Method for validating cloud mask obtained from satellite measurements using ground-based sky camera.

Error propagation in Earth's atmospheric, oceanic, and land surface parameters of the satellite products caused by misclassification of the cloud mask is a critical issue for improving the accuracy of satellite products. Thus, characterizing the accuracy of the cloud mask is important for investigating the influence of the cloud mask on satellite products. In this study, we proposed a method for validating multiwavelength satellite data derived cloud masks using ground-based sky camera (GSC) data. First, a cloud cover algorithm for GSC data has been developed using sky index and bright index. Then, Moderate Resolution Imaging Spectroradiometer (MODIS) satellite data derived cloud masks by two cloud-screening algorithms (i.e., MOD35 and CLAUDIA) were validated using the GSC cloud mask. The results indicate that MOD35 is likely to classify ambiguous pixels as "cloudy," whereas CLAUDIA is likely to classify them as "clear." Furthermore, the influence of error propagations caused by misclassification of the MOD35 and CLAUDIA cloud masks on MODIS derived reflectance, brightness temperature, and normalized difference vegetation index (NDVI) in clear and cloudy pixels was investigated using sky camera data. It shows that the influence of the error propagation by the MOD35 cloud mask on the MODIS derived monthly mean reflectance, brightness temperature, and NDVI for clear pixels is significantly smaller than for the CLAUDIA cloud mask; the influence of the error propagation by the CLAUDIA cloud mask on MODIS derived monthly mean cloud products for cloudy pixels is significantly smaller than that by the MOD35 cloud mask.

Quantification of hepatitis C virus in patients treated with peginterferon-alfa 2a plus ribavirin treatment by COBAS TaqMan HCV test.

Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG-IFN-alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non-SVR patients with greater accuracy.

Interactions of the drug amphotericin B with phospholipid membranes containing or not ergosterol: new insight into the role of ergosterol.

Amphotericin B (AmB) is an amphipathic polyene antibiotic which permeabilizes ergosterol-containing membranes, supposedly by formation of pores. In water, AmB forms chiral aggregates, modelled as stacks of planar dimers in which the joined polyene chains in each dimer turn round, from one dimer to the following in these stacks, by forming a helical array. Studies of the binding of AmB with L-dipalmitoylphosphatidylcholine (L-DPPC) and L-dilauroylphosphatidylcholine (L-DLPC) bilayers disclose the main following results. (1) An inversion of the helicity of the L-DPPC-bound AmB aggregates, when the L-DPPC bilayers are in the gel phase, is inferred from the evolution of the circular dichroism spectra of AmB+L-DPPC mixtures. (2) An AmB-induced gel-to-subgel transformation of L-DPPC bilayers, in the previous mixtures, is revealed by a differential scanning calorimetry study. (3) The role played by ergosterol in the location of phospholipid-bound AmB aggregates with respect to a phospholipid bilayer is directly demonstrated from atomic force microscopy observations of mica-supported AmB+L-DLPC mixtures, in the presence or absence of ergosterol. While in the absence of ergosterol AmB aggregates remained at the surface of the bilayer, in the presence of ergosterol they appeared embedded within this bilayer and became hollow-centered. As such an embedding in the hydrophobic core of a bilayer requires a rearrangement of the aggregates with respect to their architecture in water, this rearrangement is held responsible for the hollowing of aggregates. The hollow-centered sublayer-embedded AmB aggregates are thought to be the precursors of the formation of AmB pores.

The donor cell type controls anti-hapten (fluorescein isothiocyanate) primary antibody response to hapten-modified syngeneic cells.

Hapten (fluorescein isothiocyanate, FITC)-sensitized syngeneic red blood cells (FITC-RBC) are exceptionally active for induction of anti-hapten primary antibody response, and FITC-modified syngeneic spleen cells depleted of RBC (FITC-SSC) are not immunogenic [4]. The present study has demonstrated that FITC-SSC injected simultaneously with FITC-RBC inhibit partially the anti-FITC response to the latter. Either the immunogenicity of FITC-RBC or the response-inhibiting activity of FITC-SSC was increased as the concentration of hapten-sensitizing cells was raised from 0.005 mg/ml to 2 mg/ml. The inhibition of anti-FITC response by FITC-SSC strictly required live donor cells, but was not dependent on T-cell activity of either the donor or recipient. Neither FITC-thymocytes nor the FITC-T-cell-rich fraction of SSC showed a definite activity for inhibition, whereas the FITC-B-cell-rich fraction of SSC acted very effectively. These results suggest that the primary anti-hapten antibody response to hapten-modified syngeneic cells is primarily controlled by antigen-bearing live donor cells of different cell types.

Initiation-stage enhancement by uracil of N-ethyl-N-hydroxyethylnitrosamine-induction of kidney carcinogenesis in rats.

The present study was conducted to clarify the effects of N-ethyl-N-hydroxyethylnitrosamine (EHEN) and uracil in combination on renal carcinogenesis in female F344 rats. Group 1 animals (n = 30) received a 3-week simultaneous administration of 0.05% EHEN and 3% uracil, and group 2 (n = 26) 0.05% EHEN with a lower 1.5% dose of uracil. Group 3 (n = 30) was treated with 0.05% EHEN alone and group 4 (n = 28) received only 3% uracil for 3 weeks. In all the above four groups, the rats were given basal diet and water without chemical addition for a 48-week period after the 3-week treatment period. Group 5 (n = 33) received no chemicals for the entire 52 weeks. At the end of week 52, renal adenocarcinomas were found in 53%, 31% and 13% of the rats in groups 1, 2, and 3, respectively. The present study thus demonstrated that simultaneous administration of uracil enhances the occurrence of EHEN-induced renal adenocarcinomas in rats.

Expression of aldolase C isozyme in renal cell carcinoma.

The authors localized aldolase C in renal tubules and renal cell carcinoma by immunohistochemical study and quantitative analysis by an enzyme immunoassay. Aldolase C was localized in epithelial cells of loops of Henle and collecting ducts and in those of Bowman's capsules. In renal cell carcinoma, aldolase C was immunohistochemically demonstrated in 95% (41 of 43) of cases, including one sarcomatoid variant. The tissue concentrations of aldolase C in the renal cortex (n = 8) were 12.7 +/- 6.2 micrograms/g protein (mean +/- standard deviation), and those of the medulla (n = 8) were 20.3 +/- 6.9 micrograms/g protein. On the other hand, the concentrations in renal cell carcinoma (n = 26) were 93.5 +/- 95.9 micrograms/g protein: about seven times higher than that in renal cortex (P less than 0.001). These findings indicate that aldolase C was first expressed in renal cell carcinoma, which is derived from proximal renal tubules, because proximal renal tubules had aldolase B but not aldolase C.

Primary transitional cell carcinoma of prostate: case with lymph node metastasis eradicated by neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) therapy.

A case of transitional cell carcinoma of the periurethral prostatic ducts received neoadjuvant chemotherapy consisting of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC), which eradicated pelvic lymph node metastasis, followed by cystoprostatectomy. M-VAC therapy may be indicated for metastatic transitional cell carcinoma of the periurethral prostatic ducts.

Sensitive enzyme immunoassay for human 28 kDa calbindin-D.

A sandwich-type enzyme immunoassay for human 28 kDa vitamin D-dependent calcium binding protein (calbindin-D) was established with a sensitivity of 1 pg/tube. Antisera were generated in rabbits injected with highly purified human kidney calbindin-D, and specific antibodies to calbindin-D were purified by the use of a column of calbindin-D-coupled Sepharose. The purified antibodies showed a single band at the position corresponding to calbindin-D on an immunoblotting test with a crude extract of human kidney. The assay system consisted of polystyrene balls with immobilized F(ab')2 antibodies and the same antibodies labeled with beta-D-galactosidase from Escherichia coli. The assay was specific to 28 kDa calbindin-D, showing no cross-reactivity with other calcium binding proteins such as S-100a0 (alpha alpha), S-100b (beta beta), parvalbumin and calmodulin. The assay was also reproducible (coefficients of variation between assays were less than 10%). With the present method, immunoreactive calbindin-D could be detected in various human tissues, with major concentrations in kidney and brain. The values for immunoreactive calbindin-D in various body fluids of healthy subjects varied from undetectable in serum and semen to 3.8 +/- 2.0 (SD) micrograms/g creatinine in urine and 2.9 +/- 0.8 (SD) micrograms/l in cerebrospinal fluid. Immunohistochemically, the calbindin-D in human kidney was localized in epithelial cells of distal tubules.

Grade 3 bladder cancer with lamina propria invasion (pT1): characteristics of tumor and clinical course.

To determine the clinical characteristics of grade 3 tumors with lamina propria invasion (pT1), we reviewed the data of 217 patients with superficial bladder cancer who had initially been treated by transurethral resection (193 patients) and fulguration (4), supravesical resection (13) or partial cystectomy (7). We classified the patients into four groups according to histological grade and stage of disease: group 1) grade 0 or 1, pTa tumors (n = 58); group 2) grade 2, pTa tumors (n = 106); group 3) grade 2, pT1 tumors (n = 30); and group 4a) grade 3, pT1 tumors (n = 23). Grade 3, pT1 tumors were significantly related to nonpapillary growth (p = 0.0002), multiple tumors (p = 0.005) and irritative bladder symptoms (p = 0.01). The 5-year progression rates were 0% for group 1, 5% for group 2, 8% for group 3, and 18% for group 4a. The respective 5-year survival rates were 97%, 91%, 83% and 79%. All five patients with grade 3, pT1 tumors who had originally undergone total cystectomy (group 4b) remained alive free of disease for a median follow-up 57 months, establishing a far better survival rate than that for group 4a. These findings show that patients with grade 3, pT1 tumors face a high probability of progression and poor chance of survival. Immediate radical treatment is indicated when tumors recur after initial transurethral resection.

Clinicopathological characteristics of small renal cell carcinomas.

To clarify the clinicopathological characteristics of small renal cell carcinomas (RCCs) the authors reviewed data for 154 RCC patients treated between January 1980 and September 1992. Of 20 patients with tumours of 3 cm or less in diameter, 12 (60%) had no related symptoms: 6 (30%) were found during routine physical check-ups and 6 (30%) were incidentally detected during examinations for diseases other than RCC. The remaining 8 (40%) patients demonstrated indicative symptoms. Most small tumours showed expansive growth and nuclear atypia was minimal or moderate. In all 20 cases, the lesions of 3 cm or less were confined to the kidney (pT1 to pT2b) and no lymph node metastasis was found. Only one (5%) had a distant metastasis, and venous involvement was also microscopically observed in only one patient (5%). The 5-year survival rates were 95% for patients with tumours of 3 cm or smaller, 74% for those of 3.1 to 5 cm, and 68% for those of greater than 5 cm. These findings revealed small RCC to demonstrate biologically less malignant behaviour. Early detection of such small lesions by ultrasonography should therefore improve the overall survival of patients with RCC.

Surgical treatment of renal cell carcinoma metastases: prognostic significance.

Between January 1980 and March 1993, 166 patients with renal cell carcinoma were treated at Nagoya University Hospital. Among them 16 (9.6%) underwent surgical removal of 21 metastatic lesions: 12 patients had distant metastases at diagnosis and the other 4 demonstrated new distant metastases during their clinical course after nephrectomy. The metastatic lesions involved the brain in 6 patients, bone in 4, lung in 2, contralateral adrenal glands in 2, soft tissues in 2, lymph nodes in 2, pleura in 1, pancreas in 1, and contralateral renal pelvis in 1. All of the 16 patients underwent nephrectomy and 15 of them (93%) received interferon-alpha therapy. Patients with lesions which were completely resected had significantly longer survival than those with lesions which were palliatively treated and those with metastatic lesions at other sites (p = 0.02). Improvement of performance status was observed in 5 of 6 (83%) patients undergoing palliative surgical treatment. The present study suggests that surgical removal of metastatic lesions prolongs survival in a limited number of renal cell carcinoma patients and that it improves performance status in those symptoms related to metastasis.

Superficial bladder cancer treated by total cystectomy: tumour characteristics and patient survival.

Of 113 patients with bladder cancer who underwent total cystectomy from January 1980 to December 1990, 30 (27%) had superficial tumours (pTa, pTis, and pT1). Nineteen of these 30 patients (63%) were primarily treated by total cystectomy and the remaining 11 (37%) had a past history of treatment for bladder cancer. Major reasons for choice of total cystectomy were multifocal tumours, frequent recurrence, and diffuse carcinoma in situ. Histologically stage pT1, grade 3 tumours were frequently accompanied by carcinoma in situ and often by lymphatic invasion. None of the 24 patients undergoing pelvic lymphadenectomy had lymph node metastasis. Of 25 male patients 15 (60%) underwent simultaneous prophylactic urethrectomy. Two of the remaining 10 males (20%) not undergoing this additional operation died of subsequent urethral recurrence. The 5-year actuarial survival rate was 80% for the 30 patients when all causes of death were considered. It was concluded that patients with superficial bladder cancer who undergo total cystectomy without prophylactic urethrectomy require close follow-up with urethral washings for cytology to detect early urethral recurrence, an important determinant for survival.

Evaluation of multiple recurrence events in superficial bladder cancer patients treated with intravesical bacillus Calmette-Guérin therapy using the Andersen-Gill's model.

To evaluate factors affecting recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy (Tokyo 172 strain), we reviewed data for 101 patients with superficial bladder cancer (pTa [n = 80] and pT1 [n = 21]) treated between 1985 and 1999. The median follow-up period was 58.9 months. Factors affecting the first tumour recurrence were evaluated using Cox's proportional hazards model and those affecting multiple recurrence with Andersen-Gill's model. The 5-year recurrence-free rate was 63% for all 101 patients. The recurrence frequency, defined as times per 100 patient-months of follow-up, greatly decreased from 7.3 +/- 9.6 (SD) before the instillation to 2.6 +/- 5.6 after the therapy (p < 0.0001). Patients with pT1 tumours tended to have earlier recurrence than those with pTa tumours (p = 0.06). Multivariate analysis using Cox's proportional hazards model revealed that a history of bladder cancer and pathological stage were independent factors affecting the first tumour recurrence after the BCG therapy. When multiple endpoints of recurrence were evaluated using the Andersen-Gill's model, number of tumours as well as a history of bladder cancer and pathological stage demonstrated significant links to tumour recurrence after the BCG therapy. The 5-year progression-free and 5-year survival rates were 89.3% and 85.3% for all the 101 patients, respectively. Because intravesical recurrence may involve multiple events during the clinical course of patients with bladder cancer, the Andersen-Gill's model appears useful for evaluation of risk factors.

Evaluation of a low-dose intravesical bacillus Calmette-Guérin (Tokyo strain) therapy for superficial bladder cancer.

To examine whether intravesical instillation of low-dose bacillus Calmette-Guérin (BCG) therapy is effective with low toxicity, we reviewed data for 111 patients with superficial bladder cancer (stages Ta and T1). Among them, 74 received the BCG treatment for prophylaxis of intravesical recurrence after transurethral resection, and the remaining 37 therapeutically for Ta or T1 tumours. The patients were divided into two groups by instillation dose of BCG (Tokyo 172 strain): 40 mg (n = 55) and 80 mg (n = 56), and statistically compared for recurrence, antitumour effect and toxicity. The mean instillations were done 8.4 times in the 40 mg dose group and 8.6 times in the 80 mg dose group. Among the 74 patients with BCG therapy for prophylaxis those with a previous episode of bladder cancer treatment (n = 47) experienced a significantly (p = 0.006) shorter recurrence-free interval than those with no episode (n = 27). Among 47 patients with a previous treatment episode, those receiving the 80 mg dose demonstrated a significantly longer recurrence-free interval than those given the 40 mg dose (p = 0.03). Among the 27 patients without previous treatment no significant difference in recurrence-free intervals was found between the two dose groups. Univariate and multivariate analyses using Cox's proportional hazards model confirmed the above findings. The recurrence index was also significantly reduced after BCG therapy in the 80 mg and 40 mg groups and similar antitumour effects for Ta or T1 tumours were observed in the two dose groups. The degree of toxicity due to BCG therapy was significantly (p = 0.02) lower with the 40 mg dose. The present study suggests that (1) a 40 mg BCG low-dose (Tokyo 172 strain) regimen is useful for preventing recurrence, with sufficient therapeutic efficacy and low frequency of toxicity, among patients without a previous treatment, and (2) prophylactic effects with the 80 mg dose regimen are much superior for previous treatment cases.

Multivariate evaluation of prognostic determinants for renal cell carcinomas which are metastatic at initial diagnosis.

To clarify the relative importance of clinicopathological factors potentially affecting the survival of individuals initially diagnosed as having metastatic renal cell carcinoma (RCC), univariate and multivariate analyses using Cox's proportional hazards model were performed for 111 RCC patients who were admitted to four hospitals in Nagoya, Japan, between 1978 and 1993. Survival time was calculated from the date of diagnosis to the date of death or the end of May, 1995. Nineteen factors (17 clinically applicable before treatment and 2 histological in nature) were included for assessment. Univariate analysis revealed that 10 of the total 19 factors were significantly associated with patient survival. Multivariate analysis found 7 factors to be statistically significant determinants. Survival was further evaluated by categorizing the patients into three groups according to the number of the 7 factors. These groups showed clearly different survivals (log-rank test, p < 0.0001), confirming the importance of the 7 factors as definite determinants. They should therefore prove to be of advantage for classifying metastatic RCC patients when designing clinical prospective studies of immunotherapy and chemotherapy.

Use of diagnostic categories in urinary cytology in comparison with the bladder tumour antigen (BTA) test in bladder cancer patients.

In recent years the use of diagnostic categories for extragenital cytology has increasingly been discussed as an approach to improve the quality of reports. Diagnostic categories reflect the adequacy of the materials for interpretation and the presence or absence of cancer cells. There is a tendency to add intermediate groups as qualifying probably malignant cases or findings associated with a serious cancer risk. Since 1971 we have added one of the following to the final diagnosis in all cases: unsatisfactory for cytological diagnosis, negative for cancer, repeat test suggested, suspicious of cancer, and positive for cancer. To evaluate whether diagnostic categories are useful for comparison of cytological results with those of an alternative test, cytological data were compared with the results of the Bard bladder tumour antigen (BTA) test in voided urine from 119 patients (76 with and 43 without bladder cancer). The diagnostic categories enabled us to calculate sensitivities and specificities of cytology based on different thresholds or decision levels. The BTA test had significantly higher sensitivity (79%) and lower specificity (60%) than urinary cytology with three different thresholds in cytology results (sensitivities: 16-43%, specificities: 81-100%). The present findings suggest that diagnostic categories improve comparison of cytologic results with those of alternative screening and diagnostic aids such as the BTA test.

Significant elevation of urinary 28-kD calbindin-D and N-acetyl-beta-D-glucosaminidase levels in patients undergoing extracorporeal shock wave lithotripsy.

Calbindin-D, a vitamin D-dependent calcium binding protein with a molecular mass of 28 kD, is found predominantly in distal renal tubules and central nervous system tissues in man. We have developed a highly sensitive enzyme immunoassay for human 28-kD calbindin-D and demonstrated its advantages as a new marker for damage to distal renal tubules. Urinary N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme of the proximal renal tubules, is another segment-specific indicator of renal damage. To clarify whether both proximal and distal renal tubules are similarly affected by extracorporeal shock wave lithotripsy (SWL) treatment, urinary 28-kD calbindin-D and NAG were measured before, then immediately, 2 and 24 hours after SWL in 17 renal lithiasis patients. Levels of urinary calbindin-D were markedly elevated immediately and 2 hours after SWL and then decreased. In sera, levels of calbindin-D also increased, closely correlated with the changes in urinary values. Levels of urinary NAG were also significantly elevated immediately after SWL and then decreased. The results indicate that damage to both proximal and distal renal tubules occurs simultaneously with SWL and that the two markers can be applied as sensitive indicators of such side effects and their alleviation with protective agents.

Total cystectomy after intravesical bacillus Calmette-Guérin (Tokyo strain) therapy for superficial bladder cancer: experience in Japan.

To clarify which patients might most require total cystectomy after intravesical bacillus Calmette-Guérin (BCG) therapy, we reviewed data for 111 individuals with superficial bladder cancer. Of the 111 patients, 73 received the BCG treatment for prophylaxis of intravesical recurrence after transurethral resection (group 1), 24 therapeutically for Ta or T1 tumours (group 2), and 14 for eradicating carcinomas in situ (CIS, group 3). Although the BCG therapy significantly reduced frequencies of recurrence in group 1, 27 patients (37%) did develop tumours again. Tumours disappeared in 18 of 24 patients (75%) in group 2, and in 11 of 14 (79%) in group 3. The rate of disease progression was 6% for all 111 patients: 3% (2/73) for group 1, 17% (4/24) for group 2, and 7% (1/14) for group 3. A total of 16 of the 111 patients (14%) underwent total cystectomy, the respective figures being 7% in group 1, 29% in group 2, and 29% in group 3. Indications for total cystectomy were progression in 7, recurrent multiple tumours in 5, persistent CIS in 2, a contracted bladder in 1, and occurrence of bilateral renal pelvic cancer in 1. Thus, 4 of 6 patients (67%) who had tumours unresponsive to BCG therapy in group 2 demonstrated progression and necessitated total cystectomy. Because tumours persisting after BCG therapy are frequently of the muscle-invasive type, such cases should be regarded as candidates for immediate total cystectomy.

Possible factors affecting response to intravesical bacillus Calmette-Guérin (Tokyo 172 strain) therapy for carcinoma in situ of the bladder: a multivariate analysis.

To evaluate clinicopathological factors affecting response to intravesical instillation therapy with the bacillus Calmette-Guérin (BCG) Tokyo 172 strain for carcinoma in situ (CIS) of the bladder, we reviewed data for 84 patients treated between 1985 and 1996. Median follow-up was 56 months. The patients comprised three groups: primary (only the in situ lesion, 31 patients), subsequent (found after treatment of a gross neoplasm, 20), and concomitant (found together with a gross neoplasm, 33). A complete response was found in 62 (74%) of the 84 patients. Intravesical BCG therapy eradicated tumour cells in 74% of the primary group, 70% of the subsequent group, and 76% of the concomitant group. Multivariate logistic regression analysis revealed that the presence of gross haematuria and patient age were significantly associated with a complete response to the intravesical BCG therapy (p<0.05). On the other hand, gender, irritative bladder symptoms, type of extent of CIS, histological grade of CIS, BCG dose, and number of times BCG was given did not exert any significant influence. The 5-year recurrence rate was 33% for the 62 patients for whom a complete response was once achieved. Patients aged 60 or older had a higher probability of recurrence than those less than 60 years of age (p<0.05). Disease progression was found in 13% of the 84 patients and total cystectomy was performed in 19%. The present finding that patient age is related to the response to intravesical BCG therapy may point to a role for the reduced host immunocompetence in elderly individuals.

Multivariate evaluation of factors affecting recurrence, progression, and survival in patients with superficial bladder cancer treated with intravesical bacillus Calmette-Guérin (Tokyo 172 strain) therapy: significance of concomitant carcinoma in situ.

To evaluate the relative importance of clinicopathological factors affecting recurrence, progression, and survival in patients with superficial bladder cancer (pTa and pT1) undergoing bacillus Calmette-Guerin (BCG) therapy (Tokyo 172 strain), we reviewed data for 146 patients treated between 1985 and 1998. The median follow-up period was 64.7 months. Tumour recurrence, progression, and death were evaluated as endpoints using Cox's proportional hazards model. The 5-year recurrence-free rate was 56% for all 146 patients. Those with a past history of bladder cancer (n = 73) had significantly earlier recurrence than those without (n = 73, p = 0.017) and this tended to be the case for concomitant CIS (n = 34) although this did not reach statistical significance. The 5-year progression rate was 15% for all 146 patients and univariate analysis revealed that the presence of concomitant CIS was significantly associated with disease progression (p = 0.002). Multivariate analysis using the proportional hazards model confirmed the finding that only one factor, concomitant CIS, was significantly associated with progression. The 5-year survival rate was 84% for all 146 patients. Furthermore, univariate and multivariate analyses revealed that patient age, history of bladder cancer, and concomitant CIS were variables significantly related to patient survival. The present findings suggest that careful follow-up is mandatory after BCG instillation therapy for patients with superficial bladder cancer and concomitant CIS because of their relatively poor prognosis.