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Background/aim: We evaluated the clinical outcomes of patients with metastatic germ cell tumors (GCT) treated at our hospital, which belongs to a regional cancer center., Patients and Methods: Data pertaining to patients with metastatic GCT were obtained between April 2007-October 2017 and was retrospectively analyzed. Key outcome measures included objective response rates and survival rates., Results: All 42 patients received chemotherapy [complete response: eight (19.0%); partial response: 21 (50.0%); stable disease (SD): nine (21.4%); progressive disease: four patients (9.5%)]. Post-chemotherapeutic surgery was performed for seven out of 21 cases of partial response and two out of nine of stable disease. The 5-year survival rates of patients with good, intermediate and poor prognosis (International Germ Cell Consensus Classification) were 100%, 100%, and 71.4%, respectively. Patients who received induction chemotherapy at other hospitals had significantly poorer prognosis than those at our hospital (p=0.0043)., Conclusion: Patients with metastatic GCT should preferably receive chemotherapy at an experienced institution., Competing Interests: The Authors declare no conflicts of interest associated with this article., (Copyright 2021, International Institute of Anticancer Research.)

Background/aim: To investigate the blood markers for predicting pembrolizumab efficacy in advanced urothelial carcinoma (UC)., Patients and Methods: This study included 91 advanced UC patients. The relationship between prognosis and markers from peripheral blood cell counts, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI=monocytes × neutrophils/lymphocytes), was evaluated., Results: Multivariate analysis indicated that pretreatment NLR and the 1-month-change NLR were both significantly associated with overall survival (OS) after pembrolizumab initiation. When the patients were divided into four groups according to calculated cutoffs using Cox proportional hazard model, the pretreatment NLR <2.9 and 1-month change NLR <+43% groups had a significantly better OS than the pretreatment NLR ≥2.9 and 1-month-change NLR ≥+43% groups., Conclusion: NLR, MLR, PLR and SIRI before pembrolizumab and 1-month-change NLR in advanced UC correlated with OS after pembrolizumab treatment., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Histiocytic sarcoma is considered an extremely rare condition. We herein report on a case of histiocytic sarcoma following combination chemotherapy for a primary mediastinal germ cell tumor in a 26-year-old Asian man who visited the General Medicine Department of a hospital with complaints of cough and high fever. Chest computed tomography (CT) imaging revealed a tumor (diameter 10.5 cm) in the anterior mediastinum, with no signs of metastasis, and CT-guided biopsy of the mediastinal tumor revealed the presence of some necrotic cartilages. The patient's serum α-fetoprotein (AFP) level was determined to be high at 160.4 ng/mL and a primary mediastinal non-seminomatous germ cell tumor was suspected, so the patient was referred to the Department of Urology. Despite the presence of severe thrombocytopenia, the patient was treated using a combination of chemotherapy and intermittent transfusion, which was able to normalize his serum AFP level. However, resection of the mediastinal tumor was unsuccessful due to persistent thrombocytopenia and the patient was subsequently transferred to our hospital for further examination and treatment. Despite management by hematologists, the condition of the patient did not improve; although his AFP level remained normal, the tumor increased in size and then metastasized to the liver and spleen. The general condition of the patient deteriorated and he died 9 months after his first visit. The patient was diagnosed with histiocytic sarcoma following a pathological autopsy. Due to the extremely rare incidence of histiocytic sarcoma, this condition should be a differential diagnosis and the appropriate tests must be conducted to give an exact treatment., Competing Interests: Conflict of interestAll authors declare that they have no conflicts of interest., (© The Japan Society of Clinical Oncology 2021.)

Background/aim: To investigate whether surgical margin (SM) status would affect the biochemical recurrence (BCR) after robot-associated RP (RARP)., Patients and Methods: We evaluated BCR after RARP and the association between pre- and postoperative predictive factors and BCR., Results: Positive SM (PSM) was observed in 97 out of 365 enrolled patients. On multivariate analysis, preoperative prostate specific antigen, biopsy Gleason score (GS), clinical stage, GS ≥7 at the PSM and pathological GS ≥7 were predictive factors for BCR. The 5-year BCR-free survival rate was 84.1% in the negative SM (NSM), 87.4% when GS=6 at the PSM, and 47.6% when GS ≥7 at the PSM. There was no statistically significant difference in BCR-free survival between the NSM group and GS=6 at the PSM group (p=0.966)., Conclusion: It would be desirable to evaluate GS at PSM when PSM is present in a specimen removed by RP., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The efficacy and safety of keishibukuryogan, a traditional Japanese medicine, were investigated for the treatment of hot flashes in prostate cancer (PC) patients receiving androgen deprivation therapy., Methods: Thirty patients were enrolled and orally administered 2.5 g keishibukuryogan three times daily for 12 weeks. The frequency, strength, and duration of hot flashes were self-evaluated by the patients in a diary every 4 weeks. All patients also completed a questionnaire to determine their aging male symptoms (AMS) scale score and underwent blood biochemical testing., Results: Twenty-five patients completed the 12-week treatment. Hot flash strength significantly improved 4, 8, and 12 weeks after treatment. Their frequency was significantly reduced at the 8-week visit, and duration was significantly shorter after the 8-week visit. In addition, the score of the AMS somatic subscale was improved at the 8- and 12-week visits. Among the somatic items, questions 3 (excessive sweating) and 5 (increased need for sleep) were significantly improved. Obesity, radiation, and a longer duration of PC were predictive factors for treatment response. Prostate specific antigen and total testosterone levels were unchanged, and no patients had severe adverse effects., Conclusions: Keishibukuryogan was an effective and safe treatment for hot flashes in PC patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-901). The authors have no conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)

Five mg tadalafil was administered once-daily to 48 patients for 6 months. Their International Prostatic Symptoms Score (IPSS), Overactive Bladder Symptoms Score (OABSS), Sexual Health Inventory for Men (SHIM), post-voided residual (PVR) volume, free testosterone (FT) level, prostate-specific antigen level, and highly sensitive C-reactive protein (hsCRP) value obtained before and 6 months after the treatment were analyzed. The treatment significantly improved the IPSS, OABSS, SHIM score, and PVR volume (P<0.05), and significantly increased the mean FT level from 6.68 to 7.10 pg/ml ; P<0.05. We observed no significant changes in the hsCRP value and PSA level. However, elevated FT values were noted in 25 (52.1%) patients 6 months after the treatment (FT-increased group). Compared with the non-FT-increased group, the FT-increased group had markedly lower baseline FT value and higher prostatic volume. In both groups, IPSS and OABSS improved considerably. Moreover, the PVR volume, SHIM score, and hsCRP value markedly improved in the FT-increased group (P<0.05). Thus, 5 mg tadalafil administered oncedaily improved IPSS, OABSS, and erectile function, and increased the FT value, in hypogonadal patients with lower urinary tract symptoms. Furthermore, the hsCRP value declined considerably in patients with posttreatment elevated FT level.

Background/aim: Hypertension is a risk factor for occurrence of renal cell carcinoma; however, it remains unclear whether hypertension affects development and prognosis of renal cell carcinoma. This study evaluated the impact of hypertension on the progression of renal cell carcinoma., Patients and Methods: Renal cell carcinoma patients who were treated from October 2007 to December 2018 at our Institution were retrospectively analyzed., Results: Of 462 patients, the number of patients with and without hypertension was 234 (including 227 treated with anti-hypertensive agents) and 228, respectively. The tumor size was significantly smaller in the hypertension group than in the non-hypertension group (median 32 and 45 mm, respectively, p=0.010). The 5-year cancer-specific and metastasis-free survival in the hypertension group were significantly better than those in the non-hypertension group (93.6% and 80.4%, and 84.6% and 73.0%, respectively, p=0.021 and p=0.017). Propensity score matching revealed significantly better metastatic-free survival in the hypertension group than the non-hypertension group (p=0.022)., Conclusion: Renal cell carcinoma patients with hypertension show better prognosis with low metastasis possibility., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The best sequential treatment for castration-resistant prostate cancer (CRPC) remains unclear. This study evaluated the therapeutic effects of ethinylestradiol (EE) on CRPC., Patients and Methods: A total of 80 patients with CRPC, treated with 0.5-1.5 mg/day of EE, were retrospectively assessed., Results: The median duration from the initial treatment to the beginning of EE was 48.3 months. A decline in the prostate-specific antigen (PSA) from the baseline was noted in 60 patients (75%) and a >50% PSA decline in 27 patients (34%). The median time of PSA progression, overall survival, and cancer-specific survival after EE were 5.60 months, 24.00 months, and 27.93 months, respectively., Conclusion: EE administration for CRPC showed a relatively high PSA response regardless of timing of sequential treatment. The frequency of cardiovascular adverse events was not significantly high. EE administration is a potential treatment option for CRPC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to assess the efficacy and toxicity of second-line chemotherapy, especially combination chemotherapy, for advanced or metastatic urothelial cancer., Patients and Methods: This retrospective analysis included patients who received second-line chemotherapy after disease progression during first-line chemotherapy between January 2009 to May 2018. Progression-free survival (PFS), overall survival (OS) and toxicity associated with second-line chemotherapy were assessed., Results: In total 25 patients received second-line chemotherapy; 21 patients had combination chemotherapy and 4 had single-agent chemotherapy. Median PFS and OS were 3.6 months (range=0.2-23.5) and 11.9 months (range=0.5-29.0), respectively. Twenty patients (80%) exhibited grade 3 or more severe toxicities., Conclusion: PFS and OS benefits of second-line combination chemotherapy corresponded to those of the phase 3 study of pembrolizumab, but adverse events were more severe. Pembrolizumab is potentially a better second-line treatment than combination chemotherapy., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This study investigated tumor-associated macrophages activity in the microenvironment of renal cell carcinoma. Via a co-culture with macrophage-like cells differentiated from human monocyte cell line THP-1 and U937 cells, the migration ability of ACHN and Caki-1 cells, which are human renal cell carcinoma cell line cells, was significantly increased, as was the epithelial-mesenchymal transition change. A chemokine array identified the CCL20-CCR6 axis as a concentration-dependent signal in ACHN and Caki-1 cell migration. Akt in the ACHN and Caki-1 cells was activated by macrophage-like cells, and the CCL20 neutralizing antibody suppressed migration ability, epithelial-mesenchymal transition, and Akt phosphorylation in the ACHN and Caki-1 cells. Akt inhibitor AZD5363 also decreased the epithelial-mesenchymal transition change and migration ability in the ACHN and Caki-1 cells. In 42 renal cell carcinoma tissues, patients with CCR6 and macrophage infiltration indicated poor prognoses. In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelial-mesenchymal transition and an acquired migration ability. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma.

Background: The present study was conducted to investigate whether baseline serum carbohydrate antigen (CA) 19-9 predicts prognosis or treatment effect in patients with advanced urothelial carcinoma (UC)., Materials and Methods: We retrospectively analyzed data of patients diagnosed with locally advanced or metastatic or recurrent UC between April 2008 and November 2014. CA19-9 was determined using enzyme-linked immunosorbent assay (ELISA) and the relationship between CA19-9 and prognosis were analyzed., Results: Of 40 patients, seven with CA19-9 ≤2 U/ml who were suspected of having Lewis A-negative blood type and two patients with advanced metastatic liver disease were excluded. UC-specific survival in metastatic disease significantly correlated with prognosis (p=0.018). Overall survival in patients with high serum CA19-9 demonstrated a significantly better prognosis than in those with low concentrations (log-rank test, p=0.032)., Conclusion: High baseline serum CA19-9 may predict a good prognosis in patients with advanced UC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Combination chemotherapy with gemcitabine and cisplatin is the standard first-line treatment for advanced urinary tract urothelial cancer. Carboplatin is often substituted for cisplatin in patients who are cisplatin-ineligible, such as those with a glomerular filtration rate less than 60 ml/min. However, carboplatin-based chemotherapy has not been not confirmed as meeting the standard of care based on randomized controlled trials, and it is still unclear whether carboplatin can offer prognosis comparable to that with cisplatin., Patients and Methods: Patients with advanced urothelial cancer who underwent gemcitabine/cisplatin (GC) split or gemcitabine/ carboplatin (GCarbo) for renal dysfunction with a glomerular filtration rate of approximately 40-60 ml/min between 2008 and 2015 were chosen and reviewed using their charts. Patients with normal renal function treated with GC were also reviewed as a reference group., Results: A total of 41 patients, including 10 treated with GCsplit, 16 treated with GCarbo, and 15 treated with GC, were analyzed. The median overall and progression-free survival in GCsplit and GCarbo groups were 18.1 and 12.5 months (p=0.0454) and 9.9 and 6.4 months (p=0.0404), respectively. Neutropenia was relatively more severe in the GCsplit group than the GCarbo group (p=0.0103)., Conclusion: GCsplit may be a better treatment option for patients with advanced urothelial cancer with cisplatin-ineligible renal function. However, a prospective randomized controlled trial with a large-sized population is warranted to confirm our preliminary results., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To evaluate the treatment outcomes, toxicity and health-related quality of life (HRQOL) in prostate cancer (PCa) patients who underwent single-fraction high-dose-rate brachytherapy (single-fraction HDR-BT) with external beam radiotherapy (EBRT)., Materials and Methods: From April 2014 to October 2017, treatment outcomes and toxicity of 85 patients who underwent single-fraction HDR-BT of 13 Gy, followed by 46 Gy EBRT in 23 fractions, were examined. HRQOL of 53 patients was evaluated using the Expanded Prostate Cancer Index Composite (EPIC), International Prostate Symptom Score (IPSS)/QOL index, International Index of Erectile Function 5 (IIEF-5), and 36-Item Short Form Survey (SF-36) scores through one year., Results: The median follow-up period was 28.8 months. Only three patients had biochemical recurrence. Toxicities included less than grade 3 lower urinary tract symptoms and grade 1 diarrhea. Urethral stricture, a problem related to late toxicity in conventional HDR-BT, was not observed. The urinary and bowel functions in EPIC scores significantly worsened until three or six months after treatment, respectively., Conclusion: Single-fraction HDR-BT with EBRT showed promising biochemical control, tolerant toxicities, and preservation of HRQOL, and can be efficiently performed in a shorter time than conventional HDR-BT., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To evaluate the clinicopathological characteristics and prognosis of squamous cell carcinoma (SCC) of the urinary tract (UT) urothelium, and investigate the utility of perioperative chemotherapy., Patients and Methods: Thirty-three patients diagnosed with SCC in renal pelvis, ureter and bladder at the Kanazawa University between 2007 and 2017 were included in this retrospective study. Cancer-specific survival (CSS) rates according to cancer stage and neoadjuvant chemotherapy (NAC) were determined., Results: Among the entire cohort, two-year CSS rates were 100%, 75%, 47% and 0% in stages I, II, III and IV, respectively, with a significant correlation between CSS and cancer stage (p=0.0063). Sixteen patients underwent radical surgery, and seven patients received NAC; however, there were no significant differences in CSS rates among patients stratified by NAC (p=0.7043)., Conclusion: Worse cancer stage for SCC of UT urothelium was associated with worse prognosis. Given the poor efficacy of NAC in these patients, surgical treatment should be preferred., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To investigate how androgen-sensitive LNCaP cells crosstalk with androgen-insensitive DU145 or PC-3 cells., Materials and Methods: The numbers of LNCaP cells were counted when co-cultured with DU145 or PC-3 cells and vise versa. Androgen receptor (AR) activity in LNCaP cells was examined by luciferase reporter assay after transfection with a luciferase reporter driven by PSA promoter in the presence of DU145 or PC-3 cells. Concentration of androgens in the medium was measured by liquid chromatography-mass spectrometry (LC-MS/MS). The ability of migration and invasion of PC-3 and DU145 cells was investigated using a 2-layer chamber, in the presence of LNCaP cells., Results: Co-culture of LNCaP cells with DU145 cells resulted in the conversion of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT), which stimulated cell proliferation and PSA promoter activity in LNCaP cells. The increased cell proliferation rate and AR activity, induced in LNCaP cells after DHT treatment, was further enhanced by co-culture with DU145 cells. LNCaP cells also stimulated the proliferation of DU145 and PC-3 cells, via secreting soluble factors. Finally, LNCaP cells promoted migration and invasion of PC-3 cells, in a co-culture system; however inhibited migration and invasion of DU145 cells., Conclusion: Crosstalk between androgen-sensitive PCa cells and androgen-insensitive PCa cells might develop the progression of PCa., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Androgen-androgen receptor (AR) signal is known as a powerful driver of prostate cancer progression. We previously reported the limitation of prostate-specific antigen (PSA) at diagnosis as a prognostic biomarker of prostate cancer. Although serum total testosterone (TT) level has been reported as a prognostic biomarker for prostate cancer, its usability is still controversial. We examined the potential and characteristics of TT as a biomarker., Patients and Methods: Serum TT levels of patients who underwent prostate biopsy were measured, and prostate cancer-specific survival (PCaSS), overall survival (OS), and the correlation between staging and serum TT level were analyzed., Results: Of 379 biopsied patients, 255 were diagnosed with prostate cancer. The patients were divided into five groups according to their serum TT levels; patients with serum TT levels of <2 or ≥8 ng/ml (ENDs) had worse PCaSS and OS compared with those with middle serum TT levels between 2 and 8 ng/ml (MIDs). Moreover, ENDs showed a tendency of having castration-resistant cancer with advanced stage (T4 or N1 or M1). The TNM stage in ENDs was significantly higher than in MIDs., Conclusion: Although low serum TT level has been reported to indicate worse outcome in patients with prostate cancer, this study showed that both low as well as high serum TT levels indicate poor prognosis., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The aims of the study were to investigate desirable evaluation methods for post-prostatectomy incontinence (PPI) by analyzing the urinary status before robot-assisted radical prostatectomy (RARP).Questionnaires were evaluated from 155 patients prior to operation. The 24-h pad test before RARP revealed a weight of 1.1 g. The mean scores were as follows: total International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score, 1.2; total International Prostate Symptom Score (IPSS), 10.0; IPSS quality of life, 2.7; Overactive Bladder Symptom Score (OABSS), 2.9; and Expanded Prostate Cancer Index Composite urinary summary, 92.8. The abdominal leak point pressure test in 111 patients before RARP was negative in all cases. Desirable evaluation methods for PPI should be based on a combination of subjective and objective evaluations and comparisons between pre- and post-RP. ICIQ-SF is considerably convenient for evaluating incontinence, and the 24-h pad test enables evaluation of the incontinence volume in a highly objective manner., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Prostate-specific antigen (PSA) is regarded as the most sensitive biomarker for prostate cancer. Although androgen/androgen receptor (AR) signaling promotes prostate cancer progression, suppression of AR signaling induces chemokine (CC motif) ligand 2 (CCL2), which enables prostate cancer cells to gain metastatic potential. AR-controlled PSA alone may be an unreliable biomarker for patients receiving androgen deprivation therapy. Therefore, we investigated the validity of CCL2 as a complementary biomarker to PSA for prostate cancer. Our in vitro approach of enriching for prostate cancer cells with higher migration potential showed that CCL2 activated cellular migration. Importantly, we found that CCL2 levels were significantly different between men (n = 379) with and without prostate cancer. Patients with CCL2 ≥ 320 pg/mL had worse overall survival and prostate cancer -specific survival than those with CCL2 < 320 pg/mL. A novel risk classification was developed according to the risk factors CCL2 ≥ 320 pg/mL and PSA ≥ 100 ng/mL, and scores of 2, 1, and 0 were defined as poor, intermediate, and good risk, respectively, and clearly distinguished patient outcomes. CCL2 may serve as a novel biomarker for prostate cancer. The novel risk classification based on combining CCL2 and PSA is more reliable than using either alone.

Purpose: The current tumor-node-metastasis (TNM) classification system has been used for many years. The prognosis of patients with metastatic prostate cancer (mPC) treated using primary androgen deprivation therapy (PADT) was analyzed according to the TNM classification., Methods: A total of 5618 cases with lymph node metastases only (N1M0), non-regional lymph node metastasis (M1a), bone metastasis (M1b), and distant metastasis (M1c) were selected from the Japanese Study Group of Prostate Cancer database. Overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) rates were calculated using Kaplan-Meier analysis. The influence of clinical variables on patient prognosis was evaluated using the Cox proportional hazard regression model., Results: The 5-year OS, CSS, and PFS were 76.0, 83.2, and 38.8% in N1M0, 57.5, 69.0, and 23.0% in M1a, 54.0, 63.1, and 23.0% in M1b, and 40.0, 51.5, and 16.6% in M1c, respectively. OS, CSS, and PFS worsened as the stages progressed. OS, CSS, and PFS were all significantly worse in N1M1b compared with N0M1b. Multivariate analysis revealed that OS and CSS were worse in patients with a Gleason score ≥8 and that combined androgen blockade (CAB) treatment provided better OS than non-CAB treatments at any tumor stage. However, OS and CSS were worse in individuals with a prostate-specific antigen >100 ng/ml only in M1b., Conclusions: Patient prognosis worsened with stage progression; therefore, current TNM classification system of mPC for PADT was shown to be trustworthy. Each PC cell that develops bone or lymphoid metastasis may exhibit different characteristics.

Background: Prostate-specific antigen (PSA) is a useful biomarker for risk classification in patients with prostate cancer. However, it is unclear whether a correlation exists between low PSA levels (<10 ng/ml) at diagnosis and prognosis., Methods: Of the 642 Japanese patients who underwent prostate biopsy and were diagnosed with prostate cancer at Kanazawa University Hospital from 2000 to 2010, 406 patients with a PSA level <20 ng/ml were retrospectively reviewed., Results: PSA levels in 275 (68%) patients were <10 ng/ml. Although the percentage of Gleason score 8-10 in patients with a PSA level of <3.5 ng/ml was higher than that in patients with a PSA level between 3.5 and 10 ng/ml, it was not statistically significant. On the other hand, the percentage of higher stage (T3 and T4) patients with a PSA level <3.5 ng/ml was significantly greater than that in patients with a PSA level between 3.5 and 10 ng/ml (P < 0.0001). The percentage of metastases (N1 and M1) in patients with a PSA level <3.5 ng/ml was also significantly higher than that in patients with a PSA level between 3.5 and 10 ng/ml (P = 0.0112)., Conclusions: Patients with prostate cancer with a PSA level <3.5 ng/ml at diagnosis had a more advanced stage of cancer compared with those with a PSA level between 3.5 and 10 ng/ml. Therefore, risk classification using PSA levels at diagnosis may need to take into consideration this specific PSA range in order to better predict survival., (© 2015 Wiley Periodicals, Inc.)

Background: Platinum-based chemotherapy is the first-line treatment for advanced urinary tract urothelial cancers. However, the optimal second-line treatment is unclear. Although tegafur-uracil is sometimes used for advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy, there is little evidence regarding its use as a second-line treatment., Patients and Methods: Advanced urothelial cancer patients previously treated with platinum-based chemotherapy were retrospectively analyzed. Overall survival (OS) was compared between patients with and without tegafur-uracil treatment., Results: Thirty-one patients (27 and 4 patients with and without tegafur-uracil treatment, respectively) were analyzed. OS from the last day of the final chemotherapy course was better in patients with tegafur-uracil treatment than in those without (p<0.001, 358 and 66.5 days of the median survival time, respectively)., Conclusion: Tegafur-uracil may be a candidate for the secondary treatment of advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: To investigate the cumulative probability of developing prostate cancer according to prostate-specific antigen (PSA) velocity (PSAV) from first-to second-round PSA-based population screening in men with low baseline serum PSA levels., Patients and Methods: A total of 11,913 men aged between 54 and 69 years with baseline PSA levels of ≤2.0 ng/ml at the first population screening and who underwent population screening at least twice, were enrolled. The cumulative probability of developing prostate cancer according to age, baseline PSA and PSAV was investigated. The clinicopathological features of screen-detected cancer were also investigated., Results: Out of the 11,913 men, 110 (0.92%) were pathologically diagnosed with prostate cancer during the observation period. The cumulative probability of developing prostate cancer in all participants after 5 and 10 years was 0.64% and 1.79%, respectively. Univariate and multivariate analyses determined that baseline PSA levels and PSAVs were significant predictors of developing cancer and the hazard ratio increased with increasing baseline PSA levels and PSAVs. The optimal PSAV cut-off levels for prostate cancer development were 0.069, 0.106 and 0.285 for the baseline PSA ranges of 0.0-1.0, 1.1-1.5 and 1.6-2.0 ng/ml, respectively. There were no significant differences in baseline PSA levels and PSAVs according to the clinical characteristics of the screen-detected prostate cancer patients., Conclusion: The present study demonstrated that serum PSA levels at second round screening were a strong predictor of cancer development in men with baseline PSA levels≤2.0 ng/ml at the first population screening., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: We investigated the relationship between a new index considering the estimated working space and difficulty of robot-assisted radical prostatectomy (RARP) using our database., Patients and Methods: Working height was calculated by the obstetric conjugate diameter minus the bladder and rectal wall thicknesses minus the thickness of postvesical fat minus the rectal fat thicknesses measured using preoperative magnetic resonance imaging (MRI). The proportion of working height was calculated by dividing the working height by the obstetric conjugate diameter., Results: A total of 112 RARP cases were enrolled. The mean obstetric conjugate was 105 mm and the mean proportion of working height was 72.5%. Multivariate linear regression analysis indicated that the proportion of working height was an independent predictive factor for both console time and estimated blood loss., Conclusion: The difficulty of RARP can be predicted by measuring the fat thicknesses around the rectum and bladder by MRI before surgery., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The functions of superoxide dismutase-3 (SOD3), which acts on the cell surface and protects cells from oxidative stress, remain uncertain in the progression of prostate cancer., Materials and Methods: To verify SOD3 expression in human prostate tissue, immunohistochemistry was performed using tissue microarrays. To investigate the effects of SOD3 on proliferation, migration, and invasion, SOD3 was overexpressed and recombinant SOD3 was employed in PC-3 prostate cancer cells. H2O2 levels, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, catalase activity, and 8-oxo-2'-deoxyguanosine (8-OHdG) were estimated in SOD3-overexpressing PC-3 cells., Results: Immunohistochemistry revealed reduced expression of SOD3 in prostate cancer tissue. SOD3 overexpression in PC-3 cells inhibited cell proliferation, migration, and invasion. Recombinant SOD3 had the same effect. H2O2 accumulation was increased by SOD3 overexpression, GSH/GSSG ratio was decreased, and catalase activity was decreased. DNA damage in SOD3-overexpressing cells was confirmed by 8-OHdG elevation., Conclusion: Since SOD3 acts as a tumor suppressor, SOD3 overexpression and recombinant SOD3 might lead to treatment for prostate cancer., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Although laparoscopic radical nephroureterectomy is the standard treatment for localized upper urinary tract urothelial carcinoma, open radical nephroureterectomy has been reported to have a different rate of intravesical recurrence., Patients and Methods: Intravesical recurrence-free, progression-free, and overall survival rates among patients undergoing open and laparoscopic radical nephroureterectomy from 2002 to 2013 were analyzed., Results: Although no single factor predicted intravesical recurrence-free survival, a past history of bladder cancer or grade 3 was related to poorer intravesical recurrence-free survival rate in patients treated with laparoscopic radical nephroureterectomy. Moreover, the novel proposed risk classification based on our data clearly showed better progression-free survival and overall survival, as well as intravesical recurrence-free survival, in patients treated with laparoscopic radical nephroureterectomy., Conclusion: The findings reported here may help urologists predict oncological outcomes and to plan follow-up schedules after laparoscopic radical nephroureterectomy.

Background: Neoadjuvant chemotherapy before radical cystectomy for muscle-invasive bladder cancer is a commonly used treatment modality. However, in terms of chemotherapeutic regimens and the number of cycles of neoadjuvant chemotherapy, there is yet no international consensus, as various studies indicate the efficacy of several platinum-based combination chemotherapeutic regimens. We determined the efficacy of two cycles of neoadjuvant chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin followed by radical cystectomy., Patients and Methods: The study population included patients with clinical stage T2 - T4a, N0, M0 bladder cancer who underwent radical cystectomy. Clinical courses were compared between 27 patients treated with two cycles of M-VAC neoadjuvant chemotherapy and 25 treated with cystectomy alone., Results: The incidence of pT0 was 25.9% in the group treated with neoadjuvant chemotherapy. The probabilities of disease-free and cause-specific survival were significantly higher in patients treated with, than without neoadjuvant chemotherapy. On univariate Cox proportional hazards regression analysis for the patients treated with neoadjuvant chemotherapy, pathological stage and the pathological findings of venous involvement were significant prognostic factors., Conclusion: The results of this retrospective study demonstrated the clinical effectiveness of two cycles of neoadjuvant M-VAC chemotherapy for muscle-invasive bladder cancer.

Background: Percutaneous radiofrequency ablation (RFA) for small renal tumors has been reported to be effective in patients with poor surgical status. We retrospectively analyzed clinical outcomes, including renal function, after RFA., Patients and Methods: We retrospectively analyzed data of 24 patients with small renal tumors treated by RFA in our institution from January 2007 to November 2012., Results: A total of 36 tumors (35 renal cell carcinomas and one colon cancer metastasis) with a mean diameter of 21.1 mm (10-45 mm) in 24 patients were treated. Complete ablation was achieved in 22 patients (91.7%). There were two recurrences in other sites of the kidney (8.3%) and two distant metastases (8.3%) during the mean follow-up period of 21 months (1-57 months). No severe perioperative complications were observed. No significant difference in serum creatinine levels before and after RFA procedures in the 22 evaluable patients, nor in seven patients with a solitary kidney., Conclusion: RFA for small renal tumors is a safe treatment with sufficient preservation of renal function, even in patients with a solitary kidney.

Background: Prevention of the development of castration-resistant from hormone-naïve prostate cancer is an important issue in maintaining the quality of life of the patients. We explored the effect of 2'-hydroxyflavanone on proliferation and androgen responsiveness using prostate cancer cell lines., Materials and Methods: To investigate the effect of 2'-hydroxyflavanone on proliferation, prostate cancer cells were treated with 2'-hydroxyflavanone. Androgen-responsiveness in LNCaP cells was confirmed by luciferase assay after transfection of luciferase reporter driven by prostate specific antigen promoter. To detect androgen receptor (AR) expression, reverse transcriptase polymerase chain reaction and western blot analysis were conducted., Results: 2'-Hydroxyflavanone inhibited the proliferation of PC-3 and DU145 cells by induction of apoptosis. 2'-Hydroxyflavanone inhibited the proliferation of LNCaP cells stimulated by androgens and attenuated androgen-responsiveness through down-regulation of AR protein., Conclusion: 2'-Hydroxyflavanone not only inhibited proliferation of prostate cancer cells, but also repressed androgen-responsiveness, suggesting that it might be a useful agent in preventing recurrence of prostate cancer.

Background: The matricellular protein secreted protein acidic and rich in cysteine (SPARC) plays an important role on tumor metastasis and progression in several cancers. However, the roles of SPARC in prostate cancer (PCa) remain unclear., Methods: To identify SPARC protein in prostate tissue, immunohistochemical analysis of SPARC was conducted using human prostate tissue microarray. To detect SPARC expression in prostate cancer (LNCaP, DU145, and PC-3) and stromal cells, RT-PCR, western blot analysis, and ELISA was conducted. To reveal the function of exogenous SPARC in PCa cells, AKT phosphorylation was confirmed by western blot analysis after coculture with stromal cells. Proliferation and migration of PCa cells were examined by addition of SPARC. The interaction between SPARC and integrin β1 was confirmed by western blot analysis after immunoprecipitation., Results: SPARC protein was expressed well in normal tissue compared with PCa tissue. ELISA showed high secreted SPARC protein in normal prostate-derived stromal cell (PrSC) compared with PCa-derived stromal cell (PCaSC) and PCa. PCa cells cocultured with PrSC showed reduced AKT phosphorylation more than with PCaSC. PCa cells cocultured with PrSC whose SPARC was knocked-down restored AKT phosphorylation. Moreover, PCa cells treated with SPARC led to reduced AKT phosphorylation. Immunoprecipitation with SPARC revealed interaction of SPARC and integrin β1 in PCa cells. Inhibited proliferation and migration of PCa cells by SPARC was restored by integrin β1 neutralizing antibody., Conclusions: Reduced SPARC secretion from stromal cells might affect PCa progression mediating through limiting AKT phosphorylation after interaction with integrin β1., (Copyright © 2013 Wiley Periodicals, Inc.)

Aim: In order to investigate which types of localized prostate cancer can be treated most effectively by androgen deprivation therapy (ADT), cases of no residual cancer in radical prostatectomy specimens (pT0) after neoadjuvant ADT were analyzed., Patients and Methods: Patients with localized prostate cancer who underwent radical prostatectomy after neoadjuvant ADT were investigated retrospectively., Results: Thirty-two patients (24.2%) were diagnosed with pT0 disease by pathological evaluation. The positive-core proportion of prostate biopsy was lower, the duration of neoadjuvant ADT was longer, and prostate-specific antigen (PSA) nadir before radical prostatectomy was lower in pT0 cases compared to non-pT0 cases, and these differences were statistically significant. The percentage of pT0 cases with PSA nadir <0.2 ng/ml and <0.008 ng/ml before radical prostatectomy were 29.2% (21 out of 72 cases) and 83.3% (5 out of 6 cases), respectively. The positive-core proportion of prostate biopsy and PSA nadir before radical prostatectomy had a significant impact on pT0 status after neoadjuvant ADT., Conclusion: ADT for localized prostate cancer is thought to be highly effective in cases with low cancer volume. ADT is effective in cases of localized prostate cancer with PSA below the levels of detection by supersensitive PSA assay, and such cases show no cancer recurrence. Treatment options in such cases include intermittent or discontinuation of ADT.

Background: Robot-assisted laparoscopic radical prostatectomy (RALP) requires a steep Trendelenburg position and CO2 pneumoperitoneum for several hours to secure the surgical visual field. The present study was performed to investigate the influence of each angle of Trendelenburg position during RALP on cardiovascular and respiratory homeostasis., Methods: Forty-seven ASA physical status 1 and 2 patients underwent open retropubic radical prostatectomy (RRP) or RALP. Patients receiving RALP were randomized to undergo the operation in the 20°, 25° or 30° Trendelenburg position. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), end-tidal CO2 pressure (PetCO2 ), tidal volume (Vt), peak inspiratory pressure (PIP) and dynamic compliance (Cdyn) were recorded during the operation., Results: Angle of head-down tilt was significantly correlated with MAP, PIP and Cdyn, but not with HR, RR or PetCO2 . MAP decreased gradually over time in each group in the Trendelenburg position with pneumoperitoneum. As the angle of head-down tilt became stronger, MAP, RR, PetCO2 and PIP tended to increase and Cdyn tended to decrease., Conclusions: This study demonstrated that the degree of the head-down angle at RALP affected the cardiovascular and respiratory parameters. Pneumoperitoneum with head-down position in RALP influenced the cardiovascular and respiratory system to a greater extent than RRP, and these effects were stronger with deeper head-down angle., (Copyright © 2013 John Wiley & Sons, Ltd.)

Objective: We performed a retrospective review of clinical T1a renal cell carcinoma patients treated in our institution. The clinicopathological findings and patients' prognoses were analyzed according to tumor size, and risk factors for tumor recurrence were elucidated., Methods: A total of 140 cases of sporadic renal cell carcinoma with a diameter of 4 cm or less on computed tomography findings for preoperative evaluation were treated as clinical T1a. Patients underwent radical nephrectomy or nephron-sparing surgery, and were evaluated postoperatively every 3-6 months to screen for metastatic disease. Patients' medical records were reviewed retrospectively and the status of each patient was assessed., Results: There were four cases of clinically metastatic disease at diagnosis. There were no correlations between tumor size and pathological stage, Fuhrman nuclear grade or histological type. The rate of cases with microvascular invasion on pathological findings increased according to tumor diameter. Disease recurrence occurred in six patients (5.7%) during a mean postoperative follow-up of 41.7 months. There was a significant difference in the recurrence-free rate between pT1a patients with a tumor diameter of 31 mm or more and other patient groups. In terms of microvascular invasion on histological findings, the probability of non-recurrence at 7 years was 0% for patients with and 92.9% for those without microvascular invasion., Conclusions: Among T1a renal cell carcinoma, tumors over 30 mm in diameter may have aggressive biological potential, possibly due to microvascular invasion. Long-term follow-up is needed for these tumors.

Background: Ethinylestradiol was used as palliative treatment for patients with advanced prostate cancer (PCa). However, its use has declined after the development of combined androgen blockade. In the present study, we analyzed the effects of ethinylestradiol on pretreated castration-resistant PCa patients., Patients and Methods: Twenty-four Japanese patients were orally administered ethinylestradiol at a dose of 1.5 mg/day and prostate-specific antigen (PSA) was examined. We retrospectively analyzed the proportion of patients achieving a decline in PSA of >50% and progression-free and overall survival rates., Results: All patients had already been treated with combined androgen blockade followed by one or more salvage therapies. Median follow-up time was 227 (range: 42-1490) days and median ethinylestradiol treatment time was 195 (range: 3-791) days. The proportion of patients achieving a decline in PSA >50% was 70%. Median progression-free survival was estimated as 300 days. At the end of the follow-up period, one patient had died from PCa. Adverse events occurred in three patients, namely elevation of liver enzymes, anorexia, and heart failure in one patient each., Conclusion: Oral ethinylestradiol administration may be useful for treatment of advanced castration-resistant PCa after salvage therapy with a high PSA response rate and low adverse event rate.

Background: Tranilast is a therapeutic agent used in treatment of allergic diseases, although it has been reported to show anti-tumor effects on some cancer cells. To elucidate the effects of tranilast on prostate cancer, we investigated the mechanisms of its anti-tumor effect on prostate cancer., Methods: The anti-tumor effects and related mechanisms of tranilast were investigated both in vitro on prostate cancer cell lines and bone-derived stromal cells, and in vivo on severe combined immunodeficient (SCID) mice. We verified its clinical effect in patients with advanced hormone refractory prostate cancer (HRPC)., Results: Tranilast inhibited the proliferation of LNCaP, LNCaP-SF, and PC-3 cells in a dose-dependent manner and growth of the tumor formed by inoculation of LNCaP-SF in the dorsal subcutis and in the tibia of castrated SCID mice. Flow cytometry and TUNEL assay revealed induction of cell cycle arrest and apoptosis by tranilast. Tranilast increased expression of proteins involved in induction of cell cycle arrest and apoptosis. Coculture with bone-derived stromal cells induced proliferation of LNCaP-SF cells. Tranilast also suppressed secretion of transforming growth factor beta1 (TGF-beta1) from bone-derived stromal cells, which induced their differentiation. Moreover, tranilast inhibited TGF-beta1-mediated differentiation of bone-derived stromal cells and LNCaP-SF cell migration induced by osteopontin. In the clinical investigation, PSA progression was inhibited in 4 of 16 patients with advanced HRPC., Conclusions: These observations suggest that tranilast may be a useful therapeutic agent for treatment of HRPC via the direct inhibitory effect on cancer cells and suppression of TGF-beta1-associated osteoblastic changes in bone metastasis.

A 62-year-old man consulted our hospital complaining of macroscopic hematuria. Intravenous urography showed a dilated terminal portion of the left ureter resembling a cobra head. Cystoscopy revealed multiple tumors on the ureterocele. There were no metastatic lesions on CT and MRI. Transurethral resection of the tumor and the ureterocele was performed and the pathological examination revealed transitional cell carcinoma on the ureterocele. This is the 4th case of urothelial cancer on a simple ureterocele reported in Japan.

A 63-year-old man was admitted to our hospital complaining of painful urination. Urinalysis demonstrated pyuria and microscopic hematuria. Cystoscopy revealed the bladder tumor and the reddish mucosa. Transurethral biopsy was performed and the pathological examination showed transitional cell carcinoma in the bladder tumor and epithelioid granuloma in the reddish mucosa. Acid-fast bacilli smeas of urine sample and urine culture of Mycobacterium tuberculosis were positive. Therefore the treatment of urinary tuberculosis was started and the patient received intra-arterial chemotherapy combined with radiation. After the therapy, radical cystectomy and bilateral cutaneous ureterostomies were performed. Pathological study revealed transitional cell carcinoma and epithelioid granuloma in the removed bladder. The reports of urinary epithelial carcinoma with urinary tract tuberculosis were rare and, including our case, the 10 cases in Japanese literature are reviewed.