Tomoaki Terakawa

Risk factors for intravesical recurrence after surgical management of transitional cell carcinoma of the upper urinary tract.

OBJECTIVES To identify risk factors for developing subsequent bladder cancer in patients undergoing surgical management of transitional cell carcinoma (TCC) of the upper urinary tract. METHODS This study included 177 patients who were diagnosed as having clinically localized upper urinary tract TCC and thereafter underwent nephroureterectomy after exclusion of those with a previous and/or concurrent history of bladder cancer. Univariate and multivariate analyses using both the logistic regression model and the Cox proportional hazards model were carried out in these 177 patients to determine the risk factors for intravesical recurrence after nephroureterectomy. RESULTS Of the 177 patients, 63 (35.6%) developed recurrent bladder cancer after a median interval of 7.5 months. Intravesical recurrence-free survival rates for these 177 patients at 1, 3, and 5 years were 75.7%, 63.7%, and 54.1%, respectively. Univariate analyses showed that patients with low-stage tumors and those with multifocal tumors were likely to undergo subsequent intravesical recurrence; however, there was no significant impact of other factors on subsequent intravesical recurrence, including age, tumor side, tumor location, surgical modality, operation time, management of the distal ureter, tumor grade, lymph node metastasis, microvascular invasion, lymphatic invasion, and margin status. Furthermore, pathologic stage and tumor multifocality were identified as independent predictors for the development of recurrent bladder cancer by multivariate analyses. CONCLUSIONS The incidence of intravesical recurrence after nephroureterectomy for upper urinary tract TCC is comparatively high. It could be important to perform careful follow-up targeting intravesical recurrence for such patients after nephroureterectomy, particularly those with low-stage tumors and/or multifocal tumors.

Clinical outcome of surgical management for patients with renal cell carcinoma involving the inferior vena cava

Background:  The objective of this study was to evaluate the clinical outcome after surgical management of renal cell carcinoma (RCC) extending to the inferior vena cava (IVC).

Expression level of vascular endothelial growth factor receptor-2 in radical nephrectomy specimens as a prognostic predictor in patients with metastatic renal cell carcinoma treated with sunitinib

OBJECTIVES To investigate the expression levels of multiple molecular markers in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (RCC) treated with sunitinib in order to identify factors predicting susceptibility to this agent. MATERIALS AND METHODS This study included a total of 40 consecutive patients undergoing radical nephrectomy, who were diagnosed as having metastatic RCC and subsequently treated with sunitinib. Expression levels of 10 molecular markers, including Bcl-2, Bcl-xL, Bax, phosphorylated Akt, p44/42 mitogen-activated protein kinase, and signal transducers and activation of transcription 3, vascular endothelial growth factor receptor (VEGFR)-1 and -2, and platelet-derived growth factor receptor-α and -β, in primary RCC specimens were assessed by immunohistochemical staining. RESULTS Of several factors examined, tumor grade and the expression level of VEGFR-2 were shown to have significant impacts on response to sunitinib in these 40 patients. Progression-free survival (PFS) was significantly associated with the expression levels of VEGFR-2 in addition to tumor grade, performance status, Memorial Sloan-Kettering Cancer Center risk classification and pretreatment c-reactive protein level on univariate analysis. Of these significant factors, only VEGFR-2 expression appeared to be independently related to PFS on multivariate analysis. In fact, PFS in patients with strong expression of VEGFR-2 was significantly favorable compared with that in those with weak expression of VEGFR-2. CONCLUSIONS Collectively, these findings suggest that it would be useful to consider expression levels of potential molecular markers, particularly VEGFR-2, as well as conventional clinical parameters to select metastatic RCC patients likely to benefit from treatment with sunitinib.

Expression profile of E-cadherin and N-cadherin in non-muscle-invasive bladder cancer as a novel predictor of intravesical recurrence following transurethral resection

The objective of this study was to investigate the impact of the expression profile of E-cadherin and N-cadherin in newly diagnosed non-muscle-invasive bladder cancer (NMIBC) on the probability of intravesical recurrence in patients undergoing transurethral resection (TUR). This study included 115 consecutive patients diagnosed as having NMIBC following TUR. Expression levels of E-cadherin and N-cadherin in TUR specimens from these patients were measured by immunohistochemical staining. In this series, intravesical recurrence occurred in 35 of 115 patients (30.4%). Immunohistochemical study showed that positive expression of E-cadherin and N-cadherin were noted in 62 (53.9%) and 48 (41.7%) specimens, respectively. Intravesical recurrence was detected in only 7 of 62 patients (11.3%) with positive E-cadherin expression, while 33 of 48 patients (68.8%) with positive N-cadherin expression developed intravesical recurrence. When patients were divided into 4 groups according to the positivities of E-cadherin and N-cadherin expression, intravesical recurrence was detected in 27 of 30 patients (90.0%) with negative E-cadherin as well as positive N-cadherin expression, and the intravesical recurrence-free survival of this group was significantly poorer than those of the remaining 3 groups. Furthermore, negative E-cadherin as well as positive N-cadherin expression was identified as the most powerful independent predictor for intravesical recurrence following TUR on multivariate analysis. These findings suggest that the loss of E-cadherin and gain of N-cadherin expression in on NMIBC appeared to be significantly associated with postoperative recurrence; therefore, the switch from E-cadherin to N-cadherin expression might be involved in the mechanism underlying intravesical recurrence of on NMIBC.

Inverse association between histologic inflammation in needle biopsy specimens and prostate cancer in men with serum PSA of 10-50 ng/mL.

OBJECTIVES To investigate the effect of the presence of histologic inflammation in needle biopsy specimens on the detection of prostate cancer (PCa) in men with a high serum prostate-specific antigen (PSA) level. METHODS This study included 143 consecutive patients with serum a PSA level of 10-50 ng/mL who had undergone initial needle biopsies of the prostate. We defined moderate or severe inflammation in the biopsy specimens, according to De Marzo et al., as the presence of histologic inflammation. RESULTS Of the 143 patients, 86 and 57 were diagnosed with PCa (PCa group) or benign prostatic disease (BPD group), respectively. The prostate volume and transition zone volume in the PCa group were significantly smaller than those in the BPD group, and the serum PSA level, PSA density (PSAD), and PSAD in the transition zone were significantly greater than those in the BPD group. A significant difference was found in the incidence of histologic inflammation between the PCa (40.7%) and BPD (73.7%) groups. Among the factors examined, the PSAD and the presence of histologic inflammation appeared to be independently associated with the detection of PCa. Furthermore, the combined consideration of these 2 independent factors could differentiate PCa from BPD in the biopsy specimens with a sensitivity, specificity, positive predictive value, and negative predictive value of 87.2%, 63.2%, 78.1%, and 76.6%, respectively. CONCLUSIONS It seems possible to avoid unnecessary repeat biopsy using the PSAD and the presence of histologic inflammation in biopsy specimens in patients with continuously elevated serum PSA levels after the initial biopsy.

Surgical margin status of open versus laparoscopic radical prostatectomy specimens

Objectives:  To compare the surgical margin (SM) status between open and laparoscopic radical prostatectomy (RRP and LRP, respectively) specimens.

Gender as a significant predictor of intravesical recurrence in patients with urothelial carcinoma of the upper urinary tract following nephroureterectomy.

OBJECTIVES To retrospectively assess the significance of gender as a predictor of intravesical recurrence following nephroureterectomy for urothelial carcinoma of the upper urinary tract (UC-UUT). MATERIALS AND METHODS This study included 502 consecutive patients (360 male and 142 female) who were diagnosed as having clinically localized UC-UUT and underwent nephroureterectomy. Clinicopathologic outcomes of these patients were analyzed focusing on the impact of gender. RESULTS The incidence of intravesical recurrence in male patients (41.9%) was significantly greater than that in female patients (27.5%). Despite the lack of significant differences in cancer-specific and overall survivals with respect to gender, the intravesical recurrence-free survival in male patients was significantly worse than that in female patients. Of several parameters examined, univariate analysis identified gender, tumor site, and tumor focality as significant predictors of intravesical recurrence following nephroureterectomy. Of these, only gender and tumor site appeared to be independently associated with intravesical recurrence-free survival on multivariate analysis. Furthermore, there was a significant difference in intravesical recurrence-free survival according to positive numbers of these two independent factors; that is, intravesical recurrence occurred in 12 of 55 patients who were negative for both risk factors (21.8%), 96 of 280 positive for a single risk factor (34.3%), and 82 of 167 positive for both risk factors (49.1%). CONCLUSIONS The incidence of intravesical recurrence following nephroureterectomy for UC-UUT is comparatively high. Therefore, it would be potentially important to perform careful follow-up targeting intravesical recurrence for such patients, particularly for male patients and/or patients with tumor located at the ureter.

Oncological outcome of docetaxel-based chemotherapy for Japanese men with metastatic castration-resistant prostate cancer

OBJECTIVES To retrospectively review the oncologic outcomes of docetaxel-based chemotherapy in Japanese men with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS This study included 257 consecutive Japanese patients with mCRPC who were treated with docetaxel-based chemotherapy between April 2007 and March 2010. The prognostic significance of several clinicopathologic factors in these patients was analyzed. RESULTS In these 257 patients, the median age and serum value of prostate-specific antigen (PSA) prior to docetaxel-based chemotherapy were 72 years and 43.0 ng/ml, respectively. Of these patients, 64 (24.9%) and 193 (75.1%) received docetaxel as a weekly (30 mg/m(2)) and 3-weekly (70-75 mg/m(2)) regimen, respectively, and estramustine (EM) was administered in combination with docetaxel in 137 (53.3%). PSA decline was observed in 205 patients (79.8%), including 143 (55.6%) achieving PSA decline ≥ 50%. The median progression-free survival and overall survival (OS) were 4.3 and 25.4 months, respectively. Of several factors examined, univariate analysis identified performance status (PS), PSA value, significant clinical pain, bone metastasis, prior treatment with EM, treatment cycle, and PSA response as significant predictors of OS, of which only PS, significant clinical pain, prior treatment with EM, treatment cycle, and PSA response appeared to be independently related to OS on multivariate analysis. Furthermore, there were significant differences in OS according to positive numbers of these 5 independent risk factors. CONCLUSIONS Oncologic outcomes in Japanese mCRPC patients receiving docetaxel-based chemotherapy is generally favorable, and the risk stratification presented in this study may contribute to precisely predicting the prognosis of such patients.

Prognostic significance of tumor extension into venous system in patients undergoing surgical treatment for renal cell carcinoma with venous tumor thrombus

AIMS The objective of this study was to evaluate the prognostic significance of the extent of a tumor thrombus in renal cell carcinoma (RCC) involving the venous system. METHODS This study included 135 consecutive RCC patients with a venous tumor thrombus undergoing radical nephrectomy and tumor thrombectomy between 1985 and 2009. These patients were classified based on the maximal level of the tumor thrombus extending into the venous system, as follows: group 1, renal vein; group 2, infradiaphragmatic; and group 3, supradiaphragmatic. RESULTS Of the 135 patients, 65, 49 and 21 were classified into groups 1, 2 and 3, respectively. The 1, 3 and 5-year cancer-specific survival (CSS) rates in these 135 patients were 89.2, 56.9 and 49.2%, respectively. Among several factors examined, tumor size, tumor grade, perirenal fat invasion and presence of metastasis, but not extent of tumor thrombus, were significantly associated with CSS on univariate analysis. Of these significant factors, only tumor size and presence of metastasis appeared to be independently related to CSS on multivariate analysis. When the patients without metastasis were analyzed separately, CSS in groups 2 and 3 was significantly poorer than that in group 1. CONCLUSIONS These findings suggest the absence of a significant prognostic impact of the level of the tumor thrombus in a complete cohort of RCC patients with a venous tumor thrombus; however, it is warranted to determine whether the level of the tumor thrombus has different effects on the prognosis according to the presence of metastatic diseases.

Expression Profile of E-cadherin and N-cadherin in Urothelial Carcinoma of the Upper Urinary Tract is Associated with Disease Recurrence in Patients Undergoing Nephroureterectomy

OBJECTIVE To investigate the impact of the expression profile of E-cadherin and N-cadherin in urothelial carcinoma of the upper urinary tract (UC-UUT) on the probability of intra- and extravesical disease recurrence in patients undergoing nephroureterectomy. METHODS This study included 59 consecutive patients diagnosed as having clinically localized UC-UUT who underwent nephroureterectomy. Expression levels of E-cadherin and N-cadherin in resected specimens from these patients were measured by immunohistochemical staining. RESULTS In this series, intra- and extravesical recurrence occurred in 20 (33.9%) and 19 (32.2%) patients, respectively. Both intra- and extravesical recurrence-free survivals significantly favored patients with positive E-cadherin or negative N-cadherin expression compared with those of patients with reduced E-cadherin or positive N-cadherin expression, respectively. Univariate analysis identified pathologic T stage, multifocality, and N-cadherin expression as significant predictors of intravesical recurrence, of which multifocality and N-cadherin expression were independently related to intravesical recurrence-free survival on multivariate analysis. Furthermore, pathologic T stage, grade, lymph node metastasis, E-cadherin expression, and N-cadherin expression were significantly associated with extravesical recurrence-free survival on univariate analysis. Of these significant factors, pathologic T stage, grade, lymph node metastasis, and N-cadherin expression were shown to be independent predictors of extravesical recurrence on multivariate analysis. CONCLUSION These findings suggest that expression profiles of E-cadherin and N-cadherin, particularly the gain of N-cadherin rather than loss of E-cadherin expression, in UC-UUT appeared to be significantly associated with disease recurrence after nephroureterectomy.