Masatoshi Noda

Optimal Starting Time for Flutamide to Prevent Disease Flare in Prostate Cancer Patients Treated with a Gonadotropin-Releasing Hormone Agonist

Objective: Flare-up phenomena, such as an increase in prostate-specific antigen (PSA) and/or deterioration of symptoms, are observed in some patients undergoing gonadotropin-releasing hormone (GnRH) agonist therapy. This study was carried out to determine the optimal time for starting the administration of flutamide to prevent flare-up phenomena. Patients and Methods: Twenty-six patients with prostate cancer and elevated serum levels of PSA were randomly assigned to 5 groups. Group A patients (n = 6) were treated with a subcutaneous injection of 3.75 mg leuprorelin acetate depot alone. Group B, C, D and E patients (5 patients in each group) were treated with 375 mg/day of orally administered flutamide combined with leuprorelin. Flutamide was initiated on the day of leuprorelin injection in group B, and at 1, 2 and 4 weeks before leuprorelin injection in groups C, D and E, respectively. Serum PSA and testosterone levels were measured in each patient. Results: Pretreatment with flutamide increased the serum testosterone level, but the testosterone surge after leuprorelin administration was almost the same in all 5 treatment groups. In patients who had been treated with flutamide in combination with leuprorelin, the mean PSA level did not exceed the pretreatment levels after leuprorelin administration. The rate of decrease in PSA in the group receiving simultaneous administration of flutamide with leuprorelin showed a decline comparable to that during the period before leuprorelin administration in the flutamide pretreatment groups. Conclusion: Simultaneous administration of flutamide with a GnRH agonist is sufficient to prevent flare-up phenomena.

Clinical Evaluation of Serum Prostate‐Specific Antigen‐Alpha1 ‐ Antichymotrypsin Complex Values in Diagnosis of Prostate Cancer: A Cooperative Study

Background We studied the clinical significance of serum prostate‐specific antigen bound to α1‐antichymotrypsin (PSA‐ACT) values determined with a newly developed enzyme immunoassay.

Absorption of Epirubicin Instilled Intravesically Immediately after Transurethral Resection of Superficial Bladder Cancer

As postoperative adjuvant therapy for superficial bladder cancer, intravesical instillation therapy is commonly conducted. In this case, from the view point of prevention of intraoperative dissemination, commencement of instillation therapy at an early postoperative period is preferred. However, increased drug permeability is suspected because of damage to the bladder mucosa during operation. Therefore, this study was conducted to investigate the plasma level of epirubicin (EPI) instilled immediately after transurethral operation. EPI (20 mg/40 ml or 50 mg/100 ml) was instilled immediately after a transurethral operation, and retained in the bladder for 1 h. Blood samples were obtained before instillation, as well as 30, 60, 120 and 240 min after instillation, and EPI levels were assayed. The mean EPI concentrations (ng/ml) among the 20-mg/40 ml group (n = 5) were <2.5 and <2.0 at 30 and 60 min, respectively, after which they were undetectable. The 50-mg/100 ml group (n = 5) recorded 5.0, 4.4 and <3.0 after 30, 60 and 120 min, respectively, and after 240 min it was undetectable. Intravesical instillation of EPI immediately after a transurethral operation causes a small increase in the plasma level and it is thought to cause small systemic side effects.

Study of the nephrotoxicity of iron oxide fumes released by welding in an experimental model

Abstract Wistar male rats were tested for effects on their kidneys after inhalation of freshly formed iron oxide welding fumes. An aggregation of iron pigment was found in the lungs of rats which were exposed to these fumes in a box for 30 min. Macrophages in the lungs took in some of the iron immediately. Twenty Wistar male rats were studied after exposure to fumes in a box for 3 h a day, 3 days a week, for 3 months. The rats were sacrificed and observed over a period of 1 year. Most of the iron was taken in by the macrophages, but remained in the lungs even after 1 year. Some of the iron was discharged from the lungs through lymphatics and some reached the mediastinal lymph nodes. Some of the iron reached the kidneys, forming an aggregate in renal tubular epithelial cells, and some regenerative changes with swelling of nuclei and cystic changes were seen in the kidneys of rats 4 months after exposure to the fumes. Although we could not induce renal cancer in the present experiment, we have concluded that inhalation of iron oxide fumes may cause some renal toxicities and ultimately renal cancer as observed in the welding population.