Efficacy of a hydrogel spacer for improving quality of life in patients with prostate cancer undergoing low-dose-rate brachytherapy alone or in combination with intensity-modulated radiotherapy: An observational study using propensity score matching.

BACKGROUND: It is unclear whether a hydrogel spacer can improve quality of life (QOL) in patients undergoing low-dose-rate brachytherapy (LDR-BT) alone or in combination with intensity-modulated radiotherapy (IMRT). METHODS: We enrolled patients with prostate cancer who underwent LDR-BT alone with (n = 186) or without (n = 348) a hydrogel spacer, or underwent LDR-BT in combination with IMRT with (n = 70) or without (n = 217) a hydrogel spacer. QOL was evaluated using Expanded Prostate Cancer Index Composite (EPIC) questionnaires at baseline and 1, 3, 6, 12, and 24 months after implantation. The groups were compared using propensity score matching analysis. RESULTS: Among patients who underwent LDR-BT alone, there were no differences regarding changes in urinary, bowel, sexual, or hormonal domain scores between the spacer and no-spacer groups; however, the dose at the bowel was significantly lower in the spacer group than in the no-spacer group. Among patients who underwent LDR-BT in combination with IMRT, there were no differences regarding changes in urinary, sexual, or hormonal domain scores between the spacer and no-spacer groups. However, the changes in the bowel domain score were significantly lower in the spacer group than in the no-spacer group (p < 0.001). CONCLUSIONS: A hydrogel spacer may not improve impaired urinary, bowel, or sexual QOL in patients undergoing LDR-BT alone. However, in patients undergoing LDR-BT in combination with IMRT, a hydrogel spacer can improve impaired bowel QOL but not sexual or urinary QOL.

Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort.

OBJECTIVE: Real-world evidence regarding enfortumab vedotin for unresectable or metastatic urothelial carcinoma is scarce, particularly in Japan. We investigated real-world data focusing on patient background, previous treatments, response, survival and adverse events in patients receiving enfortumab vedotin. METHODS: A multicentre database was used to register 556 patients diagnosed with metastatic urothelial carcinoma from 2008 to 2023; 34 patients (6.1%) treated with enfortumab vedotin were included. Best radiographic objective responses were evaluated using the Response Evaluation Criteria in Solid Tumors (v1.1) during treatments. Overall survival and progression-free survival were estimated (Kaplan-Meier method). Toxicities were reported according to the Common Terminology Criteria for Adverse Events, version 5.0. The relative dose intensity, which could impact oncological outcomes, was calculated. RESULTS: The median number of enfortumab vedotin therapy cycles was 5. The best objective response to enfortumab vedotin was partial response, stable disease and progressive disease in 19 (56%), 5 (15%) and 10 (29%) patients, respectively. The median overall survival and progression-free survival after the first enfortumab vedotin dose were 16 and 9 months, respectively. No significant relationship was observed between survival outcomes after enfortumab vedotin initiation and the enfortumab vedotin relative dose intensity. The median overall survival from first-line platinum-based chemotherapy initiation was 42 months. Twenty-six (76%) patients experienced any grade of enfortumab vedotin-related toxicities; eight (24%) experienced Grades 3-4 toxicities, the most common being skin toxicity (any grade, 47%; Grades 3-4, 12%). CONCLUSIONS: Here, we report real-world evidence for enfortumab vedotin therapy in Japan. Tumour responses and safety profiles were comparable with those of clinical trials on this novel treatment.

Prognostic role of nutritional and inflammatory indicators for patient survival and death with functional graft in living kidney transplant recipients.

BACKGROUND: The clinical importance of nutrition and inflammation in patients with end-stage renal disease is well established. In this study, we investigated the role of nutritional and inflammatory indicators in the patient outcomes of living donor kidney transplant recipients. METHODS: We included 204 consecutive patients who underwent kidney transplantation at our institute between 2003 and 2022. We retrospectively reviewed medical charts to obtain clinical information. Six nutritional indicators and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored. RESULTS: The median patient age and follow-up period were 48 years and 99 months, respectively. The cohort included patients with preoperative malnutrition and microinflammation. No significant differences in graft survival were identified according to nutritional and inflammatory indicators, whereas the survival index, controlled nutritional status, and C-reactive protein levels were associated with patient survival. The survival index was an independent indicator of survival and death in patients with functioning grafts (P = 0.047 and P = 0.013, respectively). Furthermore, the C-reactive protein level could distinguish between low and high mortality risks in patients with good nutrition (P = 0.019). CONCLUSIONS: Our findings suggest that nutrition and inflammation indicators play important roles in predicting outcomes in living donor kidney transplantation recipients. Further research is warranted to establish optimal management strategies.

Impact of nutrition and inflammation indicators on peritoneal dialysis initiation and management.

BACKGROUND: The clinical significance of nutrition and inflammation in dialysis patients is well established. This study aimed to evaluate the association between prognosis and indicators of nutrition and inflammation. METHODS: A total of 253 consecutive patients who underwent peritoneal dialysis (PD) as primary renal replacement therapy at our institute between 2006 and 2021 were included. We retrospectively reviewed the patient's medical charts and obtained their clinical information. Nine nutritional and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored. RESULTS: The median age and follow-up period were 65 years and 54 months, respectively. Most nutritional indicators and C-reactive protein (CRP) levels showed a significant correlation with residual renal function. Multivariate analysis revealed that the survival index, nutritional risk index for Japanese hemodialysis patients, and CRP levels were independent indicators of patient survival (P < 0.001, P = 0.034, and P = 0.005, respectively) and cardiovascular disease-free survival (P = 0.009, P = 0.04, and P = 0.017, respectively). Patients with a survival index < 19 and CRP ≥ 0.5 had a high risk of mortality and cardiovascular death (P < 0.0001 and P = 0.0002, respectively). CONCLUSIONS: Our findings suggest that indicators of nutrition and inflammation play important roles in predicting patient outcomes. Further research is warranted to establish optimal management strategies for patients on PD.

Difference of oncological efficacy between two immune checkpoint inhibitors following first-line platinum-based chemotherapy in patients with unresectable, metastatic, advanced urothelial carcinoma: a multicenter real-world Japanese cohort.

BACKGROUND: Maintenance avelumab is currently recommended for patients with unresectable and/or metastatic (mUC) achieving at least stable disease (SD) on first-line platinum-based chemotherapy (1L-CT). Pembrolizumab is an alternative therapeutic avenue for this patient cohort in clinical practice. We investigated real-world data, focusing on the correlation between response to 1L-CT and oncological efficacy of subsequent immune checkpoint inhibitor (ICI) therapy with avelumab or pembrolizumab. METHODS: A multicenter database registered 626 patients with mUC diagnosed from 2008-2023; among these, 175 receiving 2-6 cycles of 1L-CT followed by ICI therapy. Patients were categorized based on response to 1L-CT using the Response Evaluation Criteria in Solid Tumors (v1.1). Objective response rate on ICI, progression to ICI-free survival (ICI-PFS), and overall survival from start of 1L-CT were compared between avelumab-treated and pembrolizumab-treated patients in each response subgroup. RESULTS: ICI-PFS was significantly longer in patients achieving partial response on 1L-CT and subsequently receiving pembrolizumab compared to those receiving avelumab. Notably, patients achieving SD on 1L-CT and subsequently receiving pembrolizumab manifested significantly higher objective response rate (14% and 41%, respectively) and prolonged ICI-PFS relative to those receiving avelumab. In contrast, overall survival did not delineate difference between patients treated with avelumab versus pembrolizumab. Similar findings were discerned in the subanalysis of patients having favorable SD (tumor shrinkage, from - 29 to 0%) and unfavorable SD (tumor enlargement, from + 1 to + 19%) on 1L-CT. CONCLUSIONS: Our study provides real-world evidence regarding difference of oncological efficacy between maintenance avelumab and subsequent pembrolizumab in patients with mUC who achieved partial response or SD on 1L-CT.

Probiotics enhances anti-tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer.

Chemotherapy drugs, such as gemcitabine and cisplatin (GC), are frequently administered to patients with advanced urothelial carcinoma, however the influence of the gut microbiota on their action is unclear. Thus, we investigated the effects of GC on the gut microbiome and determined whether oral supplementation with a probiotics mixture of Lactobacillus casei Shirota and Bifidobacterium breve enhanced the anti-tumor immune response. After subcutaneous inoculation with MBT2 murine bladder cancer cells, syngenic C3H mice were randomly allocated into eight groups. The gut microbiome cluster pattern was altered in both the GC and oral probiotics groups (p = 0.025). Both tumor-bearing conditions (no treatment) and GC chemotherapy influenced Pseudoclostridium, Robinsoniella, Merdimonas, and Phocea in the gut. Furthermore, comparison of the GC-treated and GC + probiotics groups revealed an association of four methyltransferase family enzymes and two short-change fatty acid-related enzymes with oral probiotics use. A significant difference in tumor volume was observed between the GC and GC + probiotics groups at week 2 of treatment. Additionally, decreased recruitment of cancer-associated fibroblasts and regulatory T cells, and activation of CD8+ T cells and dendritic cells were observed in the tumor microenvironment. Our findings reveal the positive effects of a probiotics mixture of Lactobacillus and Bifidobacterium in enhancing anti-tumor effects through the gut-tumor immune response axis. Future clinical trials are needed to evaluate the full benefits of this novel supplement with oral probiotics in patients with advanced urothelial carcinoma.

Quality of life in patients who underwent robot-assisted radical prostatectomy compared with those who underwent low-dose-rate brachytherapy.

BACKGROUND: To compare the quality of life (QOL) in patients who underwent robot-assisted radical prostatectomy (RARP) or low-dose-rate brachytherapy (LDR-BT) for prostate cancer. METHODS: We enrolled patients who underwent LDR-BT (LDR-BT alone [n = 540] or LDR-BT plus external beam radiation therapy [n = 428]) and RARP (n = 142). QOL was evaluated using the International Prostate Symptom Score, Expanded Prostate Cancer Index Composite (EPIC), Sexual Health Inventory for Men (SHIM), and 8-item Short Form (SF-8) health survey. The two groups were compared using propensity score matching analysis. RESULTS: At 24 months after treatment, the number of patients with worsened urinary QOL in the urinary domain of EPIC compared with baseline was 78/111 (70%) and 63/137 (46%) in the RARP and LDR-BT groups, respectively (p < 0.001). In the urinary incontinence and function domain, this number was higher in the RARP group versus the LDR-BT group. However, in the urinary irritative/obstructive domain, the number of patients with improved urinary QOL at 24 months compared with baseline was 18/111 (16%) and 9/137 (7%), respectively (p = 0.01). Regarding the SHIM score, sexual domain of EPIC, and mental component summary of SF-8, there were more number of patients with worsened QOL in the RARP group than in the LDR-BT group. In the EPIC bowel domain, the number of patients with worsened QOL was lower in the RARP group versus the LDR-BT group. CONCLUSION: The differences in QOL observed between patients treated with RARP and LDR-BT could assist in treatment selection for prostate cancer.

The Japanese health care system-based cost-effectiveness of photodynamic diagnosis-assisted transurethral resection of bladder tumor for non-muscle invasive bladder cancer.

BACKGROUND: Photodynamic diagnosis-assisted transurethral resection of bladder tumor reduces the risk of intravesical recurrence compared with conventional white light-transurethral resection of bladder tumor. However, the patient burden of costs for photodynamic diagnosis-transurethral resection of bladder tumor is higher than that for white light-transurethral resection of bladder tumor per installment, and the impact of the medical economics of photodynamic diagnosis-transurethral resection of bladder tumor is unclear. Therefore, we evaluated the Japanese health care system-based cost-effectiveness of photodynamic diagnosis-transurethral resection of bladder tumor compared with that of white light-transurethral resection of bladder tumor. METHODS: We conducted a retrospective chart review of 100 patients who underwent initial white light- or photodynamic diagnosis-transurethral resection of bladder tumor for non-muscle invasive bladder cancer from February 2012 to August 2019. Cumulative intravesical recurrences during 1000 post-operative days after the initial transurethral resection of bladder tumor were counted. Furthermore, the cumulative costs were calculated using the Diagnostic Procedure Combination and Per-Diem Payment System unique to Japan. The costs/year/person calculated using the person-year method was compared between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. RESULTS: Among the 100 patients, 40 (40%) and 60 (60%) underwent the initial white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The cumulative incidence of bladder recurrence requiring hospitalization and transurethral resection of bladder tumor was 20 and 5% for the white light-transurethral resection of bladder tumor and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The costs for hospitalization and surgical procedures per white light- or photodynamic diagnosis-transurethral resection of bladder tumor were 348 228 and 481 820 Japanese yen, respectively. The cost/year/person by the person-year method was 8073 and 8557 Japanese yen for the white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. CONCLUSIONS: The cost/year/person for hospitalization and surgical procedures was slightly different between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. Furthermore, photodynamic diagnosis-transurethral resection of bladder tumor can reduce intravesical recurrence and is more cost-effective than white light-transurethral resection of bladder tumor.

Clinical practice of UroVysion® urine test in patients with bladder carcinoma in situ treated with intravesical Bacillus Calmette-Guerin.

In January 2019, the use of the UroVysion® urine test for surveillance of non-muscle invasive bladder cancer with carcinoma in situ (CIS) was approved in Japan. Clinical evidence of its use remains limited. Herein, we report the real-world clinical practice of the UroVysion test. Of 29 patients underwent at least one UroVysion test at our hospital from 2019 to 2022, only two (6.9%) tested positive without any visible tumor on the cystoscopy after the initial transurethral resection: a 77-year-old man with T1 high-grade tumor and concomitant CIS and a 76-year-old woman with CIS. The remaining 27 patients (93.1%) tested negative post-transurethral resection. This study was the first to report the Japanese real-world practice of the UroVysion test, demonstrating relatively low positive rate as compared to the previous reports from other countries. Further clinical evidence from other Japanese institutes needs to be accumulated to update the true value of this test.

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study.

OBJECTIVE: To develop the first Japanese real-world evidence of switch-maintenance avelumab in advanced, unresectable or metastatic urothelial carcinoma (aUC). METHODS: A multicenter-derived database registered 505 patients diagnosed with aUC between 2008 and 2021. Of these, 204 patients (40%) were selected and stratified according to the type of therapy used: maintenance avelumab group (27 [5.3%]), second-line (2 L) pembrolizumab group (103 [20%]) and 2 L cytotoxic chemotherapy group (74 [15%]). The progression-free survival and overall survival from the initiation of following therapy were compared. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors guideline v1.1 during the treatment period. A detailed analysis was performed in the maintenance avelumab group to investigate possible factors associated with response to avelumab therapy. RESULTS: The maintenance avelumab group had a longer overall survival, not progression-free survival, compared with the other two treatment groups. The median treatment-free interval between the last dose of first-line (1 L) chemotherapy and the initiation of avelumab therapy was 6 weeks (range, 3-22). Disease control rate of maintenance avelumab therapy in patients with a treatment-free interval of ≤6 weeks was higher than that in patients with a treatment-free interval of >6 weeks (77 vs 40%, P = 0.029). The patients showing objective response to 1 L chemotherapy were less likely to experience tumor relapse (4 of 19) after the initiation of avelumab therapy compared with those showing stable disease (7 of 8). CONCLUSIONS: Objective response to 1 L chemotherapy and early induction of maintenance avelumab therapy may be associated with increased benefit from maintenance avelumab therapy.

Clinical impact of catheter insertion for peritoneal dialysis on patient survival and catheter-related complications.

OBJECTIVES: The stepwise initiation of peritoneal dialysis (PD) using Moncrief and Popovich's technique (SMAP) for catheter insertion is recommended for the systemic introduction of PD and prevention of catheter-related infections. In this study, we investigated patient outcomes in patients who underwent insertion of a PD catheter with a direct method versus the SMAP method. METHODS: We enrolled 295 consecutive patients who underwent PD as a primary renal replacement therapy and underwent insertion of a PD catheter at our institute between 2006 and 2021. We retrospectively reviewed their data and investigated patient outcomes, including mortality and PD catheter-related complications. RESULTS: Median age at PD induction was 65 years in the direct insertion group and 65 years in the SMAP group (P = 0.80). The rate of PD introduction after emergency hemodialysis was significantly higher in the direct insertion group than in the SMAP group (P < 0.001). There was no significant difference in survival between the direct insertion and SMAP groups during the median follow-up period of 54 months (P = 0.12). Additionally, patients who transitioned to hemodialysis or kidney transplantation after PD showed significantly longer survival (P < 0.001). The incidence of PD catheter-related complications was not significantly different between the two groups. A body mass index ≥ 23 kg/m2 was an independent risk factor for peritonitis and exit-site infection (P = 0.006 and P = 0.011, respectively). CONCLUSIONS: Planned sequential renal replacement therapy including hybrid hemodialysis, complete hemodialysis, and kidney transplantation after PD is important for improving patient outcomes. PD catheter insertion by SMAP may not be mandatory in our clinical practice.

Clinical significance of limited and extended pelvic lymph node dissection during robot-assisted radical prostatectomy for patients with localized prostate cancer: A retrospective, propensity score matching analysis.

OBJECTIVES: We investigated the diagnostic and therapeutic benefits of limited or extended pelvic lymph node dissection during a robot-assisted radical prostatectomy for localized prostate cancer. METHODS: Diagnostic and therapeutic benefits were assessed according to the rates of pN1 and biochemical recurrence, respectively. The primary outcome was the biochemical recurrence-free rate, and secondary outcomes included the diagnostic and therapeutic benefits of pelvic lymph node dissection. RESULTS: A total of 534 patients were analyzed. Out of the 534 patients, 207 (38.8%) received limited pelvic lymph node dissection while 134 (25.1%) received extended dissection. There were 297 patients with a Briganti index ≥5%. Extended dissections yielded significantly more resected lymph nodes (p < 0.0001), and 72.2% of cases of pN1 were located outside the obturator. The incidence rate of pN1 was 6.1%, and performance of extended lymph node dissection was an independent predictor for pN1 (odds ratio 9.0, 95% confidence interval 2.5-33.1). The rate of biochemical recurrence was 14.9%, and Cox proportional hazards regression analysis of the propensity score matched population revealed that patients with high or very-high risk tended to benefit from limited lymph node dissection (hazard ratio 8.4, 95% confidence interval 0.8-82.3) while the therapeutic benefit of extended dissection was unclear by comparison. CONCLUSIONS: Extended pelvic lymph node dissection significantly improves diagnostic accuracy; however, the therapeutic benefit of pelvic lymph node dissection was not observed in this study.

[The Relationship Between Prognosis and Duration of Drug Holidays after Docetaxel Therapy for Castration-Resistant Prostate Cancer].

The next treatment strategy after drug holidays following docetaxel (DTX) therapy for patients with castration-resistant prostate cancer (CRPC) is unclear. This study investigated the relationship between the duration of drug holidays and prognosis after DTX therapy. This study retrospectively assessed 26 patients treated with DTX in our hospital. Overall survival duration was significantly longer in the long-term withdrawal group (duration of drug holidays ≥6 months) than in the short-term withdrawal group (duration of drug holidays ＜6 months) (P＝0.015). Similarly, progression-free survival duration was significantly longer in the long-term withdrawal group than in the short-term withdrawal group (P＝0.008). The short-term withdrawal group had a significantly lower body mass index (P＝0.009) and higher prostate-specific antigen (PSA) (P＝0.017) at the initiation of DTX therapy, higher PSA nadir during DTX therapy (P＝0.009), and higher PSA at the end of DTX therapy (P＝0.022), compared to the long-term withdrawal group. This study suggests that the optimal opportunity to introduce DXT therapy is when the patients with CRPC are physically able to tolerate chemotherapy and their tumor volume remains a lower burden. This may provide a clinical benefit, longer drug holidays, and a better prognosis.

5-Aminolevulinic acid overcomes hypoxia-induced radiation resistance by enhancing mitochondrial reactive oxygen species production in prostate cancer cells.

BACKGROUND: The naturally occurring amino acid 5-aminolevulinic acid (5-ALA) is a precursor of protoporphyrin IX (PpIX) biosynthesised in the mitochondria. When accumulated PpIX is excited by light (wavelength of 625-635 nm), reactive oxygen species (ROS) are generated. Here, we investigated whether 5-ALA may increase the sensitisation of prostate cancer (PCA) cells to radiotherapy through the generation of ROS via its metabolite, PpIX. METHODS: Effect of 5-ALA on PC-3 and DU-145 PCA cell lines treated with ionising radiation (IR) was examined in vitro and in vivo with assessment by clonogenic assay, mitochondrial function and ROS production under normoxia or hypoxia condition. RESULTS: 5-ALA enhanced intra-mitochondrial ROS production immediately after exposure to IR and decreased mitochondrial membrane potential via increase of intra-cellular PpIX. IR with 5-ALA induced mitochondrial dysfunction and increased ATP production, switching energy metabolism to the quiescence. Under hypoxic condition, ROS burst and mitochondrial dysfunction were induced by IR with 5-ALA resulting reducing cancer stemness and radiation resistance. CONCLUSION: These results suggest that combined therapy with 5-ALA and radiation therapy is a novel strategy to improve the anti-cancer effects of radiation therapy for PCA.

Association between urine 6-sulfatoxy-melatonin level and intravesical Bacillus Calmette-Guerin treatment-induced sleep quality deterioration in patients with non-muscle invasive bladder cancer.

PURPOSE: The level of 6-sulfatoxy-melatonin (SaMT), a metabolite of melatonin, in first-void morning urine reflects blood melatonin levels from the previous night. We investigated the association between urine SaMT and sleep quality deterioration in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical Bacillus Calmette-Guerin induction therapy (iBCG). METHODS: We enrolled 51 patients who received iBCG once weekly for 6 or 8 weeks. Patient-reported outcomes were assessed with questionnaires including the International Prostate Symptom Score (IPSS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQC30). Questionnaires were completed before (baseline), during, at completion, and 1 and 3 months after iBCG. Melatonin and SaMT levels at baseline were measured in serum and first-void morning urine samples, respectively. RESULTS: Based on changes in the QLQC30 insomnia subscale, 28 (55%) patients experienced sleep quality deterioration (deterioration group). Urine SaMT values in the deterioration group were lower than those in the non-deterioration group (P = 0.0015; 7.5 vs 15.4 ng/mg creatinine, respectively). Nocturia scores in the non-deterioration group decreased over time, while those of the deterioration group remained high after completion of iBCG. A binary logistic regression analysis revealed that low urine SaMT levels (≤ 9.6 ng/mg creatinine), high IPSS nocturia scores at baseline, and high IPSS storage subscores at baseline were associated with BCG-induced sleep quality deterioration. CONCLUSIONS: This study confirmed the association among urine SaMT levels, nocturia, and sleep disturbance in patients with NMIBC who receive iBCG. We should be aware of treatment-induced impairments to aid in appropriate decision-making.

Intravesical Bacillus Calmette-Guerin treatment-induced sleep quality deterioration in patients with non-muscle invasive bladder cancer: functional outcome assessment based on a questionnaire survey and actigraphy.

PURPOSE: We investigated sleep parameters and patient-reported outcomes before, during, and after induction Bacillus Calmette-Guerin therapy using questionnaires and actigraphy in patients with non-muscle invasive bladder cancer. METHODS: We investigated 10 patients who received Bacillus Calmette-Guerin therapy once weekly for 8 weeks. The International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, Functional Assessment of Cancer Therapy-Bladder, and multi-item Short Form-8 tools were used to assess patient-reported outcomes. Participants completed all questionnaires before (baseline), at the 4th and 8th doses, and 1 month after the last Bacillus Calmette-Guerin dose. The MotionWatch8 was fastened to patients' waist throughout the study. Composite sleep quality was determined based on sleep duration, efficiency, and fragmentation. RESULTS: We observed a transient increase in frequency/nocturia subscores and the insomnia subscore. The number of patients with poor sleep quality increased from 0 (0%) at baseline to 7 (70%) at the 4th dose and to 6 (60%) patients at the 8th dose. Among 10 patients, 6 (60%) were assigned to the sleep deterioration group and 4 (40%) to the non-deterioration group. Sleep quality was restored to baseline levels in 5 of 6 patients (83%) within 1 month after the last dose in the sleep deterioration group, and the nocturia subscore of the International Prostate Symptom Score was significantly increased only in this group (P=0.03). CONCLUSIONS: This is the first study that confirms intravesical Bacillus Calmette-Guerin-induced sleep quality deterioration based on a questionnaire survey and actigraphy.

Erectile dysfunction and sexual quality of life in patients who underwent low-dose-rate brachytherapy alone for prostate cancer.

This study evaluated erectile function and sexual quality of life (QoL), and predictive factors for erectile dysfunction (ED) and the deterioration of sexual QoL in 70 patients who underwent low-dose-rate brachytherapy (LDR-BT) alone for prostate cancer without androgen deprivation therapy. Erectile function and sexual QoL were evaluated before and 1, 3, 6, 12, 24, 36, 48 and 60 months after LDR-BT. Binary logistic regression analysis was used to determine whether age, prostate volume, hypertension, diabetes, Brinkman's index, testosterone, baseline Sexual Health Inventory for Men (SHIM) score and post-implant dosimetry parameters could predict ED and deterioration of sexual QoL at 24 and 60 months after LDR-BT. After 24 and 60 months, ED was noted in 39 of 70 patients and 42 of 64 patients respectively. Furthermore, sexual QoL worsened in 42 of 70 and 43 of 64 patients respectively. Baseline SHIM score was identified as a significant predictor of ED (24 months: odds ratio [OR]: 0.83, p = 0.02; 60 months: OR: 0.83, p = 0.03) and the deterioration of sexual QoL (24 months: OR: 0.84, p = 0.03). LDR-BT for prostate cancer promoted decreased erectile function and sexual QoL, with high preimplant potency being a significant predictor of ED and the deterioration of sexual QoL.

Relevance of the perioperative edema index measured by bioelectrical impedance analysis for prediction of cardiovascular disease in living-donor kidney transplantation.

OBJECTIVES: Perioperative management of fluid status during kidney transplantation is important, because volume overload can increase the risk of cardiovascular disease in recipients. The edema index calculated by bioelectrical impedance analysis is commonly used to correctly evaluate fluid status. We evaluated the relevance of the edema index for cardiovascular disease in kidney transplant recipients, and searched for predictors of high edema index in the perioperative period during kidney transplantation. METHODS: A total of 88 recipients were included in this study. The group in which the edema index at discharge was >0.40 was termed as the "high edema index group", and that with ≤0.40 was termed as the "low edema index group". We assessed cardiovascular disease-free survival and cardiovascular disease-specific survival in the two groups by using Cox proportional regression analyses adjusted by inverse probability of treatment weighting analysis. The patients' background and conventional cardiovascular disease risk factors were assessed to estimate predictors for a high edema index. RESULTS: A high edema index was significantly associated with short cardiovascular disease-free survival after kidney transplantation (hazard ratio 10.01; P < 0.05) in the inverse probability of treatment weighting model. There were no significant differences in the cardiovascular disease-specific survival. In multivariate logistic regression analyses, non-pre-emptive kidney transplantation and dyslipidemia were significant independent predictors of a high edema index (odds ratio 3.59, P < 0.05 and odds ratio 4.05, P < 0.01, respectively). CONCLUSIONS: A high edema index is associated with the incidence of cardiovascular disease. Overhydration should be especially avoided in recipients with these factors, and their fluid volume should be carefully managed.

Trends in primary treatment for localized prostate cancer according to the availability of treatment modalities and the impact of introducing robotic surgery.

OBJECTIVES: We aimed to investigate the effect of available treatment modalities on primary treatment selection in patients with localized prostate cancer and that of introducing robotic surgery. METHODS: We retrospectively studied 12 061 patients diagnosed with localized prostate cancer between 2004 and 2018 from 21 institutions. These institutions were divided into five groups according to the availability of surgery and radiotherapy. Differences in primary treatment selection between the institutions were investigated, and the predictive factors involved in the selection were explored. RESULTS: Surgery, radiotherapy, androgen deprivation therapy, and active surveillance/watchful waiting were selected as primary treatment in 4115, 3621, 3188, and 821 patients, respectively, while the remaining 316 patients selected other modalities. The number of patients, particularly young patients, was much higher in institutions with both surgery and radiotherapy. With the introduction of robotic surgery, open radical prostatectomy has decreased, and robotic surgery made up approximately 70% of all prostatectomies. Institutions with both surgery and radiotherapy tended to treat patients with very low or low risk by surgery or radiotherapy, while institutions without surgery and radiotherapy tended to select active surveillance or watchful waiting. Multivariate analysis revealed that primary treatment selection for prostate cancer was affected not only by clinical factors, but also by the available modalities in each institution. CONCLUSIONS: Differences in available treatment modalities affect the selection of primary treatment for localized prostate cancer. Introduction of robotic surgery also has a strong influence on the number of patients in each institution.

Local dose (biologically effective dose ≥180 Gy2) is an important predictor of biochemical recurrence in patients undergoing low-dose-rate brachytherapy.

OBJECTIVES: To evaluate prognostic factors of biochemical recurrence (BCR) in each risk group of prostate cancer patients who underwent low-dose-rate brachytherapy (LDR-BT). METHODS: A total of 944 patients with clinically confirmed prostate cancer (cT1c-3aN0M0) who had underwent LDR-BT were enrolled. The low-, intermediate-, and high-risk groups included 278, 498, and 168 patients, respectively. The median age, PSA value at diagnosis, and the follow-up period were 70 years (range: 48-84), 7.2 ng/ml (range: 1.2-113), and 91 months (range: 2-192), respectively. We evaluated the BCR-free rate, BCR-free survival, clinical recurrence-free rate, overall survival (OS), and cancer-specific survival (CSS). We conducted multivariate analysis to elucidate prognostic factors of BCR for all patients and for each risk group. RESULTS: The 5- and 10-year OS rates were 96.0% and 89.5% and the 5- and 10-year CSS rates were 99.8% and 99.1%, respectively, while the 5- and 10-year BCR-free rates were 96.6% and 92.5% in low-risk patients, 95.7% and 90.7% in intermediate-risk patients and 93.8% and 89.0% in high-risk patients, respectively. There were no significant differences between the risk groups. Age-adjusted multivariate analysis indicated biologically effective dose (BED) <180 Gy2 as an independent prognostic factor of BCR in all patients (p = 0.005). There were no independent factors in the low- and high-risk groups, but neoadjuvant androgen deprivation therapy (ADT) (p = 0.022) and BED <180Gy2 (p = 0.042) were independent prognostic factors in the intermediate-risk group. CONCLUSIONS: LDR-BT can achieve a higher recurrence-free survival with an adequate local radiation dose (BED ≥ 180 Gy2).