Transperitoneal vs retroperitoneal laparoscopic radical nephrectomy: a double-arm, parallel-group randomized clinical trial.

OBJECTIVE: To compare the outcomes of patients undergoing Retroperitoneal laparoscopic Radical nephrectomy (RLRN) and Transperitoneal laparoscopic Radical nephrectomy (TLRN). METHODS: A total of 120 patients with localized renal cell carcinoma were randomized into either RLRN or TLRN group. Mainly by comparing the patient perioperative related data, surgical specimen integrity, pathological results and tumor results. RESULTS: Each group comprised 60 patients. The two group were equivalent in terms of perioperative and pathological outcomes. The mean integrity score was significantly lower in the RLRN group than TLRN group. With a median follow-up of 36.4 months after the operation, Kaplan-Meier survival analysis showed no significant difference between RLRN and TLRN in overall survival (89.8% vs. 88.5%; P = 0.898), recurrence-free survival (77.9% vs. 87.7%; P = 0.180), and cancer-specific survival (91.4% vs. 98.3%; P = 0.153). In clinical T2 subgroup, the recurrence rate and recurrence-free survival in the RLRN group was significantly worse than that in the TLRN group (43.2% vs. 76.7%, P = 0.046). Univariate and multivariate COX regression analysis showed that RLRN (HR: 3.35; 95%CI: 1.12-10.03; P = 0.030), male (HR: 4.01; 95%CI: 1.07-14.99; P = 0.039) and tumor size (HR: 1.23; 95%CI: 1.01-1.51; P = 0.042) were independent risk factor for recurrence-free survival. CONCLUSIONS: Our study showed that although RLRN versus TLRN had roughly similar efficacy, TLRN outperformed RLRN in terms of surgical specimen integrity. TLRN was also significantly better than RLRN in controlling tumor recurrence for clinical T2 and above cases. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=24400 ), identifier: ChiCTR1800014431, date: 13/01/2018.

Correlation of serum ß2-microglobulin levels with prostate-specific antigen, Gleason score, clinical stage, tumor metastasis and therapy efficacy in prostate cancer.

BACKGROUND AND AIMS: Despite previous reports implying a role of ß2-microglobulin (ß2M) in the development of prostate cancer (PCa), the correlation of serum ß2M with the clinicopathological features, therapy efficacy and prognosis of patients with PCa have not been fully clarified. The present study aims to investigate the serum levels of ß2M in patients with PCa and explore the potential use of ß2M as a tumor marker for diagnosis, treatment and prognosis of PCa. METHODS: Serum ß2M levels in 120 patients with PCa, 50 patients with benign prostate hyperplasia (BPH) and 85 healthy age-matched controls were measured by enzyme immunoassay. The correlation of serum ß2M with the clinicopathological features, therapy efficacy and the prognosis of PCa were subsequently assessed. RESULTS: Our results showed that: (i) PCa patients had significantly higher levels of ß2M compared to those of patients with BPH or those of healthy controls. (ii) Serum ß2M were markedly elevated in patients with high stage or grade PCa as compared to patients with low stage or grade PCa. (iii) We measured significantly higher levels of ß2M in patients with metastasis as compared to patients lacking metastasis. (iv) During follow-up, serum ß2M showed a marked decrease after successful therapy and a significant further increase in recurrent disease. CONCLUSIONS: Our results demonstrate that serum ß2M is correlated closely with the clinical stage, Gleason grade, PSA, distant metastasis and therapy efficacy in patients with PCa. Serum ß2M may be a useful biomarker for clinical diagnosis, follow-up and prognosis of PCa.

The effects of transrectal radiofrequency hyperthermia on patients with chronic prostatitis and the changes of MDA, NO, SOD, and Zn levels in pretreatment and posttreatment.

OBJECTIVE: To assess the effect of transrectal radiofrequency hyperthermia (TRFH) in 159 patients with chronic prostatitis (CP) and explore the changes of reactive oxygen species in CP patients pretreatment and posttreatment. METHODS: Patients diagnosed with CP were randomized to 6 weeks of tamsulosin plus clarithromycin, TRFH, or TRFH with tamsulosin plus clarithromycin group. The primary outcome measure was evaluated by the National Institutes of Health Chronic Prostatitis Symptom Index. Malondiadehyde (MDA), superoxide dismutase (SOD), and nitrogen monoxide (NO) were measured by biochemical assay. Zinc (Zn) content was assayed by atomical spectrophotography. RESULTS: All 105 patients in the TRFH or TRFH with tamsulosin plus clarithromycin group showed statistically significant improvement of pain, quality of life, and micturition domains compared with the tamsulosin plus clarithromycin group. Regardless of type IIIa or type IIIb CP, there was a significant improvement in the TRFH or TRFH with tamsulosin plus clarithromycin group compared with tamsulosin plus clarithromycin group (P<.05). Compared with pretreatment, MDA, NO, and Zn were decreased in type II and IIIa, whereas SOD was only increased significantly in type II (P<.05). CONCLUSION: Our study reveals TRFH as an effective therapy option for CP, especially type IIIa or type IIIb CP. The results of TRFH with tamsulosin plus clarithromycin group was superior to the TRFH group or the tamsulosin plus clarithromycin group alone. In comparison with pretreatment, differences in reactive oxygen species levels and Zn in CP patients suggest that these factors could be used as a biomarker to evaluate the symptoms of CP and the effects of treatment.

Effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine pharmacokinetics after renal transplantation.

1. The calcineurin inhibitor cyclosporine is widely used to prevent allograft rejection after solid organ transplantation. It has a narrow therapeutic index and shows considerable interindividual differences in its pharmacokinetics. Interindividual differences in the activity and expression of the metabolising enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp) contribute considerably to cyclosporine pharmacokinetics. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes. 2. The aim of the present study was to evaluate retrospectively the effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine dose adjusted trough blood concentration during the early period after renal transplantation in Chinese patients. 3. One hundred and six renal transplant recipients in China were genotyped by polymerase chain reaction-restriction fragment length polymorphism for CYP3A4*18A, CYP3A5*3 and MDR1 C3435T. Cyclosporine whole blood levels were measured by fluorescence polarization immunoassay. Dose-adjusted trough blood concentrations (C(0)) were determined and compared among the different genotype groups. 4. The frequency of the CYP3A4*18A, CYP3A5*3 and MDR1 C3435T variant alleles were 0.005 (95% confidence interval (CI) 0.048, 0.0049), 0.783 (95% CI 0.781, 0.785) and 0.528 (95% CI 0.526, 0.531), respectively, and these alleles exhibited incomplete linkage disequilibrium. The median cyclosporine dose-adjusted C(0) in CYP3A5*1/*1 genotype subjects (n = 6) was 14.8 ng/mL per mg per kg (range 11.1-26.8 ng/mL per mg per kg), in CYP3A5*1/*3 patients (n = 34) it was 23.7 ng/mL per mg per kg (range 9.0-61.0 ng/mL per mg per kg) and for CYP3A5*3/*3 patients (n = 66) it was 26.4 ng/mL per mg per kg (range 9.8-85.8 ng/mL per mg per kg; P = 0.012, Kruskal-Wallis test). Accordingly, cyclosporine dose-adjusted C0 was larger in CYP3A5 non-expressors than expressors in the first week after renal transplantation. In addition, wild-type homozygotes (n = 21) for MDR1 C3435T had a slight but significantly lower dose-adjusted C0 compared with heterozygotes (n = 58): 17.7 (10.3-60.8) versus 26.4 (9.0-67.3) ng/mL per mg per kg, respectively (P = 0.014, Mann-Whitney U-test). 5. In conclusion, the present study shows that genetic polymorphisms in CYP3A5 may be responsible, in part, for the large interindividual variability of cyclosporine pharmacokinetics during the early phase after renal transplantation in Chinese patients. Patients with the CYP3A5*3 variant genotype require a low dose of cyclosporine to reach target levels compared with those with the CYP3A5*1 allele.

Free graft two-stage urethroplasty for hypospadias repair.

OBJECTIVE: To evaluate the effectiveness of free graft transplantation two-stage urethroplasty for hypospadias repair. METHODS: Fifty-eight cases with different types of hypospadias including 10 subcoronal, 36 penile shaft, 9 scrotal, and 3 perineal were treated with free full-thickness skin graft or (and) buccal mucosal graft transplantation two-stage urethroplasty. Of 58 cases, 45 were new cases, 13 had history of previous failed surgeries. Operative procedure included two stages: the first stage is to correct penile curvature (chordee), prepare transplanting bed, harvest and prepare full-thickness skin graft, buccal mucosal graft, and perform graft transplantation. The second stage is to complete urethroplasty and glanuloplasty. RESULTS: After the first stage operation, 56 of 58 cases (96.6%) were successful with grafts healing well, another 2 foreskin grafts got gangrened. After the second stage operation on 56 cases, 5 cases failed with newly formed urethras opened due to infection, 8 cases had fistulas, 43 (76.8%) cases healed well. CONCLUSIONS: Free graft transplantation two-stage urethroplasty for hypospadias repair is a kind of effective treatment with broad indication, comparatively high success rate, less complications and good cosmatic results, indicative of various types of hypospadias repair.

The role of superoxide anion in the regulation of epidermal growth factor or the expression and proliferation of its receptor in prostate cancer cell line PC3.

The purpose of this study was to investigate the role of superoxide anion(O2-) in the regulation of epidermal growth factor (EGF) or epidermal growth factor receptor (EGFR) expression and proliferation in the prostate cancer cell line PC3. Cell proliferation was tested by a 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay in the presence of O2-, EGF or their combination. Immunohistochemistry was carried out to assay the expression of EGF or EGFR. EGF or EGFR mRNA expression in the cells treated with O2- was examined by in situ hybridisation. The proliferation was significantly inhibited by O2- in a concentration-dependent manner ranging from 9 to 36 micromol/l nicotinamide adenine dinucleotide (NADH) combined with 2-8 micromol/l N-methylphenazonium methyl sulfate (PMS). The enhancement of proliferation induced by 5 ng/ml EGF was significantly overcome by O2-. Although O2- was not able to alter EGFR mRNA expression, O2- at the concentration of 18 micromol/l NADH and 4 micromol/l PMS reduced EGFR protein expression. O2- at the concentration of 18 micromol/l NADH and 4 micromol/l PMS can downregulate EGF and EGF mRNA expression.