Hidetoshi Ehara

Efficacy of primary hormonal therapy for patients with localized and locally advanced prostate cancer: A retrospective multicenter study

Aim: A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long‐term prognosis in these patients.

Utility of Bcl-2, P53, Ki-67, and caveolin-1 immunostaining in the prediction of biochemical failure after radical prostatectomy in a Japanese population.

OBJECTIVES To identify predictive markers for biochemical failure after radical prostatectomy in patients with clinically confined prostate cancer. METHODS Immunohistochemistry of bcl-2, p53, Ki-67, and caveolin-1 was performed in samples of paraffin-embedded prostate cancer from 119 Japanese patients. The clinicopathologic significance of staining with these markers was analyzed in relation to biochemical failure (prostate-specific antigen [PSA] >0.2 ng/mL). RESULTS Univariate analysis showed the pretreatment PSA level (P = 0.03), postoperative Gleason score (P = 0.04), pathologic stage (P <0.001), seminal vesicle invasion (P <0.001), p53 staining (P <0.001), Ki-67 staining (P = 0.04), and caveolin-1 staining (P <0.0001) to be associated with biochemical failure. Multivariate Cox proportional hazards modeling showed that pretreatment PSA in group A (clinicopathologic parameters), caveolin-1 staining in group B, biomarkers, and the combination (group C) were independently associated with prediction of biochemical failure. The accuracy rate of each group was 76.2% (group A), 75.1% (group B), and 83.1% (group C), respectively. CONCLUSIONS The combination of clinicopathologic parameters and biomarkers (group C) showed the highest accuracy rate. Caveolin-1 staining is an independent predictor of biochemical failure after radical prostatectomy.

The potential role of prebiopsy magnetic resonance imaging combined with prostate-specific antigen density in the detection of prostate cancer.

Aim:  Two‐thirds of patients with a gray‐zone prostate‐specific antigen (PSA) level undergo unnecessary biopsy. Sensitivity is not yet sufficient to permit the use of modified PSA parameters or magnetic resonance (MR) imaging alone for prostate cancer screening. Thus, we evaluated the combination of MR imaging and PSA density (PSAD) for specificity and sensitivity.

Retrospective study of 101 cases with incidental prostate cancer stages T1a and T1b

Purpose: The purpose of this retrospective study was to clarify the character of incidental prostate cancer, stages T1a and T1b.

Expression of mitotic Aurora/Ipl1p-related kinases in renal cell carcinomas: an immunohistochemical study

The Aurora/Ipl1p-related kinases, AIRK1, AIRK2 and AIRK3, are members of a novel family of oncogenic serine/threonine kinases regulated by cell cycle progression and involved in chromosome segregation and cytokinesis. In this study, we examined expression of members of the AIRK family in human renal cell carcinomas. Expression of AIRK subfamilies was examined in 64 renal cell carcinomas by immunohistochemistry. Immunostaining of AIRK1, AIRK2 and AIRK3 was observed in 95%, 47% and 98% of specimens, respectively. Moreover, in specimens from the same patient, staining of AIRK2 was correlated with proliferating cell nuclear antigen labeling. Here we provide the first description of AIRK isozyme immunostaining in human renal cell carcinoma. Although the precise physiological functions of these kinases are not known, AIRK subfamily expression may play a role in renal cell carcinoma tumorigenesis.

Clear Cell Melanoma of the Renal Pelvis Presenting as a Primary Tumor

TO date only 3 cases of malignant melanoma presenting as a renal pelvic mass have been reported in adulthood.1.2 To our knowledge we report the first primary malignant melanoma composed of clear cells in the renal pelvis of a child. CASE REPORT A 3-year-old girl was found to have microscopic hematuria during a routine medical examination. Excretory urography revealed a filling defect in the left renal pelvis. Abdominal sonography showed a 2 cm. isoechoic tumor with normal renal parenchyma within the lesion. Abdominal computerized tomography confirmed the lesion in the renal pelvis and demonstrated no evidence of visceral metastasis (fig. 1). Left radical nephrectomy was performed for the presumed diagnosis of Wilms tumor. Histological evaluation of the surgical specimen revealed a solid tumor composed of clear cells with focal pigmentation in the renal pelvis. The transitional cell epithelium was intact (fig. 2). Fontana-Masson staining was positive for melanin and tumor cells were immunoreactive for HMB-45. The patient had no history of malignant melanoma and postoperative clinical and radiological evaluation failed to reveal any other focus of melanoma. Microscopic hematuria resolved postoperatively. The patient remained asymptomatic and without evidence of residual disease 13 months after surgery. DISCUSSION

Indications for Extended 14-Core Transrectal Ultrasound-Guided Prostate Biopsy

OBJECTIVES We compared the cancer detection rate of extended 14-core biopsy with that of sextant biopsy to assess whether additional biopsy cores are useful for detection of prostate cancer and to clarify the indications for obtaining additional cores. METHODS Study subjects were 313 patients who underwent transrectal ultrasound-guided 14-core biopsy because of a prostate-specific antigen (PSA) level greater than 4.0 ng/mL and/or abnormalities found on digital rectal examination (DRE). In addition to the standard 6 biopsy cores, 6 lateral cores were obtained as well as 2 transition zone cores. PSA density (PSAD) was determined as the total PSA level divided by the prostate volume as estimated by transrectal ultrasound. RESULTS Prostate cancer was diagnosed in 127 patients (40.6%). In 28 (22%) patients, the cancer would not have been detected by the sextant method alone. Among 211 patients with normal DRE findings, the cancer detection rate with 14-core biopsy was statistically higher than that with 6-core biopsy in the 141 patients with a PSA level of 4.01 ng/mL to 10.0 ng/mL, and 14 (38.9%) of 36 cancers were diagnosed in additional cores only, not in the standard sextant biopsy cores. Among the 141 patients with a gray-zone PSA level, the cancer detection rate with extended biopsy was statistically higher in those with PSAD greater than 0.13 ng/mL. CONCLUSIONS Lateral biopsy should be used in conjunction with sextant biopsy in patients with a PSA level of 4.01 ng/mL to 10.0 ng/mL with normal DRE findings, especially in those with PSAD greater than 0.13 ng/mL.

A pretreatment nomogram predicting recurrence- and progression-free survival for nonmuscle invasive bladder cancer in Japanese patients

PurposeOur aim was to provide nomograms that allow urologists to easily calculate a nonmuscle invasive bladder cancer patient’s risk of recurrence and progression.Materials and methodsWe retrospectively analyzed 800 nonmuscle invasive bladder cancer patients newly diagnosed between 1991 and 2001 from the Gifu urothelial cancer registry program. We developed the nomogram using the original 500 patients and validated it using the remaining 300 patients. The prognostic factors of recurrence and progression were identified by multivariate analysis in 500 patients.ResultsIn the multivariate analysis, tumor number, shape, grade, and intravesical instillation were associated with recurrence-free survival. Tumor shape and grade were associated with progression-free survival. Six factors for recurrence and three factors for progression were used to make the nomogram. Using the original 500 patients who were modeled for the nomogram, the areas under the receiver operating characteristic curves (AUCs) were calculated to be 0.61 for recurrence and 0.71 for progression. To validate nomogram performance, we applied an additional 300 patients to the nomograms. The AUCs were 0.57 for recurrence and 0.67 for progression.ConclusionsThe nomograms that have been developed can be used to predict the probability of recurrence and progression of nonmuscle invasive bladder cancer.

Global update on defining and treating high-risk localized prostate cancer with leuprorelin: an Asian perspective

Data from the Japanese Urological Society showed that, in Japan, almost half of patients with localized prostate cancer are treated with hormone therapy (HT), regardless of disease stage, and that radiation therapy (RT) is also widely used to treat high‐risk patients. A retrospective study was undertaken in Japan to evaluate the potential benefits of using primary HT in locally advanced prostate cancer. Of 628 patients in the study, 63.5% were treated with combined androgen blockade (CAB; luteinizing hormone‐releasing hormone agonists plus an antiandrogen) and 36.5% with medical or surgical castration. CAB treatment was significantly better than hormone monotherapy for disease‐specific survival. The results also showed that, even if a patient is classified as ‘high‐risk’, a good prognosis could normally be predicted based on certain variables: if their initial prostate‐specific antigen (PSA) level was ≤ 20 ng/mL, their Gleason score was ≤ 6, and their nadir PSA decreased to ≤ 0.2 ng/mL within 6 months of HT. In this subgroup of ‘good responders’, any treatment, be it prostatectomy, RT or CAB, is likely to be effective. However, in ‘poor responders’, combined therapies with CAB and high‐dose rate brachytherapy are likely to be needed for a clinical response. While HT is effective, it might be associated with a reduction in the patient’s quality of life (QoL) due to adverse effects, e.g. a reduction in sexual function. Results from the analysis of QoL questionnaires completed by men of different ages with prostate cancer found that only sexual function, and not other QoL variables, in men aged 50–59 years appeared to be reduced in men who had HT, compared to age‐matched controls.

Possible roles of vinexinβ in growth and paclitaxel sensitivity in human prostate cancer PC-3 cells

Purpose: Vinexinβ is an adaptor protein supposed to play pivotal roles in cell adhesion, cytoskeletal organization and signaling. Vinexinβ is reported to be phosphorylated by extracelluler signal-regulated kinase (ERK) and the phosphorylation has been shown to be involved in cell adhesion, migration and growth. However, physiological function as well as pathophysiological relevance of vinexinβ in cancer cells is almost unknown. Methods: By use of biochemical and cell biological techniques, we analyzed the effects of over-expression or RNAi-mediated silencing of vinexinβ on the growth and paclitaxel sensitivity in a prostate cancer cell line PC-3. Results: Vinexinβ was highly expressed in androgen-independent prostate cancer cell lines, PC-3 and DU145, but not in androgen-dependent LNCaP cells. We established two PC-3 cell lines, PC-3/Vinβ#1 and #2, stably expressing GFP-tagged vinexinβ and found that growth rate of these lines was significantly increased compared to a mock-transfected cell line. In addition, we found that PC-3/Vinβ#1 and #2 became resistant to the treatment with 100 nM paclitaxel for 48 h. On the other hand, when siRNA-mediated vinexinβ gene silencing was performed, PC-3 cell growth was suppressed. In addition, by vinexinβ silencing, PC-3 cells became significantly sensitized to 10 nM paclitaxel treatment for 48 h. Conclusions: Vinexinβ plays an important role in PC-3 cell growth, and abrogation of vinexinβ may be effective for therapeutic cell death and enhanced chemotherapy sensitization in androgen-independent prostate cancer cells.