BACKGROUND Routinely, after receiving prostate specific antigen (PSA) testing and digital rectum examination, patients with suspected prostate cancer are required to undergo prostate biopsy. However, the ability of ul...BACKGROUND Routinely, after receiving prostate specific antigen (PSA) testing and digital rectum examination, patients with suspected prostate cancer are required to undergo prostate biopsy. However, the ability of ultrasound-guided prostate biopsy to detect prostate cancer is limited. Nowadays, a variety of diagnostic methods and more sensitive diagnostic methods, such as multi-parameter prostate magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) can be applied clinically. Furthermore, laparoscopic/robot-assisted prostatectomy is also a safe and effective procedure for the treatment of benign prostatic hyperplasia. So maybe it is time to reconsider the necessary to perform prostate biopsy before radical prostatectomy. AIM To explore the feasibility of radical prostatectomy without prostate biopsy in the era of new imaging technology and minimally invasive techniques. METHODS From June 2014 to November 2018, 11 cases of laparoscopic radical prostatectomy without prostate biopsy were performed at the three tertiary medical centers involved in this study. All patients received prostate magnetic resonance imaging and prostate cancer was suspected, including six patients with positive 68Ga- PSMA PET/CT results. Laparoscopic radical prostatectomy and pelvic lymph node dissection were performed for all patients. RESULTS All surgeries were accomplished successfully. The mean age was 69 ± 7.7 year, the mean body mass index was 24.7 ± 1.6 kg/m2, the range of serum PSA was 4.3 to >1000 ng/mL, and the mean prostate volume was 40.9 ± 18.3 mL. The mean operative time was 96 ± 23.3 min, the mean estimated blood loss was 90 ± 90.9 mL, and the median duration of catheter placement was 14 d. The final pathology confirmed that all specimens were prostate cancer except one case of benign prostatic hyperplasia. No major complications occurred in 90 d postoperatively. CONCLUSION The current practice of mandating a prostatic biopsy before prostatectomy should be reconsidered in the era of new imaging technology and minimally invasive techniques. Radical prostatectomy could be carried out without the evidence of malignancy. Large-sample randomized controlled trials are definitely required to confirm the feasibility of this new concept.展开更多
Castration-resistant prostate cancer demonstrates intrinsic or acquired resistance to second-generation androgen-targeted therapies,posing a challenge in clinical treatment.In this study,on the basis of in vivo self-a...Castration-resistant prostate cancer demonstrates intrinsic or acquired resistance to second-generation androgen-targeted therapies,posing a challenge in clinical treatment.In this study,on the basis of in vivo self-assembly nanotechnology,we designed a PSMA-targeted nano-PROTAC with a proximity degradation effect.Nano-PROTAC not only precisely degrades the AR receptor but also cleverly degrades the HSP90 that is closely bound to the AR receptor,utilizing the spatial distance self-adaptive characteristics of its nanostructure.In the 22Rv1 cell model,Nano-PROTAC degraded 80%of the AR protein and 65%of the HSP90 protein.More importantly,nano-PROTAC could degrade 74%of the AR splice variant AR-V7 protein,showing the potential ability to overcome drug resistance.We further constructed an enzalutamide-resistant xenograft tumor mouse model to evaluate the therapeutic effect of the Nano-PROTAC.Compared with the combination treatment group of AR and HSP90 inhibitors(enzalutamide and pimitespib),the nano-PROTAC treatment group presented a high tumor growth inhibition value of up to 78%and a median survival extension of 15 days.Nano-PROTACs that simultaneously degrade AR and HSP90 can overcome the resistance of prostate cancer to PSMA-and AR-positive castration-resistant prostate cancer,except for neuroendocrine prostate cancer,which provides a new therapeutic strategy for the treatment of prostate cancer.展开更多
Background： Robot-assisted/laparoscopic intracorporeal ileal conduit （ICIC） has been reported in many experienced centers. Whether laparoscopic ICIC is superior to extracorporeal ileal conduit （ECIC） and whether ...Background： Robot-assisted/laparoscopic intracorporeal ileal conduit （ICIC） has been reported in many experienced centers. Whether laparoscopic ICIC is superior to extracorporeal ileal conduit （ECIC） and whether laparoscopic ICIC should be promoted is still controversial. The aim of the study was to compare surgical and early oncological outcomes between patients undergoing laparoscopic radical cystectomy （LRC） with ICIC and ECIC. Methods： From January 2011 to June 2016, a total of 45 patients with bladder cancer underwent LRC with ileal conduit at our department, of whom 20 patients underwent LRC with ECIC and 25 patients underwent LRC with ICIC. Data of each patient＇s characteristics, surgical outcomes, and short-term oncological outcomes were collected and analyzed. Results： LRC with ileal conduit was performed successfully on all 45 patients. There were no significant differences in patients＇ characteristics, mean total operative time, and mean estimated blood loss between the ICIC and ECIC groups. Median time of flatus and oral intake was shorter in the ICIC group compared with the ECIC group （3 vs. 5 days, P = 0.035; 4 vs. 5 days, P = 0.002）. The complications rates did not show significant difference between the two groups within the first 90 days postoperatively （P = 0.538）. Cancer staging showed 45% of patients in the ECIC group and 36% in the ICIC group had a pathologic stage of T3 or T4, and 50% of patients in the ECIC group and 44% in the ICIC group had a pathologic stage of N1 or N1＋. Kaplan-Meier analysis showed no significant difference in overall survival at 24 months （60% vs. 62%, P = 0.857） between the ECIC and ICIC groups. Conclusions： ICIC after LRC may be successful with the benefits of faster recovery time. No significant difference was found in complications and oncological outcomes between ICIC and ECIC. However, larger series with longer follow-up are needed to validate this procedure.展开更多
文摘BACKGROUND Routinely, after receiving prostate specific antigen (PSA) testing and digital rectum examination, patients with suspected prostate cancer are required to undergo prostate biopsy. However, the ability of ultrasound-guided prostate biopsy to detect prostate cancer is limited. Nowadays, a variety of diagnostic methods and more sensitive diagnostic methods, such as multi-parameter prostate magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) can be applied clinically. Furthermore, laparoscopic/robot-assisted prostatectomy is also a safe and effective procedure for the treatment of benign prostatic hyperplasia. So maybe it is time to reconsider the necessary to perform prostate biopsy before radical prostatectomy. AIM To explore the feasibility of radical prostatectomy without prostate biopsy in the era of new imaging technology and minimally invasive techniques. METHODS From June 2014 to November 2018, 11 cases of laparoscopic radical prostatectomy without prostate biopsy were performed at the three tertiary medical centers involved in this study. All patients received prostate magnetic resonance imaging and prostate cancer was suspected, including six patients with positive 68Ga- PSMA PET/CT results. Laparoscopic radical prostatectomy and pelvic lymph node dissection were performed for all patients. RESULTS All surgeries were accomplished successfully. The mean age was 69 ± 7.7 year, the mean body mass index was 24.7 ± 1.6 kg/m2, the range of serum PSA was 4.3 to >1000 ng/mL, and the mean prostate volume was 40.9 ± 18.3 mL. The mean operative time was 96 ± 23.3 min, the mean estimated blood loss was 90 ± 90.9 mL, and the median duration of catheter placement was 14 d. The final pathology confirmed that all specimens were prostate cancer except one case of benign prostatic hyperplasia. No major complications occurred in 90 d postoperatively. CONCLUSION The current practice of mandating a prostatic biopsy before prostatectomy should be reconsidered in the era of new imaging technology and minimally invasive techniques. Radical prostatectomy could be carried out without the evidence of malignancy. Large-sample randomized controlled trials are definitely required to confirm the feasibility of this new concept.
基金supported by the National Natural Science Foundation of China(52322308,52273126)the National Key R&D Program of China(2022YFA1205700,2022YFE0200800)the Beijing Nova Program(20240484673,20230484237).
文摘Castration-resistant prostate cancer demonstrates intrinsic or acquired resistance to second-generation androgen-targeted therapies,posing a challenge in clinical treatment.In this study,on the basis of in vivo self-assembly nanotechnology,we designed a PSMA-targeted nano-PROTAC with a proximity degradation effect.Nano-PROTAC not only precisely degrades the AR receptor but also cleverly degrades the HSP90 that is closely bound to the AR receptor,utilizing the spatial distance self-adaptive characteristics of its nanostructure.In the 22Rv1 cell model,Nano-PROTAC degraded 80%of the AR protein and 65%of the HSP90 protein.More importantly,nano-PROTAC could degrade 74%of the AR splice variant AR-V7 protein,showing the potential ability to overcome drug resistance.We further constructed an enzalutamide-resistant xenograft tumor mouse model to evaluate the therapeutic effect of the Nano-PROTAC.Compared with the combination treatment group of AR and HSP90 inhibitors(enzalutamide and pimitespib),the nano-PROTAC treatment group presented a high tumor growth inhibition value of up to 78%and a median survival extension of 15 days.Nano-PROTACs that simultaneously degrade AR and HSP90 can overcome the resistance of prostate cancer to PSMA-and AR-positive castration-resistant prostate cancer,except for neuroendocrine prostate cancer,which provides a new therapeutic strategy for the treatment of prostate cancer.
文摘Background： Robot-assisted/laparoscopic intracorporeal ileal conduit （ICIC） has been reported in many experienced centers. Whether laparoscopic ICIC is superior to extracorporeal ileal conduit （ECIC） and whether laparoscopic ICIC should be promoted is still controversial. The aim of the study was to compare surgical and early oncological outcomes between patients undergoing laparoscopic radical cystectomy （LRC） with ICIC and ECIC. Methods： From January 2011 to June 2016, a total of 45 patients with bladder cancer underwent LRC with ileal conduit at our department, of whom 20 patients underwent LRC with ECIC and 25 patients underwent LRC with ICIC. Data of each patient＇s characteristics, surgical outcomes, and short-term oncological outcomes were collected and analyzed. Results： LRC with ileal conduit was performed successfully on all 45 patients. There were no significant differences in patients＇ characteristics, mean total operative time, and mean estimated blood loss between the ICIC and ECIC groups. Median time of flatus and oral intake was shorter in the ICIC group compared with the ECIC group （3 vs. 5 days, P = 0.035; 4 vs. 5 days, P = 0.002）. The complications rates did not show significant difference between the two groups within the first 90 days postoperatively （P = 0.538）. Cancer staging showed 45% of patients in the ECIC group and 36% in the ICIC group had a pathologic stage of T3 or T4, and 50% of patients in the ECIC group and 44% in the ICIC group had a pathologic stage of N1 or N1＋. Kaplan-Meier analysis showed no significant difference in overall survival at 24 months （60% vs. 62%, P = 0.857） between the ECIC and ICIC groups. Conclusions： ICIC after LRC may be successful with the benefits of faster recovery time. No significant difference was found in complications and oncological outcomes between ICIC and ECIC. However, larger series with longer follow-up are needed to validate this procedure.
