Clinical outcomes by relative docetaxel dose and dose intensity as chemotherapy for Japanese patients with castration-resistant prostate cancer: a retrospective multi-institutional collaborative study.

BACKGROUND: The aim of this study was to retrospectively investigate clinical outcomes by relative dose and dose intensity of docetaxel (DOC) as chemotherapy for Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: A total of 145 CRPC patients who received more than 4 courses of DOC chemotherapy at 14 hospitals between 2005 and 2011 were enrolled. Patients were divided into two groups--those receiving a higher or lower dose (mg/m(2)) or dose intensity (mg/m(2)/week). Differences between the groups regarding treatment outcomes and adverse events (AEs) were determined. Additionally, prognostic factors predictive of cancer-specific survival (CSS) in these patients were identified by both univariate and multivariate analysis. RESULTS: The total patient group underwent a mean of 11.2 ± 7.4 DOC cycles, and the mean CSS after therapy was 15.6 ± 10.1 months. The higher-dose group had a better prostate-specific antigen (PSA) response than the lower-dose group. However, there was no significant difference between the groups in prognosis after DOC chemotherapy. Leukopenia and neutropenia were observed more frequently in the higher-dose group. Serum biomarkers (including PSA, lactate dehydrogenase and alkaline phosphatase), hemoglobin levels and presence of pain at initiation of chemotherapy, as well as the PSA nadir level on first-line hormone therapy, all were significant predictors of CSS. CONCLUSIONS: In the Japanese population, relatively low-dose DOC chemotherapy had no deleterious effect on the CSS of CRPC patients, and a lower incidence of AEs occurred, in spite of a diminished PSA response compared with those receiving a higher dose.

Associations between N-Terminal Pro-B-Type Natriuretic Peptide, Body Fluid Imbalance and Quality of Life in Patients Undergoing Hemodialysis: A Cross-Sectional Study.

Natriuretic peptides may be associated with the complex interaction between malnutrition and fluid overload. This study assessed the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP), body fluid composition, and quality of life (QOL) domains. A multicenter, cross-sectional study was conducted between 2019 and 2022. The QOL survey of 322 patients undergoing maintenance hemodialysis (227 men and 95 women; mean age, 65 ± 12 years) was conducted using the Kidney Disease QOL-Short Form v. 1.3. The patients in the higher NT-proBNP quartile group were older and had a longer dialysis vintage; lower body mass index, serum albumin, blood urea nitrogen, creatinine, sodium, uric acid, total cholesterol, triglycerides, and hemoglobin levels; lower geriatric nutritional risk index (GNRI), skeretal mascle mass index, and phase angle (PhA); and higher pre- and post-dialysis systolic blood pressure (BP), cardiothoracic index, and C-reactive protein (CRP) (p < 0.05). Multivariate analysis revealed that post-dialysis systolic BP, CRP, and GNRI or PhA were independently associated with NT-proBNP. The higher NT-proBNP group experienced muscle attenuation and/or inflammation and an enlarged left atrium. Consequently, the elevated NT-proBNP by such an imbalance in body fluid composition is associated with lower health-related QOL.

Association between Intra- and Extra-Cellular Water Ratio Imbalance and Natriuretic Peptides in Patients Undergoing Hemodialysis.

Natriuretic peptides are associated with malnutrition and volume overload. Over-hydration cannot simply be explained by excess extracellular water in patients undergoing hemodialysis. We assessed the relationship between the extracellular and intracellular water (ECW/ICW) ratio, N-terminal pro-B-type natriuretic peptide (NT-proBNP), human atrial natriuretic peptide (hANP), and echocardiographic findings. Body composition was examined by segmental multi-frequency bioelectrical impedance analysis in 368 patients undergoing maintenance dialysis (261 men and 107 women; mean age, 65 ± 12 years). Patients with higher ECW/ICW ratio quartiles tended to be older, were on dialysis longer, and had higher post-dialysis blood pressure and lower body mass index, ultrafiltration volume, serum albumin, blood urea nitrogen, and creatinine levels (p < 0.05). The ECW/ICW ratio significantly increased with decreasing ICW, but not with ECW. Patients with a higher ECW/ICW ratio and lower percent fat had significantly higher natriuretic peptide levels. After adjusting for covariates, the ECW/ICW ratio remained an independent associated factor for natriuretic peptides (ß = 0.34, p < 0.001 for NT-proBNP and ß = 0.40, p < 0.001 for hANP) and the left ventricular mass index (ß = 0.20, p = 0.002). The ICW-ECW volume imbalance regulated by decreased cell mass may explain the reserve capacity for fluid accumulation in patients undergoing hemodialysis.

Changes in blood pressure and arterial stiffness monitored using the cardio-ankle vascular index during hemodialysis.

During hemodialysis (HD), blood pressure (BP) changes are frequently observed. However, the mechanism of BP changes during HD has not been fully clarified. The cardio-ankle vascular index (CAVI) reflects the arterial stiffness of the arterial tree from the origin of the aorta to the ankle independent from BP during measurement. Additionally, CAVI reflects functional stiffness in addition to structural stiffness. We aimed to clarify the role of CAVI in regulating the BP system during HD. We included 10 patients undergoing 4-hour HD (total 57 HD sessions). Changes in the CAVI and various hemodynamic parameters were evaluated during each session. During HD, BP decreased and CAVI significantly increased (CAVI, median [interquartile range]; 9.1 [8.4-9.8] [0 min] to 9.6 [9.2-10.2] [240 min], p < 0.05). Changes in CAVI from 0 min to 240 min were significantly correlated with water removal rate (WRR) (r = -0.42, p = 0.002). Changes in CAVI at each measurement point were negatively correlated with ΔBP (Δsystolic BPeach MP, r = -0.23, p < 0.0001; Δdiastolic BPeach MP, r = -0.12, p = 0.029). Whereas one patient exhibited a simultaneous decrease in BP and CAVI during the initial 60 min of HD. Arterial stiffness monitored with CAVI generally increased during HD. CAVI elevation is associated with decreased WWR and BP. An increase in CAVI during HD may reflect the contraction of smooth muscle cells and play an important role in BP maintenance. Hence, measuring CAVI during HD may distinguish the cause of BP changes.

Relation of Maximum Lifetime Body Mass Index with Age at Hemodialysis Initiation and Vascular Complications in Japan.

OBJECTIVE: The aim of this study was to investigate the association of the maximum lifetime body mass index (max BMI) with hemodialysis initiation and comorbidities in Japanese hemodialysis patients. METHODS: In a retrospective cross-sectional study on 724 hemodialysis patients, max BMI, age at hemodialysis initiation, and comorbidities including sleep apnea syndrome, cerebro-cardiovascular diseases, and proliferative diabetic retinopathy (PDR) were analyzed. Early hemodialysis initiation was defined as age <50 years. RESULT: Diabetes patients showed a higher max BMI and prevalence of atherosclerotic diseases than nondiabetes patients, despite almost the same age at hemodialysis initiation. Patients with early hemodialysis initiation showed higher male ratio, prevalence of PDR, and max BMI than those with later initiation, despite almost equal prevalence of diabetes. Receiver-operating characteristic curve analysis determined a max BMI of 28.4 kg/m2 as a reliable cutoff value for predicting early hemodialysis initiation, and this parameter was identified as an independent predictor of early hemodialysis initiation using bivariate logistic regression analysis. Vitrectomy for PDR also tended to contribute independently to early hemodialysis initiation. CONCLUSION: A high max BMI contributed to early hemodialysis initiation independent of diabetes. Furthermore, PDR was associated with a high max BMI and early hemodialysis initiation. These results suggest that weight reduction in young chronic kidney disease patients with obesity may prevent hemodialysis and blindness.

The Role of Cardio-Ankle Vascular Index as a Predictor of Mortality in Patients on Maintenance Hemodialysis.

AIM: Mortality rate of maintenance hemodialysis patients is known to be high. Cardio-ankle vascular index (CAVI) is an index reflecting the proper stiffness of the arterial tree from the origin of the aorta to the ankle. We aimed to clarify the utility of CAVI as a predictor of mortality in hemodialysis patients. The roles of age and nutritional conditions on survival were also examined. METHODS: We followed 242 patients undergoing hemodialysis for 6 consecutive years. Data from 209 patients (mean age was 60 ± 11 years) excluding those with ankle-brachial index <0.90 were then analyzed. CAVI and heart to ankle pulse wave velocity (haPWV) were measured using Vasera 1500. RESULTS: Thirty-eight hemodialysis patients who died during the 6-year period had higher age, cardiothoracic ratio (CTR), CAVI, and haPWV, and lower diastolic blood pressure, albumin, phosphate, and calcium phosphate product. The Kaplan-Meier curves for cumulative survival among the tertile groups showed that the mortality rate was higher in the highest tertile (T3) compared to T1/T2 for both CAVI and haPWV. Receiver operating characteristic (ROC) analysis revealed that CAVI had better discriminatory power for all-cause mortality compared to haPWV. In the Cox-proportional hazards analyses, 1 SD increase in both parameters contributed independently to all-cause mortality [CAVI: HR 1.595 (95% CI 1.108-2.297), haPWV: HR 1.695 (95% CI 1.185-2.425)], as well as age and CTR. Both parameters above the cut-offs estimated in the ROC analysis (CAVI ≥ 9.2, haPWV ≥ 8.9) also had independent contributions to mortality. CONCLUSION: Through the 6 consecutive years of follow-up in 209 HD patients, increased CAVI might represent a major modifiable risk factor for all-cause mortality. Further research is needed to examine whether CAVI-lowering interventions contribute to improved prognosis.

The effect of eicosapentaenoic acid on prostate-specific antigen.

The "Study of EPA Effects on Prostate Cancer" (SEEPC) Group has been conducting a clinical trial with patients who underwent radical prostatectomy. The main purpose of the SEEPC is to evaluate whether eicosapentaenoic acid (EPA) prevents prostate cancer (PC) recurrence. As the surrogate marker of recurrence, the prostate-specific antigen (PSA) level was measured. However, if EPA affects the PSA values independently of PC, PSA may not be a good marker of recurrence in the event of EPA treatment. Thus, in the present study, whether EPA affected the PSA values was investigated using non-PC volunteers. Twenty men, of at least 50 years of age, were recruited, mostly from hospital staff The volunteers were randomly allocated either to the EPA group or the control. The subjects in the EPA group were administered EPA-ethyl ester a dose of 2400 mg/day for 12 weeks, whereas the controls were administered none. Fasting blood samples were obtained before the start of EPA administration and 4 and 12 weeks later. The EPA concentrations in erythrocytes increased in all the subjects in the EPA group (174+/-96%) with no significant changes in the control group (8.5+/-14.0%). There were no significant differences between the two groups in the serum PSA levels, allowing the conclusion that the PSA is an appropriate surrogate marker of recurrence in prostate cancer.

Occult hepatitis B virus infection in Japanese chronic hemodialysis patients.

We investigated the prevalence of occult hepatitis B virus (HBV) infection in Japanese chronic hemodialysis patients. Hemodialysis patients (n = 1041) were screened for occult HBV. The presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (anti-HBc) was determined by various chemiluminescent immunoassays. HBV-DNA was quantified in patients positive for anti-HBc using quantitative real-time polymerase chain reaction. Among the 1041 patients, six (0.6%) were HBsAg-positive and 218 (20.9%) were anti-HBc-positive. All HBsAg-positive patients also tested positive for the presence of HBV DNA. Of 212 HBsAg-negative and anti-HBc-positive patients, three were positive for HBV DNA. Our study showed that the prevalence of occult HBV infection in chronic hemodialysis patients from eastern Japan was 0.3%.

Preoperative parameters to predict tumor volume in Japanese patients with nonpalpable prostate cancer.

BACKGROUND: Serum prostate-specific antigen (PSA) determination has led to the increased detection of nonpalpable prostate cancer (T1c cancer). Some T1c cancers are small and may pose no threat. To examine the characteristics of patients with T1c cancer in Japan, patients treated with radical prostatectomy were reviewed. To predict potentially insignificant cancer, which is a candidate for delayed treatment, patients whose biopsy specimen showed relatively favorable features were also examined. METHODS: In 40 patients with T1c cancers treated with radical prostatectomy, the pretreatment parameters of serum PSA, PSA density, biopsy Gleason score, and number of cancer-positive cores were determined and compared with the histological features in the surgical specimens. Pretreatment parameters were also determined in patients whose biopsy Gleason score was 6 or less, and whose biopsy specimen contained one or two cancer-positive cores, with 50% or less cancer involvement in any cancer-positive cores. RESULTS: At the time of radical prostatectomy, 73% of patients had organ-confined disease. When insignificant cancer was defined as a volume of less than 0.5 cm3 and a Gleason score of 6 or less, in 9 of the 40 (23%) patients with clinical T1c disease, the cancer was clinically insignificant. Multiple regression analysis of the pretreatment variables, including pretreatment PSA level, PSA density, and number of cancer-positive cores demonstrated that the pretreatment PSA level and number of cancer-positive cores were independent factors that predicted tumor volume. From the biopsy features, 19 patients were assessed as having clinically insignificant disease. Nine (47%) of them had tumors of less than 0.5 cm3, whereas 2 (11%) had tumors of more than 2 cm3. The values for pretreatment PSA density and PSA density adjusted for the transition zone volume for those with a cancer volume of 0.5 cm3 or more were significantly higher than the values for those patients with a cancer volume of less than 0.5 cm3. CONCLUSION: T1c cancers in Japanese patients included various cancers, from clinically insignificant to locally advanced ones. Pretreatment PSA level and the number of cancer-positive cores are useful parameters with which to predict cancer volume in the surgical specimen.

Intermittent androgen suppression for locally advanced and metastatic prostate cancer: preliminary report of a prospective multicenter study.

OBJECTIVES: To clarify the effect of intermittent androgen suppression on the time to androgen-independent progression and changes in quality of life (QOL). METHODS: Patients with locally advanced or metastatic prostate cancer were treated with a combination of leuprolide acetate and flutamide for 36 weeks. When the serum prostate-specific antigen (PSA) levels at 24 and 32 weeks were less than 4.0 ng/mL, treatment was withheld until the PSA level reached 15 ng/mL or the pretreatment level. This cycle of on-treatment and off-treatment was repeated until PSA failure (three consecutive increases in PSA level greater than 4.0 ng/mL during the on-treatment period) or symptomatic progression was observed. Changes in QOL were assessed by a self-assessment questionnaire. RESULTS: Forty-nine patients (26 with T3N0M0, 8 with T2-T3N1M0, 2 with T4N0M0, and 13 with T2-T3N0M1) were enrolled. The mean follow-up period was 136.5 weeks. Thirty-one patients finished cycle 1, six finished cycle 2, and three finished cycle 3. The mean off-treatment duration in cycles 1, 2, and 3 was 46.1, 36.9, and 23.3 weeks, respectively. In the off-treatment period, statistically significant improvements in the QOL score were observed in the categories of potency (11.4 versus 2.4) and social/family well-being (20.3 versus 16.1) compared with those in the on-treatment period. PSA failure occurred in 6 patients (3 with T3N0M0 and 3 with T2-T3N1M0), and all patients were alive at last follow-up. CONCLUSIONS: Our interim analysis indicated that QOL is remarkably improved during the off-treatment period. Intermittent androgen suppression would be a viable option for treatment of advanced prostate cancer, although a randomized controlled study is required to determine whether intermittent androgen suppression prolongs the time to androgen-independent cancer. We will continue follow-up in this study to a minimum of 3 years.