Soluble Immune Checkpoint Molecules as Predictors of Efficacy in Immuno-Oncology Combination Therapy in Advanced Renal Cell Carcinoma.

Immuno-oncology (IO) combination therapy is the first-line treatment for advanced renal cell carcinoma (RCC). However, biomarkers for predicting the response to IO combination therapy are lacking. Here, we investigated the association between the expression of soluble immune checkpoint molecules and the therapeutic efficacy of IO combination therapy in advanced RCC. The expression of soluble programmed cell death-1 (sPD-1), soluble programmed cell death ligand-1 (sPD-L1), soluble PD-L2 (sPD-L2), and lymphocyte activation gene-3 (sLAG-3) was assessed in plasma samples from 42 patients with advanced RCC who received first-line IO combination therapy. All IMDC risk classifications were represented among the patients, including 14.3, 57.1, and 28.6% with favorable, intermediate, and poor risk, respectively. Univariate analysis revealed that prior nephrectomy, sPD-L2 levels, and sLAG-3 levels were significant factors affecting progression-free survival (PFS), whereas multivariate analyses suggested that sPD-L2 and sLAG-3 levels were independent prognostic factors for PFS. In a univariate analysis of the overall survival, prior nephrectomy and sPD-L2 levels were significant factors; no significant differences were observed in the multivariate analysis. No significant correlation was observed between the sPD-L2 and sLAG-3 levels and PD-L2 and LAG-3 expression via immunohistochemistry. In conclusion, sPD-L2 and sLAG-3 expression may serve as a potential biomarker for predicting IO combination therapy efficacy.

Clinicopathological characteristics of adrenocortical carcinoma in the Kyushu-Okinawa area of Japan.

OBJECTIVE: Adrenocortical carcinoma is a rare condition, with limited comprehensive reports from Japan. This study aimed to review Japan's data on adrenocortical carcinoma by assessing information from 46 patients-with adrenocortical carcinoma across 10 Japanese university hospitals. METHODS: We conducted a retrospective multi-institutional analysis of the clinical characteristics of adrenocortical carcinoma in Japan. We evaluated data from 46 patients across 10 university hospitals over 10 years and analyzed the relationship between clinicopathological characteristics and overall survival. RESULTS: Five- and 10-year overall survival rates were 59% and 53%, respectively. Overall survival was significantly different among the tumor-node-metastasis system for adrenocortical carcinoma of the American Joint Committee on Cancer/International Union Against Cancer, with the worst prognosis in stage IV (p = 0.0044). In our cohort, neither the Weiss score nor the Ki-67 proliferation index correlated with overall survival. Adjuvant treatment did not yield improved overall survival, whereas resection of the primary tumor in stage IV disease was significantly associated with improved overall survival (p = 0.0262). Out of the cases evaluated for plasma hormones, plasma cortisol, aldosterone, testosterone, and DHEA-S levels were measured at 23%, 42%, 29%, and 62%, respectively, demonstrating higher levels than the upper normal limits. CONCLUSION: Patients with stage IV adrenocortical carcinoma had a poor prognosis; however, resection of the primary tumor in stage IV disease was associated with prolonged survival. The results of this study are expected to contribute to future treatment of adrenocortical carcinoma in Japan.

Investigation of Effect Predictors of Desmopressin in Nocturia Patients With Nocturnal Polyuria.

BACKGROUND/AIM: Effect predictors of desmopressin for nocturia associated with nocturnal polyuria are understudied. Herein, we investigated the effects of desmopressin on sleep and patient quality of life. We defined cases in which administration of desmopressin led to hours of undisturbed sleep (HUS) ≥3 hours as "marked response cases" and examined predictive factors of desmopressin treatment response. PATIENTS AND METHODS: Our study included 129 patients who were administered desmopressin 50 µg for nocturia associated with nocturnal polyuria at our hospital. Efficacy and safety of desmopressin were examined using bladder diaries, International Prostate Symptom Score, Overactive Bladder Symptom Score, Athens Insomnia Scale, Patient Global Impression of Improvement (PGI-I) score, physical examinations, blood tests, and body composition analyzers, and the predictors of desmopressin efficacy were investigated. RESULTS: Significant improvements in all endpoints were observed from the early stage onward after desmopressin treatment compared with before treatment. After treatment, HUS was significantly longer in patients with good PGI-I scores, which indicated patient satisfaction. Variation in nocturnal micturition frequency did not affect the improvement in patient satisfaction. Examination of cases defined as "marked response cases" showed that the mean night-time urine volume was an independent predictor of treatment response. CONCLUSION: Desmopressin can improve patients' quality of life and sleep by extending HUS. This suggests that desmopressin may be effective in patients with high mean night-time urine volumes based on their bladder diary.

Metyrosine-associated endocrinological changes in pheochromocytoma and paraganglioma.

Objective: Metyrosine (alpha-methyl-para-tyrosine) effectively reduces catecholamine levels in patients with pheochromocytoma/paraganglioma. However, improvements in physiological and metabolic parameters and changes in endocrine function associated with metyrosine administration should be validated in comparison to surgery. This study was performed to confirm the effects of metyrosine on the physiological, metabolic, and endocrinological functions of patients with pheochromocytoma/paraganglioma in the perioperative period. Design: This retrospective cohort study was performed at a single university hospital. Methods: We included ten patients with pheochromocytoma/paraganglioma who received oral metyrosine after α-blocker therapy and consecutive surgeries. Urinary catecholamine metabolite levels and other clinical parameters were evaluated before and after metyrosine administration, and 1 week after surgery. Results: The mean age was 53.1 ± 16.1 years. Of the ten participants (four men and six women), nine had pheochromocytoma and one had paraganglioma. The median maximum metyrosine dose was 750 mg/day. Urinary catecholamine metabolite levels significantly decreased in a dose-dependent manner after metyrosine administration. Both systolic and diastolic blood pressure significantly decreased after metyrosine and surgical treatment. Metyrosine administration significantly improved insulin sensitivity, although surgery improved the the basal insulin secretion. Additionally, serum prolactin and thyroid-stimulatory hormone levels were significantly increased by metyrosine treatment, whereas plasma renin activity was decreased. Conclusions: Metyrosine significantly reduced catecholamines in patients with pheochromocytoma/paraganglioma and ensured the safety of the surgery. Adjustment of metyrosine administration may make surgical pretreatment more effective in achieving stabilized blood pressure and improving glucose metabolism. Endocrine parameters may manifest as the systemic effects of metyrosine administration.

Sarcopenia and the Therapeutic Effects of Androgen Receptor-axis-targeted Therapies in Patients With Castration-resistant Prostate Cancer.

BACKGROUND/AIM: Sarcopenia is a syndrome characterized by the progressive and generalized loss of skeletal muscle mass and has been reported to be a poor prognostic factor for taxane-treated castration-resistant prostate cancer (CRPC). However, whether sarcopenia affects androgen receptor axis-targeted therapies (ARATs) remains unknown. In the present study, we investigated the association between sarcopenia in CRPC and treatment outcomes of ARATs. PATIENTS AND METHODS: From January 2015 to September 2022, 127 patients who received ARATs as 1st-line treatment for CRPC at our two hospitals were included in the study. We retrospectively evaluated sarcopenia using computed tomography images and investigated whether sarcopenia affects the progression-free survival (PFS) and overall survival (OS) of patients with CRPC treated with ARATs. RESULTS: Out of 127 patients, 99 were diagnosed with sarcopenia. The PFS of the sarcopenic group administered ARATs was significantly better than that of the non-sarcopenic group. Furthermore, in the multivariate analysis of PFS, sarcopenia was an independent favourable prognostic factor. However, there was no significant difference in the OS between the sarcopenic and non-sarcopenia groups. CONCLUSION: ARATs could more effectively treat patients with CRPC and sarcopenia than patients with CRPC without sarcopenia. Sarcopenia may positively influence the therapeutic effects of ARATs.

Prognostic Value of Absolute Lymphocyte Count in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab Plus Ipilimumab.

Nivolumab and ipilimumab (NIVO + IPI) is standard therapy for patients with advanced renal cell carcinoma (RCC). Absolute lymphocyte count (ALC) is a valuable prognostic factor in patients with various cancers treated with immune checkpoint inhibitors. Herein, we determined the prognostic value of pretreatment ALC in advanced RCC patients treated with NIVO + IPI as first-line therapy. Data from 46 advanced RCC patients treated with NIVO + IPI between September 2018 and August 2022 were retrospectively reviewed and analyzed. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with low than high ALC (PFS: p = 0.0095; OS: p = 0.0182). Multivariate analysis suggested that prior nephrectomy [hazard ratio (HR) = 3.854, 95% confidence interval (CI) = 1.433-10.359, p = 0.0075] and pretreatment ALC (HR = 2.513, 95% CI = 1.119-5.648, p = 0.0257) were independent factors for PFS. Our new prognostic ALNx model based on ALC and prior nephrectomy suggested that the poor-risk group was a predictor of significantly worse PFS (p < 0.0001) and OS (p = 0.0016). Collectively, the developed ALNx model may be a novel predictor of response in advanced RCC patients treated with NIVO + IPI.

Determining the optimal initial dose for Japanese patients with nocturnal polyuria using an initial dose of desmopressin 50 µg.

OBJECTIVE: There is no consistent opinion on the optimal initial dose of desmopressin for patients with nocturnal polyuria. Over a period of 12 weeks, we investigated the safety and efficacy of an initial dose of 50 µg of desmopressin for elderly men. METHODS: Eighty patients (mean age: 78.8 years) were started on an initial dose of 50 µg of desmopressin for nocturia associated with nocturnal polyuria. Safety and efficacy were evaluated after 1, 4, and 12 weeks using a frequency-volume chart, Athens Insomnia Scale, Patient Global Impression of Improvement scale, physical examination, blood tests, and a body composition analyzer. RESULTS: Along with reduction in the frequency and volume of night-time urination, improvements in hours of undisturbed sleep, nocturnal polyuria index, and International Prostate Symptom Score, and Overactive Bladder Symptom Scores on quality of life measures were also observed. Hyponatremia was observed in 15 patients (18.7%). However, only 5.0% of patients had hyponatremia after the dose was reduced to 25 µg, and the continuation rate at 12 weeks was high at 87.5%. Age and other physical factors, such as body mass index, body water content, body fat mass, and muscle mass were not significant predictors of adverse events. CONCLUSIONS: Our study suggests that an initial dose of 50 µg is more effective than a uniformly minimum dose based on factors such as age and physique. Furthermore, a high continuation rate can be achieved by appropriately reducing the dose, if adverse events occur.

Sarcopenia and excess visceral fat accumulation negatively affect early urinary function after I-125 low-dose-rate brachytherapy for localized prostate cancer.

OBJECTIVES: To evaluate the effects of sarcopenia and excess visceral fat accumulation on early urinary function after I-125 low-dose-rate brachytherapy for prostate cancer. METHODS: We retrospectively reviewed consecutive patients who underwent brachytherapy for prostate cancer. Pre-treatment computed tomography was used to measure skeletal muscle index at the L3 level to assess sarcopenia and visceral fat area at the umbilical level. The International Prostate Symptom Score and the University of California Los Angeles Prostate Cancer Index were used to assess quality of life during the 24 months after brachytherapy. Logistic regression analysis was used to examine whether sarcopenia and excess visceral fat accumulation had clinically significant effects on post-treatment quality of life. RESULTS: Among 246 patients, 92 (37.4%) were stratified into the sarcopenia group and 141 (57.3%) into the excess visceral fat accumulation group. The sarcopenia group had significantly lower University of California Los Angeles Prostate Cancer Index urinary function than the non-sarcopenia group 24 months post-brachytherapy. The excess visceral fat accumulation group had significantly poorer International Prostate Symptom Score total, storage, and voiding scores than the non-excess accumulation group 12 months post-brachytherapy. In the multivariate analysis, sarcopenia had a clinically significant adverse effect on the University of California Los Angeles Prostate Cancer Index urinary function at 12 months. Excess visceral fat accumulation had a clinically significant adverse effect on the International Prostate Symptom Score voiding and storage scores at 12 months. CONCLUSIONS: Sarcopenia and excess visceral fat accumulation negatively affect urinary function early after I-125 low-dose-rate brachytherapy for prostate cancer.

Improved Survival of Real-world Japanese Patients With Advanced Renal Cell Carcinoma Treated With Immuno-oncology Combination Therapy.

BACKGROUND/AIM: Immuno-oncology (IO) combination therapy has become the standard of treatment for advanced renal cell carcinoma (RCC). In this retrospective study, we compared the efficacy of first-line molecular targeted therapy (MTT), administered as monotherapy, and IO combination therapy using real-world data of Japanese patients. PATIENTS AND METHODS: The clinical information of 202 patients with RCC who received MTT (n=144) or IO combination therapy (n=58) at the Kurume University Hospital from May 2008 to May 2022 was collected and retrospectively analyzed. The Cox proportional hazards model was used for univariate and multivariate analyses, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated. RESULTS: The patients treated with IO combination therapy had a prolonged progression-free survival (PFS) compared with those treated with MTT (p=0.0038). IO combination therapy was significantly associated with a better PFS in patients with intermediate (p=0.0072) and poor risk (p=0.0411) but not in those with favorable risk (p=0.5434). Furthermore, overall survival with IO combination therapy was significantly better in patients at poor risk (p=0.0335). Multivariate analyses suggested that prior nephrectomy (HR=1.501, 95%CI=1.048-2.150, p=0.0268) and first-line therapy (HR=1.962, 95%CI=1.288-2.986, p=0.0017) were independent prognostic factors for PFS. CONCLUSION: IO combination therapy significantly improved the PFS of patients with advanced RCC, especially those with intermediate- and poor-risk disease. Further investigations focusing on the improvement of survival are warranted.

Clinical outcomes of iodine-125 low-dose-rate brachytherapy for localized prostate cancer: a single-institution review in Japan.

Purpose: To evaluate the oncological outcomes and genitourinary and gastrointestinal adverse events in acute and late-phases of iodine-125 low-dose-rate brachytherapy for localized prostate cancer. Material and methods: We retrospectively evaluated 334 patients treated for localized prostate cancer with low-dose-rate brachytherapy. Bio-chemical relapse-free survival, cause-specific survival, and overall survival were evaluated using Kaplan-Meier method and log-rank test. Incidence of adverse events was calculated using National Cancer Institute common terminology criteria for adverse events, version 5. Logistic regression was used to identify independent predictors of acute and late-phase genitourinary and gastrointestinal adverse events. Results: National Comprehensive Cancer Network's low-, intermediate-, and high-risk groups included 133 (39.8%), 163 (48.8%), and 38 (11.3%) patients, respectively. The 5-year cause-specific survival rate was 100%. The 5-year bio-chemical relapse-free survival rates for the low-, intermediate-, and high-risk groups were 98.3%, 95.8%, and 100%, respectively. One patient had a ≥ grade 3 acute adverse event. The 5-year cumulative ≥ grade 1, ≥ grade 2, and ≥ grade 3 genitourinary adverse event rates were 27.9%, 14.4%, and 0.5%, respectively. The 5-year cumulative ≥ grade 1, ≥ grade 2, and ≥ grade 3 gastrointestinal adverse event rates were 3.1%, 1.5%, and 0.5%, respectively. A high pre-treatment international prostate symptom score and non-use of α1-blockers were associated with an increased risk of acute genitourinary adverse events. Conclusions: Low-dose-rate brachytherapy had good oncological outcomes, with acceptable adverse event rates. Pre-treatment urinary function and use of α1-blockers may be useful in predicting and preventing acute genitourinary adverse events.

Impact of Gleason score of the tumor at the positive surgical margin as a prognostic factor.

Although numerous studies have reported that a positive surgical margin (PSM) is the most important predictive factor for biochemical recurrence (BCR) of prostate cancer (PCa), only a small number of studies have evaluated the predictive value of the Gleason score (GS) of the tumor at the margin in radical prostatectomy (RP). The present study aimed to investigate the preoperative factors that predict PSM and the significant predictive factors for BCR in cases with PSM. In addition, it was examined whether documenting the GS of the tumor at the margin in pathological reports is useful as a predictive factor for BCR. Data of 241 patients with PCa who underwent RP at Kurume University Hospital (Kurume, Japan) between January 2007 and December 2011 were retrospectively reviewed. The median follow-up period was 72 months and 122 patients had at least one PSM. The time to BCR was significantly shorter in patients with PSM than in those with a negative surgical margin. Multivariate analysis demonstrated that >10 ng/ml prostate-specific antigen at diagnosis (P=0.024) and >25% positive core at biopsy (P=0.041) were independent prognostic preoperative factors for PSM. The GS of the tumor at the margin was equal, lower and higher than those of the main tumor in 74 (60.7%), 16 (13.1%) and 32 (26.2%) RPs, respectively. The BCR rates were 35.7, 55.1 and 82.1% in patients whose GS of the tumor at the margin was 6, 7 and 8-10, respectively (P=0.0017). The GS of the tumor at the PSM (P=0.038) and anatomic location of the PSM (P=0.04) were identified as independent prognostic preoperative factors for BCR, whereas the GS of the main tumor and margin length were not. These results suggest that documenting the GS at the margin in pathological reports is useful as a predictive factor for BCR.

Survival outcomes of non-definitive therapy for muscle-invasive bladder cancer.

To analyze the risks and survival outcomes of non-definitive therapy (nDT) for muscle-invasive bladder cancer (MIBC), which may provide useful information for future treatment selection, the present study analyzed 124 patients who were diagnosed with MIBC (cT2-4aN1-2M0) and treated at Kurume University Hospital (Kurume, Japan) with definitive therapy (DT; including radical cystectomy and trimodal therapy) or nDT [transurethral resection of bladder tumor (TURBT) monotherapy or TURBT plus chemotherapy]. Differences in survival outcomes between the two groups were estimated using the Kaplan-Meier method and analyzed using the log-rank test. Cox proportional hazards regression models were used for multivariate analysis of each survival outcome. Of the 124 patients, 45% were treated with nDT, and among these, 50% were treated with TURBT monotherapy and 50% were treated with TURBT plus chemotherapy. Of the patients who chose definitive treatment, 69% were treated with radical cystectomy. The median age in the nDT group was 77 years, which was significantly higher than that in the DT group. Additionally, the proportion of patients with poor performance status, high Charlson comorbidity index and high neutrophil-lymphocyte ratio values was significantly higher in the nDT group. nDT was associated with significantly reduced overall survival, cancer-specific survival and progression-free survival rates, and was a poor prognostic factor for all survival outcomes compared with DT. In conclusion, nDT was associated with a high cancer-related mortality risk. The most appropriate treatment method should be discussed with the patients after providing them with sufficient information on the risks and benefits of each treatment method.

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab.

BACKGROUND: Immune checkpoint inhibitors cause various immune-related adverse events. The present study examined the association between the incidence of immune-related adverse events and survival outcomes in patients treated with nivolumab plus ipilimumab for patients with advanced renal cell carcinoma. In addition, we compared the effect of adverse event profiles on survival for patients receiving nivolumab plus ipilimumab. METHODS: A total of 35 patients with advanced renal cell carcinoma who were treated with nivolumab plus ipilimumab from August 2018 to August 2021 were retrospectively reviewed and analyzed. Cox proportional hazards models were used for univariate and multivariate analyses, and hazard ratio and 95% confidence intervals were calculated. RESULTS: Of the 35 patients, 22 (62.9%) experienced immune-related adverse events. The median progression-free survival (P = 0.0012) and overall survival (P = 0.0147) were significantly longer in patients with immune-related adverse events than in those without immune-related adverse events. Multivariate analysis showed that the incidence of immune-related adverse events was an independent factor for progression-free survival (hazard ratio = 4.940, 95% confidence interval: 1.558-15.664, P = 0.0067). Skin reaction was a positive predictive immune-related adverse events for progression-free survival (hazard ratio = 9.322, 95% confidence interval: 1.954-44.475, P = 0.0051). CONCLUSION: Patients with advanced renal cell carcinoma with immune-related adverse events had superior clinical outcomes of nivolumab plus ipilimumab treatment than those without immune-related adverse events. Skin immune-related adverse events may be effective biomarkers in patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab.

[EFFICACY AND SAFETY OF INITIAL DESMOPRESSIN DOSE OF 50 µg IN ELDERLY MALE PATIENTS WITH NOCTURNAL POLYURIA].

(Introduction) Low-dose desmopressin is now available for the treatment of nocturia associated with nocturnal polyuria in men, and its usefulness in a dose-dependent manner has been reported. Since side effects such as hyponatremia have reported frequently, the initial dose has been set at 25 µg in many cases considering age and other factors. In the present study, we investigated the efficacy and safety of an initial dose of 50 µg in elderly patients. (Subjects and methods) At Chikugo city hospital, 45 patients were started on desmopressin at an initial dose of 50 µg for nocturia with nocturnal polyuria. Efficacy and safety after one and four weeks were evaluated based on bladder (micturition) diary. The investigated parameters included frequency of nocturnal urination, nocturnal polyuria index, time to first nocturnal void, first nocturnal urine volume, nocturnal urine volume, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and Athens Insomnia Scale. Physical examinations were also carried out, along with blood tests. (Results) The mean age of the patients was 78.3 years, which was higher than that reported in prior studies. After one week of treatment, there was a significant decrease in the frequency of nocturnal urination and nocturnal urine volume, as well as a prolongation of the time to first nocturnal void, improvement in nocturnal polyuria index, and improvement in IPSS, IPSS-QOL, OABSS, and Athens Insomnia Scale. In terms of safety, adverse events were observed in eight patients (17.8%), and hyponatremia was observed in seven patients (15.6%), which was comparable to the findings of prior reports. (Conclusion) Good therapeutic results were obtained in elderly patients at an initial desmopressin dose of 50 µg, indicating that the drug could be safely administered to elderly patients with regular follow-ups and appropriate withdrawal and dose reductions.

Absolute lymphocyte count is an independent predictor of survival in patients with metastatic renal cell carcinoma treated with nivolumab.

OBJECTIVE: Programmed cell death-1 antibody therapy has demonstrated improved progression-free survival and overall survival in patients with metastatic renal cell carcinoma. However, there are limited studies on biomarkers that can predict the efficacy of immune checkpoint inhibitors. We examined the influence of peripheral inflammatory biomarkers on the clinical outcomes of patients with metastatic renal cell carcinoma treated with nivolumab. METHODS: Data of 38 patients with metastatic renal cell carcinoma, who were treated with nivolumab monotherapy after receiving at least one molecular targeted therapy from November 2016 to February 2021, were retrospectively reviewed and analyzed. RESULTS: Median progression-free survival and overall survival were significantly shorter in patients with low absolute lymphocyte count (<1300/µl) versus those with high absolute lymphocyte count (progression-free survival: P = 0.0102; overall survival: P = 0.0026). Median overall survival was shorter in patients with high neutrophil-lymphocyte ratio (≥3.0) versus those with low neutrophil-lymphocyte ratio (P = 0.0344). Multivariate analysis showed that absolute lymphocyte count was an independent factor for progression-free survival (hazard ratio = 2.332, 95% confidence interval = 1.012-5.375, P = 0.0468) and overall survival (hazard ratio = 4.153, 95% confidence interval = 1.108-15.570, P = 0.0347). Increased absolute lymphocyte count, 1 month after nivolumab initiation, was a positive predictive factor for progression-free survival (hazard ratio = 0.419, 95% confidence interval = 0.189-0.926, P = 0.0317) and overall survival (hazard ratio = 0.285, 95% confidence interval = 0.091-0.890, P = 0.0308). CONCLUSION: Our study indicates that peripheral absolute lymphocyte count, before nivolumab initiation, is a predictor of poor response in metastatic renal cell carcinoma. Additionally, increased absolute lymphocyte count, 1 month post-nivolumab initiation, can be a predictor of the effects of nivolumab.

Analysis of radioactive implant migration in patients treated with iodine-125 seeds for permanent prostate brachytherapy with MRI-classified median lobe hyperplasia.

PURPOSE: Prostate cancer with median lobe hyperplasia (MLH) is a relative contraindication for permanent prostate brachytherapy (PPB) because of an increased risk of post-implant dysuria and technical difficulties associated with achieving stability while implanting within the intravesical tissue. We examined treatment outcome, seed migration, and urination disorders after treatment in MLH patients in order to determine to what degree MLH implants could be stabilized. MATERIAL AND METHODS: Between March 2007 and December 2016, 32 patients had MLH identified radiologically on magnetic resonance imaging, and 193 patients did not have MLH (non-MLH). All patients were treated with loose seeds. In this study, seed migration was defined as a seed distant from the target (≥ 1.5 cm) and/or with no dosimetric contribution to the target. The MLH patients were divided into 2 MLH groups of mild (< 10 mm) and severe (≥ 10 mm) MLH by measuring the distance between the posterior transitional zone and the prostatic tissue protruding into the bladder. We retrospectively analyzed seed migration, dose-volume histograms (DVH), and genitourinary toxicity. RESULTS: MLH was classified as mild in 24 patients and severe in 8. Seed migration occurred in 61 (31.6%) of 193 non-MLH patients and 10 (31.5%) of 32 MLH patients. Implant seed migration and low-dose level of median lobe tended to be high in severe MLH cases. International Prostate Symptom Score (IPSS) peaked one month after implantation, but then resolved slowly and returned to around the pre-treatment level after one year. There were no severe complications. CONCLUSIONS: MLH does not appear to be a strong contraindication for low-dose-rate brachytherapy. However, we found that the seed migration and degree of cold spots tended to be higher in severe MLH cases than in others; therefore, close attention when treating severe MLH cases must be paid.

Longitudinal Changes in Health-related Quality of Life After 125I Low-dose-rate Brachytherapy for Localized Prostate Cancer.

BACKGROUND/AIM: The factors associated with longitudinal changes in health-related quality of life (HRQOL) are unclear. In this study we aimed to evaluate the longitudinal changes and predictors of HRQOL after 125I low-dose-rate brachytherapy (LDB) for localised prostate cancer (PCA). PATIENTS AND METHODS: We evaluated 180 patients with localised PCA treated with LDB. The HRQOL was evaluated at 3 weeks before LDB and at 1, 3, 6, 12, 18, 24, 36, and 48 months after LDB using the International Prostate Symptom Score, Medical Outcome Study 8-Items Short Form Health Survey (SF-8), and University of California Los Angeles Prostate Cancer Index (UCLA-PCI). RESULTS: All HRQOL scores, except for UCLA-PCI sexual function and SF-8 mental component summary (MCS), were improved to baseline after an early transient deterioration. In contrast, the sexual function did not return to baseline after early deterioration. Meanwhile, the MCS scores showed no significant decline after implantation and trended upward. The prostate V100 and baseline UCLA-PCI sexual function scores predicted a clinically significant decrease in sexual function in the late post-implantation period. CONCLUSION: Most aspects of the HRQOL of PCA patients who underwent LDB improved to baseline. The results that V100 and baseline sexual function were predictors of late post-LDB may provide more accurate information for patients with preserved sexual function before treatment and for their partners.

Paraganglioma of the urinary bladder: Case report and literature review.

INTRODUCTION: Paraganglioma of the urinary bladder is a very rare disease accounting for 0.06% of all bladder tumors. Owing to their rarity and symptomatic variability, preoperative diagnosis is often difficult. CASE PRESENTATION: A 70-year-old male was referred to our department for hematuria. Cystoscopy showed a non-papillary broad-based tumor. Computed tomography and magnetic resonance imaging revealed a 32-mm bladder tumor at the top of the bladder, which suggested muscle-invasive bladder tumor. We diagnosed muscle-invasive bladder cancer or urachal carcinoma, and transurethral resection of the bladder tumor was performed. At the initiation of transurethral resection of the bladder tumor, the systolic blood pressure was elevated to over 200 mmHg. The pathological findings revealed paraganglioma of the urinary bladder, and afterward, a partial cystectomy was performed. CONCLUSION: We herein reported the case of paraganglioma in the bladder whose blood pressure became extremely elevated during transurethral resection of the bladder tumor. In addition, we analyzed important factors for preoperative diagnosis using 162 cases reported in Japan.

The Prognostic Value of Systemic Inflammatory Markers in Advanced Renal Cell Carcinoma Patients Treated With Molecular Targeted Therapies.

BACKGROUND/AIM: The present study examined the impact of systemic inflammatory markers including C-reactive protein (CRP)/Albumin (Alb) and neutrophil lymphocyte ratio (NLR)/Alb on the prognosis of patients treated with first line molecular targeted therapy for advanced RCC. PATIENTS AND METHODS: A total of 131 patients with advanced RCC treated with molecular targeted therapy as first line treatment from May 2008 to April 2019 were retrospectively analyzed. RESULTS: High CRP, high NLR, low Alb and high CRP/Alb showed significantly worse progression-free survival (PFS) and overall survival (OS) than low CRP, low NLR, high Alb, low CRP/Alb and low NLR/Alb, respectively. In multivariate analyses, prior nephrectomy (p=0.0321) and NLR/Alb ratio (p=0.0327) were independent prognostic factors for PFS. Furthermore, prior nephrectomy (p=0.0013) and CRP/Alb ratio (p=0.0020) were independent prognostic factors for OS. CONCLUSION: CRP/Alb and NLR/Alb ratios are useful and independent prognostic biomarkers in patients with advanced RCC treated with molecular targeted therapy.

The Impact of Antibiotics on Prognosis of Metastatic Renal Cell Carcinoma in Japanese Patients Treated With Immune Checkpoint Inhibitors.

BACKGROUND/AIM: The present study aimed to examine the influence of antibiotics (AB) on the clinical outcomes of Japanese patients treated with immune check point inhibitors (ICIs) for metastatic renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: A total of 31 patients with metastatic RCC treated with ICIs from November 2016 to April 2019 were retrospectively reviewed and analyzed. RESULTS: Five patients were treated with AB prior to ICIs treatment. Median progression free survival (PFS) of patients treated with AB vs. patients not treated with AB was 2.8 months and 18.4 months, respectively. The difference between PFS was statistically significant (p=0.0004). In multivariate analyses, AB use (p=0.0377) and presence of immune related adverse events (p=0.0042) were independent prognostic factors for PFS in association with ICIs therapy. CONCLUSION: The use of AB before ICIs treatment was a predictor of poor ICIs response in metastatic RCC.