The Urinary Bladder is Rich in Glycosphingolipids Composed of Phytoceramides.

Glycosphingolipids (GSLs) are composed of a polar glycan chain and a hydrophobic tail known as ceramide. Together with variation in the glycan chain, ceramides exhibit tissue-specific structural variation in the long-chain base (LCB) and N-acyl chain moieties in terms of carbon chain length, degree of desaturation, and hydroxylation. Here, we report the structural variation in GSLs in the urinary bladders of mice and humans. Using TLC, we showed that the major GSLs are hexosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, Neu5Ac-Gal-Glc-Ceramide, and Neu5Ac-Neu5Ac-Gal-Glc-Ceramide. Our LC-MS analysis indicated that phytoceramide structures with a 20-carbon LCB (4-hydroxyeicosasphinganine) and 2-hydroxy fatty acids are abundant in hexosylceramide and Neu5Ac-Gal-Glc-Ceramide in mice and humans. In addition, quantitative PCR demonstrated that DES2 and FA2H, which are responsible for the generation of 4-hydroxysphinganine and 2-hydroxy fatty acid, respectively, and SPTLC3 and SPTSSB, which are responsible for the generation of 20-carbon LCBs, showed significant expressions in the epithelial layer than in the subepithelial layer. Immunohistochemically, dihydroceramide:sphinganine C4-hydroxylase (DES2) was expressed exclusively in urothelial cells of the urinary bladder. Our findings suggest that these ceramide structures have an impact on membrane properties of the stretching and shrinking in transitional urothelial cells.

Feasibility of magnetic resonance imaging-ultrasound guided high-dose-rate brachytherapy for localized prostate cancer: Preliminary results from a prospective study.

OBJECTIVE: This study aimed to investigate preliminary outcomes of a prospective trial of magnetic resonance imaging-ultrasound fusion-guided ultrafocal high-dose-rate brachytherapy in localized prostate cancer. METHODS: In our prospective study, data from patients who underwent this treatment between April 1, 2020 and March 31, 2021 were analyzed. In the procedure, the applicator needle was inserted through the perineum to target the lesion on the multiparametric magnetic resonance imaging, which was fused onto the transrectal ultrasound image. The prescription dose was set at a single fraction of 19 Gy. Data from patients who received whole-gland high-dose-rate brachytherapy were extracted and compared with data from patients who received ultrafocal high-dose-rate brachytherapy, to evaluate the frequency of acute adverse events. RESULTS: Eight patients underwent ultrafocal high-dose-rate brachytherapy with a median observation period of 7.75 months (range 5.96-15.36 months). No acute genitourinary or gastrointestinal adverse events were observed in this cohort. The planned procedure was completed in all patients, and no unexpected adverse events were observed; however, prostate-specific antigen failure was detected in one patient. In the 25 patients who underwent whole-gland high-dose-rate brachytherapy, acute genitourinary and gastrointestinal adverse events were observed in 88% and 20% of the patients, respectively. Ultrafocal high-dose-rate brachytherapy was a significant factor in avoiding acute adverse genitourinary events in univariate and multivariate analyses (P < 0.001 and P = 0.032, respectively). CONCLUSIONS: Magnetic resonance imaging-ultrasound fusion-guided ultrafocal high-dose-rate brachytherapy in localized prostate cancer is a safe and feasible treatment without acute genitourinary and gastrointestinal adverse events. Long-term observation and further investigation are warranted.

Comparison of Biparametric and Multiparametric MRI for Clinically Significant Prostate Cancer Detection With PI-RADS Version 2.1.

BACKGROUND: Biparametric MRI (bpMRI) without dynamic contrast-enhanced MRI (DCE-MRI) results in an elimination of adverse events, shortened examination time, and reduced costs, compared to multiparametric MRI (mpMRI). The ability of bpMRI to detect clinically significant prostate cancer (csPC) with the Prostate Imaging and Reporting Data System version 2.1 (PI-RADS v2.1) compared to standard mpMRI has not been studied extensively. PURPOSE: To compare the interobserver reliability and diagnostic performance for detecting csPC of bpMRI and mpMRI using PI-RADS v2.1. STUDY TYPE: Retrospective. POPULATION: In all, 103 patients with elevated prostate-specific antigen (PSA) levels who underwent mpMRI and subsequent MRI-ultrasonography fusion-guided prostate-targeted biopsy (MRGB) with or without prostatectomy. FIELD STRENGTH/SEQUENCES: T2 -weighted imaging (T2 WI), diffusion-weighted imaging (DWI), and DCE-MRI at 3T. ASSESSMENT: Three readers independently assessed each suspected PC lesion, assigning a score of 1-5 for T2 WI, a score of 1-5 for DWI, and positive and negative for DCE-MRI according to PI-RADS v2.1 and determined the overall PI-RADS assessment category of bpMRI (T2 WI and DWI) and mpMRI (T2 WI, DWI, and DCE-MRI). The reference standard was MRGB or prostatectomy-derived histopathology. STATISTICAL TESTING: Statistical analysis was performed using the kappa statistic and McNemar and Delong tests. RESULTS: Of the 165 suspected PC lesions in 103 patients, 81 were diagnosed with csPC and 84 with benign conditions. Interobserver variability of PI-RADS assessment category showed good agreement for bpMRI (kappa value = 0.642) and mpMRI (kappa value = 0.644). For three readers, the diagnostic sensitivity was significantly higher for mpMRI than for bpMRI (P < 0.001 to P = 0.016, respectively), whereas diagnostic specificity was significantly higher for bpMRI than for mpMRI (P < 0.001 each). For three readers, the area under the receiver operating characteristic curve (AUC) was higher for bpMRI than for mpMRI; however, the difference was significant only for Reader 1 and Reader 3 (Reader 1: 0.823 vs. 0.785, P = 0.035; Reader 2: 0.852 vs. 0.829, P = 0.099; and Reader 3: 0.828 vs. 0.773, P = 0.002). DATA CONCLUSION: For detecting csPC using PI-RADS v2.1, the interobserver reliability and diagnostic performance of bpMRI was comparable with those of mpMRI. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

VI-RADS: Multiinstitutional Multireader Diagnostic Accuracy and Interobserver Agreement Study.

BACKGROUND. The Vesical Imaging Reporting and Data System (VI-RADS), based on multiparametric MRI (mpMRI), was developed to provide accurate information for the diagnosis of muscle-invasive bladder cancer (MIBC). OBJECTIVE. The purpose of our study was to evaluate the interobserver agreement and diagnostic performance of VI-RADS among readers with different levels of experience. METHODS. This retrospective study included 91 consecutive patients who underwent mpMRI before transurethral resection of bladder tumor (TURBT) from July 2010 through August 2018. After attending a training session, seven radiologists (five radiologists experienced in bladder MRI and two inexperienced radiologists) reviewed and scored all MRI examinations according to VI-RADS. The interobserver agreement was assessed by kappa statistics. ROC analysis was used to evaluate the diagnostic performance for MIBC. AUCs were estimated. RESULTS. Among 91 patients (72 men and 19 women; mean age ± SD, 73.2 ± 10.2 years), 48 (52.7%) had MIBC and 43 (47.3%) had non-muscle-invasive bladder cancer. Sixty-eight patients were treated with TURBT, and 23 were treated with radical cystectomy. Interobserver agreement was moderate to substantial (κ = 0.60-0.80) among the experienced readers, substantial (κ = 0.67) between the two inexperienced readers, and moderate to substantial (κ = 0.55-0.75) between the experienced and inexperienced readers. The pooled AUC was 0.88 (range, 0.82-0.91) for experienced readers and 0.84 (range, 0.83-0.85) for inexperienced readers, and 0.87 for all readers. Using a VI-RADS score of 4 or greater as the cutoff value for MIBC, the pooled sensitivity and specificity were 74.1% (range, 66.0-80.9%) and 94.1% (range, 88.6-97.7%) for experienced readers and 63.9% (range, 59.6-68.1%) and 86.4% (range, 84.1-88.6%) for inexperienced readers. Using a VI-RADS score of 3 or greater as the cutoff value, the pooled sensitivity and specificity were 83.4% (range, 80.9-85.1%) and 77.3% (range, 61.4-88.6%) for experienced readers and 82.0% (range, 80.9-83.0%) and 73.9% (range, 72.7-75.0%) for inexperienced readers. CONCLUSION. We observed moderate to substantial interobserver agreement and a pooled AUC of 0.87 among radiologists of different levels of expertise using VI-RADS. CLINICAL IMPACT. VI-RADS could help determine the depth and range of excision in TURBT, decreasing the risk of complications and enhancing the accuracy of pathologic diagnosis.

[The Liaison Service Models of Care for Metastatic Spinal Tumor].

Advances in cancer treatment helped in increasing the life expectancy of patients with cancer. However, a concomitant increase in the number of patients with bone metastases can be expected. A new multidisciplinary treatment strategy for patients with metastatic spinal tumors was designed, and has been practiced from 2013 in our hospital. The benefits of liaison treatment for metastatic spinal tumors is useful for early detection and early treatment before the collapse of the stabilization mechanism and the appearance of neurological symptoms, and enables team medical care by various experts. This system is a useful treatment for metastatic spinal tumors, because it enables radiotherapy and/or surgery before the onset of skeletal related events(SRE)and will also help maintain the activities of daily living(ADL)and quality of life(QOL)for patients with metastatic spinal tumors.

Prospective randomized controlled trial of postoperative early intravesical chemotherapy with pirarubicin (THP) for solitary non-muscle invasive bladder cancer comparing single and two-time instillation.

PURPOSE: Single immediate intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) has been the gold standard treatment for patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Herein, we conducted a multicenter prospective randomized controlled trial in Japan, comparing recurrence-free survival between single and two-time instillation of pirarubicin (THP) for solitary NMIBC. METHODS: Between 2005 and 2009, 257 patients with solitary NMIBC were enrolled and randomized to single instillation of THP (30 mg/50 mL) immediately after TURBT (Group A) or two-time instillation of THP immediately after and 1 day after TURBT (Group B). The primary endpoint was recurrence-free survival. Secondary endpoints included rates of recurrence and adverse effects, including hematuria, micturition pain, difficult urination, pollakiuria, systemic symptoms, and other complications. This study was registered as UMIN C000000266. RESULTS: Of 257 patients, 99 in Group A and 102 in Group B could be evaluated for recurrence. Median follow-up was 71 months. The overall recurrence rate was 39 and 31%, respectively (p = 0.2704). Although the 5-year recurrence-free survival rates were 55.9% and 67.7% in groups A and B, respectively, the difference between groups was not significant (p = 0.2031). No significant differences in adverse effects were observed between groups, except for pollakiuria (7 vs 22%, p = 0.0031). Multivariate analyses did not show that the treatment group was a significant risk factor for bladder cancer recurrence. CONCLUSIONS: Postoperative two-time intravesical instillation of THP was not superior to single immediate instillation for preventing recurrence after complete resection of a solitary NMIBC.

Tadalafil for male lower urinary tract symptoms improves endothelial function.

OBJECTIVES: To investigate the effects of tadalafil on vascular endothelial function and cardiovascular risk in patients with prostatic hyperplasia. METHODS: Tadalafil 5 mg was given to 20 patients with prostatic hyperplasia for whom an α1-blocker was ineffective. Voiding symptoms and vascular endothelial function were investigated before and after 4 and 12 weeks of administration, using commercial tests for vascular function and vascular endothelial function. RESULTS: The participants had a median age of 65 years, a mean body mass index of 24.2 and a mean prostate volume of 36.2 mL measured using transabdominal sonography. Voiding symptoms were significantly improved by tadalafil, based on the International Prostate Symptom Score, quality of life index and overactive bladder symptom score (P < 0.05). There were also significant improvements in vascular function (change of brachial-ankle pulse wave velocity from 1701 [before] to 1657 [4 weeks tadalafil] and 1525 [10 weeks tadalafil] cm/s [P < 0.05]) and vascular endothelial function (change of reactive hyperemia index from 1.36 to 1.56 and 1.89 [P < 0.05]). The change in reactive hyperemia index was significantly correlated with International Prostate Symptom Score, quality of life index and brachial-ankle pulse wave velocity. CONCLUSIONS: The improvement in intrapelvic blood flow by tadalafil can result in improved vascular endothelial function, in addition to improvement of voiding symptoms. The change in reactive hyperemia index seems to correlate with the severity of voiding symptoms, with tadalafil being most effective in patients with mild voiding symptoms.

Incremental value of high b value diffusion-weighted magnetic resonance imaging at 3-T for prediction of extracapsular extension in patients with prostate cancer: preliminary experience.

PURPOSE: To investigate whether high b value diffusion-weighted imaging (DWI) contributes to the improvement of diagnostic ability of extracapsular extension (ECE) in prostate cancer (PC). MATERIALS AND METHODS: Forty-three patients with PC underwent multiparametric MRI including DWI (b values: 0, 2000 s/mm2) at 3-T. Two radiologists assessed the presence of ECE and the diagnostic certainty degree using conventional diagnostic method by consensus. Tumor apparent diffusion coefficient (ADC, ×10-3 mm2/s) was also measured. Independent predictors of ECE were identified among PSA, tumor ADC, Gleason score, and conventional MRI. ECE in patients with low diagnostic certainty by conventional MRI was further reevaluated using ADC cutoff value, and the results were combined with those of patients with high diagnostic certainty by conventional MRI (MRI + ADC method). RESULTS: Tumor ADC was an independent predictor of ECE, and the ADC cutoff value was 0.72. The sensitivity, specificity, and accuracy of conventional MRI and MRI + ADC method in the diagnosis of ECE were 44, 92, and 72%, and 78, 96, and 88%, respectively. Among MRI findings leading to the judgement of low diagnostic certainty, broad tumor contact was most common (72% of the patients). CONCLUSIONS: The addition of ADC obtained with high b value DWI at 3-T to conventional MRI improved the diagnostic ability of ECE.

Value of preoperative 3T multiparametric MRI for surgical margin status in patients with prostate cancer.

PURPOSE: To examine the value of preoperative multiparametric magnetic resonance imaging (MRI) as a predictor of surgical margin (SM) status in patients with prostate cancer (PC). MATERIALS AND METHODS: The Institutional Review Board approved this retrospective study; the requirement for informed consent was waived. Fifty-six male patients with histologically proven PC underwent preoperative 3T multiparametric MRI including high b value (0, 2000 s/mm(2) ) diffusion-weighted imaging. In each patient, clinical data, such as biopsy Gleason score and D'Amico clinical risk score, and multiparametric MRI findings, such as tumor location, tumor size, tumor extension in the apical or proximal region, tumor apparent diffusion coefficient (ADC), and the presence or absence of MRI findings of extracapsular extension (ECE) were evaluated. Statistical evaluations included the Fisher's exact test, χ(2) test, Mann-Whitney U-test, and logistic regression analysis. RESULTS: On histopathological evaluation, 15 patients (27%) were SM-positive (SMP group), and 41 (73%) were SM-negative (SMN group). The tumor ADC was significantly lower in the SMP group than in the SMN group (P = 0.001). The frequency of tumor extension in the apex or base and suspected ECE on MRI were significantly higher in the SMP group than in the SMN group (P = 0.037 and 0.011, respectively). On multivariate analysis, tumor ADC was the only predictor of SM status in PC (P = 0.003). CONCLUSION: PC with positive SM was characterized by tumor extension in the apical and proximal regions, lower tumor ADC, and tumors with positive MRI findings of ECE, compared to tumors with negative SM. J. Magn. Reson. Imaging 2016;44:584-593.

Practical application of color Doppler ultrasonography in patients with ejaculatory dysfunction.

We describe two cases in which dynamic analysis of ejaculation using color Doppler ultrasonography was useful in diagnosis of ejaculatory dysfunction and planning of therapy. The first patient was a 32-year-old man with a diagnosis of retrograde ejaculation. A bladder neck collagen injection was carried out, as the main cause was thought to be the bladder neck remaining open during ejaculation. The patient had antegrade ejaculation 1 week later. The second patient was a 48-year-old man with a diagnosis of anorgasmia accompanied by decreased seminal emission and insufficient function of the rhythmic pelvic striated muscles. The patient was prescribed etilefrine hydrochloride 15 mg/day. The symptom improved 2 weeks after starting this drug. These cases suggest that the use of color Doppler ultrasonography during ejaculation can improve the understanding of ejaculatory dysfunction and therapy for this condition.

Long-term outcomes of high-dose-rate brachytherapy and external beam radiotherapy without hormone therapy for high-risk localized prostate cancer.

PURPOSE: Until March 2018, patients with high-risk localized prostate cancer had been administered high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) without additional hormone therapy (HT) at our institution. In this study, we aimed to evaluate long-term outcomes of this treatment. MATERIALS AND METHODS: Patients with prostate cancer who received HDR-BT and EBRT between April 1997 and March 2021 and who were followed up for at least 6 months were included in the study. High-risk groups were classified into five levels according to the National Comprehensive Cancer Network guidelines. The EBRT and HDR-BT doses were 39-45 Gy/13-25 fractions. and 16.5-22 Gy/2-4 fractions, respectively. None of the patients received HT during initial treatment. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. Biochemical failure was also determined. RESULTS: Seventy-two patients were enrolled in the study, with a median follow-up of 91.9 months. The median age and initial prostate-specific antigen (iPSA) level were 71 years and 10.95 ng/mL, respectively. The median biologically effective dose for HDR-BT plus EBRT was 270.3 Gy. The 5- and 7-year bFFF, CSS, and OS rates were 85.2 and 74.2%, 100 and 100%, and 95.7 and 91.9%, respectively. Only the iPSA ≤ 20 group was associated with the higher bFFF rate. The 7-year bFFF rates in the groups with iPSA ≤ 20 and iPSA > 20 were 86.6 and 48.6%, respectively. CONCLUSION: HDR-BT plus EBRT without HT might be an alternative treatment option for patients with high-risk localized prostate cancer and iPSA levels ≤ 20. Further studies are required to validate the efficacy of this treatment strategy.

Factors associated with non-completion of palliative radiotherapy for spinal metastasis in patients with terminal cancer: a retrospective study.

BACKGROUND: Predictors of non-completion of radiotherapy (RT) should be identified to determine the optimal RT dose. Therefore, this study aimed to explore factors associated with non-completion of palliative RT in patients with terminal cancer. METHODS: In this retrospective study, patients with terminal cancer who received RT (not including single-fraction RT) for relief of pain caused by spinal metastasis were categorized into complete and incomplete groups. Baseline characteristics, hematologic test data [e.g., total lymphocyte count (TLC)], performance status, palliative performance scale (PPS) score, psoas muscle index (PMI), Charlson comorbidity index, and age-adjusted Charlson comorbidity index of the patients were compared between the two groups. RESULTS: The complete group comprised 58 patients (median age: 68 years; female/male: 17/41; number of irradiation fractions: ≥2 to <10, 20 patients; 10, 34 patients; and >10, 4 patients), and the incomplete group comprised 9 patients (median age: 68 years; female/male: 3/6; number of irradiation fractions: ≥2 to <10, 2 patients; 10, 7 patients; and >10, 0 patient). The proportion of patient death within 1 week or 1 month was higher in the incomplete group than in the complete group. Compared with that in the incomplete group, TLC measured 1 week before RT (pre-TLC) and PMI recorded before RT were significantly higher in the complete group (P=0.013 and P=0.012, respectively). In multivariable analyses, pre-TLC was significantly associated with the incomplete group (P=0.048). Compared with the complete group, the incomplete group included several patients whose PPS scores rapidly decreased. CONCLUSIONS: Pre-TLC can predict non-completion of palliative RT in patients with terminal cancer.

Short repetition time diffusion-weighted imaging improves visualization of prostate cancer.

PURPOSE: This study aimed to assess whether short repetition time (TR) diffusion-weighted imaging (DWI) could improve diffusion contrast in patients with prostate cancer (PCa) compared with long TR (conventional) reference standard DWI. MATERIALS AND METHODS: Our Institutional Review Board approved this retrospective study and waived the need for informed consent. Twenty-five patients with suspected PCa underwent multiparametric magnetic resonance imaging (mp-MRI) using a 3.0-T system. DWI was performed with TR of 1850 ms (short) and 6000 ms (long) with b-values of 0, 1000, and 2000s/mm2. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), visual score, apparent diffusion coefficient (ADC), and diagnostic performance were compared between short and long TR DWI for both b-values. The statistical tests included paired t-test for SNR and CNR; Wilcoxon signed-rank test for VA; Pearson's correlation and Bland-Altman plot analysis for ADC; and McNemar test and receiver operating characteristic analysis and Delong test for diagnostic performance. RESULTS: Regarding b1000, CNR and visual score were significantly higher in short TR compared with long TR (P = .003 and P = .002, respectively), without significant difference in SNR (P = .21). Considering b2000, there was no significant difference in visual score between short and long TR (P = .07). However, SNR and CNR in long TR were higher (P = .01 and P = .04, respectively). ADC showed significant correlations, without apparent bias for ADC between short and long TR for both b-values. For diagnostic performance of DWI between short and long TR for both b-values, one out of five readers noted a significant difference, with the short TR for both b-values demonstrating superior performance. CONCLUSIONS: Our data showed that the short TR DWI1000 may provide better image quality than did the long TR DWI1000 and may improve visualization and diagnostic performance of PCa for readers.

Long-term outcomes of salvage transurethral high-dose-rate brachytherapy combined with external beam radiation therapy for anastomotic recurrence of prostate cancer after radical prostatectomy: A retrospective analysis.

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) delivers high-dose radiation to local lesions within a short treatment period. There are no reports of salvage transurethral HDR-BT for biochemical recurrence (BCR) after radical prostatectomy. Thus, we aimed to evaluate the usefulness of salvage transurethral HDR-BT with external beam radiation therapy (EBRT) for anastomotic prostate cancer recurrence. METHODS AND MATERIALS: Patients with postoperative prostate cancer who underwent salvage transurethral HDR-BT with EBRT for anastomotic recurrence at our hospital between January 2002 and July 2009 were retrospectively evaluated. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. RESULTS: Nine patients were included in this study. The median follow-up period and age were 13.1 (range 4.3-18.4) years and 67 (range 63-78) years, respectively. The dose of HDR-BT ranged from 13 to 24 Gy per 2 to 5 fractions, while that of EBRT ranged from 30 to 44 Gy per 15 to 22 fractions. The 1-year, 5-year, and 10-year bFFF rates were 77.8%, 41.7%, and 13.9%, respectively. The 10-year and 15-year CSS rates were 100% each. The 10-year and 15-year OS rates were 100% and 64.3%, respectively. Six patients were diagnosed with BCR. Two patients experienced Grade 3 hematuria as a late adverse event. There was no exacerbation of urinary incontinence. CONCLUSIONS: No prostate cancer-related deaths were observed, even after a long-term follow-up. Salvage transurethral HDR-BT after radical prostatectomy is safe and feasible and may be a useful treatment option.

Effect of Antacids on the Survival of Patients With Metastatic Urothelial Carcinoma Treated With Pembrolizumab.

INTRODUCTION: Concomitant medications can affect the efficacy of immune checkpoint inhibitors. The association between histamine-2 receptor antagonists (H2RAs), major antacids similar to proton pump inhibitors (PPIs), and the efficacy of pembrolizumab for metastatic urothelial carcinoma (mUC) treatment has been poorly evaluated. We evaluated the impact of PPIs and H2RAs on oncological outcomes in mUC patients treated with pembrolizumab. PATIENTS AND METHODS: This retrospective multicenter study included patients with mUC treated with pembrolizumab. Patients prescribed PPIs or H2RAs within 30 days before and after the initial administration were extracted. The overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rates (ORR) were assessed. Kaplan-Meier survival curve analysis and multivariable Cox proportional hazard models were employed to assess the association between PPIs or H2RAs and survival outcomes. RESULTS: Overall, 404 patients were eligible for this study; 121 patients (29.9%) used PPIs, and 34 (8.4%) used H2RAs. Kaplan-Meier analysis showed significantly worse OS, CSS, and PFS in patients using PPIs compared to no PPIs (P = .010, .018, and .012, respectively). In multivariable analyses, the use of PPIs was a significant prognostic factor for worse OS (HR = 1.42, 95% CI 1.08-1.87, P = .011), CSS (HR = 1.45, 95% CI 1.09-1.93, P = .011), and PFS (HR = 1.35, 95% CI 1.05-1.73, P = .020). PPIs were not associated with ORRs. The use of H2RAs was not associated with survival or ORRs. CONCLUSION: PPIs were significantly associated with worse survival of patients with mUC treated with pembrolizumab, and H2RAs could be an alternative during administration. Both the oncological and gastrointestinal implications should be carefully considered when switching these antacids.

Prognostic impact of radiological tumor burden in patients with metastatic urothelial carcinoma treated with pembrolizumab.

PURPOSE: Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC. METHODS: We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab. Radiological tumor burden was represented by baseline tumor size (BTS) and baseline tumor number (BTN). Optimal cut-off value of BTS was determined as 50 mm using the Youden index (small BTS: n = 194, large BTS: n = 114). Overall (OS), cancer-specific (CSS), progression-free survival (PFS), and objective response rate (ORR) were compared. Non-linear associations between BTS and OS and CSS were evaluated using restricted cubic splines. RESULTS: Patients with large BTS were less likely to have undergone the surgical resection of the primary tumor (P = 0.01), and more likely to have liver metastasis (P < 0.001) and more metastatic lesions (P < 0.001). On multivariable analyses controlling for the effects of confounders (resection of primary tumor, metastatic site, number of metastases and lactate dehydrogenase level), large BTS and high BTN were independently associated with worse OS (HR 1.52; P = 0.015, and HR 1.69; P = 0.018, respectively) and CSS (HR 1.59; P = 0.01, and HR 1.66; P = 0.031, respectively), but not PFS. Restricted cubic splines revealed BTS was correlated with OS and CSS in linear relationships. Additionally, large BTS was significantly predictive of lower ORR and complete response rate on univariable analyses (P = 0.041 and P = 0.032, respectively), but its association disappeared on multivariable analyses. CONCLUSION: Radiological tumor burden has independent prognostic value with a linear relationship in pembrolizumab-treated patients with mUC and might help drive the earlier introduction of second-line pembrolizumab and/or switching to subsequent therapies.

Long-term safety and efficacy of two different antimuscarinics, imidafenacin and solifenacin, for treatment of overactive bladder: a prospective randomized controlled study.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of long-term treatment with two different antimuscarinics, imidafenacin and solifenacin, in patients with overactive bladder (OAB). PATIENTS AND METHODS: Male or female patients 20 years of age or older who had urgency (more than 1 episode in 24 h) were randomized into two groups: group I, imidafenacin (0.1 mg twice daily), and group S, solifenacin (5 mg once daily) for a 12-month treatment regimen. Subjective and objective symptoms were assessed before, and 1, 3, 6 and 12 months after treatment. RESULTS: A total of 109 patients, including 55 (mean age: 72.0 years) in group I and 54 (mean age: 70.4 years) in group S, were treated. Subjective symptoms were significantly improved in group I and S after treatment. Dry mouth significantly worsened in both groups. However, the duration of dry mouth in group I was significantly shorter than that in group S. Three (5.8%) and 7 (13.5%) patients discontinued treatment due to adverse events in group I and group S, respectively. CONCLUSIONS: Imidafenacin and solifenacin were efficacious, safe, and well-tolerated treatments for OAB. As for adverse events, group I had fewer than group S.

Spinal Instability as a Prognostic Factor in Patients With Spinal Metastasis of Castration-resistant Prostate Cancer.

BACKGROUND/AIM: To evaluate the Spinal Instability Neoplastic Score (SINS) for prediction of survival in patients with spinal column metastasis of castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: A retrospective study of spinal instability was performed in patients with CRPC using SINS. Overall survival was evaluated starting from the time of SINS evaluation. The subjects were 42 patients with CRPC among 261 cases diagnosed with metastatic spinal tumors by radiologists, among 42,152 cases that underwent a body computed tomography scan at Kawasaki Medical School Hospital within 32 months from December 2013 to July 2016. RESULTS: The median age was 78 (range=55-91 years), the median prostate-specific antigen (PSA) level at SINS evaluation was 42.1 (0.1-3,121.6) ng/ml, and 11 patients had visceral metastasis. The median periods from diagnosis of bone metastasis and development of CRPC to SINS evaluation were 17 (0-158) and 20 (0-149) months, respectively. The spine was stable in 32 cases (group S) and potentially unstable or unstable in 10 (24%) (group U). The median observation period was 17.5 (0-83) months and 36 patients died. The median survival period after SINS evaluation was longer in group S than that in group U (20 vs. 10 months, p=0.0221). In multivariate analysis, PSA level, visceral metastasis, and spinal instability were significant prognostic factors. The hazard ratio for patients in group U was 2.60 (95%CI=1.07-5.93, p=0.0345). CONCLUSION: Spinal stability evaluated using SINS is a new prognostic factor for survival of patients with spinal metastasis of CRPC.

Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radiotherapy - preliminary results.

OBJECTIVE: To assess the preliminary clinical results of salvage high-dose-rate brachytherapy (HDR-BT) applied in cases of suspected local recurrence or of residual tumour after radiotherapy. PATIENTS AND METHODS: The subjects were 11 patients who met the above conditions and underwent salvage HDR-BT between December 2006 and January 2009. The T stage at the initial treatment was T1c in three patients, T2 in three patients and T3 in five patients. Ten patients received HDR-BT ± electron beam radiation therapy and one patient received proton beam irradiation. Follow-up after the completion of salvage HDR-BT lasted 18-41 months (mean 29 months). A dose of 11.0 Gy radiation was delivered twice (22.0Gy in total), separated by a 6-h interval, on the day the applicators were inserted. RESULTS: Seven of the 11 cases remained in a biochemical non-evidence of disease state. The prostate-specific antigen (PSA) level continuously rose after salvage HDR-BT in three of the four other cases. Hormone administration was initiated in the four cases of PSA recurrence. No G3 or more severe events occurred, and the incidence of G2 was low during this study period. CONCLUSION: Of the 11 cases treated with salvage HDR-BT, PSA levels remained low in seven cases and the incidence of complications was also low. This suggests that salvage HDR-BT is effective as an option for treatment of local prostate cancer recurrence after radiotherapy.

Preoperative positive urine cytology is a risk factor for subsequent development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

PURPOSE: To determine the independent risk factors of bladder recurrence in patients with upper urinary tract urothelial carcinoma (UUT-UC). METHODS: A total of 364 patients underwent nephroureterectomy (NUx) for UUT-UC between January 2005 and April 2009 in Okayama University and 17 affiliated hospitals. Patients with concomitant bladder cancer were excluded from the analysis. The clinicopathologic data for the remaining 288 patients with UUT-UC were retrospectively reviewed. Median follow-up after NUx was 20.2 months. The following variables were evaluated for any association with bladder recurrence: sex, age, tumor stage, tumor grade, venous invasion, lymphatic invasion, tumor location, multifocality, surgical modalities, time of ligation of the ureter, and preoperative urine cytology. The significance of each variable was tested univariately using the log-rank test. The simultaneous effects of multiple risk factors were estimated by multiple regression analysis using the Cox proportional hazards model. RESULTS: Bladder recurrence occurred in 103 patients (35.8%). Median time to first bladder recurrence was 6.9 months. Significant risk factors for bladder recurrences on univariate analysis were tumor location (P = 0.046) and preoperative positive urine cytology (P < 0.001). Multivariate analysis revealed that preoperative urine cytology positive was significant for bladder recurrence (HR: 1.977; 95% CI: 1.310-2.983, P = 0.001). CONCLUSION: Risk factor for subsequent development of bladder cancer after NUx was preoperative positive urine cytology.