Kazuhiro Kurosawa

Impact of aging on penile hemodynamics in men responding normally to prostaglandin injection : A power Doppler study

Abstract

Loss of BAP1 protein expression in the first metastatic site predicts prognosis in patients with clear cell renal cell carcinoma

OBJECTIVES To investigate the intratumoral heterogeneity of BAP1 and PBRM1 expression at the primary site and metastatic sites and to evaluate whether BAP1 and PBRM1 expression in metastatic sites of clear cell renal cell carcinoma (ccRCC) has prognostic value. METHODS AND MATERIALS We collected paired samples from the primary site and the first metastatic site in 41 patients with ccRCC. Immunohistochemistry analyses were performed for the expression of BAP1 and PBRM1 proteins. We retrospectively analyzed the associations between the expression of BAP1 and PBRM1 and overall survival (OS). RESULTS The most common first metastatic sites were lung (68.3%) and lymph node (12.2%). BAP1 protein expression was negative in 8 (19.5%) primary sites and in 11 (26.8%) metastatic sites. PBRM1 protein expression was negative in 9 (22.0%) primary sites and in 11 (26.8%) metastatic sites. The incidences of intratumoral heterogeneity for BAP1 and PBRM1 protein expression in primary/metastatic sites were 9.8%/2.4% and 24.4%/7.3%, respectively. The concordance rates between primary and metastatic sites for BAP1 and PBRM1 protein expression were 82.9% and 63.4%, respectively. Median OS from the first occurrence of metastasis in patients with BAP1-positive and BAP1-negative metastatic sites were 97 months (95% CI: 58-136) and 51 months (95% CI: 13-82), respectively (P = 0.0077). Median OS in patients with PBRM1-positive and PBRM1-negative metastatic sites were 82 (95% CI: 42-97) and 120 (95% CI: 52-120) months, respectively (P = 0.25). CONCLUSION Intratumoral heterogeneity of BAP1 protein expression is more frequent in primary tumor than in metastatic sites. The loss of BAP1 protein expression in metastatic sites predicts poor prognosis in patients with ccRCC.

Clinicopathological characteristics of patients with upper urinary tract urothelial cancer with loss of immunohistochemical expression of the DNA mismatch repair proteins in universal screening

To assess the detection rate of putative Lynch syndrome‐associated upper urinary tract urothelial cancer among all upper urinary tract urothelial cancers and to examine its clinicopathological characteristics.

Effect of Lymphadenectomy During Radical Nephroureterectomy in Locally Advanced Upper Tract Urothelial Carcinoma

Micro‐Abstract The role of lymph node dissection (LND) for upper tract urothelial carcinoma (UTUC) patients remains controversial. We investigated the effect of LND on clinical outcomes during radical nephroureterectomy. In the ≥pT3 subgroup, disease‐free survival and cancer‐specific survival times were significantly prolonged in the pN0 group. LND for patients with locally advanced UTUC might improve disease prognosis. Background: The role of lymph node dissection (LND) for upper tract urothelial carcinoma (UTUC) patients remains controversial. The aim of this study was to evaluate the effect of LND on clinical outcomes during radical nephroureterectomy (RNU) and to determine prognostic factors of survival. Patients and Methods: From 1985 to 2013, 404 patients with UTUC underwent RNU; 5 patients who received neoadjuvant chemotherapy were excluded. Among them, 182 (46%) were pathologically negative for lymph node metastasis (pN0), 177 (44%) were non‐LND (pNx), and 40 (10%) were positive for lymph nodes metastasis (pN1/2). Results: The 5‐year disease‐free survival (DFS) and cancer‐specific survival (CSS) rate were higher in pN0 patients than in pNx patients and in pN1/2 patients. According to multivariate analysis, non‐LND was an independent predictive factor of DFS (hazard ratio [HR], 1.91; P = .004) and CSS (HR, 2.28; P = .003). In the subgroup with muscle‐invasive UTUC, the 5‐year DFS and CSS rates were higher in pN0 patients than in pNx patients. However, there was no statistical difference between pN0 and pNx groups in terms of DFS and CSS in the pT2 cases. DFS and CSS times were significantly prolonged in the pN0 group in the locally advanced UTUC patients (≥pT3). Conclusion: In the ≥pT3 subgroup, the 5‐year DFS and CSS were significantly prolonged in the pN0 group, but there were no statistical differences between pN0 and pNx groups in terms of DFS and CSS in the pT2 subgroup. LND for patients with locally advanced UTUC might improve disease prognosis.

The loss of BAP1 protein expression predicts poor prognosis in patients with nonmetastatic clear cell renal cell carcinoma with inferior vena cava tumor thrombosis

OBJECTIVES Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC) and is associated with poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts poor prognosis. The aim of this study was to elucidate the association between BAP1 protein expression and clinicopathological outcomes in patients with nonmetastatic ccRCC with an IVC tumor thrombus (IVCTT). MATERIAL AND METHODS Thirty-five patients with nonmetastatic ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy at our institution from 1999 to 2010 were retrospectively evaluated. Immunohistochemical (IHC) analyses were performed for the expression of BAP1 protein, and the associations between the expression of BAP1 and clinical outcomes were assessed. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate analyses of the associations between disease-free survival (DFS) and clinical variables including BAP1 protein expression, tumor size, Karnofsky performance status (KPS) score, and the extension level of the tumor thrombus were performed using a Cox proportional hazard model. RESULTS The median follow-up time was 58.8 months (range: 2-130 months). The median age was 68 years (range: 37-80 years). The median size of the primary tumor was 9.6cm (range: 3.0-15.0cm). The IVCTT extended above and below the diaphragm in 10 (28.6%) and 25 (71.4%) patients, respectively. The KPS score was>80 in 23 patients (65.7%). BAP1 protein expression on IHC was positive in 24 cases (68.8%) and negative in 11 cases (31.2%). The median overall survival in cases with BAP1-negative and -positive tumor on IHC staining were 44.7 and 81.5 months, respectively (P = 0.052). BAP1-negative tumor on IHC staining was associated with a significantly shorter DFS than BAP1-positive tumor (median DFS = 10.0 vs. 26.0 months, respectively; P = 0.011). Multivariate analysis showed that only BAP1-negative tumor on IHC staining was significantly associated with shorter DFS (P = 0.004). CONCLUSIONS Patients whose tumors had loss of BAP1 protein expression were significantly associated with poor prognosis in patients with ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy.

Effect of tadalafil add-on therapy in patients with persistant storage symptoms refractory to α1-adrenoceptor antagonist monotherapy for benign prostatic hyperplasia: A randomized pilot trial comparing tadalafil and solifenacin

The aim of this study was to investigate the efficacy and safety of tadalafil add‐on therapy with α1‐adrenoceptor antagonists.

IMPORTANCE OF SCREENING FOR LUNG LYMPHANGIOLEIOMYOMATOSIS AMONG RENAL ANGIOMYOLIPOMA CASES

(Background) Multiple renal angiomyolipoma (AML) may develop concurrently with tuberous sclerosis complex (TSC) and lung lymphangioleiomyomatosis (LAM). In recent years, an increase in subjects undergoing chest computed tomography examinations, including medical examinations, has been accompanied by an increase in LAM cases that are diagnosed while still asymptomatic. Surgical treatment may also be performed for renal AML to prevent bleeding. We clarified the clinical features of AML that is complicated by LAM, and discussed the significance of screening for LAM. (Methods) Between January 1, 2006 and April 30, 2014 two groups, comprising 7 patients with LAM (LAM-AML group) and another 26 patients without LAM (sporadic AML group), were compared with regard to findings for renal AML such as imaging examinations, pathological features, and treatment course. Screening for LAM was chest CT scanning. (Results) In the LAM-AML group, there were younger and more female cases and tumors tended to be multiple, large and bilateral. 85.7% of cases underwent surgery. On the other hand, in the sporadic group 73.1% of cases were followed up without treatment. There was no preoperative lung screening except the one TSC case and all 5 LAM cases were diagnosed postoperatively. One LAM patient was symptomatic and eventually required lung transplantation, while all other LAM cases were handled by monitoring the course, without treatment. (Conclusion) Many cases of asymptomatic LAM are untreated. However, the poor prognosis, risk of a need for general anesthesia, and potential for renal sparing by selection of pharmacotherapy must be taken into account. In that light-especially in the case of young women-patients with multiple renal AML should undergo preoperative screening for LAM.

Impact of adjuvant chemotherapy on patients with pathological Stage T3b and/or lymph node metastatic bladder cancer after radical cystectomy

OBJECTIVE To evaluate the effectiveness of adjuvant chemotherapy in patients with pathological Stage T3 bladder cancer who had undergone radical cystectomy, and to determine the prognostic survival factors for adjuvant chemotherapy treatment. METHODS From January 1990 to October 2013, 202 patients underwent radical cystectomy and pelvic lymphadenectomy. Among them, 65 patients with non-organ-confined disease (pT3, N0-3, M0) diagnosed were investigated in this study. Thirty-one patients (48%) were treated with adjuvant chemotherapy and the remaining 34 patients (52%) were not. RESULTS Median age of all patients was 66 years, and median follow-up was 26.1 months. For all pT3 patients, overall survival and disease-free survival times were similar in the adjuvant chemotherapy and non-adjuvant chemotherapy groups. However, in the pT3b subgroup, median overall survival (47.0 vs. 10.6 months) and median disease-free survival (35.5 vs. 5.3 months) times were significantly prolonged for those who underwent adjuvant chemotherapy (P = 0.009 and 0.025). In patients with pathological lymph node metastatic (pN+), median overall survival (30.1 vs. 6.4 months) and median disease-free survival (15.7 vs. 3.5 months) times were significantly prolonged in the adjuvant chemotherapy group (P = 0.016 and 0.027). In addition, according to multivariate analysis in pT3b and/or pN+ subgroup patients, adjuvant chemotherapy status was an independent predictive factor for overall survival and disease-free survival. CONCLUSION Adjuvant chemotherapy did not significantly improve overall survival and disease-free survival when compared with all patients with pT3 who had received radical cystectomy in the non-adjuvant chemotherapy group. However, in the pT3b and pN+ subgroup, adjuvant chemotherapy demonstrated statistically significant benefits regarding overall survival and disease-free survival. Although these results could not support adjuvant chemotherapy use for all pT3 patients, the pT3b substage and/or pN+ may help identify patients with pT3 who could benefit from adjuvant chemotherapy.