Association depressive symptoms with memory function and social capital before and during COVID-19 in community-dwelling older adults in rural Japan: A retrospective study with a longitudinal data.

OBJECTIVES: This study aimed to investigate the impact of memory function and social capital on depressive symptoms during the COVID-19 pandemic among older adults in rural Japan. METHODS: A retrospective study with longitudinal data was conducted during COVID-19 from May 2021 to November 2021 (T2) in Kurogawa, Japan. The candidate population for this study was 145 with the following requirements: (1) older individuals aged 65 years or above who were registered in the Kurogawa study, and (2) those with previous data (from November 2016 to February 2020; T1 as pre-pandemic). Memory function was assessed using the Wechsler Memory Scale-Revised Logical Memory II delayed recall part A (LM II-DR). Depressive symptoms were assessed using the Japanese version of the 15-item Geriatric Depression Scale (GDS-15). Social capital was evaluated through civic participation, social cohesion, and reciprocity. Fear of the COVID-19 infection (FCV-19S) was evaluated. RESULTS: The final analysis included 96 participants (mean age = 81.0 years, SD = 4.8) Multivariate analysis for GDS-15 score by Mixed Model Repeated Measures (MMRM) revealed significant associations between LM II-DR (ß = -0.13, 95% CI: -0.21-0.05, p = 0.002) and FCV-19S during COVID-19 (ß = 0.08, 95% CI: 0.01-0.15, p = 0.02) with GDS-15 score. However, civic participation, social cohesion and reciprocity were not associated with GDS-15 score. CONCLUSIONS: Among older adults in rural Japan, memory function and fear of the COVID-19 infection were significantly associated with depressive symptoms in MMRM analysis. However, social capital was not associated with depressive symptoms. This highlights the need to address memory function and fear of the COVID-19 infection in interventions for older adults during crises like the COVID-19 pandemic.

Novel image-guided marker aimed at organ-preserving therapies for prostate cancer.

OBJECTIVE: We developed fiducial imaging-guidance markers for the prostate with less imaging artifacts than currently commercially available markers. The aim of this study was to evaluate the imaging artifacts and potential usefulness and safety of these novel fiducial imaging markers in preclinical experiments. METHODS: We selected specific metal materials and a shape that can minimize artifacts in line with a license we obtained for a metal with a gold-platinum (Au-Pt) alloy composition that maximized artifact-free MRI images. Both phantom and canine prostate tests were conducted in order to evaluate the imaging artifacts for three imaging modalities, MRI, CT and ultrasound, and the risk of migration of the markers from the site of insertion to elsewhere, as well as crushing. RESULTS: The newly developed Au-Pt material had less imaging artifacts in the MRI, CT and ultrasound imaging modalities in comparison with current commercially available fiducial markers made from gold materials only. The Au-Pt markers had sufficient strength and durability and were considered to be potentially clinically useful and safe markers. CONCLUSION: The developed Au-Pt markers could be potential tools for accurate lesion-targeted, organ-preserving therapies such as lesion-targeted focal therapy and active surveillance in addition to conventional radiation therapies.

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.

Microwave focal therapy of prostate cancer: a non-clinical study and exploratory clinical trial.

OBJECTIVE: To examine the safety and efficacy of microwave tissue coagulation (MTC) for prostate cancer and assess its use in lesion-targeted focal therapy in a non-clinical study and a clinical phase II trial. METHODS: In the non-clinical study using Microtaze® -AFM-712 (Alfresa Pharma Corporation, Osaka, Japan) with an MTC needle, MTC was performed using a transperineal approach to targeted canine prostatic tissue under real-time ultrasonography guidance. Using various MTC output and irradiation time combinations, the targeted and surrounding tissues (rectum, bladder and fat) were examined to confirm the extent of coagulative necrosis or potential cell death, and to compare intra-operative ultrasonography and pathology findings. The exploratory clinical trial was conducted to examine the safety and efficacy of MTC. Five selected patients underwent transperineal MTC to clinically single lesion magnetic resonance imaging (MRI)-visible lesions with Gleason score 3 + 4 or 4 + 4. Prostate-specific antigen (PSA), MRI and Expanded Prostate Cancer Index Composite questionnaire findings were compared before and 6 months after surgery. RESULTS: The region of coagulative necrosis was predictable by monitoring of ultrasonically visible vaporization; thus, by placing the MTC needle at a certain distance, we were able to perform a safe procedure without adverse events affecting the surrounding organs. Based on the non-clinical study, which used various combinations of output and irradiation time, MTC with 30-W output for 60-s irradiation was selected for the prostate. Based on the predictable necrosis, the therapeutic plan (where to place the MTC needle to achieve complete ablation of the target and how many sessions) was strictly determined per patient. There were no serious adverse events in any patient and only temporary urinary symptoms related to MTC therapy were observed. Furthermore, post-treatment satisfaction was very high. All preoperative MRI-visible lesions disappeared, and PSA decreased by 55% 6 months after surgery. CONCLUSION: Microwave tissue coagulation may be an option for lesion-targeted focal therapy for prostate cancer.

Predictive factors for the efficacy of abiraterone acetate therapy in high-risk metastatic hormone-sensitive prostate cancer patients.

PURPOSE: There is a discrepancy in the efficacy of abiraterone acetate for overall survival (OS) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study aimed to identify predictive factors for the efficacy of abiraterone acetate for OS in high-risk mHSPC patients by analyzing them over a longer observation period. METHODS: Five hundred high-risk mHSPC patients were retrospectively identified at our hospital and affiliated hospitals in the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2022. Two hundred patients were treated with abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) combined with androgen deprivation therapy (ADT). A total of 300 patients were treated with bicalutamide (80 mg/day) in combination with ADT. RESULTS: OS was not significantly different between the two treatments in the overall cohort (p = 0.1643). In the subgroup without Gleason pattern 5 at the primary lesion, OS was significantly better in patients treated with abiraterone acetate than in those treated with bicalutamide (p = 0.0192). In the subgroup with Gleason pattern 5 at the primary lesion, no significant difference was found between the two treatments (p = 0.1799). Univariate and multivariate analyses in the subgroup without Gleason pattern 5 at the primary lesion suggested that abiraterone therapy may be an important and independent predictor of OS in high-risk mHSPC patients. CONCLUSION: The presence of Gleason pattern 5 at the primary lesion may be a predictor for high-risk mHSPC patients who could benefit from abiraterone acetate treatment.

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.

Impact of prostate-specific antigen screening on tumor size in patients with prostate cancer in a super-aging district in Kyoto, Japan.

BACKGROUND: Population-based prostate-specific antigen (PSA) screening is effective for reducing prostate cancer (PCa)-related mortality rates. In this study, we assessed biopsy-proven maximum cancer core length (MCCL) and maximum cancer diameter on magnetic resonance imaging (MRI; MCDM) in prostate biopsy and multiparametric MRI (mp-MRI) by PCa detection. METHODS: We retrospectively assessed 214 male PCa patients and 187 PCa patients with Prostate Imaging Reporting and Data System version 2 (PI-RADS) category 3-5 lesions in pre-biopsy mp-MRI and targeted biopsy characteristics. The mean biopsy-proven MCCL and MCDM were compared among three PSA screening groups, namely the population-based PSA screening (PBS), opportunistic PSA screening (OPS), and symptomatic outpatient PSA examination (SOP) groups. RESULTS: The median age and PSA value of the 214 participants were 75 years and 7.9 ng/mL, respectively. In the PBS, OPS, and SOP groups, the median ages were 73, 76, and 76 years, respectively (p = 0.046); PSA values were 7.2, 9.5, and 11.5 ng/mL, respectively (p < 0.001); and biopsy-proven MCCL and MCDM were significantly increased to 7, 10, and 14 mm (p < 0.001) and to 11, 15, and 17 mm (p < 0.001), respectively. In the 187 PCa patients with PI-RADS category 3-5 lesions on mp-MRI, MCDM were 11, 14, and 17 mm (p < 0.001), respectively. CONCLUSIONS: The biopsy-proven MCCL and MCDM were significantly smaller in the PBS and OPS groups than in the SOP group, which suggests that PSA screening detected PCa earlier than in symptomatic patients. PSA screening with MRI could objectively lead to earlier diagnosis based on tumor size.

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.

Higher expression of phosphodiesterase type 5 in the anterior fibromuscular stroma of the human prostate.

PURPOSE: To examine phosphodiesterase type 5 (PDE5) expression in the anterior fibromuscular stroma (AFMS) of the prostate. Although PDE5 expression was identified in the human prostate, differences in PDE5 expression in intra-prostatic regions are unknown. The AFMS in the prostate has peculiar innervations that could contribute to voiding function. Here, we examined regional differences in PDE5 expression in the prostate with special reference to the AFMS. METHODS: A total 18 human prostate and bladder specimens were obtained. Tissue specimens were processed by hematoxylin-eosin (H&E) staining and immunohistochemistry for PDE5. Immunoreactivity with PDE5 was evaluated using computer-assisted image analysis in the following regions: the AFMS, bladder neck, stromal hyperplasia in the transition zone, glandular hyperplasia in the transition zone (TZ gland), and the peripheral zone (PZ). The correlation between PDE5 expression in the AFMS and clinical data was analysed. RESULTS: Image analysis revealed that the median ratio of the PDE5-immunoreactive area to smooth muscle area by H&E staining was 74.7% in the AFMS. There was significantly higher PDE5 expression in the AFMS than in the TZ gland (p = 0.034) and PZ (p = 0.002). PDE5 expression in the AFMS was not significantly correlated with age, prostate volume, transition zone volume, or transition zone index. However, older men had a tendency to have higher PDE5 expression in the AFMS. CONCLUSIONS: We found higher PDE5 expression in the AFMS compared with other prostatic regions, which suggested that the AFMS is a target region of PDE5 inhibitors in the prostate.

Magnetic resonance imaging-guided targeted prostate biopsy: Comparison between computer-software-based fusion versus cognitive fusion technique in biopsy-naïve patients.

OBJECTIVE: To compare magnetic resonance imaging-guided cognitive fusion-targeted biopsies versus computer-software-based fusion-targeted biopsies in prostate biopsy-naïve patients. METHODS: This was a retrospective review of 298 consecutive patients, in which suspected clinically significant prostate cancer lesions were detected on pre-biopsy magnetic resonance imaging, and cognitive fusion-targeted biopsies or software-guided magnetic resonance imaging-ultrasound fusion-targeted biopsies was carried out. The positivity rates of any cancer and clinically significant prostate cancer, Gleason score, and maximum cancer core length were compared between the cognitive fusion-targeted biopsies and software-guided magnetic resonance imaging-ultrasound fusion-targeted biopsies groups. RESULTS: The any-cancer positivity rate was 79.6% (90/113 patients) in the cognitive fusion-targeted biopsies group and 84.8% (157/185 patients) in the software-guided magnetic resonance imaging-ultrasound fusion-targeted biopsies group (P = 0.516), and the clinically significant prostate cancer positivity rate was 72.5% (82/113 patients) in the cognitive fusion-targeted biopsies group and 75.7% (140/185 patients) in the software-guided magnetic resonance imaging-ultrasound fusion-targeted biopsies group (P = 0.498). Among the patients in which the largest lesion diameter on magnetic resonance imaging was ≤5.0 mm, the clinically significant prostate cancer positivity rate was 39.2% (11/28 patients) in the cognitive fusion-targeted biopsies group and 66.6% (24/36 patients) in the software-guided magnetic resonance imaging-ultrasound fusion-targeted biopsies group (P = 0.043). The median maximum cancer core length was 7.5 mm (0.25-16 mm) in the cognitive fusion-targeted biopsies group and 8 mm (0.2-19 mm) in the software-guided magnetic resonance imaging-ultrasound fusion-targeted biopsies group (P = 0.040). CONCLUSIONS: Software-guided magnetic resonance imaging-ultrasound fusion-targeted biopsies offers a greater detection rate for smaller targeted lesions and also superior ability to sample greater cancer core length compared with cognitive fusion-targeted biopsies. The present results suggest that software-guided magnetic resonance imaging-ultrasound fusion-targeted biopsies might improve biopsy outcomes compared with cognitive fusion-targeted biopsies.

Focal salvage low-dose-rate brachytherapy for recurrent prostate cancer based on magnetic resonance imaging/transrectal ultrasound fusion biopsy technique.

OBJECTIVE: To examine the effect of permanent salvage brachytherapy in prostate cancer patients suffering recurrence after three-dimensional conformal external beam radiotherapy. METHODS: The ultra-focal (target lesion alone), hemi-lobe (within a hemi-lobe) or focused whole-gland (focusing on the lesion, but extending into the whole gland) pattern was selected based on the Gleason score for the targeted biopsy, the numbers of positive cores in the targeted and systematic biopsies, and the locations of the positive cores. Novel dosimetry criteria derived from three-dimensional cancer mapping, which was based on targeted magnetic resonance imaging/transrectal ultrasound fusion biopsies, were used in these cases. RESULTS: Permanent salvage brachytherapy was carried out in 13 patients who suffered prostate-specific antigen failure (prostate-specific antigen 2.1-6.8 ng/mL; age range 57-75 years; Gleason score ≤7 [n = 10], Gleason score ≥8 [n = 2] and Gleason score not available [n = 1]) since 2012. The targeted biopsy showed a single focus in three patients. The ultra-focal, hemi-lobe and focused whole-gland patterns were chosen in three, five and five patients, respectively. During the follow-up period (median duration 48 months), prostate-specific antigen failure occurred in zero of three, one of five and three of five of the patients treated with the ultra-focal, hemi-lobe and focused whole-gland patterns, respectively. The 4-year biochemical recurrence-free survival rate was 74%. No grade 3-4 adverse intestinal or urological events occurred. CONCLUSIONS: Targeted fusion biopsy-based three-dimensional cancer mapping should be used for permanent salvage brachytherapy treatment planning to reduce the incidence of treatment-related adverse events while maintaining good oncological outcomes.

Less nephrotoxicity of paclitaxel and ifosfamide plus nedaplatin for refractory or relapsed germ cell tumors in patients with impaired renal function.

OBJECTIVES: To determine the safety and efficacy of the combined regimen of paclitaxel and ifosfamide plus nedaplatin for patients with refractory or relapsed germ cell tumors and impaired renal function. METHODS: Of a total of 68 patients who received paclitaxel, ifosfamide and nedaplatin chemotherapy for germ cell tumors, those with an estimated glomerular filtration rate <60 mL/min/1.73 m2 before paclitaxel, ifosfamide and nedaplatin treatment were defined as having renal dysfunction. The combination chemotherapy regimen included paclitaxel (210 mg/m2 on day 1) and ifosfamide (1.2 g/m2 on days 2-6) with nedaplatin (100 mg/m2 on day 2) on a 3-week cycle. RESULTS: A total of 10 patients had renal dysfunction with a median estimated glomerular filtration rate of 49.97 mg/mL/1.73 m2 (range 31.7-57.5 mg/mL/1.73 m2 ). Paclitaxel, ifosfamide and nedaplatin chemotherapy was given as second-line therapy in four patients, third-line in four and fourth-line or later in two. Patients with impaired renal function received pretreatment of a median of 5.5 cycles of platinum-based chemotherapy (range 3-11 cycles) with a median cisplatin dose of 550 mg/m2 . The patients were given two to six cycles of paclitaxel, ifosfamide and nedaplatin chemotherapy with no dose reduction, with an overall response rate of 60%. Chemotherapy-induced kidney dysfunction was not observed in any patient with decreased renal function. Furthermore, there was no difference in the frequency of adverse events between patients with renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2 ) and those with normal renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2 ). CONCLUSIONS: Paclitaxel, ifosfamide and nedaplatin chemotherapy can be considered a safe and effective regimen that results in less nephrotoxicity in germ cell tumor patients with renal dysfunction.

Prostate cancer meeting the Japanese active surveillance criteria and diagnosed by community-based prostate-specific antigen screening: A 21-year follow-up study.

OBJECTIVES: To evaluate the oncological outcomes of Japanese patients with prostate cancer diagnosed by community-based prostate-specific antigen screening during a 21-year period who satisfied the criteria for active surveillance. METHODS: Active surveillance candidates were extracted from the community-based screening registry of Otokuni district in Kyoto prefecture. The frequency of active surveillance candidates before and after publication of the active surveillance criteria in Japan was analyzed. In addition, we examined the frequency of switching to curative intervention and treatment failure among active surveillance candidates, including the patients who selected active surveillance. RESULTS: During the study period, 868 patients were diagnosed with prostate cancer and 780 of these patients were analyzed. Among them, 190 patients (24%) satisfied our active surveillance criteria (21 and 169 in the pre-active surveillance era and active surveillance era, respectively). Of the 169 patients in the active surveillance era, 74 initially selected active surveillance. The number of active surveillance candidates increased with increasing age, and the proportion of active surveillance candidates among prostate cancer patients also increased significantly each year (P < 0.001). In the active surveillance group, the median follow-up period was 4 years and 35% switched to curative intervention. Among the 190 active surveillance candidates, seven died of other causes, but there were no deaths from prostate cancer. CONCLUSIONS: Changes of active surveillance candidates in one district of Japan were successfully analyzed by using consistent active surveillance selection criteria and data obtained by a single pathologist. Oncological outcomes were good among active surveillance candidates in the low-risk group.

Magnetic resonance imaging/transrectal ultrasound fusion-targeted prostate biopsy using three-dimensional ultrasound-based organ-tracking technology: Initial experience in Japan.

OBJECTIVE: To evaluate the impact of magnetic resonance imaging/transrectal ultrasound fusion-targeted prostate biopsy on the diagnosis of clinically significant prostate cancer using real-time three-dimensional ultrasound-based organ-tracking technology. METHODS: The present study was a retrospective review of 262 consecutive patients with prostate-specific antigen of 7.1 ng/mL (interquartile range 4.0-19.8). All patients received pre-biopsy magnetic resonance imaging and had a suspicious lesion for clinically significant prostate cancer. All patients underwent a combination of systematic biopsy (6 cores) and three-dimensional ultrasound-based magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (2 cores). The positive rate of any cancer, positive rate of clinically significant prostate cancer, Gleason score and maximum cancer core length were compared between systematic biopsy versus magnetic resonance imaging/transrectal ultrasound fusion-targeted prostate biopsy. RESULTS: Overall, the positive rate of any cancer per patient was 61% (160/262) in systematic biopsy versus 79% (207/262) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001); and that of clinically significant prostate cancer per patient was 46% (120/262) in systematic biopsy versus 70% (181/262) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001). The positive rate of any cancer per core was 21.7% (330/1523) in systematic biopsy versus 68.6% (406/592) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001), and that of clinically significant prostate cancer per core was 12.7% (193/1423) in systematic biopsy versus 60.3% (357/592) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001). Adding systematic biopsy leads to 13 more cancer cases (5%). The distribution of Gleason score (6/7/8/9/10) was 59/71/23/6/1 in systematic biopsy versus 48/105/36/15/2 in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P = 0.005). The maximum cancer core length was 5 mm (0.5-16) in systematic biopsy versus 8 mm (1-19 mm) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001). CONCLUSIONS: Three-dimensional ultrasound-based magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy seems to be associated with a higher detection rate of clinically significant prostate cancer, with fewer cores than systematic random biopsy. However, significant cancer can still be detected by the systematic technique only. A combination of systematic biopsy with the targeted biopsy technique would avoid the underdiagnosis of clinically significant prostate cancer.

Current status and progress of focal therapy in Asia.

PURPOSE OF REVIEW: With the increasing incidence of low-to-intermediate risk of prostate cancer (PCa) by the introduction of prostate-specific antigen (PSA) screening, focal therapy has become one of the promising treatment options in the world. In Asia, same movement are occurring using several technologies including cryoablation, high-intensity focused ultrasound, brachytherapy and irreversible electroporation. However, these are still not common strategies to treat organ-confined PCa. The purpose of this review is to summarize the most updated experience and future direction of focal therapy in Asian countries. RECENT FINDINGS: The prevalence and diagnosis of PCa are increasing in Asian countries. This increase is related to various factors including the widespread implementation of PSA testing and lifestyle changes to more Westernized diets. With the increasing detection rate of early stage PCa, overdetection and overtreatment are recognized even in Asia. In this setting, accumulating data on multiparametric MRI and MRI-targeted biopsy as well as MRI-transrectal ultrasound (TRUS) fusion biopsy suggest the potential in improving the detection of clinically significant PCa in Asia. Furthermore, targeted focal therapy has emerged as a promising treatment strategy aiming for both providing oncological outcome and maintaining functional preservation in many Asian countries. SUMMARY: At present, focal therapy is not a current standard choice for the treatment of localized PCa in Asian countries. However, with the increase of localized PCa and patient's preference for less invasive treatment with preservation of organ-function, focal therapy should become a definite treatment option for localized PCa in Asia.

Chemotherapy for metastatic testicular cancer: The first nationwide multi-institutional study by the Cancer Registration Committee of the Japanese Urological Association.

OBJECTIVES: To assess clinicopathological data and oncological outcomes focused on metastatic testicular cancer patients, who received chemotherapy as the initial treatment, in the nationwide multi-institutional study by the Cancer Registration Committee of the Japanese Urological Association. METHODS: A testicular cancer survey was carried out by the Japanese Urological Association in 2011 to register newly diagnosed testicular cancers in 2005 and 2008. Among 1121 registered patients, 278 patients with metastases who received chemotherapy as the initial treatment and could be categorized by the Japanese Urological Association classification were eligible for the analysis. RESULTS: As first-line chemotherapy, bleomycin, etoposide and cisplatin, and etoposide and cisplatin therapies were chosen for 260 patients (93.5%). As second-line therapy, vinblastine, ifosfamide and cisplatin/etoposide, ifosfamide and cisplatin; and paclitaxel, ifosfamide and cisplatin/paclitaxel, ifosfamide and nedaplatin therapies were carried out in 23 out of 63 (36.5%) and 29 out of 63 (46.0%) patients, respectively. The response rate and serum tumor marker normalization rate were 93.4% and 81.3% at first line, 75.4% and 60.7% at second line, and 41.7% and 16.7% at third line, respectively. The Japanese Urological Association classification (≥IIIB2 vs ≤IIIB1) and choriocarcinoma component in primary histology were independent prognostic factors of overall survival before starting chemotherapy. Furthermore, in patients with non-seminomatous germ cell tumors, serum tumor marker normalization was an independent factor that was associated with better outcome of overall survival after completion of the initial series of chemotherapies. CONCLUSIONS: The initial accurate diagnosis and risk stratification is an important prognostic factor to achieve better oncological outcomes. In patients with non-seminomatous germ cell tumors, aiming for serum tumor marker normalization with continuous sequential chemotherapy could improve overall survival.

Morphometric analysis of prostate zonal anatomy using magnetic resonance imaging: impact on age-related changes in patients in Japan and the USA.

OBJECTIVES: To evaluate the impact of morphometric magnetic resonance imaging (MRI) analysis of the prostate zonal anatomy on aging, prostatic hypertrophy and lower urinary tract symptoms in patients from Japan and the USA. SUBJECTS AND METHODS: A retrospective analysis of 307 men, including 156 men from Japan and 151 from the USA, who consecutively underwent 3-Tesla MRI and International Prostate Symptom Score (IPSS) assessment because of elevated PSA levels. Using Synapse-Vincent (Fujifilm), the prostatic zones were segmented in each axial step-section of the T2-weighted MRI to reconstruct a three-dimensional model of the prostate, which was used to calculate: zonal volumes (whole-gland prostate, transition zone and peripheral zone volumes); the presumed circle area ratio (PCAR); and PZ thickness. Bivariate associations were quantified using Spearman's rank correlation coefficients. RESULTS: The USA subgroup had a greater prostate volume (49 vs 42 mL; P = 0.003) and TZ volume (26 vs 20 mL; P < 0.001) than the Japan subgroup, with no difference in PZ volume (19 vs 20 mL; P = 0.2). There was no age-related increase in PZ volume in either of the subgroups or in the entire cohort (P = 0.9, P = 0.2, P = 0.3, respectively). PZ thickness had a significant negative correlation with PCAR (P < 0.001) and TZ volume (P < 0.001). The greater the increase in the TZ volume with the increase in PCAR, which probably correlates with obstructive pressure, the thinner the PZ became. PCAR had a significant positive correlation with IPSS (P = 0.003) and obstructive symptoms (P = 0.007), while PZ thickness had a significant negative correlation (P = 0.018). CONCLUSIONS: No age-related increases and no differences between the Japanese and the US subgroups were found with regard to PZ volume. The more TZ volume increased, the higher the obstructive pressure and the thinner the PZ became; these changes were associated with increased obstructive symptoms. MRI analysis of prostate zonal anatomy enhanced our understanding of age-related changes in morphology and urinary symptoms.

Reversible Interconversion between 2,5-Dimethylpyrazine and 2,5-Dimethylpiperazine by Iridium-Catalyzed Hydrogenation/Dehydrogenation for Efficient Hydrogen Storage.

A new hydrogen storage system based on the hydrogenation and dehydrogenation of nitrogen heterocyclic compounds, employing a single iridium catalyst, has been developed. Efficient hydrogen storage using relatively small amounts of solvent compared with previous systems was achieved by this new system. Reversible transformations between 2,5-dimethylpyrazine and 2,5-dimethylpiperazine, accompanied by the uptake and release of three equivalents of hydrogen, could be repeated almost quantitatively at least four times without any loss of efficiency. Furthermore, hydrogen storage under solvent-free conditions was also accomplished.

PAX2 promoted prostate cancer cell invasion through transcriptional regulation of HGF in an in vitro model.

Elucidating the mechanism of prostate cancer cell invasion may lead to the identification of novel therapeutic strategies for its treatment. Paired box 2 (PAX2) and hepatocyte growth factor (HGF) proteins are promoters of prostate cancer cell invasion. We found that PAX2 protein activated the HGF gene promoter through histone H3 acetylation and upregulated HGF gene expression. Deletion analysis revealed that the region from -637 to -314 of the HGF gene was indispensable for HGF promoter activation by PAX2. This region contains consensus PAX2 binding sequences and mutations of the sequences attenuated HGF promoter activation. Using an in vitro invasion model, we found that PAX2 and HGF promoted prostate cancer cell invasion in the same pathway. Knockdown of HGF expression attenuated the cells' invasive capacity. Moreover, in tissue samples of human prostate cancers, HGF and PAX2 expression levels were positively correlated. These results suggested that upregulation of HGF gene expression by PAX2 enhanced the invasive properties of prostate cancer cells. The PAX2/HGF pathway in prostate cancer cells may be a novel therapeutic target in prostate cancer patients.