Is neoadjuvant androgen deprivation therapy beneficial in prostate cancer treated with definitive radiotherapy?

PURPOSE: To determine whether neoadjuvant androgen deprivation therapy (NADT) improves clinical outcomes in patients with prostate cancer treated with definitive radiotherapy. MATERIALS AND METHODS: We retrospectively reviewed medical records of 201 patients with prostate cancer treated with radiotherapy between January 1991 and December 2008. Of these, 156 patients with more than 3 years of follow-up were the subjects of this study. The median duration of follow-up was 91.2 months. NADT was given in 103 patients (66%) with median duration of 3.3 months (range, 1.0 to 7.7 months). Radiation dose was escalated gradually from 64 Gy to 81 Gy using intensity-modulated radiotherapy technique. RESULTS: Biochemical relapse-free survival (BCRFS) and overall survival (OS) of all patients were 72.6% and 90.7% at 5 years, respectively. BCRFS and OS of NADT group were 79.5% and 89.8% at 5 years and those of radiotherapy alone group were 58.8% and 92.3% at 5 years, respectively. Risk group (p = 0.010) and radiation dose > or =70 Gy (p = 0.017) affected BCRFS independently. NADT was a significant prognostic factor in univariate analysis, but not in multivariate analysis (p = 0.073). Radiation dose > or =70 Gy was only an independent factor for OS (p = 0.007; hazard ratio, 0.261; 95% confidence interval, 0.071-0.963). CONCLUSION: NADT prior to definitive radiotherapy did not result in significant benefit in terms of BCRFS and OS. NADT should not be performed routinely in the era of dose-escalated radiotherapy.

Recent Changes in the Clinicopathologic Features of Korean Men with Prostate Cancer: A Comparison with Western Populations

PURPOSE: The aim of this study was to evaluate the recent changes in the clinicopathologic features of prostate cancer in Korea and to compare these features with those of Western populations. MATERIALS AND METHODS: We retrospectively reviewed the data of 1582 men undergoing radical prostatectomy for clinically localized prostate cancer between 1995 and 2007 at 10 institutions in Korea for comparison with Western studies. The patients were divided into two groups in order to evaluate the recent clinicopathological changes in prostate cancer: Group 1 had surgery between 1995 and 2003 (n=280) and Group 2 had surgery between 2004 and 2007 (n=1302). The mean follow-up period was 24 months. RESULTS: Group 1 had a higher prostate-specific antigen level than Group 2 (10.0 ng/mL vs. 7.5 ng/mL, respectively; p<0.001) and a lower proportion of biopsy Gleason scores < or =6 (35.0% vs. 48.1%, respectively; p<0.001). The proportion of patients with clinical T1 stage was higher in Group 2 than in Group 1. Group 1 had a lower proportion of organ-confined disease (59.6% vs. 68.6%; p<0.001) and a lower proportion of Gleason scores < or =6 (21.3% vs. 33.0%; p<0.001), compared to Group 2. However, the relatively higher proportion of pathologic Gleason scores < or =6 in Group 2 was still lower than those of Western men, even though the proportion of organ-confined disease reached to that of Western series. CONCLUSION: Korean men with prostate cancer currently present better clinicopathologic parameters. However, in comparison, Korean men still show relatively worse pathologic Gleason scores than Western men.

The Incidence and Risk Factors for Inguinal Hernia after Radical Retropubic Prostatectomy / 대한비뇨기과학회지

PURPOSE: The aim of this study was to determine the risk factors for developing an inguinal hernia after undergoing radical retropubic prostatectomy(RRP). MATERIALS AND METHODS: We retrospectively investigated the hospital records of 382 patients who underwent RRP and who were followed over 12 month periods at our institute between January 2000 and December 2006. All the operations were performed by a single surgeon. The clinical and pathological parameters were compared between the patients with and without inguinal hernia, and the risk factors were analyzed using the Cox proportional hazards model. RESULTS: The mean age of the patients was 64.6 years(range, 40 to 83). 32(8.3%) of the 382 patients developed an inguinal hernia at a mean time of 14 months. 8(25.8%) of 32 patients developed an inguinal hernia within 6 months, 23(61.8%) within 1 year, 26(83.9%) within 2 years and 28 (90.3%) developed an inguinal hernia within 3 years. 25(78.1%) developed an inguinal hernia in the right side, 3(9.4%) in left and 4(12.5%) developed an inguinal hernia in both sides. The operative time(p50cc, p=0.012) were independent predictors for post-prostatectomy inguinal hernia. CONCLUSIONS: The results of our study show that the duration of surgery, pelvic lymph node dissection, the presence of transfusion and the prostate volume all increase the risk of post-radical retropubic prostatectomy inguinal hernia.

Safety of Adjuvant Chemotherapy after Orthotopic Bladder Substitution: Comparison to Ileal Conduit / 대한비뇨기과학회지

PURPOSE: Radical cystectomy with urinary tract reconstruction currently remains the standard treatment for invasive bladder cancer, and adjuvant chemotherapy is usually considered for patients with a clinical stage >T2 or nodal metastasis. The aim of this study was to assess the safety of adjuvant chemotherapy in patients with orthotopic bladder substitution in comparison to ileal conduit. MATERIALS AND METHODS: We retrospectively analyzed the patients who underwent radical cystectomy and urinary diversion between 1990 and 2005. The patients who underwent adjuvant chemotherapy were stratified into two groups: those who had orthotopic bladder substitution and those who had ileal conduit. The chemotherapy regimen, renal function change, complications from adjuvant chemotherapy and other relevant data were analyzed. RESULTS: Overall, 341 patients had radical cystectomy, 89 had adjuvant chemotherapy, 28 had orthotopic bladder substitution and 61 had ileal conduit. The patient characteristics, including age, stage and follow-up, were similar in both groups. In all, 42% of patients had grade 1 toxicity, 16% had grade 2, 14% had grade 3 and 0% had grade 4. No patients had serious organ toxicity and none died. There were no significant differences in the chemotherapy toxicity and renal function change among the two groups. CONCLUSIONS: Adjuvant chemotherapy is safe and well tolerated by patients with either orthotopic bladder substitution or ileal conduit. There was no increased morbidity or mortality due to adjuvant chemotherapy in the patients who had orthotopic bladder substitution. Hence, orthotopic bladder substitution should not be denied to those patients with bladder cancer and who might require adjuvant chemotherapy.

Clinico-pathological Characteristics of Prostate Cancer in Korean Men and Nomograms for the Prediction of the Pathological Stage of the Clinically Localized Prostate Cancer: A Multi-institutional Update / 대한비뇨기과학회지

PURPOSE: In this multi institutional study, the data of 604 men with clinically localized prostate cancer, who underwent radical prostatectomy, with updated nomograms predicting the pathological stage, were analyzed. MATERIALS AND METHODS: Prostate biopsies and prostatectomy specimens from men treated with radical prostatectomy, obtained between 1990 and 2003, were included. The patient distribution with respect to clinical stage, serum prostate-specific antigen (PSA) and biopsy Gleason score, as well as final pathological findings, including organ-confined disease (OCD), extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node metastasis (LNM), were analyzed for the construction of nomograms representing the percent probabilities of each respective pathological outcome. RESULTS: The median serum PSA at the time of surgery and biopsy Gleason score were 9.9ng/ml and 7, respectively. The preoperative serum PSA was 4ng/ml or less in 38 (6.3%) patients and the tumor was impalpable in 292 (48.2%) of patients. The biopsy Gleason scores were 7 and 8 or higher in 186 (30.7%) and 169 (27.9%), respectively. Throughout the clinical stages and PSA ranges, the Gleason score was 7 or higher in more than 50% of patients, but 8-10 in 20-30%. The overall OCD, ECE, SVI and LNM rates were 57.1, 27.8, 10.9 and 4.2%, respectively. CONCLISIONS: A significantly high proportion of prostate cancers arising in Korean men exhibited poor differentiation, with Gleason scores of 7 or higher, regardless of the clinical stage or initial serum PSA. Updated nomograms acknowledging such characteristics have been developed, which may aid in the treatment planning of these individuals.

The Usefulness of the Critical Pathway for Radical Retropubic Prostatectomy / 대한비뇨기과학회지

PURPOSE: The critical pathway (CP) for radical retropubic prostatectomy (RRP), which is the efficient standardized guideline of clinical practice, was established for all the medical staff, nurses, patients and hospital managers for managing patients with RRP. The aim of this study was to evaluate the usefulness of this CP for RRP. MATERIALS AND METHODS: Our series consisted of 256 consecutive patients who had undergone RRP at a single institution from March 1, 2002 till May 31, 2005. The CP of RRP was implemented January 1, 2004. The patients were subdivided into two groups: (1) the non critical pathway (NCP) group that was made of 91 patients who were treated other than by the CP (from March, 2002 through December, 2003) and (2) the CP group of 134 patients who were placed on CP (from January, 2004 through May, 2005). The factors compared in this study included the average length of stay (LOS), the average hospital charges, the postoperative complications and the patient satisfaction between the two groups. RESULTS: There were no significant differences in the parameters between the two groups including age, the prostate-specific antigen (PSA) level, the Gleason score and the stage. The average LOS decreased significantly after implementation of CP without increasing the incidence of postoperative complications. The average hospital charges were significantly lower for the CP group than for the group without CP. The patients in the CP group were more satisfied than the other patients. CONCLUSIONS: The CP for RRP seems to be effective practical guidelines for managing radical retropubic prostatectomy patients.

The Impact of PSA on Pathologic Characteristics in the Radical Prostatectomy with PSA Level of 4-10ng/ml / 대한비뇨기과학회지

PURPOSE: We evaluated the effect of the serum prostate specific antigen (PSA) levels in the range 4.1 to 10.0ng/ml on the pathologic characteristics after a radical prostatectomy. MATERIALS AND METHODS: Between July 1997 and June 2004, 117 men (64 years: 44-75) with an intermittent PSA level underwent radical retropubic prostatectomy. The patients were divided into 6 groups according to the PSA level (4.1-5.0, 5.0-6.1, 6.1-7.0. 7.1-8.0, 8.1-9.0 and 9.1-10.0ng/ml), and compared the age, prostate volume, Gleason score of biopsy specimen and pathologic stage, grade and margin status of prostatectomy specimen between the 6 groups. RESULTS: The mean age, prostate volume and Gleason score of the biopsy were not significantly different between the 6 groups. The pathologic stage and margin status also were not significantly different between the 6 groups. The mean Gleason score was higher in the high PSA group, but this was not statistically significant. When divided into two groups (group with PSA 4.1-7.0 and 7.1-10.0ng/ml), the pathologic stage and margin status were no different. However, the mean Gleason score and the rate of high grade (Gleason score 8-10) prostate cancer were higher in the high PSA group. The mean high grade prostate cancer rates were 22 and 7% in the PSA 7.1-10.0 and 4.1-7.0ng/ml groups, respectively (p=0.019). CONCLUSIONS: A PSA level above 7.0ng/ml in the intermediate group influenced the pathologic grade of the radical prostatectomy. This result suggests that prostate cancer with a PSA level higher than 7.0ng/ml may have a more aggressive feature.

Preliminary Study of Tissue Engineered Bladder Regeneration with Poly (epsilon-caprolactone) (PCL) Sheet Seeded with Autologous Muscle-derived Stem Cell / 대한비뇨기과학회지

PURPOSE: To investigate the feasibility of using a poly (epsilon-caprolactone) (PCL) sheet seeded with autologous muscle-derived stem cells as a bladder substitute. MATERIALS AND METHODS: Muscle-derived stem cells were isolated from the gastrocnemius muscle of 9 female Sprague-Dawley rats using a preplate technique, and cultured on a 5x5mm PCL sheet. The sheets were implanted into the mesentery of the rats in an autologous manner. Three rats were sacrificed 2, 4 and 8 weeks after implantation, and the morphological changes were assessed by H&E and immunofluorescence staining including DAPI, myosin heavy chain (MHC) and choline acetyl transferase (CAT). RESULTS: All the rats survived for the scheduled time. A mild inflammatory reaction was observed around the PCL sheet in the postoperative 2-week specimen but this receded with time. Muscle cells on the sheet were observed over the experimental period. The 8-week specimen showed a moderate amount of muscle cells on the sheet, and MHC and CAT immunofluorescence staining showed a positive reaction. The muscle layer was not well organized. Angiogenesis was quite noticable between the sheet and the muscle cells on the 8-week specimen. CONCLUSIONS: A PCL sheet seeded with autologous muscle-derived stem cells showed skeletal muscle differentiation on the sheets 8 weeks after mesenteric implantation in an autologous manner. This suggests the feasibility of using a PCL sheet seeded with autologous muscle-derived stem cell as a bladder substitute.

The Evaluation of Concordance of the Gleason Score between Prostatectomy and Biopsies Showing more than Two Different Gleason Scores in Positive Cores / 대한비뇨기과학회지

Purpose: We evaluated the variables that may predict the final Gleason score of a radical prostatectomy in the patients showing more than two different Gleason scores in their positive core biopsy specimens. Materials and Methods: We reviewed the pathological data of patients diagnosed with prostate cancer using extended (12 site or more) needle biopsies who underwent a radical retropubic prostatectomy. A total of 73 patients showed more than two different Gleason scores in their biopsy specimen. The following parameters were assessed: highest Gleason score in the biopsy specimen, the Gleason score of the highest tumor percentage in the core and the highest tumor ratio score (Gleason score of highest total tumor length of same Gleason score/total core length of same Gleason score). Concordance of the Gleason scores between the biopsy specimen and prostatectomy was also examined. Results: The highest tumor ratio score showed the highest (64.4%) concordance rate. The concordance rates of the Gleason scores of the highest tumor percentage in the core and the largest linear cancer length were 59 and 58%, respectively. The concordance rate of the highest Gleason score in the biopsy specimens was only 47%. When stratified by grade: well differentiated (Gleason score=6), moderate (7) and poorly differentiated (8-10), the grade concordance rate of the highest tumor ratio score was 73%. The grade concordance rates of the highest and largest linear cancer length Gleason scores were 64.4 and 64.3%, respectively. Conclusions: If a biopsy specimen shows more than two different Gleason scores in positive cores, the highest tumor ratio score may be the most useful variable for predicting the final Gleason score from radical prostatectomy specimens.

The Efficacy of 12-Site Biopsy Protocol in Men with Elevated Serum Prostate-Specific Antigen Level Only / 대한비뇨기과학회지

Purpose: We evaluated the improvement in the rate of prostate cancer detection with the use of an extensive 12-site biopsy protocol in patients with only an elevated level of serum prostate-specific antigen (PSA). Materials and Methods: A total of 109 men with elevated PSA levels between 3 and 20ng/ml, but with no abnormal finding on digital rectal and transrectal ultrasound examinations, received transrectal ultrasound- guided prostate biopsies, which were performed at 12 sites, including the routine sextant and 6 far lateral regions (lateral apex, mid-lobe and base). The improvement in the detection rate was assessed according to the PSA level and prostate volume. Results: The mean age and PSA level of the patients were 63.5 8.6 years and 7.0 3.7ng/ml, respectively. Twenty-eight (25.7%) out of 109 men were diagnosed with prostate cancer. A traditional sextant biopsy detected 19 (67.9%) of the 28 prostate cancer patients, while 9 (32.1%) cancers were detected in the lateral region only. Overall, this extensive protocol resulted in a significant improvement, 8.3% (17.4 to 25.7%), in the detection rate (p=0.032). The improvement in men with a PSA of 10 ng/ml or less was 8.1% (14.0% to 22.1%, p=0.007) and in those with a PSA greater than 10 ng/ml the improvement was 8.7% (30.4% to 39.1%, p=0.162). The improvement in men with a prostate volume of 50cc or less was 8.0% (22.3% to 30.3%, p=0.083) and in those with a prostate volume greater than 50cc this was 9.1% (6.1% to 15.2%, p=0.043). Conclusions: The twelve-site biopsy protocol is a more efficient method in men with a PSA and prostate volume of 10ng/ml or less and greater than 50cc, respectively, compared to the sextant protocol.

The Effects of Local Anesthetics on the Human Bladder Contractility: Organ Bath Study / 대한비뇨기과학회지

PURPOSE: We investigated the in vitro effects of local anesthetics on the contractility of the human bladder. MATERIALS AND METHODS: Using human bladder strips obtained from 20 patients undergoing cystectomy, we investigated the effects of tetracaine, bupivacaine, lidocaine, and ropivacaine on the basal spontaneous contractions and contractions induced by various stimuli: KCl, carbachol (CCh), and electrical field stimulation (EFS). The effect of local anesthetic agents on the Ca2+ -independent sustained tonic contraction (SuTC) was also investigated. RESULTS: Spontaneous contraction was not observed in 181 out of 187 bladder strips. Local anesthetics inhibited nerve-mediated contractions (EFS, 0.8msec) in a concentration-dependent manner and also inhibited non-nerve mediated contractions induced by KCl, long pulse EFS (direct muscle stimulation, 100msec), and CCh. The rank order of inhibitory potency on nerve-mediated contractions and CCh-induced contractions was ropivacaine, tetracaine, bupivacaine, and lidocaine, while the rank order on KCl-induced contractions was ropivacaine, tetracaine, lidocaine, and bupivacaine, both in decreasing order. Higher concentrations of local anesthetics were needed to inhibit the non-nerve-mediated bladder contraction than the nerve-mediated contraction. SuTC was also suppressed by all local anesthetics in a concentration dependent manner. CONCLUSIONS: Our study demonstrates that local anesthetics have inhibitory effects on the contraction of human bladder that is induced by various stimuli. These effects suggest that local anesthetics may be useful as diagnostic and therapeutic agents for bladder dysfunction.

The Impact of Pelvic Lymphadenectomy on the Survival of Patients Who Underwent Radical Cystectomy for Transitional Cell Carcinoma of the Bladder / 대한비뇨기과학회지

PURPOSE: We assessed the impact of pelvic lymphadenectomy on the survival of patients who had undergone radical cystectomy. MATERIALS AND METHODS: We retrospectively reviewed 107 patients who underwent radical cystectomy for transitional cell carcinoma of the bladder between January 1991 and December 2000. We preoperatively excluded patients with evidence of pelvic lymphadenopathy and distant metastases from the study. Among 107 patients, 61 patients (Group A) underwent pelvic lymphadenectomy while 46 patients (Group B) did not. The clinicopathological parameters were not significantly different in the two groups. RESULTS: In group A, 12 patients (19.6%) were found to have pelvic node metastases. Five-year overall survival and recurrence-free survival rates were 68% and 75% for Group A, respectively. In group B, 5-year overall survival and recurrence-free survival rates were 36% and 56%, respectively. Multivariate analysis revealed that T stage (p=0.004) and lymphadenectomy (p=0.044) were significant prognostic factors for survival. CONCLUSIONS: The overall survival rates between the two groups were significantly different. Our findings suggested that lymphadenectomy may improve the prognosis of patients who underwent radical cystectomy for transitional cell carcinoma of the bladder.

Influence of Blood Vessels, Lymphatics and Perineural Invasion on Prognosis of Patients Treated with Radical Cystectomy for Transitional Cell Carcinoma of Bladder / 대한비뇨기과학회지

PURPOSE: The relationship between pathological parameters, such as blood vessel, lymphatic and perineural invasions, and prognosis, are controversial. We retrospectively analyzed the charts of patients with bladder cancer to identify the prognostic significance of these parameters. MATERIALS AND METHODS: A retrospective review of 125 of 181 patients with bladder cancer treated with radical cystectomy was conducted. Patients treated with neoadjuvant or adjuvant chemotherapy and those who were found to have lymph node metastasis after cystectomy were excluded from the study. RESULTS: The mean patient age was 62.5 years(range 39-84) and the overall median follow-up was 40.1months(range 1 to 146). Blood vessel, lymphatic, and perineural invasions were present in 8.8%, 20.8%, 8.8% of the specimens, respectively, and 28% of the patients had at least one of three factors. Univariate analysis revealed that blood vessel lymphatic, and perineural invasions were prognostic predictors of survival. However, only tumor stage and blood vessel invasion were calculated to be independent factors of survival on multivariate analysis. CONCLUSIONS: In this series, the pathological stage and blood vessel invasion are significant parameters of tumor-free survival in patients who have undergone cystectomy for bladder cancer. Our findings suggest that blood vessel, lymphatic, and perineural invasions should be examined more carefully.

The Impact of Transurethral Resection of Bladder Tumor: Clinicopathologic Analysis of Cystectomy Specimen to Evaluate Residual Tumor / 대한비뇨기과학회지

PURPOSE: We analyzed the impact of transurethral resection of the bladder (TUR-B) in patients with bladder cancer, in whom a subsequent cystectomy was performed. MATERIALS AND METHODS: We reviewed the records of 93 patients, with clinical stage T2 or less transitional cell carcinomas of the bladder that underwent a radical cystectomy at our institute. Before the radical cystectomy, TUR-B was performed for diagnostic and therapeutic purposes in all patients. We used the term "complete TUR" for the following procedures. No residual tumors were found after the TUR endoscopically, also, muscle layer should be present in the TUR specimens and no gross residual tumors were found in the cystectomy specimens by the pathologist. RESULTS: Eleven (26.8%) of the 41 patients with superficial bladder cancer had no evidence of residual tumors. Of the 19 patients with superficial bladder cancer that underwent complete TUR-B, 10 (52.6%) had no residual tumors. For the invasive tumors, 10 (19.2%) of the 52 patients that had a T2 stage disease had no residual tumors, and 10 (29.4%) of the 34 patients with a T2 stage disease, who underwent complete TUR-B, had no residual tumors. In the 38 patients with superficial bladder cancer, 17 (44.7%) changed to a higher stage. Of the 17 patients who underwent complete TUR-B, 3 (17.7%) changed to a higher stage. Among the patients with a T2 stage disease, those with the pT0 stage had a better survival than those with the pT2 stage with residual tumors (p=0.04). CONCLUSIONS: The completeness of TUR-B is important in evaluating residual tumors after a previous TUR-B in those patients with both superficial and invasive bladder cancers.

Change of Cellular Immunity and T Cell Subset of Mouse Immunocytes Activated by Fractionated Bacillus Calmette-Guerin / 대한비뇨기과학회지

PURPOSE: To develope the bacillus Calmette-Guerin(BCG) antitumor component therapy which could reduce the adverse effect of intravesical BCG therapy, we investigated the effect of the fractions of BCG on the immune responses of mouse and compared with whole BCG. MATERIALS AND METHODS: Seven fractions, 4(fraction 1, 2, 3, 4) from BCG cell wall and 1 (fraction 7) front BCG cytoplasm and 2(fraction 5, 6) mixed, were collected by multiple ultrasonification and centrifugation of BCG solution and the difference of each fraction was confirmed by spectrophotometric absorbance. Change of lymphokine killer(LAK), natural killer(NK) and tumor cell dependent cytotoxic(TCDC) activities of mouse spleen cells were investigated by 51Cr releasing assay and proportion of T cell subset in mouse spleen and peritoneal lymhocytes were investigated by flow cytometric analyses using monoclonal antibodies to mouse CD4, CD8 and CD2S cells. RESULTS: In LAK and NK activities, fraction 1, 2 and 3 showed similar results with whole BCG. In TCDC activity, the all 7 fraction showed lower activities compared with BCG. In T cell subset analyses, similar results were found in fraction 1, 2 and 3 compared with whole BCG. CONCLUSIONS: We could suggest that the antitumor activity of BCG seems to be mediated by some component in cell wall. Further investigations which could elucidate these findings should be necessary.

Morphological and Quantitative Analysis on the Expression of Bax in the Rat Prostate following Castration / 대한비뇨기과학회지

PURPOSE: Bax promotes apoptosis and is up-regulated by p53, which is not required for androgen ablation-induced apoptosis of the prostatic cells. We investigated the change of lax during the involution of the rat prostate following castration. MATERIALS AND METHOD: Adult male rats were castrated and the ventral prostatic glands were removed daily for a week following castration. Western blot and immunohistochemical analysis of lax protein were performed using anti-bax rabbit polyclonal IgG. RESULTS: The prostatic weight decreased and the apoptotic cells began to appear 2 days following castration. Western blot analysis showed that lax was absent in the control prostate but began to increase 4 days following castration. Immunohistochemical analysis showed that bars was confined to the cells which had morphological characteristics of the late stage of programmed cell death. CONCLUSIONS: Present results suggest that bars might be involved in the late stage of castration-induced apoptosis of the rat prostatic cells.

Change of Chemosensitivity and Cellular Characteristics of Cisplatinum Resistant Human Bladder Cancer Cells Induced by Long-term Cisplatinum Treatment / 대한비뇨기과학회지

PURPOSE: Cisplatinum has the therapeutic efficacy against a bladder cancer. However, the response is often limited due to appearance of drug-resistant tumor cells. The studies of establishment and characterization of cisplatinum-resistant tumor cells are considered to be helpful in elucidating the underlying mechanism of acquired resistance to cisplatinum in human tumors. MATERIALS AND METHODS: We established cisplatinum-resistant cell lines sequentially, T24Rl and T24R2, which show resistance to cisplatinum at a concentration of 1 and 2microgram /ml, respectively, by the stepwise exposure of T24 human bladder cancer cell to increasing concentrations of cisplatinum. RESULTS: The resistance to cisplatinum of T24Rl and T24R2 cells was 13- and 18-fold that of the parental T24 cells, respective1y. Growth, DNA synthesis and cell cycle distribution of T24Rl and T24R2 cells were not different from those of the parental T24 cells. CONCLUSIONS: These cisplatinum-resistant bladder tumor cell lines could be a useful model to elucidate the biochemical and molecular mechanism Involved In the cisplatinum resistance.