[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Is prostate biopsy necessary before radical prostatectomy? New concept and clinical practice].

The current diagnosis and treatment concept of prostate cancer is that if prostate cancer is suspected through one or more examination methods, prostate biopsy should be performed to confirm the diagnosis of prostate cancer and then subsequent treatment should be given. Nowadays, the application of multi-parameter magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) PET/CT has further improved the imaging diagnosis of prostate cancer, and the diagnostic accuracy of clinically significant prostate cancer has reached almost 100%. In addition, minimally invasive techniques represented by robot-assisted laparoscopic surgery have developed rapidly, and the safety and postoperative recovery of radical prostatectomy have been significantly improved. Therefore, we proposed the concept of radical prostatectomy avoiding biopsy (RPAB), that is, the patients with high suspicion of prostate cancer by multi-parameter MRI and PSMA PET/CT can be directly treated by radical surgery. Preliminary clinical practice confirmed that this concept is feasible. However, RPAB is not suitable for all prostate cancer patients, and any new concept needs to be supported by long-term and high-quality clinical studies. We predict that RPAB will become a new clinical option and produce good economic and social benefits.

[China guideline for the screening and early detection of prostate cancer (2022, Beijing)].

Prostate cancer (PC) is one of the malignant tumors of the genitourinary system that occurs more often in elderly men. Screening, early diagnosis, and treatment of the PC high risk population are essential to improve the cure rate of PC. The development of the guideline for PC screening and early detection in line with epidemic characteristics of PC in China will greatly promote the homogeneity and quality of PC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. This guideline strictly followed the World Health Organization Handbook for Guideline Development and combined the most up-to-date evidence of PC screening, China's national conditions, and practical experience in cancer screening. A total of fifteen detailed evidence-based recommendations were provided with respect to the screening population, technology, procedure management, and quality control in the process of PC screening. This guideline aimed to standardize the practice of PC screening and improve the effectiveness and efficiency of PC prevention and control in China.

[The preliminary clinical study on radical prostatectomy without preoperative prostate biopsy].

Objective: To investigate the feasibility and safety of minimally invasive radical prostatectomy for prostate cancer patients without preoperative prostate biopsy in the new era of the continuous development of comprehensive new imaging diagnostic mode and minimally invasive surgery technology. Methods: From August 2018 to October 2019, 17 patients with prostate cancer were enrolled in this study in the Cancer Hospital, Chinese Academy of Medical Sciences. All patients were highly suspected of prostate cancer by PSMA-PET/CT-based imaging diagnostic techniques and underwent 3D laparoscopic radical prostatectomy without prostate biopsy. The perioperative data, postoperative pathology, postoperative complications and follow-up results were recorded and analyzed. Results: The average age of 17 patients with prostate cancer was (65±7) years. The body mass index (BMI) average was (24.4±3.0) kg/m(2). The American Society of Anesthesiologists (ASA) score was 1 (1-2) and the Charlson comorbidity index (CCI) score was 1 (0-4). The preoperative value of PSA was (19±11) µg/L. The PSMA PET/CT showed abnormally high expression foci and the great possibility of prostate cancer for all the 17 patients. Prostate puncture biopsy: the results of prostate biopsy were negative in 3 cases. The digital rectal examination found that the prostate volume was Ⅰ or Ⅱ degree large, 10 cases touched hard and the nodule was touched in two cases. Three patients had undergone a previous prostate biopsy, but prostate cancer was not found. All the 17 operations were successfully performed without conversion to open surgery. The surgery time was (85±21) (range from 45 to 120) min, the estimated blood loss was (25±18) (range from5 to 100) ml, the time of intake of liquid diet was (14.3±4.4) h, the intestinal recovery time was (23±10) h, the postoperative activity time was (22±7) h, the drainage duration was (3.7±0.8) d, the postoperative hospital stay was (4.9±1.2) days, and the catheter removal time was (7.4±1.5) days. In the early postoperative period (within 30 days after surgery), no obvious complications occurred. The postoperative final pathology confirmed that all the 17 specimens were prostate cancer. After a median follow-up of 6.5 months, the patient's urinary control rate reached 81.3% at postoperative 1 month, 92.3% at postoperative 3 months after surgery, and the urinary control rate reached 100% at postoperative 6 months. Postoperative PSA value was (0.08±0.08) µg/L, significantly lower than preoperative PSA level (P<0.001). There was significant difference between the preoperative and postoperative QOL (Quality of life) score (57±5 and 47±5 respectively, P<0.001) which indicated that the patients' postoperative quality of life was greatly improved. Conclusions: It is safe and feasible to perform minimally invasive radical prostatectomy without preoperative prostate biopsy for patients with highly suspected prostate cancer by comprehensive diagnostic mode based on modern new imaging technology.

[Application of Endo-GIA stapler in laparoscopic radicalcystectomy].

Objective: To explore the application of Endo-GIA stapler in laparoscopic radical cystectomy, especially in the treatment of lateral bladder ligament, and to evaluate its clinical feasibility and practicability. Methods: A retrospective analysis of clinical data about 38 cases of laparoscopic radical cystectomy (LRC) treated in the Department of Urology, Chaoyang Hospital of Beijing and Cancer Hospital, Chinese Academy of Medical Sciences from July 2017 to June 2019 were conducted. The patients were divided into Endo-GIA stopler group(18 cases) and non-Endo-GIA stopler group (20 cases) according to whether Endo-GIA stapler were used. The basic clinical data, operation time of bladder lateral ligament, operation time of bladder lateral wall, operation time of bladder resection, amount of bleeding during operation, pathological data after operation and related indicators of recovery after operation were compared between the two groups. Results: All 38 patients underwent radical cystectomy (RC) successfully under 3-D laparoscopy without conversion to open surgery. The operation time of bladder lateral ligament in Endo-GIA stapler group was significantly shorter than that in non-Endo-GIA stapler group [(3.25±0.75) min vs (9.20±2.95) min, P=0.042]; the operation time of bladder lateral wall in Endo-GIA stapler group was significantly shorter than that in non-Endo-GIA stapler group [(8.06±1.66) min vs (14.30±3.37) min, P=0.016]. The operation time of cystectomy in the Endo-GIA stapler group was significantly shorter than that in the non-Endo-GIA stapler group [(47.06±4.70) min vs (61.60±14.91) min,P=0.003]. The amount of bleeding in the Endo-GIA stapler group was significantly shorter than that in the non-Endo-GIA stapler group [(37.77±21.30) ml vs (114.50±39.80) ml, P=0.015]. The time of drainage tube removal in Endo-GIA group was significantly shorter than that in the non-Endo-GIA group [(5.83±1.54) d vs (7.30±3.00) d, P=0.002]. The length of post-hospitalization in Endo-GIA group was significantly shorter than that in the non-Endo-GIA group [(7.67±1.78) d vs (9.60±3.25) d,P=0.036]. However, there was no significant difference in other basic clinical data, post-operative pathology and post-operative recovery related indicators. Conclusions: Laparoscopic radical cystectomy using Endo-GIA stapler device is safe and feasible. It is easy to operate, shorten the operation time significantly, and reduce the amount of bleeding. To a certain extent, it is conducive to the recovery of patients after operation to some extent, and worthy of clinical application.

[The role of Wnt/ß-catenin/TCF-4 pathway on biological behavior of renal cell carcinoma and its mechanism].

Objective: To investigate the role of Wnt/ß-catenin/TCF-4 pathway in renal cancer cells and to analyze its possible mechanism. Methods: ß-catenin and TCF-4 were inhibited by siRNA in 786-O cells. The proliferation of transfected cells was detected by CCK8. The cell death of transfected cells was detected by acridine orange -ethidium bromide staining. The expressions of TCF-4, bcl-2, bax and Caspase-3 were detected in transfection group, empty vector group and negative control groups by western blot. Results: The cell proliferation ability of the ß-catenin transfection group was significantly lower than that of the control group (0.443±0.145 vs 0.910±0.721), meanwhile, the cell death rate was significantly increased (16.38±5.32 vs 6.61±1.04), the expression level of Caspase 3 and bax was increased, and the expression of anti-apoptotic protein Bcl-2 was decreased. Decreased TCF-4 led to the same results as inhibition of ß-catenin (all P<0.05). Conclusion: The Wnt/ß-catenin/TCF-4 pathway may play a role in the regulation of proliferation and apoptosis in 786-O renal cancer cells. The mechanism might through regulating of the downstream apoptosis proteins Caspase 3, bax and anti-apoptotic protein Bcl-2.

[Clinical experiences of laparoscopic radical cystectomy and urinary diversion in the elderly patients with bladder cancer].

Objective: To optimize the surgical procedures of laparoscopic radical cystectomy and urinary diversion for the elderly patients with bladder cancer, generalize operating technique, summarize clinical experiences. Methods: From July 2004 to October 2016, laparoscopic radical cystectomy (LRC) and urinary diversion was performed in 68 elderly patients (≥75 years old) diagnosed with bladder cancer in urology department of Beijing Chaoyang Hospital, Capital Medical University, and the relevant clinical and follow-up data were retrospectively reviewed. All the patients were pathologically diagnosed and their perioperative data, postoperative pathological results, postoperative complications and follow-up outcomes were recorded and analyzed. Results: Among 68 elderly patients with bladder cancer, fifty patients were male and 18 were female, the age of whom were (79±4) (range 75 to 91) years old. The Charlson comorbidity index (CCI) score was 6±1 (range 5 to 7). All the 68 operations were successfully performed without conversion to open surgery. There were 26 cases receiving cutaneous ureterostomy, 34 cases receiving ileal conduit (intracorporeal for 16 cases and extracorporeal for 18 cases) and 8 cases receiving orthotopic ileal neobladder (intracorporeal for 4 cases and extracorporeal for 4 cases; Xing's technique for 4 cases, T-Pouch for 2 cases and Studer-Pouch for 2 cases) respectively, and the operation time of these three groups were (221±47) min, (315±70) min and (358±90) min respectively, the estimated blood loss were 100 (87, 200)ml, 300 (250, 500) ml and 250 (113, 725) ml respectively, the time of intake of liquid diet were 3 (2, 4) d, 6 (5, 7) d and 9 (5, 12) d respectively, and the postoperative hospital stay were (12±6) d, (24±11) d, and (27±11) d respectively. Postoperative pathological results showed urothelial carcinoma in 64 patients, squamous cell carcinoma in 2 patients and adenocarcinoma in 2 patients. Sixty patients received laparoscopic pelvic lymphadenectomy and the number of dissected lymph nodes was 17.1±7.0. There were 46 cases with T stage greater than or equal to T2 (46/68, 67.6%), 4 cases of low grade (4/68, 5.9%) and 60 cases of high grade (60/68, 88.2%). All the early postoperative (within 30 days after the operation) complications were grade Ⅰ-Ⅱ mainly manifested as fever, pain and infection that could get better with symptomatic treatment, and the incidence rate were 30.8% for cutaneous ureterostomy, 29.4% for ileal conduit and 37.5% for orthotopic ileal neobladder. The patients were followed up for a median period of 93.5 months without obvious hydronephrosis and impaired renal function. The 5-year cancer specific survival rate and overall survival rate were 57% and 50% respectively. There was significant difference between the preoperative and postoperative QOL (quality of life) score (56.0±10.0 and 47.4±5.8 respectively, P<0.05) which indicated that the patients' postoperative quality of life was greatly improved. Conclusions: Laparoscopic radical cystectomy and urinary diversion for the elderly patients with bladder cancer is safe and feasible, and owns great therapeutic value.

[Clinical analysis of 8 cases of the mixed epithelial and stromal tumour family of kidney].

Objective: To investigate the diagnosis and treatment of the mixed epithelial and stromal tumour family of kidney. Methods: Eight cases of the mixed epithelial and stromal tumour family of kidney were retrospectively analyzed. Before operation, radiologic evaluation was performed in all cases, including CT and MRI scan. Three cases were diagnosed as cystic renal cell carcinoma, 5 cases were diagnosed as renal complex cysts. Radical nephrectomy was performed in 4 cases and partial nephrectomy was performed in 4 cases. Results: The manifestation of the pathological specimens were multilocular cystic or cystic solid tumors grossly. Microscopically, the tumors were composed of two components, epithelial and stromal. Immunohistochemical staining showed that the epithelial components of the tumors were positive for AE1/AE3 (8/8), CK18 (3/3), and CK-7 (1/1). The stromal components were positive for PR (8/8), ER (6/8), Vim (6/6), Desmin (5/5), and SMA (5/5). HB-45 staining were negative (7/7) and Ki-67 staining were negative (7/8). All cases were diagnosed as the mixed epithelial and stromal tumour family of kidney. All patients were followed up for 3-124 months, with a median follow-up of 41 months. No tumour recurrence or metastasis were observed. Conclusion: The mixed epithelial and stromal tumour family of kidney mostly occurs in women, but have no specific clinical manifestations. They were often misdiagnosed as cystic renal cell carcinoma before operation. These following imaging features may be helpful for diagnosis. The definite diagnosis of the disease depends on the pathological examination, and immunohistochemistry plays an important role in differential diagnosis. Surgical treatment is the first choice, and partial nephrectomy is feasible. Most of the tumors are benign, and the patients can be cured after complete excision.

[Effect of 2-methoxyestradiol combined with quercetin on prostate cancer in vitro].

OBJECTIVE: To detect the effects of quercetin (Que) combined with 2-methoxyestradiol (2-ME) on the proliferation of androgen-dependent LNCaP human prostate cancer cells line and androgen-independent PC-3 human prostate cancer cells line, and to evaluate the antitumor effects of different combos of the two drugs. METHODS: After LNCaP and PC-3 cells were treated with different concentration of quercetin (0, 3.125, 6.25, 12.5, 25, 50, 100, 200 µmol/L) or 2-ME (0, 0.312 5, 0.625, 1.25, 2.5, 5, 10 µmol/L) for 48 h, the inhibitory rates of cell growth were tested using trypan blue staining method respectively. Then the concentration-effect curves were drawn and IC(50) values were calculated. According to the fitted dose-effect curves and IC(50) values, appropriate concentrations of quercetin and 2-ME were selected to compose 16 different combos. Then cells were treated with different combos of Que and 2-ME for 48 h, and then the growth inhibitory rates of cell growth were detected. According to the equation and median-effect principle, the CI values of 16 different combos of Que and 2-ME were calculated to evaluate their antitumor effects. RESULTS: The inhibition rate of LNCaP or PC-3 cell growth treated with varying doses of quercetin or 2-ME alone showed a dose-dependent increase respectively. The IC(50) values of quercetin and 2-ME were 23.29 µmol/L and 1.89 µmol/L for LNCaP cells; and 22.12 µmol/L and 1.74 µmol/L for PC-3 cells respectively. After treated with 16 combos of Que (5, 10, 20, 40 µmol/L) and 2-ME (0.5, 1, 3, 5 µmol/L) for 48 h, for LNCaP cells, lower dose of Que (5 and 10 µmol/L) with higher dose of 2-ME (3 and 5 µmol/L) showed synergistic activity, whereas for PC-3 cells, besides the above combination of Que 10 µmol/L and 2-ME 3 µmol/L, higher dose of quercetin (20 and 40 µmol/L) with higher dose of 2-ME (3 and 5 µmol/L) also showed synergistic activity. CONCLUSIONS: Both quercetin and 2-methoxyestradiol could inhibit the growth of LNCaP and PC-3 human prostate cancer cells in a dose dependent manner. We confirmed that combinations of quercetin and 2-ME at appropriate concentrations have the potential for synergetic antiproliferative activity in vitro.

Unilateral perirenal fibrosis without aorta involvement.

Retroperitoneal fibrosis (RPF) located unilateral perirenal without aorta involvement is very rare. We report a case of unilateral perirenal fibrosis which was misdiagnosed as malignancy even after biopsy. RPF should be in mind in dealing with perirenal mass.

Sildenafil citrate treatment for erectile dysfunction after kidney transplantation.

OBJECTIVE: Our goal was to analyze the morbidity of organic erectile dysfunction (ED) in kidney-transplant patients and to evaluate the efficacy and reliability of sildenafil citrate treatment. METHOD: Sixty-five ED patients with normal graft function for 3 to 12 months after kidney transplantation were involved in our study. Erectile dysfunction was diagnosed in all the patients by the International Index of Erectile Dysfunction (IIEF). Among them, 10 patients were in light degree; 32 patients in moderate degree, and 23 patients in severe degree according to IIEF score. All of the patients underwent medical history, physical and chemical examinations. In each patient, the IIEF score, blood urea nitrogen, creatinine, and trough concentrations of cyclosporine were compared before and after taking sildenafil citrate at an initial dose of 50 mg every night. RESULTS: Twenty-six patients without ED before transplantation suffered ED after the operation, and 32 patients with ED before transplantation noticed worsening. Taking sildenafil citrate was effective in 53 patients (81.54%). There were no statistical differences in blood urea nitrogen, creatinine, or trough concentrations of cyclosporine in patients before and after sildenafil treatment. CONCLUSIONS: The morbidity of organic erectile dysfunction increased after transplantation. Sildenafil citrate treatment for ED in kidney-transplant patients was effective and safe. Graft function and trough concentrations of cyclosporine were not affected by sildenafil citrate.