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In the present study, a suitable rat model for testing the modifying effect of liver injury on the rat male organ toxicity of endocrine disrupters was researched using thioacetamide (TAA) and carbon tetrachloride (CCl4) as liver toxicants. Male 8-week-old F344 rats were divided into six groups as follows. Animals in groups 1 and 2 were given 200 and 100 mg/kg body weight of TAA with PBS by intraperitoneal injection (ip.) 3 times a week for 4 weeks, respectively. Group 3 was given PBS only. Animals in groups 4 and 5 were given 2 and 1 mg/kg body weight of CCl4 with corn oil by subcutaneous injection (sc.) once a week, for 4 weeks, respectively. Group 6 was given corn oil only. Three rats from each group were sacrificed at week 4 and the rest of groups 1 and 4 were sacrificed after a further 4 weeks of withdrawal period. In the animals administered 200 mg/kg of TAA the findings of apparent liver damage on both histopathological and biochemistrical examinations could be seen: fibrosis, enlargement of Glisson's sheath and infiltration of inflammatory cells in the liver, and apparent elevation of serum aspartate aminotransferase and alanine aminotransferase levels. On the other hand, in the animals administered 2 mg/kg of CCl4 only the histopathological findings of liver damages could be seen: fatty and inflammatory changes in liver. In the animals administered 100 mg/kg of TAA or 1 mg/kg body weight of CCl4 only the histopathological findings of slight inflammatory changes in their liver samples. However these findings of liver damage were almost completely absent after the 4-week withdrawal period.

The modifying effects of liver injury on male reproductive organ toxicity of di-n-butyl phthalate (DBP) were studied using male F344 rats. Seventy-two male animals, aged 10 weeks at the commencement, were divided into 8 groups of 9 rats each. Groups 1 to 4 were given 200 mg/kg bw of thioacetamide (TAA) intraperitoneally 3 times / week, while Groups 5 to 8 were injected with the PBS vehicle only. From 1 week after the start, groups 1 and 5, 2 and 6, and 3 and 7 were given daily 500, 125, 31.25 mg/kg bw of DBP, respectively (23 times) for 4 weeks, while groups 4 and 8 served as vehicle controls. As the result of our treatment, liver injury was induced in the animals, and the liver injury was confirmed by histopathological findings and serum transaminase levels at sacrifice. Enhancement of rat male reproductive organ toxicity of DBP under liver injury status was also seen. The relative organ weights of prostate, bilateral seminal vesicles, bilateral epididymides and bilateral testes, and the sperm number and motility rate were decreased. Also the sperm abnormality rate was increased under liver injury. Furthermore histopathological abnormality of the testis, such as absence of germ cells and the presence of Sertoli cells only was seen in the rats treated with TAA and high dose of DBP, however neither the serum nor testicular testosterone levels varied in the present study. The sperm number and relative weight of bilateral epididymides were decreased by TAA treatment only, unrelated to DBP treatment. These facts suggest that liver injury can not only enhance the rat male reproductive organ toxicity of DBP, but also induce such toxicity by itself.

Urinary alpha 1-microglobulin (alpha 1-m) and beta 2-microglobulin (beta 2-m) can be used as early indicators of renal tubular dysfunction. However, low levels of lead exposure cause an increase in urinary alpha 1-m, but not in urinary beta 2-m. In order to clarify the level of tubular dysfunction in early lead nephropathy, fractional clearances of alpha 1-m (FC-alpha 1-m) and beta 2-m (FC-beta 2-m), i.e., the ratios of these clearances to the creatinine clearance, were measured in 99 male lead workers. Blood urea nitrogen, serum creatinine, uric acid, and urinary creatinine and N-acetyl-beta-D-glucosaminidase activity were also measured to diagnose the presence of other renal dysfunction. The median of FC-alpha 1-m was 0.13% in the control group. The FC-alpha 1-m increased in lead workers with blood lead (B-Pb) levels above 20 micrograms/dl. The correlation of FC-alpha 1-m with urinary alpha 1-m was highly significant, but there was no correlation with serum alpha 1-m. The median of FC-beta 2-m was 0.065% in the control group. There was a correlation of FC-beta 2-m with FC-alpha 1-m, but there was no correlation with B-Pb, or with serum beta 2-m. These results suggest the following: There was a very low excretion rate of alpha 1-m and beta 2-m in both the control group and the lead exposed groups. The excretion rate of alpha 1-m was higher than that of beta 2-m.(ABSTRACT TRUNCATED AT 250 WORDS)

A 67-year-old man, who had smoked heavily for many years, was found in 1997 to have bladder tumors, and transurethral resection of the bladder tumor (TUR-Bt) was performed. Histopathological diagnosis was urothelial carcinoma (G2G3, pTa, N0, M0, ly0, v0). In December, 1998, he noticed an oral cavity tumor. After preoperative radiation therapy (total 40 Gy, 17 times), surgical treatment was undertaken. Histopathological diagnosis was well differentiated squamous cell carcinoma (pT2, pN2b, M0). In February, 2000, gastric tumor was detected by endoscopic examination, and subtotal gastorectomy and Roux en Y operation were performed. Histopathological diagnosis was well differentiated adenocarcinoma (pT2, pN0, M0, P0, CY0). A chest computed tomographic (CT) scan revealed a solitary lung tumor in April, 2000. Partial peumonectomy was performed, and histopathological diagnosis was poorly differentiated adenocarcinoma (pT1, N0, M0, P0). In April, 2000, multiple lesions of bladder cancer in the neck of the urinary bladder and posterior urethra were found and radical cystoprostatourethrectomy combined with lymph node dissection and bilateral cutaneous ureterostomy were performed (urothelial carcinoma, G3, pT4a, pN2, M0, pL2, pV0, pR0). Since then, the patient has been followed carefully.

A case of renal cell carcinoma, found after skin metastasis is presented. A 79-year-old man visited Osaka JR hospital, complaining of a painless nodular mass on his right chest. The mass was resected and histopathological examination revealed a clear cell carcinoma (alveolar type, G1) with no involvement of the mammary gland. Abdominal ultrasound and magnetic resonance imaging revealed a heterogenous lower pole mass in the right kidney. Ultrasound-guided needle biopsy of the right renal mass was performed for histopathological diagnosis, which was clear cell carcinoma (alveolar type, G1). At that time, multiple metastases appeared in bilateral lung fields. The patient is currently receiving interferon-alpha therapy, without surgical treatment.

A 75-year-old man was admitted to our hospital for treatment of superficial bladder tumor. Transurethral resection (TUR) was performed and histopathological examination revealed a transitional cell carcinoma (G2). Despite one course of post-TUR bladder instillation therapy using pirarubicin hydrochloride, carcinoma in situ (CIS) was found 4 months later. CIS disappeared after another course of bladder instillation therapy using BCG; but, it recurred a month later. BCG bladder instillation therapy was performed again, and no malignant cells were detected in the urinary tract thereafter. Four months later, lung metastasis was diagnosed and an MVAC regimen (cisplatin, methotrexate, vinblastin adriamycin) was administered. However, anaphylactic shock was induced by intravenous injection of pirarubicin hydrochloride, so this therapy was stopped in the middle of the second course. Even though the lung metastasis disappeared once after the same MVAC treatment, it recurred the following year. At that time, 3 courses of a cisplatin-methotrexate-vinblastin regimen were administered, and a complete response was achieved.

Hyperthermic treatment was performed in 31 patients with benign prostatic hypertrophy (BPH). Eight patients of them had a urethral catheter because of urinary retention. The prostate was heated trans-rectally to 43-45 degrees C. The treatment consisted of 10 sessions of 60 min. each. To evaluate this treatment, the following parameters were determined before, during and one week after the last hyperthermia session: subjective symptoms score, and residual urine volume, uroflowmetry and transrectal ultrasound of the prostate as objective data. Symptoms score improve in all patients. Of 8 patients with a catheter, the catheter could be removed from 4 patients. There was no significant change in prostate volume, but significant decreases of residual urine volume, and increases of maximum flow rate and mean flow rate were observed. No adverse reactions were seen. Judging from the above results, this treatment is considered to be useful for patients with BPH.