Search

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Shingo Tamura,7 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki FurubayashiDepartment of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, JapanTel +81-92-541-3231Fax +81-92-551-4585Email nobumduro@gmail.comBackground: To evaluate the association of clinical outcomes with posttreatment changes in the relative eosinophil count (REC) and neutrophil-to-eosinophil ratio (NER) in patients with advanced urothelial cancer (UC) treated with pembrolizumab.Materials and Methods: We retrospectively analyzed 105 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The REC and NER before and three weeks after pembrolizumab were recorded. A receiver operating characteristic curve was used to determine the optimal cut-off values for analyzing the risk.Results: There were no significant differences in the overall survival (OS) between the REC ≥ 4.8% and < 4.8% groups and the NER ≥ 13.7 and < 13.7 groups before pembrolizumab (p=0.997 and 0.669, respectively). However, a significant difference in the OS was confirmed between the increased and decreased REC groups and between the decreased and increased NER groups at 3 weeks after pembrolizumab (p< 0.001 and 0.002, respectively). Multivariate analyses revealed that an Eastern Cooperative Oncology Group Performance Status ≥ 2 (P=0.003), albumin < 3.7 g/dl (p=0.002), LDH > 246 U/L (p=0.011), disease site ≥ 3 organs (p=0.019), decreased posttreatment REC (3 weeks later) (p=0.002) and increased posttreatment NER (3 weeks later) (p=0.022) were independent prognostic factors for a worse OS.Conclusion: An increased REC and decreased NER after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.Keywords: urothelial carcinoma, pembrolizumab, eosinophil, neutrophil-to-eosinophil ratio

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Mirii Harada,2 Shingo Tamura,7 Hiroki Kobayashi,1 Yamato Wada,1 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki Furubayashi, Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan, Tel +81-92-541-3231, Fax +81-92-551-4585, Email nobumduro@gmail.comBackground: To evaluate the eosinophil changes, efficacy and safety of pembrolizumab treatment in advanced urothelial carcinoma patients of older age and those with a poor performance status (PS).Materials and Methods: Consecutive patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy between January 2018 and June 2021 were retrospectively examined.Results: 105 patients (median age, 72 years), 71.4% of whom were men, were enrolled. Patients of ≥ 75 years of age were considered to be older patients (n=40), and patients with PS ≥ 2 were considered to have a poor PS (n=10). The objective response and disease control rates were 42.5% and 52.5%, respectively, in older patients and 0% and 10.0%, respectively, in patients with a poor PS. Overall survival (OS) in the older and younger groups did not differ to a statistically significant extent. However, a poor PS was significantly associated with poor survival. Safety analyses demonstrated no significant difference in the occurrence of any immune-related adverse events (irAEs), including grade ≥ 3, between the older and younger groups. However, a poor PS was significantly associated with the low occurrence of any irAEs. The change of the eosinophil count, the increase of the relative eosinophil count (REC) and the decrease of the neutrophil-to-eosinophil ratio (NER) did not differ to a statistically significant extent between the older and younger groups, but showed significant differences between the poor and good PS (PS 0– 1) groups.Conclusion: Pembrolizumab for advanced UC demonstrated similar changes in the eosinophil count, efficacy and toxicity in both older and younger patients. In patients with a poor PS, although toxicity was significantly lower, survival was significantly worse, and neither an increase in REC nor a decrease in NER were observed, but these values showed significant changes in patients with a good PS.Keywords: urothelial carcinoma, pembrolizumab, age, performance status, immune-related adverse events, relative eosinophil count, neutrophil-to-eosinophil ratio

Two-dimensional 1H-NMR is used to determine the intra-molecular interactions of O-(2-hydroxypropyl) cellulose (HPC) in aqueous (D2O), DMF and DMSO solutions. Four grades HPC with different molecular weights are analyzed by using NOESY (Nuclear Overhauser Effect Spectroscopy) for proton-proton cross-interactions. A strong dependence of the polymer chain structure on the HPC Molecular Weight (MW) is overserved. The lower MW HPCs exist in solutions as a more linear chain showing less proton-proton interactions whereas the higher MW HPCs are more twisted and bended and form a tangled molecule mess with very intensive interactions between the -CH3, -CH2- and -C-H protons. From all the grades, the ultra-low molecular weight HPC-UL (MW 20,000) revealed the weakest proton-proton cross-relaxations and exists in solutions probably only as an almost linear chain polymer.

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Mirii Harada,2 Shingo Tamura,7 Akihiro Miura,1 Hiroki Komori,1 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki Furubayashi, Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan, Tel +81-92-541-3231, Fax +81-92-551-4585, Email nobumduro@gmail.comBackground: To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab.Materials and Methods: This retrospective study analyzed 105 advanced UC patients treated with pembrolizumab after disease progression on platinum-based chemotherapy between January 2018 and June 2021. The association between the occurrence of irAEs and the efficacy of pembrolizumab was investigated. The change in the REC from before the initiation of pembrolizumab therapy, to three weeks after treatment and the incidence of irAEs were determined.Results: Overall irAEs were associated with a significantly higher objective response rate (ORR) (58.8% vs 25.4%, P< 0.001), a longer progression-free survival (PFS) (25.1 months vs 3.1 months, P< 0.001) and overall survival (OS) (31.2 months vs 11.5 months, P< 0.001) compared to patients without irAEs; however, grade ≥ 3 irAEs were not associated with the ORR (36.4% vs 36.2%, P=0.989), PFS (9.5 vs 5.5 months, P=0.249), or OS (not reached vs 13.7 months, P=0.335). Compared to a decreased REC at 3 weeks after pembrolizumab, an increased relative REC at 3 weeks was not associated with the incidence of any-grade irAEs (32.3% vs 32.5%, P=0.984) or of grade ≥ 3 irAEs (10.8% vs 10.0%, P=0.900). Multivariate analyses revealed a female sex (P=0.005), Eastern Cooperative Oncology Group Performance Status ≥ 1 (P=0.024), albumin < 3.7 g/dl (P< 0.001), decreased REC (3 weeks later) (P< 0.001), and the absence of irAEs of any grade (P=0.002) to be independently associated with a worse OS.Conclusion: Patients with irAEs showed a significantly better survival compared to patients without irAEs in advanced UC treated with pembrolizumab. An increased posttreatment REC may be a marker predicting improved clinical outcomes and it had no significant relationship with the incidence of irAEs.Keywords: urothelial carcinoma, pembrolizumab, immune-related adverse events, relative eosinophil count

Background/aim The novel taxane cabazitaxel has been shown to exert excellent anticancer effects after androgen receptor axis-targeting (ARAT) agents in clinical data, but not in in vitro data. We investigated the clinical outcome of cabazitaxel chemotherapy after docetaxel according to use of ARAT agents. Patients and methods Prostate specific antigen (PSA) response, progression-free survival, and overall survival were compared between cases with and without prior use of ARAT agents in 74 Japanese patients with metastatic castration-resistant prostate cancer treated with cabazitaxel chemotherapy. Results Background characteristics were comparable between patients with and without prior use of ARAT agents. PSA response, progression-free survival, and overall survival in cabazitaxel chemotherapy were comparable between patients with and without prior use of ARAT agents. Conclusion No detrimental effects of prior ARAT agents on clinical outcome were observed for cabazitaxel chemotherapy in the post-docetaxel setting, suggesting that cabazitaxel can be expected to remain active even after ARAT agent therapy.

The Halabi model predicts the overall survival (OS) of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with second-line therapy after docetaxel. We aimed to validate this model externally with an independent cohort, outside the setting of a clinical trial.In a multi-institutional study, we included 66 patients treated with cabazitaxel after docetaxel for mCRPC. Patients were stratified according to the two- and three-risk groups of the Halabi nomogram. Kaplan-Meier and Cox proportional hazard analyses were performed to estimate survival and hazard ratios (HRs). The model performance was assessed using receiver operating characteristic curves, and the associated c-index (area under the curve [AUC]).The median OS in the two-risk groups was 5.06 months in the high-risk group (n=22) and 12.9 months in the low-risk group (n=44, p0.001). High-risk patients had an HR of 9.50 (95% confidence interval (CI) 4.12-21.6, p0.001) compared to low-risk patients. For the three-risk groups, the median OS was 6.44 months in the high-risk group (n=15), 5.75 months in the intermediate-risk group (n=11), and 13.7 months in the low-risk group (n=40, p=0.84). Compared to low-risk patients, intermediate-risk patients had an HR of 7.49 (95% CI 3.08-20.4, p0.001), and high-risk patients had an HR of 8.48 (95% CI, 3.39-21.7, p0.001). The AUC was 0.72 (95% CI 0.64-0.76) for the two-risk stratification. When comparing different risks, the AUCs were 0.48 (high vs intermediate), 0.66 (high vs low), and 0.65 (intermediate vs low).The two-risk stratification version but not the three-risk group analysis confirmed the ability of the model to predict survival. These results support the value of the Halabi nomogram in men receiving post-docetaxel second-line chemotherapy for mCRPC.

Although variant urothelial carcinoma (VUC, defined here as urothelial carcinoma with any histological variant) is a clinically aggressive disease, the efficacy of pembrolizumab against VUC is not well characterized. This study assessed the therapeutic response and survival outcomes in patients with advanced VUC treated with pembrolizumab for unresectable recurrent or metastatic disease.We retrospectively evaluated 103 patients with advanced bladder and upper urinary tract cancer who received pembrolizumab after failure of platinum-based chemotherapy at 6 institutions between January 2018 and June 2021. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with VUC.We identified 81 and 22 patients with PUC and VUC, respectively. Squamous differentiation (n = 14) was the most common variant element, followed by glandular differentiation (n = 3) and micropapillary variant (n = 3). Baseline characteristics were comparable between the groups. Patients with VUC showed significantly better ORR (59.1% vs. 29.6%, P = .014) and comparable DCR (68.2% vs. 49.4%, P = .150) compared to those with PUC. There were no significant differences between the PUC and VUC groups with respect to PFS (median 5.0 months vs. 10.4 months, P = .222) or OS (median 13.5 months vs. 23.8 months, P = .497).Response of VUC to pembrolizumab was not inferior to that of PUC in patients with advanced-stage bladder and upper urinary tract cancer.

Background/aim Cabazitaxel use has usually been limited to up to 10 cycles in most countries according to the protocol in the TROPIC trial. Therefore, clinical data on cabazitaxel use beyond 10 cycles is limited. The aim of this study was to report the therapeutic outcome of cabazitaxel chemotherapy administered for >10 cycles. Patients and methods This study included 74 Japanese patients with prostate cancer between 2014 and 2017. Patients background, and treatment outcomes including PSA decline, progression-free survival, treatment-failure-free survival, overall survival, and adverse events were investigated, comparing patients treated with ≤10 and >10 cycles. Results Patients characteristics were favorable as indicated by the higher number of cycles of prior docetaxel chemotherapy, absence of pain, and absence of bony and visceral metastases among men who received >10 cycles of cabazitaxel. PSA response, progression-free survival, treatment-failure-free survival and overall survival were better among patients treated with >10 cycles of cabazitaxel compared to those treated with ≤10 cycles. The incidence of severe adverse events was similar between the two groups. Conclusion Taken together, this study suggested that continuous chemotherapy with cabazitaxel beyond 10 cycles may be beneficial.

This study aimed to reveal the efficacy and safety profiles of 4-weekly cabazitaxel in patients with castration-resistant prostate cancer (CRPC). The study included 62 Japanese patients who were treated for CRPC with ≥ 2 courses of cabazitaxel between 2014 and 2017. The oncological outcomes and adverse events were compared between 16 (25.8%) and 46 (74.2%) men who were treated with standard 3-weekly and alternative 4-weekly regimens, respectively. The prostate-specific antigen (PSA) response was comparable between the 3-weekly and 4-weekly regimens (median [interquartile range]: − 9.9% [− 64.5 to 13.0%] and − 30.7% [− 52.8 to 10.9%], P = 0.89), respectively. For patients on the 4-weekly regimen, the risks of progression (hazard ratio [HR], 95% confidence interval [CI] 1.27, 0.71–2.43, P = 0.44), treatment failure (HR, 95% CI 0.84, 0.48–1.55, P = 0.57) and any-cause mortality (HR, 95% CI 1.09, 0.58–2.17, P = 0.79) were comparable to those for patients on the 3-weekly regimen. The incidences of severe adverse events were also similar between the 3-weekly and 4-weekly regimens. 3-weekly and 4-weekly regimens of cabazitaxel showed similar efficacy and safety profiles in a real-world clinical setting. These data suggest that a 4-weekly regimen may be acceptable for selected patients.

Objectives: To evaluate the management and outcome of idiopathic retroperitoneal fibrosis (iRPF) in Japan, and identify its clinical biomarker. Methods: We retrospectively analyzed 129 patients with iRPF treated between January 2008 and May 2018 at 12 university and related hospitals. Patients treated with glucocorticoid were analyzed to identify a predictive biomarker. These patients were classified into three groups according to overall effectiveness (no change: NC, complete response: CR and partial response groups: PR), and each parameter was compared statistically.Results: Male-female ratio was 5: 1, and median age at diagnosis was 69 (33-86) years. Smoking history was reported in 59.6% of the patients. As treatment, 95 patients received glucocorticoid therapy with an overall response rate of 84%. As a result, serum concentration of IgG4 was significantly decreased in NC group compared with the other two groups (56.6mg/dL vs 255mg/dL, 206mg/dL, P=0.0059 and 0.0078). ROC analysis was performed between the non-responder (NC) and responder groups (CR+PR) to identify the cut-off value of serum IgG4 as a predictive marker. As a result, AUC was 0.793 and the values of sensitivity and specificity were 0.85 and 0.64, respectively, under the cut-off values of 67.6mg/dL. Conclusions: In the majority of iRPF patients, glucocorticoid therapy resulted in a favorable response. Pre-treatment serum IgG4 concentration may have potential as a predictive biomarker of steroid treatment.

Background/aim Despite the presence of a mixed response (MR) in patients with urothelial carcinoma (UC) who receive immune checkpoint inhibitors, the clinical outcome of these patient has not been reported. We evaluated the clinical outcome of MR to pembrolizumab for advanced UC. Patients and methods Advanced UC patients who received pembrolizumab after platinum-based chemotherapy failure with measurable disease in multiple organs were retrospectively analyzed. Results Among 31 patients, MR [including progressive disease (PD)+complete response (CR) or partial response (PR)] was confirmed in 4 (12.9%). The median overall survival (OS) of the CR+PR (including CR+SD±PR), stable disease (SD), PD (including PD±SD) and MR groups was 16.0, 5.1, 5.4 and 4.3 months, respectively. There was no significant difference in the OS between the MR and CR+PR response groups (log-rank test, p=0.069). Conclusion A mixed response to pembrolizumab in advanced UC was not uncommon. Despite the non-significant difference in the OS between the mixed and CR+PR response groups, the OS of the MR group tended to be similar to that of the SD and PD response groups.

Nobuki Furubayashi,1 Takahito Negishi,1 Naotaka Sakamoto,2 Hozumi Shimokawa,3 Futoshi Morokuma,4 Yoohyun Song,5 Yoshifumi Hori,6 Toshihisa Tomoda,7 Noriaki Tokuda,4 Narihito Seki,5 Kentaro Kuroiwa,6 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 3Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Saga-ken Medical Centre Koseikan, Saga, Japan; 5Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 6Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 7Department of Urology, Oita Prefectural Hospital, Oita, JapanCorrespondence: Nobuki FurubayashiDepartment of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-Ku, Fukuoka, 811-1395, JapanTel +81-92-541-3231Fax +81-92-551-4585Email nobumduro@gmail.comBackground: To evaluate the organ-specific therapeutic effect of pembrolizumab after the failure of platinum-based chemotherapy for advanced urothelial carcinoma (UC).Materials and Methods: Patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy and who had measurable disease were retrospectively analyzed. The objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to Response Evaluation Criteria in Solid Tumors, version 1.1.Results: We analyzed 69 patients (male, n=51; median age, 71 years) with 226 metastases. The ORR was 23.2%. In total, 32, 31, 16, 14, 13 and 7 patients had measurable lung (OSSR 31.3%), lymph node (OSSR 29.0%), local recurrence (OSSR 12.5%), primary tumor organ (OSSR 7.1%), liver (OSSR 23.1%) and bone (OSSR 28.6%) disease, respectively. The median overall survival (OS) for pembrolizumab was 10.9 months (95% confidence interval, 5.9‑13.7 months). Regarding organ-specific OS, a Log rank test significant differences in OS were confirmed between patients with and without primary tumor organ disease (p=0.046) and liver metastasis (p< 0.001).Conclusion: Metastases and primary tumor organ disease showed different tumor responses to pembrolizumab. The most prominent tumor response was found in lung metastasis and the least response was found in primary organ sites. The mechanisms of these different responses were unclear and there does not appear to be a constant trend between tumor shrinkage and OS in tumor sites. Further studies are needed.Keywords: urothelial carcinoma, platinum-based chemotherapy, pembrolizumab, organ-specific response rate, tumor microenvironment

This multi-institutional study aimed to identify prognostic factors for cabazitaxel treatment of castration-resistant prostate cancer (CRPC). This study included 74 Japanese patients with CRPC who were treated with cabazitaxel between 2014 and 2017. Associations between clinicopathological factors including serum markers and progression-free survival (PFS) and overall survival (OS) were investigated. On multivariate analysis, high Gleason score [≥9 vs. ≤7; hazard ratio (HR), 95% confidence interval (CI): 2.00 (1.01-4.34); P = 0.047], presence of pain [HR, 95% CI: 2.02 (1.14-3.58); P = 0.016], and lactate dehydrogenase (LDH) level [HR, 95% CI: 47.31 (3.79-577.49); P = 0.0019] were significantly associated with PFS. Similarly, number of docetaxel cycles [HR, 95% CI: 0.050 (0.0037-0.45); P = 0.0057], performance status [≥2 vs. 0; HR, 95% CI: 5.07 (1.57-16.24); P < 0.0001], and LDH level [HR, 95% CI: 2946 (50-420994); P = 0.0001] were significantly associated with OS. This study showed that LDH level is robustly prognostic for both PFS and OS in cabazitaxel chemotherapy for CRPC.

Inflammation is considered to be a prognostic factor for renal cell carcinoma (RCC). An inflammation-based prognostic score (modified Glasgow Prognostic Score; mGPS) is widely used for preoperative patients; however, little information is available regarding its prognostic value in patients with RCC treated with molecular-targeted drugs. A total of 32 advanced and recurrent RCC patients initially treated with molecular-targeted drugs from October, 2009 to August, 2015 were retrospectively investigated. Information on patient characteristics prior to treatment initiation and the clinical course were retrieved from clinical records. The correlation between survival and patient variables was analyzed. Survival was compared among patient groups according to the mGPS score. The median patient age was 66 years. The percentage of patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 was 87.5, and 65.6% of the RCCs were clear cell carcinomas. A Memorial Sloan-Kettering Cancer Center index of good or intermediate was determined for 75% of the patients. Sunitinib, pazopanib or sorafenib was administered to 56, 22 and 13% of the cases, respectively. An mGPS score of 0, 1 and 2 was calculated for 66, 9 and 25% of the cases, respectively. Patients in the mGPS low group (score 0) exhibited significantly better progression-free survival (PFS) and overall survival (OS) compared with patients in the mGPS high group (score 1 or 2) (median PFS, 307 vs. 70 days and median OS, 1,081 vs. 140 days, respectively). In conclusion, inflammatory status as assessed by the mGPS score was closely associated with the prognosis of RCC patients treated with molecular-targeted therapy.

In the present study, the production of propylene oxide (PO) from propylene via gas-phase epoxidation was investigated using various catalysts. Although Ag is known to be a highly active catalyst for the epoxidation of ethylene, it was not active in the present reaction. Both Al and Ti showed high levels of activity, however, which resulted in confusion. The present study was conducted to solve such confusion. Although the employment of MCM-41 modified with Ti and/or Al was reported as an active catalyst for epoxidation, the combination resulted in the formation of PO at a less than 0.1% yield. Since this research revealed that the acidic catalyst seemed favorable for the formation of PO, versions of ZSM-5 that were both undoped and doped with Na, Ti, and Ag were used as catalysts. In these cases, small improvements of 0.67% and 0.57% were achieved in the PO yield on H-ZSM-5 and Ti-ZSM-5, respectively. Based on the results of the Ti-dopant and acidic catalysts, Ag metal doped on carbonate species with a smaller surface area was used as a catalyst. As reported, Ag‒Na/CaCO3 showed a greater yield of PO at 1.29%. Furthermore, the use of SrCO3 for CaCO3 resulted in a further improvement in the PO yield to 2.17%. An experiment using CO2 and NH3 pulse together with SEM and TEM examinations for Ag‒Na/CaCO3 revealed that the greatest activity was the result of the greater particle size of metallic Ag rather than the acid‒base properties of the catalysts.

This multi-institutional study aimed to investigate the efficacy and safety profiles of cabazitaxel after prior docetaxel chemotherapy in patients with castration-resistant prostate cancer (CRPC). This study included 63 Japanese patients with CRPC who were treated with cabazitaxel from 2014 to 2017. The oncological outcomes and adverse events (AEs) were documented, and prognostic factors for oncological outcomes and predictive factors for AEs were analysed. PSA decline was observed in 68.3% of patients, including 25.4% who achieved a ≥ 50% decline. The median progression-free survival, treatment failure-free survival, and overall survival were 4.3, 4.1, and 9.0 months, respectively. More cycles of prior docetaxel therapy was identified as common favourable prognostic factors for progression-free survival, treatment failure-free survival, and overall survival. Severe neutropenia, febrile neutropenia, and severe non-haematological AEs were observed in 73.0%, 33.3%, and 23.8% of patients, respectively. However, > 10 cycles of docetaxel was not associated with increased incidence of AEs. In conclusion, cabazitaxel chemotherapy was still active in Japanese CRPC patients treated with > 10 cycles of docetaxel chemotherapy, with an acceptable risk of AE burden. Treatment with cabazitaxel after > 10 cycles of docetaxel may be an appropriate option when it can be administered.

(Objective) We investigated the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy specimens. (Materials and methods) We evaluated 441 patients treated with radical prostatectomy and analyzed data on IDC-P, lymph node metastases, Gleason score, seminal vesicle invasion, extraprostatic extension, surgical margin, total cancer volume, and zonal origin of dominant cancer focus in radical prostatectomy specimens. The median follow-up was 50 months (range 6-164 months). (Results) We identified IDC-P in 112 cases (25.4%). The five-year biochemical progression-free survival rate in patients with IDC-P was significantly lower than for those without IDC-P (35.8% vs 69.6%; p

Objective To identify risk factors of biochemical recurrence after radical prostatectomy in high-risk patients. Methods A total of 191 high-risk prostate cancer patients according to the D'Amico classification treated with radical prostatectomy at a single institution between April 2000 and December 2013 were enrolled. The pathological evaluation including intraductal carcinoma of prostate was reassessed, and the clinical and pathological risk factors of biochemical recurrence were analyzed. Results The median follow up after radical prostatectomy was 49 months. The 5-year biochemical recurrence-free survival rate after radical prostatectomy in high-risk prostate cancer patients was 41.6%. Initial prostate-specific antigen, pathological Gleason score, seminal vesicle invasion, extraprostatic extension and intraductal carcinoma of the prostate were significantly associated with biochemical recurrence-free survival. The 5-year biochemical recurrence-free survival rates in patients with zero, one, two and three of these risk factors were 92.9%, 70.7%, 38.3% and 28.8%, respectively. In patients with four or more factors, the biochemical recurrence-free survival rate was 6.1% after 18 months. Conclusions In D'Amico high-risk patients treated with radical prostatectomy, risk factors for biochemical recurrence can be identified. Patients with fewer risk factors have longer biochemical recurrence-free survival, even among these high-risk cases.

Objective The distribution of intraductal carcinoma of the prostate (IDC-P) and other intraductal lesions associated with IDC-P was evaluated in the cancer foci on radical prostatectomy specimens. Materials and methods We reviewed slide in 412 cases treated by radical prostatectomy without neoadjuvant therapy. Mapping study was performed with regard to IDC-P, other intraductal lesions associated with IDC-P and invasive carcinoma. Results We identified 98 cases (23.8%) and 102 cancer foci associated with IDC-P. In these all cancer foci, IDC-P was associated with invasive carcinoma and other intraductal neoplastic lesions with tufting, micropapillary and loose cribriform patterns were contiguous and admixed with IDC-P in 83 cancer foci (81.4%). There were lesions with invasive carcinoma around the IDC-P in 95 cancer foci (93.1%) and lesions without invasive carcinoma around IDC-P in 66 foci (64.7%). The latter lesions existed in the marginal areas of the cancer foci in 63 (61.8%) and in the central areas of the cancer foci in 14 (13.7%). In 5 cancer foci (4.9%), volume of IDC-P was larger than that of invasive carcinoma. Conclusions The distribution of IDC-P with dense cribriform and solid patterns varied in cancer foci, and intraductal lesions with tufting, micropapillary and loose cribriform patterns were frequently seen in area contiguous and admixed with IDC-P. The latter lesion may be low grade morphology of IDC-P, although the lesions could not be distinguished from high grade prostatic intraepithelial neoplasia.

We investigated to add some high functionality to the brick by controlling the porous structure of the brick. It was succeeded in this study that a great many minute continuous pores which lead to capillary action were introduced inside of bricks in order to bring about “UCHIMIZU effect” for suppressing urban heat island phenomenon. But, as for the high water retainable pavement material like that brick, it is broken by water freezing in winter, and from this reason any pavement material with “UCHIMIZU effect” are not readily spread in through the all over Japan. Then, preparation of the brick which had both water retainability and frost resistance was tried by introducing much space into the brick inside to be able to permit the solidification expansion of water, and examined influence on properties of the brick by the quantity of porosity. From results, it was suggested that water retainability and frost resistance were able to be given to the brick at the same time by using the cavity formation materials.

Spin-coated films of a lead halide, PbX: X = I and Br, layered perovskites having cyclohexenylethyl ammonium molecule as an organic layer, which were mixed with other metal halide-based layered perovskites consisting of various divalent metal halides (for example, CaI2, CdI2, FeI2, SnBr2 and so on), were prepared. The results of X-ray diffraction measurements exhibited that solid solution formation between PbX-based layered perovskite and other divalent metal halide-based layered perovskites was observed up to very high molar concentration of 50 molar% in the mixed film samples when divalent cations having ionic radius close to that of Pb2+ were employed. In the solid solution films, the exciton emission was much enhanced at room temperature. Exciton emission intensity of PbI-based layered perovskite mixed with CaI-based layered perovskite (20 molar%) is about 5 times large that of the pristine PbI-based layered perovskite, and that of PbBr-based layered perovskite mixed with SnBr-based layered perovskite (20 molar%) was also about 5 times large that of the pristine PbBr-based layered perovskite at room temperature.

Introduction: In patients with a clinically unilateral palpable and/or visible lesion confined to the prostate on digital rectal examination and transrectal ultrasonography, the findings of biopsy specimens of a clinically unsuspicious lobe do not reflect TNM staging results (2002 classification). In patients with such a unilateral lesion, we compared the biopsy results of a clinically unsuspicious lobe with the pathological assessment of the radical prostatectomy specimen and evaluated the importance of the results of biopsy specimens in an unsuspi cious lobe. Patients and Methods: Between April 2000 and August 2004, 97 prostatic cancer patients without neoadjuvant therapy underwent a radical retropubic prostatectomy. In the patients with a unilateral lesion on digital rectal examination and/or transrectal ultrasound, the preoperative prostate-specific antigen levels, the results of contralateral biopsy specimens, and contralateral cancer foci in radical prostatectomy specimens were examined. Results: Of 39 patients with a unilateral palpable and/or visible lesion, 15 had contralateral positive biopsy findings, while 24 had contralateral negative biopsy findings. In a pathological analysis of prostatectomy specimens, a significantly higher rate of clinically significant cancer foci and a larger cancer volume in a clinically unsuspicious lobe have been observed in patients with contralateral positive biopsy findings than in patients with contralateral negative biopsy findings (p < 0.001). Moreover, contralateral cancer foci in patients with a contralateral positive biopsy specimen exhibited a more ominous state, such as seminal vesicle invasion, extraprostatic extension, and a positive surgical margin, than those in patients with a contralateral negative biopsy specimen (40.0 vs. 8.3%, p = 0.017). However, in a pathological analysis of both ipsilateral and contralateral cancer foci, the proportion of ominous pathological findings did not differ between the patients with a contralateral positive biopsy and those with a contralateral negative biopsy. Conclusions: In patients with clinically unilateral palpable and/or visible tumors confined to the prostate, the results of a bilateral biopsy need not be used to determine the clinical stage. However, in patients with positive biopsy results for an unsuspicious lobe, urologists should perform an extended surgical resection.

We present a case of mucinous adenocarcinoma of intestinal type arising from the prostatic duct in a 72-year-old Japanese man. The patient presented with macroscopic hematuria. Cystourethroscopy exhibited a mucus deposit at the 5 o'clock position of the verumontanum portion. A transurethral biopsy specimen revealed mucinous adenocarcinoma. A radical retropubic prostatectomy was performed. In the prostatectomy specimen, the cancer lesion mainly showed intraductal growth in the prostatic ducts with scattered mucin lakes in the prostatic stroma. There were no abnormalities in the urethral epithelium. The cancer cells resembled the intestinal epithelium rather than either the prostatic duct or the acinar epithelium, which showed diffusely positive immunohistochemical staining for carcinoembryonic antigen, but showed negative staining for prostate-specific antigen. Therefore, these findings suggest mucinous adenocarcinoma of intestinal type arising from the prostatic duct. A number of cases with mucinous adenocarcinoma arising from the prostatic urethra resembling the present case have been reported, but this is the first known case of carcinoma arising from the prostatic duct.

The rate of incidence of febrile infection and the antimicrobial drug used at the time of prostate needle biopsy was examined retrospectively. SPFX (sparfloxacin) 400 mg (January 2007 to March 2010) and LVFX (levofloxacin) 500 mg (April 2010, onward) were administered prophylactically in 1,034 patients undergoing transrectal or transperineal prostate biopsy. One febrile infection occurred and resolved in each group. A single dose of LVFX 500 mg before the procedure effectively prevented febrile infection in both transrectal and transperineal prostate needle biopsy.

The influence of cation-mixing on photo luminescence(PL) of PbI2-based organic/inorganic perovskite thin films expressed by chemical formula (C6H9C2H4NH3)2PbI4 was investigated. Cation-mixing to inorganic layer by addition of ZnI2 or CdI2 did not affect the character of exciton in the films because all optical spectra of the (CHE)2(Pb,M)I4 films were the same profile. Dependence of PL intensity at 2.4eV of photon energy(PL2.4) on inorganic layer compositions was changed by kind of additive cation. In the case of Zn addition, PL2.4 was uniformly decreased with an increase of additive amounts of Zn. On the other hand, PL2.4 of the (C6H9C2H4NH3)2(Pb, Cd)I4 films remarkably increased with increasing of Cd concentration up to 20mol%Cd. It was obvious that cation-mixing with Cd is effective to advance the optical properties of the (C6H9C2H4NH3)2PbI4 films. Relationships between PL2.4 and layer structure of the films were discussed according to structural analysis using XRD.

Background: A recurrence of bladder tumors following surgery for transitional cell carcinoma of the upper urinary tract is not rarely observed. A prospective randomized study was conducted to examine the significance of prophylactic intravesical instillation of mitomycin C (MMC) and cytosine arabinoside (Ara-C) to prevent recurrent bladder tumors after surgery for superficial transitional cell carcinoma of the upper urinary tract. Methods: The patients were randomized into an instillation group, who received postoperative intravesical instillation of MMC (20 mg) and Ara-C (200 mg) 28 times over a period of 2 years, and a non-instillation group. The non-recurrence rate was then compared between the groups. Results: Of the 27 patients registered, 25 patients (13 with instillation and 12 without instillation) were able to be evaluated, with a median follow-up period of 45 months. The non-recurrence rate of bladder tumors in the instillation group was higher than that in the non-instillation group. Although the difference was not statistically significant, the P-value (P = 0.079) demonstrated a strong trend. When any possible bias was allowed for a multivariate analysis, the difference was almost significant (P = 0.0567). No patients withdrew from this study due to any side-effects. Conclusion: The postoperative instillation of MMC and Ara-C may be a useful approach for reducing the recurrence of bladder tumors after surgery for upper urinary tract tumors.

The emergence of drug-resistant tumors during treatment remains one of the major obstacles in cancer chemotherapy. Overexpression of P-glycoprotein encoded by the multidrug resistance 1 (MDR1) gene or multidrug resistance-associated protein (MRP) (or both) and decreased expression of DNA topoisomerase II are responsible for expression of the multidrug resistance (MDR) phenotype. The expression of P-glycoprotein is also often observed in untreated cancers showing spontaneous MDR, such as renal cell carcinoma. Regarding cisplatin resistance, decreased cisplatin accumulation, an increase in cisplatin detoxification by glutathione-related enzymes or metallothionein (or both), and increased repair of DNA damage are all considered to play an important role. The combination of reversal agents targeting such drug resistance markers may be a way to improve the outcome of chemotherapy. Regarding the presently available reversal agents, however, clinically relevant chemosensitizing doses cannot be given to humans without inducing significant toxicity. The development of new agents that reverse drug resistance without causing significant toxicity and their clinical application based on the mechanisms regulating drug sensitivity may therefore be a potentially effective new treatment strategy for genitourinary carcinomas.

We report our initial experience with a hand assisted laparoscopic radical nephrectomy for patients with renal carcinoma, and compare our results to those of conventional open radical nephrectomy.The clinical data on 6 consecutive patients who underwent hand assisted laparoscopic radical nephrectomy for stage T1N0M0 renal cell carcinoma were reviewed. We performed hand assisted laparoscopic surgery using the new LAP DISC* abdominal wall sealing device. We compared the results of this procedure with those of conventional open radical nephrectomy in 12 patients with stage T1N0M0 renal cell carcinoma.The hand assisted laparoscopic radical nephrectomy for renal carcinoma was successfully performed without any major or minor complications in all 6 patients. Mean operation time for the laparoscopic group was significantly longer than that for the open surgery group (303 minutes versus 224 minutes, p = 0.0042). However, no significant difference was observed in mean estimated blood loss for the 2 groups (264 ml. in the laparoscopic group versus 341 ml. in the open surgery group). The frequency of parenteral analgesia postoperatively in the laparoscopic group was significantly lower than that in the open surgery group (16.7% versus 75.0%, p = 0.043). In addition, the laparoscopic group seemed to recover more rapidly than the open surgery group. The abdominal wall sealing device was easy to attach to the abdominal wall, and allowed rapid hand removal and reinsertion.Our preliminary results indicate that a hand assisted laparoscopic radical nephrectomy with the abdominal wall sealing device is an effective and safe surgical procedure, and is less invasive than open radical nephrectomy.

BACKGROUND We investigated whether a new marker of bone turnover, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), could be useful in the assessment of bone metastasis and in monitoring of the response to treatment in patients with prostate cancer with bone metastasis. METHODS In all, 58 patients with prostate cancer (25 with bone metastasis and 33 without bone metastasis) and 52 patients with benign prostate hypertrophy who were treated between June 1994–August 1997 were included in this study. All patients were newly diagnosed. RESULTS Serum ICTP levels in patients with prostate cancer with bone metastasis were significantly higher than those in patients with prostate cancer without bone metastasis (P < 0.0001) or with benign prostate hypertrophy (P < 0.0001). No significant differences were observed in serum ICTP levels between patients with prostate cancer without bone metastasis and those with benign prostate hypertrophy. Serum ICTP levels correlated significantly with Soloway's grading system for bone scans. Serum ICTP levels in patients with bone metastasis showed a significant downward trend in response to hormonal treatment. CONCLUSIONS The determination of serum ICTP levels is useful in the assessment of bone metastasis and in monitoring the response of bone metastasis to treatment to prostate cancer. Prostate 39:1–7, 1999. © 1999 Wiley-Liss, Inc.

BACKGROUND Dominant cancer of transition zone origin of the prostate (TZ cancer) has been frequently detected, because ultrasound-guided systematic biopsies have been generalized. In cases of TZ cancer, we attempted to determine clinical significance of coexistent non-TZ cancer foci. MATERIALS AND METHODS Twenty cases with TZ cancer who underwent radical prostatectomy or cystoprostatectomy were clinicopathologically evaluated using step-sectioned specimens. RESULTS In TZ cancer foci, there were extraprostatic extension in 5 cases (25%), seminal vesicle invasion in 2 cases (10%), positive surgical margin in 6 cases (30%) and bladder neck invasion in 4 cases (20%). The extraprostatic extension and the positive surgical margin occurred at the anterior or anterioapical portion of the prostate in all the cases. On the other hand, 17 (85%) had coexistent non-TZ cancer foci. In non-TZ cancer foci, there were extraprostatic extension in 3 cases (15%), seminal vesicle invasion in 1 case (5%) and positive surgical margin in 1 case (5%). The extraprostatic extension and the positive surgical margin occurred at the posteriolateral portion of the prostate in all the cases. In 3 cases a coexistent non-TZ cancer focus showed the extraprostatic extension, the seminal vesicle invasion or the positive surgical margin, although a TZ cancer focus were organ-confined. CONCLUSION We should add attention to coexistent non-TZ cancer foci in TZ cancer cases. Particularly, we believe that pre-operative evaluation of non-TZ cancer foci is needed in TZ cancer cases of the candidates for nerve-sparing radical prostatectomy.

The perovskite-type oxide La0.6Sr0.4CoO3(LSCO) is noted as a material for electrodes or catalysts. In order to form LSCO powder into a green product using colloid processing such as slip casting, tape casting, extrusion moulding, etc., aqueous LSCO suspensions were prepared and their flow properties were investigated in comparison with those of aqueous YSZ (yttria-stabilized-zirconia) suspensions in this study. The aqueous LSCO suspensions were prepared with LSCO powder synthesized from acetates, ammonium polyacrylate as the deflocculant, and distilled water. The viscosity of the LSCO suspensions system was so similar to that of YSZ system, i.e., a minimum value was obtained in the relationship between viscosity and deflocculant concentration. The Bingham yield stress of the LSCO suspensions increased with aging time. It was found that the amount of Sr ions leached from LSCO powder increased with aging time, too. Consequently, it was revealed that the flow properties are remarkably influenced by the concentration of leached Sr ions. In addition, it was suggested that washing process of LSCO powder is effective in depressing the change of flow properties with aging time of aqueous LSCO suspension.

We compared the ultrasonic and histologic findings in 25 patients with benign prostatic hyperplasia (BPH) who underwent retropubic subcapsular prostatectomy. Preoperative ultrasonograms showed a fine echogenic pattern in one case, a rough echopenic pattern in four cases, and a combination of these patterns in 20 cases. In cases exhibiting a mixed pattern, we analyzed each region individually. Ultrasonic and histologic findings were compared in a total of 45 regions. In the 21 regions with a fine echogenic pattern, 14 regions corresponded to those with complicated hyperplastic glands, one region with small cystic atrophic glands, and six regions with a mixture of the two types on histology in observation. In the 24 regions with a rough echopenic pattern, 20 regions corresponded to those with large cystic atrophic glands and an equal volume of large and small cystic atrophic glands were found in the other four. Thus, the echogenic structures observed in patients with BPH were determined by the presence of complicated hyperplastic glands and small cystic atrophic glands.

Objectives We investigate the biochemical control rates and adverse events for local and locally advanced prostate cancer patients undergoing high-dose-rate brachytherapy with external beam radiotherapy (EBRT + HDR-BT) in our institute. Patients and methods From May 2004 through March 2010, 154 patients with local and locally advanced prostate cancer underwent EBRT + HDR-BT. One hundred thirteen patients with more than 6 months follow-up were evaluated. A median follow-up was 33 months. The patients consisted of 12 low-, 65 intermediate- and 36 high-risk patients. No patients received adjuvant androgen deprivation therapy with EBRT + HDR-BT. Biochemical freedom from failure (bFFF) was determined using the Phoenix definition. Results The 5-year bFFF rate was 100%, 94.7%, and 59.2% for low-, intermediate- and high-risk patients. The 58-month bFFF rate of high-risk patients with one ominous factor was significantly lower than that of high-risk patients with more than ominous two factors (87.4% vs 26.9%, p = 0.022). With respect to acute adverse events, transurethral electric coagulation was performed for vesical bleeding and tamponade after removal of applicator needles in only one patient. Regarding late adverse events 14.2% of patients had grade 3 genitourinary toxicity, mostly consisted of urethral stricture and 0.9% of patients had grade 3 gastrointestinal toxicity. Conclusions EBRT + HDR-BT without adjuvant androgen deprivation therapy yields excellent bFFF in low- and intermediate-risk prostate cancer patients. However, to challenge higher bFFF rate in a part of high-risk patients and lower rate of adverse events, modified designing protocols and therapeutic plannning of EBRT + HDR-BT may be necessary.

To evaluate the therapeutic outcomes and late toxicities in patients treated by high-dose-rate brachytherapy (HDR-BT) with external beam radiotherapy (EBRT) for localized or locally advanced prostate cancer.From May 2004 to September 2008, 86 men were treated by HDR-BT with EBRT for localized or locally advanced prostate cancer at the National Hospital Organization Kyushu Medical center. The median EBRT and HDR-BT doses were 40 Gy and 30 Gy, respectively.With a median follow-up of 24 months, the 3-year overall, disease specific, and biochemical relapse-free survival rates in all patients were 97.3%, 100%, and 83.6% respectively. The 3-year biochemical relapse-free survival rate of the patients categorized to low or intermediate risk group (91.8%) was significantly better than that of the patients categorized to the high risk group (74.3%) (p = 0.042). There was no significant difference of biochemical relapse-free survival regarding to the other clinical factors (age, T-stage, Gleason score, initial prostate-specific antigen level, neoadjuvant hormone therapy, and total dose of EBRT and HDR-BT). Late Grade2 and Grade3 gastrointestinal toxicities were observed in 8 patients (9.3%) and 2 patients (2.3%), respectively. Late Grade2 genitourinary toxicities were observed in 12 patients (13.9%). There was no patient suffered from late Grade3 or greater genitourinary toxicities.HDR-BT with EBRT can be safe and effective for localized or locally advanced prostate cancer.

A human bladder cancer cell line resistant to doxorubicin, KK47/ADM has been established in vitro by exposing KK47 parent cells to progressively higher concentrations of the drug over a period of 16 months. The KK47/ADM was 271 times more resistant to doxorubicin than the KK47 parent. The KK47/ADM exhibited cross-resistance to doxorubicin derivatives (pirarubicin, epirubicin), vinca alkaloids (vinblastine, vincristine) and etoposide, but not to cisplatin, carboplatin, mitomycin C, peplomycin and methotrexate. Unlike the KK47 parent, about 70% of the KK47/ADM cells showed a positive reaction with monoclonal antibody against P-glycoprotein, MRK16. Uptake and efflux studies with [14C]doxorubicin indicated that the resistance exhibited by the KK47/ADM line was mainly due to a lower accumulation of the drug caused by an increased active efflux, and these were reversed in the presence of verapamil. Although verapamil enhanced doxorubicin sensitivity of KK47/ADM, a complete overcoming of the resistance could not be obtained. These two lines with different chemosensitivity are thus considered to be a useful model for developing new chemotherapeutic strategies against multidrug resistant bladder cancer.

The expression of a multidrug-resistant (MDR) gene product, P-glycoprotein, was examined immunohistochemically in 41 transitional cell carcinomas (TCCs) of the urinary tract. In 23 of these, chemosensitivity to adriamycin (ADM) and vinblastine (VBL) was also assessed by a microtiter succinate dehydrogenase inhibition test and the correlation between the expression of P-glycoprotein and MDR phenotype was investigated. P-glycoprotein was detected in 13 (72.2%) of the 18 untreated TCCs of the upper urinary tract (UUT), 6 (31.6%) of the 19 untreated TCCs of the bladder, and all of the 4 TCCs treated with M-VAC chemotherapy, respectively. Fourteen (87.5%) of the 16 TCCs with a positive expression of P-glycoprotein were resistant to ADM and VBL, whereas all of the 4 TCCs sensitive to both drugs were negative in the expression of P-glycoprotein. The succinate dehydrogenase activity of TCCs with a positive expression of P-glycoprotein was significantly higher than that of TCCs with a negative expression of P-glycoprotein (P < 0.05). Thus, there was a good correlation between the expression of P-glycoprotein and MDR phenotype in the chemosensitivity test. These results suggest that intrinsic MDR exists in some TCCs of the urinary tract, particularly UUT, and that the immunohistochemical investigation of P-glycoprotein may be useful for predicting the MDR phenotype in TCCs of the urinary tract.

A retrospective analysis of 59 patients with renal pelvic and ureter cancer (56 transitional cell carcinomas, 2 squamous cell carcinomas, and 1 adenocarcinoma), which were treated surgically, was performed in relation to postoperative recurrence, particularly distant metastasis. Of the 59 cases, postoperative recurrences developed as distant metastasis in 9 cases (15.3%), as bladder cancer in 19 cases (32.2%) and as contralateral renal pelvic and ureter cancer (bilateral metachronous cancer) in 3 cases (5.1%). Three of the 9 cases with the development of distant metastasis were squamous cell carcinoma or adenocarcinoma, and the others transitional cell carcinoma. All the metastases occurred within 2 years. In cases with transitional cell carcinoma, nonpapillary tumor, grade 3, high stage (pT3 and pT4), positive vascular invasion and IFN beta or gamma had a significant influence on the rate of distant metastasis. On the other hand, location, diversity and previous or coexistent bladder cancer did not seem to be related to the frequency of the development of distant metastasis. Thus, tumor aggressiveness was the only predictive valuable of the development of distant metastasis after surgery for renal pelvic and ureter cancer.

We reviewed 57 cases of Stage IV renal cell carcinoma to clarify the factors influencingprognosis and to evaluate the value of nephrectomy. Cumulative survival from the initial diagnosis was analyzed with respect to the patients' age, sex, side of primary tumor, initial performance status (PS), site of metastasis, and nephrectomy. Overall survival for the patients was 51 percent at one year, 22 percent at three years, and II percent at five years. Age, sex, and side of primary tumor had no influence on survival. Improved survival was correlated with good PS, metastases limited to single organ, and removal of the primary tumor. With regard to histopathologylogic features in nephrectomized patients, low grade and stage were correlated with longer survival, These factors should be considered in the analysis of results of future clinical trials of metastatic renal cell carcinoma.

Background: A 64-year-old Japanese man with stage D2 prostatic cancer, after having responded dramatically to androgen ablation, demonstrated a solitary adrenal metastasis without disease progression to any other site. Methods: A surgical excision of the lesion and adjuvant systemic chemotherapy was performed. Results/Conclusions: The patient has since remained alive without any evidence of recurrence 21 months after surgery.

A patient with fibromuscular dysplasia associated with primary thrombocythemia is reported. The patient, a 46-year-old female, had recurrent episodes of ischemic cerebrovascular accidents. Cranial CT scans revealed multiple low density areas in the right frontal and parietal lobes, and cerebral angiograms showed evidence of multiple embolisms. In addition, occlusion of the right internal carotid artery developed. To our knowledge, this is the first report on fibromuscular dysplasia complicated by essential thrombocythemia. The pathogenesis of the severe thrombotic tendency is discussed.

Two new strains of Serratia marcescens were constructed by the gene manipulation method from the clinical isolate US 46, which has two kinds of pili--mannose-sensitive (MS) and mannose-resistant (MR) ones--on the cell surface. After cloning the genes of the MS and MR pili, either the MS or the MR gene was transferred to the nonpiliated Escherichia coli, and MS- or MR-piliated strains were obtained. In the experimental pyelonephritis model of rats, MS- or MR-piliated bacteria were inoculated directly to the renal parenchyma, and the following results were obtained. MS-piliated rather than MR-piliated strains stimulated severe scarring of the kidney, and this scarring was suppressed by treatment with colchicine or superoxide dismutase (SOD) during an early stage of the infection. These findings suggest that MS-piliated bacteria stimulated polymorphonuclear leukocytes, which released large amounts of superoxide resulting in renal scarring. SOD was hoped to be a drug capable of preventing renal scarring, and such a result was successfully obtained.

PURPOSE In order to assess the validity of radical prostatectomy for the prostate cancer with PSA greater than 20 ng/ml, we reviewed the clinicopathological characteristics and prognoses of radical prostatectomy cases with PSA greater than 20 ng/ml. MATERIAL AND METHODS Twenty-one radical prostatectomy cases who had a serum PSA level greater than 20 ng/ml were reviewed regarding their clinicopathological characteristics. Step-sectioned specimens were used for pathological evaluation. RESULT The serum PSA level ranged from 21 to 65 ng/ml (median : 27 ng/ml). As for the clinical stage, there were 8 T1c cases, 5 T2b cases, 5 T2c cases, and 3 T3a cases (2001. TNM classification). According to the tumor location, 10 cases were diagnosed as peripheral zone (PZ) cancer, and 10 cases were diagnosed as transition zone (TZ) cancer. One case had several small cancer foci both in PZ area and TZ area. In 10 PZ cancer cases, 2 cases had lymph node metastasis, and 8 had seminal vesicle invasion. All of 10 PZ cancer cases showed extraprostatic extension, and 7 showed positive surgical margin. On the other hands in 10 TZ cancer cases, no cases had lymph node metastasis and seminal vesicle invasion. Five TZ cancer cases showed extraprostatic extension, and 6 showed positive surgical margin. The findings of digital rectal examination (DRE) and transrectal ultrasonography (TRUS) were positive in all PZ cancer cases, but these findings were unclear in TZ cancer cases. In addition, no significant difference were observed between the PZ cancer cases and the TZ cancer cases regarding age, PSA, prostate volume, PSA density, cancer volume, and Gleason scores. PSA failure was observed in 9 PZ cancer cases, and 2 TZ cancer cases. CONCLUSION Based on our findings, the prognosis of TZ cancer cases was better than that of PZ cancer cases among the radical prostatectomy cases with PSA greater than 20 ng/ml. Radical prostatectomy might be one of the effective treatment option for TZ cancer even if the PSA shows greater than 20 ng/ml. It seems to be important to detect TZ cancer properly based on DRE and TRUS findings.