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.

Prostate brachytherapy seed migration to the right renal artery due to right-to-left shunting across a patent foramen ovale.

Introduction: The seeds used in brachytherapy for prostate cancer may migrate through the surrounding venous plexus to other sites in the body, most commonly to the pulmonary vasculature. Case presentation: A 78-year-old Japanese man received iodine-125 low-dose-rate prostate brachytherapy. Computed tomography revealed that one seed had migrated to the right kidney. No seed was observed in the ureter upon ureteroscopy. Transesophageal echocardiography confirmed a right-to-left shunt due to a patent foramen ovale, suggesting that the seed had migrated into the right renal artery. Three years after treatment, no recurrence of prostate cancer and no adverse events due to seed migration or due to the patent foramen ovale occurred. Conclusion: Arteriovenous malformations and a right-to-left shunt should be suspected if a brachytherapy seed has migrated to an artery of the systemic circulatory system.

Seed lost to perineum from hydrogel spacer after brachytherapy for prostate cancer.

Introduction: We describe a rare case of brachytherapy for prostate cancer in which a seed was lost from the perineum after a hydrogel injection. Case presentation: A 71-year-old Japanese man was diagnosed with localized high-risk prostate cancer. Trimodality therapy with I-125 brachytherapy was selected, and combined androgen blockade therapy was initiated. Brachytherapy and hydrogel injection were performed 7 months after combined androgen blockade initiation; 6 months later, the patient visited our hospital with complaints of redness and bleeding in the perineum. Serous effusion and loss of a seed on the right side of the perineal anus were observed. Pelvic magnetic resonance imaging showed a tunnel like discharge of hydrogel from the dorsal prostate to the perineum. The fistula was incised, the seed was removed, and drainage was performed. Conclusion: Appropriate diagnosis and treatment with careful follow-up are required in patients at high risk of infection after brachytherapy with hydrogel injection.

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.

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.

Tri-modality therapy with i-125 brachytherapy, external beam radiation therapy, and short-term hormone therapy for high-risk prostate cancer after holmium laser enucleation of the prostate.

Introduction: We present tri-modality therapy with i-125 brachytherapy for high-risk prostate cancer after holmium laser enucleation of the prostate. Case presentation: A 75-year-old man had visited our hospital with complaints of dysuria. Holmium laser enucleation of the prostate was performed for benign prostatic hyperplasia. The resected histopathological prostate tissue showed malignancy (Gleason score: 3 + 3 = 6). Two years thereafter, Gleason score progressed (4 + 5 = 9) concomitantly with increased prostate-specific antigen levels. Therefore, tri-modality therapy, including brachytherapy, was applied. Combined androgen blockade therapy was conducted over a 9-month period. One month after brachytherapy, external beam radiation was performed. Conclusion: Brachytherapy following transurethral prostate surgery is relatively contraindicated because of increased adverse urethral event frequency and seed placement difficulties. A tri-modality therapy, including brachytherapy, was implemented without any major problems in this patient with high-risk prostate cancer after holmium laser enucleation of the prostate, following which he had a favorable prognosis without recurrence for 6 years.

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.

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.

Distribution, shape, and immunohistochemical characteristics of serotonin-immunoreactive neuroendocrine cells in the urethra and periurethral genital organs in mice.

The aim of this study is to clarify the disibution, shape, and immunohistochemical characteristics of serotonin-immunoreactive neuroendocrine cells (SIR-NECs) in mouse prostate and in the surrounding genital organs by histological and immunohistochemical analysis of the light microscopic serial sections of urethra. We collected lower urinary tracts from 13-week-old mice and observed the distribution pattern and shape of the SIR-NECs by serial light microscopy. The organs on the sections were divided into three anatomical zones to clarify the distribution pattern of SIR-NECs: (1) zone A, the ducts near the prostatic urethra; (2) zone B, the ducts outside the urethral sphincter; and (3) zone C, the acinus areas. Sections were double immune-stained with antibodies against serotonin and one of neuroendocrine-related factors (NRFs), including 10 neural cell markers and eight neurotransmitters, and also 4',6-diamino-2-phenylindole (DAPI). In addition, SIR-NECs were double immune-stained with antibodies against cytokeratin 5 (CK5) and p63, together with DAPI. SIR-NECs were mostly localized in zone A, and no SIR-NECs were observed in zone C. The proportion of flask-shaped SIR-NECs was approximately 15% in zones A and B. No flask-shaped SIR-NECs were observed in urethral epithelia. The NRFs co-localized with SIR-NEC were calcitonin gene-related peptide, CD56, chromogranin A, neuron-specific enolase, neuron cytoplastic protein 9.5, and synaptophysin (72.3%, 73.2%, 88.9%, 92.3%, 91.7%, and 81.9%, respectively). CK5 and p63 were not co-localized with SIR-NECs.　In this study, SIR-NEC of the urethra and the surrounding genital organs was ubiquitous in the urethra and the ducts near the urethra and co-expressed specific nerve-related NRFs.

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.

Synchronous primary triple urogenital malignant tumors of kidney, prostate and bladder.

Synchronous occurrence of triple primary cancers of urinary tract is quite rare and represents a difficult treatment challenge. Here, we report a case of a 78-year-old man with synchronous renal cell carcinoma, urothelial carcinoma of urinary bladder and adenocarcinoma of prostate within a short period. To the best of our knowledge, this is the 20th reported of triple primary cancers of urinary tract and the first synchronous case with bone metastasis in the literature.

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.

Elevated Expression of EPHA2 Is Associated With Poor Prognosis After Radical Prostatectomy in Prostate Cancer.

BACKGROUND/AIM: Therapeutic targeting of receptor protein tyrosine kinases (PTKs) has proven successful in treating cancer. However, reports about PTKs in treating prostate cancer are few. Elevated expression of the erythropoietin-producing hepatocellular receptor A2 (EPHA2) receptor tyrosine kinase, a transmembrane protein, is associated with poor prognosis of certain cancer types when the enzyme is dephosphorylated. This study investigated whether EPHA2 is useful in predicting the biochemical recurrence of prostate cancer. PATIENTS AND METHODS: Data from 241 patients who had undergone total prostatectomy between 2007 and 2011 were used. EPHA2 protein expression was categorized as high or low by two pathologists. The relationship was examined between EPHA2 expression level (high vs. low) and clinicopathological factors including biochemical recurrence. Correlations were examined between EPHA2, low-molecular-weight protein tyrosine phosphatase (LMW-PTP), E-cadherin, and Ki-67. RESULTS: EPHA2 expression was high in 121 (50.2%) and low in 120 (49.8%) patients. A log-rank test revealed early biochemical recurrence in the high-expression group. Gleason score, Ki-67 labeling index, and biochemical recurrence were more frequent in the high-expression group. Furthermore, multivariate analyses revealed that high EPHA2 expression was an independent prognostic factor for biochemical recurrence (hazard ratio=3.62, 95% confidence interval=2.39-5.61). Correlations between EPHA2 and both LMW-PTP and Ki-67 labeling index were positive, whereas EPHA2 and E-cadherin were negatively correlated. CONCLUSION: EPHA2 overexpression is predictive of aggressive prostate cancer behavior. EPHA2 may be a powerful prognostic biomarker for decision-making in postoperative follow-up after total prostatectomy, and regarding the need for palliative treatment. Additionally, it may be an important therapeutic target.