Search

Abstract: The objective of this study was to characterize features of thyroid dysfunction in Japanese patients with metastatic renal cell carcinoma (RCC) who were treated with sorafenib. We performed a prospective observational study including 69 Japanese patients who were diagnosed as having metastatic RCC refractory to cytokine therapy and subsequently treated with sorafenib for at least 12 weeks. Thyroid function was assessed before and every 4 weeks after the initiation of sorafenib treatment. Of the 69 patients, 23 (33.3%) did not show any biochemical thyroid abnormality, while the remaining 46 (67.7%) developed hypothyroidism. However, 11 (23.9%) of these 46 hypothyroid patients initially had a suppressed thyroid-stimulating hormone (TSH) value accompanying the increase in free triiodothyronine (T3) and/or free thyroxine (T4) before developing hypothyroidism, suggesting sorafenib-induced thyroiditis. During the observation period of this study, 4 patients (5.8%) demonstrated severe clinical symptoms caused by hypothyroidism and received thyroid hormone replacement. Among several factors examined, only age was significantly associated with the risk for hypothyroidism. These findings suggest that although the incidence of clinically significant hypothyroidism requiring thyroid hormone replacement therapy was not very high, biochemical thyroid abnormality was frequently observed in Japanese RCC patients treated with sorafenib. Accordingly, regular surveillance of thyroid function by the measurement of TSH, free T3, and T4 is warranted during sorafenib treatment in Japanese RCC patients. [Copyright &y& Elsevier]

Abstract: The objective of this study was to retrospectively investigate clinical outcomes of combined immunotherapy with interferon-α (IFN-α) and low-dose interleukin-2 (IL-2) in Japanese patients with metastatic renal cell carcinoma (RCC). This study included a total of 52 patients with metastatic RCC who were treated by combined immunotherapy with IFN-α and low-dose IL-2 following radical nephrectomy. These patients received a subcutaneous injection of IFN-α (5 to 6 million U/d) three times per week and intravenous injection of IL-2 (1.4 million U/d) twice per week. Tumor response was evaluated every 16 weeks, and as a rule, this weekly regimen was repeated 50 times in patients with evidence of objective response or stable disease. In this series, complete response and partial response were achieved in 1 and 11 patients, respectively; however, the remaining 20 and 20 patients were diagnosed as showing stable disease and progressive disease, respectively. Of several parameters examined, presence of metastases at diagnosis and C-reactive protein (CRP) level were significantly associated with response to this combined therapy. The 1-, 3-, and 5-year cancer-specific survival rates of these 52 patients were 80.4%, 51.7%, and 38.8%, respectively. Furthermore, cancer-specific survival was significantly associated with performance status, presence of metastases at diagnosis, metastatic organ and CRP level on univariate analysis; however, only performance status and presence of metastases at diagnosis appeared to be independent predictors of cancer-specific death by multivariate analysis. Toxicities related to this therapy were generally mild and tolerable, limited to World Health Organization (WHO) grade 1 or 2 in the majority of patients. Collectively, these findings suggest that combined immunotherapy with IFN-α and low-dose IL-2 could achieve comparatively acceptable oncological outcomes in patients with metastatic RCC; however, other therapeutic options should be considered in patients with unfavorable performance status and/or those positive for metastatic diseases at diagnosis. [Copyright &y& Elsevier]

Abstract: The objective of this study was to evaluate Aurora-A expression in human renal cell carcinomas (RCCs) to clarify the clinical significance of Aurora-A expression in this disease. Expression levels of Aurora-A messenger ribonucleic acids and proteins in both normal kidney and RCC specimens obtained from 131 patients undergoing radical nephrectomy were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemical staining, respectively. Various levels of Aurora-A protein expression were noted in 127 of the 131 RCC specimens (96.9%), while only 101 of the 131 normal kidney tissues (77.1%) showed Aurora-A staining. In addition, the expression levels of Aurora-A protein in both normal and RCC specimens were in proportion to those of Aurora-A messenger ribonucleic acids. Aurora-A protein expression in RCC tissues was significantly related to tumor grade, but not with age, gender, tumor size, pathologic stage, or histologic cell type. Cell proliferative activity in RCC specimens was significantly associated with Aurora-A expression, while there was no significant correlation between the apoptotic index and Aurora-A protein expression. Furthermore, there was no significant difference in recurrence-free survival between patients with strong Aurora-A expression and those with weak expression. In conclusion, despite the detection in the majority of RCC tissues, Aurora-A expression failed to show the significant association with major pathologic factors and prognosis in patients with RCC. [Copyright &y& Elsevier]

Objective: To develop a Web-based audiovisual telementoring system for robot-assisted radical prostatectomy (RARP) and to assess the utility of this system. Methods: A telementoring system for RARP, consisting of a 3-dimensional high-definition view of the operating field, overview of the operating room, annotation function, and 2-channel audio feed with bidirectional connectivity between 2 institutions, was developed. The outcome of RARP performed for the initial 30 patients by 2 surgeons with telementoring was compared with that for 2 surgeons who received direct mentoring. Results: This system was shown to function properly with an acceptable latency. There were no significant differences in several parameters reflecting surgical outcomes, including the operating time, complication rate, early continence status, and positive margin rate between the telementoring and direct mentoring groups. Conclusion: These findings suggest the usefulness of the telementoring system for promoting the spread of precise surgical techniques associated with RARP. To our knowledge, this is the first report concerning telementoring for robot-assisted surgery. [Copyright &y& Elsevier]

Objectives: To compare the accuracy to diagnose micrometastases to pelvic lymph nodes (LNs) in patients undergoing radical prostatectomy (RP) by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) targeting several genes specifically expressed in the prostate. Materials and methods: Expression of prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), human kallikrein 2 (hK2), prostate stem cell antigen (PSCA), and differential display code 3 (DD3) in 2215 LNs isolated from 120 patients with localized prostate cancer were assessed by fully quantitative real-time RT-PCR. Results: In addition to pathologically diagnosed LN metastases in 11 patients, real-time RT-PCR targeting PSA, PSMA, hK2, PSCA, and DD3 further identified micrometastases in 23, 29, 31, 15, and 11, respectively. In this series, biochemical recurrence (BR) occurred in 32 patients, of whom 25, 22, 28, 10, and 9 were diagnosed as having micrometastases by real-time RT-PCR targeting PSA, PSMA, hK2, PSCM, and DD3, respectively. Univariate analysis identified pathologic stage, pathologic LN metastases, Gleason score, surgical margin status, and micrometastases detected by real-time RT-PCR targeting PSA. PSMA, hK2, and their combinations as significant predictors for BR-free survival (BRFS), of which only surgical margin status and micrometastases detected by real-time RT-PCR targeting PSA and hK2 appeared to be independently associated with BRFS on multivariate analysis. Conclusions: Of PSA, PSMA, hK2, PSCA, DD3, and their combinations, combined analysis of PSA and/or hK2 expression in pelvic LNs by real-time RT-PCR could provide findings most precisely predicting BRFS following RP. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to evaluate the expression levels of multiple potential molecular markers in prostate cancer to clarify the significance of these markers as prognostic indicators in patients undergoing radical prostatectomy (RP). This study included a total of 193 patients with clinically organ-confined prostate cancer who underwent RP without any neoadjuvant therapies. Expression levels of 12 proteins, including Ki-67, p53, androgen receptor (AR), matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor, Aurora-A, Bcl-2, clusterin, heat shock protein 27 (HSP27), HSP70, and HSP90, in RP specimens obtained from these 193 patients were measured by immunohistochemical staining. Of the 12 molecules, Ki-67, p53, AR, MMP-2, MMP-9, and HSP27 expression were significantly associated with several conventional prognostic factors. Univariate analysis identified these 6 markers as significant predictors for biochemical recurrence as well, while prostate-specific antigen, Gleason score, seminal vesicle invasion (SVI), surgical margin status (SMS), lymph node metastasis, and tumor volume were also significant. Of these significant factors, Ki-67 expression, SVI, and SMS appeared to be independently related to biochemical recurrence by multivariate analysis. Furthermore, there were significant differences in biochemical recurrence-free survival according to positive numbers of these three independent risk factors. These findings suggest that consideration of expression levels of potential molecular markers in RP specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of biochemical recurrence following RP in patients with clinically localized prostate cancer, and that combined evaluation of Ki-67 expression, SVI, and SMS would be particularly useful for further refinement of the system in predicting biochemical outcome. [Copyright &y& Elsevier]

Abstract: Objectives: To determine whether the expression level of clusterin in prostate cancer could be used as a prognostic predictor in patients who have undergone radical prostatectomy (RP). Methods: This study included 172 consecutive patients undergoing RP for clinically organ-confined prostate cancer without neoadjuvant hormonal therapy. Immunohistochemical staining was performed in RP specimens obtained from these patients to evaluate the expression level of clusterin protein. The cell proliferative activities and apoptotic features in these specimens were investigated using Ki-67 immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, respectively. Results: Varying levels of clusterin expression were noted in 169 of 172 prostate cancer specimens; 32 of the 172 normal prostatic tissue specimens did not exhibit any clusterin staining. Clusterin expression in prostate cancer tissue was significantly related to the Gleason score, but not to the other parameters, including age, serum prostate-specific antigen level, pathologic stage, perineural invasion, tumor volume, and lymph node metastasis. In addition, cell proliferative activity in the prostate cancer specimens was significantly associated with clusterin expression; however, no correlation was found between the apoptotic index and clusterin expression. In this series, 34 (19.8%) of 172 patients developed biochemical recurrence. No significant difference was found in biochemical/recurrence-free survival between patients with strong clusterin expression and those with weak expression. Conclusions: Despite its detection in most prostate cancer tissue, clusterin expression failed to show a significant association with prognosis in patients undergoing RP without neoadjuvant hormonal therapy. This suggests a limited role for clusterin in the progression of clinically organ-confined prostate cancer in the absence of proapoptotic stimuli. [Copyright &y& Elsevier]

Objectives: To assess whether the serum level of clusterin and its density could be used as novel biomarkers of prostate cancer. Methods: Sera were obtained from 380 patients with prostate cancer and 120 with benign prostatic hyperplasia. Serum clusterin level was measured by a sandwich enzyme immunoassay, and clusterin density, which was determined by dividing the serum clusterin level by the prostate volume, was also calculated. These findings were analyzed with respect to several clinicopathologic factors. Results: The mean serum level of clusterin in prostate cancer patients was significantly higher than that in the benign prostatic hyperplasia group. Both the serum clusterin level and clusterin density in prostate cancer patients were significantly associated with major prognostic factors other than biopsy Gleason score. Of the 380 prostate cancer patients, 162 underwent radical prostatectomy and pelvic lymphadenectomy, and 104 and 58 were diagnosed as having organ-confined and extraprostatic diseases, respectively. The clusterin density in patients with organ-confined disease was significantly higher than that in patients with extraprostatic disease; however, there was no significant difference in the serum clusterin level between these 2 groups. Furthermore, biochemical recurrence-free survival in patients with elevated clusterin density was significantly lower than that in patients with normal density. Conclusions: These findings suggest that serum clusterin level and its density could serve as a useful practical adjuncts to conventional parameters for estimating the extension of prostate cancer. [Copyright &y& Elsevier]