Go Tanigawa

Prostatic Inflammation Detected in Initial Biopsy Specimens and Urinary Pyuria are Predictors of Negative Repeat Prostate Biopsy

PURPOSE Asymptomatic prostatic inflammation may cause increased prostate specific antigen in some men, leading to unnecessary repeat prostate biopsy. We determined whether histological findings of inflammation in initial biopsy specimens and/or clinical indicators of inflammation could predict the outcome of subsequent biopsy in men with a negative initial biopsy. MATERIALS AND METHODS A total of 105 Japanese men with increased prostate specific antigen underwent repeat prostate biopsy after initial biopsy revealed no evidence of carcinoma. Of the cases 45 (42.8%) were positive for prostate cancer at repeat biopsy. We evaluated initial biopsy specimens for evidence of inflammation by mononuclear and polymorphonuclear leukocytes, serum and urinary white blood count, and C-reactive protein. RESULTS Polymorphonuclear leukocyte infiltrates, urinary white blood count, patient age, prostate specific antigen at repeat biopsy, prostate volume, prostate specific antigen velocity and prostate specific antigen density were associated with the repeat biopsy outcome (p <0.05). Multivariate analysis revealed that age, prostate specific antigen density and urinary white blood count were independent predictors of outcome. On subgroup analysis of 63 men with serum prostate specific antigen less than 10 ng/ml before initial biopsy polymorphonuclear and mononuclear leukocyte inflammation, age, prostate specific antigen at repeat biopsy, prostate volume, prostate specific antigen velocity and prostate specific antigen density were associated with the outcome of repeat biopsy (p <0.05). Multivariate analysis showed that polymorphonuclear leukocyte infiltrate, prostate specific antigen density and age were independent predictors. CONCLUSIONS Age, prostate specific antigen density, polymorphonuclear leukocyte inflammation in initial biopsy specimens and urinary pyuria are indicators of benign repeat biopsy. They help avoid unnecessary repeat biopsy in men with increased prostate specific antigen.

Clinical characteristics and risk factors for septic shock in patients receiving emergency drainage for acute pyelonephritis with upper urinary tract calculi

BackgroundAcute pyelonephritis (APN) is a common complication of ureteral obstruction caused by urolithiasis, and it can be lethal if it progresses to septic shock. We investigated the clinical characteristics of patients undergoing emergency drainage and assessed risk factors for septic shock.MethodsA retrospective study was performed of 98 patients (101 events) requiring emergency drainage at our urology department for obstructive APN associated with upper urinary tract calculi from January 2003 to January 2011. Clinical characteristics were summarized, and risk factors for septic shock were assessed by logistic regression analysis.ResultsObjective evidence of sepsis was found in 64 (63.4%) events, and 21 events (20.8%) were categorized as septic shock. Ninety-six patients recovered, but 2 patients died of septic shock. Multivariate analysis revealed that age and the presence of paralysis were independent risk factors for septic shock.ConclusionsAPN associated with upper urinary tract calculi is a severe disease that should be treated with caution, particularly when risk factors are present.

Clinical Outcome and Prognostic Factors of Sorafenib in Japanese Patients with Advanced Renal Cell Carcinoma in General Clinical Practice

OBJECTIVE Effects of sorafenib in general clinical practice, especially those with patients of Asian ethnicity, have been rarely investigated. We assessed efficacy, safety and prognostic factors for progression-free survival in Japanese patients receiving sorafenib for advanced renal cell carcinoma. METHODS We performed a retrospective analysis of 159 Japanese patients with renal cell carcinoma. Progression-free survival was estimated by the Kaplan-Meier method. Objective response (per Response Evaluation Criteria in Solid Tumors) and safety were assessed. Cox proportional hazards model was used to identify independent prognostic factors for progression-free survival. RESULTS The median progression-free survival was 9.0 months (95% confidence interval, 7.5-10.6 months). In 142 patients with measurable lesions, the objective response rate was 21.8%, and disease control was achieved in 85 (59.9%) patients. Adverse events of any grade occurred in 152 patients (95.6%). Most common adverse events causing discontinuation or interruption of sorafenib were hand-foot skin reaction (22%), rash (10.7%) and liver dysfunction (10.7%). Dose reduction or therapy interruption due to adverse events was required in 128 patients (80.5%). Univariate and multivariate analysis revealed that favorable prognosis according to Memorial Sloan-Kettering Cancer Center prognostic factors and relative dose intensity during the first month of treatment of ≥50% were significant factors for predicting superior progression-free survival with sorafenib treatment. CONCLUSIONS Sorafenib was effective in Japanese patients with advanced renal cell carcinoma in general clinical practice and was tolerated although most patients required dose reduction or interruption of therapy. Future studies should establish new strategies for treatment without sacrificing both efficacy and patient quality of life.

Impact of hyponatremia on survival of patients with metastatic renal cell carcinoma treated with molecular targeted therapy

Objectives:  Hyponatremia is reported to be associated with poor survival in localized renal cell carcinoma and metastatic renal cell carcinoma treated with immunotherapy. However, there are no reports on the relationship between hyponatremia and prognosis of metastatic renal cell carcinoma treated with molecular targeted therapy. We evaluated the prognostic significance of hyponatremia in metastatic renal cell carcinoma treated with molecular targeted therapy as first‐line therapy.

One-month relative dose intensity of not less than 50% predicts favourable progression-free survival in sorafenib therapy for advanced renal cell carcinoma in Japanese patients

BACKGROUND Sorafenib is a multikinase inhibitor used as a second-line treatment for metastatic renal cell carcinoma (mRCC). However, it is very difficult to estimate sorafenib dosage because it is difficult to maintain stable administration and dosage intervals due to several side-effects. We examined the correlation between relative dose intensity (RDI) and clinical outcome of sorafenib therapy in a multi-institutional study. METHODS A study population of 70 first-line therapy-refractory patients with pathologically confirmed RCC was eligible for this investigation. Clinical outcomes were evaluated according to clinicopathological features and RDI for 1 month (1M-RDI). RESULTS There was significant difference in progression-free survival (PFS) time but not overall survival (OS) time when the 1M-RDI cut-off value was ≥ 50%. In 15 patients (21.4%) with 1M-RDI of <50%, median PFS time was 4.1 months (95% I collagen (95% CI): 2.0-6.2), whereas it was 10.5 months (95% CI: 7.6-13.4) in the patients with 1M-RDI of ⩾50% (P=0.022). Multivariate analysis showed 1M-RDI status to be significantly associated with PFS (HR: 3.838, 95% CI: 1.658-8.883, P=0.002) but not OS (P=0.328). CONCLUSION Although this study was retrospective, a 1M-RDI cut-off value of ≥ 50% for sorafenib may be the first factor to predict PFS but not OS in cytokine pretreated mRCC patients. The data indicate that a dose of 400mg/day of sorafenib administered successively for the first one month was necessary to prolong disease stabilisation and could be tolerated by Japanese patients.

MiR-21-5p in urinary extracellular vesicles is a novel biomarker of urothelial carcinoma

Background Extracellular vesicles are lipid bilayer vesicles containing protein, messengerRNA and microRNA. Cancer cell-derived extracellular vesicles may be diagnostic and therapeutic targets. We extracted extracellular vesicles from urine of urothelial carcinoma patients and the control group to identify cancer-specific microRNAs in urinary extracellular vesicles as new biomarkers. Materials and methods microRNA from urinary extracellular vesicles extracted from 6 urothelial carcinoma patients and 3 healthy volunteers was analyzed. We verified candidate microRNAs in an independent cohort of 60 urinary extracellular vesicles samples. To normalize the microRNA expression level in extracellular vesicles, we examined the following in extracellular vesicles: protein concentration, CD9 intensity, amounts of whole miRNAs, RNA U6B small nuclear expression and the creatinine concentration of original urine correlating with the counts of extracted extracellular vesicles measured by the NanoSight™ system. RESULTS From the microarray results 5 microRNAs overexpressed in urinary extracellular vesicles of urothelial carcinoma patients were identified. Creatinine concentration of original urine correlated most with particle counts of extracellular vesicles, indicating that creatinine could be a new tool for normalizing microRNA expression. MiR-21-5p was the most potent biomarker in urinary extracellular vesicles (sensitivity, 75.0%; specificity, 95.8%) and was also overexpressed in urinary extracellular vesicles from urothelial carcinoma patients with negative urine cytology. For the subgroup with negative urine cytology, the sensitivity was 75.0% and specificity was 95.8%. Conclusion MiR-21-5p in urinary extracellular vesicles could be a new biomarker of urothelial carcinoma, especially for urothelial carcinoma patients with negative urine cytology.

Preoperative serum sodium is associated with cancer‐specific survival in patients with upper urinary tract urothelial carcinoma treated by nephroureterectomy

To assess the impact of preoperative serum sodium concentration on the prognosis of patients with upper urinary tract urothelial carcinoma treated by nephroureterectomy.

White blood cell count is positively associated with benign prostatic hyperplasia

To determine whether low‐grade systemic inflammation is associated with prostatic enlargement/benign prostatic hyperplasia.

Endoglin expression in upper urinary tract urothelial carcinoma is associated with intravesical recurrence after radical nephroureterectomy

To evaluate the expression and prognostic significance of endoglin in patients with upper urinary tract urothelial carcinoma.

Role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma and the prognostic significance of C-reactive protein: A multi-institutional, retrospective study

To analyze the role of adjuvant chemotherapy in lymph node‐positive patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy, and identified the prognostic adjuvant chemotherapy parameters.