Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia(2021 Edition)

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy;the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Downregulation of the nucleosome-binding protein 1 （NSBP1） gene can inhibit the in vitro and in vivo proliferation of prostate cancer cells

This studay is to construct a lentiviral vector harbouring an RNA interference （RNAi） sequence that targets the gene encoding the human high-mobility group nucleosomal binding protein 1 （NSBP1）; to study its role in inducing G2/M phase arrest and apoptosis in prostate cancer （PCa） DU145 cells; and to assess the effect of its knockdown on cell proliferation in vitro and in vivo. RNAi was applied to knock down NSBP1 expression in the PCa cell line DU145 by lentiviral plasmids producing an NSBP1 small hairpin RNA. After NSBP1 knockdown in DU145 cells, the growth rate of cells was analyzed by MTT, and G2/M cell cycle arrest and apoptosis were assessed using a FAC- Scalibur flow cytometer. Tumour growth was assessed in nude mice. The mRNA and protein expression levels of NSBP1, cyclin B1 and Bcl-2 were analysed in vitro and in vivo by reverse-transcriptase polymerase chain reaction and Western blotting. Knockdown of NSBP1 resulted in a 22.6% decrease in the growth rate of cells compared with the PscNC lentivirus control cells at 96 h, decreased tumour growth in nude mice, and the induction of Gz/M cell cycle arrest （8.78%） and apoptosis （2.19-fold）. Consistent with the cell cycle arrest and apoptosis, the mRNA and protein expression levels of cyclin B 1 and Bcl-2 were decreased. In conclusion, knockdown of NSBP 1 causes a statistically significant inhibition of the in vitro and in vivo growth of the PCa cell line DU145. Growth suppression is at least partially due to NSBP1 knockdown-induced Gz/M cell cycle arrest and apoptosis. The present data provide the evidence that the NSBP1 knockdown-induced G2/M phase arrest and apoptosis may result from negative regulation of cyclin B 1 and Bcl-2 by NSBP1, with the resulting reduced expression of these proteins.

Small interfering RNA targeting HMGN5 induces apoptosis via modulation of a mitochondrial pathway and Bcl-2 family proteins in prostate cancer cells

We investigated the importance of HMGN5, a nuclear protein that binds to nucleosomes, unfolds chromatin, and affects transcription, in the LNCaP prostate cancer cell line. We also examined the molecular mechanisms that promote apoptosis of LNCaP cells after infection with small interfering RNA （siRNA） targeting HMGN5 （siRNA-HMGN5）. The androgen-dependent LNCaP human prostate cancer cells were infected with siRNA-HMGN5. Apoptosis was detected using the Annexin V-PE/7-AAD double staining and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL） assays. Mitochondrial membrane potential was measured by JC-1 staining. HMGN5and GAPDHmRNA expression were determined using real-time PCR. Bcl-2 and other apoptosis-related protein levels were determined by Western blot analysis. Caspase activity was measured by cleavage of the caspase substrate. Infection with siRNA targeting HMGN5 efficiently and specifically reduced the HMGN5 expression in LNCaP cells. The downregulation of HMGN5 induced remarkable apoptosis of LNCaP cells and resulted in the reduction of mitochondrial membrane potential. The induction of cell apoptosis was accompanied by the upregulation of Bax, the Bax/Bcl-2 ratio and the activation of caspase3. The HMGN5-targeted siRNA was effective in downregulating the expression of HMGN5 in androgen-dependent prostate cancer cells and inducing cell apoptosis via the regulation of a caspase-related mitochondrial pathway and Bcl-2 family proteins. This study suggests that HMGN5 may be a potential molecular target with therapeutic relevance for the treatment of prostate cancer.

Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml^-1

Percent free prostatic-specific antigen （%fPSA） has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml^-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer （PCa） and high-grade PCa （HGPCa） was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA〉4.0 ng ml^-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA （%fPSA ＋ PSA） was determined by the area under the receivers operating characteristic curve （AUC）. %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1.

The role of tumor size,ultrasonographic findings,and serum tumor markers in predicting the likelihood of malignant testicular histology

The clin ical predictive factors for maligna nt testicular histology remain unclear because of the low prevale nee.Therefore,the aim of this study was to investigate predictors of malignant histology for testicular masses and decide more testis-sparing surgeries before surgery.This retrospective study enrolled 325 consecutive testicular mass patients who underwent radical orchiectomy(310/325)or testicular preserving surgery(15/325)from January 2001 to June 2016.The clinicopathological factors,including tumor diameter,cryptorchidism history,ultraso und fin dings,serum alpha-fetoprotein,and human chorio nic gonadotropin(HCG)levels,were collected retrospectively for statistical an alysis.A predictive no mogram was also gen erated to evaluate the qua ntitative probability.Among all patients,247(76.0%)were diagnosed with a malignant testicular tumor and 78(24.0%)with benign histology.Larger tumor diameter(percm increased,hazard ratio[HR]=1.284,P=0.036),lower ultrasound echo(HR=3.191,P=0.001),higher ultrasound blood flow(HR=3.320,P<0.001),and abnormal blood HCG(HR=10.550,P<0.001)were significant predictive factors for malignant disease in all testicular mass patients?The nomogram generated was well calibrated for all predicti ons of malig nant probability,and the accuracy of the model no mogram measured by HarrelTs C statistic(C-in dex)was 0.92.According to our data,the proportion of patients who underwent radical orchiectomy for benign tumors(24.0%)was much larger tha n gen erally believed(10.0%).Our results in dicated that the diameter,ultras onic echo,ultras onic blood flow,and serum HCG levels could predict the malignancy in testicular mass patients.

Renal Tumor Biopsy Technique

Objective： To review hot issues and future direction of renal tumor biopsy （RTB） technique. Data Sources： The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015. Study Selection： We included all the relevant articles on RTB technique in English, with no limitation of study design. Results： Computed tomography and ultrasound were usually used for guiding RTB with respective advantages. Core biopsy is more preferred over fine needle aspiration because of superior accuracy. A minimum of two good-quality cores for a single renal tumor is generally accepted. The use of coaxial guide is recommended. For biopsy location, sampling different regions including central and peripheral biopsies are recommended. Conclusion： In spite of some limitations, RTB technique is relatively mature to help optimize the treatment of renal tumors.

Validation of the Pretreatment Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor in a Large Cohort of Chinese Patients with Upper Tract Urothelial Carcinoma

Background：The pretreatment neutrophil-to-lymphocyte ratio （NLR） has been reported to be a prognostic factor in various types of carcinomas.The aim of this study was to investigate the prognostic value of pretreatment NLR in a large cohort of Chinese patients with upper tract urothelial carcinoma （UTUC）.Methods：We retrospectively analyzed the medical data of 656 UTUC patients who underwent radical nephroureterectomy （RNU） from 2001 to 2011 at Peking University First Hospital.Receiver operating characteristic （ROC） curve analysis was performed to calculate the optimal cutoffpoint of pretreatment NLR.Uni-and multi-variate analyses were used to identify the prognostic factors for cancer-specific survival （CSS） and intravesical recurrence-free survival （IVRFS）.Results：The optimal cutoff point of pretreatment NLR was 2.40 by ROC curves,by which patients with high NLR （NLR 〉2.40） and low NLR （NLR 〈2.40） accounted for 314 （47.9%） and 342 （52.1%） patients,respectively.Patients with a high pretreatment NLR tended to have high tumor grades （x2 =15.725,P〈 0.001）,high tumor stages （x2 =25.416,P〈 0.001）,tumor sizes 〉5 cm （x2 =8.213,P=0.005）,ipsilateral hydronephrosis （x2 =4.624,P =0.033）,and concomitant carcinoma in situ （CIS） （x2 =9.517,P =0.003）.A high pretreatment NLR （hazard ratio [HR] =1.820,P=0.001）,main tumor diameter 〉5 cm （HR =1.789,P =0.009）,lymph node metastasis （HR =1.863,P =0.024）,and high tumor stage （HR =1.745,P 〈 0.001） independently predicted poor CSS after surgery,while only concomitant carcinoma in situ （CIS） （HR =2.164,P =0.034）,ureteroscopy before surgery （HR =1.701,P =0.015）,and high tumor grade （HR =1.645,P =0.018） were independent predictors of IVRFS after RNU.Conclusions：The pretreatment NLR was related to some adverse clinicopathological features and was an independent predictor of CSS,although not IVRFS,in Chinese UTUC patients.

The Institute of Urology, Peking University prostatectomy score： a simple preoperative classification of prostate cancer for predicting surgical difficulty and risk

Traditional laparoscopic radical prostatectomy is a treatment choice in many developing countries and regions for most patients with localized prostate cancer; however, no system for predicting surgical difficulty and risk has been established. This study aimed to propose a simple and standard preoperative classification system of prostate cancer using preoperative data to predict surgical difficulty and risk and to evaluate the relationship between the data and postoperative complications. We collected data from 236 patients and divided them into three groups to evaluate and validate the relationships among preoperative, operative, and postoperative data. This new scoring system is based on the body mass index, ultrasonic prostate volume, preoperative prostate-specific antigen level, middle lobe protrusion, and clinical stage. In the scoring group, we classified 89 patients into two groups： the low-risk group （score of 〈4） and high-risk group （score of ~4）, and then compared the postoperative data between the two groups. The positive surgical margin rate was higher in the high-risk group than low-risk group. The results in validation Groups A and B were similar to those in the scoring group. The focus of our scoring system is to allow for preliminary assessment of surgical difficulty by collecting the patients＇ basic information. Urologists can easily use the scoring system to evaluate the surgical difficulty and predict the risks of a positive surgical margin and urinary incontinence in patients undergoing laparoscopic radical prostatectomy.

Prognostic role of chromogranin A in ：astration-resistant prostate cancer： a meta-analysis

We aimed to investigate the prognostic value of chromogranin A （CgA） in castration-resistant prostate cancer （CRPC）. We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described CgA and CRPC and performed a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies with 686 patients. The results were as follows： progression-free survival （PFS） was associated with CgA level （hazard ratio [HR] = 2.47, 95% confidence interval [CI]： 1.47-4.14, P = 0.0006）; PFS was relative to CgA change （HR = 9.22, 95% Ch 3.03-28.05, P〈 0.0001）; and overall survival （OS） was relative to CgA level （HR = 1.47, 95% Ch 1.15-1.87, P= 0.002）. When we divided the patients into two groups according to therapy status, the result for OS relative to CgA level was an HR of 1.26 （95% CI： 1.09-1.45, P = 0.001） in the first-line hormonal therapy group, and an HR of 2.33 （95% Ch 1.40-3.89, P = 0.001） in the second-line hormonal therapy or chemotherapy group. This meta-analysis indicated that a high CgA level had a negative influence on OS and PFS in CRPC patients. In addition, CRPC patients with a rising CgA had a shorter PFS. Further studies are needed to verify the prognostic value of CgA in CRPC.