A Prospective Study Comparing Cancer Detection Rates of Transperineal Prostate Biopsies Performed by Junior Urologists versus a Senior Consultant in a Real-World Setting.

INTRODUCTION: Prostate biopsy (PB) is a typical daily practice method for the diagnosis of prostate cancer (PCa). This study aimed to compare the PCa detection rates and peri- and postoperative complications of PB among 3 residents and a consultant. PATIENTS AND METHODS: A total of 343 patients who underwent PB between August 2018 and July 2019 were involved in this study. Residents were systematically trained for 2 weeks by a consultant for performing systematic biopsy (SB) and targeted biopsy (TB). And then, 3 residents and the consultant performed PB independently every quarter due to routine rotation in daily practice. The peri- and postoperative data were collected from a prospectively maintained database (www.pc-follow.cn). The primary outcome and secondary outcome were to compare the PCa detection rates and complications between the residents and consultant, respectively. RESULTS: There was no significant difference between the residents and consultant in terms of overall PCa detection rates of SB and TB or further stratified by prostate-specific antigen value and prostate imaging reporting and data system (PI-RADS) scores. We found the consultant had more TB cores (175 cores vs. 86-114 cores, p = 0.043) and shorter procedural time (mean 16 min vs. 19.7-20.1 min, p < 0.001) versus the residents. The complication rate for the consultant was 6.7% and 5%-8.2% for the residents, respectively (p = 0.875). CONCLUSIONS: The residents could get similar PCa detection and complication rates compared with that of the consultant after a 2-week training. However, the residents still need more cases to shorten the time of the biopsy procedure.

[Surgical treatment of azoospermia caused by iatrogenic injury to bilateral vas deferens].

OBJECTIVE: To investigate the treatment of azoospermia induced by iatrogenic injury to the bilateral vas deferens. METHODS: We retrospectively analyzed 11 cases of azoospermia caused by iatrogenic injury to bilateral vas deferens. The patients were aged 20－33 years, all diagnosed with azoospermia preoperatively and none with a history of pelvic operation. Seven of them had received bilateral inguinal hernia repair and the other 4 undergone bilateral orchidopexy in the childhood. RESULTS: Intraoperative exploration of the bilateral inguinal region was performed in all the patients. Bilateral vas deference atresia was found in the inguinal canal in 6 cases, which was treated by microscopic vasovasostomy following removal of the atresic segment. Vas deferens residual was observed in or near the deep inguinal ring in the other 5 cases, with the distal vas deferens inaccessible, which was treated by bilateral vasovasostomy in 3 cases and unilateral vasovasostomy in 2 (for longer defect segment than could be anastomosed) following combined laparoscopic exploration of the abdominal cavity. The patients were followed up for 3－12 months postoperatively, during which sperm were detected in 7 cases, with sperm concentration ranging from 0.4×106/ml to 35×106/ml and grade a+b sperm from 15% to 46%. CONCLUSIONS: For the diagnosis of azoospermia, especially in patients with no history of pelvic operation, special attention should be paid to iatrogenic injury to the vas deferens. For the treatment of the disease, non-tension vasovasostomy is essential and, when necessary, the vas deferens can be reconstructed by changing its anatomical path and shortening its length.

A novel urinary long non-coding RNA transcript improves diagnostic accuracy in patients undergoing prostate biopsy.

BACKGROUND: Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE). METHODS: Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis. RESULTS: 213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers. CONCLUSIONS: FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis.

Removal of numerous vesical magnetic beads with a self-made magnetic sheath.

INTRODUCTION: Sexual curiosity and the quest for sexual excitement are the most frequent reasons for patients to introduce foreign bodies into the urethra or the bladder. Imagination and surgical skill are essential for urologists to retrieve such vesical foreign bodies. AIM: The aim of this study was to describe a novel method for retrieving vesical magnetic beads, which were inserted for autoeroticism by a male adolescent, with a self-made "magnetic sheath." METHODS: A 21-year-old young man inserted more than one hundred small magnetic beads into his urethra for sexual excitement, which lately caused symptoms of gross hematuria, frequent urination, and acute lower abdominal pain when walking or urinating. We invented a magnetic sheath by fixing a magnetic bead on the tip of an F9.5 ureteral access sheath to remove the foreign bodies in a minimally invasive way. MAIN OUTCOME MEASURE: The feasibility of using magnetic sheath to remove vesical foreign bodies; and operation duration. RESULTS: Under direct visualization of an F8/9.8 ureteroscope, the magnetic sheath could firmly attach to the magnetic bead inside the bladder and could easily pull out 5 to 15 beads each time. It took about 5 minutes to remove all of the 125 magnetic beads by utilizing our magnetic sheath. CONCLUSIONS: The self-made magnetic sheath can make the task of removal of magnetic foreign bodies easy to urologists, requiring less time and surgical skills. The new equipment provides a new method for urologists to deal with the challenging task of removing metal vesical foreign bodies which were self-inserted for masturbation.

Phytochemical and Pharmacological Profile of Vitex negundo.

The article aims to review all the chemical constituents and pharmacological properties of Vitex negundo L. (Verbenaceae) (VN). VN is an important medicinal plant used as reputed herbal medicine with versatile pharmacological activities in China, India and Japan. A total of 104 referred articles about VN were compiled from major databases and academic publishers, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. As a result, a total of 120 compounds isolated from VN can be divided mainly into four classes: flavonoids, lignans, terpenoids and steroids. The crude extracts and purified compounds of VN exhibited promising bioactivities, including anti-nociceptive, antiinflammatory, anti-tumor, anti-oxidant, insecticidal, antimicrobial, anti-androgenic, anti-osteoporotic, anti-cataract, hepatoprotective and anti-hyperglycemic activity. All the reported data lead us to conclude that VN has convincing medicinal potential. However, further researches are needed to explore its bioactive constituents, the structure-activity relationship and their molecular mechanisms of action.

[Transurethral seminal vesiculoscopy for refractory or recurrent hemospermia: clinical analysis of 162 cases].

OBJECTIVE: To investigate the feasibility and effect of transurethral seminal vesiculoscopy in the diagnosis and treatment of refractory or recurrent hemospermia. METHODS: We retrospectively analyzed 162 cases of refractory or recurrent hemospermia examined and treated by transurethral seminal vesiculoscopy. The patients ranged in age from 19 to 76 years and had a hemospermia history of 3 months to 11 years, admitted due to poor therapeutic results or recurrence after 4 weeks of antibiotic medication. All the patients underwent serum PSA examination, transrectal ultrasonography, seminal vesicle ultrasonography and pelvis CT or MRI before surgery. RESULTS: Wine- or magenta-colored colloid and inflammation were found in one or both sides of the seminal vesicle in all the cases. Pathological biopsy revealed chronic inflammatory mucosa of the seminal vesicle in all the patients, and even calculi in the ejaculatory duct or seminal vesicle in 15 cases. Postoperative follow-up averaged 21.7 (12 -29) months. Hemospermia disappeared or was alleviated in 150 (92.64%) of the cases after 1-15 ejaculations, in which 7 experienced recurrence 3 months later. Four cases failed to respond, and 1 developed acute bilateral epididymitis after surgery. No such complications as retrograde ejaculation, urinary incontinence or rectal injury were observed postoperatively. CONCLUSION: Transurethral seminal vesiculoscopy is a safe, effective and feasible new method for the treatment of refractory or recrudescent hemospermia.

[Prostate cancer cell line PC-3 conditioned medium promotes proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells].

OBJECTIVE: To investigate the effects of prostate cancer cell line PC-3 conditioned medium (PC- 3-CM) on the proliferation and osteogenic differentiation of human bone marrow human basalis mesenchymal stem cells (hBMSCs). METHODS: hBMSCs were isolated and culture-expanded by density gradient centrifugation from normal volunteers. PC-3 cells were cultured till the time of logarithmic growth and then transferred to a fresh medium, which, after 24 hours of incubation, was collected as PC-3-CM. Passage 3 hBMSCs were cultured in the fresh medium alone (the control group) or that with 50% PC-3-CM (the experimental group), and the effect of PC-3-CM on the proliferation activity of the hBMSCs was detected by WST-8 assay. Based on the types of medium used, the hBMSCs were divided into Groups I (control), II (50% PC-3-CM), III (osteoblast inducer) and IV (osteoblast inducer containing 50% PC-3 CM). The effects of PC-3-CM on the osteoblastic differentiation of the hBMSCs were determined by ALP staining, ALP activity detection, Von Kossa staining, and calcium quantitation. RESULTS: At 1, 3, 5 and 7 days of incubation, the absorbance values of the cells in the experimental group were 0.4370 +/- 0.0285, 0.7980 +/- 0.0213, 1.9090 +/- 0.0612 and 2.3023 +/- 0.0610, and those in the control group were 0.4060 +/- 0.0223, 0.6643 +/- 0.0075, 1.3727 +/- 0.0176 and 1.7947 +/- 0.0115, respectively, with significant differences between the two groups (P < 0.01) except on day 1 (P > 0.05). The positive rate and intensity of ALP staining were gradually increased in the four groups, with the ALP activities of 0.29 +/- 0.03, 1.30 +/- 0.03, 2.13 +/- 0.08, and 3.80 +/- 0.03, respectively (P < 0.01), and so was the intensity of Von Kossa staining, with the calcium depositions of 0.04 +/- 0.01, 0.44 +/- 0.05, 0.98 +/- 0.03, and 1.27 +/- 0.04, respectively (P < 0.01). CONCLUSION: PC-3- CM can promote the proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells.

[Efficacy and safety of long-term small-dose tadalafil in the treatment of erectile dysfunction].

OBJECTIVE: Erectile dysfunction (ED) is now recognized as a comorbid condition, especially in men with cardiovascular disease or diabetes mellitus. This randomized controlled trial was to examine the effect of long-term small-dose tadalafil in the treatment of ED. METHODS: A total of 98 men older than 18 years with at least a 6-month ED history were enlisted and divided into two groups to receive once-daily treatment with tadalafil at 5 mg (n = 60) and 20 mg (n = 38), respectively, for 12 months. The effects of medication were analyzed and compared using IIEF, Global Assessment Questionnaire (GAQ) and Sexual Encounter Profile (SEP), and so were the safety and tolerance of the two doses. RESULTS: There were no statistically significant differences in the therapeutical results between the 5 mg and 20 mg groups (P < 0.05). The IIEF-5 score was raised by 8.1 points in the former and 7.9 points in the latter; the YES answers to SEP2 in the two groups were 51.3% and 49.2% before the treatment and 82.6% and 84.9% after it. No serious adverse events were observed, except some common ones, such as rubeosis (11.9% vs 8.7%) and headache (5.3% vs 4.9%) in the 5 mg and 20 mg groups. CONCLUSION: Oral tadalafil at 5 mg once daily is efficacious with good tolerance in the treatment of ED, and it can be an alternative to on-demand medication for some men to eliminate the inconvenience of planned intercourse within a limited timeframe.

A Multicenter Single-Arm Objective Performance Criteria Trial to Determine the Efficacy and Safety of High-Frequency Irreversible Electroporation as Primary Treatment for Localized Prostate Cancer: A Study Protocol.

INTRODUCTION: The classical pathway for the therapy of low- to intermediate-risk localized prostate cancer is radical prostatectomy or radiation therapy, which has shown a high incidence of complications, including erectile dysfunction, urinary incontinence, and bowel injury. An alternative pathway is to perform an ablation by some energy to the localized lesion, known as focal therapy. High-frequency irreversible electroporation (H-FIRE) is nonthermal energy that can be used in cancer ablation to deliver pulsed high-voltage but low-energy electric current to the cell membrane and to invoke cell death. An H-FIRE pathway has been reported to be tissue-selective, which leads to fewer side effects. METHODS AND ANALYSIS: This is a multicenter and single-arm objective performance criteria (OPC) study, in which all men with localized prostate cancer are allocated to H-FIRE ablation. This trial will assess the efficacy and safety of the H-FIRE ablation for prostate cancer. Efficacy will be assessed by prostate biopsy 6 months after treatment while safety will be assessed by adverse event reports and questionnaires. The main inclusion criteria are moderate to low-risk prostate cancer in NCCN risk classification and had no previous therapy for prostate cancer. A sample size of 110 participants is required. The primary objective is to determine whether the detection rate of clinically significant cancer by prostate biopsy is less than 20% after the H-FIRE ablation. ETHICS AND DISSEMINATION: This study has obtained ethical approval by the ethics committee of all participating centers. The results of the study will be submitted for dissemination and publication in peer-reviewed journals. CONCLUSIONS: This multicenter single-arm objective performance criteria trial will evaluate the efficacy and safety of the use of high-frequency irreversible electroporation in treating prostate cancer. STRENGTHS AND LIMITATIONS OF THIS STUDY: A comprehensive evaluation of imaging and histopathology is used to determine the effect of treatment. Questionnaires were used to assess the treatment side effects. Multicenter and pragmatic designs capacitate higher generalizability. A limitation of this trial is that the prostate biopsy as an endpoint may not be as accurate as of the specimen from prostate prostatectomy. Another limitation is the 6-month follow-up time, making this trial challenging to come to firm conclusions regarding the efficacy and safety of IRE in the long term. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03838432.

Ursolic acid overcomes Bcl-2-mediated resistance to apoptosis in prostate cancer cells involving activation of JNK-induced Bcl-2 phosphorylation and degradation.

Androgen-independent prostate cancers express high levels of Bcl-2, and this over-expression of Bcl-2 protects prostate cancer cells from undergoing apoptosis. Ursolic acid (UA) has demonstrated an anti-proliferative effect in various tumor types. The aim of this study is to evaluate the difference between UA-induced apoptosis in androgen-dependent prostate cancer cell line LNCaP cells and androgen-independent prostate cancer cell line LNCaP-AI cells and to reveal the molecular mechanisms underlying the apoptosis. We found that UA treatment in vitro can effectively induce apoptosis in LNCaP and LNCaP-AI cells. UA can overcome Bcl-2-mediated resistance to apoptosis in LNCaP-AI cells. Intrinsic apoptotic pathways can be triggered by UA treatment because c-Jun N-terminal kinase (JNK) is activated and subsequently provokes Bcl-2 phosphorylation and degradation, inducing activation of caspase-9. Although further evaluation is clearly needed, the present results suggest the potential utility of UA as a novel therapeutic agent in advanced prostate cancer.

Differential phosphoprotein levels and pathway analysis identify the transition mechanism of LNCaP cells into androgen-independent cells.

BACKGROUND: Androgen withdrawal can prolong life in men with advanced prostate cancer, but these remissions are temporary because the surviving cells progress as hormone-refractory cancer. The mechanisms that are involved in the transition of androgen-dependent prostate cancer into androgen-independent prostate cancer (AIPC) are not fully understood. OBJECTIVE: To identify globally differentially expressed phosphoproteins in the androgen-independent prostate, to elucidate the molecular mechanisms that underlie the formation of AIPC and to identify new molecular targets that can be used to develop treatments for the disease. METHODS: An androgen-independent LNCaP cell line, LNCaP-AI, was established using androgen ablation. Differentially expressed phosphoproteins in LNCaP cells and LNCaP-AI cells were enriched by immunoprecipitation, analyzed by 2D-PAGE and identified by MALDI-TOF MS. Total protein expression levels for two regulated proteins were confirmed by Western blot. Association network analysis was carried out using the STRING database. RESULTS: The phosphorylation statuses of 17 proteins were significantly (P < 0.05) different between LNCaP-AI cells and LNCaP cells. Most proteins that were identified are known to be involved in tumor progression, and several of these proteins could be constructed into an association network. A further analysis by bioinformatics indicated that P53, HSP27, and the MAPK pathway may contribute to the transition from androgen-dependence to androgen-independence. CONCLUSION: Blocking the MAPK signaling pathway may be useful in the treatment of AIPC.

[Expressions of the androgen receptor in normal prostate, benign prostatic hyperplasia and prostate cancer].

OBJECTIVE: To study the expressions of the androgen receptor (AR) in the normal prostate, benign prostatic hyperplasia and prostate cancer (PCa), and investigate the relationship of AR with prostatic hyperplasia and PCa. METHODS: The expressions of AR were detected in 15 normal prostate, 20 benign prostatic hyperplasia and 40 PCa samples by immunofluorescent staining, real-time PCR and Western blotting. RESULTS: Real-time PCR and Western blotting revealed no statistically significant differences in the expressions of AR between the normal prostate and prostatic hyperplasia groups (P < 0.05), while immunofluorescent staining exhibited an increase of the expression in the BPH tissues. All the three methods showed that the AR expression was significantly higher in the PCa than in the normal prostate and prostatic hyperplasia groups (P < 0.05), in the well differentiated than in the poorly differentiated tumor, and in the early than in the advanced stage (P < 0.05), but the lowest in the hormone-refractory PCa (HRPC) tissue. CONCLUSION: The expression of AR is higher in PCa than in normal prostate and prostatic hyperplasia tissues, and is correlated with the pathological grade and clinical stage of PCa.

[Nonsteroidal anti-inflammatory drug NS398 induces RECK expression in the animal model of prostate cancer].

OBJECTIVE: To investigate the regulatory effect of the nonsteroidal anti-inflammatory drug NS398 on the expression of the RECK gene in the animal model of prostate cancer. METHODS: Nude mouse models of prostate cancer were divided into an experimental and a control group, the former fed with NS398 at 0.1 mg/g per day for 10, 20 and 30 days, while latter left without medication. All the mice were killed at 30 days, the mRNA expressions of RECK and MMP-9 in the tumor tissues measured by RT-PCR, and the protein level of RECK evaluated by Western blot. RESULTS: Both the mRNA and protein expressions of RECK were increased, while the level of MMP-9 decreased, in an obviously time-dependent manner in the experimental group as compared with the control. CONCLUSION: NS398 obviously inhibits the pathogenesis and metastasis of prostate cancer, which may be attributed to its induction of the expression of the RECK gene and suppression of the expression of MMP-9.

[Induction of prostate cancer-specific CTLs with dendritic cells pulsed by different types of tumor antigens].

OBJECTIVE: To study the effectiveness of freeze-thaw antigens and acid eluted peptide antigens extracted from tumor cell-pulsed dendritic cells (DC) in inducing prostate cancer-specific cytotoxic T lymphocytes (CTL) in vitro. METHODS: Tumor antigens were extracted from the prostate cancer cell line PC-3 with the repeated freeze-thaw and weak acid elution methods. Peripheral blood mononuclear cells were cultured with recombinant human GM-CSF and IL-4 for inducing DCs in vitro. Then the DCs were pulsed with the two kinds of prostate cancer tumor antigens respectively and cultured with T cells for inducing CTLs. The activity of the tumor-specific CTLs were detected by LDH release assay. RESULTS: The protein content in the tumor antigens obtained from PC-3 (2 x 10(7)) by citric acid-phosphate buffer elution and that by the repeated freeze-thaw method were (212.2 +/- 7.9) microg and (963.0 +/- 25.3) microg, respectively. The two kinds of prostate cancer antigens-pulsed DCs had a significant role in inducing the PC-3 cell-specific CTLs, and the CTLs induced by acid-eluted peptide antigen-pulsed DCs exhibited an even more significant tumor-specific cytotoxicity than those induced by repeated freeze-thaw ([60.4 +/- 5.52]% vs. [43.7 +/- 4.11]%, P < 0.01). CONCLUSION: Both the weak acid elution and repeated freeze-thaw methods for extracting prostate cancer antigens can be used for in vitro sensitization of DCs. The DCs pulsed by either of the two kinds of antigens can activate CTLs, and the antigens extracted by weak acid elution are even more effective.

CD147 and VEGF expression in advanced renal cell carcinoma and their prognostic value.

AIM: To investigate the clinicopathologic characteristics of extracellular matrix (ECM) metalloproteinase inducer (CD147) and vascular endothelial growth factor (VEGF) expression in advanced renal cell carcinoma (RCC), and to evaluate the clinical significance of these two markers in the prognosis of advanced RCC. METHODS: CD147 and VEGF expression in paraffin-embedded specimens gathered from 53 patients with advanced RCC and 12 healthy controls were detected by the method of immunohistochemistry. The Spearman correlation was calculated between the expression levels of CD147 and VEGF in advanced RCC tissues. The association of CD147 and VEGF expression with the clinicopathologic features and prognosis of advanced RCC was subsequently assessed. RESULTS: CD147 and VEGF were positively expressed in 47/53 (88.7%) and 45/53 (84.9%) of patients with advanced RCC, respectively. Positive expression of CD147 (p= 0.02) and VEGF (p< 0.01) was significantly correlated with TNM stage of advanced RCC. A significant correlation was found between the expression of CD147 and VEGF in advanced RCC (r= 0.629, p= 0.04). Additionally, tumor CD147 and tumor VEGF expressions were significantly associated with the prognosis of advanced RCC patients. The survival rate of the patients with CD147-/VEGF- expression was the lowest (p< 0.01), and conjoined expressions of CD147-/VEGF- and CD147+/VEGF+ were independent prognostic indicators of advanced RCC (both p< 0.01). CONCLUSION: The expression of CD147 or VEGF may be an important feature of advanced RCC. A combined detection of CD147/VEGF coexpression may benefit us in the prediction of the prognosis of advanced RCC.

Age-specific PSA reference ranges in Chinese men without prostate cancer.

This study is to determine age-specific prostate-specific antigen (PSA) distributions in Chinese men without prostate cancer (PC) and to recommend reference ranges for this population after comparison with other studies. From September 2003 to December 2006, 9 374 adult men aged from 18 to 96 years agreed to participate in the study. After all cases of PC were excluded, 8 422 adult men participated in statistical analysis and were divided into five age groups. Simple descriptive statistical analyses were carried out and quartiles and 95th percentiles were calculated for each age group. The age-specific PSA reference ranges are as follows: 40-49 years, 2.15 ng mL(-1); 50-59 years, 3.20 ng mL(-1); 60-69 years, 4.10 ng mL(-1); 70-79 years, 5.37 ng mL(-1). The results indicate that the ethnic differences in PSA levels are obvious. The currently adopted Oesterling's age-specific PSA reference ranges are not appropriate for Chinese men. The reference ranges of this study should be more suitable to Chinese men.

[Single-port transumbilical laparoscopic nephrectomy: initial clinical experience of 3 cases].

OBJECTIVE: To evaluate the safety and efficacy of single-port transumbilical laparoscopic nephrectomy. METHODS: From December 2008 to August 2009, we have performed three cases of single-port transumbilical laparoscopic nephrectomy of nonfunctioning renal by Tri-Port system. Among three patients there were two cases of UPJO and one case of upper ureteral obstruction. Involved kidneys were not visualized in IVU and the GFR were not more than 0.90 ml/s. Tri-Port system was inserted transperitoneal through a 2 cm umbilical incision. The flexible grasper, scissors were used in addition to standard laparoscopic equipment. Renal pedicle was divided by Endoscopic Linear Stapling device. Specimens were extracted through the incision. RESULTS: The first and second case were successful, and the operation time were 85 min and 165 min. The bleeding volume were 50 ml and 100 ml. The discharge time after operation was 3 days and 5 days, respectively. The third case was converted to open surgery because of the edema and adhesion of renal pedicle. At 3 weeks of follow-up, the incisions were hidden in the umbilicus with good cosmetic benefit. CONCLUSIONS: This new method is technically feasible, which combined with these advantages of less trauma and more cosmetic benefit. However, more special instruments and long learning curving may be needed for those surgeons, who are going to carry out it.

[Experimental studies of kidney biopsy by natural orifices: transgastric and transvesical combined approach].

OBJECTIVE: To evaluate the feasibility of kidney biopsy by transgastric and transvesical combined approach in the porcine model. METHODS: Five female pigs (20 to 30 kg) were included in this study. All procedures were performed with pigs under general anesthesia. The transvesical access was established by the ureteroscope. Then monitored by ureteroscopy, the transgastric access was established by a needle knife with cautery. The puncture dilation was performed with balloon through the gastroscope. The vesical hole was enlarged with the dilator of ureteroscope sheath. The kidney biopsy was finished by the scissor from the transvesical access and the grasping forcep from the work channel of gastroscope. RESULTS: Among five cases the procedure were successful in three cases with 380 min, 180 min, 78 min respectively. Establishment of transvesical and transgastric accesses took place without complications. The exposure and biopsy of the kidney were easily achieved during operation. The transgastric and transvesical access were not closed in the end. CONCLUSIONS: This new method is a technically feasible procedure in a porcine model. But the safety and the clinical future of it needs more study.

The Long Noncoding RNA TTTY15, Which Is Located on the Y Chromosome, Promotes Prostate Cancer Progression by Sponging let-7.

BACKGROUND: The link between prostate cancer (PCa) development and aberrant expression of genes located on the Y chromosome remains unclear. OBJECTIVE: To identify Y-chromosomal long noncoding RNAs (lncRNAs) with critical roles in PCa and to clarify the corresponding mechanisms. DESIGN, SETTING, AND PARTICIPANTS: Aberrantly expressed lncRNAs on the Y chromosome were identified using transcriptome analysis of PCa clinical samples and cell lines. Biological functions and molecular mechanisms of the lncRNAs were revealed using in vitro and in vivo experimental methods. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Experiments and outcome measurements were performed in duplicate or triplicate. Wilcoxon signed-rank test was employed for comparison of RNA levels in clinical cohorts. Analysis of variance was employed for comparisons among multiple groups. RESULTS AND LIMITATIONS: In most patients with PCa, TTTY15 was the most elevated lncRNA located on the Y chromosome. Knockout of this lncRNA by two different CRISPR-Cas9 strategies suppressed PCa cell growth both in vitro and in vivo. TTTY15 promoted PCa by sponging the microRNA let-7, consequently increasing CDK6 and FN1 expression. FOXA1 is an upstream regulatory factor of TTTY15 transcription. CONCLUSIONS: The Y-chromosomal lncRNA TTTY15 was upregulated in most PCa tissues and could promote PCa progression by sponging let-7. PATIENT SUMMARY: We found that TTTY15 levels were frequently elevated in prostate cancer (PCa) tissues compared with those in paracancerous normal tissues in a large group of PCa patients, and we observed a tumour suppressive effect after TTTY15 knockout using CRISPR/Cas9. These results may have therapeutic implications for PCa patients.

Targeting an Autocrine Regulatory Loop in Cancer Stem-like Cells Impairs the Progression and Chemotherapy Resistance of Bladder Cancer.

PURPOSE: Cancer stem-like cells (CSCs) contribute to bladder cancer chemotherapy resistance and progression, but the associated mechanisms have not been elucidated. This study determined whether blocking an autocrine signaling loop in CSCs improves the therapeutic effects of cis-platinum on bladder cancer. EXPERIMENTAL DESIGN: The expression of the epithelial marker OV6 and other markers in human bladder cancer specimens was examined by IHC. The CSC properties of magnetic-activated cell sorting (MACS)-isolated OV6+ and OV6- bladder cancer cells were examined. Molecular mechanisms were assessed through RNA-Seq, cytokine antibody arrays, co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP) and other assays. An orthotopic bladder cancer mouse model was established to evaluate the in vivo effects of a YAP inhibitor (verteporfin) and a PDGFR inhibitor (CP-673451) on the cis-platinum resistance of OV6+ CSCs in bladder cancer. RESULTS: Upregulated OV6 expression positively associated with disease progression and poor prognosis for bladder cancer patients. Compared with OV6- cells, OV6+ bladder cancer cells exhibited strong CSC characteristics, including self-renewal, tumor initiation in NOD/SCID mice, and chemotherapy resistance. YAP, which maintains the stemness of OV6+ CSCs, triggered PDGFB transcription by recruiting TEAD1. Autocrine PDGF-BB signaling through its receptor PDGFR stabilized YAP and facilitated YAP nuclear translocation. Furthermore, blocking the YAP/TEAD1/PDGF-BB/PDGFR loop with verteporfin or CP-673451 inhibited the cis-platinum resistance of OV6+ bladder cancer CSCs in an orthotopic bladder cancer model. CONCLUSIONS: OV6 could be a helpful indicator of disease progression and prognosis for patients with bladder cancer, and targeting the autocrine YAP/TEAD1/PDGF-BB/PDGFR loop might serve as a remedy for cis-platinum resistance in patients with advanced bladder cancer.