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OBJECTIVE To characterize the impact of sorafenib treatment on health-related quality of life (HRQL) in Japanese patients with mRCC. PATIENTS AND METHODS We performed a prospective observational study including 85 consecutive patients undergoing radical nephrectomy who were diagnosed as having mRCC refractory to cytokine therapy and subsequently treated with sorafenib for at least 3 months. HRQL in these patients was assessed using the Medical Outcomes Study 36-Item Short Form (SF-36). RESULTS Before treatment all eight scores in the 85 patients were significantly inferior to those in the age-matched control population in Japan. Three months after sorafenib treatment, one score (mental health) in the 85 patients was significantly higher than what it was before treatment. Three scores (body pain, role limitations because of emotional problems, mental health) in patients who had some degree of tumour shrinkage were significantly better than those in the remaining patients, while there were no significant differences in all but one score (social function) between patients with and without severe AEs. Furthermore, there were no significant differences in any scores 3, 6 and 12 months after sorafenib treatment in 26 patients who could be followed for at least 12 months. CONCLUSIONS Despite non-randomized study including a comparatively small number of patients, the findings of the present study suggest that sorafenib treatment may not impair HRQL in patients with mRCC, and HRQL in patients receiving sorafenib is likely to be affected by the efficacy rather than AEs during treatment. [ABSTRACT FROM AUTHOR]

Study Type – Diagnostic (non-consecutive series) Level of Evidence 3b OBJECTIVES To characterize the anatomical extension pattern of prostate cancer arising in the peripheral zone (PZ) in radical prostatectomy (RP) specimens and to evaluate its prognostic significance. PATIENTS AND METHODS Of 174 consecutive patients undergoing RP, 128 diagnosed as having PZ cancer (PZC) were enrolled. The maximum tumour area (MTA) and maximum tumour volume (MTV) in RP specimens were measured using digital planimetry. A circle with an area equal to the MTA, in which the central point was the intersection of the longest line of the MTA and the line perpendicularly bisecting the first line, was defined as a hypothetical extension area, regardless of anatomical structure. The area within this circle that did not overlap the MTA was defined as ΔTA. RESULTS There was a significant correlation between the MTV and ΔTA/MTA, introduced as a variable representing the degree of PZC extension along the anatomical shape of the PZ. The ΔTA/MTA in patients with a MTV of >5 mL was significantly greater than that in those with a MTV of ≤5 mL. Furthermore, ΔTA/MTA was significantly associated with several prognostic indicators, including extracapsular extension, surgical margin status and perineural invasion. Multivariate analysis identified ΔTA/MTA in addition to preoperative serum prostate-specific antigen level, extracapsular extension and surgical margin status as independent predictors of biochemical recurrence after RP. CONCLUSIONS PZC tends to extend along the anatomical shape of the PZ during progression, resulting in higher ΔTA/MTA value in advanced PZC than that in early PZC. [ABSTRACT FROM AUTHOR]

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]

The aim is to evaluate the efficacy and toxicity of weekly docetaxel and estramustine for Japanese men with hormone refractory prostate cancer who were treated at a single institution. Twenty eligible patients had histologically proven adenocarcinoma of the prostate with metastases that were progressing despite complete androgen blockade and antiandrogen withdrawal. All of the patients received docetaxel 30 mg/m2 weekly (days 1, 8, 15, 22, 29, and 36). After a two week break, the treatment schedule was repeated. Patients were scheduled to receive daily oral estramustine 560 mg/day throughout the protocol. In the serum prostate specific antigen (PSA) response, three (15%) patients achieved a complete response, and 8 (40%) acheived a partial response. Overall survival and time to progression were 13.4 months and 6.4 months, respectively, however sixty-seven percent of the patients had to discontinue treatment because of toxicity. The high toxicity of this protocol suggests that the regimen and/or the timing should be altered for Japanese patients. [ABSTRACT FROM AUTHOR]

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]

Purpose: We evaluated expression levels of major heat shock proteins in radical prostatectomy specimens to clarify the significance of heat shock protein expression in prostate cancer. Materials and Methods: Expression levels of heat shock proteins 27, 70 and 90 in radical prostatectomy specimens from 172 patients with clinically organ confined prostate cancer who had not received neoadjuvant hormonal therapy were measured by immunohistochemical staining. Cell proliferative activities and apoptotic features in these specimens were investigated using Ki-67 immunostaining and TUNEL assay, respectively. These findings were analyzed with respect to several clinicopathological factors. Results: Various levels of heat shock protein 27 expression were noted in all prostate cancer specimens. Expression levels of heat shock protein 27 in prostate cancer tissues was significantly associated with pathological stage, Gleason score, surgical margin status, lymph node metastasis and tumor volume but not with other parameters, including patient age, serum prostate specific antigen and perineural invasion. Similarly most prostate cancer tissues showed heat shock protein 70 and 90 expression. However, there was no significant correlation between expression levels of these 2 heat shock proteins and several clinicopathological factors examined. Cell proliferative activity in prostate cancer specimens was significantly associated with heat shock protein 27 expression but not with that of heat shock proteins 70 and 90, while there was no significant correlation between the apoptotic index and the expression of these 3 heat shock proteins. Furthermore, despite the lack of prognostic significance in heat shock proteins 70 and 90 expression, biochemical recurrence-free survival in patients with strong heat shock protein 27 expression in radical prostatectomy specimens was significantly lower than that in those with weak heat shock protein 27 expression. However, multivariate analysis showed that strong heat shock protein 27 expression could not be an independent predictor of biochemical recurrence after radical prostatectomy. Conclusions: These findings suggest that, despite the limited significance of heat shock proteins 70 and 90 expression, heat shock protein 27 may be involved in the progression of prostate cancer. The expression level of heat shock protein 27 in prostate cancer tissue could be used as a useful predictor of biochemical recurrence in patients undergoing radical prostatectomy. [Copyright &y& Elsevier]

Introduction: The objective of this study was to review our experience with urinary reconstruction in patients undergoing surgical management for locally advanced pelvic cancer, and to evaluate the role of urologists in these procedures. Materials and Methods: This study included a total of 37 patients undergoing some type of urinary reconstruction due to invasion of the urological organs by locally advanced pelvic cancers, including 17 rectal cancers, 9 cervical cancers, 4 sigmoid cancers, 4 retroperitoneal sarcomas, 2 ovarian cancers and 1 appendiceal cancer. Among these 37, 18 were recurrent cancers following initial surgery for primary tumors. The clinical outcomes of these approaches were retrospectively analyzed. Results: Of the 37 patients, 9 underwent cystectomy (group A) with the following urinary diversions: ileal neobladder in 3, ileal conduit in 5 and colon conduit in 1, and 12 underwent partial cystectomy (group B), among whom 11 received additional urinary reconstruction as follows: bladder flap repair in 5, psoas hitch in 2, ileal ureter in 2, bladder augmentation in 1 and ureteroureterostomy in 1, while the remaining 16 (group C), in whom complete bladder preservation was possible, underwent the following types of urinary reconstruction: bladder flap repair in 6, psoas hitch in 3, en bloc removal of the rectum with prostate in 3, ileal ureter in 2, and ureteroureterostomy in 2. There were 10 early urological complications, including leakage of urine in 7 and acute pyelonephritis in 3. As a late urological complication, hydronephrosis was observed in 8 patients, but ureteral stent was not required in any of these 8. There were no significant differences in the incidence of postoperative complications, the status of surgical margin and the survival among groups A–C. Conclusion: Our experience with extended surgical management of non-urological pelvic cancer with reconstruction of the urinary tract suggests that the urological portion of this procedure can be performed with acceptable morbidity, and that the role of the urological surgeon during this procedure is potentially important. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the clinical significance of additional routine transition zone (TZ) biopsies in Japanese men undergoing transrectal ultrasound (TRUS)-guided systematic 8-core peripheral zone (PZ) biopsies. Methods: Between October 2002 and December 2004, a total of 788 consecutive patients underwent TRUS-guided systematic biopsy of the prostate for the first time. As a rule, 10 cores were taken from each patient; that is, 8 cores from the PZ, including the standard sextant cores and 2 cores from the anterior lateral horns, and 2 additional cores from the bilateral TZ. The cancer detection rate was calculated according to several parameters. We also assessed the disease extent on radical prostatectomy specimens according to the cancer location within the biopsy specimens. Results: Prostate cancer was detected by 10-core biopsies in 209 (26.5%) of the 788 patients, and 11 of these patients had positive cores only in the TZ; that is, the increase in cancer detection rate by sampling two additional cores from the TZ was 5.3%. Among 209 patients diagnosed as having prostate cancer, radical prostatectomy without any neoadjuvant therapy was performed in 59 patients with positive biopsy cores in the PZ, 7 in the TZ and 32 in both the PZ and TZ. Patients with positive cores in both zones showed significantly less favorable characteristics, indicating more advanced disease than that in those with positive cores in either zone. Conclusions: Routine TZ biopsy did not significantly increase the detection rate of prostate cancer; however, the anatomical location of positive biopsy cores could provide additional information concerning disease extension in patients undergoing radical prostatectomy. [ABSTRACT FROM AUTHOR]

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]