Mari Ohtaka

Lack of an Association between Neutrophil-to-Lymphocyte Ratio and PSA Failure of Prostate Cancer Patients Who Underwent Radical Prostatectomy

Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (p = 0.834), pathological T stage (p = 0.082), lymph node metastasis (p = 0.062), or resection margin status (p = 0.772). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy.

Low-molecular-weight protein tyrosine phosphatase expression as a prognostic factor for men with metastatic hormone-naïve prostate cancer

OBJECTIVES Recent studies have demonstrated that up-front docetaxel combined with androgen deprivation therapy (ADT) prolongs survival in some patients with metastatic hormone-naïve prostate cancer (mHNPC). However, new biomarkers for selecting personalized treatment strategies for mHNPC are warranted. We evaluated the value of low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression as a prognosticator in men with mHNPC. METHODS AND MATERIALS A total of 48 men with mHNPC diagnosed from 2003 to 2009 were enrolled in this study. Prostate cancer tissues obtained by needle biopsies were immunohistochemically stained for LMW-PTP. Correlations between LMW-PTP expression and clinicopathological characteristics were then assessed. RESULTS At the time of analysis, 29 (60.4%) patients were alive, whereas 15 (31.3%) and 4 (8.3%) died of prostate cancer and nonprostate cancer, respectively. Of these, 29 (60.4%) had low LMW-PTP expression and 19 (39.6%) had high expression. Median overall survival (OS) for patients with high LMW-PTP expression was not reached and that for patients with low LMW-PTP expression was 23.8 months. High LMW-PTP expression was significantly correlated with a shorter OS compared with low LMW-PTP expression (P = 0.01). Moreover, multivariate analysis showed that Gleason score (≥8 vs.≤7; HR = 5.8, 95% CI: 1.3-26.5, P = 0.02) and LMW-PTP expression (high vs. low; HR = 2.7, 95% CI: 1.0-7.2, P = 0.04) were independent prognostic factors for OS. CONCLUSIONS LMW-PTP is a potential biomarker to predict OS in patients with mHNPC.

RANK/RANKL expression in prostate cancer

Highlights • Expression of RANK and RANKL genes in prostate cancer is higher than non-neoplastic prostate.• RANK/RANKL expression is not related to pathological features.• There is no significant correlation of RANK/RANKL expression with biochemical recurrence after radical prostatectomy.

Prediction of Time to Castration-Resistant Prostate Cancer Using Low-Molecular-Weight Protein Tyrosine Phosphatase Expression for Men with Metastatic Hormone-Naïve Prostate Cancer

Introduction: Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression affects carcinogenesis in various cancers and has been associated with determining the overall survival among men with metastatic hormone-naïve prostate cancer (mHNPC). In this study, we analyzed the value of LMWPTP for prediction of time to castration-resistant prostate cancer (CRPC) for men with mHNPC. Materials and Methods: We retrospectively enrolled 45 men with mHNPC who were diagnosed from 2003 to 2009. All patients had received androgen deprivation therapy as first-line treatment. Prostate cancer tissues (pre-treatment needle biopsies) were immunohistochemically stained for LMW-PTP. Multivariate analyses (Cox proportional hazard model) were used to correlate baseline clinical factors of age, prostate-specific antigen (PSA), Gleason scores, T stage, N stage, extent of disease on bone scan (EOD), LMW-PTP expression and time to CRPC. Continuous variables were classified as dichotomous. Results: Median age and PSA were 70.0 years and 87.8 ng/mL respectively. Median time to CRPC was 40.2 months. Median time to CRPC was significantly shorter in the high LMW-PTP group (14.8 months) than that in the low LMW-PTP group (86.3 months, p < 0.01). In multivariate analysis, age ≥70 years and high LMW-PTP expression were significant predictors of time to CRPC.

A case of long-term survival in a kidney transplantation patient with progressive multifocal leukoencephalopathy: Case Report

Post-kidney transplantation progressive multifocal leukoencephalopathy (PML) is a rare disease on which there are very few published reports on record. PML is a demyelinating disease caused by a destructive infection of the oligodendrocytes by the JC polyomavirus. No effective therapeutic protocol has been established other than measures to revive the immune function by reducing or discontinuing the administration of immunosuppressive agents. Most cases are progressive and show a poor prognosis. We herein report a case in which renal function has been maintained for 2 years following the onset of PML, which was initially diagnosed 3 years after kidney transplantation.

Expression of receptor activator of nuclear factor kappa B ligand in bladder cancer

DOI: 10.1111/iju.13756 The bone is a frequent site of metastasis in various malignancies, such as prostate and mammary cancers. In contrast, the incidence of bone metastasis in patients with advanced bladder cancer was reported to be 40%, and approximately 13% of bladder cancer patients undergoing radical cystectomy were shown to develop bone metastasis within 5 years after surgery. Importantly, skeletal-related events consisting of pathological fracture, spinal cord compression and intractable pain reduce the quality of life. Meanwhile, denosumab (XGEVA; Amgen, Thousand Oaks, CA, USA), a human monoclonal antibody against RANKL, was found to be a new therapeutic option for bone metastasis. Cancer cells penetrate the bone marrow and induce osteoblasts to produce cytokines, which promotes the secretion of RANKL. The accelerated expression of RANKL induces osteoclast hyperplasia and facilitates bone resorption. Denosumab controls these mechanisms by inhibiting RANK. Previous studies showed that primary prostate cancer cells expressed the RANK and RANKL genes, and that their expression was further elevated in lesions of bone metastasis. Thus, denosumab is expected to exert its antitumor effect by inhibiting RANKL. To the best of our knowledge, no studies have assessed the expression of RANKL in bladder cancer. The institutional review board of Yokohama City University Medical Center (Yokohama, Japan) approved this study (no. D1507018). Sections from a bladder tissue microarray composed of 136 malignant tissues, 40 nonmalignant tissues and 36 bladder cancer tissues with prognosis information (US Biomax, Rockville, MD, USA) were subjected to immunohistochemical staining using a primary antibody to RANKL (MAB626-100, diluted to 1:200; RSD, Minneapolis, MN, USA) and RANK (sc-9072, diluted to 1:100; Santa Cruz Biotechnology, Dallas, TX, USA). Two genitourinary pathologists blinded to the identity of the sample then examined the slides. Overall, the expression levels of RANKL in bladder cancer tissue specimens were significantly (P < 0.001) higher than those in non-cancerous tissue specimens (Table 1; Fig. S1). Although the higher RANKL expression group showed a worse prognosis, no significant associations between the RANK/RANKL expression and the clinicopathological features, including the prognosis, tumor grade and pT stage, were observed (Table 1; Tables S1, S2; Fig. S2). We also carried out an in vitro study using UMUC-3 bladder cancer cells with a cell invasion assay (Fig. S3), cell migration assay (Fig. S4), cell proliferation assay (Fig. S5) and cell cycle analysis using flow cytometry (Table S3) with Si-Control and Si-RANKL RNA. The protocol has already been described in detail. When we knocked down RANKL, the cell migration of UMUC-3 decreased, and their apoptosis increased significantly. However, no significant differences were observed in the invasion. In contrast, RANKL knockdown in UMUC-3 increased the cell proliferation. Further studies are required to confirm the progression of bladder cancer through the RANKL pathway. Several studies have determined the levels of RANKL expression in urological malignancies, including renal and prostate cancers. Mikami et al. showed that the elevated expression of RANKL and RANK in renal cell carcinoma was an independent predictor of tumor recurrence and bone metastasis. Chen et al. reported that the increased expression of RANKL/RANK was correlated with higher Gleason score, TNM stage or serum prostate-specific antigen levels, as well as androgen dependence in prostate cancer patients. In the present study, we found that RANKL expression was upregulated in bladder cancers compared with non-malignant urothelial specimens. However, there were no significant correlations between RANKL expression and clinicopathological features available for the patient cohort. In summary, the present study showed that RANKL was overexpressed in bladder cancer. However, its functional role in bladder cancer, especially tumor progression and metastasis, remains uncertain. Further investigation in a larger study population is required to validate the current results. Urological Notes

The neutrophil-to-lymphocyte ratio is an effective prognostic marker in localized upper urinary tract urothelial carcinoma treated with nephroureterectomy

Background: Recent studies have revealed that the neutrophil-to-lymphocyte ratio (NLR) is an independent prognostic factor for several types of malignancies including urological cancers. We herein evaluated the significance of NLR in localized upper urinary tract urothelial carcinoma (UUT-UC) treated with surgery. Methods: A total of 60 patients who underwent radical nephroureterectomy at our institution from 1995 to 2015 were evaluated. The association between preoperative NLR and the prognosis was analyzed. Results: The higher NLR (≥2.43) group showed a significantly poorer overall survival (p = 0.007) than the lower NLR group. There was no association between NLR and recurrence-free survival (p = 0.213). High-grade tumors tended to show higher NLRs (p = 0.068), which significantly correlated with the cancer grade (p < 0.01) and muscle invasion (p=0.02). In contrast, the NLR did not correlate with lymph node metastasis (p =0.69). According to a multivariate analysis, the NLR was an independent risk factor for the overall survival (p = 0.008, HR =12.194). Conclusions: Preoperative NLR is therefore considered to be a useful biomarker to predict the prognosis of the patients with UUT-UC treated with radical nephroureterectomy. Abbreviations: NLR: Neutrophil to Lymphocyte Ratio, UUT-UC: Upper Urinary Tract Urothelial Carcinoma

Epidermal Cyst in the Scrotum Successfully Treated while Preserving the Testis: A Case Report

A 66-year-old male was referred to our hospital for further examination of a scrotal mass. Because of the risk of testicular cancer, we first clamped the vessels as a course of higher orchiectomy. Then, we approached the tumor through the scrotum and successfully resected it while preserving the testis. A histopathological diagnosis revealed an epidermal cyst. We herein report a rare case of an intrascrotal epidermal cyst successfully treated while preserving the testis.

Inflammatory Myofibroblastic Tumor in the Bladder: A Case Report.

A 36-year-old male was referred to our department for further examination of asymptomatic gross hematuria emanating from a bladder tumor. Cystoscopy revealed a broad-based tumor 40 mm in diameter. Urinary cytology was negative. Preoperative magnetic resonance imaging suggested a muscle invasive tumor. Transurethral resection was performed, and the pathological findings revealed an inflammatory myofibroblastic tumor. We herein report a rare case of bladder inflammatory myofibroblastic tumor.

Ureteroscopy-Assisted Biopsy for a Retroperitoneal Tumor: A Case Report

Introduction: Retroperitoneal tumor is often seen in urology clinical practice. To diagnose the tumor, tumor specimens must be obtained. However, in some cases, the tumor is penetrated by vessels around the ureter, and it may be difficult to detect the optimal spot for obtaining a specimen, even when performing open surgery. Case Presentation: A 53-year-old male patient was referred to our hospital for further examination of left back pain due to hydronephrosis. Enhanced computed tomography demonstrated ureter stenosis in front of the ilium, which was surrounded by a retroperitoneal tumor. The tumor was penetrated by blood vessels; therefore, we performed an open surgical biopsy on the suspicion of a retroperitoneal tumor using ureteroscopic assistance. The diagnosis of idiopathic retroperitoneal fibrosis was made according to the biopsy. Conclusion: We herein report the first case of a ureteroscopy-assisted biopsy for the pathological diagnosis of a retroperitoneal tumor.