Efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer: A single-center study in Japan.

OBJECTIVES: Cabazitaxel is a next-generation taxane that can prolong overall survival after docetaxel treatment in patients with metastatic castration-resistant prostate cancer. However, the efficacy of cabazitaxel varies among these patients. The clinical indicators of the prognosis after cabazitaxel treatment were analyzed. METHODS: A retrospective review of patients who received cabazitaxel between February 2015 and June 2021 was performed. All patients had metastatic castration-resistant prostate cancer. Prognostic factors for prostate-specific antigen progression-free and overall survival were analyzed by Cox proportional-hazards analysis and the log-rank test. RESULTS: The study comprised 57 patients who received cabazitaxel (median 4 cycles, range 1-27) at a starting dose of 15-25 mg/m2 . The median age and follow-up duration were 70 years and 9.2 months. The median prostate-specific antigen progression-free survival and overall survival were 2.6 and 10.5 months, respectively. Univariate analysis showed that previous androgen receptor-axis-targeted therapy before cabazitaxel treatment was the only significant risk factor (hazard ratio 2.784, p = 0.022) for prostate-specific antigen progression-free survival. Multivariate analysis for overall survival revealed that poor performance status (≥1) (hazard ratio 2.107, p = 0.039), low hemoglobin (hazard ratio 0.142, p = 0.010), and high neutrophil-lymphocyte ratio (hazard ratio 9.150, p = 0.032) at baseline were significantly associated with a poor prognosis. CONCLUSIONS: Previous androgen receptor-axis-targeted therapy was the only risk factor for biochemical progression. Poor performance status, anemia, and high neutrophil-lymphocyte ratio were risk factors for poor prognosis in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel. These risk factors seem useful for identifying patients with survival benefit from cabazitaxel treatment.

Sexual function using the EORTC QLQ-TC26 in testicular cancer survivors: A multi-institutional, cross-sectional study.

OBJECTIVE: To evaluate sexual function after treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 (EORTC QLQ-TC26) questionnaire in Japanese testicular cancer (TC) survivors in a multi-institutional, cross-sectional study. METHODS: This study enrolled TC survivors who visited any of eight high-volume institutions in Japan from 2018 to 2019. After obtaining informed consent, participants completed the EORTC QLQ-TC26 questionnaires. We evaluated sexual function after treatment for TC using the EORTC QLQ-TC26 and analyzed the impact of treatment on sexual function in TC survivors. RESULTS: A total of 567 TC survivors responded to the EORTC QLQ-TC26. Median age at the time of response was 43 years (interquartile range [IQR] 35-51 years), and median follow-up period after treatment was 5.2 years (IQR 2.2-10.0 years). Sexual function, particularly ejaculatory function, was significantly lower after post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) than after Surveillance or Chemotherapy groups (p < 0.05). In the PC-RPLND group, nerve-sparing procedure preserved postoperative ejaculatory function after RPLND compared with the non-nerve-sparing and offered improved ejaculatory function with time. On multivariate analysis, RPLND was a significant predictor of post-treatment ejaculatory dysfunction, particularly without nerve-sparing (odds ratio 3.0, 95% CI 1.2-7.7, p < 0.05). In addition, TC survivors with nerve-sparing RPLND had higher sexual activity than those without. CONCLUSION: This survey of the EORTC QLQ-TC26 showed that sexual function and activity in TC survivors after RPLND was reduced in the absence of nerve-sparing techniques.

Association of financial toxicity with quality of life in testicular cancer survivors.

OBJECTIVES: Most testicular cancer (TC) survivors have long-term survival. However, the association between financial toxicity (FT), which is an economic side effect of cancer treatment, and the quality of life (QOL) of TC survivors is still unclear. Thus, the impact of FT on the QOL of TC survivors was examined in a multi-institutional cross-sectional study. METHODS: We recruited TC survivors from eight high-volume institutions in Japan between January 2018 and March 2019. A total of 562 participants completed the EORTC QLQ-C30, EORTC QLQ-TC26 and the questionnaires on demographics, including annual income. Financial difficulty in the EORTC QLQ-C30 and low income were used to assess financial distress (FD) and financial burden (FB), respectively. FT was defined as FD and FB. The QOL scores were compared, and a multivariate logistic regression analysis for FT was performed. RESULTS: With severe FD, TC survivors had more treatment side effects, physical limitations, and anxiety concerning employment and future. The TC survivors who reported low income were worried about their jobs and the future. The QOL of the survivors with FT exhibited high impairment, except for sexual activity. In particular, the TC survivors with FT were physically limited and anxious concerning the future. The multivariate logistic regression analysis revealed that four or more chemotherapy cycles were substantial risk factors for FT (4 cycles, odds ratio (OR) = 4.17; ≥5 cycles, OR = 6.96). CONCLUSIONS: TC survivors who received multi-cycle chemotherapy were prone to experience FT, resulting in a decline in their health-related QOL.

[A Case of Pleural Empyema with Fistula Caused by Endobronchial Metastasis of Renal Cell Carcinoma].

A 52-year-old man complained of asymptomatic gross hematuria and cough. Chest and abdominal computed tomography (CT) revealed a right renal tumor, mediastinal lymph node metastasis, and right endobronchial metastasis. The right endobronchial metastasis was causing obstructive atelectasis in the lower lobe of the right lung. After tumor biopsy, the pathological diagnosis was clear cell renal cell carcinoma. Combination immunotherapy with ipilimumab and nivolumab was initiated, but CT showed enlargement of the metastatic lesion and lung abscess after two courses of treatment. The therapy was then switched to axitinib. Six days after initiation of axitinib, the lung abscess perforated into the pleural cavity, which resulted in the formation of pleural empyema with fistula. Ten days after initiation of axitinib, obstruction of the bronchus was relieved due to shrinkage of the right endobronchial metastasis, which resulted in development of a pneumothorax. Placement of a thoracic drainage tube and administration of an antimicrobial agent improved the pneumothorax and inflammatory response, but the drainage tube could not be removed. Long-term insertion of the thoracic drainage tube considerably diminished the patient's quality of life, and after 4 months, he was transferred to another hospital to receive the best supportive care.

Antiresorptive agent-related osteonecrosis of the jaw in prostate cancer patients with bone metastasis treated with bone-modifying agents.

INTRODUCTION: The incidence rate and risk factors of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in prostate cancer patients with bone metastasis are not clear. MATERIALS AND METHODS: We retrospectively reviewed patients' records of prostate cancer patients with bone metastasis who were treated with zoledronic acid or denosumab between 1/Dec/2008 and 31/Mar/2019. ARONJ-free survival rate was analyzed with Kaplan-Meier analysis, and risk factors for ARONJ were analyzed with Cox proportional hazard model. RESULTS: We identified 124 and 67 patients treated with zoledronic acid and denosumab, respectively. Seventy-six patients were hormone sensitive, and 115 patients were castration resistant when they started bone-modifying agents (BMA). Twenty-eight patients developed ARONJ during the observation period (median: 23 months, range 1-130 months). Their number of doses of BMA ranged 3-69 (median: 21.5). The 2-year ARONJ-free survival rate was 91.1%, and the 5-year ARONJ-free survival rate was 72.5%. There was no significant difference in the incidence rate of ARONJ between zoledronic acid and denosumab. However, multivariate analysis revealed that use of denosumab (hazard ratio [HR] 3.67, 95% confidence interval [CI] 1.01-13.31; p = 0.0484), serum calcium < 9.2 mg/dL (HR 3.16, 95% CI 1.10-9.13; p = 0.033)), and concomitant or prior use of chemotherapeutic agents (HR 4.71, 95% CI 1.51-14.71; p = 0.0076) were independent risk factors for the development of ARONJ. CONCLUSION: Almost one-quarter of patients had a risk of developing ARONJ within 5 years after starting BMA. Low serum calcium, use of chemotherapeutic agents, and use of denosumab might contribute to the development of ARONJ.

Clinical indicators for predicting prognosis after radium-223 administration in castration-resistant prostate cancer with bone metastases.

BACKGROUND: Radium-223 (Ra-223) is a targeted alpha therapy that has been shown to prolong overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. However, prognosis after Ra-223 administration varies among patients. The aim of the present study was to assess risk factors associated with the poor prognosis of patients treated with Ra-223. METHODS: We retrospectively reviewed patients' records of treatment with Ra-223 between October 2016 and December 2019. All patients had mCRPC, bone metastasis, and no known visceral metastases, and received up to six cycles of Ra-223 (55 kBq/kg). Prognostic factors for OS were analyzed by Cox proportional hazards model and log-rank test. RESULTS: We identified 42 patients who received at least one cycle of Ra-223 (median six cycles, range 1-6). Approximately two-thirds of patients had received at least two lines of therapy for mCRPC. The median age was 74 years, and the median follow-up duration was 13.6 months. The median OS time was 16.6 months. On multivariate analysis, PSA doubling time (PSADT) (0-3 months) at baseline, number of bone metastases (≥ 20), and treatment line of Ra-223 (4th-5th line) remained significantly correlated with the poor OS (HR 4.354, P = 0.003; HR 2.855, P = 0.020; and HR 4.871, P = 0.001, respectively). CONCLUSIONS: Our study demonstrated that a shorter PSADT, a heavier volume of bone metastases, and a later treatment line before Ra-223 are poor prognostic factors for mCRPC patients. These newly discovered risk factors may help select patients who potentially have long-term OS after Ra-223 treatment.

Fertility and reproductive technology use in testicular cancer survivors in Japan: A multi-institutional, cross-sectional study.

OBJECTIVE: To evaluate fertility and use of reproductive technology of testicular cancer survivors in a multi-institutional, cross-sectional study. METHODS: This study recruited testicular cancer survivors who were followed after treatment for testicular cancer at eight high-volume institutions between 2018 and 2019. The participants completed the questionnaires on marital status, fertility and use of reproductive technology. RESULTS: A total of 567 testicular cancer survivors, with a median age of 43 years, responded to the questionnaire. Chemotherapy was given to 398 survivors, including three cycles of cisplatin-based chemotherapy in 106 patients and four cycles in 147 patients. Among 153 survivors who attempted sperm cryopreservation, 133 (87%) could preserve sperm. Of the 28 survivors whose cryopreserved sperm was used, 17 (61%) fathered children. Of the 72 survivors who fathered children without the use of cryopreserved sperm, 59 (82%) fathered naturally. Whereas 33 (20%) of 169 survivors treated without chemotherapy fathered children without using cryopreserved sperm, 39 (10%) of 398 treated with chemotherapy fathered children (P < 0.05). Furthermore, the paternity rate was 12% and 5% in testicular cancer survivors with three and four cycles of cisplatin-based chemotherapy, respectively (P < 0.05). However, of 121 survivors who wanted to have children, 14 (12%) received counseling about infertility treatment. CONCLUSIONS: Testicular cancer survivors preserving their sperm have a higher paternity rate after chemotherapy, especially after four cycles, than those not using cryopreserved sperm. Physicians who give chemotherapy for testicular cancer need to take particular care not only with respect to recurrence of testicular cancer, but also to post-treatment fertility.

Validation study of the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 for patients with testicular cancer.

OBJECTIVE: To validate the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 in Japanese-speaking testicular cancer survivors. METHODS: A total of 200 testicular cancer survivors were recruited at eight high-volume institutions in Japan. The participants completed the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and the International Index of Erectile Function 15 questionnaires. A total of 40 participants completed a retest of the questionnaires 2 weeks after the first response. The psychometric properties of the Japanese version including test-retest reliability, internal consistency and concurrent validity were evaluated. RESULTS: The mean age at response was 43 years (range 22-74 years), and the mean period after treatment was 77 months (range 0-416 months). The response rate for each item, except sexual function, was high, and the percentage of missing values was less than 3.5%. For test-retest reliability, seven of 12 scales met the criteria (intraclass correlation 0.70-0.86). For internal consistency, four of seven scales met the criteria (Cronbach's alpha 0.62-0.91). For concurrent validity, treatment side effects of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were related to some domains of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. The sex-related subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were moderately correlated with some International Index of Erectile Function 15 domains. CONCLUSIONS: The psychometric properties of the Japanese version are equivalent to the properties of the original European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26. The Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 questionnaire is a useful tool to assess the health-related quality of life of testicular cancer patients.

Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial.

BACKGROUND: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). METHODS: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. RESULTS: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). CONCLUSIONS: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.

Spiky-shaped niobium pentoxide nano-architecture: highly stable and recoverable Lewis acid catalyst.

Niobium pentoxide particles with a complex three-dimensional (3D) nanostructure consisting of a spiky structure have been developed as recyclable and recoverable Lewis acid catalysts. The morphology of the niobium pentoxide was successfully controlled from 1D to 3D via a bridging-ligand-assisted hydrothermal treatment, without changing the crystal structure. Compared with dispersed one-dimensional (1D) niobium pentoxide nanorods with a major-axis length and minor-axis length of 20 nm and 5-8 nm, respectively, the spiky-shaped niobium pentoxide composed of 300 nm spherical cores and nanorods with a minor-axis length of 5 nm maintained its surface nanostructure even after calcination at 400 °C in air. The 400 °C-calcined spiky particles exhibited the highest production rate of 2-((4-methoxyphenyl)amino)-2-phenylacetonitrile (0.115 mmol m-2) in a Strecker reaction, resulting in a nanoscale and ordered surface structure of spiky particles that simultaneously exhibit high specific reactivity and high structural stability. Acid site analysis and Raman spectroscopy revealed that stable nanorods that grew in the (001) orientation functioned as Lewis acid catalysts and that the origin of the acidity was a flexible Nb-O polyhedral structure in the single-nanoscale (<10 nm) niobium oxide rods. This study proposes that the spiky-shaped niobium pentoxide exhibits sintering resistivity and high activity and has potential applications as a recoverable and recyclable solid acid catalyst.

Utility of index lesion volume assessed by multiparametric MRI combined with Gleason grade for assessment of lymph node involvement in patients with high-risk prostate cancer.

PURPOSE: We examined the potential predictors of lymph node involvement and evaluated whether index lesion volume assessed using multiparametric magnetic resonance imaging is associated with lymph node involvement among patients with high-risk prostate cancer. METHODS: Extended pelvic lymph node dissection was used to evaluate patients with lymph node involvement. We retrospectively analyzed consecutive 102 patients with high-risk prostate cancer who underwent extended pelvic lymph node dissection at our institution between 2011 and 2017. To evaluate the index lesion volume at multiparametric magnetic resonance imaging (mrV), lesions were manually contoured on each T2-weighted axial slice in combination with diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging and integrated using image analysis software. Logistic regression analysis was performed to identify predictors of lymph node involvement. RESULTS: The median mrV was 1.4 ml (range 0-30.1 ml), and the median number of resected lymph nodes was 14 (range 7-38). Among 102 patients, 28 (28%) had lymph node involvement. Multivariate analysis identified significant predictors of lymph node involvement as follows: biopsy Gleason-grade group 5 (odds ratio = 17.2; 95% confidence interval, 2.1-299.0; P = 0.005), preoperative mrV (odds ratio = 1.14; 95% confidence interval, 1.02-1.30; P = 0.025) and percentage of positive cores with highest Gleason-grade group (odds ratio = 1.05; 95% confidence interval, 1.01-1.10; P = 0.005). Lymph node involvement was prevalent (69%) among tumors with Gleason-grade group 5 and mrV ≥3.4 ml, but was infrequently (10%) present among tumors with Gleason-grade group ≤4 and mrV <3.4 ml. CONCLUSIONS: The combination of biopsy Gleason-grade and mrV may serve as a useful tool to stratify patients according to their risk of nodal metastases.

[A Case of Myocardial Metastasis of Renal Cell Cancer Treated with Nivolumab].

The patient a 48-year-old male, underwent nephrectomy for clear cell renal cell carcinoma. After surgery, the patient was treated sequentially with sunitinib, axitinib, and everolimus for multiple pulmonary metastases and iliopsoas muscle metastasis. After 16 months, subcutaneous metastasis and left ventricular myocardial metastasis developed without any symptoms. He was treated with pazopanib for these metastases. However, no shrinkage was seen and bone metastasis in right acetabulum appeared. After radiation therapy (20 Gy/5 Fr) for right acetabulum, nivolumab was administered for myocardial metastasis and subcutaneous metastasis. Significant shrinkage of metastases was seen after 3 courses of nivolumab and the patient's condition remained stable after 31 courses of nivolumab.

[A Case of Primary Central Nervous System Lymphoma that Developed during the Treatment of Castration-Resistant Prostate Cancer].

A 64-year-old man was diagnosed with metastatic prostate cancer (cT3bN0M1b) and treated with combined androgen blockade. After two years and three months, he developed castration-resistant prostate cancer. Multiple lung metastases appeared after the administration of five courses of docetaxel and four courses of cabazitaxel therapy. Pulmonary metastases disappeared following rechallenge with docetaxel. Enzalutamide administration was initiated because docetaxel had to be discontinued due to adverse events. Although enzalutamide lowered the prostate specific antigen value, the patient staggered while walking and developed homonymous hemianopsia. Magnetic resonance imaging revealed a brain tumor. Although the brain tumor was considered to have metastasized from the prostate cancer, it was diagnosed as a primary central nervous system lymphoma using open-ended tumor biopsy. The brain tumor was eliminated with whole-brain irradiation. Thereafter, he has been treated with enzalutamide for 3 years without clinical progression of either disease.

Impact of sex difference on survival of bladder cancer: A population-based registry data in Japan.

OBJECTIVE: To investigate the impact of sex on the prognosis of bladder cancer in Japan. METHODS: In total, 18 728 patients diagnosed as having bladder cancer from 1993 to 2006 were registered in population-based cancer registries of six prefectures in Japan. We estimated relative survival by sex, age, clinical stage at initial diagnosis and pathology. RESULTS: Patients included 14 203 men (75.8%) and 4525 women (24.2%). The stage at initial diagnosis in women was significantly higher than in men (P < 0.0001). Pathologically, women were more likely to have non-urothelial cancer than men (women 18.0%, men 9.5%, P < 0.0001). The 5-year relative survival was 80.3% for men and 67.7% for women. The 5-year relative survival was 93.0% for men and 87.7% for women in the localized cancer group, 34.8% for men and 23.9% for women in the locally advanced cancer group, and 7.1% for men and 8.3% for women in the metastatic cancer group. The relative survival of women was worse than that of men in the localized cancer group (hazard ratio 1.29, 95% confidence interval 1.05-1.57; P = 0.0145) and locally advanced cancer group (hazard ratio 1.32, 95% confidence interval 1.15-1.52; P = 0.0001), but not different in the metastatic cancer group (hazard ratio 1.04, 95% confidence interval 0.87-1.25; P = 0.6555). CONCLUSIONS: Population-based registry data in Japan show that the cancer stage at initial diagnosis is higher in women than in men, and women with localized or locally advanced bladder cancer have a worse prognosis compared with men.

[A Case of Retroperitoneal Liposarcoma in which Magnetic Resonance Imaging was Useful in the Decision of Resection of Primary and RecurrentTumors].

A 47-year-old female was referred to our hospital because of retroperitoneal tumor which was detected by computer tomography (CT). Since the tumor was considered to be benign by magnetic resonance imaging (MRI), she was followed by MRI every 3 months. The site of the tumor was gradually increased, and 15 months after presentation, a lesion with high signal intensity on diffusion weighted image (DWI) appeared in the tumor. At that time, we performed tumor resection considering the tumor to be malignant. Pathological diagnosis was dedifferentiated liposarcoma. Three years and two months after the operation, liposarcoma recurred in the left retroperitoneal space. Because it showed low signal intensity on DWI, which was compatible with well-differentiated liposarcoma, further follow-up was carried out. Eleven months after the recurrence, a lesion with high signal intensity on DWI appeared in the tumor. We performed tumor resection again, leading to pathological diagnosis of recurrence of dedifferentiated liposarcoma. She remained free of disease at 4 months after surgery.

Weak ferromagnetic ordering in brownmillerite Ca2Fe2O5 and its effect on electric field gradients.

Brownmillerite Ca2Fe2O5 (CFO) exhibits a magnetic transition at TN ∼ 730 K. Many studies have reported the magnetic properties of CFO. However, the magnetic structure of CFO is still debated, i.e., whether the magnetic ordering is purely antiferromagnetic or weakly ferromagnetic, which originated from canted magnetic moments. In addition, the reason for the CFO showing large magnetoresistance is still unclear. This study attempts to address the unresolved issues stated above by multiple investigations on the crystal structure, magnetization, and Mössbauer parameters. Based on the results of the investigation, we conclude that the CFO is not purely antiferromagnetic but weakly ferromagnetic. That is the reason for the disappearance of the spontaneous magnetization at the magnetic critical temperature TN. The Mössbauer spectroscopy shows that the magnetic moments slightly cant against the a-direction, resulting in the presence of a net magnetic moment along the c-direction under the space group of Pnma. A reason for the canted magnetic moments is due to the presence of the Dzyalosinskii-Moriya (DM) interaction. The electric field gradient (EFG) refined from the Mössbauer spectroscopy investigated at 287 K is larger than that at 750 K, which is higher than TN. This suggests that the EFG changes below TN. A local electric polarization induced by the DM interaction is a possible reason for the change in the EFG. As a result, strong correlations between the magnetic ordering and the electrical properties appear in the CFO. The Arrhenius plot of the total electrical conductivity showed a kink at TN, which is one of these strong correlations.

Postoperative early ultrasensitive prostate-specific antigen identifies patients at risk for biochemical recurrence in margin positive prostate cancers: a single-center study.

OBJECTIVE: To identify predictors for biochemical recurrence among patients with positive surgical margins (RM1) after radical prostatectomy and to examine the effect of ultrasensitive prostate-specific antigen measured early after prostatectomy on biochemical recurrence. METHODS: We identified 705 patients with prostate cancer who were treated with radical prostatectomy without preoperative hormonal therapy at our institution between 2000 and 2014. The patients with RM1 who had a postoperative prostate-specific antigen <0.2 ng/ml without lymph node metastasis were evaluated for biochemical recurrence-free survival. Survival rates were calculated using the Kaplan-Meier method. The Cox regression model was used for multivariate analysis. The prediction of biochemical recurrence was assessed using area under the curve of the receiver operating characteristic. RESULTS: Among the 705 patients, 190 (27%) had RM1. Biochemical recurrence was evaluated in 164 patients, excluding 26 patients who underwent adjuvant therapy with or without lymph node metastasis. With a median follow-up of 55 months, the biochemical recurrence-free survival rate of the entire RM1 cohort was 78% at 2 years and 64% at 4 years. The multivariate analysis revealed that postoperative early ultrasensitive prostate-specific antigen >0.02 ng/ml was the significant risk factor for biochemical recurrence (hazard ratio 13.10). Meanwhile, the patients with postoperative early ultrasensitive prostate-specific antigen <0.01 ng/ml had a significantly lower risk for biochemical recurrence (hazard ratio 0.12). Area under the curve for the postoperative early ultrasensitive prostate-specific antigen value to predict biochemical recurrence was 0.789. CONCLUSIONS: The ultrasensitive prostate-specific antigen value measured early after prostatectomy was the potent predictor of biochemical recurrence among the patients with RM1.

[A Case of Renal Cell Carcinoma with Malignant Pleural Effusion Showing Marked Response to Axitinib].

A 36-year-old woman had undergone left radical nephrectomy followed by interferon-α and sunitinib for the treatment of renal cell carcinoma with para-aortic lymph node and lung involvements (papillary renal cell carcinoma, G3, cT3aN1M1) in the previous hospital. She was referred to our hospital for further treatment and received serial molecular targeted agents (everolimus, sorafenib, sunitinib) and radiation therapy for right ischial and femoral bone metastases. Then she was found to have multiple metastatic lesions in the lungs and carcinomatous pleural effusion associated with dyspnea. After failure of pleurosclerosis with OK-432, the pleural effusion markedly reduced by axitinib administration, but the pleural effusion relapsed a few days after axitinib was discontinued. For this reason, axitinib was maintained in spite of appearance of new metastatic lesions in the brain. The pleural effusion was well-controlled for 16 months but she died of progressive disease, including metastatic lesions in the brain and in the lungs.

A single-center study on predicting outcomes of primary androgen deprivation therapy for prostate cancer using the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score.

OBJECTIVE: Japan Cancer of the Prostate Risk Assessment scores are reportedly useful for predicting progression-free survival after primary androgen deprivation therapy of prostate cancer patients. This study validated the risk assessment at a single institution. METHODS: We studied 255 prostate cancer patients given primary androgen deprivation therapy. Progression-free survival, cause-specific survival and overall survival were analyzed according to Japan Cancer of the Prostate Risk Assessment score-based risk classification. Cases with lymph node or distant metastases were subdivided by the risk classification. RESULTS: Ages ranged from 50 to 90 years (median: 76.5). Observation periods were 2-199 (median: 46.5) months. Primary androgen deprivation therapy includes combined androgen blockade in 150 cases (58.8%), uncombined luteinizing hormone-releasing hormone agonist in 97 (38.0%) and uncombined anti-androgenic agent in 8 (3.2%). Risk classified by Japan Cancer of the Prostate Risk Assessment scores was low in 104 cases (40.8%), intermediate in 86 (33.7%) and high in 65 (25.5%). The 5-year/10-year progression-free survival rates were 100%/80.8% in the low-risk, 82.3%/69.5% in the intermediate-risk and 34.7%/16.5% in the high-risk group. The 5-year/10-year cause-specific survival rates were 100%/100% in the low-risk, 90.7%/58.2% in the intermediate-risk and 63%/30.8% in the high-risk group. The 5-year/10-year overall survival rates were 87.5%/78.5% in the low-risk, 76.2%/43.1% in the intermediate-risk and 54.9%/25.4% in the high-risk group. For lymph node metastasis, cause-specific survival differed minimally between the intermediate- and high-risk groups (P = 0.1118). For distant metastasis, cause-specific survival differed significantly between the intermediate- and high-risk groups (P = 0.0264). CONCLUSIONS: Japan Cancer of the Prostate Risk Assessment score-based risk classification is useful for predicting post-primary androgen deprivation therapy progression-free survival, cause-specific survival and overall survival. Subtyping patients based on Japan Cancer of the Prostate Risk Assessment scores is particularly useful for predicting cause-specific survival with distant metastasis from prostate cancer.

Oxygen vacancy formation and the ion migration mechanism in layered perovskite (Sr,La)3Fe2O(7-δ).

Metal oxides are widely used in devices such as sensors, fuel cells, and oxygen permeation membranes. Understanding the oxide ion migration mechanism would provide fundamental insights into the relationships between the structure and properties such as ionic conductivity. The Ruddlesden-Popper perovskite (Sr,La)n+1(Fe,Co)nO3n+1 (n = 2) has characteristic oxygen permeation and ion conduction properties, resulting from the layered perovskite structure. To elucidate the ion migration mechanism in Sr2.46La0.54Fe2O7-δ (SLF) we used a combination of experimental techniques [X-ray powder diffraction (XRPD) and enthalpy investigations of the oxygen vacancy formation reaction] and computational techniques [the bond valence sum (BVS) approach and ab initio density functional theory (DFT)]. The structural analyses of SLF by XRPD and DFT agreed well. They showed that the oxygen vacancies in SLF are located at the O1 oxygen site, which is on the vertex shared by two FeO6 octahedra in the perovskite layer. Enthalpy of the oxygen vacancy formation changed at 830 °C. This is similar to the ionic conduction behavior reported for Sr3Fe2O7. The XRPD study indicates that the host structural framework did not change with temperature, while the oxygen/vacancy arrangement in SLF did change at 830 °C. The BVS and DFT studies suggested a change in the ion migration pathway, in which the ion migration through O1 sites becomes more important at temperatures higher than 830 °C.