and MVD had increased PCa but did not provide independent prognostic value. Increasing numbers of TAMs was not always followed by an increase in MVD. HGPIN is the most likely precursor for PCa.