Kazumi Noguchi

Pilot study of angiotensin II receptor blocker in advanced hormone-refractory prostate cancer.

BackgroundWe previously demonstrated that an angiotensin II receptor blocker (ARB) had the potential to inhibit cell proliferation of prostate cancer. In this study, we examined whether an ARB could elicit an antiproliferative effect on hormone-refractory prostate cancer, clinically.MethodsTwenty-three patients with advanced hormone-refractory prostate cancer who had already received secondary hormonal therapy using dexamethasone, and who were no longer receiving conventional therapy, were enrolled. All of the patients received candesartan 8 mg once daily per os and, simultaneously, androgen ablation. Change in prostate-specific antigen (PSA) was determined as the primary endpoint. The secondary end-point was change in performance status (PS). To investigate angiotensin II type 1 (AT1) receptor expression in prostate cancer tissue, real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed, using specimens, from untreated patients with prostate cancer.ResultsEight patients (34.8%) showed responsive PSA changes; six showed a decrease immediately after starting administration and two showed a stable level of PSA. Six men with a PSA decline of more than 50% showed an improvement in PS. The mean time to PSA progression (TTPP) in responders was 8.3 months (range, 1–24 months). Half of the patients showed stable or improved PS during treatment. With regard to toxic effects, only one patient showed hypotension during treatment. The RT-PCR showed that AT1 receptor expression in well-differentiated adenocarcinoma was higher than that in poorly differentiated adenocarcinoma.ConclusionThese data showed that an ARB had potential biological effects on prostate cancer, suggesting the usefulness of the cytostatic activity of such agents on recurrent prostate cancer.

Computerized tomographic ureteroscopy for diagnosing ureteral tumors.

PURPOSE Helical computerized tomography (CT) image acquisition has led to the availability of improved data sets for CT endoscopic imaging that represent virtual endoscopy using CT. We assessed the usefulness of CT ureteroscopic imaging for diagnosing ureteral tumors. MATERIALS AND METHODS A total of 16 patients with ureteral stenosis underwent surface rendering CT ureteroscopy after the intravenous administration of contrast material and furosemide. To distinguish ureteral tumors from ureteral strictures 2 observers blinded to other patient history and evaluation data independently and prospectively evaluated CT ureteroscopy with reformatted CT ureterograms in these 16 patients. CT ureteroscopic images were then correlated with surgical and pathological findings, which served as the gold standard. RESULTS Surgical and pathological findings in the 16 patients revealed 16 ureteral tumors, including carcinoma in 10 (carcinoma in situ in 1, fibroepithelial polyps in 2 and hyperplastic polypoids in 4), inflammatory intrinsic stricture in 2 and extrinsic stricture in 4 caused by retroperitoneal fibrosis in 2 and lymph node metastasis in 2. CT ureteroscopy correctly detected all lesions except 1 carcinoma in situ, 1 polypoid carcinoma and 1 hyperplastic polypoid. The sensitivity and specificity of CT ureteroscopy for detecting ureteral tumors and carcinoma were 81% and 100%, and 80% and 75%, respectively, when tumors without stalks were considered carcinoma. CONCLUSIONS CT ureteroscopy is useful for visualizing the complex morphology of ureteral tumors and distinguishing tumor from ureteral stricture.

Contrast-enhanced ultrasonography of the prostate: various imaging findings that indicate prostate cancer

Study Type – Diagnostic (non‐consecutive case series) 
Level of Evidence 3b

Evaluation of role of angiotensin III and aminopeptidases in prostate cancer cells

The aim of this study was to perform a comprehensive evaluation of angiotensin III (Ang‐III) and related converting enzymes, aminopeptidase A (APA) and N (APN), in prostate cancer.

Risk Factors for Metastatic Castration-Resistant Prostate Cancer (CRPC) Predict Long-Term Treatment with Docetaxel

Purpose For patients with metastatic castration-resistant prostatic cancer (mCRPC), docetaxel plus prednisone leads to superior survival and a higher response rate compared with mitoxantrone plus prednisone. We analyzed the efficacy of long-term treatment with ≥10 cycles of docetaxel, and validated the risk group classification in predicting overall survival (OS) in Japanese patients with mCRPC. Patients and Methods Fifty-two patients with mCRPC were administered 55 mg/m2 docetaxel and 8 mg dexamethasone, every 3 or 4 weeks, simultaneously with hormonal therapy and daily oral dexamethasone. They were divided into two groups, short-term (9 or fewer cycles) and long-term (10 or more cycles). Four risk factors including the presence of anemia, bone metastases, significant pain and visceral metastases were utilized for the risk group classification. Results Fourteen patients (27%) had an elevation of PSA in spite of docetaxel treatment, while 23 patients (44%) had a decline in PSA level, including 9 patients (17%) whose PSA level declined by ≥50%. The median duration of OS after the initiation of this therapy was 11.2 months in the short-term group and 28.5 months in the long-term group. The good risk group showed a significant difference in OS compared with the intermediate and poor risk groups (P<0.001). The median number of cycles of treatment was 14, 4 and 3 for each risk group, respectively (p<0.01). Conclusions The present study indicated that ≥10 cycles of this docetaxel therapy can significantly prolong survival in Japanese men with CRPC. This risk group classification for men with mCRPC at the initiation of this chemotherapy is useful.

Inhibition of PSA flare in prostate cancer patients by administration of flutamide for 2 weeks before initiation of treatment with slow-releasing LH-RH agonist

AbstractBackground. A prospective randomized study was designed to determine whether flutamide (FLU) administered before treatment with a luteinizing hormone-releasing hormone agonist (LH-RHa) prevented prostate-specific antigen (PSA) flare in prostate cancer patients. Methods. Prostate cancer patients were randomized into two groups and received either FLU (n = 11) or no pretreatment (n = 13) for 2 weeks before the initial injection of LH-RHa. LH-RHa (every 4 weeks) and FLU (every day) were administered throughout the period of this study. Blood samples, for the determination of PSA, testosterone (T), and luteinizing hormone levels, were collected before FLU administration, and before and 2, 7, 14, 28, 56, and 84 days after the first administration of LH-RHa. Results. Treatment with FLU prior to LH-RHa induced an early decline in PSA level. The mean PSA level showed no significant secondary rise after LH-RHa administration in those patients with FLU pretreatment. Patients in both groups showed T flare after the first LH-RHa administration. However, the number of patients with PSA flare was significantly lower in patients with prior FLU administration than in those with LH-RHa alone. Conclusion. These results clearly demonstrate that, in patients with prostatic cancer, the administration of FLU for 2 weeks prior to the first LH-RHa administration is effective in preventing PSA flare, as well as in inducing an early decline in PSA levels.

Transarterial ethanol ablation for sporadic and non-hemorrhaging angiomyolipoma in the kidney

PURPOSE We evaluated the efficacy and side effects of transarterial ethanol ablation in sporadic and non-hemorrhaging angiomyolipomas (AMLs) in the kidney. MATERIAL AND METHODS A total of 10 patients with solitary and sporadic AMLs underwent selective transarterial absolute ethanol ablation for prophylaxis against hemorrhage. We confirmed the ratio areas of tumor vessel on angiogram, those of infraction on post-ablation computed tomography (CT) and those of tumor reduction in a 3-, 6- and 12-month follow-up CT. RESULTS Once or twice a single infusion of 1 or 2 ml absolute ethanol achieved in a total occlusion of 22 feeding arteries which consisted of 7 proximal interlobar arteries, 12 distal interlobar arteries and 3 renal capsular arteries. Nontarget occlusion did not occur by ethanol reflux in any cases but occurred causing spasms provoked by repeated inflation and deflation of the balloon in one case. Total occlusion of tumor vessels was observed in 7 patients and 92-95% occlusion in 3. Ethanol ablation produced 1.8-22.5% (mean 8.4+/-6.8%) areas of infarctions but the outcome was not serious in all cases. Mean percentage areas of tumor reduction were 29.4+/-10.6% in a 3-month follow-up, 45.7+/-11.9% in a 6-month and 59.3+/-11.5% in a 12-month follow-up. CONCLUSIONS Absolute ethanol ablation for sporadic and non-hemorrhaging AML is safe and effective in reducing majority of tumor area in a 1-year follow-up.

Nomogram for overall survival of Japanese patients with bone-metastatic prostate cancer

BackgroundWe analyzed the relationship between prostate cancer outcomes and pretreatment clinical factors and developed a prognostic nomogram of overall survival (OS) of patients with bone metastasis.MethodsFrom 1993 to 2011, 463 consecutive patients were treated for bone-metastatic prostate cancer. Data sets from 361 patients were used to develop a nomogram (training data), and data sets of 102 patients were used for validation of the nomogram (validation data). Using the external validation data set, the nomogram was assessed for discriminatory ability, and the predictions were assessed for calibration accuracy by plotting actual survival against predicted risk.ResultsOf the 361 patients in the training data set, 205 (56.8%) patients died, 169 (46.8%) deaths of which were due to prostate cancer. The median follow-up period was 55.2 months. In the multivariate analysis, patient age, serum prostate-specific antigen level, clinical T stage, extent of disease on bone scan, and biopsy Gleason sum were independent prognostic factors. We developed a prognostic model comprising these five factors for patients with bone-metastatic prostate cancer. This nomogram can be used to estimate 1-, 3-, and 5-year survival probability. External validation of this model using 102 validation data sets showed reasonable accuracy (concordance index, 0.719).ConclusionOur pretreatment prognostic nomogram might be useful for Japanese patients with bone-metastatic prostate cancer.

Clinical Significance of Interruption of Therapy with Allylestrenol in Patients with Benign Prostatic Hypertrophy

Background: A multicenter, clinical trial investigated the effects of an interruption of antiandrogen therapy on subjective and objective clinical parameters in patients with benign prostatic hypertrophy (BPH).

Clinical Significance of Low Level Human Chorionic Gonadotropin in the Management of Testicular Germ Cell Tumor

PURPOSE The finding of an unexplainable persistent low level of serum human chorionic gonadotropin in the management of testicular cancer sometimes misleads physicians. To avoid unnecessary treatment we suggest a new classification and algorithm for testicular germ cell tumors to discriminate real human chorionic gonadotropin from false-positive results. MATERIALS AND METHODS A total of 24 patients who seemed to have no cancer with an increased but low level of serum human chorionic gonadotropin were evaluated. They included 17 patients with testicular germ cell tumors and 7 with no evidence of germ cell tumor. In these cases parallel serum and urine human chorionic gonadotropin were measured with the same assay and serum human chorionic gonadotropin was measured with a different assay. False-positive cases were identified by critical criteria according to the classification of gestational trophoblastic disease. RESULTS Of 17 cases of testicular germ cell tumor 12 were classified as false-positive and 5 were classified as true-positive. All of the other 7 cases with no evidence of cancer were classified as phantom cases. Of the 7 patients with phantom human chorionic gonadotropin who had a history of germ cell tumor unnecessary treatments had been performed in 3. After the discrimination was implemented no unnecessary treatments or intensive examinations were performed. CONCLUSIONS Appropriate management is possible based on a good understanding of the causes of low human chorionic gonadotropin. Our algorithm for classifying low human chorionic gonadotropin may help avoid unnecessary treatment in these patients.