Biomedical subjects

Hideaki Miyake

Publications and source records attributed to Hideaki Miyake.

At least 19 recordsLinked to original sources

PubMed2007

A comparison of clinical features between chlamydial and non-chlamydial urethritis in men negative for gonococcal infection who attended a urological outpatient clinic in Japan.

OBJECTIVES: The objective of this study was to investigate the clinical features of non-gonococcal urethritis in men who attended a urological outpatient clinic in Japan. MATERIALS AND METHODS: This study included a total of 194 patients diagnosed as having non-gonococcal urethritis and subsequently judged as cured following antibiotic therapy between January 2001 and June 2005. Clinical data were analyzed after dividing these patients into two groups as follows: 96 patients with chlamydial urethritis (CU) and 98 with non-chlamydial urethritis (NCU). RESULTS: The incubation period in the CU group was significantly longer than that in the NCU group (P = 0.0020). The incidence of severity of symptoms in the NCU group was significantly greater than that in the CU group (P = 0.022), and the interval between the appearance of the initial symptom and consulting the clinic was significantly shorter in the NCU group than in the CU group (P = 0.0015). The proportion of commercial sex workers (CSWs) as the causative partner in the NCU group was significantly greater that in the CU group (P < 0.001), and the incidence of oral sex as the causative mode of sexual interaction was significantly more frequent in the NCU group than that in the CU group (P = 0.021). The duration of antibiotic therapy until cured was significantly longer in the CU group than in the NCU group (P = 0.0051). Furthermore, multivariate analysis showed that whether the infection involved CU or NCU was independently associated with the treatment interval irrespective of other factors examined (P = 0.041). CONCLUSIONS: These findings suggest that the clinical characteristics of CU and NCU clearly differ and that CU tends to require a longer time to cure than NCU; therefore, among patients with non-gonococcal urethritis, it would be particularly important to effectively control the spread of CU.

Adult↗

PubMed2007

Expression of major heat shock proteins in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy.

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.

Aged↗

PubMed2006

Significance of micrometastases in pelvic lymph nodes detected by real-time reverse transcriptase polymerase chain reaction in patients with clinically localized prostate cancer undergoing radical prostatectomy after neoadjuvant hormonal therapy.

OBJECTIVE: To clarify the significance of micrometastases in pelvic lymph nodes in patients treated by radical prostatectomy (RP) for prostate cancer after neoadjuvant hormonal therapy (NHT). PATIENTS AND METHODS: The study included 52 patients with clinically localized prostate cancer who received NHT followed by RP. The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 989 lymph nodes isolated from the 52 patients were assessed by a fully quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We regarded specimens in which either PSA or PSMA mRNA were positive as showing the 'presence of micrometastasis'. Lymph node specimens were also stained immunohistochemically with an antibody against PSA. RESULTS: Pathological examinations detected tumour cells in 11 lymph nodes from four patients, and real-time RT-PCR further identified micrometastasis in 40 lymph nodes from 19 patients with no pathological evidence of nodal involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 19 lymph nodes from 11 patients with pathologically negative nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including the pretreatment serum PSA level, biopsy Gleason score and surgical margin status. The biochemical recurrence-free survival rate in patients with no micrometastasis was significantly higher than that in those with micrometastasis. Furthermore, multivariate analysis identified the presence of micrometastasis as an independent factor predicting biochemical recurrence. CONCLUSIONS: Although residual foci of atrophic prostate cancer cells in resected lymph nodes after NHT can be difficult to diagnose by routine pathological examination, the present results show the usefulness of quantitative real-time RT-PCR targeting PSA and PSMA genes for detecting micrometastatic tumour foci in pelvic lymph nodes from patients with localized prostate cancer treated by NHT followed by RP. Furthermore, the present findings suggest that micrometastases in pelvic lymph nodes might be, at least partly, important in the development of biochemical recurrence in some patients undergoing RP after NHT.

Androgen Antagonists↗

PubMed2006

Significance of radical cystectomy for bladder cancer in patients over 80 years old.

OBJECTIVES: The objective of this study was to evaluate the usefulness of radical cystectomy for bladder cancer in elderly patients. MATERIALS AND METHODS: This study included 72 patients aged > or =80 years (group A) who underwent radical cystectomy and urinary diversion between January 1995 and December 2003, and the clinical outcome of these patients were compared with those of 557 patients aged <80 years (group B) undergoing radical cystectomy during the same period as group A. RESULTS: As the procedure for urinary diversion, ureterocutaneostomy was most frequently performed in group A (87.5%), while neobladder creation was most common in group B (43.8%). Despite the absence of significant differences in tumor grade and incidence of lymph node metastasis between these two groups, pathological stage in group A was significantly greater than that in group B. The perioperative mortality rate in group A was significantly higher than that in group B, whereas the incidences of both early and late postoperative complications in group A were similar to those in group B. Cancer-specific survival in group A was significantly lower than that in group B; however, among patients with disease < or =pT2, there was no significant difference in cancer-specific survival between these two groups. CONCLUSIONS: These findings suggest that an aggressive surgical approach may be an optimal therapeutic strategy for properly selected elderly patients who require definitive therapy for locally invasive bladder cancer, particularly in those with disease < or =pT2.

Adult↗

PubMed2006

Expression of clusterin in prostate cancer correlates with Gleason score but not with prognosis in patients undergoing radical prostatectomy without neoadjuvant hormonal therapy.

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.

Aged↗

PubMed2006

Clinicopathological features of recurrence after radical cystectomy for patients with transitional cell carcinoma of the bladder.

BACKGROUND: The objective of this study was to investigate the clinicopathological features of recurrent transitional cell carcinoma (TCC) of the bladder in patients who had previously undergone radical cystectomy. MATERIALS AND METHODS: This study included 124 patients who underwent radical cystectomy for transitional cell carcinoma (TCC) of the bladder in our institution. Several clinicopathological factors were analyzed to characterize differences between patients with and without disease recurrence, and determined predictive factors for disease recurrence using multivariate analysis. We further analyzed prognostic parameters that affect survival after disease recurrence was diagnosed. RESULTS: Of the 124 patients, 24 (19.5%) developed recurrence, and the median time to recurrence was 9.5 months (range, 1-44 months). The 5-year recurrence-free survival in these 124 patients was 75.6%. The incidence of disease recurrence was significantly associated with gender, pathological stage, lymph node metastasis, lymphatic invasion and blood vessel invasion. Multivariate analysis identified gender, pathological stage and lymph node metastasis as independent predictors of disease recurrence following radical cystectomy. After disease recurrence, the 1-year cancer-specific survival of the 24 patients was 16.7%; that is, 23 of the 24 patients had died of progressive recurrent diseases, while the remaining 1 who survived had developed recurrence in the upper urinary tract. CONCLUSIONS: These findings suggest that careful follow-up should be performed after radical cystectomy for TCC of the bladder considering gender, pathological stage and nodal involvement; however, once recurrent disease develops, the prognosis of such patients is extremely poor. Therefore, it would be potentially important to establish a multimodal therapeutic approach targeting recurrent TCC of the bladder.

Aged↗

PubMed2006

Feasibility and usefulness of high-dose chemotherapy (high-dose ifosfamide, carboplatin and etoposide) combined with peripheral blood stem cell transplantation for male germ cell tumor: a single-institute experience.

Although the usefulness of high-dose chemotherapy with peripheral blood stem cell transplantation for advanced germ cell tumor is still under evaluation in phase III randomized controlled studies, this approach is currently used as one treatment option for relapsed or advanced male germ cell tumor. Clinical outcomes of high-dose chemotherapy for a single institute from Japan are presented herein. We administered 63 courses of high-dose ifosfamide, carboplatin and etoposide chemotherapy (1250 mg/m carboplatin; 1500 mg/m etoposide; 7.5 g/m ifosfamide) to 34 men with germ cell tumors. Of these, 27 patients underwent high-dose ifosfamide, carboplatin and etoposide as first-line therapy after 2-3 courses of conventional bleomycin, etoposide and cisplatin chemotherapy, and seven patients underwent high-dose ifosfamide, carboplatin and etoposide for relapsed germ cell tumor. Peripheral blood stem cells were harvested during previous chemotherapy and sufficient CD34 cells were harvested for transplantation. Although all patients experienced grade 4 hemotoxicity, leukocyte counts recovered to above 1000/mul within 8-11 days after peripheral blood stem cell transplantation. No treatment-related deaths occurred. After a mean follow-up of 45 months (range 12-118 months), 23 of 34 patients (67.6%) remained disease-free. High-dose ifosfamide, carboplatin and etoposide could be performed safely, and could offer an effective means of treating advanced or refractory germ cell tumors in men.

Adolescent↗

PubMed2006

Analysis of differences in clinicopathological features between prostate cancers located in the transition and peripheral zones.

BACKGROUND: The objective of this study was to retrospectively characterize differences in the clinicopathological features of prostate cancer according to the zonal origin. METHODS: Among 185 consecutive patients who underwent radical prostatectomy without any neoadjuvant hormonal therapies, this study included 134 patients who were diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer according to the following criteria: TZ or PZ cancers were considered when more than 70% of the cancer area was located in the TZ or PZ, respectively. The various clinicopathological features were then compared according to this classification. RESULTS: In this series, 27 patients were diagnosed as having TZ cancer, while the remaining 107 were diagnosed as having PZ cancer. The percent of positive biopsy cores in TZ cancers was significantly lower than that in PZ cancers; however, there were no significant differences in the anatomical location of positive cores between these two groups except for the middle of prostate where TZ cancer showed a significantly lower rate of positive biopsies than PZ cancer. The preoperative serum prostate-specific antigen (PSA) value in patients with TZ cancer was significantly higher than that in those with PZ cancer. Furthermore, tumor volume in TZ cancers was significantly greater than that in PZ cancers. However, there was no significant difference in biochemical recurrence-free survival between patients with TZ and PZ cancers. CONCLUSIONS: Despite the significantly high PSA value as well as great tumor volume compared with those of PZ cancers, TZ cancers had similar biochemical cure rates following radical prostatectomy, suggesting a less aggressive phenotype of TZ cancers than that of PZ cancers.

Aged↗

PubMed2006

High-dose chemotherapy for male germ cell tumor.

Today, 20-30% of male patients with advanced germ cell tumor (GCT) do not have durable, complete remission in spite of cis-platinum (CDDP)-based chemotherapy. High-dose chemotherapy (HDCT) has been tried in CDDP refractory GCT patients. Initially HDCT was performed with autologous bone marrow transplantation in heavily treated patients. However, the clinical outcome was not good and the treatment-related death rate was not ignorable. Therefore, earlier introduction of HDCT with peripheral blood stem cell transplantation was preferable as it renders HDCT more effective and less toxic, and multicycle HDCT is feasible. The durable free rate of recent HDCT for refractory GCT patients is 32-65%. HDCT is also performed as first line chemotherapy for poor prognosis GCT patients. Induction chemotherapy followed by multicycles of HDCT was tried. The durable free rate of recent HDCT as first line chemotherapy is 43-73%. Although previous reports suggest the superiority of HDCT, one recent randomized controlled trial (RCT) failed to show an improvement with one cycle of HDCT followed by three cycles of standard-dose chemotherapy (SDCT) compared with four cycles of SDCT. Ongoing RCT comparing multicycles of HDCT with SDCT for poor prognostic GCT patients will clarify the role of HDCT. Recently, new regimens of HDCT containing paclitaxel have been devised. In this review, the history, current status and future of HDCT for advanced or refractory GCT will be discussed.

Antineoplastic Agents↗

PubMed2006

Papillary renal cell carcinoma: a clinicopathological study of 35 cases.

AIM: The objective of the present study was to characterize the clinicopathological features of histologically defined papillary renal cell carcinoma (RCC). METHODS: The present study included a total of 35 patients who were treated by radical surgery and subsequently diagnosed as having papillary RCC between April 1995 and June 2004. Clinicopathological data of these patients were retrospectively reviewed according to the previously reported classification system (Mod. Pathol. 1997; 10: 537-44). RESULTS: Of these 35 patients, 23 (65.7%) and 12 (34.3%) were diagnosed as type 1 and type 2 papillary RCC, respectively. Despite the lack of significant differences in clinical parameters between these two groups, including age, gender, clinical stage and metastasis, the incidence of symptomatic disease in patients with type 2 papillary RCC was significantly higher than that in those with type 1 papillary RCC. Pathological examinations demonstrated that there were no significant differences between these two groups in pathological stage, tumor grade or vascular invasion. Furthermore, there was no significant difference between these two groups in overall or recurrence-free survival. CONCLUSIONS: Although the present study included a small number of patients with short follow-up period, the clinicopathological features including prognoses were almost similar between patients with type 1 and type 2 papillary RCC; therefore, careful postoperative follow-up should be considered for patients with papillary RCC irrespective of morphological subtype.

Aged↗

PubMed2006

Analysis of factors predicting intravesical recurrence of superficial transitional cell carcinoma of the bladder without concomitant carcinoma in situ.

BACKGROUND: The objective of this study was to investigate risk factors for intravesical recurrence in patients with superficial bladder cancer without concomitant carcinoma in situ (CIS). METHODS: In this series, we analyzed data from patients with newly diagnosed superficial Ta or T1 transitional cell carcinoma (TCC) of the bladder without concomitant CIS who underwent complete transurethral resection (TUR) without any adjuvant intravesical instillation therapies. Multivariate analysis was used to determine significant risk factors affecting intravesical recurrence after TUR. Differences in clinicopathological features between primary and recurrent tumors were also characterized. RESULTS: Among 341 patients undergoing TUR of Ta or T1 bladder cancer, 187 diagnosed as having concomitant CIS and/or treated with adjuvant intravesical therapy were excluded, and the remaining 154 were evaluated. Intravesical recurrence was detected in 64 of the 154 patients, showing a 5-year recurrence-free survival rate of 58.3%. Among several factors examined, only tumor size was significantly associated with intravesical recurrence. Multivariate analysis identified tumor size as an independent predictor for intravesical recurrence irrespective of other parameters including age, gender, multiplicity, growth pattern, grade and stage. Recurrent tumors were significantly smaller and of a lower grade and lower stage than primary tumors, despite the absence of differences in growth pattern and the multiplicity between them. CONCLUSIONS: These findings suggest that primary tumor size could be used as a potential risk factor for predicting intravesical recurrence following TUR of superficial TCC of the bladder without concomitant CIS, and that the pathological characteristics of recurrent tumors are more favorable than those of primary tumors.

Adolescent↗

PubMed2006

Limited significance of routine excretory urography in the follow-up of patients with superficial bladder cancer after transurethral resection.

OBJECTIVES: To evaluate the utility of routine excretory intravenous urography (IVU) for detecting subsequent upper urinary tract cancer (UUTC) during the follow-up of patients with superficial bladder cancer. PATIENTS AND METHODS: The study included 413 patients who had transurethral resection (TUR) of superficial bladder cancer between January 1986 and December 2003, and were followed for at least 1 year. After TUR, patients were followed by periodic cystoscopy, urinary cytology and IVU. The risk factors for UUT recurrence after TUR were analysed, and based on this outcome, we then determined whether routine IVU should be used for patients with superficial bladder cancer. RESULTS: During the observation period, UUTCs developed in 20 of the 413 patients (4.8%) within a median of 33 months from the initial TUR to the detection of UUTCs. Among several factors examined, only multiplicity was significantly associated with UUT recurrence after TUR. Of the 20 patients with secondary UUTCs, only two, who had multiple superficial bladder cancers at initial presentation, were diagnosed as having UUTCs by routine IVU, while the remaining 18 presented with symptoms suggesting possible UUT recurrence before IVU, including macrohaematuria (10 patients), intravesical recurrence (five), positive urinary cytology (five), abdominal pain (three) and high fever (two). CONCLUSIONS: Most patients with recurrent UUTCs presented with some subjective and/or objective symptoms, and routine IVU failed to detect recurrent diseases in such patients. Therefore, routine IVU may not be required for all patients who have TUR of superficial bladder cancer.

Aged↗

PubMed2006

Induction of apoptosis and enhancement of chemosensitivity in human prostate cancer LNCaP cells using bispecific antisense oligonucleotide targeting Bcl-2 and Bcl-xL genes.

OBJECTIVE: To determine whether a specifically designed bispecific (Bcl-2/Bcl-xL) antisense oligonucleotide (ASO) induces apoptosis and enhances chemosensitivity in human prostate cancer LNCaP cells, as Bcl-2 and Bcl-xL are both anti-apoptotic genes associated with treatment resistance and tumour progression in many malignancies, including prostate cancer. MATERIALS AND METHODS: Inhibition of Bcl-2 and Bcl-xL expression by the bispecific ASO was evaluated using real-time reverse transcription-polymerase chain reaction and Western blotting, while growth inhibition and induction of apoptosis were analysed by a crystal violet assay, flow cytometry and Western blotting of apoptosis-relevant proteins. The effect of combined treatment with bispecific ASO and chemotherapy or small-interference RNA (siRNA) targeting the clusterin gene was also investigated. RESULTS: Bispecific ASO reduced Bcl-2 and Bcl-xL expression in LNCaP cells in a dose-dependent manner. There was cell growth inhibition, increases in the sub-G0-G1 fraction, and cleavage of caspase-3 and poly(ADP-Ribose) polymerase proteins in LNCaP cells after bispecific ASO treatment. Interestingly, Bcl-2/Bcl-xL bispecific ASO treatment also resulted in the down-regulation of Mcl-1 and up-regulation of Bax. The sensitivity of LNCaP cells to mitoxantrone, docetaxel or paclitaxel was significantly increased, reducing the 50% inhibitory concentration by 45%, 80% or 90%, respectively. Furthermore, the apoptotic induction by Bcl-2/Bcl-xL bispecific ASO was synergistically enhanced by siRNA-mediated inhibition of clusterin, a cytoprotective chaperone that interacts with and inhibits activated Bax. CONCLUSIONS: These findings support the concept of the targeted suppression of Bcl-2 anti-apoptotic family members using multitarget inhibition strategies for prostate cancer, through the effective induction of apoptosis.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Reconstruction of urinary tract combined with surgical management of locally advanced non-urological cancer involving the genitourinary organs.

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.

Adult↗

PubMed2006

Usefulness of the nadir value of serum prostate-specific antigen measured by an ultrasensitive assay as a predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer.

INTRODUCTION: The objective of this study was to determine whether the nadir value of serum prostate-specific antigen (PSA) measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: This study included 127 patients who underwent radical prostatectomy for clinically localized prostate cancer without neoadjuvant hormonal therapy and were pathologically diagnosed as negative for lymph node metastasis. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and the findings were analyzed with respect to several clinicopathological factors. In this series, biochemical recurrence was defined as PSA persistently >0.2 ng/ml. RESULTS: Based on the nadir PSA value, we divided 127 patients into three groups as follows: group A (n=99): or=0.05 ng/ml. The nadir PSA value was significantly associated with preoperative PSA value, but not other conventional clinicopathological prognostic parameters. During the observation period (median 31 months, range 6-75 months), biochemical recurrence occurred in 16 patients, that is, 1 in group A (6.3%), 4 in group B (25.0%), and 11 in group C (91.7%). Multivariate analysis using the Cox proportional hazards regression model indicated that the nadir PSA value was an independent predictor for biochemical recurrence after radical prostatectomy. CONCLUSION: These findings suggest that the nadir serum PSA value measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer, and that careful follow-up should be considered in cases demonstrating a nadir PSA value>0.01 ng/ml because of the significantly higher probability of biochemical recurrence in such cases.

Aged↗

PubMed2006

The limited significance of a longer duration of neoadjuvant hormonal therapy prior to radical prostatectomy for high-risk prostate cancer in Japanese men.

INTRODUCTION: The objective of this study was to evaluate the therapeutic significance of a longer duration of neoadjuvant hormonal therapy (NHT) followed by radical prostatectomy (RP) in Japanese men with high-risk prostate cancer. MATERIALS AND METHODS: This study included a total of 42 patients with high-risk prostate cancer who were treated with NHT for >or=8 months prior to RP. In this series high-risk prostate cancer was defined as clinical stage T2c or T3, pretreatment serum prostate-specific antigen (PSA) >20 ng/ml and/or a biopsy Gleason score of 8-10. Biochemical recurrence was defined as a serum PSA level of >or=0.2 ng/ml. The data of these patients were retrospectively reviewed to clarify the relationships between treatment outcomes and various clinicopathological parameters. RESULTS: The clinical stage was T2c in 13 patients and T3 in 29, the median value of pretreatment serum PSA was 43.3 ng/ml (range 9.7-322.2), and the biopsy Gleason score was 6 in 3 patients, 7 in 16 and >or=8 in 23. Following NHT (median 12 months, range 8-27), the median value of serum PSA decreased to 0.05 ng/ml (<0.01-18.3 ng/ml), and 15 patients (35.7%) were pathologically downstaged. During the median follow-up of 38 months (range 8-58), 11 patients (26.2%) developed biochemical recurrence, and the multivariate analysis identified pretreatment serum PSA, biopsy Gleason score and percentage of positive biopsy core as independent predictors of biochemical recurrence. The 3-year biochemical recurrence-free survival rate of the 42 patients was 68.3%, which was not significantly different from that of 34 patients who underwent RP for high-risk prostate cancer without NHT during the same period. CONCLUSION: A longer duration of NHT followed by RP for patients with high-risk prostate cancer resulted in a comparatively favorable outcome. However, despite the nonrandomized retrospective analysis, the present findings suggest no significant impact of long-term NHT on biochemical recurrence. Longer follow-up is needed to determine whether this therapeutic strategy is beneficial for high-risk prostate cancer patients.

Aged↗

PubMed2006

Clinicopathological features of patients with biochemical recurrence after radical prostatectomy without progressive rise in serum prostate-specific antigen.

INTRODUCTION: The objective of this study was to characterize clinicopathological features of patients with biochemical recurrence after radical prostatectomy who did not exhibit a progressive rise in serum prostate-specific antigen (PSA) during the follow-up period. MATERIALS AND METHODS: We analyzed data from 162 consecutive patients who underwent radical prostatectomy for clinically organ-confined prostate cancer without neoadjuvant hormonal therapy and were followed postoperatively for at least 1 year. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and biochemical recurrence was defined as a serum PSA of >or=0.1 ng/ml. RESULTS: A total of 32 patients (19.8%) were diagnosed as having biochemical recurrence. Among these patients, we identified 10 (31.3%) with a serum PSA>0.1 ng/ml who had not shown PSA or clinical progression during a median follow-up of 34 months after radical prostatectomy. In these 10 patients, the median time to biochemical recurrence was 17 months, the median PSA velocity after biochemical recurrence was 0.034 ng/ml/year, and there was no patient whose serum PSA value became >0.4 ng/ml. There were no clinicopathological parameters except for PSA velocity that were significantly associated with the features of these 10 patients. CONCLUSION: Because of the presence of a subset of patients with biochemical recurrence after radical prostatectomy who will not show a progressive increase in serum PSA value, the indication for adjuvant therapy for such patients should be cautiously determined considering several factors, such as PSA kinetics.

Aged↗

PubMed2006

The potential of clusterin inhibiting antisense oligodeoxynucleotide therapy for prostate cancer.

This review summarise the authors' recent experience in the development of antisense (AS) oligodeoxynucleotide (ODN) therapy that targets a cytoprotective gene, clusterin, for the treatment of prostate cancer. The acquisition of resistance to a wide variety of proapototic stimuli was initially demonstrated by introducing the clusterin gene into prostate cancer cells. Furthermore, silencing clusterin expression using AS ODN synergistically enhanced the effects of several conventional therapeutic modalities through the effective induction of apoptosis in prostate cancer xenograft models. Based on these outcomes, Phase I clinical trials were conducted using AS clusterin ODN incorporating 2'-O-(2-methoxy)ethyl-gapmer backbone (OGX-011), and the optimal dose of OGX-011 capable of inducing </= 90% suppression of clusterin in human prostate cancer tissue was determined. Collectively, these findings suggest the utility of inactivating clusterin function using AS ODN technology as a novel therapeutic strategy for prostate cancer treatment. There have been four kinds of Phase II studies that have begun to further evaluate the efficacy of OGX-011 in patients with prostate, breast and lung cancers.

Animals↗