Tatsuhiko Hoshii

Serum prostate-specific antigen levels reflect the androgen milieu in patients with localized prostate cancer receiving androgen deprivation therapy: Tumor malignant potential and androgen milieu†‡

Although androgen deprivation therapy (ADT) has a marked impact on the androgen milieu in vivo and outcomes of prostate cancer (PCa), it remains unclear which parameters reflect the androgen milieu during ADT or whether the milieu is associated with PCa aggressiveness.

Oncological results, functional outcomes and health-related quality-of-life in men who received a radical prostatectomy or external beam radiation therapy for localized prostate cancer: a study on long-term patient outcome with risk stratification

Health-related quality-of-life (HRQOL) after a radical prostatectomy (RP) or external beam radiation therapy (EBRT) has not been studied in conjunction with oncological outcomes in relation to disease risk stratification. Moreover, the long-term outcomes of these treatment approaches have not been studied. We retrospectively analyzed oncological outcomes between consecutive patients receiving RP (n=86) and EBRT (n=76) for localized prostate cancer. HRQOL and functional outcomes could be assessed in 62 RP (79%) and 54 EBRT (79%) patients over a 3-year follow-up period (median: 41 months) using the Medical Outcomes Study Short Form-36 (SF-36) and the University of California Los Angeles Prostate Cancer Index (UCLA PCI). The 5-year biochemical progression-free survival did not differ between the RP and EBRT groups for low-risk (74.6% vs. 75.0%, P=0.931) and intermediate-risk (61.3% vs. 71.1%, P=0.691) patients. For high-risk patients, progression-free survival was lower in the RP group (45.1%) than in the EBRT group (79.7%) (P=0.002). The general HRQOL was comparable between the two groups. Regarding functional outcomes, the RP group reported lower scores on urinary function and less urinary bother and sexual bother than the EBRT group (P<0.001, P<0.05 and P<0.001, respectively). With risk stratification, the low- and intermediate-risk patients in the RP group reported poorer urinary function than patients in the EBRT group (P<0.001 for each). The sexual function of the high-risk patients in the EBRT group was better than that of the same risk RP patients (P<0.001). Biochemical recurrence was not associated with the UCLA PCI score in either group. In conclusion, low- to intermediate-risk patients treated with an RP may report relatively decreased urinary function during long-term follow-up. The patients HRQOL after treatment did not depend on biochemical recurrence.

Bone metabolic disorder in patients with prostate cancer receiving androgen deprivation therapy (ADT): impact of ADT on the growth hormone/insulin‐like growth factor‐1/parathyroid hormone axis

Although androgen deprivation therapy (ADT) has been associated with bone loss in patients with prostate cancer, its mechanism remains unclear. The growth hormone (GH)/insulin‐like growth factor‐1 (IGF‐1)/parathyroid hormone (PTH) axis plays a critical role in bone synthesis, but its activity during ADT is also unknown.

Insulin-like growth factor-1 is associated with regulation of the luteinizing hormone production in men receiving androgen deprivation therapy with gonadotropin-releasing hormone analogues for localized prostate cancer.

BACKGROUND Luteinizing hormone (LH) during androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone analogues (GnRHa) has been thought to be biologically inactive, and the regulation of LH during ADT with GnRHa is thus unknown. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and differentiation, and IGF-1 production in the liver is dependent on growth hormone (GH) secretion from the anterior pituitary. Despite the presence of IGF-1 receptors in the gonadotroph, associations between the GH/IGF-1 and pituitary-gonadal axes, e.g., whether IGF-1 elicits the LH secretion, remain unclear. METHODS Seventy-one patients with localized prostate cancer, who received ADT with GnRHa, were prospectively studied based on their blood samples before treatment and after ADT for 6 months. We employed highly sensitive assays for measurement of serum testosterone (electrochemiluminescence immunoassay), GH/IGF-1 (radioimmunoassay), adrenocorticotropic hormone (ACTH: immunoradiometric assay), LH (chemiluminescent immunoassay), and dehydroepiandrosterone sulfate (DHEA-S: chemiluminescent enzyme immunoassay). RESULTS No correlation was noted between the pretreatment LH and IGF-1 levels; after ADT, the serum LH level was closely correlated with the IGF-1 concentration [Spearmans correlation coefficient (rs) = 0.370, P = 0.001]. The serum levels of androgens and gonadotropins reduced following ADT (P < 0.001 in all). The serum IGF-1 level increased (22 ± 6 nmol/L) compared with that at the baseline (19 ± 5 nmol/L) (P < 0.001), but no change was observed in the serum GH concentration between before and after ADT (1.4 ± 2.3 vs. 0.9 ± 0.9 μg/L, respectively, P = 0.691). The serum testosterone level was not correlated with the LH level either before or after ADT. The testosterone and DHEA-S levels after ADT were correlated with ACTH concentration (rs = 0.367, P = 0.002 and rs = 0.354, P = 0.002, respectively). We did not identify any correlations between the serum IGF-1 concentration and Gleason score, PSA value, or androgen levels. CONCLUSIONS During ADT with GnRHa, IGF-1 possibly promotes LH production, although its role is unclear. Associations among pituitary-gonadal, pituitary-adrenal, and GH/IGF-1 axes represented by IGF-1-mediated LH secretion and ACTH-mediated androgen synthesis are of interest, since both prostate epithelium proliferation and male anabolic activity are involved in these 3 axes. Assessment of oncologic outcomes is warranted for their significance in patients with prostate cancer.

Trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, has an agonistic activity on androgen receptor in human prostate cancer cells

The intracellular androgen metabolism and cell activity in prostate cancer cells with mutated (LNCaP-FGC) or wild-type (VCaP) androgen receptors in the presence of trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, were examined. Trilostane suppressed the intracellular production of androstenedione, testosterone, and dihydrotestosterone from dehydroepiandrosterone in LNCaP-FGC cells. In both LNCaP-FGC and VCaP cell types, the prostate-specific antigen (PSA) levels in media were increased by trilostane alone in a concentration-dependent manner. Both cells pretreated with trilostane showed a dose-dependent decrease in PSA production with bicalutamide (P<0.001). Trilostane should be used with particular concern when treating prostate cancer.

Adrenocorticotropic Hormone is Involved in Regulation of Androgen Synthesis in Men Receiving Androgen Deprivation Therapy for Localized Prostate Cancer

PURPOSE We elucidated the regulatory mechanism of adrenal androgen synthesis and examined the influence of pituitary-adrenal axis activity on prostate specific antigen during androgen deprivation therapy. MATERIALS AND METHODS A total of 72 patients with localized prostate cancer were prospectively studied based on blood samples before and after androgen deprivation therapy for 6 months. Serum pituitary hormones, androgens and prostate specific antigen were measured using highly sensitive assays. RESULTS After androgen deprivation therapy serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone, dehydroepiandrosterone sulfate, androstenedione and prostate specific antigen decreased compared with those at the baseline (all values p <0.001). No difference was noted between serum levels before and after androgen deprivation therapy in growth hormone (p = 0.098) and adrenocorticotropic hormone (p = 0.101). Each serum level of luteinizing hormone, follicle-stimulating hormone and growth hormone after androgen deprivation therapy was not correlated with the serum levels of androgens or prostate specific antigen. The serum adrenocorticotropic hormone level after androgen deprivation therapy was correlated with the serum levels of testosterone (p = 0.002), dehydroepiandrosterone sulfate (p = 0.002), androstenedione (p = 0.006) and prostate specific antigen (p <0.001). Serum dehydroepiandrosterone sulfate and androstenedione levels were also correlated with serum prostate specific antigen (p <0.001 and p = 0.002, respectively). CONCLUSIONS In patients treated with androgen deprivation therapy the pituitary-adrenal axis mediated by adrenocorticotropic hormone has a central role in the regulation of androgen synthesis. Serum adrenocorticotropic hormone and adrenal androgen concentrations were correlated with the posttreatment prostate specific antigen. Adrenocorticotropic hormone mediated androgen synthesis is a potential target for advanced androgen deprivation therapy.

Evaluation of magnetic resonance imaging-based prostate-specific antigen density of the prostate in the diagnosis of prostate cancer.

Objectives:  We evaluated prostate‐specific antigen (PSA) density of the prostatic volume (PSAD) estimated using transrectal ultrasonography (TRUS; TRUS‐based PSAD), magnetic resonance imaging (MRI; MRI‐based PSAD), and PSA density of the transition zone (TZ) volume (PSATZD) estimated using MRI (MRI‐based PSATZD) in the diagnosis of prostate cancer (PCa).

Angiomyomatous Leiomyoma of a Female Urethral Meatus Recurrence After Seven Years of the Resection: A Case Report

A 20 years old woman had an external urethral orifice mass and received an excision operation. Seven years later, she complained a tumor with pain that was similar to the previous tumor. She underwent the tumor removal. Pathological diagnosis was a urethral angiomyomatous leiomyoma in the new concept of estrogen receptor-positive smooth muscle tumors.

Influence of the great earthquake in the Chuetsu district on patients managing urination with clean intermittent self-urethral catheterization

Abstract:  Natural disasters cause several medical problems for victims, especially for physically challenged people. The great earthquake in the Chuetsu district in Niigata Prefecture that occurred on October 23, 2004 caused serious damage in the disaster area. We investigated the effect of this earthquake on patients managing urination with clean intermittent self‐urethral catheterization (CIC) using a questionnaire by mailing. The questionnaire was collected from 86 patients (60 men, 25 women, one sex unknown). The average age was 64.6 years old (males 64.1, females 65.8). By the first week after the earthquake, the patients with urological symptoms made up 3.8% of subjects surveyed. All of the patients had insufficient fluid intake, and did not live in their own homes, or perform CIC at home, for the period of time after the earthquake. During disasters, it is important that we secure CIC patients a living space, where they can perform CIC, with sufficient drinking water.

Retroperitoneal fibrosis associated with IgG4-related disease diagnosed by prostate biopsy developed with acute post-renal renal failure: A case report

a Department of Urology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan b Department of Nephrology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan c Department of Pathology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan d Department of Diagnostic Radiology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan e Division of Urology, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan