Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04563936.

"Total reconstruction" of the urethrovesical anastomosis contributes to early urinary continence in laparoscopic radical prostatectomy.

PURPOSE: To demonstrate the effect of total reconstruction technique on postoperative urinary continence after laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODS: LRP was performed using a standard urethrovesical anastomosis in 79 consecutive patients (Group-A) from June 2011 to October 2012, and a total reconstruction procedure in 82 consecutive patients (Group-B) from June 2012 to June 2013. The primary outcome measurement was urinary continence assessed at 1, 2, 4, 12, 24 and 52 weeks after catheter removal. Other data recorded were patient age, body mass index, International Prostate Symptoms Score, prostate volume, preoperative PSA, Gleason score, neurovascular bundle preservation, operation time, estimated blood loss, complications and pathology results. RESULTS: In Group-A, the continence rates at 1, 2, 4, 12, 24 and 52 weeks were 7.59%, 20.25%, 37.97%, 58.22%, 81.01% and 89.87% respectively. In Group-B, the continence rates were 13.41%, 32.92%, 65.85%, 81.71%, 90.24% and 95.12% respectively. Group-B had significantly higher continence rates at 4 and 12 weeks after surgery (P<0.001 and P=0.001). There were no significant differences between the groups with respect to patient's age, body mass index, prostate-specific antigen level, prostate volume, IPSS, estimated blood loss, number of nerve-sparing procedures and postoperative complications. CONCLUSIONS: Total reconstruction technique in the procedure of urethrovesical anastomosis during LRP improved early recovery of continence.

"Total reconstruction" of the urethrovesical anastomosis contributes to early urinary continence in laparoscopic radical prostatectomy

ABSTRACT Purpose: To demonstrate the effect of total reconstruction technique on postoperative urinary continence after laparoscopic radical prostatectomy (LRP). Material and Methods: LRP was performed using a standard urethrovesical anastomosis in 79 consecutive patients (Group-A) from June 2011 to October 2012, and a total reconstruction procedure in 82 consecutive patients (Group-B) from June 2012 to June 2013. The primary outcome measurement was urinary continence assessed at 1, 2, 4, 12, 24 and 52 weeks after catheter removal. Other data recorded were patient age, body mass index, International Prostate Symptoms Score, prostate volume, preoperative PSA, Gleason score, neurovascular bundle preservation, operation time, estimated blood loss, complications and pathology results. Results: In Group-A, the continence rates at 1, 2, 4, 12, 24 and 52 weeks were 7.59%, 20.25%, 37.97%, 58.22%, 81.01% and 89.87% respectively. In Group-B, the continence rates were 13.41%, 32.92%, 65.85%, 81.71%, 90.24% and 95.12% respectively. Group––B had significantly higher continence rates at 4 and 12 weeks after surgery (P<0.001 and P=0.001). There were no significant differences between the groups with respect to patient's age, body mass index, prostate-specific antigen level, prostate volume, IPSS, estimated blood loss, number of nerve-sparing procedures and postoperative complications. Conclusions: Total reconstruction technique in the procedure of urethrovesical anastomosis during LRP improved early recovery of continence.

Increased circulating myeloid-derived suppressor cells correlate with cancer stages, interleukin-8 and -6 in prostate cancer.

AIM: Myeloid-derived suppressor cells (MDSCs) are a population of cells which negatively regulate immune response during tumor progression. In this study, we assessed the accumulation of MDSCs (CD33(+)CD11b(+)HLA-DR(-)CD14(-)) in patients with prostate cancer and its clinical relevance. METHODS: We tested the frequency of MDSCs in the peripheral blood of patients with prostate cancer or benign prostate hyperplasia and healthy donors. Serumal interleukin-8, -6 and -10 were analyzed. Effects of MDSCs on the T cell response were determined. RESULTS: MDSCs increased in cancer patients, and there was an association between MDSCs and cancer stages or overall survival. Elevated serumal interleukin-8 and -6 in cancer patients correlated with MDSCs. Moreover, accumulation of MDSCs was associated with defective T cell function. CONCLUSION: Our study showed an increased population of MDSCs in patients with prostate cancer. Interleukin-8 and -6 in serum may play a new important role companied with MDSCs in prostate cancer.

A modified technique reduced operative time of laparoendoscopic rendezvous endoscopic retrograde cholangiopancreatography combined with laparoscopic cholecystectomy for concomitant gallstone and common bile ductal stone.

Laparoendoscopic rendezvous (LERV) endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy (LC+ERCP/LERV) are considered an optimal approach for concomitant gallstones and common bile duct stones. The rendezvous technique is essential for the success of procedure. We applied two different LERV techniques, traditional technique and modified technique, in 60 consecutive cases from January 2011 to November 2012. 32 cases who underwent modified technique (group 1) from February 2012 to November 2012 were retrospectively compared to 28 cases (group 2) who underwent traditional technique from January 2011 to January 2012. There was no significant difference between two groups with respect to preoperative demographic features. Although the difference was not statistically significant, the procedure was successfully performed in 31 cases (96.9%) in group 1 and 24 cases (86.2%) in group 2. The mean operative time and time of endoscopic part were 82.6 ± 19.6 min and 26.5 ± 5.99 min in group 1 which were significantly shorter than those in group 2 (118.0 ± 23.1 min and 58.7 ± 13.3 min, resp.). There was no postoperative pancreatitis and mortality in both groups. The mean hospital stay, blood loss, incidence of complications, and residual stone were of no difference in both groups. This study proved that this modified technique can effectively reduce the operative time and time of endoscopic part of LC+ERCP/LERV compared with traditional technique.

[Transurethral bipolar plasmakinetic enucleation and resection versus transurethral bipolar plasmakinetic resection of the prostate for BPH: a randomized controlled trial on the incidence of postoperative urinary incontinence].

OBJECTIVE: To compare the incidence rates of postoperative urinary incontinence between transurethral bipolar plasmakinetic enucleation and resection of the prostate (PKERP) and transurethral bipolar plasmakinetic resection of the prostate (PKRP), and provide evidence for the clinical application of PKERP. METHODS: Totally, 180 BPH patients were equally and randomly assigned to undergo PKERP and PKRP, respectively. We measured the urinary incontinence of the patients by pad test at 24 hours after extubation and every week after surgery for 4 weeks. Meanwhile, we recorded and compared the PSA level, prostate volume, Qmax, residual urine, IPSS, QOL, and the results of pad test between the two groups before and after surgery. RESULTS: The incidence rates of urinary incontinence in the PKERP and PKRP groups were 35.56% and 18.89% (P < 0.01) at 24 hours after extubation, 20.00% and 7.78% at 1 week after surgery (P < 0.05), and 3.33% and 2.22% at 2 weeks. There was no significant difference in the severity of urinary incontinence between the two groups at any time point (P > 0.05). No permanent urinary incontinence was observed in either group. CONCLUSION: Compared with PKRP, PKERP has a higher incidence rate of short-term urinary incontinence in the treatment of BPH, but not that of genuine incontinence, with similar severity and recovery time.

The role of Toll-like receptor (TLR) 2 and 9 in renal ischemia and reperfusion injury.

OBJECTIVE: To determine the involvement of Toll-like receptor (TLR) 2, TLR9, and TLR2+9 in renal ischemia/reperfusion (I/R) injury. METHODS: Mice with gene knock-out of TLR2, TLR9, and TLR2+9 underwent renal I/R injury. Tubular damage, expression of proinflammatory cytokines and chemokines, and kidney dysfunction were evaluated on different days after reperfusion. RESULTS: Mice deficient in TLR2, but not TLR9, were protected from renal I/R injury with less tubular damage, decreased cytokine production, and lower serum creatinine and urea levels than wild-type mice. TLR2+9 double-deficiency did not have an additional effect on tissue injury compared with TLR2 deficiency alone. CONCLUSION: These results suggest that activation of TLR2 signaling contributes to the pathogenesis of renal I/R injury, whereas TLR9 may be redundant for the development of this injury.

Composition-ratio determination of Chrome Azurol S (CAS) with Cu(2+) and research on dynamic reaction process of CAS with EDTA.

The composition-ratio of Chrome Azurol S (CAS) with Cu(2+) and dynamic reaction process of CAS with EDTA were studied by spectrophotometry. The composition-ratio of Cu(2+) with CAS (2:1) was successfully determined using the method of lines and EDTA complexing substitution. The effects of temperature, time, pH, concentration of cetyltrimethylammonium bromide (CTMAB), and concentration of Cu(2+) on the absorption spectrum were also discussed. By optimizing experimental conditions, the dynamic process of displacement of CAS, which forms the ternary compound Cu-CAS-CTMAB, by EDTA were determined. The test results indicated that EDTA can replace 99.6% of the CAS quickly when heated. The system reached equilibrium finally. This research method can be applied to the qualitative and quantitative analysis of related Cu complexes.