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.

A case report of renal inflammatory myofibroblastic tumor and renomedullary interstitial cell tumor / 中华泌尿外科杂志

Inflammatory myofibroblastic tumor (IMT)is a potentially or low-grade malignant mesenchymal neoplasm, which is rare in clinic. Renomedullary interstitial cell tumor(RICT) is a clinically rare benign renal tumor. The combination of these two diseases in one patient has not been reported. A 25-year-old female patient was admitted to the hospital due to left back pain for 12 days and hematuria for 1 week. MRI of kidneys showed a mass in the left renal pelvis, which was considered as renal pelvic carcinoma. Urine cytopathological examination was negative. Robot-assisted laparoscopic radical left nephroureterectomy was performed. There was no tumor recurrence or metastasis during the follow-up for more than 6 months after operation.

A multicenter comparative study of limited and extended pelvic lymph node dissection for high-risk prostate cancer patients / 中华泌尿外科杂志

Objective:To compare the pathological results and complications of limited and extended pelvic lymph node dissection among high-risk prostate cancer patients, and to explore the risk factors that affect the rate of lymph node metastasis in high-risk prostate cancer patients.Methods:The data of 800 high-risk prostate cancer patients who underwent radical prostatectomy and pelvic lymph node dissection from January 2016 to December 2020 in three affiliated hospital of Sun Yat-sen University were analyzed retrospectively. According to the scope of pelvic lymph node dissection, they were divided into limited pelvic lymph node dissection (LPLND) group and extended pelvic lymph node dissection (EPLND) group. There were 172 patients underwent LPLND, and 628 patients underwent EPLND.The age of the patients in the LPLND group was 67 (62, 72) years old, diagnosed PSA 20.7 (10.9, 54.8) ng/ml. The biopsy Gleason score 6 in 22 cases, 7 in 59 cases, 8 in 56 cases and 9-10 in 35 cases.The clinical T stage: T 1 in 29 cases, T 2 in 102 cases, T 3 in 37 cases, T 4 in 4 cases; N 0 in 160 cases and N 1 in 12 cases. 50 patients received neoadjuvant hormonal therapy. The age of patients in the EPLND group was 67 (63, 72) years old, diagnosed PSA was 23.9 (14.0, 46.8) ng/ml. Biopsy Gleason Score 6 in 51 cases, 7 in 194 cases, 8 in 218 cases and 9-10 in 165 cases. Clinical T stage: T 1 in 114 cases, T 2 in 341 cases, T 3 in 144 cases, T 4 in 29 cases; N 0 in 526 cases and N 1 in 102 cases.158 patients received neoadjuvant hormonal therapy. There were no significant differences in the age, PSA, puncture Gleason score, clinical T stage, and whether or not to receive neoadjuvant hormonal therapy between the two groups of patients ( P>0.05). The difference in clinical N staging was statistically significant ( P=0.002). The number of postoperative lymph nodes, positive pelvic lymph nodes and postoperative complications and other related clinical and pathological data of the two groups were analyzed. Multivariate logistic regression was used to analyze the risk factors of patients with positive lymph nodes. Results:The median number of lymph nodes harvested [13(8, 19)vs. 6(4, 13), P<0.001] and the rate of positive lymph node cases[31.2%(196/628) vs. 10.5%(18/172), P<0.001] in the EPLND group was significantly higher than those in the LPLND group. Preoperative PSA, clinical N staging, Gleason score, and way of lymph node dissection were independent risk factors for postoperative positive pelvic lymph node in high-risk prostate cancer patients. Compared with the LPLND group, the ELPND group had a higher postoperative complication rate [19.9%(125/628) vs. 11.0%(11/172), P=0.007]. Conclusions:Compared with the LPLND, EPLND in high-risk prostate cancer patients can harvest more lymph nodes and increase the detection rate of positive lymph nodes. The complications of EPLND were higher than those of LPLND. Preoperative PSA, clinical N stage, Gleason score, and the way of lymph node dissection are independent risk factors for positive pelvic lymph node dissection.

Early functional and oncological outcomes of lateral prostate capsule sparing robot-assisted radical cystectomy-Orthotopic ileal neobladder / 中华泌尿外科杂志

Objective:To investigate the experience and results of the modified lateral prostate capsule sparing robot-assisted radical cystectomy-orthotopic ileal neobladder (LPCS-RARC-OIN).Methods:From December 2018 to November 2020, 19 patients received LPCS-RARC-OIN by a single surgeon in Sun Yat-sen Memorial Hospital, Sun Yat-sen University. LPCS-RARC-OIN was performed on male patients with high-risk non-muscle-invasive bladder cancer or muscle-invasive bladder cancer cT 2N 0M 0 without tumour in the bladder neck or urethra, and prostate cancer was ruled out by MRI and serum PSA<2.5ng/ml. The average age was 57.6 years, the average IIEF-5 score was 20.4. Separating the prostatic adenoma and the lateral prostate capsule from the base to the apex of the prostate, and retaining the lateral prostate surgical capsule or lateral prostate capsule about 1-2mm thickness. Patients were followed up and urinary function, sexual function and oncological outcomes were recorded. Results:All 19 operations were finished successfully. The average operation time was 279.9 (225-345) min and average estimated blood loss was 88.9 (30-200) ml. The average postoperative hospital stays was 15.8 (9 -23) days. The average lymph node yields was 23.3 (11-42). All surgical margins were negative and no incidental prostate cancer was found. 2 weeks, 1 month, 3 months and 6 months after catheter removal, the daytime and nighttime continence were 42.1% (8/19)and 36.8% (7/19), 63.2% (12/19)and 63.2% (12/19), 78.9% (15/19) and 73.7% (14/19), 94.7% (18/19) and 89.5% (17/19), respectively. 3 months and 6 months after operation, the average IIEF-5 score was 7.2 and 10.1 points respectively. The average follow-up was 10.6 months (5.4-26.1 months)and no recurrence or distant metastasis was found in this study.Conclusions:LPCS-RARC-OIN could improve the urinary and sexual function in selected patients. However, the long-term follow up is needed for functional and oncological outcomes.

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.

Review the glorious course and forge ahead: current status and prospects of research on bladder cancer in China / 中华泌尿外科杂志

In the past 40 years, the concept and technology of diagnosis and treatment of bladder cancer have developed rapidly in China. We have achieved fruitful results in the research fields of noninvasive diagnosis, minimally invasive surgery, comprehensive treatment and basic research of bladder cancer. At the same time, we aware that the research on bladder cancer in our country is still in a follow-up state, with few influential and high-quality research. In the future, we should make more use of the clinical resources to conduct multi-center research involving prospective randomized controlled study and real-world study. We should also promote multidisciplinary cooperation, nourish the translational research conditions, and ultimately promote the level of diagnosis and treatment of bladder cancer in China.

The update interpretation of 2020 EAU prostate cancer guideline(Part Ⅴ) / 中华泌尿外科杂志

EAU Guideline office updated the 2020 version of prostate cancer guideline based on novel clinical evidence. In the section of metastatic hormone sensitive prostate cancer (mHSPC), the 2020 EAU guideline introduced and strongly recommended the use of second-generation androgen receptor antagonists in combination with androgen deprivation therapy (ADT), the recommendation level of prostate radiotherapy combined with ADT to low-volume patients changed from weak to strong, and the intermittent ADT is no longer included in the recommendation.

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.

Prospective randomized controlled trial of two ureteroileal anastomosis: split-cuff nipple vs.direct anastomosis / 中华泌尿外科杂志

Objective To compare split-cuff nipple and direct ureteroileal anastomosis during ureteroileal anastomosis.Methods Between December,2014 and March,2017,a prospective randomized study was conducted on 70 patients who underwent radical cystectomy and urinary diversion.In every patient,both ureters were randomized to be implanted using an antireflux,split-cuff nipple technique (group A) or a reflux,direct technique (group B).After pelvic lymph node dissection and radical cystectomy,a Mshape orthotopic ileal neobladder was constructed and two ureters were implanted with single-J tubes placed for 10-12 days.For split-cuff nipple technique,a 0.5 cm longitudinal incision in the ureter was made,and the ureteral wall was turned back on itself,construction a nipple.The cuff was stabilized at the corners with sutures.The ureter was then placed into the bowel with 0.5 cm nipple.The ureter was sutured to the full thickness of the bowel wall with interrupted 4-0 PDS.For direct technique,a 0.5 cm incision in the ureter was made,the full thickness of the ureter was sewn to the mucosa of the bowel.Results 70 patients were enrolled in the study,63 males and 7 females,(62.5 ± 10.4) years old.Over a median follow-up of 13.2 months,one patients had bilateral anastomosis stricture 3 months after operation,1 patient in group A had stricture 6 months after operation,2 patients in group B had stricture 6 and 12 months after operation,respectively.Six patients (8.6％) in group A found reflux compared with 21 patients (30.0％) in group B (P =0.004).The reflux pressure was (23.5 ± 9.0) cmH2O and (15.5 ± 4.9) cmH2O in group A and group B (P =0.042),respectively.The GFR of group A was (38.1 ± 7.6) ml/min compared with (38.6 ± 12.9) ml/min in group B at 12 months after operation.One patient in group A and four patients in group B had acute nephropyelitis.Four patients in group A had renal stones formation compared with 1 patients in group B.The time of anastomosis was (8.8 ± 3.5) minutes and (6.7 ± 1.5) minutes (P =0.037) for group A and group B,respectively.The patients in both groups had no urine leakage.Conclusion Compared with direct technique,split-cuff nipple technique had lower reflux rate,higher antireflux pressure and longer anastomosis time than direct technique.

Computed tomography and magnetic resonance imaging evaluation of pelvic lymph node metastasis in bladder cancer / 癌症

BACKGROUND@#Accurate evaluation of lymph node metastasis in bladder cancer (BCa) is important for disease staging, treatment selection, and prognosis prediction. In this study, we aimed to evaluate the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) for metastatic lymph nodes in BCa and establish criteria of imaging diagnosis.@*METHODS@#We retrospectively assessed the imaging characteristics of 191 BCa patients who underwent radical cystectomy. The data regarding size, shape, density, and diffusion of the lymph nodes on CT and/or MRI were obtained and analyzed using Kruskal-Wallis test and χ test. The optimal cutoff value for the size of metastatic node was determined using the receiver operating characteristic (ROC) curve analysis.@*RESULTS@#A total of 184 out of 3317 resected lymph nodes were diagnosed as metastatic lymph nodes. Among 82 imaging-detectable lymph nodes, 51 were confirmed to be positive for metastasis. The detection rate of metastatic nodes increased along with more advanced tumor stage (P  6.8 mm may indicate metastatic lymph nodes in BCa.

Detecting metastases in normal-sized pelvic lymph nodes in patients with bladder cancer: comparison of computed tomography and magnetic resonance imaging / 中华泌尿外科杂志

Objective To cstimnate the diagnostic performance of computer tomography (CT) and magnetic resonance imaging (MRI) for detecting metastasis in pelvic lymph nodes with normal size in patients with bladder cancer.Methods hnaging of CT and MRI and clinical data of 118 patients who underwent radical cystectomy and pelvic lymphadenectomy were reviewed.The diagnostic efficacy of CT and MRI were analyzed when taking lymph nodes short axis diameter ≥0.3 cm and ≥ 1.0 cm respectively as diagnostic criterion of metastasis with corTelation of pathological results.Results 22.7％ (27/118) of patients were confirmed lymph nodes malignancies among 118 patients based on pathology.Totally 1 705 lymph nodes were detected in surgery and 119 of them were observed malignancy according to pathological presentation.The malignant nodes were mainly distributed in the perivesical (35.4％,41/119),internal iliac (12.6％,15/119),external iliac (30.3％,36/119),obturator region (21.0％,25/119) and presarcal region (1.7％,2/119).Imaging of CT and MRI showed that when taking nodes with ≥0.3 cm in maximum short-axis diameter (MSAD) as positive,the sensitivity (Se),specificity (Sp),and positive predictive values (PPV) were 16.0％,99.2％,54.2％ and 56.5％,99.2％,86.7％ respectively.While taking MSAD≥1.0 cm as malignant,the Se,Sp and PPV of CT and MRI were 6.2％,99.9％,83.3％ and 13％,100％,100％ respectively.When taking MSAD ≥0.3 cm as positive,the Se and PPV between CT and MR were statistically different(P ＜ 0.001 and P =0.036,respectively).When taking MSAD ≥ 1.0 cm as positive,there was no statistically difference (P =0.275 and 1.000,respectively).Conclusions The incidence of normal-sized lymph node metastasis was higher in patients with bladder cancer.At this phase the MRI evaluation was superior to that of CT.When the MSAD ≥ 1.0 cm,there was no significant difference between CT and MRI.

Stem cell associated IncRNA promotes the self-renewal in bladder cancer stem cells and acts as a predictor for recurrence of bladder cancer / 中华泌尿外科杂志

Objective To investigate the expression profile and biological function of lncRNAs in urothelial cancer stem cells and explore whether they can be biomarkers for prediction of clinical characteristics for bladder cancer patients.Methods Microarray analysis was performed to identify differentially expressed lncRNAs in cancer stem cells and parental cancer cells.Expression profiles were validated by Coding Potential Caculator analysis,real-time polymerase chain reaction.By performing in vitro sphere formation assays,J82 cells with lentivirus-based knockdown of lncRNA-BCSC (bladder cancer stem cells) were used to confirmed its function.Samples were obtained from patients who underwent TURBT between January 2009 and December 2012.All tissues were initially confirmed by pathologists.The association of the clinicpathologic of bladder cancer and lncRNA-BCSC expression was analyzed by x2 analysis.Results 750 lncRNAs were highly expressed from microarray analysis in bladder cancer stem cells.Among these,lncRNA-BCSC was identified as potentially maintaining self-renewal of cancer stem cells.Knockdown of this transcript in J82 cells inhibited spheroid formation.lncRNA-BCSC expression were higher in 54.8％ (57/104) bladder cancer tissues.Moreover,using x2 analysis,lncRNA-BCSC expression in primary tumors was found to be a predictor for recurrence following transurethral resection in patients with nonmuscle-invasive bladder cancer (P =0.009).Conclusions Our study provides strong evidence that lncRNA-BCSC are indispensable modulators of self-renewal ability of bladder cancer stem cells.Overexpression of lncRNA-BCSC may have a predictive value for early recurrence in patients suffering from nonmuscle-invasive bladder cancer.

Distribution and prognostic significance of CD8+ T cells in urothelial cell carcinoma of the bladder / 中华泌尿外科杂志

Objective The aim of this study was to investigate the distribution and clinical significance of CD8+ T cells in bladder cancer tissues in situ.Methods Immunohistochemistry were used to examine the distribution of CD8+ T cells in bladder cancer tissues,which were obtained from January 2003 to December 2009 from 302 patients.Among all the patients,262 were male while 40 were female;mean age is 60 years;tumor size ≤ 3 cm was in 235 and tumor size ＞ 3 cm was in 67;Unifocal tumor was in 214 and multifocal tumors were in 88.Amount of tumor stage Ta-T1 was 212 and T2-T4 was 90.Sixteen patients have lymph node metastasis.Histological low grade was diagnosed in 175 and histological high grade was diagnosed in 127.According to the differences between anatomic structure and cellular composition,bladder tumor tissues can be classified to two localization patterns:(1) intratumoral regions,defined as tumor cell nests;(2) stromal regions,defined as stromal areas that lack direct contact with tumor cells.Therefore,we divided 302 bladder cancer patients into two groups based on the median frequency of intratumoral CD8+ T cells (median,3/× 400 high resolution) and stromal CD8+ T cells (median,37/× 400 high resolution),respectively.x2 analysis was used to evaluated the correlation between CD8+ T cell density and clinicalpathological variables.Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival (OS).Results CD8+ T cells were predominantly located in the intratumoral regions (mean,14 ± 2/× 400 high resolution) rather than in associated stromal regions (mean,50 ± 3/× 400 high resolution,P ＜ 0.05).The density of intratumoral CD8+ T cells was inversely associated with age (P =0.026),tumor size (P ＜ 0.05) and tumor stage (P ＜ 0.05),and could represent a favorable prognostic predictor of OS (HR =0.427,P =0.003).However,the density of stromal CD8+ T cells was positively associated with age (P =0.004) and histological grade (P ＜ 0.01),and could represent an adverse prognostic predictor of OS (HR =2.206,P =0.009).Conclusions Our findings suggest that intratumoral/ stromal CD8+ T cells could potentially serve as favorable/ adverse prognostic markers for bladder cancer patients,respectively.

Prostate specific membrane antigen knockdown impairs the tumorigenicity of LNCaP prostate cancer cells by inhibiting the phosphatidylinositol 3-kinase/Akt signaling pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prostate specific membrane antigen (PSMA) can facilitate the growth, migration, and invasion of the LNCaP prostate cancer cell lines, but the underlying molecular mechanisms have not yet been clearly defined. Here, we investigated whether PSMA serves as a novel regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling by employing PSMA knockdown model and PI3K pharmacological inhibitor (LY294002) in LNCaP prostate cancer cells.</p><p><b>METHODS</b>PSMA knockdown had been stably established by transfecting with lentivirus-mediated siRNA in our previous study. Then, LNCaP cells were divided into interference, non-interference, and blank groups. We first testified the efficacy of PSMA knockdown in our LNCaP cell line. Then, we compared the expression of PSMA and total/activated Akt by Western blotting in the above three groups with or without LY294002 treatment. Furthermore, immunocytochemistry was performed to confirm the changes of activated Akt (p-Akt, Ser473) in groups. Besides, cell proliferation, migration, and cell cycle were measured by CCK-8 assay, Transwell analysis, and Flow cytometry respectively.</p><p><b>RESULTS</b>After PSMA knockdown, the level of p-Akt (Ser473) but not of total-Akt (Akt1/2) was significantly decreased when compared with the non-interference and blank groups. However, LY294002 administration significantly reduced the expression of p-Akt (Ser473) in all the three groups. The results of immunocytochemistry further confirmed that PSMA knockdown or LY294002 treatment was associated with p-Akt (Ser473) down-regulation. Decrease of cell proliferation, migration, and survival were also observed upon PSMA knockdown and LY294002 treatment.</p><p><b>CONCLUSIONS</b>Taken together, our results reveal that PI3K/Akt signaling pathway inhibition may serve as a novel molecular mechanism in LNCaP prostate cancer cells of PSMA knockdown and suggest that Akt (Ser473) may play a critical role as a downstream signaling target effector of PSMA in this cellular model.</p>

Retrograde ureteroscopy lithotomy assisted antegrade percutaneous nephrolithotomy for complex upper ureteral calculi / 中国医师进修杂志

ObjectiveTo assess the safety and efficacy of retrograde ureteroscopy lithotomy (URSL)assisted antegrade percutaneous nephrolithotomy (PCNL) for complex upper ureteral calculi in semisupine-lithotomy position.MethodsFrom March 2007 to December 2010,a total of 95 patients with complex upper ureteral calculi underwent retrograde URSL assisted antegrade PCNL in semisupine-lithotomy position.Ureteral calculi size was 12 mm × 6 mm to 38 mm × 15 mm,24 cases combined with renal calculus.Firstly retrograde URSL was performed,once the stone fragments moved up to renal pelvis,a 16-22 F PCNL working channel was established under the ultrasound guidance through which lithotripsy was performed using an ureteroscope.Finally a 6-7 F double-J tube was indwelled.ResultsOperations were successfullycompleted in 93 patients.However,in it 2 patients were converted to open surgery because of significantureteral distortion due to previous open surgery.Operative time was(42.7 ± 14.9) min; estimated blood loss was(34.5 ± 26.1 ) ml.The ureteral calculi clearance rate was 100.0％,and renal calculus clearance rate inthose combined with renal calculus was 95.8％ (23/24).There were no major intraoperative and postoperative complications excepted early urinary leakage in 2 cases and fever ≥39℃ in 3 cases.ConclusionsRetrograde URSL assisted antegrade PCNL in semisupine-lithotomy position is safe and feasible for complex upperureteral calculi,especially non-opaque calculi,combined with renal calculus,easily ascending ureteral calculi and large calculi burden which has low calculi clearance rate after URSL.The outcomes are encouraging with fewer complications.It also avoids intraoperative change of patient's position.

Extraperitoneal transumbilical single-port laparoscopic radical prostatectomy: A report of 11 cases / 中华泌尿外科杂志

Objective To present our initial experience in laparoscopic radical prostatectomy performed through an umbilical incision using a home-made multichannel port. Methods From August 2009 to March 2010, we performed single-port laparoscopic radical prostatectomy in 11 patients with localized prostate cancer. A home-made multichannel port was inserted extraperitoneally through a 3-cm umbilical incision. The single port extraperitoneal procedures included obturator fossa lymphadenectomy, radical prostatectomy and urethro-vesical anastomosis, while the urethro-vesical anastomosis was performed by a slip-knot running suture technique. Data were collected and analyzed prospectively. Results All cases were completed successfully, without conversion to a standard laparoscopic approach or open surgery except adding an additional port in one case. The average operative time was 256 minutes (range195-315), and the mean blood loss was 90 ml (range 20- 180), without any blood transfusion. The postoperative hospital stay was 15.4 days (range13- 24), and the Foley catheter was removed 12 days after surgery. No intraoperative complications occurred. One patient developed a vesico-rethralanastomosis leakage, 2 had lymphatic leakage and 1 had urinary tract infection,all of the cases were managed successfully with conservative treatment. Histopathological results showed negative surgical margine and negative lymph node dissection. All patients had no biochemical relapse after an average follow-up of 7 months. Conclusions Single-port laparoscopic radical prosta tectomy is feasible, cosmetic and minimally invasive with a low complication rate and good short-term outcome. Additional investigation is needed to evaluate the long-term safety and oncologic adequacy of this new approach.

miR-124 suppresses multiple steps of breast cancer metastasis by targeting a cohort of pro-metastatic genes in vitro / 癌症

Metastasis is a multistep process involving modification of morphology to suit migration, reduction of tumor cell adhesion to the extracellular matrix, increase of cell mobility, tumor cell resistance to anoikis, and other steps. MicroRNAs are well-suited to regulate tumor metastasis due to their capacity to repress numerous target genes in a coordinated manner, thereby enabling their intervention at multiple steps of the invasion-metastasis cascade. In this study, we identified a microRNA exemplifying these attributes, miR-124, whose expression was reduced in aggressive MDA-MB-231 and SK-3rd breast cancer cells. Down-regulation of miR-124 expression in highly aggressive breast cancer cells contributed in part to DNA hypermethylation around the promoters of the three genes encoding miR-124. Ectopic expression of miR-124 in MDA-MB-231 cells suppressed metastasis-related traits including formation of spindle-like morphology, migratory capacity, adhesion to fibronectin, and anoikis. These findings indicate that miR-124 suppresses multiple steps of metastasis by diverse mechanisms in breast cancer cells and suggest a potential application of miR-124 in breast cancer treatment.

Nursing cooperation of patients with extraperitoneal transumbilical single-port laparoscopic radical prostatectomy / 中国实用护理杂志

Objective To present the intraoperative nursing of laparoscopic radical prostatectomy performed through extraperitoneal transumbilical single-port.Methods The cooperation experience for 11 cases receiving extraperitoneal transumbilical single-port laparoscopic radical prostatectomy were summarized.The measures included:full preoperative preparation and various inspection,mastering of cooperative main points by participated nurses,familiar with property and handling of apparatuses,cooperating with doctor during operation,closely monitoring of patients' condition,and perfect various intraoperative care.Results The operations were successful,no intraoperative complications occurred and the patients recovered very well postoperatively.Conclusions The success of this operation requires not only complicate surgical techniques and special instruments,but also perfect intraoperative nursing.

Efficacy and safety of diffirent hormonal therapy regiments in advanced prostate cancer patients / 中华泌尿外科杂志

Objective To compare the efficacy,toxicitis and side-effects of Casodex and Flutamide in the hormonal therapy of advanced prostate cancer patients.Methods One hundred and thirty-six advanced prostate cancer patients were treated with with hormonal therapy.The patients were divided into 3 groups,of which 52 patients (group A) used LHRHa and Casodex as intermittent hormonal therapy;60 patients(group B) used LHRHa and Flutamide as intermittent hormonal therapy;24 patients(group C) were treated with surgical castration only.The difference of clinical symptoms,serum PSA,disease progression risk,survival rate,toxicitis and side-effects of 3 groups were compared.Results The relief rates of group A and B were 80.8% (42/52)and 81.7% (49/60) respectively,higher than 70.8% (17/24) of group C.The mean serum PSA of group A and B decreased from 133.3 ng/ml(17.9-982.8 ng/ml) to 15.8 ng/ml(0.02-28.9 ng/ml),142.6 ng/ml (20.2-1001.0 ng/ml)to 16.1 ng/ml(0.07-53.8 ng/ml),respectively,both better than that of group C,which decreased from 142.3 ng/ml (27.1-988.0 ng/ml) to 27.6 ng/ml(6.0-62.1 ng/ml).The mean chemical recurrence rates of group A and B were 34.7% (18/52) and 36.7% (22/60),respectively,lower than 58.3% (14/24) of group C.The mean chemical recurrence time of group A and B was 22(5-52)months and 22(6-65)months,respectively,longer than 11(5-54)months of group C.The mortality rates of group A and B were 26.9% (14/52) and 31.7% (19/60),respectively,lower than 66.7%(16/24) of group C.88.5% (46/52)of group A were treated continuously,while group B had 66.7% (40/60).The side-effects rate of group A was lower than group B.Conclusions Both Cadosex and Flutamide are effective for prostate cancer,and decrease the disease progression risk.Casodex is more effective and safer as for the treatment of prostate cancer compared to Flutamide.

Effect of TNF-α on production and activation of caspase-3 in primary rat renal proximal tubule cells / 中国病理生理杂志

AIM:To investigate the production and activation of caspase-3 in primary rat renal proximal tubule cells in response to tumor necrosis factor-α(TNF-α) and the implication of nuclear factor-κB (NF-κB) in the process. METHODS:Isolated rat renal proximal tubule cells (PTCs) from male adult Sprague Dawley rats were treated with TNF-α according to the indicated time courses. A specific NF-κB inhibitor,Bay11-7082,was used alone or as a pretreatment for 1 h followed by exposure to TNF-α for 24 h.The protein levels of cleaved caspase-3,caspase-3,I-κBα,phosphorylated I-κBα,and GAPDH were detected by Western blotting using specific antibodies. RESULTS:The protein level of cleaved caspase-3 relative to caspase-3 was significantly increased in the presence of TNF-α for 6 h,12 h,and 24 h. Protein levels of caspase-3 were significantly decreased by 12 h and returned to baseline by 24 h in the presence of TNF-α. Treatment with Bay11-7082 for 25 h alone or pretreatment with Bay11-7082 for 1 h followed by addition of TNF-α for 24 h caused a remarkable reduction in both cleaved caspase-3 and caspase-3 as compared to control and TNF-α treated groups. An increase in phosphorylated I-κBα was observed from 15 min to 60 min after treatment with TNF-α at a dose of 10 μg/L in PTCs. CONCLUSION:NF-κB is not only associated with the activation of caspase-3 but also the production of caspase-3 in primary rat renal proximal tubule cells in response to TNF-α.