Associations of remaining teeth number, periodontal disease, and occlusal support status with erectile dysfunction in community-dwelling men.

OBJECTIVES: Several systematic reviews and meta-analyses have reported positive relationships between erectile dysfunction (ED) and periodontal disease. However, no study has evaluated the relationships of occlusal support status and the number of remaining teeth with ED. The aim of the present study was to investigate the relationships between ED and the remaining teeth number, periodontal disease, and occlusal support status. METHODS: This study included 400 community-dwelling men. Periodontal health status and occlusal support condition were evaluated using the Community Periodontal Index (CPI) and Eichner classification. Multivariable analyses were performed to evaluate the relationships between ED and the remaining teeth number, periodontal disease, and occlusal support status. RESULTS: The median age was 53 years. Of the 400 men, 333 (83%) were classified into ED group. In univariable analyses, remaining teeth number, CPI score, and Eichner classification were significantly associated with ED. In multivariable analyses, the remaining teeth number (odds ratio [OR]: 0.907, p = 0.114) and CPI score (OR: 0.978, p = 0.864) were not significantly associated with ED, whereas the Eichner classification was independently and significantly associated with ED (OR: 3.490, p = 0.042). CONCLUSIONS: Poor occlusal support status was significantly associated with ED in community-dwelling men, as opposed to remaining teeth number and periodontal health status.

Treatment trends in patients with de novo metastatic prostate cancer in the era of upfront combination therapy.

OBJECTIVES: The objective of this study is to assess the trends in treatment selection for patients with de novo metastatic castration-sensitive prostate cancer in the era of upfront combination therapy. METHODS: This multicenter retrospective study included 595 patients treated with either upfront combination therapy (upfront novel hormonal therapies and taxane-based chemotherapy) or vintage therapy (androgen deprivation therapy with or without bicalutamide) between 2016 and 2021. High tumor burden metastatic disease was defined when a patient met the CHAARTED or LATITUDE criteria. We evaluated trends in treatment selection and reasons for selecting vintage therapy. RESULTS: Of the 595, 123 and 472 patients were classified as having low and high tumor-burden disease, respectively. The Use of upfront combination therapy was found to be rapidly increasing with utilization rates of 72% and 54% in 2021 for high and low tumor-burden disease, respectively. Multivariable logistic regression analysis found older age, poor performance status, and nonacademic center were significantly associated with the selection of vintage therapy. Of the 163 patients who received vintage hormone therapy after approval of upfront therapy, 74.2% had a specific reason for avoiding upfront therapy. The reasons for selecting vintage therapy included refusal (39.8%), older age (67.6%), frailty (56.3%), and comorbidity (40.8%). Furthermore, 16.9% of patients declined upfront combination therapy due to cost concerns. CONCLUSION: Upfront combination therapy use has 72% and 54% prevalence among patients with high and low tumor burden diseases, respectively, in this current practice. Older age, poor performance status, and facility bias were negatively associated with the use of upfront combination therapy.

Effects of apalutamide dose reduction on skin-related adverse events in patients with advanced prostate cancer: A multicenter retrospective study.

BACKGROUND: We aimed to evaluate the effects of apalutamide dose reduction on skin-related adverse events (AEs) and castration-resistant prostate cancer (CRPC)-free survival in patients with advanced prostate cancer (PC). METHODS: We retrospectively evaluated 35 patients with nonmetastatic CRPC and 72 patients with treatment-naïve metastatic castration-sensitive PC (mCSPC) who were treated with apalutamide. The primary outcome was the effect of apalutamide dose reduction on skin-related AEs. The secondary outcomes were the effect of apalutamide dose reduction on skin-related AEs in patients with small body size, postskin AE apalutamide discontinuation rate, and CRPC-free survival in patients with mCSPC treated with upfront apalutamide plus androgen deprivation therapy. RESULTS: Of the 107 patients, 65 (60.7%) and 42 (39.3%) were treated with full and reduced doses of apalutamide, respectively. The skin-related AE rate was not significantly different between the groups (55% vs. 43%, p = 0.761). In the group receiving reduced apalutamide dose, the incidence of skin-related AEs was significantly lower in patients with small body sizes (body weight <67 kg and body mass index <24 kg/m2 ) than in those with other body sizes. The postskin AE apalutamide discontinuation rate was significantly differed between patients receiving the full (50%) and reduced (16.7%) doses. In the 72 patients with mCSPC, CRPC-free survival was not significantly different between the full and reduced dose groups. CONCLUSION: Apalutamide dose reduction was not significantly associated with the incidence of skin-related AEs. However, dose reduction in patients with small body sizes may alleviate skin-related AEs without sacrificing oncological outcomes.

Comparison of efficacy and medical costs between upfront docetaxel and abiraterone treatments of metastatic hormone-sensitive prostate cancer patients in real-world practice: a multicenter retrospective study.

PURPOSE: We compared the real-world efficacy and medical costs for treatment with upfront docetaxel (DOC) and abiraterone acetate (ABI) up to progression-free survival 2 (PFS2) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: This multicenter retrospective study included 340 patients with mHSPC treated with either upfront DOC or upfront ABI between October 2015 and December 2021. We compared PFS2 and medical costs between the two treatment groups. PFS2 was defined as the time from first-line therapy to progression on second-line therapy. Medical costs were estimated using the National Health Insurance drug prices in 2022 in Japan. RESULTS: The upfront DOC and ABI groups included 107 and 233 patients, respectively. The incidence of metastatic castration-resistant PC progression was significantly higher in the upfront DOC group compared with the incidence in the upfront ABI group. However, no significant differences in PFS2 were observed between the two treatment groups. Monthly medical costs per patient were significantly higher in the upfront ABI group ($3453) compared with the costs in the upfront DOC group ($1239, P < 0.001). The cost differences were significantly influenced by differences in the length of androgen deprivation therapy monotherapy (DOC group, 13.4 months vs. ABI group, 0.0 months). CONCLUSIONS: We observed a significant cost benefit in the upfront DOC group in Japanese real-world practice, while the PFS2 rates were similar between the groups. Upfront DOC was a more cost-effective option for men with mHSPC who were eligible for toxic chemotherapy.

Trends in the age of hospitalized patients with urological cancers: A 17-year experience.

OBJECTIVES: To investigate the impact of global aging on the trends in the age of hospitalized patients with a urological cancer diagnosis. METHODS: We retrospectively evaluated a cumulative total of 10 652 cases of referred patients (n = 6637) with a urological disease who were hospitalized in our institution between January 2005 and December 2021. We compared age and the proportion of patients aged ≥80 years among patients who were hospitalized in the urological ward between the period of 2005-2013 and that of 2014-2021. RESULTS: We identified 8168 hospitalized patients with urological cancer. The median age was significantly increased in patients with urological cancer between the periods of 2005-2013 and 2014-2021. The proportion of hospitalized patients with urological cancer aged ≥80 years was significantly increased between the periods of 2005-2013 (9.3%) and 2014-2021 (13.8%). The median ages of the patients with urothelial cancer (UC) and renal cell carcinoma (RCC), but not the median age of those with prostate cancer (PC), were significantly increased between the study periods. The proportion of hospitalized patients with UC, but not the proportions of those with PC and RCC, aged ≥80 years was significantly increased between the study periods. CONCLUSIONS: The age of patients with urological cancer who were hospitalized in the urological ward and the proportion of patients with UC aged ≥80 years significantly increased over the entire study period.

Relationship between lower urinary tract symptoms and frailty.

OBJECTIVE: To elucidate the relationship between frailty and lower urinary tract symptoms (LUTS). METHODS: We longitudinally evaluated the temporal changes and the relationships between frailty and LUTS in 247 community-dwelling adults (45 years or older) at baseline and at a 5-year follow-up. We used the Fried phenotype (phenotype-based frailty), 5-item modified frailty index (5i-mFI; comorbidity-based frailty), and frailty discriminant score (comprehensive frailty assessment) to evaluate frailty. LUTS were evaluated using the international prostate symptom score (IPSS) and overactive bladder symptom score (OABSS). RESULTS: We analyzed 247 participants with a median age of 60 years. The median IPSS and OABSS were significantly increased over the 5 years. The proportion of frail individuals did not increase significantly over the 5 years. Of the three frailty assessment tools, the 5i-mFI score significantly increased between 2014 and 2019. Multiple linear regression analyses showed that the 5i-mFI score was significantly associated with the severity of LUTS in 2014 to 5i-mFI in 2019 but not with 5i-mFI in 2014 to the severity of LUTS in 2019. CONCLUSION: The effect of LUTS on frailty might be greater than the effect of frailty on LUTS. Further large-scale studies are needed to elucidate the relationship between LUTS and frailty.

Impact of nephroureterectomy on postoperative renal function in upper tract urothelial carcinoma: A multicenter retrospective study.

OBJECTIVE: To assess the impact of radical nephroureterectomy on postoperative renal function in patients with upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively evaluated 645 patients with UTUC treated with radical nephroureterectomy between January 2000 and May 2022. The primary outcome was the rate of postoperative estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 . Secondary outcomes included the rate of eGFR decline, identification of factors related to eGFR decline, and the impact of comorbidities (diabetes or cardiovascular disease) on postoperative eGFR at 1 year. RESULTS: The median preoperative and postoperative eGFR levels were 55.6 and 43.3 mL/min/1.73 m2 , respectively. The rate of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m2 was 40.9% and 9.0%, respectively. The median decline in eGFR after surgery was 25.1%. The presence of preoperative unilateral hydronephrosis and eGFR <60 mL/min/1.73 m2 was significantly associated with a low decline of postoperative eGFR and poor survival. The impact of the presence of comorbidities on postoperative eGFR at 1 year was significant (p < 0.001). CONCLUSION: Impaired renal function is prevalent in patients with UTUC. The rate of patients with postoperative eGFR ≥60 mL/min/1.73 m2 was 9.0%. The presence of preoperative renal impairment was significantly related to a low decline in postoperative eGFR and poor survival. The presence of comorbidities had a significant effect on eGFR decline 1 year after radical nephroureterectomy.

The cell surface hyaluronidase TMEM2 is essential for systemic hyaluronan catabolism and turnover.

As a major component of the extracellular matrix, hyaluronan (HA) plays an important role in defining the biochemical and biophysical properties of tissues. In light of the extremely rapid turnover of HA and the impact of this turnover on HA biology, elucidating the molecular mechanisms underlying HA catabolism is key to understanding the in vivo functions of this unique polysaccharide. Here, we show that TMEM2, a recently identified cell surface hyaluronidase, plays an essential role in systemic HA turnover. Employing induced global Tmem2 knockout mice (Tmem2iKO), we determined the effects of Tmem2 ablation not only on the accumulation of HA in bodily fluids and organs, but also on the process of HA degradation in vivo. Within 3 weeks of tamoxifen-induced Tmem2 ablation, Tmem2iKO mice exhibit pronounced accumulation of HA in circulating blood and various organs, reaching levels as high as 40-fold above levels observed in control mice. Experiments using lymphatic and vascular injection of fluorescent HA tracers demonstrate that ongoing HA degradation in the lymphatic system and the liver is significantly impaired in Tmem2iKO mice. We also show that Tmem2 is strongly expressed in endothelial cells in the subcapsular sinus of lymph nodes and in the liver sinusoid, two primary sites implicated in systemic HA turnover. Our results establish TMEM2 as a physiologically relevant hyaluronidase with an essential role in systemic HA catabolism in vivo, acting primarily on the surface of endothelial cells in the lymph nodes and liver.

The cell surface hyaluronidase TMEM2 regulates cell adhesion and migration via degradation of hyaluronan at focal adhesion sites.

The extracellular matrix (ECM) plays an important role in maintaining tissue homeostasis and poses a significant physical barrier to in vivo cell migration. Accordingly, as a means of enhancing tissue invasion, tumor cells use matrix metalloproteinases to degrade ECM proteins. However, the in vivo ECM is comprised not only of proteins but also of a variety of nonprotein components. Hyaluronan (HA), one of the most abundant nonprotein components of the interstitial ECM, forms a gel-like antiadhesive barrier that is impenetrable to particulate matter and cells. Mechanisms by which tumor cells penetrate the HA barrier have not been addressed. Here, we demonstrate that transmembrane protein 2 (TMEM2), the only known transmembrane hyaluronidase, is the predominant mediator of contact-dependent HA degradation and subsequent integrin-mediated cell-substrate adhesion. We show that a variety of tumor cells are able to eliminate substrate-bound HA in a tightly localized pattern corresponding to the distribution of focal adhesions (FAs) and stress fibers. This FA-targeted HA degradation is mediated by TMEM2, which itself is localized at site of FAs. TMEM2 depletion inhibits the ability of tumor cells to attach and migrate in an HA-rich environment. Importantly, TMEM2 directly binds at least two integrins via interaction between extracellular domains. Our findings demonstrate a critical role for TMEM2-mediated HA degradation in the adhesion and migration of cells on HA-rich ECM substrates and provide novel insight into the early phase of FA formation.

TMEM2 expression is downregulated as bladder cancer invades the muscle layer.

Cell surface hyaluronidase transmembrane protein 2 (TMEM2), which also serves as a reportedly functions in malignancy of several solid tumors. However, TMEM2 involvement in bladder cancer (BCa) is unknown. Therefore, we investigate potential changes in expression of TMEM2 during BCa invasion and over the course of the epithelial mesenchymal transition (EMT). Immunohistochemical analysis of 127 clinical specimens revealed that TMEM2 expression changed with pathological stage (pT) and infiltration pattern (INF) and was highest in pTa-pT1 of INFa tumors and significantly lower at stages from pTa-pT1 to pT2 or 3 in INFb or INFc. E-cadherin expression was highest in INFa and lowest in INFc, a pattern comparable to TMEM2 expression. TMEM2 protein expression analysis of BCa cell lines showed that muscle-invasive T24 and YTS-1 cells with low TMEM2 expression exhibited EMT phenotypes in vitro, in contrast to high TMEM2-expressing non-muscle invasive RT4 cells. EMT-induced non-muscle invasive RT4 cells also showed significantly decreased plasma membrane expression of TMEM2. Our data suggested TMEM2 expression is higher in non-invasive cancers, whereas invasive cancer cells are less likely to express TMEM2 during muscle-invasion and "partial EMT".

Associations of impaired grip strength and gait function with the severity of erectile dysfunction in men undergoing dialysis: a cross-sectional study.

OBJECTIVE: To investigate the associations of impaired muscle strength and gait function with the severity of erectile dysfunction (ED) in men undergoing dialysis. METHODS: This cross-sectional study included 63 men undergoing dialysis. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Correlations between variables were analyzed using Spearman's rank correlation coefficient. Multivariable logistic regression analyses were performed to evaluate the impact of impaired grip strength and gait function on the severity of ED. RESULTS: The median age of the study participants was 62 years; all had ED, with 67% having severe ED. Spearman's rank correlation test demonstrated significant negative and positive correlations between gait function and SHIM score (ρ = -0.257, p = 0.042) and between grip strength and SHIM score (ρ = 0.305, p = 0.015), respectively. In the multivariable analyses, impaired grip strength was significantly associated with severe ED (odds ratio [OR]: 4.965, p = 0.017), whereas gait function was not (OR: 3.147, p = 0.064). CONCLUSION: Impaired muscle strength was significantly associated with severe ED, whereas impaired gait function had a marginal effect on this erectile condition.

Real-world effectiveness of nivolumab plus ipilimumab and second-line therapy in Japanese untreated patients with metastatic renal cell carcinoma: 2-year analysis from a multicenter retrospective clinical study (J-cardinal study).

BACKGROUND: Nivolumab plus ipilimumab combination therapy is one of the standard therapies for untreated renal cell carcinoma patients with an International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor risk. We have previously reported the 1-year analysis results of the effectiveness and safety of nivolumab plus ipilimumab combination therapy in the real-world setting in Japan. Here, we report the effectiveness of nivolumab plus ipilimumab combination therapy and of second-line therapy, using 2-year analysis. METHODS: This retrospective observational study enrolled Japanese patients with previously untreated metastatic renal cell carcinoma who initiated nivolumab plus ipilimumab combination therapy between August 2018 and January 2019. Data were collected from patients' medical records at baseline and at 3 months, 1 year and 2 years after the last enrollment. RESULTS: Of the 45 patients enrolled, 10 patients (22.2%) each had non-clear cell renal cell carcinoma and Eastern Cooperative Oncology Group performance status ≥2 at baseline. Median follow-up period was 24.0 months; objective response rate was 41.5%, with 6 patients achieving complete response; median progression-free survival was 17.8 months and 24-month progression-free survival and overall survival rates were 41.6 and 59.1%, respectively. Second-line therapy achieved an objective response rate of 20%; median progression-free survival was 9.8 months. Median progression-free survival 2 was 26.4 months. CONCLUSIONS: The effectiveness of nivolumab plus ipilimumab combination therapy at 2-year analysis in the real-world setting in Japan was comparable to that reported in CheckMate 214. The current analysis also demonstrated the effectiveness of second-line therapy after nivolumab plus ipilimumab combination therapy.

Effect of active anticancer therapy on serologic response to SARS-CoV-2 BNT162b2 vaccine in patients with urothelial and renal cell carcinoma.

OBJECTIVES: To evaluate the serologic response to the BNT162b2 messenger ribonucleic acid vaccine in patients with urothelial carcinoma and renal cell carcinoma. METHODS: Between June 2021 and November 2021, we retrospectively evaluated blood samples from 60 healthy controls (control group), 57 patients with urothelial carcinoma, and 28 patients with renal cell carcinoma who had received two doses of the BNT162b2 vaccine at Hirosaki University Hospital. We determined the immunoglobulin G antibody titers against the severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain. Seropositivity was defined as ≥15 U/mL. We investigate factors associated with antibody titers and seropositivity in the patients with urothelial carcinoma and renal cell carcinoma. RESULTS: Antibody titers in the control, urothelial carcinoma, and renal cell carcinoma groups were 813, 431, and 500 U/mL, respectively. Seropositivity was 100%, 90%, and 96% in the control, urothelial carcinoma, and renal cell carcinoma groups, respectively. Of the 85 patients, 37 of 57 (65%) and 21 of 28 (75%) were actively undergoing anticancer treatment for urothelial carcinoma and renal cell carcinoma, respectively. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers and seropositivity was not significantly different between the patients with urothelial carcinoma and renal cell carcinoma. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers were not significantly associated with active anticancer therapy or steroid treatment for immune-related adverse events. Univariable logistic regression analysis revealed that older age and metastatic disease were significantly and negatively associated with seropositivity. CONCLUSIONS: Patients with urothelial carcinoma or renal cell carcinoma exhibited an adequate antibody response to the BNT162b2 vaccine. Active anticancer therapy was not significantly associated with seropositivity following vaccination with severe acute respiratory syndrome coronavirus 2 BNT162b2 in patients with urothelial carcinoma and renal cell carcinoma.

Single immediate instillation of chemotherapy is associated with decreased recurrence and progression in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy.

OBJECTIVES: To investigate whether a single intravesical instillation of chemotherapy is associated with improved oncological outcomes in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy. METHODS: This multi-institutional retrospective study included 205 patients with high-risk non-muscle-invasive bladder cancer who received adjuvant induction bacillus Calmette-Guérin therapy. Patients were divided into two groups: those who received the combined therapy of a single instillation of chemotherapy plus subsequent adjuvant induction bacillus Calmette-Guérin therapy (combined therapy group), and those who received adjuvant induction bacillus Calmette-Guérin therapy alone (bacillus Calmette-Guérin monotherapy group). Multivariable analyses using the inverse probability of treatment weighting method and Fine-Gray competing risk regression models were performed to evaluate the impact of a single instillation of chemotherapy on intravesical recurrence-free survival and muscle-invasive bladder cancer-free survival. RESULTS: Among the 205 patients, 130 (63%) and 75 (37%) were classified as the combined therapy and bacillus Calmette-Guérin monotherapy groups, respectively. Multivariable analyses using the inverse probability of treatment weighting method showed that a single instillation of chemotherapy was significantly associated with longer intravesical recurrence-free survival (hazard ratio 0.279; P < 0.001) and muscle-invasive bladder cancer-free survival (hazard ratio 0.078; P < 0.001). Fine-Gray competing risk regression model revealed that a single instillation of chemotherapy was associated with a significantly lower probability of intravesical recurrence and muscle-invasive bladder cancer progression, with an adjusted subdistribution hazard ratio of 0.477 (P = 0.008) and 0.261 (P = 0.043), respectively. CONCLUSION: A single intravesical instillation of chemotherapy may be a potential treatment option in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy.

Effects of artificial CO2-rich cold-water immersion on repeated-cycling work efficiency.

We investigated the acute effects of cold-water immersion (20°C) with higher CO2 concentration (CCWI) following a high-intensity Wingate anaerobic exercise test (WAnT) on subjects' sublingual temperature (Tsub), blood lactate ([La]b), heart rate (HR), and aerobic cycling work efficiency (WE) compared to cold tap-water immersion (20°C; CWI) and passive recovery (PAS). Fifteen subjects completed three testing sessions at 1-week intervals. Each trial consisted of a first WE and WAnT, and a 20-min recovery intervention (randomized: CCWI, CWI, and PAS) before repeating a second WE and WAnT. The WE was measured by the metabolic demand during 50% V.O2max exercise. HR, Tsub, and [La]b were recorded throughout the testing sessions. There was a significant decline in the WE from 1st bout to 2nd bout at each recovery intervention. The WAnT was also significantly reduced at 2nd bout. Significantly reduced [La]b was achieved at CCWI compared to PAS, but not to the CWI. Likewise, the reduction in HR following immersion was the largest at CCWI compared to the other conditions. These findings indicate that CCWI is an effective intervention for maintaining repeated cycling work efficiency, which might be associated with reduced [La]b and HR.

Characteristics of α2,3-sialyl N-glycosylated PSA as a biomarker for clinically significant prostate cancer in men with elevated PSA level.

BACKGROUND: The presence of glycosylated isoforms of prostate-specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3-sialylated prostate-specific antigen (S23PSA) by tissue-based sialylation-related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA. METHODS: Tissue-based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI-RADS) scores in 98 men prospectively enrolled in a single-center MRI-targeted biopsy (MRI-TBx) cohort. The primary outcome was the PC-diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI-RADS. RESULTS: S23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI-RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI-RADS + DRE + tPSA was superior to DRE + tPSA+PI-RADS with avoidance rate of MRI-TBx (13% vs. 1%) at 30% risk threshold. CONCLUSIONS: The diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.

Trends in the use of neoadjuvant chemotherapy and oncological outcomes for high-risk upper tract urothelial carcinoma: a multicentre retrospective study.

OBJECTIVE: To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin- or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. RESULTS: Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011-2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin- and carboplatin-based regimens. CONCLUSIONS: The use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.

The association between serum serotonin levels and overactive bladder: results from a community-based cross-sectional study in Japan.

PURPOSE: To investigate the association between serum serotonin (5-HT) levels and overactive bladder (OAB) in a community-dwelling population. METHODS: This cross-sectional study analyzed 1024 subjects who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. OAB was assessed using the Overactive Bladder Symptom Score (OABSS). OAB was defined as an occurrence of urinary urgency at least once a week and an OABSS of ≥ 3. We assessed serum 5-HT levels, laboratory data, and comorbidities of each participants. Participants' mental health status was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale. The association of serum 5-HT levels and OAB was analyzed by multivariable logistic regression analysis. RESULTS: This study included 394 men and 630 women. Of those, 118 (44 male and 74 female) were OAB sufferers. There were significant group differences in age, history of cardiovascular disease, chronic kidney disease, hypertension, diabetes mellitus, and CES-D score. Participants' serum 5-HT levels in the OAB group were significantly lower than those in the non-OAB group (100 vs. 127 ng/mL, P < 0.001). Multivariable analysis showed that age (odds ratio [OR]; 1.06, 95% confidence interval [CI]; 1.04-1.08, P < 0.001) and log serum 5-HT level (OR; 0.25, 95% CI; 0.10-0.68, P = 0.006) were independently associated with OAB. CONCLUSIONS: Lower serum 5-HT levels could independently be associated with the presence of OAB. Further study is necessary to elucidate a possible causal relationship between serum 5-HT levels and OAB.

Altered gut microbiome associated with overactive bladder and daily urinary urgency.

PURPOSE: To explore associations between the gut microbiome and overactive bladder (OAB) with daily urinary urgency among individuals reporting this diagnosis within a single community. METHODS: This cross-sectional study surveyed 1113 individuals who participated in the Iwaki Health Promotion Project in Japan. OAB was defined as urinary urgency at least once per week and an Overactive Bladder Symptom Score (OABSS) of ≥ 3. OAB with urinary urgency at least once a day was defined as daily urgency. The gut microbiomes were assessed by next-generation sequencing of 16S rRNA genes extracted from fecal samples. The participants were divided into two groups: OAB-daily urgency and non-OAB. Cases were selected for inclusion on the basis of 1:1 propensity score matching; we assigned 58 individuals to each group (23 men and 35 women) for our analysis. RESULTS: Individuals reporting OAB with daily urinary urgency demonstrated a lower bacterial diversity between individuals (Bray-Curtis distance 0.48 vs. 0.53, P < 0.001); the results cluster differently in the non-OAB groups. The relative abundance of genus Bifidobacterium was significantly lower among those reporting daily urgency (2.41% vs. 4.23%, P = 0.014). By contrast, the relative abundance of genus Faecalibacterium (9.25% vs. 6.26%, P = 0.006) was significantly higher in this group. CONCLUSION: We observed significant differences in gut microbial contents and specific bacterial genera in association with OAB with daily urgency. Further study will be necessary to assess causal relationships between the gut microbiome and OAB.

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.