Significance of pelvic lymph node dissection during radical prostatectomy in high-risk prostate cancer patients receiving neoadjuvant chemohormonal therapy.

We aimed to determine the survival and staging benefit of limited pelvic lymph node dissection (PLND) during radical prostatectomy (RP) in high-risk prostate cancer (PC) patients treated with neoadjuvant chemohormonal therapy. We retrospectively analyzed 516 patients with high-risk localized PC (< cT4N0M0) who received neoadjuvant androgen-deprivation therapy plus estramustine phosphate followed by RP between January 2010 and March 2020. Since we stopped limited PLND for such patients in October 2015, we compared the surgical outcomes and biochemical recurrence-free survival (BCR-FS) between the limited-PLND group (before October 2015, n = 283) and the non-PLND group (after November 2015, n = 233). The rate of node metastases in the limited-PLND group were 0.8% (2/283). Operation time was significantly longer (176 vs. 162 min) and the rate of surgical complications were much higher (all grades; 19 vs. 6%, grade ≥ 3; 3 vs. 0%) in the limited-PLND group. The inverse probability of treatment weighting-Cox analysis revealed limited PLND had no significant impact on BCR-FS (hazard ratio, 1.44; P = 0.469). Limited PLND during RP after neoadjuvant chemohormonal therapy showed quite low rate of positive nodes, higher rate of complications, and no significant impact on BCR-FS.

Effect of advanced glycation end products on nocturia or sleep disorders: A longitudinal study.

Objective: This study aimed to investigate the effect of advanced glycation end products (AGEs) on nocturia and sleep disorders in community-dwelling adults. Materials and Methods: This longitudinal study evaluated AGEs level, sleep disorders and nocturia frequency in 447 community-dwelling adults between May 2011 and May 2016. Sleep disorders were evaluated using the Pittsburgh Sleep Quality Index (PSQI) score. Participants were divided into two groups: AGEs-low (≤1.80) and AGEs-high (>1.80). The longitudinal nocturia and PSQI changes for 5 years between the AGEs-low and AGEs-high groups were compared. The effect of baseline oxidative stress on worsening of nocturia or PSQI score 5 years later was evaluated using multivariable logistic regression analyses. Results: There was no significant difference in PSQI score and nocturia frequency between the AGEs-low (n = 223) and AGEs-high (n = 224) groups at baseline. The PSQI score and nocturia frequency increased significantly over 5 years in both groups. However, the PSQI score increased significantly in the AGEs-high group compared with the AGEs-low group, although there was no difference in nocturia. Background-adjusted multivariable analysis showed that the AGE-high was significantly associated with PSQI score worsening, but AGE-high was not significantly associated with nocturia worsening. Conclusions: Oxidative stress may be significantly associated with worsening sleep disorders, although oxidative stress may not significantly worsen nocturia frequency.

Utility of total cell-free DNA levels for surgical damage evaluation in patients with urological surgeries.

The evaluation of surgical damage is challenging because of the lack of specific biomarkers. Total cell-free DNA (cfDNA) levels have been reported to increase with external trauma and may be a biomarker for tissue damage. To investigate the utility of perioperative total cfDNA levels in evaluating surgical damage in urological surgeries. This multicenter, prospective, observational study included 196 patients scheduled for urological surgeries between September 2020 and July 2021. The primary outcome was the change in total cfDNA levels before and after urological surgery. The secondary outcome was the effect of surgical type on total cfDNA ratio before and after urological surgery. The postoperative median total cfDNA level of the 196 patients was significantly increased 2.5-fold compared to the preoperative level (185.2 ng/mL vs. 406.7 ng/mL, P < 0.001). The median total cfDNA before/after ratio was greater than four-fold for kidney transplantation, open cystectomy, and open adrenalectomy. The ratio was less than two-fold for laparoscopic adrenalectomy and robot-assisted radical prostatectomy. Major surgery showed a significant postoperative increase in total cfDNA levels, while minor surgery did not. Total cfDNA levels increased 2.5-fold after urological surgery and it can be used as an acute-phase biomarker for surgical damage.

The effect of number of treatment cycles of platinum-based first-line chemotherapy on maximum radiological response in patients with advanced urothelial carcinoma.

OBJECTIVE: The number of cycles of platinum-based first-line chemotherapy associated with the maximum tumor response in patients with advanced urothelial carcinoma is not yet established. We investigated the association between the number of cycles and the maximum radiological response of first-line chemotherapy. METHODS: We retrospectively evaluated 167 patients with advanced urothelial carcinoma treated with platinum-based first-line chemotherapy between May 2003 and December 2020. The primary outcome was estimating the number of cycles associated with the maximum radiological response and progression disease rate within the 6 cycles. The radiological response was evaluated by the RECIST v1.1. The secondary outcomes included the difference in radiological response rate and the impact on overall survival between the cisplatin-based and carboplatin-based regimens. RESULTS: The maximum radiological response was -22% at Cycles 2. It was significantly decreased at Cycles 4 (-15%) compared with Cycles 2 (P < 0.001). The progression disease rate within the first 2, 4, and 6 cycles were 21% and 63%, and 84%, respectively. Radiological response was no significant difference between the cisplatin-based and carboplatin-based regimens. However, it was significantly decreased in the carboplatin-based regimen at Cycles 4 (-17%) compared with Cycles 2 (-22%; P = 0.004). Background-adjusted overall survival was not significantly different in between the cisplatin-based and carboplatin-based regimens (hazard rate 1.27; P = 0.337). CONCLUSION: The maximum radiological response was -22% at Cycles 2. The radiological response was significantly different between Cycle 2 and 4. More than half of patients had disease progression within the first 4 cycles.

Prognostic significance of total plasma cell-free DNA level and androgen receptor amplification in castration-resistant prostate cancer.

PURPOSE: To investigate the prognostic significance of total cell-free DNA (cfDNA) level and androgen receptor amplification (AR-amp) in patients with castration-resistant prostate cancer (CRPC). METHODS: We retrospectively compared the total cfDNA level and AR-amp in 42 individuals without prostate cancer, 57 patients with localized prostate cancer without androgen-deprivation therapy (ADT), 97 patients with castration-sensitive prostate cancer (CSPC) with ADT, and 97 patients with CRPC. The association of these cfDNA biomarkers on disease status and overall survival was evaluated using Kaplan-Meier analysis and multivariable Cox regression analysis. Finally, a simple risk model was developed including total cfDNA and AR-amp to predict poor prognosis. RESULTS: The median total cfDNA level and AR-amp in patients with CRPC was 387 pg/µL and 1.07 copies, respectively. The total cfDNA levels and AR-amp were significantly higher in the patients with CRPC than in individuals without prostate cancer, patients with localized prostate cancer without ADT, and patients with CSPC with ADT. Total cfDNA-high (> 600 pg/µL) and AR-amp-high (> 1.26 copies) were significantly associated with poor overall survival. Multivariable Cox regression analysis showed cfDNA-high and AR-amp-high were significantly associated with poor overall survival in patients with CRPC. We developed a risk model using cfDNA-high (score 1) and AR-amp-high (score 1). The risk score 1-2 was significantly associated with worse overall survival than score 0. CONCLUSION: Total cfDNA level and AR-amp are potential biomarkers for poor prognosis in patients with CRPC.

Overactive bladder and sleep disturbance have a significant effect on indoor falls: Results from the community health survey in Japan.

OBJECTIVES: To evaluate the effect of overactive bladder (OAB) and frailty on indoor fall events in community-dwelling adults aged 50 or older. METHODS: We conducted a cross-sectional study involving 723 adults between 2016 and 2017 in Hirosaki, Japan. OAB symptoms and sleep disturbance were assessed using the Overactive Bladder Symptom Score (OABSS) and the Pittsburgh Sleep Quality Index (PSQI). Indoor fall events (falls or near-falls) within 1 year were evaluated. Frailty was evaluated by the frailty discriminant score. We investigated the association of OAB symptoms with sleep disturbance, frailty, and indoor fall events. Multivariate logistic regression analysis was performed to investigate the effect of OAB symptoms on fall events controlling for confounding factors such as age, gender, comorbidity, frailty, and sleep disturbance. RESULTS: The median age was 64. We observed OABSS ≥6 in 98 participants (14%), nocturia ≥2 in 445 (62%), urgency score ≥3 in 80 (11%), urge incontinence score ≥3 in 36 (5.0%), PSQI ≥6 in 153 (21%), frailty in 169 (23%), and indoor fall events in 251 (35%). Older age, diabetes, OABSS, nocturia, urgency, urge incontinence, and the PSQI were significantly associated with indoor fall events. Multivariate logistic regression analyses showed that OAB symptoms and sleep disturbance were significantly associated with fall events. CONCLUSIONS: The effect of OAB symptoms and sleep disturbance on indoor fall events was significant. The causal relationship between OAB and falls needs further study.

A Longitudinal Study of Bidirectional Relationships between Sleep Disorder and Frequency of Nocturia: Results from the Iwaki Health Promotion Project.

INTRODUCTION: The causal relationship between sleep disorder and frequency of nocturia remains unclear. METHODS: We longitudinally evaluated sleep disorder and frequency of nocturia in 547 community-dwelling adults between baseline and 5-year follow-up. We included participants ≥50 years old who have no sleep disorder (the Pittsburgh Sleep Quality Index [PSQI] ≥ 5) nor nocturia (≥1). For 5 years, we evaluated the temporal changes in sleep disorder and nocturia and the bidirectional relationships between sleep disorder and nocturia. RESULTS: Of the 547 participants, we included 268 adults with a median age of 61 years in this study. Median PSQI and nocturia were significantly increased for 5 years from 2 to 3 and from 1 to 2, respectively. New onset of sleep disorder (PSQI > 5) and nocturia >1 was observed in 42 (16%) and 137 (51%) participants, respectively. The cross-lagged panel analysis showed that the path coefficient from PSQI to nocturia (ß = 0.22, p = 0.031) was significantly higher than that from nocturia to PSQI (ß = 0.02, p = 0.941). CONCLUSIONS: Our longitudinal study showed the effect of sleep disorder on nocturia was significant, although nocturia may not significantly worsen sleep disorder in community-dwelling adults.

Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: A single-center, open-label, prospective randomized study.

The efficacy and safety of zinc acetate hydrate (ZAH) for zinc supplementation in patients on maintenance hemodialysis (MHD) remains unknown. In this prospective, single-center, open-label, parallel-group trial for MHD patients with serum zinc level <70 µg/dL, we compared ZAH (zinc; 50 mg/day) and polaprezinc (PPZ; zinc; 34 mg/day) beyond 6-month administration in a 1:1 randomization manner. The ZAH and PPZ groups had 44 and 47 patients, respectively. At 3 months, the change rate of serum zinc levels in the ZAH group was significantly higher than that in the PPZ group. Three months after the study, serum copper levels significantly decreased in the ZAH group, but not in the PPZ group. No significant differences were noted in anemia management in either group. ZAH was superior to PPZ in increasing serum zinc levels. Clinicians should note the stronger decline in serum copper levels when using ZAH for MHD patients.

The Relationship Between Gait Function and Erectile Dysfunction: Results from a Community-Based Cross-Sectional Study in Japan.

INTRODUCTION: Although physical activity is associated with a decreased risk of erectile dysfunction (ED), the association of ED with physical function remains unclear. AIM: To investigate the relationship between gait function and ED in a community-dwelling population. METHODS: This cross-sectional study analyzed 324 men who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. ED was assessed with the 5-Item International Index of Erectile Function (IIEF-5). The participants were divided into 2 groups: low IIEF-5 score (≤16) and high IIEF-5 score (>16). We evaluated physical function, including gait function and grip strength. Gait function was evaluated by 10-meter gait speed and 2-step score (the ratio of the maximum length of 2 strides to height). We assessed daily physical activity, comorbidities, mental status, and laboratory data. The association between physical function and a low IIEF-5 score was analyzed by multivariate logistic regression analysis. MAIN OUTCOME MEASURE: The main outcome measure was to assess whether gait function was an independent indicator for erectile dysfunction. RESULTS: Of 324 men, 154 (48%) had a low IIEF-5 score. Grip strength, 2-step score, and 10-meter gait speed in the low IIEF-5 group were significantly inferior to those in the high IIEF-5 group. Multivariate analysis showed that the 2-step score (odds ratio = 0.08), age, and total testosterone were independently associated with a low IIEF-5. CLINICAL IMPLICATIONS: This study may motivate clinicians to investigate predictive values of physical function for ED. STRENGTHS & LIMITATIONS: The strength of this study was the use of simple, objective, and feasible tests for gait function to assess its association with ED. The limitations of this study were selection bias, regional bias, and nature of the cross-sectional study. CONCLUSIONS: Of the gait functional tests, not the 10-meter gait speed but 2-step score was an independent indicator for the presence of ED. Okamoto T, Hatakeyama S, Imai A, et al. The Relationship Between Gait Function and Erectile Dysfunction: Results from a Community-Based Cross-Sectional Study in Japan. J Sex Med 2019; 16:1922-1929.

Validation of the IMDC Prognostic Model in Patients With Metastatic Renal-Cell Carcinoma Treated With First-Line Axitinib: A Multicenter Retrospective Study.

BACKGROUND: The objective of the study was to validate the characteristics of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model in patients treated with first-line axitinib in clinical practice. PATIENTS AND METHODS: We retrospectively evaluated 143 patients with metastatic renal-cell carcinoma who were treated with axitinib as the first-line therapy between October 2008 and February 2019. Overall survival (OS) was evaluated according to the IMDC prognostic model. We investigated the intragroup heterogeneity in the intermediate-risk group and divided these patients according to abnormal C-reactive protein (CRP) levels. An inverse probability of treatment-weighted (IPTW)-adjusted Cox regression analysis was performed to evaluate the effects of the CRP-risk model of OS in the patients in the IMDC intermediate-risk group. RESULTS: A significant difference in OS was observed in patients in the IMDC intermediate- and poor-risk group, although no significant difference was observed between the IMDC favorable- and intermediate-risk group. Significantly shorter prognosis was observed in patients in the IMDC intermediate-risk group who had 2 risk factors and CRP ≥0.3 mg/dL (inter-high group) than in those with 1 risk factor or 2 risk factors with CRP <0.3 mg/dL (inter-low group). IPTW-adjusted Cox regression analysis revealed significant differences in the OS between the inter-low and inter-high groups. CONCLUSION: The IMDC prognostic model was active in patients who received first-line axitinib treatment. The combination of CRP value with the number of positive risk factors in the IMDC model might predict prognosis in patients with IMDC intermediate-risk treated with first-line axitinib.

C-reactive protein/albumin ratio is a predictive factor for prognosis in patients with metastatic renal cell carcinoma.

OBJECTIVES: To evaluate the effect of pretreatment C-reactive protein/albumin ratio and modified Glasgow prognostic score on the prognosis in patients with metastatic renal cell carcinoma. METHODS: A retrospective study was carried out in 176 patients with metastatic renal cell carcinoma who received first-line tyrosine kinase inhibitors. The effect of adding inflammatory prognostic scores to the International Metastatic Renal Cell Carcinoma Database Consortium model (International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio and International Metastatic Renal Cell Carcinoma Database Consortium-Glasgow prognostic score models) on overall survival was evaluated using receiver operating characteristic curves. The prognostic value of inflammatory prognostic scores (C-reactive protein/albumin ratio-modified Glasgow prognostic score) was tested using the Kaplan-Meier method and Cox proportional regression models. RESULTS: Patients were stratified into two groups using the cut-off value of 0.05: C-reactive protein/albumin ratio-low (<0.05) and C-reactive protein/albumin ratio-high (≥0.05). The area under the curve was significantly higher in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio model (0.720) than that of the International Metastatic Renal Cell Carcinoma Database Consortium model (0.689) and the International Metastatic Renal Cell Carcinoma Database Consortium-modified Glasgow prognostic score model (0.703). Significant differences were observed in overall survival stratified by the number of risk factors in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio risk model between one or two and three or four factors (P < 0.001), and three or four and five or more factors (P = 0.001). For the patients in the International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk group, overall survival was significantly different between the C-reactive protein/albumin ratio-low and -high groups (P = 0.001), whereas it was not significantly different between the patients with one and two International Metastatic Renal Cell Carcinoma Database Consortium risk factors (P = 0.106). CONCLUSION: The C-reactive protein/albumin ratio is a simple and independent predictor of overall survival in patients with metastatic renal cell carcinoma. The predictive activity was significantly improved in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio model compared with the International Metastatic Renal Cell Carcinoma Database Consortium/International Metastatic Renal Cell Carcinoma Database Consortium-modified Glasgow prognostic score models.

Relationship between oxidative stress and lower urinary tract symptoms: results from a community health survey in Japan.

OBJECTIVE: To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community-dwelling population. MATERIALS AND METHODS: The cross-sectional study included 1 113 people who participated in the Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed using structured questionnaires, including the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS > 5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to severe symptoms. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and advanced glycation end products (AGEs) were measured by urine analysis and skin autofluorescence, respectively. The relationship between oxidative stress and LUTS was investigated using logistic regression analyses. RESULTS: This study included 431 men and 682 women. AGEs and 8-OHdG levels were significantly higher in severe forms of LUTS. Multivariate logistic regression analyses showed that AGE levels were significantly associated with a higher frequency of nocturia but were not associated with IPSS, OABSS or urge incontinence. No significant association was observed between LUTS and 8-OHdG levels. CONCLUSIONS: We observed a significant association between AGE levels and nocturia score > 1. Further research is necessary to clarify a possible causal relationship between oxidative stress and nocturia.

Postoperative weight loss followed by radical cystectomy predicts poor prognosis in patients with muscle-invasive bladder cancer.

We aimed to investigate the impact of postoperative weight loss following radical cystectomy (RC) on patients' prognoses. RC and urinary diversion were performed in 512 consecutive patients with muscle-invasive bladder cancer at our hospitals between May 1996 and July 2018. Demographic clinical information, pre- and postoperative serum albumin, hemoglobin, and weight were evaluated retrospectively at 1 month. We also evaluated the association of weight loss with complications and overall survival (OS) as estimated using the Kaplan-Meier method and compared using the log-rank test. Risk factors for poor OS were determined by Inverse Probability of Treatment Weighted (IPTW)-adjusted Cox regression analysis. In 385 patients who met the study search criteria, median postoperative weight loss from baseline at 1 week and 1 month was 1.1 (- 1.8%) and 3.2 (- 5.4%) kg, respectively. Patients with significant weight loss (defined as ≥ 7.5% at 1 month) had higher-grade complications within 1 month and had significantly shorter OS than those with weight loss of < 7.5%. Type of urinary diversion, loss of serum albumin, and loss of hemoglobin were not significantly associated with weight loss. IPTW-adjusted Cox regression analysis showed that such significant weight loss was an independent risk factor for poor OS. Weight loss followed by radical cystectomy was significantly associated with poor prognosis in patients with muscle-invasive bladder cancer.

Comparison of axitinib and sunitinib as first-line therapies for metastatic renal cell carcinoma: a real-world multicenter analysis.

We aimed to compare oncological outcomes and safety of axitinib and sunitinib in patients with treatment-naïve metastatic renal cell carcinoma (mRCC). We retrospectively evaluated 169 patients with mRCC who were treated with axitinib or sunitinib as the first-line therapy in five hospitals between October 2008 and August 2018. Oncological outcomes and safety were compared between axitinib (n = 68) and sunitinib (n = 101) groups. Inverse probability of treatment weighted (IPTW)-adjusted Cox regression analysis was performed to evaluate effects of first-line therapies on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Patients in the axitinib group were significantly older (66 vs. 72 years) than those in the sunitinib group. Median relative dose intensity was significantly higher in the axitinib group (94 ± 62%) than in the sunitinib group (65 ± 20%; P = 0.001). Objective response rate was significantly higher in the axitinib group (21%) than in the sunitinib group (10%; P = 0.042). IPTW-adjusted Cox regression analysis revealed significant differences in CSS and OS but not in PFS between the two groups. Safety in terms of grade ≥ 3 adverse events was significantly different between the axitinib (34%) and sunitinib (55%) groups (P = 0.006). Compared with sunitinib, axitinib significantly prolonged CSS and OS and showed a safer profile as the first-line therapy for treatment-naïve mRCC.

Low serum butyrylcholinesterase is independently related to low fetuin-A in patients on hemodialysis: a cross-sectional study.

PURPOSE: Fetuin-A, which plays a protective role against the atherosclerosis and progression of vascular calcification, is decreased in patients on hemodialysis (HD). Fetuin-A and serum butyrylcholinesterase (BChE) levels decrease during malnutrition. We explored whether BChE was independently related to fetuin-A in patients on HD. METHODS: Laboratory data including BChE and serum fetuin-A were acquired from 230 patients on HD between August 2017 and April 2018. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI). Abdominal aortic calcification index (ACI) was measured using computed tomography. Patients were stratified into two groups: low fetuin-A (< lowest quartile) and non-low fetuin-A (≥ lowest quartile) groups. Patient background, medication, and laboratory data were compared. The receiver operating characteristic analysis was conducted to determine the optimal cutoff values of BChE and GNRI for lower fetuin-A level. Factors independently related with lower fetuin-A levels were determined using multivariate logistic regression analysis. RESULTS: The lowest quartile value of fetuin-A and optimal cutoff values of BChE and GNRI were 0.213 g/L, 200 IU/L, and 92.6, respectively. The study included 57 and 173 patients in the low fetuin-A and non-low fetuin-A groups, respectively. Significant between-group differences were observed for age, C-reactive protein (CRP), history of cardiovascular disease, serum albumin, GNRI, and BChE. Multivariate analysis showed that BChE of < 200 IU/L [odds ratio (OR) 3.05], CRP (OR 2.49), and GNRI of < 92.6 (OR 2.34) were independent factors for lower fetuin-A level after adjusting for confounders. CONCLUSIONS: BChE was a significant independent marker for fetuin-A levels in patients on HD, in addition to GNRI.

Speciation analysis of selenium metabolites in urine and breath by HPLC- and GC-inductively coupled plasma-MS after administration of selenomethionine and methylselenocysteine to rats.

Selenium is an essential trace element found in vegetables as selenomethionine (SeMet) and methylselenocysteine (MeSeCys). In the present study, we used stable isotopes of Se to investigate differences between how SeMet and MeSeCys are metabolized, using methylseleninic acid (MSA) as a reference methylselenol source. A mixture containing (76)Se-SeMet, (77)Se-MeSeCys, and (82)Se-MSA (each 25 microg Se/kg b.w.) was orally administered to rats, and then, speciation analyses of Se in urine and exhaled gas were conducted using HPLC-inductively coupled plasma (ICP)-MS and GC-ICP-MS, respectively. The proportions of (76)Se-, (77)Se-, and (82)Se-selenosugar (Se-sugar) to total urinary Se metabolites originating from each tracer were very similar, while the proportion of (77)Se-tirmethylselenonium (TMSe) was much less than that of(76)Se- and (82)Se-TMSe in urine, suggesting that(77)Se-SeMet is less efficiently metabolized to TMSe. Similarly, there was significantly less (77)Se-dimethylselenide (DMSe) originating from (77)Se-SeMet than(76)Se- and (82)Se-DMSe originating from (76)Se-MeSeCys and (82)Se-MSA in exhaled gas. It is generally accepted that DMSe and TMSe are metabolites of methylselenol, a putative metabolic intermediate in Se metabolism. Methylselenol is believed to be responsible for the cancer chemoprevention effects of Se. These results suggest that MeSeCys is converted to methylselenol more efficiently than is SeMet and that urinary TMSe and exhaled DMSe might be useful biomarkers for the generation of cancer chemopreventive forms of Se.