Takehiro Oikawa

Tissue elasticity imaging for diagnosis of prostate cancer: A preliminary report

Background: Elastography is a diagnostic imaging technique that evaluates the hardness of a lesion. It is expected to become a new diagnostic modality for prostate cancer. The aim of this study was to examine the usefulness of elastography in the diagnosis of prostate cancer.

Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling

The Wnt signaling pathway is involved in normal embryonic development and controls the homeostatic self-renewal of stem cells in adult tissues. Constitutive activation of Wnt signaling contributes to cancer development and progression. We identified a CXXC4 homozygous deletion at 4q24 in an aggressive renal cell carcinoma (RCC) using single-nucleotide polymorphism (SNP) arrays. CXXC4 encodes Idax, which negatively regulates Wnt signaling by binding to the PDZ domain of Dishevelled. CXXC4 mRNA levels in tumor samples were significantly lower in patients with metastases compared with those without (P=0.0016). Patients whose tumors had lower CXXC4 expression than normal kidney showed a poorer cause-specific survival outcome than those with higher expression (P=0.0095). Decreased expression of CXXC4 also correlated with cytoplasmic staining of β-catenin. Knockdown of CXXC4 induced the nuclear translocation of β-catenin and altered expression of a set of genes involved in cell proliferation, invasion and survival. Furthermore, reduced expression of CXXC4 by small interfering RNAs promoted cell proliferation and inhibited apoptosis after 5-FU and doxorubicin treatment in RCC cells. These data suggest that CXXC4 plays a critical role in tumor progression of RCC through Wnt signaling. Wnt signaling could thus be a potential molecular target in RCC indicating decreased CXXC4 expression.

Intraoperative transesophageal echocardiography for inferior vena caval tumor thrombus in renal cell carcinoma

Background : We investigated the advantages of intraoperative transesophageal echocardiography (TEE) during inferior vena caval tumor thrombectomy in renal cell carcinoma (RCC).

Negative Impact of Metabolic Syndrome on the Responsiveness to Sildenafil in Japanese Men

INTRODUCTION Several recent studies suggested that the prevalence of erectile dysfunction (ED) was higher in men with metabolic syndrome (MS). AIM We analyzed the impact of MS on the responsiveness to sildenafil. METHODS A total of 133 ED patients were evaluated for the prevalence of MS and graded on severity of ED. MS was diagnosed according to the International Diabetes Federation (IDF) definition. The severity of ED was evaluated by the International Index of Erectile Function (IIEF) questionnaire. Hormonal parameters were measured for all patients, and the IIEF questionnaire was conducted after administration of eight tablets of 50-mg doses of sildenafil. If the scores to questions 3 and 4 of the IIEF were 4 or higher after administration, the patients were defined as responders to sildenafil. MAIN OUTCOME MEASURES To clarify the negative impact of MS on the responsiveness to sildenafil. RESULTS The mean age of the patients was 56.9 years, and 25 patients were diagnosed with MS. The IIEF-erectile function score and the response rate for sildenafil decreased as the number of MS components increased. Logistic regression analysis showed that the presence of MS along with severity of ED and history of pelvic surgery were significant independent risk factors of nonresponse for sildenafil. The hazard ratio for the presence of MS was 3.30 (95% confidence interval [CI]: 1.17-9.73). No meaningful association was observed between total testosterone or free testosterone levels and MS in this population. CONCLUSION We demonstrated the negative impact of MS on the responsiveness to sildenafil. Erectile function and response rate for sildenafil decreased as the number of MS components increased.

Clinical utility of the prostate cancer gene 3 (PCA3) urine assay in Japanese men undergoing prostate biopsy

It is known that a prostate cancer gene 3 (PCA3) urine assay is superior to serum PSA level or PSA‐related indices for predicting a positive biopsy result in European and US men. This is the first report on PCA3 in a large cohort of Japanese men. The diagnostic value of the PCA3 score in Japanese men was similar to those reported in European and US men. The study concludes that a combination of PSA density and PCA3 score may be useful for selecting patients who could avoid an unnecessary biopsy.

Uroepithelial cells can directly respond to Mycobacterium bovis bacillus Calmette-Guérin through Toll-like receptor signalling

To investigate, in a human urinary tract cell line, the interaction of Toll‐like receptor (TLR) signals with cytoplasmic adapter proteins MyD88 and bacillus Calmette‐Guérin (BCG), and evaluate the epithelial cytokine response to BCG infection. Intravesical BCG therapy is effective against carcinoma in situ and as prophylaxis for recurrence, but although immunological mechanisms have been assumed, the mechanisms of the antitumour effects of BCG have not been completely elucidated.

FOXO1 and TCF7L2 genes involved in metastasis and poor prognosis in clear cell renal cell carcinoma

The goal of this study was to identify genes related to the metastasis of clear cell renal cell carcinoma (CRCC). We analyzed copy number alterations in renal tissue specimens of patients with CRCC patients with or without metastasis by using high‐resolution single‐nucleotide polymorphism (SNP) arrays and then integrated these data with gene expression profiling data obtained using oligonucleotide microarrays. The expression levels of target genes were determined by quantitative real‐time RT‐PCR (qRT‐PCR) with an independent tumor set. An analysis of specimens from 23 CRCC cases with SNP arrays revealed that hemizygous deletions at 10q and 13q were found only in cases of metastatic disease. We found the homozygous deletion of TCF7L2 at 10q25.2 in an aggressive case that had hemizygous deletions at 10q. In addition, a qRT‐PCR analysis of TCF7L2 mRNA levels in tumor samples revealed significantly lower levels in patients with metastasis when compared with those without metastasis. FOXO1 was identified as a down‐regulated gene in the minimal overlapping region of the 13q hemizygous deletion in CRCC. Decreased FOXO1 expression was significantly correlated with metastasis and poor survival outcome. Knockdown of FOXO1 inhibited apoptosis after doxorubicin treatment in CRCC cells and reduced the expression of downstream genes involved in cell proliferation (CDKN1B) and survival (BCL2L11). Lower levels of FOXO1 expression were associated with decreased expression of CDKN1B and BCL2L11 in CRCC specimens. We conclude that FOXO1 and TCF7L2 are involved in metastasis and that molecules in these signaling pathways may be targets for diagnostic procedures and therapies for CRCC.

Pattern of intravesical recurrence after surgical treatment for urothelial cancer of the upper urinary tract: a single institutional retrospective long-term follow-up study.

Objectives:  To estimate the risk of intravesical recurrence in patients with primary urothelial cancer of the upper urinary tract.

Analysis of Intravesical Recurrence After Bladder-preserving Therapy for Muscle-invasive Bladder Cancer

OBJECTIVE The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer. METHODS The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed. RESULTS With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non-muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P= 0.0001, 0.0442 and 0.0412, respectively). CONCLUSIONS Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle-invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence.

Risk Factors for Intravesical Recurrence in Patients with High-grade T1 Bladder Cancer in the Second TUR Era

OBJECTIVE We aimed to elucidate risk factors for intravesical recurrence of high-grade T1 bladder cancer in the second transurethral resection era. METHODS The analysis included 73 patients with high-grade T1 bladder cancer on initial transurethral resection. The median follow-up period was 49.2 months. Recurrence-free survival, progression-free survival and risk factors related to the presence of residual tumors or recurrence-free survival were statistically analyzed. RESULTS The pathological findings for second transurethral resection were pT0 36 (49%), pTis/a 21 (29%), pT1 13 (18%) and pT2 3 (4%), respectively. The risk factor for residual tumors at second transurethral resection was the presence of concomitant carcinoma in situ at the initial transurethral resection (P < 0.01). The bladder was preserved in all 57 patients with pT0/is/a tumors on second transurethral resection, and 43 patients (75%) received intravesical BCG therapy. Of these patients, 3-year recurrence-free survival and 3-year progression-free survival rates were 81 and 96%, respectively. In addition, the presence of pTis/a residual tumors on second transurethral resection had a significant impact on the recurrence. Five of the 13 patients with pT1 on second transurethral resection were immediately treated by radical cystectomy or radiation therapy combined with chemotherapy, and two (25%) of the eight who were treated by intravesical BCG therapy had progression including distant metastasis. CONCLUSIONS High recurrence-free survival and progression-free survival were achieved by a second transurethral resection and intravesical BCG therapy in the patients with pT0/is/a on the second transurethral resection. In this group, the residual tumors at second transurethral resection are risk factors for intravesical recurrence.