Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial / 中华医学杂志(英文版)

BACKGROUND@#LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.@*METHODS@#We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.@*RESULTS@#On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).@*CONCLUSION@#LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04563936.

Identification of risk factors for urethrovesical anastomotic leakage following laparoscopic radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the risk factors of urethrovesical anastomotic leakage after laparoscopic radical prostatectomy.Methods:The clinical data of 292 patients who underwent laparoscopic radical prostatectomy in the Tenth People's Hospital Affiliated to Tongji University from January to December 2021 were retrospectively analyzed. According to whether there was anastomotic leakage, the patients were divided into leakage group (27 cases) and non-leakage group (265 cases). There were no significant differences in age [(71.5±6.5) years vs. (70.2±6.4) years], body mass index [(24.5±3.6) kg/m 2 vs. (24.2±3.0) kg/m 2], prostate volume[40(27.3, 63.2)ml vs. 38(28.1, 56.2)ml], Gleason score, clinical stage, and risk classification between the leakage group and the non-leakage group ( P>0.05), but the total prostate-specific antigen in the leakage group was significantly higher than that in the non-leakage group[20.0 (9.6, 79.0) ng/ml vs. 13.7 (8.5, 25.0) ng/ml, P=0.049]. Propensity score matching (PSM) was used to match the above indicators between the leakage group and the non-leakage group as 1∶1, so that the baseline of the two groups was balanced. The perioperative indicators of the matched two groups of patients were compared and analyzed. Statistically significant indicators were selected and included in univariate and multivariate logistic regression to analyze the risk factors of anastomotic leakage after radical prostatectomy. Finally, the receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated. The accuracy of each factor in predicting urine leakage was obtained. Results:After PSM, 24 cases were successfully matched. The leakage group had shorter membranous urethral length (MUL) [(15.5±2.2)mm vs. (17.5±1.5)mm, P<0.001], thinner membranous urethral wall thickness (UWT) [(9.5±1.9)mm vs. (10.6±1.5)mm, P=0.024], longer anastomotic time of urethrovesical neck[(21.6±4.1)min vs. (16.9±2.9)min, P<0.001] and higher failure rate of water injection test [16.7% (4/24) vs. 4.2% (1/24), P=0.045] than the non-leakage group. There was no significant difference in other indicators between the two groups. The results of multivariate logistic regression analysis showed that short MUL ( OR=0.544, 95% CI 0.335-0.884, P=0.014), narrow UWT ( OR=0.538, 95% CI 0.313-0.924, P=0.025) and long anastomotic time of urethrovesical neck ( OR=1.519, 95% CI 1.122-2.110, P=0.009) were independent risk factors for anastomotic urine leakage. ROC curve analysis showed that the AUC of MUL, UWT, and anastomotic time were 0.789 (95% CI 0.651-0.927), 0.715 (95% CI 0.562-0.868), and 0.842 (95% CI 0.731-0.953), respectively. Conclusions:Narrow and short membranous urethra and long anastomosis time in patients with laparoscopic radical prostatectomy may be independent risk factors for postoperative anastomotic leakage, which may predict the occurrence of anastomotic leakage.

Blood glucose fluctuation and risk factors in type 2 diabetic patients with asymptomatic hypoglycemia / 中华内分泌代谢杂志

Objective:To investigate the characteristics of blood glucose fluctuation and risk factors in type 2 diabetic patients with asymptomatic hypoglycemia.Methods:From September 2018 to July 2021, 342 patients with type 2 diabete mellitus who were hospitalized in the Department of Endocrinology of Hefei Hospital Affilitated to Anhui Medical University were enrolled for a retrospective study. The mean amplitude of glycemic excursions(MAGE), coefficient of variation (CV), 24 hour mean blood glucose level (MG), and time in range (TIR) were obtained by continuous glucose monitoring (CGM). According to the results of CGM and whether the patients have hypoglycemia symptoms, they were divided into three groups: no hypoglycemia group, symptomatic hypoglycemia group, and asymptomatic hypoglycemia group. The differences in blood glucose fluctuations were compared among the three groups. Multivariate logistic regression analysis was used to evaluate the risk factors in type 2 diabete mellitus patients with asymptomatic hypoglycemia. The predictive value of MAGE for asymptomatic hypoglycemia was analyzed by receiver operating characteristic (ROC) curve.Results:Compared with the non-hypoglycemia group, the TIR in asymptomatic hypoglycemia group was higher ( Z=-2.042, P=0.041). The asymptomatic hypoglycemia group had lower MG, higher MAGE and CV compared with the other two groups(all P<0.05). Multivariate logistic regression analysis showed that urinary albumin/creatinine ratio (UACR), MAGE, and CV were the risk factors for asymptomatic hypoglycemia, while MG was the protective factor. After adjustment for other risk factors, MAGE was still associated with asymptomatic hypoglycemia ( OR=1.111, 95% CI 0.999-1.235, P=0.049). The sensitivity and specificity of MAGE in predicting asymptomatic hypoglycemia were 0.769 and 0.776, respectively. Conclusions:Patients with asymptomatic hypoglycemia present with larger TIR and MAGE. MAGE, UACR, and CV were risk factors for asymptomatic hypoglycemia. Moreover, MAGE has some predictive value for the occurrence of asymptomatic hypoglycemia.

A long-term clinical report of a modified unilateral cutaneous ureterostomy in bladder cancer patients receiving radical cystectomy / 中华泌尿外科杂志

Objective:To explore the long-term efficacy of a modified unilateral cutaneous ureterostomy in bladder cancer patients receiving radical cystectomy.Methods:The medical data of 104 bladder cancer patients who underwent ureterostomy in our hospital from Janurary 2013 to December 2020 were retrospectively analyzed. The patients were divided into unilateral and bilateral group. The unilateral group contained 66 cases, with 53 males and 13 females, average age (71.8±9.8) years, body mass index (BMI)(23.3±3.2)kg/m 2. The bilateral group contained 38 cases, with 33 males and 5 females, average age (75.1±10.8) years; BMI (22.7±3.0)kg/m 2. There was no significant difference in the above characteristics between the two groups ( P>0.05). The pathology, survival status, long-term complications between the two groups were compared. Quality of life was assessed during follow-up using the European Core Questionnaire for Quality of Life in Cancer Patients (EORTC QLQ-C30). Results:The unilateral group contained 46(69.7%) muscle invasive bladder cancer (MIBC) cases, 15 (22.7%) cases with lymph node metastasis, 7 (10.6%) cases with distant metastasis. The bilateral group contained 24(63.2%) muscle invasive bladder cancer(MIBC) cases, 6 (15.8%) cases with lymph node metastasis, 2 (5.3%) cases with distant metastasis. There was no significant difference in disease specific survival between the two groups ( P>0.05). During the follow-up, the incidence of overall complication rate in the unilateral group was significantly lower than that in the bilateral group [43.9% (29/66) vs. 63.2% (24/38), P<0.001]. The incidence of pyelonephritis in unilateral group was significantly lower than that in the bilateral group [16.6%(11/66) vs. 42.1%(16/38), P=0.006]. There was no statistical significance in terms of quality of life before operation in the two groups. After operation, both physical function score[(54.9±7.1) vs.(49.2±6.7)] and emotional function score [(63.1±6.4) vs.(59.9±6.7)] in unilateral group were higher than that in bilateral group ( P<0.05). Conclusions:The modified unilateral cutaneous ureterostomy could achieve relatively low complication rate, and improve the quality of life to some extent compared with bilateral ureterostomy.

The experience of surgical treatment in T 4 stage prostate cancer / 中华泌尿外科杂志

Objective:To investigate the effectiveness of surgical treatment for patients with T 4 stage prostate cancer. Methods:The clinical data and prognosis of 18 patients with T 4 stage prostate cancer treated in Shanghai Tenth People's Hospital from July 2013 to December 2019 were retrospectively analyzed. The average age of these 18 patients was 68.3 (53-81)years. 10 patients were castration resistant prostate cancer (CRPC) and 8 patients were hormone-sensitive prostate cancer (HSPC). 10 CRPC patients were treated with surgical treatment due to bladder clot packing and/or lower urinary tract obstruction. 8 HSPC patients had severe hematuria, severe dysuria and local symptoms. The KPS scores of all patients were ≥80 points with an average score of 84 (80-90). The average QOL score of 18 patients was 28 (21-32). 2 cases in 18 patients underwent total pelvic resection for rectal invasion (one CRPC and one HSPC). 7 cases underwent radical cystoprostatectomy for ureteral invasion (5 cases of CRPC, 2 cases of HSPC), 9 cases underwent bladder preservation surgery for bladder neck invasion (4 cases of CRPC, 5 cases of HSPC), of which 4 cases of enlarged lymph node dissection were all HSPC patients. Results:All cases of T 4 stage prostate cancer patients operation were successfully completed, the average operation time was 256 (219-310)min and the median intraoperative blood loss was about 300 (250-350)ml. Four of them (3 cases of CRPC and 1 case of HSPC) received blood transfusion after operation. The average postoperative hospital stay was 21(11-37) days. All 18 cases were followed up and the median follow-up time was 23.8 months. There was no perioperative death, and no bladder-preserving patients had true urinary incontinence or bladder outlet stenosis.2 CRPC cases died 8 and 15 months after surgery respectively, 7 patients were PSA relapse treated with docetaxel or abiterone therapy, and 1 HSPC patient with rectal invasion was followed up for 58 months after total pelvic resection, the PSA level was still 0.003ng/ml, no distant metastasis was found. 8 cases of hormone-sensitive patients were treated with endocrine therapy, and PSA was less than 0.2 ng/ml. The average QOL of 18 patients 3 months after operation was 37 points (25-45), which was significantly higher than that before operation. The average maximum urine flow rate of patients with bladder preservation was 23(19-25)ml/s. Conclusions:For T 4 stage prostate cancer, surgical treatment is feasible and safe for doctors with extensive surgical experience. For CRPC patients, the surgery can significantly improve short-term symptoms and quality of life, and long-term benefits need to be further evaluated with a large sample. For HSPC patients, it can not only improve clinical symptoms and QOL of patients, but also provide long-term benefits.

The efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation: a randomized, controlled, multi-center clinical trial with 2 years’ follow-up / 中华泌尿外科杂志

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

The efficacy and safety of BCG in the prevention of postoperative recurrence of intermediate and high-risk non-muscle invasive bladder cancer: a randomized, controlled, multi-center clinical trial (mid-term report) / 中华泌尿外科杂志

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

Urodynamic analysis of extraperitoneal Studer orthotropic ileal neobladder following radical cystectomy / 中华泌尿外科杂志

Objective To evaluate changes of the urodynamics of extraperitoneal Studer orthotropic ileal neobladder after radical cystectomy.Methods Between July 2013 and October 2017,Retrospective analysis was performed on 58 bladder cancer patients.58 patients who underwent retrograde extraperitoneal approach of radical cystectomy and Studer orthotopic ileal neobladder.The patients were comprised of 56 male and 2 female patients with average age of 62 years.There were 9 cases of T1,26 cases of T2,20 cases of T3,and 3 cases of T4.All operations were completed by open suprapubic extraperitoneal approach,then entered the abdominal cavity.An ileal segment 50-55 cm long was isolated which was 25 cm proximal to the ileocecum.The 35-40 cm ileal segment was detubularized along its antimesenteric border.The anterior wall was folded forward with U-shaped and the edges were sutured to formed a neobladder.The proximal 15cm was reserved for the double isoperistaltic afferent limb.The lowest part of the neobladder was anastomosed with urethral stump,the peritoneum was closed at the mesentery,and the neobladder was completely placed extraperitoneal.Upper urinary tract function was examined by renal function test,enhanced CT,IVU or cystography.Uroflowmetry,urodynamic evaluation,diurnal and nocturnal continence were performed at 3,6,12,24 months following the surgery.Results After removed of the catheter,all patients were able to urinate through the urethra.The 3,6,12,24 month follow-up data of urodynamic were compared.The maximum neobladder capacity was[(378 ±66) vs.(381 ± 102)vs.(438 ± 75)vs.(472 ±96)] ml,the maximum flow rate [(10.2 ± 2.8) vs.(14.9 ± 4.3) vs.(16.4 ± 3.6) vs.(17.6 ± 2.1)] ml/s,maximum bladder pressure during filling was [(23.0 ± 4.6) vs.(21.7 ± 7.1) vs.(20.6 ± 6.4) vs.(18.8 ±6.3)] cmH2 O,the PVR was[(68.0 ± 33.2) vs.(36.2 ± 10.1) vs.(30.6 ± 11.9) vs.(14.0 t 9.6)] ml.There were significant differences between the 6-month and 12-month.There were no significant differences in the maximum bladder pressure during flowing [(38.6 ± 7.4) vs.(49.2 ± 6.8) vs.(58.4 ± 10.5) vs.(56.8 ± 7.4)] cmH2O.53 cases were followed up 12 months after surgery.Excellent daytime and nighttime continence was 98％ (52/53)and 83 ％ (44/53)in the first year.Mild unilateral hydronephrosis occurred in 2 cases 1 month after surgery.Blood electrolytes and renal function were within the normal range.1 case presented bilateral mild hydronephrosis 12 months after surgery,without bladder and ureter regurgitation.The blood electrolyte and renal function of the other patients were in normal range with no signs of ureteral stricture and upper urinary tract hydronephrosis.Conclusions Extraperitoneal Studer orthotopic ileal neobladder reduced the interference of postoperative intraperitoneal intestinal tract on neobladder function.Postoperative patients have a smooth urination,a safe pressure during the storage period.The urination period,and the function of day and night urinary control is close to normal physiological characteristics.

Effect of early continuous renal replacement therapy on the prognosis of urosepsis / 中华泌尿外科杂志

Objective To investigate the effect of early continuous renal replacement therapy on the prognosis of urinary sepsis after surgery for upper urinary tract calculi.Methods The clinical data of 59 patients with urinary sepsis after surgery for upper urinary tract calculi were retrospectively analyzed.In 59 patients with urinary sepsis,9 patients with early persistent renal replacement therapy were selected as the experimental group and 50 patients without early continuous renal replacement therapy as the control group. The age,sex ratio,diabetes,hypertension,the average operation time were no significant difference(P>0.05).Preoperative urinary tract infection,the experimental group preoperative urinary tract infection was significantly higher than the control group(77.8% vs.32.0%,P<0.05).In the results of preoperative urine culture positive ratio,the experimental group was also significantly higher than the control group,the difference was statistically significant(P<0.05).The changes of prognostic factors in patients with or without continuous renal replacement therapy were analyzed.Results In terms of the changes of postoperative laboratory results,the decrease of procalcitonin(PCT),C-reactive protein,white blood cell count and neutrophil ratio in the experimental group was significantly larger than that in the control group, and the difference was statistically significant;on the increase of hemoglobin,platelet count,fibrinogen,the standard bicarbonate level from blood gas analysis in the experimental group increased significantly more than the control group,the difference between the two groups were statistically significant.Conclusions Early renal replacement therapy in patients with urinary sepsis after upper urinary tract calculi surgeries can improve the prognosis of patients.

Inhibition of YAP gene by siRNA suppresses the proliferation and migration of T24 bladder cancer cells / 中国癌症杂志

Background and purpose:Urothelial carcinoma of the bladder (UCB) is the most common cancer in urinary system. Yes associated protein (YAP) gene is closely associated with urothelial carcinoma of the bladder. The study was aimed to explore the effect of siRNA targeting the YAP gene on cell proliferation and migration of T24 cells. Methods:Small interfering RNA (siRNA) was transfected together with LipofectamineTM2000 in T24 human bladder cancer cells to block the YAP signal pathway. The effect of siRNA on cell proliferation and invasiveness was assessed by cell counting kit-8 (CCK-8) assay, Transwell migration assay and wound healing assay. Quantitative real time-Polymerase chain reaction (qRT-PCR) and Western blot analysis were used to conifrm the successful suppression of YAP gene and protein by siRNA. Results:Expression of YAP gene and protein was successfully suppressed after transfected with siRNA which verified by qRT-PCR and Western blot(RNA:F=93.91, P<0.000 1; Protein: F=4.62, P<0.05). As CCK-8 test showed, the proliferation of T24 bladder cancer cells was successfully restrained by inhibition of YAP gene compared with blank control and negative control(12 h: F=6.00, P=0.037;24 h: F=41.72, P=0.000 3;36 h:F=462.8, P<0.000 1;48 h:F=236.6, P<0.000 1;72 h:F=140.5, P<0.000 1). Transwell and wound healing test were performed after YAP gene was interfered by siRNA. The result demonstrated that migration of T24 bladder cancer cells was signiifcantly inhibited (Transwell: F=43.55, P<0.05;Wound healing: F=43.55, P<0.05). Conclusion:This study suggested that YAP gene was an important enhancer for the proliferation and migration of bladder cancer cells.

Validation of the MSKCC score model in advanced renal cell carcinoma patients treated with VEGF-targeted agents in China / 中华泌尿外科杂志

Objective To validate the Memorial Sloan-Kettering Cancer Center(MSKCC)score model and evaluate the clinical efficacy of vascular endothelial growth factor(VEGF)-targeted agents in the treatment of advanced renal cell carcinoma(RCC)in China.Methods Three hundred and forty-five patients with advanced RCC and average age of 57(17-90)years were treated with VEGF-targeted agents.There were 306 cases of clear cell RCC,20 cases of papillary RCC,4 cases of chromophobe RCC,5 cases of renal collecting duct carcinoma,3 cases of medullary carcinoma and 7 cases of unclassified RCC.The main metastatic lesions were located at lung,bone and lymph nodes.Of them,205 cases were given the treatment of sorafenib 400 mg bid without off treatment,while 140 cases received sunitinib treatment in repeated six week cycles consisting of four weeks of sunitinib 50 mg daily followed by two weeks off treatment.Overall survival(OS)was estimated by the Kaplan-Meier method.Log-rank test and Harrell concordance index analysis were used to validate the MSKCC score model.Results The median follow-up period were 23(1-68)months in the whole group.The OS was 33 months,and survival rates at 1,2,3 year were 77.6％,59.3％,46.6％,respectively.According to the MSKCC score model,the patients were segregated into three risk categories: the favorable-risk group(no prognostic factors;n =169;49.0％),in which median OS(mOS)was 46 months and 2 year OS was 75.8％;the imtermediate-risk group(one or two prognostic factors;n =150;43.5％),in which mOS was 24 months and 2 year OS was 47.7％;and the poorrisk group(three to five prognostic factors;n =26;7.5％),in which mOS was 8 months and 2 year OS was 10.1％(log-rank P ＜ 0.01).The concordance index was 0.687.Conclusions VEGF-targeted agents are effective in Chinese advanced RCC patients.The MSKCC score model can be incorporated into judging individualizing tumor prognosis and communicating about the treatment options with patients who are using VEGF-targeted agents.

Construction of eukaryotic expression vector and package of lentivirus vector encoding prostate cancer antigen 3 / 中国癌症杂志

Background and purpose: The increased of specific expression of prostate cancer antigen 3 (PCA3), as one of long non-coding RNA, has been observed in prostate cancer, indicating that PCA3 may contribute to the development of prostate cancer. To further study its roles in prostate cancer, we construct a lentivirus expression vector carrying the whole PCA3. Methods: PCA3 was amplified from prostate cancer cell line LNCaP by reverse transcriptase polymerase chain reaction (RT-PCR). After the sequence was proved to be correct, we recombined the pCDH-CMV-MCS-EF1-copGFP-PCA3. After transformation into E.coli cells, the candidate clones were identified by PCR amplifying, restricting enzyme digestion analysis and DNA sequencing, and the viral titer was determined. Results: Through the Blast analysis software, we compared the results of PCA3 sequence amplified by PCR with GeneBank sequence, ifnding that the homology is 99.8%. The lentivirus vector was constructed successfully, and the virus in the supernatant reached a titer of 2*108. Conclusion: The successful construction of the lentivirus vector encoding PCA3 not only lays the foundation for the further research into the effect of PCA3 gene on the prostate cancer but also provides a new therapy for advanced prostate cancer.

The value of preoperative platelet to lymphocyte ratio in predicting of clinical stage and prognosis in upper tract urothelial carcinoma / 中国癌症杂志

Background and purpose: Platelet to lymphocyte ratio (PLR) is an important factor reflected systematic inflammation. The clinical value of PLR has not been confirmed. The present study was to explore the value of preoperative PLR in predicting clinical stage and prognosis in upper tract urothelial carcinoma. Methods:Patients who underwent surgical therapy with postoperative pathology upper tract urothelial carcinoma without metastasis from Jan. 2007 to Mar. 2012, were collected. Following up was done by telephone and clinic work, 150 vs 1 was taken as the threshold value of PLR, and the association of PLR with tumor stage, whether suffered bladder cancer as comorbidity, recurrent or metastasis, overall survival, tumor lesion, preoperative hematuria, gender and age was analyzed. We further analyzed the association difference of disease free survival (DFS) time and overall survival (OS) time between different PLR groups. Results:Fifty-one cases of UTUC were collected, and the postoperative mean following up time is 21 (9–51) months. Twenty cases recurred or metastasis and 9 cases died. The mean DFS time was 15 (2–51) months,and the mean OS time was 21 (9–51) months. One-factor analysis of variance showed that preoperative PLR was associated with tumor stage, overall survival rate, hematuria and gender, and the P value were 0.028, 0.008, 0.045, 0.036 respectively. High PLR group was intended to be non-organ confined disease, the sensitivity was 57%and the specificity was 74%. Survival analysis by Kaplan-Meier method showed there is no statistical difference in DFS between high and low PLR groups (P=0.155). But OS time in high PLR group was significantly less than that in low PLR group (P=0.006). Cox regression confirmed that only tumor stage is an independent prognostic factor of OS (P=0.029). Conclusion:PLR has potential clinical value in predicting advanced stage disease and Cox regression confirmed that only tumor stage is an independent prognostic factor of OS.

Prognosic analysis of chemotherapy for patients with castration resistant prostate cancer / 中华泌尿外科杂志

Objective To analyze prognosic factors for patients with hormone refractory prostate cancer (HRPC) after chemotherapy of docetaxel/mitoxantrone plus prednisone and to explore the relationship between prostate specific antigen (PSA) parameters and prognosis. Methods Data from 68 patients with CRPC after chemotherapy were collected and analyzed retrospectively.The median age of these patients were 65 years old with 28 cases of biopsy Gleason score ＜ 8 and 35 cases of ≥ 8.The median serum PSA at diagnosis,nadir and pre-chemotherapy baseline were 142 ng/ml,0.5 ng/ml and 33.0 ng/ml,respectively.There were 38 patients in docetaxel group and 30 in mitoxantrone group.PSA doubling time ( PSADT),progression free survival (PFS) and overall survival (OS) was calculated.Chi square test was used in analysis of chemotherapy effect and Cox proportional hazards regression model was applied to identify the predictors for PFS and OS.The median value of continuous variable as cutoff point was used to divide patients into two groups to compare.Risk ratio and 95％ confidence interval (CI) was calculated. Results 38 (55.9％)patients experienced effective chemotherapy. The effective rate were 33％ and 74％ for PSADT ＜ 1.6 months and ≥ 1.6 months group,85％ and 49％ for M0 and M1 stage group,and 69％ and 40％ for docetaxel and mitoxantrone group,(P ＜ 0.05).The median PFS was (3.5 ± 0.5) months for all patients,which were (2.7 ±0.4) months and (5.9 ±0.6) months for patients with PSADT ＜ 1.6 months and ≥ 1.6 months group,(5.0 ± 0.6) months and (2.7 ± 0.5 ) months for patients with docetaxel and mitoxantrone group,and (5.7 ± 0.8) months and ( 3.4 ± 0.6) months for patients with Gleason score ＜ 8 and ≥ 8 group (P ＜0.05).26 case died in the end and the median OS was (28.3 ± 2.6) months for these patients,which were (15.7 ± 3.4) months and (31.6 ± 1.2) months for patients with PSADT ＜ 1.6 months and ≥1.6 months group,(29 ± 4.1 ) months and (28 ± 3.2) months for patients with docetaxel and mitoxantrone group,and (28.7 ± 2.6) months and (24.3 ± 5.6) months for patients with Gleason score ＜ 8 and ≥ 8 group (P ＜ 0.05). Conclusions The effective rate of chemotherapy was related with PSADT,chemotherapy strategy and M stage.PSADT,chemotherapy strategy and Gleason score may be independent predictors for patients with HRPC taking chemotherapy.Patients with PSADT ≥ 1.6 months,docetaxel chemotherapy and Gleason score ＜ 8 will have longer PFS and OS.

Construction of a nomogram predicting the risk of peri-operative complications after open radical prostatectomy / 中华泌尿外科杂志

Objective To construct and evaluate a nomogram for predicting the risk of peri-operative complications after radical retro-pubic prostatectomy (RRP) with standard classification criteria.Methods The peri-operative complications and clinicopathological data of 240 patients (50-82 years old) who had undergone RRP for prostate cancer from June 2006 to June 2011 were retrospectively collected.Gleason score:95 cases ＜ 7; 145 patients ≥ 7;Clinical staging:cT1 is 1 case (0.4％),T2a 5 cases (2.1％),T2b 7 cases (2.9％),T2c 162 cases (67.5％),T3a 26 cases (10.8％),T3b 39 cases (16.3％).The peri-operative complications (in 30 days after surgery) were classified by Clavien-Dindo Classification system (the occurrence rates are as follows:rectum injury 1.6％,wound infection 2.0％,deep venous thrombosis 1.2％,urinary leak 5.0％,lymphocele 4.5％,myocardial infarction 5.8％,second look operation 1.6％),and a logistic regression model was used to construct the nomogram.Results BMI,N staging and Blood loss more than 200ml during surgery were independent prognostic factors of RRP morbidity in multivariate logistic regression.The nomogram predicting the risk of peri-operative complications showed relative good concordance index (0.633) and good calibration. Conclusions Based on the clinicopathological factors,a nomogram to predict the probability of peri-operative complications in patients undergone RRP was constructed.This statistical tool may be beneficial in judging operation risk and help consulting with patient before or after surgery.

Patterns of recurrence and prognostic factors of disease free survival in penile squamous cell carcinoma treated with lymphadenectomy / 中华泌尿外科杂志

Objective To evaluate the recurrence patterns and possible prognostic factors in primary penile cancer treated with penectomy and standard lymphadenectomy.Methods The records of 73 patients with penile squamous cell carcinoma who underwent penile amputation and regional lymphadenectomy between 1990 and 2005 were reviewed.The median follow up was 32 ( 16 - 183) months.Molecular markers including p53 and Ki-67 were detected using immunohistochemistry.Recurrence patterns,pathological characteristics,and patient outcomes were analyzed.ResultsTwenty( 27.4％ ) patients developed recurrences at a mean of 11 (6 - 17 ) months postoperatively and 3 cases remained alive at last follow-up.The mean cancer specific survival of the recurrent patients was 26 ( 16 - 83 ) months.Distant metastasis and multiple recurrences were common among patients with high-grade tumor (P =0.017 ).Univariate analysis revealed that higher primary tumor stage,higher pathological grade,lymph node metastasis,extra-nodal involvement and positive p53 protein expression were significantly associated with decreased 3-year disease free survival rates.Cox regression identified that only pathological grade ( P =0.025 ) and lymph node status ( P =0.024 ) were independent predictors of disease free survival.ConclusionsPathological grade and lymph node status were independent predictors of disease free survival in patients with penile squamous cell carcinoma in this cohort.Patients with high-grade disease are likely to recur in a distant or multiple pattern.

Construction of a nomogram to predict disease free survival in node-positive penile cancer treated with surgery / 中华泌尿外科杂志

Objective To construct a nomogram for estimating disease free survival of node-positive penile cancer treated with surgery.MethodsThe clinicopathological data of 32 node-positive penile squamous cell carcinoma patients were retrospectively reviewed.All patients had undergone primary tumor excision and regional lymphadenectomy.The pathological records showed that 10 were N1,13 were N2 and 9 were N3.Median level of preoperative squamous cell carcinoma antigen (SCCAg) was O.9 μg/L.With a median follow-up of 16.5 months,13 patients developed recurrence.Based on the stage,histological grade and preoperative serum squamous cell carcinoma antigen level,a nomogram was drawn on the basis of the Cox regression model.Results Stage and preoperative serum SCCAg levels were independent prognostic factors for disease free survival in node-positive penile cancer treated with surgery.The hazard ratio of SCCAg level and N stage was 2.76 (95％ CI:1.40-5.44,P=0.0034) and 28.51 (95％ CI:2.55 -319.11,P =0.0066).The nomogram demonstarted good discrimination and calibration with a concordance index of 0.855.Conclusions Based on the N stage and preoperative serum SCCAg level,a nomogram to predict disease free survival in node-positive penile cancer treated with surgery was set up.The prediction model could be helpful in predicting the risk of recurrence.

Clinical efficacy and tolerance of sunitinib in the treatment of advanced renal cell carcinoma / 中华泌尿外科杂志

Objective To evaluate the clinical efficacy and side effects of sunitinib in the treatment of advanced renal cell carcinoma. Methods Forty-five patients with advanced renal cell carcinoma and an average age of 48.6 yrs were treated with sunitinib. Among the study group, 25 were male and 20 were female. In group one, patients received sunitinib treatment in repeated six week cycles consisting of four weeks of sunitinib 50 mg daily followed by two weeks off treatment (schedule 4/2). In group two, a single daily dose of sunitinib 37.5 mg was administrated to 20 patients without off treatment. A CT scan was used to evaluate the treatment efficacy after each cycle and the side effects were recorded accordingly. Results Clinical efficacy could be evaluated in 40 patients. Of these, two achieved complete response, eight achieved partial response, 27 were stable and the remaining eight experienced disease progression with four patients dying during the study period. The side effects of sunitinib in group one and in group two included hypertension 32% (8/25) and 10% (2/20), P=0.02; liver function impairment 32% (8/25) and 20% (4/20), P=0.011; hand-foot skin reaction 68% (17/25) and 60% (12/20), respectively. The incidence of major side effects of sunitinib were different in Chinese patients than from what had been previously reported in studies conducted in US and Europe. Generally, most of the sunitinib side effects were easy to manage. Conclusions There weredifferences between the two groups of Chinese patients treated with different sunitinib protocols. The protocol of sunitinib 37.5mg daily without off-treatment was better than the protocol of sunitinib 50mg daily (schedule 4/2) in regard to liver function impairment and hypertension.

Efficacy of Sunitinib in treating metastatic non-clear cell renal cell carcinoma / 中华泌尿外科杂志

Objective To investigate the efficacy of Sunitinib in treating metastatic non-clear cell renal cell carcinoma (RCC).Methods Twenty-two metastatic non-clear cell subtype renal cell carcinoma patients with a median age of 46 years (29 -76 years) were treated with Sunitinib.Fourteen cases were found have metastasis post radical nephrectomy,and the remaining eight cases with metastasis received cytoreductive surgery.Pathological diagnosis showed 12 papillary RCCs,one chromophobe RCC,three collecting duct RCCs,and six unclassified RCCs.The metastatic lesions were located in the lung,lymph nodes,adrenal gland,bone,liver,and thyroid gland.The patients were given the treatment of sunitinib 50 mg qd four weeks on and two weeks off.The median time of treatment was 11 months (4.5 - 24 months).Results The objective control rate was 73％.Three papillary RCC and one chromophobe RCC reached partial remission (PR) and 12 cases maintained stable disease (SD) for more than 12 weeks.And the remaining six cases progressed (PD).Conclusions Sunitinib has definitive efficacy in metastatic papillary RCC,chromophobe RCC,collecting duct RCC and unclassified RCC.Metastatic lesions in lungs and lymph nodes might be more sensitive to Sunitinib.

Prognostic value of bilateral inguinal lymph node metastases in node-positive penile cancer / 肿瘤研究与临床

Objective To evaluate the prognostic value of bilateral inguinal lymph node metastases in node-positive penile cancer. Methods Sixty patients with surgically resected node-positive penile cancer were analyzed. All the patients underwent regional lymph node dissection. Recurrence free survival curves were plotted by Kaplan-Meier method and compared by the Log-rank test. Multivariate survival analysis was performed using Cox regression model. Results Of all the patients, 18 cases had bilateral inguinal lymph node metastases. The 3-year recurrence free survival rate in patients with bilateral invovlement was significantly lower than those with unilateral disease (26.7 % vs 65.3 %, χ2 =10.6, P=0.001). In order to evaluate wether the prognostic significance of bilateral lymph node metastases was dependent of increased number of positive nodes, the two predictors were included in multivariate survival analysis.Both the number of metastatic nodes and bilateral nodal disease were independent prognostic factors (P ＜0.05).Comparisons of survival curves showed those patients with bilateral nodal disease and more than 2 metastatic nodes had worst outcome. Conclusion Bilateral inguinal lymph node metastases is an important prognostic factor in penile cancer irrespective of the number of positive lymph node.