Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management...Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.展开更多
We evaluated contemporary trends in radical prostatectomy(RP)in men aged>70 years and investigated associations of selected variables with recovery of urinary continence(UC)in two age groups:>70 and<70 years....We evaluated contemporary trends in radical prostatectomy(RP)in men aged>70 years and investigated associations of selected variables with recovery of urinary continence(UC)in two age groups:>70 and<70 years.A retrospective cohort of 2301 eligible patients attending our institution from 2004 to 2015 was reviewed.Patients were divided into two groups based on age at surgery(>70 years[n=610]vs<70 years[n=1691])and four groups by year of surgery.Over the study period,the proportion of patients aged>70 years gradually increased up to 30.0%,and the rate of robot-assisted RP and neurovascular bundle(NVB)saving increased continually to 80.0%and 67.4%of older patients,respectively.Although the rate of recovery of UC within 12 months(3 months)in patients aged>70 years was lower than that in those aged S70 years(81.5%[52.6%]vs 88.6%[60.9%],respectively;both P<0.001),the gap between age groups in the rate of recovery within 12 mon ths n arrowed from the sec ond quarter of the study period.Among youn ger patie nts,age,robot-assisted RP,prostate volume,membra nous urethral length(MUL),and NVB savi ng were predictors of recovery of UC within 3 or 12 months.In contrast,only age and MUL were predictors of recovery of UC within 3 and 12 months in patients aged>70 years.Therefore,unlike younger patients,only variables(age and MUL),possibly associated with the inhere nt fun ction of the urinary sphi ncter,were predictors of recovery of UC in patients aged>70 years.展开更多
Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under reported....Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under reported.To study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic case.The VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)cells.Renal tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic potential.Combined tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic mechanism.The poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+cells.Periostin(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape.Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models.This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.展开更多
基金suppor ted by the National Key Research and Development Plan of China(Technology helps Economy 2020,2016YFC0106300)the National Natural Science Foundation of China(82174230)the Major Program Fund of Technical Innovation Project of Department of Science and Technology of Hubei Province(2016ACAl52)。
文摘Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.
文摘We evaluated contemporary trends in radical prostatectomy(RP)in men aged>70 years and investigated associations of selected variables with recovery of urinary continence(UC)in two age groups:>70 and<70 years.A retrospective cohort of 2301 eligible patients attending our institution from 2004 to 2015 was reviewed.Patients were divided into two groups based on age at surgery(>70 years[n=610]vs<70 years[n=1691])and four groups by year of surgery.Over the study period,the proportion of patients aged>70 years gradually increased up to 30.0%,and the rate of robot-assisted RP and neurovascular bundle(NVB)saving increased continually to 80.0%and 67.4%of older patients,respectively.Although the rate of recovery of UC within 12 months(3 months)in patients aged>70 years was lower than that in those aged S70 years(81.5%[52.6%]vs 88.6%[60.9%],respectively;both P<0.001),the gap between age groups in the rate of recovery within 12 mon ths n arrowed from the sec ond quarter of the study period.Among youn ger patie nts,age,robot-assisted RP,prostate volume,membra nous urethral length(MUL),and NVB savi ng were predictors of recovery of UC within 3 or 12 months.In contrast,only age and MUL were predictors of recovery of UC within 3 and 12 months in patients aged>70 years.Therefore,unlike younger patients,only variables(age and MUL),possibly associated with the inhere nt fun ction of the urinary sphi ncter,were predictors of recovery of UC in patients aged>70 years.
基金supported by the NCI/NIH (grant number 1R21CA216770)Tobacco-Related Disease Research Program (grant number 27IR-0016)+5 种基金CDMRP Kidney Cancer Research Program (grant number W81XWH-20-1-0918)Cancer Research Coordinating Committee (grant number CRC15-380768)2021 Kure It Cancer Research Grant (www.kureit.org) to L.W.UCLA institutional support grants included the UCLA Jonsson Comprehensive Cancer Center (grant number P30CA016042)the UCLA Clinical and Translational Science Institute (grant number UL1TR001881)UCLA 3 R grant (Office of Vice Chancellor of Research) to L.W.UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Research Award Program.
文摘Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under reported.To study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic case.The VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)cells.Renal tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic potential.Combined tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic mechanism.The poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+cells.Periostin(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape.Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models.This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.