[A case of neurogenic bladder patient whose pre-void bladder capacity was correlated with the post-void residual volume].

A 62-year-old male came to our clinic complaining of residual sensation of urine and urinary frequency. He was diagnosed with neurogenic bladder, and has been performing clean intermittent self catheterization once or twice a day. According to his urination record of voided volume (VV) and post-void residual urine volume (PVR) on every urination, we investigated the relationship between pre-void bladder capacity (BC) and PVR. BC was expressed as the sum of VV and PVR. The PVR of BC 300-400, 400-500, 500-600 and ≧600 ml was 141.1, 167.7, 186.8 and 193.3 ml, respectively. PVR significantly increased as BC increased (p＜0.01). Although there are few reports about the relationship between BC and PVR, the present results show that bladder over distension may reduce the contractility of the urinary bladder.

[Serum pancreatic enzyme elevation under treatment with sorafenib].

OBJECTIVE: Sorafenib is an oral multi-kinase inhibitor of Raf-1, VEGF and PDGF receptors and others, resulting in tumor regression and anti-angiogenesis. We studied serum pancreatic enzyme increase associated with sorafenib treatment. PATIENTS AND METHODS: In a phase II study of Japanese patients with metastatic renal cell carcinoma, a total of 131 patients received sorafenib 400 mg twice per day. Serum levels of lipase and amylase were measured on day 7 and every 3-4 weeks thereafter during treatment period. When grade 3 or 4 enzyme abnormalities were observed, ultrasound or computed tomography scan was performed to detect pancreatitis. RESULTS: The incidence of all-grades lipase and amylase increases were 55. 7% and 38. 2%, respectively, while those of grade 3 or 4 were 30. 5% and 5. 3%, respectively. The majority of these events were observed in the first 3 weeks of sorafenib treatment. Grade 3 or 4 lipase increase was detected in 32 patients (24. 4%)on day 7 measurement. These abnormal elevations spontaneously resolved in all patients. Regarding grade 3 lipase increase, the median time to recovery to grade 2 and 1 were 7 and 14 days, respectively. Three patients required interruption of the treatment. No patient showed any clinical manifestation or abnormal imaging finding suggesting pancreatitis. CONCLUSION: Pancreatic enzyme increases observed frequently under sorafenib treatment were transient and asymptomatic. They were not related to symptomatic pancreatitis.

Overall survival and good tolerability of long-term use of sorafenib after cytokine treatment: final results of a phase II trial of sorafenib in Japanese patients with metastatic renal cell carcinoma.

UNLABELLED: What's known on the subject? and What does the study add? Interim result of this study had shown promising efficacy, with response rate of 14.7% and median PFS of 7.4 months, and good tolerability of sorafenib in previously-treated Japanese patients with metastatic RCC. Final result of the study adds: (1) the median overall survival of 25.3 months, which is longer than that in the global phase III study TARGET; (2) the response rate which elevated to 19.4% because of 6 late responders achieved after 9.2 months or longer of SD period; (3) lack of either unknown adverse events nor cumulative toxicity in the long-term use of sorafenib. OBJECTIVE: • To explore the long-term efficacy and safety of sorafenib in Japanese patients with metastatic renal cell carcinoma (RCC) in a phase II trial. PATIENTS AND METHODS: • In all, 131 Japanese patients with metastatic RCC who had received nephrectomy and failed at least one cytokine-containing systemic therapy received continuous sorafenib 400 mg twice daily, and the efficacy and safety parameters were evaluated in these patients, including objective response rate, progression-free survival and overall survival. RESULTS: • Of the total, 129 patients were valid for intention-to-treat analyses and 131 patients were valid for safety analyses. • Twenty-five patients (19.4%) had confirmed partial response and 87 patients (67.4%) had stable disease as best overall response. The 25 patients included six late-responders who achieved response after 9.2 months or longer of stable disease. The objective response rate and disease control rate were 19.4% and 73.6%, respectively. • The median overall survival and median progression-free survival were 25.3 and 7.9 months, respectively. • Safety profile was consistent with those previously reported, with hand-foot skin reaction (58.0%), lipase elevation (57.3%) and diarrhoea (42.7%) as the most frequently observed drug-related adverse events. Neither unknown adverse event nor cumulative toxicity was observed over the long-term use of sorafenib. • Despite the dose discontinuation/interruption/reduction, the mean and median relative dose intensities were 86.4% and 97.4%, respectively. CONCLUSION: • The final results of this trial showed that long-term use of sorafenib after cytokine treatment was well tolerated and provided new efficacy data, including late-response events and favourable overall survival in Japanese patients with metastatic RCC.

Tumour architecture is an independent predictor of outcomes after nephroureterectomy: a multi-institutional analysis of 1363 patients.

OBJECTIVE: To assess whether tumour architecture can help to refine the prognosis of patients treated with nephroureterectomy (NU) for urothelial carcinoma (UC) of the upper urinary tract (UT), as the prognostic value of tumour architecture (papillary vs sessile) in UTUC remains elusive. PATIENTS AND METHODS: The study included 1363 patients with UTUC and treated with radical NU at 12 centres worldwide. All slides were re-reviewed according to strict criteria by genitourinary pathologists who were unaware of the findings of the original pathology slides and clinical outcomes. Gross tumour architecture was categorized as sessile vs papillary. RESULTS: Papillary growth was identified in 983 patients (72.2%) and sessile growth in 380 (27.8%). The sessile growth pattern was associated with higher tumour grade, more advanced stage, lymphovascular invasion, and metastasis to lymph nodes (all P < 0.001). In multivariable Cox regression analyses that adjusted for the effects of pathological stage, grade and lymph node status, tumour architecture (sessile or papillary) was an independent predictor of cancer recurrence (hazard ratio 1.5, P = 0.002) and cancer-specific mortality (1.6, P = 0.001). Adding tumour architecture increased the predictive accuracy of a model that comprised pathological stage, grade and lymph node status for predicting cancer recurrence and cancer-specific death by a minimal but statistically significant margin (gain in predictive accuracy 1% and 0.5%, both P < 0.001). CONCLUSION: The tumour architecture of UTUC is associated with established features of biologically aggressive disease, and more importantly, with prognosis after radical NU. Including tumour architecture in predictive models for disease progression should be considered, aiming to identify patients who might benefit from early systemic therapeutic intervention.

Decreased acetylation of histone H3 in renal cell carcinoma: a potential target of histone deacetylase inhibitors.

PURPOSE: Recent studies suggest that alterations in chromatin structure by histone acetylation may have an important role in the neoplastic process. We evaluated histone H3 acetylation in renal cell carcinoma and the effects of a histone deacetylase inhibitor on renal cancer cell lines. MATERIALS AND METHODS: The expression of acetylated histone H3 (Lys9) in renal cell carcinoma and corresponding nonneoplastic tissue specimens was evaluated. We next assessed immunohistologically the relationships between acetylated histone H3 expression and clinicopathological parameters in 44 cases of renal cell carcinoma. Furthermore, we evaluated the effects of the histone deacetylase inhibitor depsipeptide on the renal cancer cell lines Caki-1, ACHN, 769P and 786O (ATCC). RESULTS: Acetylated histone H3 expression was decreased in 85.0% of renal cell carcinomas compared to levels in nonneoplastic tissue. Decreased expression was related to high nuclear tumor grade and advanced pathological tumor stage (p = 0.048 and 0.032, respectively). Depsipeptide inhibited cell line proliferation in a time and dose dependent manner. Depsipeptide induced apoptosis in Caki-1, ACHN and 786O, and induced G2 cell cycle arrest in 769P. Concomitantly depsipeptide increased acetylated histone H3 and p21(WAF/CIP1) expression, and induced Bcl-2 phosphorylation. CONCLUSIONS: These results suggest that the decreased acetylation of histone H3 is a common alteration in a malignant phenotype of renal cell carcinoma. Increasing the amount of acetylated histone H3 might be a therapeutic option for renal cell carcinoma.

Validation of Partin tables and development of a preoperative nomogram for Japanese patients with clinically localized prostate cancer using 2005 International Society of Urological Pathology consensus on Gleason grading: data from the Clinicopathological Research Group for Localized Prostate Cancer.

PURPOSE: We validated the 2001 Partin tables and developed an original nomogram for Japanese patients using the 2005 International Society of Urological Pathology consensus on Gleason grading. MATERIALS AND METHODS: Prostatectomy specimens from 1,188 Japanese men who underwent radical prostatectomy for clinically localized prostate cancer (cT1-2) between 1997 and 2005 were analyzed. Polychotomous logistic regression analysis was used to construct a nomogram to predict final pathological stage (organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement) from 3 variables, including serum prostate specific antigen, clinical stage and biopsy Gleason score. The area under the ROC curve was used to compare the new nomogram with the Partin tables. RESULTS: Preoperative serum prostate specific antigen and biopsy Gleason score were higher in the Japanese cohort than in the Partin cohort. The distribution of clinical and final pathological stages was similar in the 2 cohorts. The AUC for predicting organ confined disease was 0.699 and 0.717 for data applied to the Partin tables and to the new nomogram, respectively. The AUC for predicting lymph node involvement was 0.793 and 0.863, respectively. CONCLUSIONS: To our knowledge this is the first preoperative nomogram developed for clinically localized prostate cancer in Japanese patients. Although the new nomogram predicted the pathological stage of prostate cancer in Japanese patients more accurately than the Partin tables, it did not satisfactorily predict organ confined disease. However, other predictive variables, such as more detailed pathological features of biopsy specimens or magnetic resonance imaging, may further improve prediction accuracy.

Simple stratification of survival using bone scan and serum C-reactive protein in prostate cancer patients with metastases.

BACKGROUND: IL-6 has been reported to be a significant prognostic factor for prostate cancer and induces synthesis of C-reactive protein (CRP) by hepatocytes. The present study was undertaken to evaluate the clinical value of serum CRP in prostate cancer patients with metastases. METHODS: The prognostic significance of serum CRP as well as tumor histology, extent of disease (EOD) on bone scan, serum levels of prostate-specific antigen (PSA) and alkaline phosphatase (ALP) and hemoglobin was assessed using Cox's proportional hazards model analyses in 126 prostate cancer patients with metastases treated with endocrine therapy. RESULTS: Serum levels of CRP, PSA and ALP significantly increased and hemoglobin significantly decreased with advancing EOD grade. Univariate analysis demonstrated that EOD, CRP, PSA, ALP, hemoglobin and tumor histology are significantly associated with disease-specific survival. Multivariate analysis demonstrated that serum CRP and EOD were significant prognostic factors. The 5-year survival rates in low-risk patients (CRP < or = 0.15 mg/dl and EOD < or = 1) and high-risk patients (CRP > 0.15 mg/dl and EOD > or = 2) were 74 and 24%, respectively. CONCLUSION: These results indicate that a combination of serum CRP and EOD can identify patients with a poor prognosis who may be candidates for innovative treatments among prostate cancer patients with metastases.

Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer.

OBJECTIVE: The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated. METHODS: TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis. RESULTS: Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without (P < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers. CONCLUSIONS: Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.

Prediction of extraprostatic extension by prostate specific antigen velocity, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer.

OBJECTIVES: To investigate the clinical value of prostate specific antigen velocity (PSAV) in predicting the extraprostatic extension of clinically localized prostate cancer. METHODS: One hundred and three patients who underwent radical prostatectomy for clinically localized prostate cancer were included in the analysis. The correlation between preoperative parameters, including PSA-based parameters, clinical stage, and histological biopsy findings, and the pathological findings were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for the local extent of the disease. RESULTS: Sixty-four (60.2%) patients had organ confined prostate cancer and 39 (39.8%) patients had extraprostatic cancer. The biopsy Gleason score, PSA, PSA density, PSA density of the transition zone, and PSAV were significantly higher in the patients with extraprostatic cancer than in those with organ confined cancer. Multivariate logistic regression analysis indicated that the biopsy Gleason score, endorectal magnetic resonance imaging findings, and PSAV were significant predictors of extraprostatic cancer (P < 0.01). Probability curves for extraprostatic cancer were generated using these three preoperative parameters. CONCLUSIONS: The combination of PSAV, endorectal magnetic resonance imaging findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.

[Bladder stone secondary to migration of an acupuncture needle].

A 61-year-old man who had been suffering from benign prostatic hyperplasia (BPH) for ten years visited our hospital complaining of dysuria and bladder pain. Abdominal X-ray showed a 2 cm calculus containing a needle-like shadow in the pelvis. Transurethral lithotripsy and trunsurethral resection of the prostate (TURP) were done. The calculus was a brown club-shaped bladder stone with the core being a 2 cm needle one side of which was broken. It was supposed to be an acupuncture needle that was retained in his back twenty years ago. This is the first case of a bladder stone secondary to migration of an acupuncture needle.

Angiotensin II type 1 receptor antagonist as an angiogenic inhibitor in prostate cancer.

BACKGROUND: Angiotensin II (AII) type 1 receptor (AT1R) antagonists are used widely as antihypertensive agents, and long-term AT1R blockade may have a protective effect against cancer. We previously demonstrated that specific AT1R blockade with candesartan, an AT1R antagonist, inhibited vascular endothelial growth factor (VEGF) production and dramatically decreased lung metastasis of renal cancer by inhibiting tumor angiogenesis. This study was then undertaken to investigate the effects of AT1R blockade using candesartan in prostate cancer (PCa). METHODS: We first determined whether hormone-independence is associated with tumor angiogenesis and AT1R expression. Accordingly, we postulated that AT1R blockade may affect angiogenesis in androgen-independent PCa rather than in androgen-dependent PCa, and investigated the effects of AII and candesartan on PCa cell lines and a tumor xenograft model. RESULTS: A human hormone-refractory PCa (HRPC) and C4-2 androgen-independent PCa cell line showed significantly higher expression of VEGF, MVD, and AT1R than did human androgen-dependent PCa and an LNCaP androgen-dependent PCa cell line. In vitro, AII and candesartan did not directly affect the proliferation of LNCaP and C4-2 cells, but candesartan significantly suppressed VEGF production in C4-2 cells. In vivo, candesartan significantly suppressed VEGF expression, serum PSA concentration and tumor growth (1.1 +/- 0.2, 45.0 +/- 17.6 ng/ml, 235.8 +/- 37.4 mm(3)) in C4-2 xenografts in castrated mice, compared with the controls (2.4 +/- 0.6, 376.7 +/- 74.2 ng/ml, 830.8 +/- 147.6 mm(3)). CONCLUSIONS: Candesartan exerted preventive effects on HRPC, rather than on androgen-sensitive PCa, through the inhibition of tumor angiogenesis.

Angiotensin II type 1 receptor antagonist candesartan as an angiogenic inhibitor in a xenograft model of bladder cancer.

PURPOSE: There have been several studies on the antitumor activity of angiotensin II type 1 receptor (AT1R) antagonists. In this study, we evaluated the efficacy of the AT1R antagonist candesartan in bladder cancer. EXPERIMENTAL DESIGN: For the study in vitro, human bladder cancer cells (KU-19-19) were cultured with or without angiotensin II and candesartan. Various cytokines and cell viability were analyzed. For the study in vivo, a tumor xenograft model was prepared in nude mice using KU-19-19 cells. Mice were given candesartan daily by oral gavage. Microvessel density, expression of vascular endothelial growth factor (VEGF), and apoptosis were assessed. RESULTS: Candesartan did not induce direct toxicity in KU-19-19 cells, but VEGF and interleukin-8 were significantly lower in candesartan-treated cells (2.55 +/- 0.25 and 6.58 +/- 0.48 pg/10(3) cells) than in the angiotensin II-treated control cells (3.16 +/- 0.42 and 7.91 +/- 0.69 pg/10(3) cells). In mice, candesartan both at doses of 2 and 10 mg/kg/d significantly suppressed tumor growth in mice (35.4% and 33.5% reduction in tumor volume). Microvessel density was significantly decreased by candesartan (9.8 +/- 2.8 per field) compared with the control group (17.6 +/- 6.0 per field), and VEGF expression was significantly suppressed by this AT1R antagonist. However, candesartan did not induce apoptosis of cancer cells in the tumor. CONCLUSIONS: Specific blockade of AT1R prevented bladder tumor growth by inhibiting angiogenesis. However, its antitumor effect was not due to direct toxicity. Because AT1R antagonists are widely used to treat hypertension, and a 2 mg/kg/d dose level of candesartan is clinically achievable, this AT1R antagonist could also be used to treat bladder cancer.

Phase II study to investigate the efficacy, safety, and pharmacokinetics of sorafenib in Japanese patients with advanced renal cell carcinoma.

OBJECTIVE: Sorafenib (Nexavar) is an oral multi-kinase inhibitor that targets tumor growth and angiogenesis. This phase II study investigated efficacy, safety, and pharmacokinetics of sorafenib in Japanese patients with advanced renal cell carcinoma (RCC). METHODS: Nonrandomized, open-label study in Japanese patients with metastatic renal cell carcinoma who had received nephrectomy and failed >/=1 cytokine-containing therapy. The primary endpoint was response rate. Patients received sorafenib 400 mg twice daily (b.i.d.) on a continuous dosing schedule. RESULTS: A total of 129 patients (median age 63 years) were valid for intention-to-treat analyses. Confirmed partial responses were observed in 16 (12.4%) patients, and investigators assessed that 19 (14.7%) of the patients achieved a partial response. Stable disease was reported in 93 (72.1%) patients, and 103 (80.5%) patients had tumor shrinkage. Median progression-free survival was 224 days and the 25th percentile of overall survival was estimated at 288 days. The most frequently occurring drug-related adverse events (any grade) were elevated lipase (56%), hand-foot skin reaction (55%), alopecia (39%), increased amylase (38%), rash/desquamation (37%), and diarrhea (34%). A total of 14 (10.7%) patients had serious sorafenib-related adverse events, including one adverse event of worst grade 5 (dyspnea occurred 35 days after the last dose of study medication). The C(trough,steady state) values in RCC patients (n = 63) receiving sorafenib 400 mg b.i.d. were similar to those obtained from a Japanese phase I study involving patients with mixed solid tumors. CONCLUSION: Sorafenib showed encouraging efficacy and was well tolerated in Japanese patients with metastatic RCC.

Current status of endocrine therapy for prostate cancer in Japan analysis of primary androgen deprivation therapy on the basis of data collected by J-CaP.

BACKGROUND: Based on the data of current status of endocrine therapy for prostate cancer registered in the Japan Study Group of Prostate Cancer (J-CaP), we conducted an analysis of primary androgen deprivation therapy (PADT) and an interim analysis of the prognosis. METHODS: Of the 26 272 cases registered in the server of J-CaP, the 19 409 cases initially receiving PADT were included in this study. The initial therapy was divided into eight categories according to its features. RESULTS: Of the 19 409 patients, 1513 (7.8%) were given anti-androgen monotherapy, 955 patients (4.9%) surgical castration only, 1001 patients (5.2%) surgical castration + anti-androgen, 3015 patients (15.5%) LHRH monotherapy, 1658 patients (8.5%) LH-RH + short-term anti-androgen, 10 434 patients (53.8%) LH-RH + anti-androgen, 37 patients (0.2%) watchful waiting and 796 patients (4.1%) other therapy. In progression-free survival, the prognosis was slightly better following maximum androgen blockade (MAB) in each stage. CONCLUSIONS: The pattern of PADT is more typical in Japan compared with that in the United States. Patients who received MAB accounted for 59.0% of all the patients. MAB tends to be more often selected for patients who are rated as being at high risk on the basis of high Gleason score or PSA level upon diagnosis in each clinical stage of the disease. Investigations of the outcome are on-going and they will make clear the significance of this trend in Japan.

Effect of angiotensin II type 1 receptor antagonist on tumor growth and angiogenesis in a xenograft model of human bladder cancer.

Several authors have investigated the antitumor activity of angiotensin II type 1 receptor (AT1R) antagonists, which are widely used as antihypertensive drugs. In this study, we evaluated the efficacy of the AT1R antagonist candesartan against bladder cancer. For the study in vitro, human bladder cancer cells (KU-19-19) were cultured with and without angiotensin II (A II) and candesartan, and cell viability and vascular endothelial growth factor (VEGF) secretion were analyzed. Also for the study in vivo, a tumor xenograft model was prepared in nude mice using KU-19-19 cells. Mice were administered candesartan daily by oral gavage, and paclitaxel via intravenous infusion. Microvessel density, VEGF expression, and apoptosis were investigated. Candesartan did not induce direct toxicity in KU-19-19 cells, but VEGF was significantly lower in candesartan-treated cells than in the A II-treated control cells. In mice, candesartan, paclitaxel and candesartan-paclitaxel significantly suppressed tumor growth to 46.0%, 35.8% and 17.3%, respectively, of the tumor volume in the control group, showing that combined treatment significantly inhibited tumor growth compared to the candesartan group. Microvessel density and VEGF were significantly decreased in the candesartan and candesartan-paclitaxel groups compared to the control group. The apoptotic index was significantly increased in the paclitaxel and candesartan-paclitaxel groups compared to the control and candesartan groups. In our experimental model, candesartan prevented bladder cancer growth by inhibiting angiogenesis. Furthermore, combined treatment with candesartan and paclitaxel enhanced paclitaxel-induced cytotoxicity. These results suggest that the AT1R antagonist candesartan may be a candidate for innovative therapy for bladder cancer.

The 5th Conference on Asian Trends in Prostate Cancer Hormone Therapy.

The Conference on Asian Trends in Prostate Cancer Hormone Therapy is an annual forum for Asian urologists now in its 5th year. The 2006 conference, held in Bali, Indonesia, was attended by 27 leading urologic oncologists from China, Indonesia, Japan, Korea, Singapore, and Taiwan and featured a packed program of presentations and discussions on a wide range of topics such as relationships among clinicians and the newly opened Asia Regional Office for Cancer Control of the International Union Against Cancer (UICC), detection rates of prostate cancer by biopsy in each of the 6 Asian countries, and favored treatment modalities for hormone-refractory prostate cancer (HRPC) in each country. The first session of the conference kicked off with a keynote lecture entitled "Activities of the UICC ARO". UICC's new office will be the nerve center for its activities in the Asia region. Along with the Asian Pacific Organization for Cancer Prevention (APOCP), UICC aims to shift the focus of attention to cancer control. As such APOCP's long-running publication the APJCP is to be re-launched as the Asian Pacific Journal of Cancer Control. Although UICC is primarily concerned with cancer, several risk factors for cancer are common also to other non-communicable diseases such as diabetes and heart disease, and an important strategy is to implement measures to control these various pathologic conditions as a whole. Apart from contributing to an Asian prostate cancer registry the UICC-ARO will provide training courses, working groups, and assistance in collecting and processing data. The keynote lecture was followed by a roundtable discussion on possible ways in which clinicians from each Asian country can work with UICC. A number of suggestions were put forth including better registration, epidemiology research, possible implementation of UICC prostate cancer guidelines, early detection and screening, and roles of diet and phytotherapy. The underlying reasons for the large but dwindling difference in incidence rates of prostate cancer in various regions of Asia should be studied while the opportunity lasts. Session 2 was devoted to 6 presentations on detection rates by biopsy in each country. Although biopsy is the gold standard for detecting prostate cancer in most areas, indications for conducting biopsy are different in each country. For example, in Indonesia doctors may use PSAD 0.15 as the cutoff level. TRUS-guided biopsy is most widely used in Asian countries. Traditional sextant biopsy is often performed, although multiple-core biopsy is commonly available and associated with better detection rates, especially in men with large prostate volume. Positive DRE, high PSA, and older age were identified as factors associated with high biopsy detection rate, although elevated PSA has limited specificity. First biopsy in men with elevated PSA had a positive detection rate of approximately 30% in all countries. Community-based screening in some countries has an overall detection rate of approximately 1%. The favorable treatment modality for HRPC was the subject of the final session. First priority for doctors in all 6 countries is to maintain serum testosterone at castration level. Many therapeutic options are available, from cytotoxic drugs to traditional herbal medicines Chemotherapeutic agents such as estramustine, docetaxel, cyclophosphamide, and mitoxantrone are often given to patients with HRPC although not all are available in every country. Prednisone and dexamethasone are used for secondary hormonal therapy. External beam radiotherapy, radioisotopic drugs such as strontium 89, and bisphosphonates are common choices to control bone pain.

[Case of nephrotic syndrome due to AL-type primary amyloidosis associated with renal cell carcinoma].

An 80-year-old man was admitted because of appetite loss, mild proteinuria, and leg edema. A computed tomography examination revealed a tumor in his left kidney, and a left nephrectomy was performed. The tumor was histologically diagnosed as a clear cell type renal cell carcinoma, and hematoxylin eosin staining of the non-tumor region of the resected kidney showed an almost normal morphology. Three months later, he was readmitted because of the development of nephrotic syndrome with a urinary protein excretion of 4.2 g/day, a serum total protein concentration of 5.0 g/dL, a serum albumin concentration of 2.4 g/dL, a serum total cholesterol concentration of 214 mg/dL, and generalized edema. A full examination revealed no evidence of metastasis or recurrence of the renal cell carcinoma or any other malignant tumor. Congo red staining and immunohistochemical staining were performed using the non-tumor region of his resected kidney, and the presence of amyloid deposits in the microvascular walls and glomeruli that did not disappear when treated with potassium permanganate was disclosed. In this manner, the patient was diagnosed as having AL-type primary amyloidosis. Bence-Jones proteinuria and gastric amyloidosis were also observed, but a bone marrow examination showed no signs of multiple myeloma. Previous studies have reported an association between renal cell carcinoma and renal amyloidosis, mainly AA-type secondary amyloidosis. To our knowledge, only two cases of renal cell carcinoma associated with primary amyloidosis have been previously reported. Therefore, the present patient not only represents a rare case of renal cell carcinoma associated with primary amyloidosis, but also reminds us that careful histological examination of the non-tumor region of the resected kidney is needed to evaluate the proteinuria associated with renal cell carcinoma, particularly in elderly patients.

Survivin associates with cell proliferation in renal cancer cells: regulation of survivin expression by insulin-like growth factor-1, interferon-gamma and a novel NF-kappaB inhibitor.

Although survivin has been widely recognized as an attractive target for cancer therapy, the exact mechanism regarding the regulation of survivin and its effect on cell proliferation have yet to be clearly defined in renal cell carcinoma (RCC). We investigated herein the association between survivin expression and cell proliferation in a RCC cell line, KU19-20. In KU19-20 cells, cell proliferation and survivin expression were significantly induced by IGF-1, whereas they were inhibited by a novel NF-kappaB inhibitor dehydroxymethyl-epoxyquinomicin (DHMEQ) and IFN-gamma. The combination of DHMEQ and IFN-gamma inhibited cell proliferation synergistically with a pronounced attenuation of survivin expression. Furthermore, treatment with survivin-specific siRNA reduced expression of survivin and significantly inhibited cell proliferation. Survivin expression was thus associated with cell proliferation in KU19-20 cells. The regulation of survivin by IFN-gamma and/or an NF-kappaB inhibitor may therefore be a potential treatment modality for RCC.

Prevention of cancer cachexia by a novel nuclear factor {kappa}B inhibitor in prostate cancer.

PURPOSE: To investigate the association between serum interleukin-6 (IL-6) and cachexia in patients with prostate cancer and the inhibitory effect of a new nuclear factor kappaB (NF-kappaB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on IL-6 production and cachexia in an animal model of hormone-refractory prostate cancer. EXPERIMENTAL DESIGN: The association between serum IL-6 levels and variables of cachexia was evaluated in 98 patients with prostate cancer. The inhibitory effects of DHMEQ on IL-6 secretion and cachexia were investigated in in vitro and in vivo studies using JCA-1 cells derived from human prostate cancer. RESULTS: Serum IL-6 levels were significantly elevated and cachexia developed in JCA-1 tumor-bearing mice as well as in prostate cancer patients with progressive disease. IL-6 secretion was significantly inhibited in JCA-1 cells exposed to DHMEQ. Intraperitoneal administration of DHMEQ (8 mg/kg) to tumor-bearing mice produced a significant amelioration of the reduction in body weight, epididymal fat weight, gastrocnemius muscle weight, hematocrit, and serum levels of triglyceride and albumin when compared with administration of DMSO or no treatment. DHMEQ caused a significant decrease of serum IL-6 level in JCA-1 tumor-bearing mice (all P < 0.05). CONCLUSIONS: These results suggested an association between serum IL-6 and cachexia in patients with prostate cancer and in JCA-1 tumor-bearing mice and that a new NF-kappaB inhibitor, DHMEQ, could prevent the development of cachexia in JCA-1 tumor-bearing mice presumably through the inhibition of IL-6 secretion. DHMEQ seems to show promise as a novel and unique anticachectic agent in hormone-refractory prostate cancer.

Endocytoscopy: novel endoscopic imaging technology for in-situ observation of bladder cancer cells.

BACKGROUND AND PURPOSE: Recent advances in endoscopy have enabled microscopic imaging of live bladdercancer cells in situ. The newly developed Endocystoscopy system (Olympus Medical Systems Co., Tokyo, Japan) is a flexible digital endoscope that has more than a 450-fold magnifying power on a video monitor. PATIENTS AND METHODS: This supermagnifying endoscope was used to evaluate bladder carcinoma in five patients through the working channel of a rigid cystoscope. RESULTS: The cell structure and nuclear morphology were imaged adequately compared with conventional hematoxylin and eosin staining of a biopsy specimen. The tumors were graded correctly in four of five cases. CONCLUSION: This novel technology appears to be useful for histologic diagnosis during endoscopic examinations, potentially allowing us to avoid a conventional biopsy.