Yoshitatsu Fukabori

Prostate cancer detection with 3 T MRI: Comparison of diffusion‐weighted imaging and dynamic contrast‐enhanced MRI in combination with T2‐weighted imaging

To evaluate the diagnostic ability of diffusion‐weighted imaging (DWI) and dynamic contrast‐enhanced imaging (DCEI) in combination with T2‐weighted imaging (T2WI) for the detection of prostate cancer using 3 T magnetic resonance imaging (MRI) with a phased‐array body coil.

Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma

BackgroundThe system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer.MethodsTo clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting.ResultsExpression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors.ConclusionsThese findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC.

Moderate dose diethylstilbestrol diphosphate therapy in hormone refractory prostate cancer.

Objective: To examine the efficacy and toxicity of a moderate dose (250 mg/day) of diethylstilbestrol diphosphate (DES-DP) intravenously administered to patients with hormone refractory prostate cancer (HRPC) as well as the influence of this agent on the endocrine system. Patients and methods: Sixteen patients with HRPC were treated with a daily intravenous injection of 250 mg of DES-DP for 28 days. Eastern Cooperation Oncology Group (ECOG) performance status and pain score were used for subjective evaluation and PSA was used for objective evaluation. Testosterone, free testosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were used for hormonal parameters. Results:OBJECTIVE To examine the efficacy and toxicity of a moderate dose (250 mg/day) of diethylstilbestrol diphosphate (DES-DP) intravenously administered to patients with hormone refractory prostate cancer (HRPC) as well as the influence of this agent on the endocrine system. PATIENTS AND METHODS Sixteen patients with HRPC were treated with a daily intravenous injection of 250 mg of DES-DP for 28 days. Eastern Cooperation Oncology Group (ECOG) performance status and pain score were used for subjective evaluation and PSA was used for objective evaluation. Testosterone, free testosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were used for hormonal parameters. RESULTS Fourteen patients were eligible. The mean patient age was 75.2 years. With respect to the ECOG pain score, 5 patients scored 1 or higher, in 4 patients, the pain completely disappeared, and in 1 patient, the pain score improved from 4 to 1. The PSA level decreased significantly from 528 +/- 556 ng/ml (mean +/- SD) to 154 +/- 197 ng/ml. The DHEA level was not changed during DES-DP administration. The DHEA-S level decreased significantly from 882 +/- 430 ng/ml to 480 +/- 236 ng/ml. Testosterone and free testosterone were in the castration level before and during the treatment. Toxicity was minimal. None of the patients developed cardiovascular disorder. CONCLUSION A moderate dose (250 mg/day) of DES-DP decreased PSA levels and relieved pain without causing serious toxicity in patients with HRPC. It is suggested that the mechanism of the DES-DP effect on the decrease in PSA and pain relief involves a decrease in DHEA-S.

Clinically significant association between the maximum standardized uptake value on 18F-FDG PET and expression of phosphorylated Akt and S6 kinase for prediction of the biological characteristics of renal cell cancer

BackgroundThe relationship between the clinicopathological features and molecular changes associated with standardized uptake value (SUV) determined by Positron emission tomography (PET) with [18F] fluorodeoxyglucose (18F-FDG PET) in human renal cell carcinoma (RCC) has not been elucidated. On the other hand, overactivation of the phosphatidylinositol 3’kinase (PI3K), serine/threonine kinase Akt, and mammalian target of rapamycin (mTOR) pathway has been detected in a variety of human cancers, including RCC. So far, little is known about the relationship between the SUV and these proteins in human RCC. Thus, it is important to study the relevance of SUV with clinicopathological features in human RCCs from a molecular point of view.MethodsSeventy-seven consecutive patients with RCC who underwent nephrectomy and pretreatment determination of the maximum SUV (SUVmax) by 18F-FDG PET were analyzed. We investigated the relationship between the SUVmax, phosphorylated-Akt (Ser-473) (pAkt(Ser-473)), phosphorylated-Akt (Thr-308) (pAkt(Thr-308), and phosphorylated-S6 ribosomal protein (Ser-235/236) (pS6) protein levels in the primary tumor and various clinicopathological features.ResultsThe average SUVmax of the primary tumor was 6.9 (1.5 to 40.3). A higher SUVmax was correlated with higher expression of pAkt(Ser-473), pAkt (Thr-308), and pS6 protein in the primary tumor. A higher SUVmax and increased expression of pAkt (Ser-473), pAkt (Thr-308), and pS6 of the primary tumor was associated with less tumor differentiation, a higher pT stage, regional lymph node involvement, microscopic vascular invasion, and distant metastasis, as well as with early relapse following radical nephrectomy in patients who had localized or locally advanced RCC without distant metastasis (cTanyNanyM0) and with shorter overall survival in all patients.ConclusionsA higher SUVmax on 18F-FDG PET is associated with elevated tumor levels of pAkt and pS6 protein and with aggressive behavior and metastatic potential of RCC, as well as with early relapse following radical nephrectomy and shorter overall survival. These findings suggest that SUVmax may be useful for predicting the biological characteristics of RCC.

The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells

BackgroundActivation of Rho, one of the small GTPases, and its major downstream target Rho-kinase (ROCK) promotes the development and metastasis of cancer. We previously showed that elevation of Rho and ROCK expression was associated with tumor invasion, metastasis, and an unfavorable prognosis in patients with urothelial cancer of the bladder or upper urinary tract.MethodsWe investigated the effects of a ROCK inhibitor on the growth, migration, and apoptosis of bladder cancer cells. We also examined phosphorylation of RhoA (RhoA activity) by measuring its GTP-bound active form and assessed the expression of ROCK to explore the underlying molecular mechanisms.ResultsLysophosphatidic acid (LPA) and geranylgeraniol (GGOH) induced an increase of cell proliferation and migration in association with promotion of RhoA activity and upregulation of ROCK expression. The ROCK inhibitor fasudil (HA-1077) suppressed cell proliferation and migration, and also induced apoptosis in a dose-dependent manner. HA-1077 dramatically suppressed the expression of ROCK-I and ROCK-II, but did not affect RhoA activity.ConclusionsThese findings suggest that ROCK could be a potential molecular target for the treatment of urothelial cancer.

A simple and reliable monitoring system to confirm the preservation of the cavernous nerves

Abstract Background: It is important to establish a procedure with which to confirm the preservation of the cavernous nerves during nerve‐sparing radical surgery. For this purpose, we examined changes in intracavernous pressure (ICP) following electrical stimulation of the neurovascular bundle (NVB) with respect to the continuity of the cavernous nerves.

Clinical significance of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma.

To clarify the role of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (CCRCC), we measured the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble B7-H3 (sB7-H3), and soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in 70 CCRCC patients and 35 healthy controls. We investigated correlations between the serum levels of these soluble T cell regulatory molecules and the pathological grade, clinical stage, and prognosis of CCRCC. We also assessed the relations among each of these soluble molecules. As a result, the serum level of sIL-2R was significantly higher in CCRCC patients than in healthy controls (P < 0.05). In addition, elevation of serum sIL-2R was significantly correlated with the clinical stage (P < 0.001), and the survival of patients with high sIL-2R levels was shorter than that of patients with low sIL-2R levels (P < 0.05). Furthermore, the serum level of sB7-H3 was also significantly correlated with the clinical stage (P < 0.05), while the sIL-2R and sB7-H3 levels showed a positive correlation with each other (R = 0.550, P < 0.0001). These results indicate that the serum level of sIL-2R reflects tumor progression in CCRCC patients. In addition, the possibility was suggested that the IL-2/IL-2R and B7-H3 pathways may be involved in the progression of CCRCC.

Prognostic significance of global grading system of Gleason score in patients with prostate cancer with bone metastasis

Study Type – Prognosis (case series)
Level of Evidence 4

Renal Metanephric Adenoma Mimicking Papillary Renal Cell Carcinoma on Computed Tomography: A Case Report

We present a case of renal metanephric adenoma (MA) mimicking papillary renal cell carcinoma (PRCC) on computed tomography (CT). In the present case, double-phase enhanced CT showed a hypovascular right renal tumor with gradual and prolonged enhancement. The renal tumor was surgically removed. Histological examination of the resected specimen showed renal MA. Although the radiological features of renal MA have been described by some authors, only a few reports have mentioned the pattern of enhancement on multiphase enhanced CT. The pattern of enhancement of a renal tumor is likely to be correlated with its pathological features. Since renal MA is thought to be genetically related to PRCC, these two tumors are likely to demonstrate similar radiological features, so that differentiating between them becomes difficult. In patients with a hypovascular renal mass that shows gradual and prolonged enhancement on multiphase enhanced CT, the diagnosis of renal MA should be considered.

Axitinib for preoperative downstaging of renal cell carcinoma with sarcomatoid differentiation and direct invasion of the duodenum and inferior vena cava: a case report.

Background Renal cell carcinoma (RCC) with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS) trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen. Methods We present a 73-year-old man who had a large (13 cm in diameter) right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy. Results Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed successfully. The pathological treatment effect of axitinib was grade 2 (two-thirds necrosis). The resected tumor showed a heterogeneous reaction for phosphorylated Akt (Ser-473) by Western blotting and immunohistochemistry, indicating that parts of the tumor were sensitive to axitinib and other parts were not. Conclusion Axitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1).