The effect of bladder function on the efficacy of transurethral prostatectomy in patients with benign prostatic hyperplasia:a retrospective,single-center study

We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia(BPH)on the efficacy of transurethral prostatectomy.Symptomatic,imaging,and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University(Chengdu,China)from July 2019 to December 2021 were collected.Follow-up data included the quality of life(QoL),International Prostate Symptom Score(IPSS),and IPSS storage and voiding(IPSS-s and IPSS-v).Moreover,urinary creatinine(Cr),nerve growth factor(NGF),brain-derived neurotrophic factor(BDNF),and prostaglandin estradiol(PGE2)were measured in 30 patients with BPH and 30 healthy participants.Perioperative indicators were determined by subgroup analyses and receiver operating characteristic(ROC)curve analysis.Among the 313 patients with BPH included,patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms.Similarly,good bladder sensation,compliance,and detrusor contractility(Dc)were predictors of low postoperative IPSS and QoL.The urinary concentrations of BDNF/Cr,NGF/Cr,and PGE2/Cr in patients were significantly higher than those in healthy participants(all P<O.oo1).After evaluation,only DC was significantly related to both urinary indicators and postoperative recovery of patients.Patients with good DC,as predicted by urinary indicators,had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively(both P<0.05).In summary,patients with impaired bladder function had poor recovery.The combined levels of urinary BDNF/Cr,NGF/Cr,and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladderfunction and postoperative recovery.

ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression

Background Cell metabolism plays a pivotal role in tumor progression,and targeting cancer metabolism might effectively kill cancer cells.We aimed to investigate the role of hexokinases in prostate cancer(PCa)and identify a crucial target for PCa treatment.Methods The Cancer Genome Atlas(TCGA)database,online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase(ADPGK)in PCa.The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo.Quantitative proteomics,metabolomics,and extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)tests were performed to evaluate the impact of ADPGK on PCa metabolism.The underlying mechanisms were explored through ADPGK overexpression and knockdown,co-immunoprecipitation(Co-IP),ECAR analysis and cell counting kit-8(CCK-8)assays.Results ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival(OS)in prostate adenocarcinoma(PRAD).Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs.non-PCa tissues.High ADPGK expression indicates worse survival outcomes,and ADPGK serves as an independent factor of biochemical recurrence.In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration,and ADPGK inhibition suppressed malignant phenotypes.Metabolomics,proteomics,and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa.Mechanistically,ADPGK binds aldolase C(ALDOC)to promote glycolysis via AMP-activated protein kinase(AMPK)phosphorylation.ALDOC was positively correlated with ADPGK,and high ALDOC expression was associated with worse survival outcomes in PCa.Conclusions In summary,ADPGK is a driving factor in PCa progression,and its high expression contributes to a poor prognosis in PCa patients.ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling,suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.

The preoperative serum cystatin-C as an independent prognostic factor for survival in upper tract urothelial carcinoma

Cystatin-C(Cys-C)has been reported as a valuable prognostic biomarker in various malignancies.However,its effect on upper tract urothelial carci noma(UTUC)patie nts has not bee n investigated before.Thus,to explore the impact of Cys-C on survival outcomes in patients undergoing radical nephroureterectomy(RNU),a total of 538 patients with UTUC who underwent RNU between 2005 and 2014 in our center(West China Hospital,Chengdu,China)were included in this study.Kaplan-Meier method and Cox regressi on an a lyses were performed to assess the relationship betwee n Cys-C and survival outcomes using SPSS versi on 22.0.The cutoff value of Cys-C was set as 1.4 mg I1 using the receiver operating characteristic(ROC)curves and Youden index.The mean age of patients included was 66.1±11.1 years,and the media n follow-up durati on was 38(interquartile ran ge:19-56)mon ths.Overall,162(30.1%)patients had elevated Cys-C,and they were much older and had worse renal function than those with Cys-C<1.4 mg I^-1(both P<0.001).Meanwhile,Kaplan-Meier analysis revealed that the group with elevated Cys-C had worse cancer-specific survival(CSS,P=0.001),disease recurrence-free survival(RFS,P=0.003),and overall survival(OS,P<0.001).Multivariable Cox analysis suggested that the elevated Cys-C was identified as an independent prognostic predictor of CSS(hazard ratio[HR]:1.997,95%confidential interval[CI]:1.331-2.996),RFS(HR:1.429,95%CI:1.009-2.023),and OS(HR:1.989,95%CI:1.366-2.896).In conclusion,our result revealed that the elevated preoperative serum Cys-C was significantly associated with worse outcomes in UTUC patients undergoing RNU.

Neoadjuvant chemotherapy for patients with locally advanced penile cancer:an updated evidence

Neoadjuvant chemotherapy(NAC)has shown promising results in patients with locally advanced penile cancer.However,no consensus exists on its applications for locally advanced penile cancer.Thus,it is unclear which kind of chemotherapy regimen is the best choice.Consequently,a systematic search of PubMed,Web of Science,and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer.The Newcastle–Ottawa Scale was used to assess the risk of bias in each study.This study synthesized 14 published studies.The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response.In addition,the objective response rates(ORRs)and pathological complete response(pCR)rates were 0.57 and 0.11,respectively.The incidence of grade≥3 toxicity was 0.36.Subgroup analysis found that the ORR and pCR of the taxane–platinum(TP)regimen group performed better than those of the nontaxane–platinum(NTP)regimen group(0.57 vs 0.54 and 0.14 vs 0.07,respectively).Moreover,the TP regimen group had more frequent toxicity than the NTP regimen group(0.41 vs 0.26).However,further studies were warranted to confirm the findings.

Pretreatment elevated fibrinogen level predicts worse oncologic outcomes in upper tract urothelial carcinoma

This study aimed to further validate the prognostic role of fibrinogen in upper tract urothelial carcinoma(UTUC)in a large Chinese cohort.A total of 703 patients who underwent radical nephroureterectomy were retrospectively identified.Fibrinogen levels of≥4.025 g l?1 were defined as elevated.Logistic regression analysis was performed to determine the association between fibrinogen and adverse pathological features.Kaplan–Meier analysis and Cox regression models were used to assess the associations of fibrinogen with cancer-specific survival(CSS),disease recurrence-free survival(RFS),and overall survival(OS).Harrell c-index and decision curve analysis were used to assess the clinical utility of multivariate models.The median follow-up duration was 42(range:1–168)months.Logistic regression analysis revealed that elevated fibrinogen was associated with higher tumor stage and grade,lymph node involvement,lymphovascular invasion,sessile carcinoma,concomitant variant histology,and positive surgical margins(all P<0.05).Multivariate Cox regression analysis demonstrated that elevated fibrinogen was independently associated with decreased CSS(hazard ratio[HR]:2.33;P<0.001),RFS(HR:2.09;P<0.001),and OS(HR:2.09;P<0.001).The predictive accuracies of the multivariate models were improved by 3.2%,2.0%,and 2.8%for CSS,RFS,and OS,respectively,when fibrinogen was added.Decision curve analysis showed an added benefit for CSS prediction when fibrinogen was added to the model.Preoperative fibrinogen may be a strong independent predictor of worse oncologic outcomes in UTUC;therefore,it may be valuable to apply this marker to the current risk stratification in UTUC.

Tumor microenvironment-based drug discovery:a novel insight into bladder cancer immunotherapy

Tb the Editor:Bladder cancer(BCa)is one of the most common urological malignant tumors.With a worldwide incidence of 573,278 cases in 2020,it ranks eleventh among all tumors.Despite having different approved immune checkpoint inhibitors for use among patients with BCa,the response rate to those drugs has remained limited,varying from 20%to 40%.