Yawen Xu

A Randomized Trial Comparing Diode Laser Enucleation of the Prostate with Plasmakinetic Enucleation and Resection of the Prostate for the Treatment of Benign Prostatic Hyperplasia

PURPOSE We compared the safety and efficacy of diode laser enucleation of the prostate (DiLEP) with plasmakinetic enucleation and resection of the prostate (PKERP). PATIENTS AND METHODS A total of 80 patients with bladder outflow obstruction from benign prostatic hyperplasia (BPH) were randomly assigned to either DiLEP or PKERP prospectively. All patients were assessed preoperatively and followed up at 3, 6, and 12 months postoperatively. Baseline characteristics of the patients, perioperative data, and postoperative outcomes were compared. The operative data and perioperative and postoperative complications were also recorded. RESULTS The preoperative data were comparable between the two groups. The DiLEP group had significantly shorter operative time, postoperative irrigation, time and catheterization time than the PKERP group (P=0.000, P=0.000 and P=0.000). The drop in hemoglobin level was statistically significantly less in the DiLEP group (P=0.002). There were no statistical differences in complications between the two groups except irritative symptoms (P=0.018). At the 3, 6, and 12-month follow-up, no statistically significant differences were observed between the two groups in International Prostate Symptom Score, maximum flow rate, quality of life, postvoid residual, prostate volume, and prostate-specific antigen level (P>0.05). CONCLUSIONS The efficacy of DiLEP and PKERP were similar for relieving obstruction and low urinary tract symptoms. DiLEP provides less risk of hemorrhage, reduced bladder irrigation, and catheter times. The downward morcellation technique is more efficient than the resection technique. Future well designed randomized trials with extended follow-up and larger sample sizes may be needed to better verify the advantage of DiLEP in treating patients with symptomatic BPH.

Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin

A small population of cells with stem cell‐like properties in prostate cancer (PCa), called prostate cancer stem cells (PrCSCs) or prostate stemness‐high cancer cells, displays highly tumorigenic and metastatic features and may be responsible for the therapy resistance. A small molecule, napabucasin (BBI608), recently have been identified with suppression of stemness‐high cancer cells in a variety of cancers. However, the effects of napabucasin on PCa cells as well as PrCSCs isolated from PCa cells have not yet been defined. The effect of napabucasin on PCa cells in cell proliferation, colony formation, and cell migration in vitro were measured by MTS, colony formation assay, and Transwell, respectively. Flow cytometry was employed to evaluate cell cycle and cell apoptosis, and the effect on tumorigenesis in vivo was examined by tumor growth assays. Furthermore, the role of napabucasin on self‐renewal and survival of PrCSCs was evaluated by their ability to grow spheres and cell viability assay, respectively. Western Blot and qRT‐PCR were used to determine the effect of napabucasin on the expressions of stemness markers. Decrease in cell viability, colony formation, migration, and survival with cell cycle arrest, higher sensitivity to docetaxel in vitro, and repressed tumorigenesis in vivo was observed upon napabucasin treatment. More importantly, napabucasin can obviously inhibit spherogenesis and even kill PrCSCs in vitro. Downregulation of stemness markers was observed after PrCSCs were treated with napabucasin. This study demonstrates that napabucasin may be a novel approach in the treatment of advanced PCa, specifically for castration‐resistant prostate cancer (CRPC).

Clinical significance of CD24 as a predictor of bladder cancer recurrence

Cluster of differentiation (CD)24 was originally described as a B lymphocyte marker and has recently received considerable attention in cancer research as its overexpression has been observed in several types of carcinoma. The CD24 molecule is a glycosyl-phosphatidylinositol-linked cell surface protein that appears to be associated with aggressive cancers involving invasion and metastasis. However, the expression of CD24 in human bladder cancer and its clinical significance remains largely unknown and no association has been reported between CD24 overexpression and human bladder tumor recurrence. In the present study, the CD24 expression in cancer tissues obtained during transurethral surgery and the subsequent intra-bladder tumor recurrence following surgery were assessed. Immunohistochemical staining was performed and the intensity of CD24 staining was semi-quantitatively evaluated. CD24 expression was observed more frequently in high-grade bladder tumors (G2–G3) than low-grade tumors (G1). Positive CD24 expression was significantly associated with intra-bladder tumor recurrence following surgery and increased staining intensity was also correlated with recurrence. The positive association between CD24 expression and tumor recurrence was observed in each tumor category (stages Ta and T1, low and high grade). The results demonstrated that CD24 expression is significantly associated with bladder tumor recurrence. To the best of our knowledge, this is the first study to reveal the significance of CD24 as a predictor of bladder cancer recurrence. These insights may lead to future therapeutic strategies targeting CD24 to prevent the dissemination of bladder cancer cells and tumor recurrence.

Loss of miR-26a-5p promotes proliferation, migration, and invasion in prostate cancer through negatively regulating SERBP1

The biological role of miR-26a involved in the carcinogenesis of prostate cancer (PC) has been controversial. Besides, the underlying mechanism by which miR-26a plays a role in PC has been unclear. To investigate the role of miR-26a-5p in the PC, miR-26a-5p was detected and statistically analyzed in clinical PC tissues and a panel of PC cell lines. Using bioinformatics analysis, we found that serpine1 messenger RNA (mRNA) binding protein 1 (SERBP1) was a potential downstream target of miR-26a-5p. Using luciferase reporter and western blot, we identified that miR-26a-5p negatively regulated SERBP1 on the PC cell line level. It was confirmed that miR-26a-5p was markedly downregulated in PC tissues compared with normal controls whose reduced expression was significantly associated with metastasis and poor overall prognosis and found that miR-26a-5p was able to prevent proliferation and motility of PC cells in vitro. Additionally, SERBP1 was identified as a downstream target of miR-26a-5p. Moreover, it was observed that SERBP1 was markedly upregulated in prostate cancer tissues and was significantly associated with tissue metastasis and Gleason score. Taken together, our results for the first time demonstrate that the loss of miR-26a-5p promotes proliferation, migration, and invasion through targeting SERBP1 in PC, supporting the tumor-suppressing role of miR-26a-5p in PC.

Orthotopic Detaenial Sigmoid Neobladder after Radical Cystectomy: Technical Considerations, Complications and Functional Outcomes

PURPOSE In recent years the orthotopic neobladder has gained increasing popularity in patients who undergo radical cystectomy. However, there are only a few reports of orthotopic neobladders reconstructed from the sigmoid without detubularization. We investigated the complications and functional outcomes of the orthotopic sigmoid neobladder reconstructed using our detaenial technique. MATERIALS AND METHODS We performed a retrospective study of the detaenial sigmoid neobladder in 210 consecutive patients who underwent radical cystectomy at our institution from January 2003 to March 2010. ANOVA was used to investigate urodynamic finding differentials with time. Univariable and multivariable analyses were done to determine factors influencing continence. RESULTS Median followup was 48 months. Early complications (90 days or less) were observed in 65 patients (31%). Late complications (greater than 90 days) were observed in 45 patients (21.5%). Five-year daytime and nighttime complete continence rates were 74.6% and 57.1%, respectively. Younger age was the only independent factor associated with complete continence during the day (OR 2.342, 95% CI 1.803-3.041, p <0.001) and night (OR 1.193, 95% CI 1.087-1.310, p <0.001). Mean maximal capacity and post-void residual urine were 328.8 and 22.2 ml, respectively. The mean maximal flow rate was 18.5 ml per second. The mean end filling pressure, pressure at maximal capacity and maximal intravesical pressure were 35.8, 55 and 60.6 cm H2O, respectively. These parameters remained stable with time (each p >0.05). CONCLUSIONS This study confirms that detaenial sigmoid neobladder is a safe, feasible alternative for urinary diversion.

Percutaneous Nephrolithotomy Under Local Infiltration Anesthesia: A Single-center Experience of 2000 Chinese Cases

OBJECTIVE To determine the feasibility and safety of percutaneous nephrolithotomy (PCNL) in treating upper urinary calculi under local infiltration anesthesia. METHODS A series of 2000 patients with upper urinary calculi underwent PCNL under local infiltration anesthesia. Of the 2000 patients, 536 had upper ureteral calculi, 805 patients had pelvic calculi, and 659 patients had complex renal calculi. Pethidine premedication (75-100 mg) and Phenergan (25 mg) were used half an hour preoperatively. The mean pain scores at 0, 6, 24, and 48 hours postoperatively, the demographic characteristics, and the stones characteristics were evaluated to determine the feasibility. The complications were evaluated to determine the safety, and stone-free rate was evaluated to determine effectivity. RESULTS The mean American Society of Anesthesiologists score was 1.55 ± 0.54 (range, 1-3). The mean operative time was 48 minutes (range, 20-125). The mean Visual Analogue Scale scores at 0, 6, 24, and 48 hours postoperatively were 3.62, 3.02, 2.27, and 2.09, respectively. The mean hemoglobin drop was 1.06 g/dL (range, 0.2-6.8). Sixty-five patients (3.3%) received transfusions, 10 patients (0.5%) required selective renal angioembolism (Clavien grade II), and 1 patient (0.05%) received chest drainage therapy (Clavien grade II). The total stone-free rate was 85.8%. CONCLUSION Local infiltration anesthesia is a well-tolerated alternative anesthesia technique that provides effective intraoperative and postoperative analgesia for PCNL. PCNL performed under local infiltration anesthesia in a selected group of patients is feasible and provides satisfactory clinical outcomes. Comparative studies should be performed to classify efficacy, safety, tract quantity, dilation method, and the best candidates.

Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma

Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation). Moreover, T cell checkpoint blockade therapy with antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4) has improved outcomes in cancer patients. However, the anti-tumor efficacy of combined lycorine and anti-CTLA-4 therapy remains unknown. Thus, we investigated a combination therapy of lycorine hydrochloride and anti-CTLA-4 using a murine RCC model. As a means of in vitro confirmation, we found that lycorine hydrochloride inhibited the viability of various RCC cell lines. Furthermore, luciferase-expressing Renca cells were implanted in the left kidney and the lung of BALB/c mice to develop a RCC metastatic mouse model. Lycorine hydrochloride and anti-CTLA-4 synergistically decreased tumor weight, lung metastasis, and luciferin-staining in tumor images. Importantly, the observed anti-tumor effects of this combination were dependent on significantly suppressing regulatory T cells while upregulating effector T cells; a decrease in regulatory T cells by 31.43% but an increase in effector T cells by 31.59% were observed in the combination group compared with those in the control group). We suggest that a combination of lycorine hydrochloride and anti-CTLA-4 is a viable therapeutic option for RCC patients.

Bipolar transurethral enucleation and resection of the prostate: Whether it is ready to supersede TURP?

Objective According to the EAU Guidelines, transurethral resection of the prostate (TURP) has so far still been considered as the gold standard for surgical treatment for patients with obstructing clinical benign prostate hyperplasia (BPH). However, its relatively high rate of complications and postoperative recurrence necessitates further modification and innovation on the surgery technique. We reported the patient outcomes with our technique. Methods We retrospectively analyzed 52 patients with obstructing clinical BPH who underwent bipolar transurethral enucleation and resection of the prostate (B-TUERP) between March 2015 and September 2015. Pre- and perioperative parameters were obtained from medical charts. Postoperative follow-ups were administrated at 1, 3, 6, 12 and 24 month(s) after surgery, respectively. Results All the operations were performed successfully with a mean operative time of 43.1 min and an average tissue removal rate of 74.7%. Qmax was significantly improved immediately after surgery, followed by a continuous improvement throughout the follow-ups. Following a steep decrease in mean prostate specific antigen (PSA) and post void residual (PVR) observed within the first half year after surgery, the serum PSA was then maintained at a constant level of 0.61 ng/mL. Temporary urinary retention was found in four cases (7.7%). Stress urinary incontinence occurred in five patients (9.6%), with the condition resolved in 1–2 weeks without extra treatment. Urethral strictures and bladder neck contractures, as the most commonly observed long-term complications, developed in four patients (7.7%). No recurrence was found during 2 years of follow-ups. An improvement in International Index of Erectile Function (IIEF-5) scores was witnessed in 17 patients preoperatively with normal sexual function during the first 6 months after surgery, and sustained throughout the 24-month period. Conclusions Enucleation reflects an improvement on surgical technique in many ways with a need for surgical equipment that can be broadly accessible in clinical practice. Currently, bipolar resection is a commonly employed procedure in clinical settings, and its similarity shared with bipolar enucleation technique warrants a quick learning of B-TUERP by urologists. Based on these findings, we believe that the substitution of TURP by TUERP as the gold standard for prostate endoscopic procedure can be expected in the future.

Can the lower urinary tract storage symptoms be completely resolved after plasmakinetic enucleation of the prostate

The aim of this study was to determine whether the lower urinary tract storage symptoms of benign prostatic obstruction (BPO) could be completely resolved after plasmakinetic enucleation of the prostate (PKEP) and the possible predictors of persistent symptoms. Two hundred and sixty-seven cases of BPO performed PKEP from July 2008 to June 2009 were retrospectively analyzed. Five-year postoperative data were collected and compared with the preoperative data. According to the urodynamic results, the patients were divided into involuntary detrusor contraction (IDC) group (n = 95) and no IDC group (n = 172) preoperatively; the patients with IDC were divided into IDC-persistent group (n = 33) and IDC-resolved group (n = 62) after PKEP. The predictors of persistent IDC were analyzed. Compared with the preoperative data, the 5-year postoperative data showed that the IDC rate was lower (P = 0.000), Overactive Bladder Symptom Score (OABSS) was lower (P = 0.000), maximum cystometric capacity (MCC) was larger (P = 0.000), Prostate volume (PV) was smaller (P = 0.000), and prostate-specific antigen (PSA) was lower (P = 0.000). Compared with the no IDC group, the IDC group showed that the age was older (P = 0.016), MCC was smaller (P = 0.004), PSA was higher (P = 0.016), and Chronic Inflammation rate was higher (P = 0.004). Compared with IDC-resolved group after PKEP, IDC-persistent group showed that the age was older (P = 0.019), MCC was smaller (P = 0.000), PSA was higher (P = 0.013), and Chronic Inflammation rate was higher (P = 0.032). The present study shows that the storage symptoms are still needed to be focused on after PKEP. The advanced patient age, MCC, PSA, and chronic inflammation may be the important clinical predictors of persistent IDC.

Sodium phenylbutyrate antagonizes prostate cancer through the induction of apoptosis and attenuation of cell viability and migration

Background Prostate cancer (PCa) is a leading cause of cancer-related death in men. Sodium phenylbutyrate (SPB) has shown its potential as an anticancer therapy in numerous cancer types. In the present study, we attempted to assess the effect of SPB against PCa and whether this treatment was associated with the regulation of survivin. Methods Two human PCa cancer cell lines, DU145 and PC3, were used in the present study. Cell Counting Kit-8 (CCK-8) assay was conducted to measure the proliferation of PCa cells incubated with SPB. The effect of SPB on the cell apoptosis, cell colony formation ability, and cell morphological change was also assessed. Transwell experiment and Western blotting assay were performed to determine the effect of SPB on the migration and invasion ability of both cell types. Moreover, the expression pattern of survivin and MAPK members in both cell types after the treatment of SPB was also detected. Additionally, an in vivo tumor formation assay was performed to evaluate the treatment potential of SPB against PCa. Results We found that the viability of PCa cells was significantly inhibited by SPB treatment. As illustrated by flow cytometry, for DU145 cell line the average apoptotic rate of SPB-treated cells was significantly lower than that of the control group (P<0.05); similar results were also seen for PC3 (P<0.05). SPB administration also attenuated the colony formation and migration abilities in both cell lines. The expression level of survivin in SPB-treated cells was significantly downregulated, while the phosphorylation of p-38 and ERK was enhanced. Furthermore, in vivo tumor formation of both cell lines was suppressed by SPB as well. Conclusion The above results confirmed the potential of SPB as an effective therapeutic agent for the prevention or treatment of PCa. This amelioration might be due to the blockade of the survivin pathway.