Isoji Sasagawa

Therapeutic Outcome of Primary Aldosteronism: Adrenalectomy Versus Enucleation of Aldosterone-Producing Adenoma

Our followup study of 48 patients with primary aldosteronism concerns the results of 2 different operative methods. After preoperative localization of the unilateral solitary tumor 22 patients underwent unilateral adrenalectomy and 26 underwent enucleation of aldosterone-producing adenoma. Both operative methods improved hypertension, hypokalemia, the low urinary sodium-to-potassium ratio, suppressed plasma renin activity, high plasma aldosterone concentration, high urinary aldosterone excretion and high urinary kallikrein excretion in similar orders of magnitude for 5 years. Levels of plasma cortisol and plasma adrenocorticotropic hormone following respective operations were also identical. Five years postoperatively, ambulation and furosemide administration under low sodium diet stimuli remarkably enhanced plasma renin activity and plasma aldosterone concentration in the aldosterone-producing adenoma enucleation group (p < 0.001), almost similar to that of normal subjects but increment magnitudes were slight (p < 0.05 to < 0.01) in the adrenalectomy group. Preoperatively, angiotensin II infusion failed to increase plasma aldosterone concentration in patients with primary aldosteronism. After respective operations, responses of plasma aldosterone concentration to angiotensin II infusion and of plasma cortisol to adrenocorticotropic hormone administration in the aldosterone-producing adenoma enucleation group were more sensitive than those in the adrenalectomy group. There was no remission of recurrent hyperaldosteronism in either group throughout the study. These results suggest that angiotensin II induces aldosterone release by an activation of tumor uninvolved cortical cells and that the enucleation of aldosterone-producing adenoma is more preferable than unilateral adrenalectomy.

Elevated levels of telomerase activity in malignant pheochromocytoma.

Although malignant pheochromocytoma is a life‐threatening illness, there is no excretory profile that is predictive of malignancy. Reliable prediction of malignant behavior on the basis of histopathology is also notoriously difficult. Although DNA ploidy can be a helpful indicator, aneuploidy per se is not considered to be a specific marker of malignancy. Mutations in p53 have been reported to occur frequently in cases of benign pheochromocytoma. Thus, molecular analysis of this protein is not a useful diagnostic tool. The authors analyzed telomerase activity in benign and malignant pheochromocytomas and assessed its utility as a prognostic marker.

Apoptosis and expression of apoptosis-related genes in the mouse testis following heat exposure.

OBJECTIVE To investigate molecular mechanisms of germ cell apoptosis induced by heat exposure in mice. DESIGN Controlled laboratory study. SETTING Departments of Urology and Biochemistry, Yamagata University School of Medicine, Yamagata, Japan. ANIMAL(S) Forty-four male B6D2F1 mice. INTERVENTION(S) Heat exposure, 43 degrees C for 15 minutes. MAIN OUTCOME MEASURE(S) Testicular germ cell apoptosis (percentages of apoptotic tubules and apoptotic cells) was assessed by using DNA nick-end labeling, and expression of Bcl-2 family, Fas-FasL system, and p53 was evaluated by using Western analysis. RESULT(S) Bilateral testicular weights decreased significantly from 3 days after heat exposure. Percentages of apoptotic tubules and apoptotic germ cells increased significantly from 1 day after heat exposure. There were no significant changes in the levels of Bcl-xl, Bad, and Bax after heat exposure. However, Bcl-2 expression level decreased significantly 7 days after heat exposure. In contrast, the expression level of Fas and p53 increased significantly from 1 day to 3 days after heat exposure, respectively. Expression level of FasL elevated significantly at days 1 and 2 but declined from day 3. CONCLUSION(S) Germ cell apoptosis induced by heat exposure is mainly mediated by the Fas-FasL system.

Stress and testicular germ cell apoptosis.

Chronic immobilization stress provokes an increase in serum corticosterone, which causes the decline in testosterone concentration. The stress and glucocorticoid administration induce germ cell apoptosis in rat testes. The cell type that has been shown to undergo apoptosis is spermatogonia. Since a potent glucocorticoid receptor agonist completely suppressed glucocorticoid induced germ cell apoptosis, the regulation of transcription of gene mediated by the glucocorticoid receptor may enhance apoptosis of testicular germ cells. The apoptosis of testicular germ cells would involve certain specific gene activities and proteins, including Bc1-2 family, p53, and Fas. Molecular investigations may help to determine whether the different pathways possess mechanisms of germ cell apoptosis induced by somatic stress and glucocorticoids.

Dendritic Cell-Based Immunotherapy of Renal Cell Carcinoma

Dendritic cells potently stimulate antigen-specific immune responses and recent data indicate that they are also capable of eliciting antitumor immune responses. We are performing a pilot study which tests the safety and efficacy of antigen-loaded, cultured blood dendritic cells in patients with metastatic renal cell carcinoma. Dendritic cells are simultaneously pulsed with lysate from autologous tumor cells and with the immunogenic protein keyhole limpet hemocyanin. During the pulse, the cells are activated with a combination of tumor necrosis factor-alpha and prostaglandin E2. Patients receive 5-10 X 10(6) dendritic cells per intravenous infusion and up to six infusions at monthly intervals. The first results demonstrate that this treatment modality is very well tolerated and can be associated with strong immunological and clinical responses. The present article discusses the importance of dendritic cell maturation and the role of helper antigens in dendritic cell-based immunotherapy.

Posterior Retroperitoneoscopic Partial Adrenalectomy: Clinical Experience in 47 Procedures

OBJECTIVES We evaluated posterior retroperitoneoscopic partial adrenalectomy with regard to operative complications, operation time, intraoperative blood loss. PATIENTS AND METHODS Between January 1997 and April 2002, we performed 47 posterior retroperitoneoscopic partial adrenalectomies. There were 18 males and 29 females with a mean age of 48 years (range 28-82 years). The average adrenal tumor size was 26 mm (range 10-50mm). All procedures required three trocars. RESULTS There was no mortality and conversion rate to open surgery was 2.1%. Average operative time and average blood loss was 198.0 ml (range 71-420 ml) and 40.8 ml (range 0-1100 ml), respectively. There was a significant correlation of operative time with the number of procedures performed. However, no significant correlation was observed between intraoperative blood loss and the number of procedures. Tumor size did not correlate with intraoperative blood loss and operative time. No significant correlation was found between body mass index and operative time. The operative time in the initial 20 cases was significantly longer than that in the subsequent 26 cases. CONCLUSION Posterior retroperitoneoscopic partial adrenalectomy is a safe and less invasive method for treatment of adrenal tumors. With improved operative technique, the time required for this procedure has been decreased.

Tumour angiogenesis and Ki-67 expression in phaeochromocytoma

Objective To determine the expression of CD34 (to evaluate vascularity) and Ki‐67 (as a proliferative index) in a variety of phaeochromocytomas and thus assess the utility of these markers as possible predictors of malignancy.

Spontaneous Hemorrhage during Pregnancy Secondary to Renal Angiomyolipoma

We report a case of spontaneous hemorrhage secondary to renal angiomyolipoma treated with percutaneous transcatheter arterial embolization. Fourteen and 18 months after the procedure, the patient showed repeated spontaneous hemorrhage during pregnancy. However, a healthy female infant was delivered at the 39th week of the pregnancy. We discuss the management of renal angiomyolipoma in young married women before pregnancy.

Modulation of the urethral pressure by high-frequency block stimulus in dogs

Nerve conduction block by high-frequency stimulus has been used as a method to modulate the contractile force of skeletal muscles. This paper describes the effect of block stimulus on the modulation of urethral closure pressure in dogs. Tetanic stimulus was applied through a pair of electrodes wrapped about the bilateral pudendal nerves and high-frequency stimulus was superimposed through another pair of electrodes wrapped about 1 cm distalward along the nerves. Urethral closure pressure was measured through a transurethral UPP catheter. High-frequency stimulus over 300 Hz reduced elevated urethral closure pressure, which was induced by tetanic stimulus, up to 30-45%.

Therapeutic experience of hyperbaric oxygenation in radiation colitis

PURPOSE: The usefulness of the hyperbaric oxygenation in a patient with radiation colitis was evaluated. METHODS: The patient had severe bleeding from the large bowel which resulted from a pelvic radiation therapy for prostatic carcinoma and was histologically diagnosed as radiation colitis. Hyperbaric oxygenation therapy consisting of 100 percent oxygen inhalation at two absolute atmospheric pressures 90 minutes daily for 30 days was performed. RESULTS: The treatment succeeded in stopping gross hemorrhage and reversed endoscopic bowel findings. CONCLUSION: The effect of the hyperbaric oxygenation therapy of radiation colitis is elucidated.