Biomedical subjects

Isao Hara

Publications and source records attributed to Isao Hara.

At least 73 records · Page 4Linked to original sources

PubMed2005

Clinical outcome of maximum androgen blockade using flutamide as second-line hormonal therapy for hormone-refractory prostate cancer.

OBJECTIVES: To investigate the efficacy of maximum androgen blockade (MAB) using flutamide as second-line hormonal therapy for advanced hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: The study included 55 patients with HRPC who were treated with MAB using flutamide (375 mg daily) as second-line hormonal therapy. All patients had previously received bicalutamide combined with either surgical or medical castration as first-line hormonal therapy, which failed. The effect of the second-line therapy was evaluated by serum prostate-specific antigen (PSA) level alone, and the response defined as a decrease of >50% from the baseline PSA at the start of second-line therapy. RESULTS: On initiating second-line hormonal therapy there was a reduction in the PSA level in 25 of the 55 patients (45%), among whom 12 (22%) were regarded as responders, while the PSA level continued to increase in the remaining 30 (55%). The median (range) duration of the PSA response was 6 (1-13) months. During the observation period there were no severe side-effects from the second-line MAB therapy. Patients without bone metastases or whose disease progressed >1 year after first-line therapy had a significantly higher incidence of PSA response to second-line therapy, despite no significant effect of other factors examined on the PSA response to second-line therapy. Furthermore, the cause-specific survival in responders to second-line therapy was significantly better than that in nonresponders; however, multivariate analysis showed that no factors, including response to second-line therapy, could be used as independent predictors of cause-specific survival. CONCLUSIONS: MAB using flutamide as second-line hormonal therapy can give a comparatively favourable PSA response with no severe side-effects; therefore, this therapy may be suitable for patients with HRPC after primary MAB using bicalutamide has failed, particularly in those with no bone metastases or whose disease has progressed for >1 year after first-line therapy.

Aged↗

PubMed2005

Prognostic significance of the tumor volume in radical prostatectomy specimens after neoadjuvant hormonal therapy.

INTRODUCTION: The objective of this study was to determine whether the tumor volume in radical prostatectomy specimens of patients with prostate cancer who underwent neoadjuvant hormonal therapy (NHT) could be used as a prognostic predictor. PATIENTS AND METHODS: In this study, we included 96 patients who underwent NHT followed by radical prostatectomy between January 1995 and July 2003 in our institutions. Several clinicopathological factors of these patients were analyzed, focusing on the association between tumor volume in radical prostatectomy specimens and disease recurrence. RESULTS: The tumor volume in radical prostatectomy specimens after NHT was significantly associated with capsular penetration, seminal vesicle invasion, and lymph node metastases, among the factors examined in this study. The biochemical recurrence-free survival rates in patients with tumor volumes <1.0 cm(3) were significantly higher than in those having tumor volumes > or =1.0 cm(3). However, multivariate analysis showed that the tumor volume could not be used as an independent predictor for biochemical recurrence. CONCLUSIONS: In patients who received NHT prior to radical prostatectomy, the tumor volume was shown to correlate with other prognostic indicators. Furthermore, a higher probability of biochemical recurrence was noted, when there was a residual tumor volume > or =1.0 cm(3) after NHT. Thus, careful follow-up and, if necessary, additional treatment should be considered in cases demonstrating tumor volumes > or =1.0 cm(3) after NHT.

Aged↗

PubMed2005

Antisense oligodeoxynucleotide therapy for bladder cancer: recent advances and future prospects.

Despite remarkable progress in therapeutic options for the management of bladder cancer, it remains a challenge for urologists to achieve successful outcomes in the treatment of both superficial and invasive bladder cancers. In this review, recent advances in the field of antisense oligodeoxynucleotide therapy targeting several genes playing functionally important roles in the progression and recurrence of bladder cancer are summarized. Data showing the synergistic antitumor activities of antisense oligodeoxynucleotide therapy, combined with several treatments, including cytotoxic chemotherapy, radiation and other molecular targeting therapies, are also presented. Finally, the future direction of antisense oligodeoxynucleotide therapy in the therapeutic strategy of bladder cancer is discussed. These findings may help clarify the significance of antisense oligodeoxynucleotide therapy as an attractive alternative to conventional strategies.

Clinical Trials as Topic↗

PubMed2005

Therapeutic efficacy of adenoviral-mediated p53 gene transfer is synergistically enhanced by combined use of antisense oligodeoxynucleotide targeting clusterin gene in a human bladder cancer model.

To establish a more effective therapeutic strategy against advanced bladder cancer, we investigated the effects of combined treatment with antisense (AS) oligodeoxynucleotide (ODN) targeting the anti-apoptotic gene clusterin and adenoviral-mediated p53 gene transfer (Ad5CMV-p53) using the human bladder cancer KoTCC-1 model. Clusterin expression in KoTCC-1 cells was highly upregulated by Ad5CMV-p53 treatment; however, AS clusterin ODN treatment further suppressed clusterin expression in KoTCC-1 cells after Ad5CMV-p53 treatment. AS clusterin ODN treatment synergistically enhanced the cytotoxic effect of Ad5CMV-p53, and DNA fragmentation characteristic of apoptosis was observed only after combined treatment with AS clusterin ODN and Ad5CMV-p53, but not after treatment with either agent alone. Administration of AS clusterin ODN and Ad5CMV-p53 into nude mice resulted in a significant inhibition of KoTCC-1 tumor growth as well as lymph node metastases compared to administration of either agent alone. Furthermore, combined treatment with AS clusterin ODN, Ad5CMV-p53, and cisplatin completely eradicated KoTCC-1 tumors and lymph node metastases in 60% and 100% of mice, respectively. These findings suggest that combined treatment with AS clusterin ODN and Ad5CMV-p53 could be a novel strategy to inhibit bladder cancer progression, and that further additional use of a chemotherapeutic agent may substantially enhance the efficacy of this combined regimen.

Adenoviridae↗

PubMed2005

Introduction of insulin-like growth factor binding protein-2 gene into human bladder cancer cells enhances their metastatic potential.

Overexpression of insulin-like growth factor binding protein-2 (IGFBP-2) has been shown to be associated with tumor progression in several human malignant tumors; however, the significance of IGFBP-2 expression in bladder cancer remains poorly defined. The objective of this study was to investigate the effect of IGFBP-2 overexpression in human bladder cancer KoTCC-1 cells on their phenotype associated with tumor progression. We introduced IGFBP-2 cDNA into KoTCC-1 cells, which do not express a detectable level of IGFBP-2 protein, thus generating an IGFBP-2 overexpressing cell line (KoTCC-1/BP2). We also generated a vector-only-transfected cell line (KoTCC-1/C) as a control. Despite the absence of a significant difference in in vitro cell growth rates and motilities among KoTCC-1 sublines, KoTCC-1/BP2 exhibited significantly higher invasive ability than KoTCC-1/C. Gelatin zymography showed a marked increase in matrix metalloproteinase-2 (MMP-2) production by KoTCC-1/BP2 compared with that by KoTCC-1/C. Furthermore, there was no significant difference in sub-cutaneous tumor growth among KoTCC-1 sublines; however, more advanced tumor progression, including lymph node metastasis and hemorrhagic ascites formation, was observed after the implantation of KoTCC-1/BP2 into the bladder wall of nude mice than after the implantation of KoTCC-1/C. These findings suggest that overexpression of IGFBP-2 induces an increase in MMP-2 production, resulting in the enhanced metastatic potential of bladder cancer.

Animals↗

PubMed2005

Synergistic inhibition of tumor growth and metastasis by combined treatment with TNP-470 and docetaxel in a human prostate cancer PC-3 model.

TNP-470, a potent inhibitor of angiogenesis, was reported to synergistically enhance the antitumor effects of cytotoxic agents. The objective of this study was to evaluate the effectiveness of combined treatment with TNP-470 and docetaxel both in vitro and in vivo using androgen-independent human prostate cancer PC-3 cells. The in vitro growth-inhibitory and apoptotic effects of docetaxel and/or TNP-470 on PC-3 cells were assessed using MTT and TUNEL assays. The combined effect of docetaxel and TNP-470 therapy after subcutaneous and orthotopic injection of PC-3 cells into athymic nude mice was evaluated. In vivo effects of this combined regimen on PC-3 tumors were analyzed by the TUNEL assay and immunohistochemical staining of CD31 to quantify microvessel density (MVD). Combined treatment with TNP-470 and docetaxel synergistically inhibited PC-3 cell growth in vitro through the enhanced induction of apoptotic cell death compared with treatment with either agent alone, a result explained, at least in part, by the down-regulation as well as phosphorylation of potential anti-apoptotic genes, Bcl-2 and Bcl-XL. Combined treatment with TNP-470 and docetaxel synergistically suppressed subcutaneous PC-3 tumor growth compared with treatment with either agent alone. Furthermore, this combined regimen significantly inhibited orthotopic PC-3 tumor growth and reduced the incidence of lymph node metastasis. Immunohistochemical analysis of the subcutaneous tumor after each treatment demonstrated that administration of docetaxel as well as TNP-470 significantly induced apoptotic cell death; in contrast, a significant reduction in MVD was observed only after TNP-470. These findings suggest that docetaxel and TNP-470 act synergistically to inhibit PC-3 tumor growth and metastasis, by enhancing apoptosis and suppressing angiogenesis.

Angiogenesis Inhibitors↗

PubMed2005

Synergistic antitumor effect of combined use of adenoviral-mediated p53 gene transfer and antisense oligodeoxynucleotide targeting clusterin gene in an androgen-independent human prostate cancer model.

Our recent studies showed that antisense oligodeoxynucleotide targeting antiapoptotic gene, clusterin, enhanced apoptosis induced by conventional therapeutic modalities using several prostate cancer models. In this study, to establish a more effective therapeutic strategy against prostate cancer, we investigated the effect of combined treatment with antisense clusterin oligodeoxynucleotide and adenoviral-mediated p53 gene transfer (Ad5CMV-p53) in an androgen-independent human prostate PC3 tumor model. Treatment of PC3 cells with 500 nmol/L antisense clusterin oligodeoxynucleotide decreased clusterin mRNA by >80% compared with that with 500 nmol/L mismatch control oligodeoxynucleotide. Clusterin mRNA expression in PC3 cells was highly up-regulated by Ad5CMV-p53 treatment; however, antisense clusterin oligodeoxynucleotide treatment further suppressed clusterin expression in PC3 cells after Ad5CMV-p53 treatment. Antisense clusterin oligodeoxynucleotide treatment significantly enhanced the sensitivity of Ad5CMV-p53 in a dose-dependent manner, reducing the IC50 of Ad5CMV-p53 by 75%. Apoptotic cell death was detected after combined treatment but not after treatment with either agent alone. In vivo administration of antisense clusterin oligodeoxynucleotide and Ad5CMV-p53 resulted in a significant inhibition of s.c. PC3 tumor growth as well as lymph node metastases from orthotopic PC3 tumors compared with administration of either agent alone. Furthermore, combined treatment with antisense clusterin oligodeoxynucleotide, Ad5CMV-p53, and mitoxantrone completely eradicated s.c. PC3 tumors and lymph node metastases from orthotopic PC3 tumors in 60% and 100% of mice, respectively. These findings suggest that combined treatment with antisense clusterin oligodeoxynucleotide and Ad5CMV-p53 could be a novel strategy to inhibit progression of hormone-refractory prostate cancer and that further addition of chemotherapeutic agents may help to enhance the efficacy of this combined regimen.

Adenoviridae↗

PubMed2005

[Gene therapy].

We selected bone-metastatic prostate cancer as the target form of recurrent prostate cancer and developed a suicide-gene therapy based on an adenovirus vector with an organ-specific osteocalcin promoter. Related clinical studies have already been conducted in the United States at the University of Virginia, where results so far have established the safety of this therapy. In the present paper, in addition to presenting the results of these gene-therapy studies from the basic research to the clinical stage, we discuss the clinical studies begun by our group in August 2003. In the 21st century, therapeutic systems in use are undergoing major changes. Gene therapy is likely to become an important therapeutic option in recurrent prostate cancer. In terms of theory and technology however, this form of treatment is still at a very immature stage of development. We look forward to evolution in this field to provide an established treatment for recurrent prostate cancer and are committed to actively continuing with the development of gene therapy through translational research.

Adenoviridae↗

PubMed2005

Enhanced radiosensitivity by inhibition of the anti-apoptotic gene clusterin using antisense oligodeoxynucleotide in a human bladder cancer model.

Clusterin has been shown to be implicated in the acquisition of resistant phenotype to various kinds of apoptotic stimuli, including radiation. In bladder cancer, our previous study demonstrated that overexpression of clusterin is closely associated with disease progression and recurrence. The objective of this study was to investigate whether radiation sensitivity was enhanced by suppressing clusterin gene expression with antisense (AS) oligodeoxynucleotide (ODN) in the human bladder cancer KoTCC-1 model. Clusterin mRNA in KoTCC-1 cells after radiation was up-regulated in a dose-dependent manner; however, AS clusterin ODN treatment resulted in a marked inhibition of clusterin mRNA even after irradiation. Combined treatment of KoTCC-1 cells with radiation and AS clusterin ODN synergistically decreased plating efficacy and induced apoptotic cell death compared with either radiation or AS clusterin ODN treatment alone. In vivo systemic administration of AS clusterin ODN enhanced radiation sensitivity, significantly reducing subcutaneous KoTCC-1 tumor volume in nude mice, compared with that of mismatch control ODN. Moreover, additional administration of cisplatin to this combined regimen further achieved potential antitumor effects on subcutaneous KoTCC-1 tumor growth in nude mice. Collectively, these findings suggest that clusterin acts as a cell survival protein mediating radioresistance through the inhibition of apoptosis, and that inactivation of clusterin using AS technology might offer a novel strategy to improve the outcome of radiation therapy for patients with bladder cancer.

Animals↗

PubMed2005

Limited value of perineural invasion in radical prostatectomy specimens as a predictor of biochemical recurrence in Japanese men with clinically localized prostate cancer.

The objective of this study was to determine whether the presence of perineural invasion (PNI) in radical prostatectomy specimens could be a useful prognostic parameter in Japanese men with prostate cancer. Between January 1995 and September 2003, 202 Japanese men underwent radical retropubic prostatectomy for prostate cancer without any neoadjuvant therapies prior to surgery. We retrospectively analyzed the relationship between PNI in radical prostatectomy specimens and other prognostic factors, and also assessed the significance of PNI in biochemical recurrence after radical prostatectomy. The presence of PNI was significantly related to clinical stage, pathological stage, Gleason score, seminal vesicle invasion, lymph node metastasis and tumor volume, but not pretreatment serum prostate specific antigen value. During the observation period, biochemical recurrence occurred in 20 patients (3 in patients without PNI and 17 in those with PNI), and the biochemical recurrence-free survival rate in patients with PNI was significantly lower than that in patients without PNI. In addition to-PNI, pathological stage, seminal vesicle invasion, lymph node metastasis and tumor volume were significantly associated with the biochemical recurrence-free survival rate; however, among these five factors, only seminal vesicle invasion was an independent predictor of biochemical recurrence on multivariate analysis. Despite a significant association between several prognostic parameters, PNI was not an independent predictor of biochemical recurrence; therefore, it may not provide an additive effect to consider the presence of PNI in predicting the prognosis of Japanese men who underwent radical prostatectomy if there are other conventional parameters available.

Aged↗

PubMed2005

Clinical outcome of oral uracil/tegafur (UFT) therapy for patients with hormone refractory prostate cancer.

There is no standard therapeutic strategy for advanced hormone refractory prostate cancer after the initial hormonal therapy fails. The objective of this study was to retrospectively evaluate the clinical outcome of the oral anticancer agent, uracil/tegafur (UFT) for patients with hormone refractory prostate cancer. This study included 68 patients with hormone refractory prostate cancer treated by oral administration of UFT (300-600 mg/day). All patients had previously received maximum androgen blockade (MAB) which failed. In this series, response was defined as more than 50% decrease from the baseline prostate specific antigen (PSA) value at the start of second line therapy. Upon initiating administration of UFT, a reduction in PSA value was observed in 41 of the 68 patients (60.3%), among whom 13 (19.1%) were regarded as responders; however, PSA value continued to increase in the remaining 27 (39.7%). Median duration of PSA response was 7 months (range 1-22 months). During the observation period, there were no severe side effects due to UFT administration, but 7 patients transiently presented appetite loss. Patients without bone metastasis at the initial diagnosis or whose serum PSA value at the start of UFT therapy was less than 2.0 ng/ml showed a significantly higher incidence of PSA response to UFT; however, other factors examined had no significant impact on PSA response to UFT. Furthermore, cause-specific survival in responders to UFT therapy was significantly better than that in non-responders. These findings suggest that administration of UFT after the failure of initial MAB therapy can achieve a comparatively favorable PSA response without severe side effects; therefore, it may be worthy to consider administering UFT to patients with hormone refractory prostate cancer.

Administration, Oral↗

PubMed2005

[Is second course intravesical Bacillus Calmette-Guerin therapy for recurrent carcinoma in situ of the bladder useful?].

We evaluated the usefulness of second course intravesical bacillus Calmette-Guerin (BCG) therapy for carcinoma in situ (CIS) of the bladder that failed to respond to the initial BCG therapy. Between January 1995 and December 2000, 185 patients with CIS of the bladder underwent an initial 6- or 8-week course of intravesical BCG instillation with an average follow-up period of 40.9 months (range: 3.8 to 94.8 months). Of the 185 patients, 160 (86.5%) completely responded to an initial course of BCG therapy. During follow up, 49 (30.6%) of the complete responders had recurrent transitional cell carcinoma. Overall, 9 (36.0%) of the 25 patients who did not respond completely to the initial 6- or 8-week course of BCG therapy and 22 (44.9%) of the 49 who had recurrent tumor after initial complete response, a total of 31 patients received the second course intravesical BCG therapy. Of the 9 incomplete responders, 8 (88.9%) achieved a complete response after the second course BCG therapy. With an average follow-up period of 39.6 months (range: 2.8 to 62.2 months), 2 (22.2%) of the 8 had recurrence. On the other hand, 17 (77.3%) of the 22 with recurrent tumor after the initial complete response developed recurrence with an average follow-up period of 14.1 months (range: 2.8 to 55.2 months). Seven (31.8%) of the 17 patients had disease progression to muscle invasion. Subsequently, cystectomy was done in 10 (58.8%) and radiation in 1 (5.9%). Our results suggest that a selected group of incomplete responders with initial BCG therapy may benefit from continued second course BCG. However, in patients who had recurrence after initial BCG success, the benefits of second course BCG therapy are limited. Careful surveillance and aggressive therapy on optimal timing are mandatory.

Adjuvants, Immunologic↗

PubMed2005

Enhanced expression of the secreted form of clusterin following neoadjuvant hormonal therapy as a prognostic predictor in patients undergoing radical prostatectomy for prostate cancer.

The objective of this study was to characterize changes in clusterin expression in prostate cancer before and after neoadjuvant hormonal therapy (NHT), and to assess the prognostic significance of clusterin expression following NHT in patients undergoing radical prostatectomy. Paired needle biopsy and corresponding radical prostatectomy (RP) specimens obtained from 76 patients were analyzed for expression of clusterin protein by immunohistochemical staining with an antibody recognizing all of the clusterin isoforms. RP specimens following NHT demonstrated stronger expression of clusterin than the corresponding needle biopsy specimens. Clusterin protein was present in the cytoplasm of both biopsy and RP specimens; however, there was no nuclear staining identified in any specimens. The expression level of clusterin in biopsy specimens was significantly associated with the biopsy Gleason score, but not with other parameters available before RP. Furthermore, clusterin expression in RP specimens was significantly associated with the preoperative prostate specific antigen value and pathological stage, but not with other pathological factors. Biochemical recurrence-free survival in patients with strong clusterin expression in RP specimens was significantly lower than that in those with weak clusterin expression; however, the level of clusterin expression could not be used as an independent predictor of biochemical recurrence. These findings suggest that despite the lack of independent significance, the expression level of the secreted form of clusterin in prostate cancer tissue after NHT, which may inversely reflect the therapeutic effect of NHT, could be a useful parameter predicting biochemical recurrence in patients undergoing RP.

Aged↗

PubMed2004

Protection of androgen-dependent human prostate cancer cells from oxidative stress-induced DNA damage by overexpression of clusterin and its modulation by androgen.

BACKGROUND: Recent studies reported that oxidative stress is one of the major factors associated with the progression of prostate cancer through the accumulation of DNA damage. In the present study, we investigated the effect of oxidative stress on cell injury using androgen-dependent human prostate cancer LNCaP cells overexpressing clusterin, which has been shown to play crucial roles in the acquisition of resistance to several apoptotic stimuli. METHODS: We introduced clusterin cDNA into LNCaP cells which do not express a detectable level of clusterin expression, and generated a clusterin-overexpressing cell line (LNCaP/Cl) and a control vector only-transfected cell line (LNCaP/Co). The effects of hydrogen peroxide (H2O2) treatment on the LNCaP sublines with and without the addition of dihydrotestosterone (DHT) were analyzed using the in vitro mitogenic assay and lipid peroxidation assay, and morphological changes in the LNCaP sublines after H2O2 treatment were examined by staining with Hoechst 33258. The degrees of DNA damage induced by H2O2 into the LNCaP sublines were evaluated by the measurement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) level. RESULTS: H2O2-induced apoptosis in LNCaP/Cl was significantly suppressed compared with that in LNCaP/Co through the inhibition of membrane damage; however, the measurement of 8-OHdG level demonstrated that DNA damage was more intensively accumulated in LNCaP/Cl cells than LNCaP/Co cells. Furthermore, DHT suppressed the incidence of apoptotic cell death and enhanced the formation of 8-OHdG in both LNCaP/Cl and LNCaP/Co cells after H2O2 treatment in a dose-dependent manner. CONCLUSIONS: These findings suggest that clusterin may contribute to conferring resistance to oxidative stress-mediated cellular injury on prostate cancer cells, especially in the presence of androgen.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2004

Clinical outcome of transrectal ultrasound-guided prostate biopsy, targeting eight cores, for detecting prostate cancer in Japanese men.

BACKGROUND: The objective of this study was to evaluate the clinical usefulness of transrectal ultrasound (TRUS)-guided eight-core prostate biopsy for detecting prostate cancer in Japanese men. METHODS: Between January 1998 and September 2002, a total of 628 consecutive patients underwent TRUS-guided biopsy of the prostate. As a rule, eight cores were taken from each patient; that is, standard sextant cores from the peripheral zone and two additional cores from the bilateral anterior lateral horns (ALHs). The present study included 428 patients who underwent an initial biopsy, whose age was between 50 and 79 years, and whose prostate-specific antigen (PSA) value was less than 20.0 ng/ml. The cancer detection rate was calculated according to age, PSA, digital rectal examination (DRE) and TRUS findings, prostate volume, and PSA density (PSAD). We also assessed whether the sampling of the two extra cores from the ALHs increased the cancer detection rate. RESULTS: Of the 428 patients, 101 (23.6%) were diagnosed as having cancer by eight-core prostate biopsies. The cancer detection rate was significantly associated with the PSA value (ng/ml; < or =4 versus 4-10, versus 10-20), DRE findings (normal versus abnormal), TRUS findings (normal versus abnormal), and PSAD (ng/ml2; < or =0.15 versus >0.15). but not with age (years: < or =70 versus >70) on prostate volume (ml; < or =30 versus 30-50, versus >50). Of the 101 patients diagnosed as having prostate cancer, 11 had positive cores only in the ALH; that is, the increase in the cancer detection rate yielded by obtaining two extra cores from the ALHs was 10.9%. CONCLUSION: Despite the reasonable strategy, systematic prostate biopsy targeting eight cores did not significantly improve the cancer detection rate compared with that of standard sextant biopsy in Japanese men. However, the increased cancer detection rate yielded by additional sampling from the ALHs was comparatively prominent in the subgroup whose PSA value was in the gray zone (4-10 ng/ml) or whose prostate volume was greater than 50 ml.

Adult↗

PubMed2004

Limited usefulness of the free-to-total prostate-specific antigen ratio for the diagnosis and staging of prostate cancer in Japanese men.

BACKGROUND: The objective of this study was to evaluate the clinical significance of measuring the free-to-total (f/t) prostate-specific antigen (PSA) ratio for the differentiation of prostate cancer from benign prostatic hypertrophy (BPH) and for the staging of prostate cancer in Japanese men. METHODS: Before treatment, tPSA and fPSA were measured in 147 patients with prostate cancer and in 253 with BPH, using immunofluorometric techniques. Furthermore, the f/t PSA ratio and the tPSA density of the whole prostate (PSAD) were calculated. RESULTS: The tPSA and PSAD levels in patients with prostate cancer paralleled the clinical stage, and were significantly higher than the levels in patients with BPH, while the f/t PSA ratio was not associated with clinical stage, despite the significantly lower values in prostate cancer patients than in BPH patients. Furthermore, the tPSA and PSAD values, but not the f/t PSA ratio, were significantly different between patients with pathologically extraprostatic disease and those with organ-confined disease. Calculation of the specificity of each assay within the range of 80%-95% sensitivity showed that tPSA and PSAD provided better specificities than the f/t PSA ratio. However, there was no significant difference in specificities among these three assays. In prostate cancer and BPH patients with PSA values of 4.1-10 ng/ml, the specificities of tPSA and PSAD were also superior to that of the f/t PSA ratio. CONCLUSION: These findings suggest that measurement of the f/t PSA ratio does not provide any significant additional information for the diagnosis and staging of prostate cancer in Japanese men when tPSA and PSAD values are available.

Biomarkers, Tumor↗

PubMed2004

Clinicopathological features of recurrence after radical surgery for nonmetastatic renal cell carcinoma.

BACKGROUND: The objective of this study was to clarify the clinicopathological features of recurrent renal cell carcinoma (RCC) in patients who had undergone curative surgical resection of primary disease. METHODS: The study included 171 patients treated by radical surgery for nonmetastatic RCC in our institution. Several clinicopathological factors were analyzed to determine differences between patients with and without disease recurrence. We further investigated predictive factors for disease recurrence, as well as prognostic factors after disease recurrence, using univariate and multivariate analyses. RESULTS: Thirty-four of the 171 patients (19.9%) developed recurrence, and the median time from surgery to recurrence was 11 months (range, 1 to 146 months). The incidence of disease recurrence was significantly associated with sex, mode of detection, tumor size, pathological stage, tumor grade, and microvascular invasion (MVI). Univariate analysis showed that five factors--mode of detection, tumor size, pathological stage, tumor grade, and MVI--were found to be significant risk factors for recurrence after surgery, while only the pathological stage was an independent predictor of recurrence by multivariate analysis. After disease recurrence, the 1-, 3-, and 5-year cancer-specific survival rates were 66.3%, 45.9%, and 13.4%, respectively. Despite the absence of independent prognostic predictors after recurrence, recurrence more than 1 year after surgery and complete resection of recurrent lesions were shown to be significant prognostic factors by univariate analysis. CONCLUSION: These findings suggest that careful follow-up should be performed for patients showing a high pathological stage after radical surgery for nonmetastatic RCC, because of the higher probability of disease recurrence, and that after recurrence, intensive treatment should be considered, particularly for patients with unresectable recurrent disease occurring within 1 year after initial radical surgery.

Aged↗

PubMed2004

Oncocytic adrenocortical carcinoma.

Oncocytic adrenocortical carcinoma is rare. To our knowledge, only 6 cases have been previously reported. We describe an additional case of oncocytic adrenocortical carcinoma. A 54-year-old man presented with a right subcostal mass. Computed tomography demonstrated a massive tumor in the right abdomen. Because renal or adrenal cancer was suspected, right adrenalectomy and nephrectomy were performed. Histologic examination revealed an oncocytic adrenocortical carcinoma. Five months postoperatively, multiple metastases had developed and were treated with surgical resection, chemotherapy, vascular embolization, and radiotherapy. At last follow-up, the patient was alive with pulmonary and adrenal metastases and undergoing treatment with mitotane.

Adenocarcinoma↗