Abai 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.

PIK3R1 negatively regulates the epithelial-mesenchymal transition and stem-like phenotype of renal cancer cells through the AKT/GSK3β/CTNNB1 signaling pathway

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway has been identified as an important pathway in renal cell carcinoma (RCC). We have reported a nonsense mutation in PIK3R1, which encodes the regulatory subunit of PI3K, in a metastatic RCC (mRCC), while the mutation was absent in the corresponding primary RCC (pRCC). To identify the function of PIK3R1 in RCC, we examined its expression in normal kidney, pRCC and mRCC by immunohistochemistry and real-time polymerase chain reaction. The expression of PIK3R1 significantly decreased in pRCC and was further reduced in mRCC compared with normal tissue. Besides, its expression levels were negatively correlated with T-category of tumor stage. Additionally, 786-O and A-704 cells with PIK3R1 depletion introduced by CRISPR/Cas9 system displayed enhanced proliferation, migration and epithelial-mesenchymal transition (EMT), and acquired a stem-like phenotype. Moreover, the PIK3R1 depletion promoted the phosphorylation of AKT in the cells. The knockdown of AKT by shRNA reduced p-GSK3β and CTNNB1 expression in the cells, while the depletion of CTNNB1 impaired stem-like phenotype of the cells. Overall, PIK3R1 down-regulation in RCC promotes propagation, migration, EMT and stem-like phenotype in renal cancer cells through the AKT/GSK3β/CTNNB1 pathway, and may contribute to progression and metastasis of RCC.

An epigenetic biomarker combination of PCDH17 and POU4F2 detects bladder cancer accurately by methylation analyses of urine sediment DNA in Han Chinese

To develop a routine and effectual procedure of detecting bladder cancer (BlCa), an optimized combination of epigenetic biomarkers that work synergistically with high sensitivity and specificity is necessary. In this study, methylation levels of seven biomarkers (EOMES, GDF15, NID2, PCDH17, POU4F2, TCF21, and ZNF154) in 148 individuals—which including 58 urothelial cell carcinoma (UCC) patients, 20 infected urinary calculi (IUC) patients, 20 kidney cancer (KC) patients,20 prostate cancer (PC) patients, and 30 healthy volunteers (HV)—were quantified by qMSP using the urine sediment DNA. Receiver operating characteristic (ROC) curves were generated for each biomarker. The combining predictors of possible combinations were calculated through logistic regression model. Subsequently, ROC curves of the three best performing combinations were constructed. Then, we validated the three best performing combinations and POU4F2 in another 72 UCC, 21 IUC, 26 KC and 22 PC, and 23 HV urine samples. The combination of POU4F2/PCDH17 has yielded the highest sensitivity and specificity of 90.00% and 93.96% in all the 312 individuals, showing the capability of detecting BlCa effectively among pathologically varied sample groups.

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.

Single-cell analyses of transcriptional heterogeneity in squamous cell carcinoma of urinary bladder

Cell-to-cell expression heterogeneity within a single tumor is a common phenotype among various cancer types including squamous cell carcinoma. To further study the fundamentals and importance of heterogeneity of cell functions and its potential mechanisms, we performed single-cell RNA-seq (scRNA-seq) on human squamous cell carcinoma of the bladder (SCCB) and its corresponding physiologically normal epithelia. Extensive differentially expressed genes were uncovered by comparing cancer and normal single cells, which were preferentially enriched in cancer-correlated pathways, such as p53 signaling and bladder cancer pathway. Furthermore, the most diversely expressed genes were particularly enriched in MAPK signaling pathway, such as CACNG4, CACNA1E and CACNA1H, which involve in cancer evolution and heterogeneity formation. Co-expression network and hub-gene analyses revealed several remarkable “hub genes” of each regulatory module. Some of them are cancer related, such as POU2F3, NKD1 and CYP2C8, while LINC00189, GCC2 and OR9Q1 genes are rarely reported in human diseases. The genes within an interesting module are highly correlated with others, which could be treated as potential targets for SCCB patients. Our findings have fundamental implications for SCCB biology and therapeutic strategies.

Laparoendoscopic single-site surgery for symptomatic renal cyst decortication using a homemade glove port device: initial experience.

Objectives: Laparoendoscopic single-site surgery (LESS) has recently gained popularity in urology. There are few large series reports on LESS for symptomatic renal cysts. We evaluated the clinical utility and safety of LESS in 62 symptomatic renal cyst decortication patients by using a homemade glove port device. Materials and Methods: We reviewed our series of 62 LESS for symptomatic renal cyst (20 Bosniak type I and 42 Bosniak type II) decortication performed from November 2009 to December 2010. A homemade glove port device was placed through an umbilical incision. The perioperative clinical parameters were reviewed retrospectively. Results: Of 62 cases that underwent LESS for renal cyst ablation successfully, there were no major perioperative complications, but 2 minor complications (transient fever and mild ileus) were found. The mean operative time was 61.4 ± 27.4 min and the mean estimated blood loss was 20.1 ± 11.3 ml. The mean pre- and postoperative pain scores were 6.94 ± 1.1 (range 5–10) and 1.3 ± 1.2 (0–5), respectively (p = 0.000). Conclusions: Our results suggest that LESS is a safe and feasible alternative to conventional laparoscopic surgery for the treatment of symptomatic renal cysts.

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.

Efficacy of intravesical Bacillus Calmette-Guérin therapy against tumor immune escape in an orthotopic model of bladder cancer

The aim of this study was to evaluate the antitumor immune response of the Bacillus Calmette-Guérin (BCG) in an orthotopic bladder cancer model. The murine bladder cancer cell line MBT-2 was transurethrally implanted in the bladder of syngeneic female C3H/He mice. The animals were randomly divided into three treatment groups: Phosphate-buffered saline (PBS), low-dose BCG and high-dose BCG. The analyses of luciferin-stained tumor images 28 days after each treatment showed significant tumor growth inhibition in the high-dose group in comparison with that in the low-dose- or PBS-treated groups. In addition, the percentage of myeloid-derived suppressor cells in the high-dose group was significantly suppressed in comparison with that in the PBS and low-dose agent treatment groups. These findings are notable in terms of the clinical evaluations of this therapy for patients with bladder cancer. The outcomes of this study also provide important implications regarding antitumor immune responses in human cancer.

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.