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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

Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported.The study included 97 patients with advanced UC whose lesions were classified according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median age was 73 years. Nineteen patients (20%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The efficacy, safety, and risk factors for prognosis were evaluated for patients with and without measurable lesions.The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8-4.7) and 11.8 months (95% CI: 6.7-17.0), respectively. Twenty-one (22%) patients had no measurable lesions per RECIST. In univariate and multivariate analysis, PS 2-4 and lesions by RECIST were identified as factors associated with short overall survival (OS). The median OS of 18.3 months in patients without lesions by RECIST was significantly longer than the median OS of 6.7 months in patients with lesions by RECIST (p = .012).We demonstrated that good PS 0-1 and no measurable lesions, especially small lesions, by RECIST were favorable prognostic factors in patients with advanced UC treated by pembrolizumab.

Background: Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported.Methods: The study included 98 patients with advanced UC who were treated with pembrolizumab after platinum-based chemotherapy at eight hospitals. The efficacy, safety, and risk factors for prognosis were evaluated. Results: The median age was 73 years. Nineteen patients (19%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8–4.7) and 11.8 months (95% CI: 6.7–17.0), respectively. Poor PS, liver metastasis, and higher C-reactive protein were poor prognostic factors. Hyperprogression was observed in nine patients (9%), who were mostly of poor PS and had high-volume lesions. Severe adverse events (AEs) were observed in 18 patients (19%), and five patients died because of AEs (5%). Atypical AEs, such as pneumocystis pneumonia and acute myeloid leukemia, were observed in our cohort. Conclusion: The efficacy of pembrolizumab for advanced UC in our cohort was better than a previous phase III trial (KEYNOTE-045), possibly owing to lower cancer volume and fewer visceral metastases in our patients.

金沢大学医学部附属病院泌尿器科, Aim: Bisphosphonates are well established for the management of cancer-induced skeletal complications. Recent studies suggest that bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites. To determine the direct effects of bisphosphonate on prostate cancer, we examined the effects of minodronate on prostatic cancer cell growth and the expression of apoptosis-related proteins and osteoclastogenic factors. Methods: PC-3, DU145 and LNCaP cells were treated with amino-bisphosphonate minodronate. Then proliferation, apoptosis and expression of bcl-2, bax, poly (ADP)-ribose polymerase (PARP), caspase-3, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinases-2 (MMP-2), and parathyroid hormone related protein (PTHrP) were assessed. Results: The proliferation of prostatic cancer cells was inhibited by minodronate. DNA fragmentation and TUNEL-positive nuclei were observed in minodronate-treated PC-3 cells. Minodronate decreased bcl-2 expression and induced bax expression, caspase-3 activity and degradation of PARP in DU145 and PC-3 cells. Minodronate decreased expression of RANKL, PTHrP and MMP-2 in PC-3 cells. Conclusions: Our results suggest that bisphosphonate not only promotes apoptosis directly but also decreases pro-osteoclastic gene expression in prostate cancer cells.

Objective To investigate the relationship between the expression of the 150-kDa oxygen-regulated protein (ORP150, which functions as a molecular chaperone in the endoplasmic reticulum for the folding and trafficking of newly synthesized proteins) and the aggressiveness of bladder cancer, and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs), as the former is a secreting protein through the endoplasmic reticulum and the latter are closely involved in tumour invasion. Materials and methods Thirty-nine cystectomy specimens, comprising 12 superficial (pT1) and 27 invasive (pT2–pT4) tumours, were immunohistochemically analysed using antibodies against ORP150, VEGF, MMP-1, MMP-2 and MMP-9. Staining was scored from 0 to 3, according to the ratio of positively staining cells. Results Staining was positive (score 1–3) for ORP150 in 10 of 12 superficial and 25 (93%) of the invasive tumours, with a significantly higher staining score for stage T4 than stage T1 tumours. The trend was the same for the staining score of MMP-2, and there was a significant correlation between ORP150 and MMP-2 expression. Conclusions The expression of ORP150 was common in bladder cancer, with a tendency for greater expression in higher stages. The significant correlation between ORP150 and MMP-2 expression suggests that ORP150 acts as a molecular chaperone for MMP-2 secretion and thus tumour invasion.

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 with localized prostate cancer who underwent radical prostatectomy after neoadjuvant ADT were investigated retrospectively.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 nadir0.2 ng/ml and0.008 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.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.

Bone is the most common site of metastatic disease in prostate cancer, and bone metastases are a significant cause of morbidity due to pain, pathological fractures and hypercalcemia. Bisphosphonates, which inhibit osteoclast mediated bone resorption, are standard care for tumor associated hypercalcemia, and have been shown to decrease bone pain, improve quality of life and delay skeletal events. Recently bisphosphonates have been demonstrated to exhibit antitumorigenic effects. We report a case of hormone refractory prostate cancer in which serum prostate specific antigen (PSA) and bone pain were decreased with bisphosphonate treatment. To our knowledge this is the first such case reported in the literature. CASE REPORT

A distance learning experiment was conducted to examine differences in learning performance and to obtain subjective evaluations of three types of learning methods: face-to-face (LIVE), distance learning using high-definition television (HDTI9, and distance learning using normal TV (NTSC). Five sites were used for HDTV and six sites for NTSC, where the same lecture was watched at the same time. There were 74 voluntary participants for the LIVE lecture, 144 for HDTV, and 139 for NTSC. Based on pretest, posttest, and questionnaire results, the authors found that, as far as the learners’ performance level is concerned the LIVE method is more effective than the others, while there was no significant difference between HDTV and NTSC. It was also found that HDTV is better at showing the atmosphere of the lecture, and motivates learners more than NTSC. Third HDTV still has difficulty in showing a high-resolution computer screen, though it is perceived better than NTSC. As for other points, HDTV’s image quality is satisfactory to learners as a whole.