Jun-ichi Teranishi

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.

Long-Term Analysis of Suprapubic Cystostomy Drainage in Patients with Neurogenic Bladder

Objective: We assessed the roles of suprapubic cystostomy in patients with neurogenic bladder and analyzed the complications and their courses. Patients and Methods: We reviewed 118 patients with neurogenic bladder managed with suprapubic cystostomy. The original diseases were spinal cord injury in 90, degenerative disease of the central nervous system in 15, spina bifida in 6, cerebral palsy in 3, pontine bleeding in 1, Parkinson’s disease in 1, brain tumor in 1, and dysgenesis of the external sphincter in 1. Fifty-six (62.2%) of spinal cord-injured patients demonstrated cervical damage. Renal function, urinary pH and white blood cell values were measured and evaluated after insertion. The stone-free rate after insertion was estimated by the Kaplan-Meier method. Results: Indications for cystostomy were failure of clean intermittent catheterization in 62 (52.5%) and Credé’s maneuver in 2, severe urethral damage in 30 (25.4%), replacement of urethral catheter in 3, worsening of the original disease in 15 (12.7%), deterioration of the general condition in 2, mental retardation in 2, and traumatic vesical rupture in 1. Frequent complications were formation of the bladder calculi in 30 (25%) and urinary leakage through the urethra in 11 (10%). No fatal complications occurred. The stone-free rates 5 and 10 years after insertion were 77 and 64%, respectively. The urinary pH of the stone-forming group was significantly higher than that of the stone-free group. The high urinary pH group (>7.24) had a higher risk of stone formation. Conclusions: Although continuous cystostomy drainage is not considered to be ideal management for bladder emptying, some patients with neurogenic bladder may benefit from this procedure.

Regulation of androgen receptor expression through angiotensin II type 1 receptor in prostate cancer cells.

Although the local renin‐angiotensin system (RAS) of the prostate gland is related to cell proliferation and angiogenesis, the detailed mechanism remains unclear. We examined the effects of the angiotensin II type 1 receptor (AT1R) on androgen receptor (AR) expression in prostate cancer cells.

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.

Detection of germline deletions using real-time quantitative polymerase chain reaction in Japanese patients with von Hippel–Lindau disease

Germline mutations of the VHL gene are responsible for VHL. Approximately 70% of VHL families display small intragenic mutations detectable by sequencing, whereas partial‐ or whole‐gene deletions have been described in the majority of the remaining families. For such large deletions, complex genetic techniques other than sequencing might have to be used. In this study, we describe an RQ‐PCR assay with TaqMan fluorescent probes to detect germline VHL deletions. The RQ‐PCR primer/probe sets were designed for the three VHL coding exons as well as for the 5′ promoter and 3′ untranslated regions. The RQ‐PCR assay for 30 normal and 10 known VHL deletion control samples demonstrated high sensitivity and specificity. We then screened 29 individuals from 19 classical VHL families (16 type 1, 2 type 2A, and one type 2B) and one PHEO family, as well as four solitary suspected cases, none displaying any sequence changes, for VHL deletions by the RQ‐PCR assay. We detected germline deletions in 17 (89%) classical families including 15 type 1, one type 2A, and one type 2B. We also identified two mutation carriers and two non‐carriers in our family cohort. The one PHEO family and four solitary cases did not display any deletion patterns. These findings indicated that the TaqMan‐based RQ‐PCR assay is a simple and potent technique for the rapid, sensitive, and specific investigation of VHL genetic diagnoses that could be used profitably before more complex large‐deletion detection techniques. (Cancer Sci 2006; 97: 400 –405)

Pretreatment neutrophil-to-lymphocyte ratio predicts the prognosis in patients with metastatic prostate cancer.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR), a simple marker of the systemic inflammatory response in critical care patients, has been suggested as an independent prognostic factor for several solid malignancies. We investigated the utility of pretreatment NLR as a prognosticator in patients who presented with metastatic prostate cancer.MethodsWe first investigated the correlation between NLR and prostate-specific antigen (PSA) levels in 1464 men who had both tests and were found to have prostate cancer on their biopsies at our institution from 1999 to 2015. We then assessed the relationship between pretreatment NLR and the prognosis in 48 patients who were diagnosed with prostate cancer metastasized to the lymph node and/or bone.ResultsThe NLR value was significantly elevated in men with higher PSA than in those with lower PSA (p < 0.001). In patients with metastatic prostate cancer, NLR (cut-off point of 3.37 determined by the AUROC curve) was correlated with both cancer-specific (p = 0.018) and overall (p = 0.008) survivals.ConclusionsPretreatment NLR may function as a new biomarker that precisely predicts the prognosis in patients with metastatic prostate cancer.

Analysis of NSAID-activated gene 1 expression in prostate cancer.

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce expression of NSAID-activated gene 1 (NAG-1). NAG-1 expression in prostate cancer has previously been detected by microarray and immunohistochemical analyses. We examined the mRNA expression of NAG-1 by quantitative real-time polymerase chain reaction using 51 human prostate cancer tissue specimens. The level of NAG-1 expression was higher in prostate cancer than in normal prostate tissues (p = 0.025). The level of NAG-1 expression was also significantly higher in well-differentiated prostate cancer than in moderately (p = 0.04) and poorly differentiated adenocarcinomas (p = 0.03). These data suggest that NAG-1 may be a new biomarker for evaluating the grade of malignancy in prostate cancer.

Increased neutrophil-to-lymphocyte ratio is associated with disease-specific mortality in patients with penile cancer.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR), a simple marker of the systemic inflammatory response, has been demonstrated to correlate with patient outcomes for various solid malignancies. We investigated the utility of the pretreatment NLR as a prognosticator in patients who presented with penile cancer.MethodsA total of 41 patients who underwent complete blood count with differential and subsequent radical penectomy from 1988 to 2014 were analyzed. We assessed the correlation between the NLR and the prognosis of penile cancer.ResultsThe median and mean (± SD) NLRs in 41 penile cancer patients were 3.42 and 5.03 ± 4.99, respectively. Based on the area under receiver operator characteristic curve, the cut-off value of NLR was determined to be 2.82. Patients with a high NLR (≥2.82) showed a significantly poorer cancer-specific survival (p = 0.023) than those with a low NLR.ConclusionsThe pretreatment NLR may function as a biomarker that precisely predicts the prognosis in patients with penile cancer.

Onco-testicular sperm extraction (onco-TESE) for bilateral testicular tumors: two case reports

BackgroundMost patients with testicular cancer are infertile; thus, the preservation of the sperm after surgery is an important factor to consider. We report two cases of bilateral testicular cancer in patients who underwent bilateral higher orchiectomy and simultaneous testicular sperm extraction.Case presentationTwo Asian-Japanese men were referred to our hospital with bilateral testicular tumors. Both of the patients were preoperatively diagnosed with azoospermia and requested testicular sperm extraction at the time of higher orchiectomy. In one patient, sperm was successfully harvested and then frozen. In the other patient, sperm could not be retrieved from the patient’s testis. In both patients, the pathological diagnosis was seminoma. Testicular tumors often occur in patients of reproductive age. The preservation of sperm before chemotherapy or bilateral orchiectomy is necessary for patients with testicular tumors who wish to be fathers.ConclusionsOnco-testicular sperm extraction might be an option for patients with testicular cancer and azoospermia or severe oligospermia.