Clinical application of an in vitro chemosensitivity test, the Histoculture Drug Response Assay, to urological cancers: wide distribution of inhibition rates in bladder cancer and renal cell cancer

To investigate the variations in chemosensitivity of individual cancers, we performed an in vitro chemosensitivity test, the Histoculture Drug Response Assay (HDRA), on fresh biopsied or surgical specimens. They were 26 bladder cancers and 19 renal cell cancers. Ten anticancer drugs were tested. By prolonging the drug exposure time to 7 days, we obtained reliable results. The mean inhibition rates (IRs) were higher for bladder cancer than for renal cell cancer, and the difference was significant for cisplatin, carboplatin, vinblastine, mitomycin C, and adriamycin. There was no significant correlation between the histological grade of the tumor and HDRA sensitivity. IR values showed a wide distribution and cancers could be classified into two groups of sensitive and resistant. This was especially true for 4-hydroxy-ifosfamide. Three bladder cancer patients with evaluable lesions were treated with drugs selected on the basis of the results of the HDRA. One patient achieved a complete response and the other patients showed a partial response. Our results suggest that chemosensitivity is independent of the clinicopathological classification of cancer, and that the HDRA may be useful for selecting the effective anticancer drug for patients with urological cancer. Received: 17 July 1998 / Accepted: 25 March 1999     

A new in-vitro drug sensitivity test (collagen-gel droplet embedded-culture drug sensitivity test) in carcinomas of pancreas and biliary tract: possible clinical utility

The collagen-gel droplet embedded-culture drug sensitivity test (CD-DST), a chemosensitivity test, evaluate the efficacy of anticancer drugs and to was used clinically to thus plan rational postoperative chemotherapy for patients with pancreatic and biliary tract carcinomas. The CD-DST solves some problems inherent in other conventional assays. This method: (1) allows evaluation of four chemotherapeutic agents, using small quantities of cells (1 × 10⁵ cells), (2) shows high primary culture success rates, (3) maintains the original growth characteristics of the cultured cells, (4) eliminates the effects of fibroblasts by employing image analysis, and (5) permits evaluation using physiologic drug concentrations. Primary cultures of tumor cell samples from all 25 patients with pancreatic or biliary tract carcinomas studied were successful. Against pancreatic carcinomas, the efficacy rates, assessed by CD-DST, of four anticancer drugs evaluated were: 25.0% for mitomycin (MMC), followed by 23.5% for adriamycin, 18.8% for 5-fluorouracil (5-FU), and 11.8% for cisplatin (CDDP). Against biliary tract carcinomas, the rates were highest for 5-FU and MMC (50.0%) and lowest for CDDP (25.0%). The efficacy rates for all four anticancer drugs evaluated were higher against biliary tract carcinomas than against pancreatic carcinomas. Tumor cultures from 10 of 17 patients with pancreatic cancer and 3 of 8 patients with biliary tract cancer showed no sensitivity to any of the drugs tested. The in-vitro results with CD-DST suggest the risk of administering non-selective postoperative chemotherapy to patients with pancreatic and biliary tract carcinomas, and emphasize the importance of carefully selecting effective chemotherapeutic agents based on adequate chemosensitivity testing. Received for publication on July 29, 1998; accepted on Aug. 13, 1998     

p53 in noncancerous bladder mucosa as a marker of disease recurrence in patients with superficial transitional cell carcinoma of the bladder

We investigated the prevalence and clinical relevance of p53 nuclear overexpression in histologically benign bladder mucosa in patients with superficial transitional cell cancer (TCC) of the bladder to look for "premalignant" lesions as the source of tumor recurrence. p53 Accumulation in representative tumor and normal-looking bladder mucosa was studied in 53 patients with Ta and T1 TCC. Histologically normal bladder specimens from 20 prostate cancer patients served as controls. We used a biotin streptavidine-peroxidase system to stain deparaffinized tissue sections with the p53 monoclonal antibody DO7. Specimens from 42 (79%) of the 53 TCC patients stained for p53 in the tumor area. There was no statistically significant difference between pTa and pT1 lesions (pTa, 71.4%; pT1, 87.5%), and staining correlated weakly with tumor grade (G1, 62%; G2, 82%; G3, 100%). Evaluation of histologically normal bladder mucosa showed positive p53 staining in 13 (24.5%) of the 53 patients. Disease recurred in 20 patients. Among them, 12 had positive staining in the normal bladder mucosa. Although p53 expression in tumor areas showed only slight correlation with tumor recurrence (p = 0.043, Cochran-Armitage test), p53 accumulation in healthy bladder mucosa correlated strongly with disease recurrence (p < 0.0001, Fisher's exact test). p53 Overexpression in histologically normal bladder mucosa in patients with TCC might identify premalignant alterations in tumor-surrounding areas. Our data suggest that p53 accumulation in histologically benign bladder mucosa of TCC patients is a possible marker of disease recurrence.     

Multiple primary cancers limited to the urological field

We analyzed the clinical features of multiple primary cancers arising from the urogenital organs. Between January 1980 and December 1999, 300 patients with renal cell carcinoma (RCC), 661 patients with urothelial carcinoma (bladder cancer and renal pelvic-ureteral cancer) (TCC) and 391 patients with prostate cancer (PC) were treated at our hospital. Of these patients, 20 patients had double genitourinary cancers. The double cancers consisted of RCC and TCC in 1 case, RCC and PC in 6 cases, and TCC and PC in 13 cases. Seven cases had synchronous tumors. The average interval in the metachronous cases was 68 (range: 12-209) months. The age at diagnosis of the second cancer was 68-94 (mean: 77.6) years old. The follow-up period ranged from 4-168 (mean: 38) months; Six patients are alive with no evidence of disease and 6 patients died of cancer. Even when limited to the urological section, the frequency of multiple primary cancers is increasing.     

Clinical outcome of conservative therapy for stage T1, grade 3 transitional cell carcinoma of the bladder

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed. RESULTS: In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT. CONCLUSION: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.     

Experimental and clinical studies on chemosensitivity tests of anticancer agents by human tumor clonogenic assay

In vitro chemosensitivity tests of anticancer agents for 119 fresh human tumors were performed by the human tumor clonogenic assay (HTCA) technique and the following results were obtained. Colony growth (greater than or equal to 5 colonies/dish) was observed in 35 of 50 gastric cancers (70.0%), 10 of 17 colon cancers (58.8%), 13 of 14 breast cancers (92.9%), two of six esophageal cancers (33.3%), three of six sarcomas (50.0%), three of 16 hematological malignancies (18.8%) and seven of 10 other tumors (70.0%). Colony growth rate differed according to the type of tumor. Fifty four tumors formed adequate colony growth (greater than or equal to 30 colonies/dish) for the chemosensitivity test. Mitomycin C (MMC), 5-Fluorouracil (5-FU), 4-hydroperoxy cyclophosphamide (CPM), Adriamycin (ADM), Cis-dichlorodiammineplatinum (CDDP), and alpha-interferon (IFN-alpha) were tested. The average positive rates of MMC, 5-FU, CPM, CDDP, and IFN-alpha were 26.9, 21.6, 10.5, 26.9, 36.8, and 23.3% respectively for all the tumors tested. In gastric cancer, the positive rates of MMC and 5-FU were 24.0 and 21.6% respectively, whereas the rates were 33.3 and 33.3% in colon cancer and 18.2 and 16.7% in breast cancer respectively. Each tumor exhibited its own chemosensitivity rates against various anticancer agents. Eighteen of the results obtained were comparable to clinical responses. The true positive rate was 50.0% (2/4) and the true negative rate 92.9% (13/14). A statistically significant correlation was observed between the results of HTCA and clinical responses (chi 2 test, p less than 0.05). The combined effects of IFN-alpha and MMC were surveyed against 20 gastroenterological tumors. Nine tumors exhibited synergistic effect, though antagonistic effect was observed in three tumors. The effects of oxygen tension (2%, 5%, 20%) on colony growth were investigated. The greatest development of colonies occurred at an oxygen of five percent, which is considered to be physiological oxygen tension, and statistically significant increases of plating efficiencies at 5% O2 as compared to those at 20% O2 were observed (t-test, p less than 0.025).     

Renal cell and transitional cell carcinoma in a Japanese population undergoing maintenance dialysis

PURPOSE: We verified differences in the incidence, clinical characteristics and outcomes between patients on chronic dialysis for end stage renal disease with renal cell carcinoma (RCC) and those with transitional cell carcinoma (TCC). MATERIALS AND METHODS: Data regarding RCC and TCC were reviewed in the medical records of 6,201 patients with end stage renal disease who underwent chronic dialysis between January 1990 and June 2003 in our 38 affiliated dialysis centers, and data were compared with those reported in Australia and New Zealand. RESULTS: Among the patients RCC developed in 38 (0.61%) and TCC developed in 16 (0.26%) during maintenance dialysis. The primary renal disease was chronic glomerulonephritis in patients with RCC (68.4%) and diabetic nephropathy in patients with TCC (43.8%, p = 0.002). Mean patient age at initiation of dialysis was 45 years for those with RCC and 63 for those with TCC (p < 0.001). Mean interval from dialysis induction to tumor diagnosis was 143 months for patients with RCC and 54 months for patients with TCC (p < 0.001). Of 38 RCCs 23 (60.5%) were incidentally detected by regular abdominal imaging examinations while painless gross hematuria was the cardinal symptom in 13 (81.2%) of 16 TCCs. Overall and cancer specific survivals after tumor diagnosis were significantly superior in patients with RCC compared to those with TCC (p = 0.0001 and p = 0.0003, respectively), and the cancer specific 5-year survival was 88.9% for RCC and 29.5% for TCC. In both cancers tumor stage significantly increased the risk of cancer specific death. Compared with patients from Australia and New Zealand, the incidence of RCC was higher and that of TCC was lower in our patients (p <0.001). CONCLUSIONS: In the Japanese population on dialysis RCC is more common than TCC. Since long-term dialysis is a risk factor for RCC, regular imaging examinations may have contributed to the favorable outcome of our patients on dialysis with RCC. In contrast, the unfavorable outcome of TCC suggests the need for effective diagnostic measures for early detection of TCC in patients on dialysis.     

Bladder tumor recurrence after primary surgery for transitional cell carcinoma of the upper urinary tract

OBJECTIVE: Primary transitional cell carcinoma (TCC) of the upper urinary tract represents 6-8% of all TCC cases. Nephroureterectomy with removal of a bladder cuff is the treatment of choice. The rates of TCC recurrence in the bladder after primary upper urinary tract surgery described in the literature range between 12.5 and 37.5%. In a retrospective analysis we examined the occurrence of TCC after nephroureterectomy for upper tract TCC in patients without a previous history of bladder TCC at the time of surgery. METHODS: Between 1990 and 2002, 29 patients underwent primary nephroureterectomy for upper tract TCC. The mean age of the patients was 69.5 years. In 5 cases upper urinary tract tumors were multilocular, in the remaining cases unilocular in the renal pelvis (n=12) or the ureter (n=12). The follow-up was available for 29 patients with a mean follow-up of 3.37 (0.1-11.2) years. RESULTS: 11/29 (37.9%) patients had TCC recurrence with 9/11 patients having bladder TCC diagnosed within 2.5 years (0.9-6.0) after nephroureterectomy. 13/29 patients are alive without TCC recurrence, 3/29 patients died due to systemic TCC progression and 5/29 died of unrelated causes without evidence of TCC recurrence. CONCLUSION: Our data indicate a high incidence of bladder TCC after nephroureterectomy for primary upper tract TCC of up to 6 years after primary surgery. Because of the high incidence of bladder TCC within the first 3 years of surgery, careful follow-up is needed over at least this period.     

Diagnostic value of voided urine and bladder barbotage cytology in detecting transitional cell carcinoma of the urinary tract.

In this article we report on our experience with the use of urine cytology for the screening and diagnosis of transitional cell carcinoma (TCC) of the bladder and upper urinary tracts at our institution between January 1987 and December 1995. A total of 76 patients were included in the study. All patients had voided urine cytology studies read as positive or highly suspicious for malignancy and no prior history of TCC of the urinary tract. All these patients subsequently underwent cystoscopy, bladder/ureteral barbotage cytology, random bladder biopsies, and radiographic studies of the upper tracts. Of the 76 patients with positive urine cytology, 53 also had barbotage urine cytologies which were positive. Six of these patients were found to have cystoscopically evident TCC of the bladder, and 1 patient had upper tract TCC. Three other patients subsequently went on to develop TCC of the bladder at 52, 89 and 111 months of follow-up. An additional patient was diagnosed with upper tract TCC at 12 months of follow-up. Among the 23 patients with negative bladder/ureteral barbotage cytology, 3 patients, 2 at the time of initial cystoscopy, and one 15 months later, showed evidence of TCC. Median patient follow-up was 97 (range 35-132) months. Thus of 76 patients with initial positive voided urine cytology studies, only 9 proved to have TCC at initial work-up, while 5 other patients were diagnosed with TCC during a median follow-up of 97 months. The statistical diagnostic values of the bladder/ureteral barbotage urine cytology studies at the time of cystoscopic work-up were: sensitivity 77%; specificity 31%; positive predictive value 13%, and negative predictive value 91%. Our data suggest that in patients without a previous history of TCC, the diagnostic value of bladder barbotage urine cytology is insignificant, and therefore not cost effective to be included as part of the routine work-up of TCC. Moreover, in patients with initially positive voided urine cytology and negative work-up, if the cytology subsequently becomes negative, the likelihood of the development of TCC is low. However, if the initially positive cytology continues to remain positive, there is a much higher probability of TCC being detected in this population.     

Pyruvate kinase type tumor M2 in urological malignancies

INTRODUCTION: The dimeric form of pyruvate kinase type M2 is overexpressed in tumor cells (TuM2-PK). The aim of the present study was to evaluate the clinical value of TuM2-PK as a tumor marker for renal cell carcinoma (RCC), transitional cell carcinoma of the bladder (TCC) and prostate cancer (PCA) by using a commercially available enzyme-linked immunosorbent assay for detection of TuM2-PK in plasma. MATERIAL AND METHODS: The TuM2-PK concentration in EDTA plasma was determined quantitatively and immunologically using an ELISA (ScheBoTech, Germany). We measured the TuM2-PK plasma levels of 83 patients with RCC, 30 patients with TCC and 30 patients with PCA before any therapy. 100 patients with various non-malignant urological disorders were recruited as the control group. RESULTS: Only patients with RCC showed significantly elevated plasma levels of TuM2-PK compared to the control group (p < 0.01). We found a sensitivity of 42.6% and a specificity of 80.4% using a cut-off value of 15 U/ml (manufacturer's recommendation). During follow-up, only 50% showed increasing plasma levels of TuM2-PK in case of metastases. Significant differences could not be detected in either TCC or PCA. CONCLUSIONS: Our data suggest that TuM2-PK is not a useful marker for TCC and PCA. Due to low sensitivity and specificity, TuM2-PK is not suitable for the diagnosis of RCC. Whether TuM2-PK may be useful in advanced RCC to control success of palliative treatment regimens is still unclear.     

膀胱移行细胞癌组织中黑色素瘤抗原基因及蛋白的表达

目的探讨膀胱移行细胞癌(TCC)中黑色素瘤抗原(MAGE)基因mRNA的表达及其临床意义。方法采用逆转录聚合酶链反应(RT PCR)技术检测3个膀胱TCC细胞株和20例膀胱TCC患者癌组织(新鲜标本,T1期7例,T2期5例,T3期6例,T4期2例;G11例,G211例,G38例)MAGE A1,A2,A3,A4mRNA表达,免疫组化法检测105例膀胱TCC患者癌组织(石蜡标本,T1期35例,T2期12例,T3期26例,T4期13例,另19例无法确定分期;G113例,G244例,G348例)MAGE A4蛋白的表达。结果3个膀胱TCC细胞株均有MAGE基因mRNA的表达;20例膀胱TCC新鲜标本组织MAGEmRNA阳性:A112例(60%),A216例(80%),A311例(55%),A418例(90%),A1～A4均阳性8例(40%)。105例膀胱TCC石蜡标本组织中MAGE A4蛋白阳性53例(50%),高分级膀胱TCC组织中强表达(++或+++)率为27%(13/48),显著高于低分级的4%(2/57)(F=12.00,P<0.01),高分期膀胱TCC组织中强表达率为27%(14/51),显著高于低分期的0%(0/35)(F=11.48,P<0.01)。结论MAGE基因在膀胱TCC中有较高表达,分级或分期高的膀胱TCC中MACE A4蛋白明显强表达。     

组织培养加药物敏感性测定在表浅膀胱癌术后丝裂霉素灌注化疗中的指导作用

目的 探讨组织培养加药物敏感性测定在指导表浅膀胱癌术后丝裂霉素(MMC)膀胱灌注化疗中的应用价值.方法 原发表浅膀胱移行细胞癌患者41例.男30例,女11例.平均年龄55岁.TNM分期:Ta 10例、T1 31例.病理分级:G1 9例、G2 22例、G3 10例.采用经尿道电切或膀胱部分切除术保留膀胱.肿瘤标本依次行三维组织培养和改良噻唑盐(MTT)法药物敏感性测定.生长抑制率>70%为高度敏感,50%～70%为中度敏感,<50%为不敏感.41例患者术后均行MMC标准膀胱灌注化疗.无复发随访时间5年,中途复发者则随访结束.结果 41例患者癌组织经1 g/L浓度MMC作用2 h后不敏感13例,其中Ta 1例、T1 12例(P=0.009),G1 1例、G2 7例、G35例(P=0.101).灌注化疗后随访3～5年,复发16例(39%),其中Ta 1例、T1 15例(P=0.059),G210例、G3 6例(P=0.016).对MMC不敏感组的复发率为77%(10/13),敏感组仅为21%(6/28,P=0.004).单因素Kaplan-Meier生存分析和Log-rank检验结果显示,平均无肿瘤复发时间不敏感组为16.5个月,敏感组为49.2个月(P<0.001).多因素Cox回归分析显示对MMC敏感性是独立预后因子(P=0.008).此法预测MMC膀胱灌注化疗效果的准确率为78%.结论 利用组织培养药物敏感性测定方法指导表浅膀胱癌术后MMC灌注化疗,可提高疗效,降低肿瘤复发率.     

Prospective study of transitional cell carcinoma in the prostatic urethra and prostate in the cystoprostatectomy specimen. Incidence, characteristics and preoperative detection

OBJECTIVES: To prospectively evaluate the incidence of transitional cell carcinoma (TCC) in the prostatic urethra and prostate in the cystoprostatectomy specimen, investigate characteristics of bladder tumours in relation to the risk of involvement of the prostatic urethra and prostate and examine the sensitivity of preoperative loop biopsies from the prostatic urethra. MATERIAL AND METHODS: Preoperatively, patients were investigated with cold cup biopsies from the bladder and transurethral loop biopsies from the bladder neck to the verumontanum. The prostate and bladder neck were submitted to sagittal whole-mount pathological analysis. RESULTS: The incidence of TCC in the prostatic urethra and prostate in the cystoprostatectomy specimen was 29% (50/175 patients). Age, previous bacillus Calmette-Guérin treatment, carcinoma in situ (Cis) in the cold cup mapping biopsies and tumour grade were not associated with the risk of TCC in the prostatic urethra/prostate. Cis, multifocal Cis (> or = 2 locations) and tumour location in the trigone were significantly more common in cystectomy specimens with TCC in the prostatic urethra and prostate: 21/50 (42%) vs 32/125 (26%), p=0.045; 20/50 (40%) vs 27/125 (22%), p=0.023; and 20/50 (40%) vs 26/125 (21%), p=0.01, respectively. Preoperative resectional biopsies from the prostatic urethra in the 154 patients analysed identified 31/47 (66%) of patients with TCC in the prostatic urethra/prostate, with a specificity of 89%. The detection of stromal-invasive and non-stromal involvement was similar: 66% and 65%, respectively. CONCLUSIONS: The incidence of TCC in the prostatic urethra and prostate was 29% (50/175) in the cystoprostatectomy specimen. Preoperative biopsies from the prostatic urethra identified 66% of patients with such tumour growth. Our findings suggest that preoperative cold cup mapping biopsies of the bladder for detection of Cis add little extra information with regard to the risk of TCC in the prostatic urethra and prostate.     

Thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell carcinoma: relationship between histological parameters and chemosensitivity to 5-fluorouracil

OBJECTIVES: Thymidine phosphorylase (TdR-Pase) and dihydropyrimidine dehydrogenase (DPD) are thought to be key enzymes in the metabolic pathway of 5-fluorouracil (5-FU). Theoretically, cancer cells which have high TdR-Pase activity and/or low DPD activity should be sensitive to 5-FU. TdR-Pase is also known to have angiogenic activity which helps tumor progression and metastasis. On the other hand, little is known concerning the relationship of DPD activity with clinical malignant potential in renal cell carcinoma (RCC). In this study, we measured both TdR-Pase and DPD activities in surgically obtained RCC tissues and examined the relationship between these enzymatic activities and histological parameters. In addition, the results of in vitro chemosensitivity testing were also analyzed to determine whether TdR-Pase and/or DPD activity in carcinoma cells can predict the efficacy of 5-FU. METHODS: RCC tissues from 53 patients were obtained. TdR-Pase and DPD activities were measured by ELISA and radioenzyme assay, respectively. Sensitivity to 5-FU was assessed by histoculture drug response assay (HDRA), an in vitro chemosensitivity test, for 20 of the 53 specimens. RESULTS: Both TdR-Pase and DPD activities of RCC increased with histological grade. There was a significant positive correlation between the TdR-Pase activity and 5-FU sensitivity. In addition, a stronger positive correlation was found between TdR-Pase / DPD ratio and 5-FU sensitivity. DPD exhibited no correlation with 5-FU sensitivity. CONCLUSIONS: The activity of both enzymes increased with malignant potential of RCC. TdR-Pase appeared to be the enzyme regulating activation of 5-FU in RCC.     

浅表性膀胱肿瘤对化疗药物的敏感性研究

目的:探讨敏感化疗药物预防浅表性膀胱癌术后复发的作用。方法:对30例表浅性膀胱癌体外原代细胞培养,用表阿霉素、羟基喜树碱、吡柔比星、丝裂霉素和盐酸米托蒽醌进行MTT法药物敏感实验(敏感实验组),用最敏感药物行膀胱灌注;同期选择30例患者用吡柔比星灌注作为对照(对照组)。结果:敏感实验组17例对吡柔比星最敏感,6例对盐酸米托蒽醌最敏感,3例对丝裂霉素最敏感,1例对羟基喜树碱最敏感,1例对表阿霉素最敏感,2例对5种化疗药物都不敏感。28例患者分别选择最敏感药物灌注后随访2年,2例复发(7.1%)。对照组吡柔比星灌注后随访2年,有8例复发(26.7%)。两组比较差异有统计学意义(P<0.05)。结论:5种化疗药物对膀胱肿瘤的体外细胞毒作用不同,其中吡柔比星的抑制作用最强。根据药物敏感实验对浅表性膀胱肿瘤行灌注治疗,对预防肿瘤复发有较好效果。     

Telomerase activity in solid transitional cell carcinoma, bladder washings, and voided urine

Telomerase activity has been detected in a wide variety of human malignancies. It appears to be one of the fundamental ingredients necessary for cellular immortality. We sought to determine the incidence of telomerase activity in solid transitional cell carcinoma (TCC) specimens, benign urothelium, bladder washings, and voided urine from patients with TCC identified cystoscopically compared with controls. Telomerase activity was measured in 26 solid bladder cancers and 13 benign urothelial specimens using the telomere repeat amplification protocol (TRAP), a polymerase chain reaction (PCR) based assay. Telomerase activity was further measured in the centrifuged cellular material obtained from the bladder washings of 26 patients with TCC and 40 with benign urologic disease found to have a normal cystoscopy. All patients with hematuria were additionally evaluated with an upper tract radiographic examination and found to be free of malignancy. Voided urine was likewise evaluated in 11 patients with TCC, 12 with benign urologic diseases, and 56 asymptomatic control subjects. Telomerase activity was detected in 25 of 26 (96%) solid specimens, 21 of 26 (81%) bladder washings, and 6 of 11 (54%) voided urine specimens from patients with histologically confirmed TCC. In the control group, 2 of 13 (15%) benign urothelial specimens and 2 of 56 (4%) voided urine specimens from the asymptomatic volunteer group demonstrated telomerase activity. Of those with benign urologic disease, 16 of 40 (40%) bladder barbotage specimens and 6 of 12 (50%) voided urine specimens demonstrated telomerase activity. Sensitivity and specificity of telomerase as a marker for TCC were 81% and 60%, respectively, in the bladder washings group and 54% and 50%, respectively, in voided urine. These data indicate that activation of telomerase is frequent in solid TCC and appears to be a sensitive marker in bladder washings of patients with TCC. We noted an unexpectedly high false positive detection rate in patients with benign urologic diseases, especially those with symptomatic benign prostatic hyperplasia. An additional study of a larger number of both bladder cancer patients and those at risk is necessary to determine if telomerase activity could play a role as a diagnostic and/or surveillance marker of TCC. Published by Elsevier Science Inc.     

肾盂输尿管癌术后膀胱灌注化疗对复发膀胱癌的影响

目的 探讨肾盂输尿管癌术后膀胱灌注化疗对膀胱复发癌的影响.方法 对96 例获随访的原发性肾盂输尿管癌患者的临床资料进行回顾性研究总结.结果 行肾盂输尿管膀胱部分切除术术后未进行膀胱灌注化疗的患者膀胱癌复发率为34.4%(11/32),术后行膀胱灌注化疗者膀胱癌复发率为18.8%(12/64),差异有显著性意义(pO.05).术中先行输尿管末端结扎者术后膀胱癌复发率较未采取结扎措施者低,但两者相比未见统计学意义(P>O.05).结论 肾盂输尿管癌行肾输尿管膀胱酃分切除术后预防性膀胱灌注化疗可有效降低复发件膀胱癌的发生率.术中游离肾输尿管前行输尿管末端结扎并同时行预防性膀胱灌注化疗对预防肾盂输尿管癌术后再发膀胱癌可能有效.     

肾盂输尿管癌术后膀胱灌注化疗对复发膀胱癌的影响

目的 探讨肾盂输尿管癌术后膀胱灌注化疗对膀胱复发癌的影响.方法 对96 例获随访的原发性肾盂输尿管癌患者的临床资料进行回顾性研究总结.结果 行肾盂输尿管膀胱部分切除术术后未进行膀胱灌注化疗的患者膀胱癌复发率为34.4%(11/32),术后行膀胱灌注化疗者膀胱癌复发率为18.8%(12/64),差异有显著性意义(pO.05).术中先行输尿管末端结扎者术后膀胱癌复发率较未采取结扎措施者低,但两者相比未见统计学意义(P>O.05).结论 肾盂输尿管癌行肾输尿管膀胱酃分切除术后预防性膀胱灌注化疗可有效降低复发件膀胱癌的发生率.术中游离肾输尿管前行输尿管末端结扎并同时行预防性膀胱灌注化疗对预防肾盂输尿管癌术后再发膀胱癌可能有效.     

肾盂输尿管癌术后膀胱灌注化疗对复发膀胱癌的影响

目的 探讨肾盂输尿管癌术后膀胱灌注化疗对膀胱复发癌的影响.方法 对96 例获随访的原发性肾盂输尿管癌患者的临床资料进行回顾性研究总结.结果 行肾盂输尿管膀胱部分切除术术后未进行膀胱灌注化疗的患者膀胱癌复发率为34.4%(11/32),术后行膀胱灌注化疗者膀胱癌复发率为18.8%(12/64),差异有显著性意义(pO.05).术中先行输尿管末端结扎者术后膀胱癌复发率较未采取结扎措施者低,但两者相比未见统计学意义(P>O.05).结论 肾盂输尿管癌行肾输尿管膀胱酃分切除术后预防性膀胱灌注化疗可有效降低复发件膀胱癌的发生率.术中游离肾输尿管前行输尿管末端结扎并同时行预防性膀胱灌注化疗对预防肾盂输尿管癌术后再发膀胱癌可能有效.     

肾盂输尿管癌术后膀胱灌注化疗对复发膀胱癌的影响

目的 探讨肾盂输尿管癌术后膀胱灌注化疗对膀胱复发癌的影响.方法 对96 例获随访的原发性肾盂输尿管癌患者的临床资料进行回顾性研究总结.结果 行肾盂输尿管膀胱部分切除术术后未进行膀胱灌注化疗的患者膀胱癌复发率为34.4%(11/32),术后行膀胱灌注化疗者膀胱癌复发率为18.8%(12/64),差异有显著性意义(pO.05).术中先行输尿管末端结扎者术后膀胱癌复发率较未采取结扎措施者低,但两者相比未见统计学意义(P>O.05).结论 肾盂输尿管癌行肾输尿管膀胱酃分切除术后预防性膀胱灌注化疗可有效降低复发件膀胱癌的发生率.术中游离肾输尿管前行输尿管末端结扎并同时行预防性膀胱灌注化疗对预防肾盂输尿管癌术后再发膀胱癌可能有效.