Prostate cancer in Asia:A collaborative report

The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly.This collaborative report summarized the latest epidemiology information,risk factors,and racial differences in PCa diagnosis,current status and new trends in surgery management and novel agents for castration-resistant prostate cancer.We believe such information would be helpful in clinical decision making for urologists and oncologists,health-care ministries and medical researchers.

Current status of diagnosis and treatment of bladder cancer in China-Analyses of Chinese Bladder Cancer Consortium database

Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases from 44 CBCC centers were included.Data of diagnosis,treatment and pathology were collected.Results:The average age was 63.5 year-old and most patients were male(84.3%).The most common histologic types were urothelial carcinoma(91.4%),adenocarcinoma(1.8%),and squamous carcinoma(1.9%).According to 1973 and 2004 WHO grading system,42.0%,41.0%,and 17.0% of patients were grade 1,2,and 3,and 16.0%,48.7%,and 35.3% of patients were papillary urothelial neoplasms of low malignant potential,low,and high grade,respectively.Non-muscle invasive bladder cancer(NMIBC)and muscle invasive bladder cancer(MIBC)were 25.2% and 74.1%,respectively(0.8% not clear).Carcinoma in situ was only 2.4%.Most patients were diagnosed by white-light cystoscopy with biopsy(74.3%).Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%,respectively.Diagnostic transurethral resection(TUR)provided detection rate of 16.9%.Most NMIBCs were treated with TUR(89.2%).After initial TUR,2.6%accepted second TUR,and 45.7%,69.9%,and 58.7% accepted immediate,induced,and maintenance chemotherapy instillation,respectively.Most MIBCs were treated with radical cystectomy(RC,59.7%).Laparoscopic RCs were 35.1%,while open RC 63.4%.Extended and standard pelvic lymph node dissection were 7% and 66%,respectively.Three most common urinary diversions were orthotopic neobladder(44%),ileal conduit(31%),and ureterocutaneostomy(23%).Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18%of T3 and T4 patients accepted adjuvant chemotherapy.Conclusion:Disease characteristics are similar to international reports,while differences of diagnosis and treatment exist.This study can provide evidences for revisions of the guideline on bladder cancer in China.

Adjuvant hormone therapy after radical prostatectomy in highrisk localized and locally advanced prostate cancer: First multicenter, observational study in China

Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrence rate and quality of life(Qo L) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy(HT) after radical prostatectomy(RP).Methods: This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor(preoperative PSA>20 ng/m L or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice.Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate(FACT-P) Qo L scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.Results: A total of 189 patients(mean age: 66.9±6.5 years) were recruited, among which 112(59.3%) patients showed serum PSA>20 ng/m L preoperatively. The highest postoperative pathological advancement noticed was from clinical T2(c T2) to pathological T3(p T3)(43.9%) stage. The majority of the patients(66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence(15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist(LHRHa)(16.1%), and antiandrogen(19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P Qo L score of119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.Conclusions: Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in highrisk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens(AA) or LHRHa therapy. Further long-term therapy(>12 months) significantly improved Qo L compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving Qo L.

Percent free prostate-specific antigen for prostate cancer diagnosis in Chinese men with a PSA of 4.0-10.0 ng/mL:Results from the Chinese Prostate Cancer Consortium

Objective:To test the diagnostic performance of percent free prostate-specific antigen(%fPSA)in predicting any prostate cancer(PCa)and high-grade prostate cancer(HGPCa)in a retrospective multi-center biopsy cohort with a PSA level of 4.0e10.0 ng/mL in China.Methods:Consecutive patients with a PSA of 4.0-10.0 ng/mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st,2010 to December 31st,2013.Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization(WHO)standard.The diagnostic accuracy of PSA,%fPSA,and %fPSA in combination with PSA(%fPSA t PSA)was determined using the area under the receiver operating characteristic(ROC)curve(AUC).Results:A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng/mL were included,and the detection rate of PCa was 25.1%.The AUC of%fPSA and %fPSA t PSA in predicting any PCa was superior to PSA alone in men aged≥60 years(0.623 vs.0.534,p<0.0001)but not in men aged 40e59 years(0.517 vs.0.518,p=0.939).Similar result was yield in predicting HGPCa.Conclusion:In a clinical setting of Chinese men with 4.0e10.0 ng/mL PSA undergoing initial prostate biopsy,adding %fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients≥60 but not in patients aged 40-59 years.

Comparison of the oncological,perioperative and functional outcomes of partial nephrectomy versus radical nephrectomy for clinical T1b renal cell carcinoma:A systematic review and metaanalysis of retrospective studies

Objective:To conduct a meta-analysis assessing the perioperative,functional and oncological outcomes of partial nephrectomy(PN)and radical nephrectomy(RN)for T1b tumours.The primary endpoints were the oncological outcomes.The secondary endpoints were the perioperative and functional outcomes.Methods:A systematic literature review was performed by searching multiple databases through February 2019 to identify eligible comparative studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement.Identified reports were assessed according to the Newcastle-Ottawa Scale for nonrandomized controlled trials.Results:Overall,13 retrospective cohort studies were included in the analysis.Patients undergoing PN were younger(weighted mean difference[WMD]3.49 years,95%confidence interval[CI]5.16 to1.82;p<0.0001)and had smaller masses(WMD0.45 cm,95%CI0.59 to0.31;p<0.0001).There were no differences in the oncological outcome,which was demonstrated by progression-free survival(hazard ratio[HR]0.70;pZ0.22),cancerspecific mortality(HR 0.91;pZ0.57)and all-cause mortality(HR 1.01;pZ0.96).The two procedures were similar in estimated blood loss(WMD16.47 mL;pZ0.53)and postoperative complications(risk ratio[RR]1.32;pZ0.10),and PN provided better renal function preservation and was related to a lower likelihood of chronic kidney disease onset(RR 0.38;pZ0.006).Conclusion:PN is an effective treatment for T1b tumours because it offers similar surgical morbidity,equivalent cancer control,and better renal preservation compared to RN.

Clinical assessment and genomic landscape of a consanguineous family with three Kallmann syndrome descendants

Although some genes that cause Kallmann syndrome （KS） have been identified by traditional linkage analysis and candidate gene techniques, the syndrome＇s molecular etiology in the majority of patients remains poorly understood. In this paper, we present the clinical assessments of a consanguineous Hart Chinese family with three KS descendants. To understand the molecular etiology of KS from a genome-wide perspective, we investigated the genome-wide profile of structural variation in this family using the Affymetrix Genome-Wide Human SNP Array 6.0 platform. The results revealed that the three affected individuals had common copy number variants （microdeletions） on chromosomes lp21.1, 2q32.2, 8q21.13, 14q21.2 and Xp22.31. Moreover, the copy number variants on Xp22.31 were located in the intron of KAL 1, which causes X-linked KS. Two PCR assays were performed on these regions to validate the results obtained using the chips. In addition, genomic microdeletions in this region were verified in one of 29 Han Chinese sporadic KS cases and one of four other family cases, but not in 26 Han Chinese sporadic normosmic idiopathic hypogonadotropic hypogonadism cases and 100 unrelated Han Chinese normal controls. Our results provide a novel insight into the relative contributions of certain copy number variants to KS＇s molecular etiology and generate a list of interesting candidate regions for further studies.

PTEN induces anoikis through its phosphatase activity in human bladder transitional carcinoma cells BIU-87

Objective:To investigate the effects and mechanisms of tumor suppressor gene PTEN on the induction of anoikis of human bladder transitional carcinoma cells BIU-87.Methods:BIU-87 cells were transfected with GFP plasmids containing wild-type PTEN or phosphatase inactivating mutant PTEN(C124A-PTEN)in vitro.The PTEN expression and the phosphorylation levels of focal adhesion kinase(FAK)and protein kinase B(PKB/Akt)were detected by Western blotting.Flow cytometry assay and laser scanning confocal microscopy were used to analyze apoptosis in adherent and non-adherent cells.Results: Compared with the control group,PTEN expression in the cells transfected with wild-type PTEN increased to 210%–260%, while the phosphorylation level of FAK and Akt decreased 59%(P<0.01)and 89%(P<0.01),respectively.And the anoikis percentage increased from 8.32±0.57%to 37.62±2.12%.In the cells transfected with C124A-PTEN,neither the phos- phorylation of FAK and Akt nor the anoikis percentage had obviously changed,although the PTEN expression enhanced remarkably in comparison with the control.Conclusion:Through its phosphatase activity,tumor suppressor gene PTEN can suppress the phosphorylation of FAK and Akt,and induce anoikis in human bladder transitional carcinoma cells BIU-87.

Metformin suppresses calcium oxalate crystal-induced kidney injury by promoting Sirt1 and M2 macrophage-mediated anti-inflammatory activation

Dear Editor,Kidney stones are one of the most common clinical diseases in urology.Approximately 80%of renal calculi are composed of calcium oxalate(CaOx)crystals,which are gradually deposited in the medullary collecting duct or in the renal interstitium,causing nephrocalcinosis.1 Although CaOx nephrocalcinosis is usually asymptomatic.

Junction plakoglobin regulates and destabilizes HIF2α to inhibit tumorigenesis of renal cell carcinoma

Background:Increased hypoxia-inducible factor 2α(HIF2α)activation is a common event in clear cell renal cell carcinoma(ccRCC)progression.However,the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated.We conducted this study to access the potential link between junction plakoglobin(JUP)and HIF2αin ccRCC.Methods:Affinity purification and mass spectrometry(AP-MS)screening,glutathione-s-transferase(GST)pull-down and co-immunoprecipitation(Co-IP)assays were performed to detect the interacting proteins of HIF2α.Quantitative PCR(qPCR)and Western blotting were used to detect the expression of JUP in human ccRCC samples.Luciferase reporter assays,chromatin immunoprecipitation(ChIP),cycloheximide chase assays,and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α.Cell Counting Kit-8(CCK-8)assays,colony formation assays,transwell assays,and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells.Results:We identified JUP as a novel HIF2α-binding partner and revealed an important role of JUP in recruiting von Hippel-Lindau(VHL)and histone deacetylases 1/2(HDAC1/2)to HIF2α to regulate its stability and transactivation.JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo.Importantly,the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes.Conclusion:Taken together,these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.

A giant Müllerian duct cyst in the perineum:a case report

The authors present a case report of a giant Müllerian duct cyst in the perineum.A 37-year-old man presented with a mass with the size of 50 cm×40 cm×30 cm in the perineum.Computed tomography(CT)scan and magnetic resonance imaging(MRI)of the pelvis and perineum found a huge multilocular cystic mass.X-ray film of the pelvis showed a giant soft-tissue shadow of high density in the perineum.Voiding cystourethrogram did not show any cyst interlinked to posterior urethra.After related examinations,the patient underwent open surgical resection of the cyst.Pathologic examination confirmed the presence of a Müllerian duct cyst.Huge Müllerian duct cyst is uncommon in clinic.Treatments of Müllerian duct cysts depend on their sizes and symptoms.