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Caffeine consumption is associated with the evening chronotype, and caffeine administration in mice results in prolonged period of the circadian rhythm in locomotor activity. However, as caffeine is bitter, sweetened caffeine is preferred by humans and mice; yet, its impact on the circadian clock has not been explored. In this study, mice were provided with freely available sweetened caffeine to investigate its effects on behavioral rhythms and peripheral clocks. Mice that freely consumed sweetened caffeine shifted from nocturnal to diurnal activity rhythms. In addition to the light-dark entrained behavioral rhythm component, some animals exhibited free-running period longer than 24-h. Intraperitoneal administration of caffeine at the beginning of the light phase also acutely induced diurnal behavior. The behavioral rhythms with long period (26–30 h) due to sweetened caffeine were observed even in mice housed under constant light or with a lesioned central circadian clock located in the suprachiasmatic nucleus of the hypothalamus; however, the rhythmicity was unstable. PER2::LUCIFERASE rhythms in peripheral tissues, such as the kidney, as measured via in vivo whole-body imaging during caffeine consumption, showed reduced amplitude and desynchronized phases among individuals. These results indicate that consumption of sweetened caffeine induces diurnal and long-period behavioral rhythms irrespective of the central clock, causing desynchronization of the clock in the body. [ABSTRACT FROM AUTHOR]

Objective: Novel androgen receptor axis‐targeted agents (ARATAs) have been developed for mCRPC and improved overall survival (OS). Here, we aimed to find predictors who will receive the greatest benefits from ARATAs. Methods: We previously performed a multicenter study to identify prognostic factors for metastatic hormone‐sensitive prostate cancer (mHSPC, n = 148) and mCRPC (n = 99), and showed that the bone scan index (BSI) was one of the significant prognostic factors for 3‐year OS (PROSTAT‐BSI study). mHSPC progressed to mCRPC (n = 101), for which 69 patients were treated with (n = 39) or without ARATAs (n = 30, prior to the approval of ARATAs). The 69 patients were divided into two groups according to patient factors, and these cohorts were further divided into two subgroups by usage of ARATAs. OS was compared between subgroups in each group. Results: The predictors were age (<71.4 years), serum levels of C‐reactive protein (≥0.16 ng/ml) and alkaline phosphatase (≥548 U/L), time to PSA progression after ADT (<8.9 months), the lowest PSA level (≥1 ng/ml) after ADT, and the rate of PSA decline 3 months after ADT (<0.987), whereas hemoglobin levels, PSA before ADT, Gleason scores, existence of visceral metastases, and BSI were not. Conclusions: The present study identified predictors for the effectiveness of ARATAs. The number of bone metastases (≒BSI), existence of visceral metastases, and Gleason scores, which were identified as high‐risk factors in the LATITUDE study and disease volume in CHAARTED criteria, did not appear to be useful for predicting effectiveness from ARATAs. [ABSTRACT FROM AUTHOR]

Objective: To determine prognostic factors including the Bone Scan Index in prostate cancer patients receiving standard hormonal therapy and chemotherapy. Methods: This multicenter Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index study involved 30 hospitals and enrolled 247 patients (age 71 ± 8 years) with metastatic hormone‐sensitive prostate cancer (n = 148) under hormone therapy and metastatic castration‐resistant prostate cancer (n = 99) under chemotherapy. The Bone Scan Index (%) was determined by whole‐body bone scintigraphy using 99mTc‐methylenediphosphonate. Patients were classified into tertiles and binary groups, and predictors of all‐cause death including Bone Scan Index, prostate‐specific antigen, and bone metabolic markers were determined using survival and proportional hazard analyses. Results: During a mean follow‐up period of 716 ± 404 days, 81 (33%) of the patients died, and 3‐year mortality rates were 20% and 52% in the metastatic hormone‐sensitive prostate cancer and metastatic castration‐resistant prostate cancer groups, respectively. Survival analysis showed that a Bone Scan Index >3.5% was a significant determinant of death in the metastatic hormone‐sensitive prostate cancer group, whereas prostate‐specific antigen >55 ng/mL before chemotherapy was a determinant of prognosis in the metastatic castration‐resistant prostate cancer group. A Bone Scan Index >3.5% was also associated with a high incidence of prostate‐specific antigen progression in the metastatic hormone‐sensitive prostate cancer group. Patients with metastatic hormone‐sensitive prostate cancer and a better Bone Scan Index response (>45%) to treatment had lower mortality rates than those without such response. Conclusion: The Bone Scan Index and hot spot number are significant determinants of 3‐year mortality, and combining the Bone Scan Index with prostate‐specific antigen should contribute to the management of prostate cancer patients with bone metastasis. [ABSTRACT FROM AUTHOR]

Background: We aimed to assess the short-term oncological outcomes of robot-assisted laparoscopic radical prostatectomy to determine the predictive factors associated with biochemical recurrence in high-risk prostate cancer patients. Methods: A total of 331 patients with localized prostate cancer underwent robot-assisted laparoscopic radical prostatectomy. Of them, 113 patients were diagnosed with high-risk prostate cancer according to the D'Amico risk group classification. We evaluated the association between pre- or postoperative predictive factors and biochemical recurrence using Cox regression analysis. Results: The 2-year biochemical recurrence-free survival rate was 65.0% in the high-risk group. On univariate analyses, PSA level > 20 ng/mL, Gleason pattern 5 component on biopsy, pathological stage T3 or higher, perineural invasion, and positive surgical margin were predictive factors for biochemical recurrence. On multivariate analysis, PSA level > 20 ng/mL, Gleason pattern 5 component on biopsy, perineural invasion, and positive surgical margin were identified as independent predictive factors. The 2-year biochemical recurrence-free survival rate was 36.5% for patients with PSA level > 20 ng/mL and/or Gleason pattern 5 component on biopsy. Conclusions: PSA level > 20 ng/mL and/or presence of the Gleason pattern 5 component on biopsy are predictive factors for early biochemical recurrence after robot-assisted laparoscopic radical prostatectomy in high-risk prostate cancer patients. We considered that these patients require a combined modality therapy to improve their prognosis. [ABSTRACT FROM AUTHOR]

Objective: To present the study design and rationale of Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index, a prospective study aiming to determine the role of the bone scan index, the amount of bone metastasis, in the treatment and prognosis of prostate cancer patients. Methods: A total of 237 patients were recruited at 30 hospitals in Japan. All had prostate cancer with bone metastasis and were scheduled to undergo either hormonal therapy (group H) or chemotherapy (group C). Bone scans were carried out with 99mTc‐methylenediphosphonate. Follow‐up studies are planned to continue for 3 years, and changes in biochemical and tumor markers in response to hormonal therapy and chemotherapy will be recorded in addition to skeletal‐related events, recurrence, disease progression and death. Results: The basic characteristics of the patients (n = 200) at the time of registration during December 2016 were as follows: mean age 71 ± 8 years; median bone scan index calculated on‐site 1.9% (range 0.02–13.3%); median number of hot spots 18 (range 1–128); median prostate‐specific antigen 155 ng/mL (range 0.04–22 412 ng/mL); and the most frequent Gleason score 9 (47%). The prostate‐specific antigen value was higher in group H than group C (288 vs 33 ng/mL, P < 0.0001), whereas bone scan indexes were comparable (1.7 vs 2.3%, not significant) between the two groups. Liver metastasis was more frequent in group C than group H (6.1% vs 0.8%, P = 0.035). Conclusions: The baseline characteristics of the Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index database have been established. This collaborative study can now proceed with clarifying the role of the bone scan index for patient management including treatment strategies and prognosis. [ABSTRACT FROM AUTHOR]

Purpose: We investigated that preoperative membranous urethral length (MUL) would be associated with the recovery of urinary continence after robot-assisted laparoscopic prostatectomy (RALP). Patients and methods: We studied 204 patients who underwent RALP between May 2013 and March 2016. All patients underwent pelvic magnetic resonance imaging (MRI) preoperatively to measure MUL. Urinary continence was defined as the use of one pad or less (safety pad). The 204 patients were divided into two groups: continence group, those who achieved recovery of continence at 3, 6, and 12 months after RALP, and incontinence group, those who did not. We retrospectively analyzed the patients in terms of preoperative clinical factors including age, body mass index (BMI), estimated prostate volume, neurovascular bundle salvage, history of preoperative hormonal therapy, and MUL. Results: The safety pad use rate was 69.6%, 86.9%, and 91.1% at 3, 6, and 12 months, respectively. On univariate and multivariate analyses, MUL were significant factors in every term of recovery of urinary continence in both groups. According to the receiver operating characteristic (ROC) curve analysis, the preoperative MUL that could best predict early recovery of urinary continence at 3 months after RALP was 12 mm. Conclusions: We suggest that preoperative MUL > 12 mm would be a predictor of early recovery of urinary continence after RALP. [ABSTRACT FROM AUTHOR]