Keizo Fukuma

Tamoxifen in the treatment of infertility associated with luteal phase deficiency

A group of 17 patients with suspected luteal phase deficiency was treated with tamoxifen. Tamoxifen therapy was found to lengthen the luteal phase in all patients and resulted in pregnancy in 6 of 17 patients. The integrated luteal phase progesterone (P) concentration in the nontreatment cycle of seven patients was significantly lower (P less than 0.01) than that of five normal women. Therapy with tamoxifen increased the P concentration to 186.0 +/- 24.4 ng/ml/cycle (mean +/- standard error of the mean), i.e., twice that of the control cycle. The mean estradiol (E2) concentration at the midcycle peak was about twice that observed during the nontreatment cycle. The glycogen content of the endometrial tissue at the midluteal phase in the tamoxifen cycle was significantly higher (P less than 0.025) than that of endometrial tissue in the nontreatment cycle, indicating improvement of the endometrial function.

Uterine papillary serous carcinoma with high levels of serum carcinoembryonic antigen. Response to combination chemotherapy

A case of metastatic uterine papillary carcinoma with elevated serum carcinoembryonic antigen (CEA) is reported. The patient presented with ascites and pleural effusions and with a high level of CEA (258 ng/ml) 3 months after primary surgical resection and postoperative irradiation had been performed. Her complete response, although temporary, to two kinds of combination chemotherapy was evaluated using serial estimations of the serum CEA.

A graduated regimen of clomiphene citrate: its correlation to glycogen content of the endometrium and serum levels of estradiol and progesterone in infertile patients at the midluteal phase

The glycogen content, glycogen synthetase level, and glycogen phosphorylase level were studied in endometrial samples obtained from 14 infertile patients during the midluteal phase before and after clomiphene citrate (Clomid, Shionogi & Company, Ltd., Osaka, Japan) treatment, simultaneously with measurement of the serum concentrations of estradiol and progesterone. Increase in the endometrial glycogen content in the clomiphene cycle was accompanied by a corresponding increase of the dosage of clomiphene. Also, the midluteal concentrations of estradiol and progesterone in the clomiphene cycle were significantly higher (P less than 0.005 and P less than 0.005, respectively) than those in the nontreatment cycle. Clomiphene therapy at 50 mg/day resulted in pregnancy in three of ten patients, while clomiphene at 100 mg/day resulted in pregnancy in three of six patients. These results suggest a fair correlation between the dosage of clomiphene and the improvement of endometrial function in infertile patients following stimulated ovarian steroidogenesis.

Angiosarcoma of the vagina: A light and electronmicroscopy study

A 73‐year‐old woman, whose medical history reported radical hysterectomy and radiotherapy for squamous cell carcinoma of the cervix uteri 20 years earlier, was found to have an angiosarcoma of the vagina. The histological diagnosis was confirmed by immunohistochemical staining of tumor cells for factor VIH‐related antigen and ultrastructurally defined vasoformative structures. Primary angiosarcoma of the vagina is quite rare and reported in only two published cases. The present case is a third in general, and the first report confirmed by light microscopy, immunohistochemical, and electronmicroscopy studies.

Effect of Progestogen on Glycogen Metabolism in the Endometrium of Infertile Patients During the Menstrual Cycle

The glycogen content and glycogen synthetase and glycogen phosphorylase levels were studied in endometrial samples obtained from 19 normal and 37 infertile patients during the menstrual cycle before and after administration of progestogen. Each of the above groups received the progestogen Lyndiol (lynestrenol, 5.0 mg, and mestranol, 0.15 mg) daily for 7 days during the follicular phase of the menstrual cycle. In both groups an increase in the endometrial glycogen deposition and an increase in glycogen synthetase enzyme levels were seen. When the administration of progestogen was started on day 7 after ovulation, during the luteal phase, the glycogen content of endometrial tissue from infertile patients increased significantly; no change was found in endometrial samples from normal patients. No difference was found in the serum progesterone levels of normal and infertile patients in the midsecretory phase of menstrual cycle, and Lyndiol reduced the serum level of progesterone to approximately that found during the follicular phase in untreated normal women. These studies suggest that the proliferative endometrium of infertile patients may be less stimulated by ovarian estrogen than is normal endometrium, whereas endometrial tissue obtained from both groups during the luteal phase responded similarly to progesterone in glycogen synthesis and storage.

A case of verrucous carcinoma of the uterine cervix: Clinical, light, and electron microscopic, and immunohistological observations

A case of verrucous carcinoma of the uterine cervix in a 67-year-old patient is reported. On transmission electron microscopy, virus-like particles with a diameter of 45 to 55 nm were found in the nuclei of koilocytotic cells. However, human papilloma virus antigen could not be detected by immunohistochemistry, using the peroxidase-antiperoxidase technique.

Pseudomyxoma Peritonei: Effect of Chronic Continuous Immunotherapy with a Streptococcal Preparation, OK-432 after Surgery

Three cases of pseudomyxoma peritonei with ovarian neoplasma were treated by adjunctive immunother‐apy with OK‐432 after surgery. in 2 of the 3 cases, the periods of intramuscular injection of OK‐432 were 11 and 16 months, respectively, and the 2 patients remain clinically free from evidence of disease, 7 and 6 years after surgery. the third patient is still undergoing treatment, with no evidence of recurrence at 4 months after surgery. These results, although for a small number of patients, clearly suggest that adjunctive immunotherapy with OK‐432 may be suitable for treating pseudomyxoma peritonei of ovarian tumor origin.

Eccrine adenocarcinoma of the vulva producing isolated alpha-subunit of glycoprotein hormones.

A rare case of adenocarcinoma of the sweat glands of the vulva producing isolated alpha-subunit of glycoprotein hormones is reported. By an immunohistochemical method, eccrine gland adenocarcinoma tissues obtained from the right vulva and from its metastatic lesion in the right subclavicular lymph nodes were found to react with human chorionic gonadotropin (hCG), alpha-hCG but not beta-hCG. The concentrations of alpha-subunit in the serum and urine were markedly elevated to 6000 ng/mL and 55,000 ng/mL, respectively, just before the death of the patient.

Activities of glycogen synthetase and glycogen phosphorylase in the human endometrium: Relative distribution in isolated glands and stroma

The activities of glycogen synthetase and glycogen phosphorylase were studied in endometrial samples obtained from 51 premenopausal women during the menstrual cycle. The total activities of glycogen synthetase and glycogen phosphorylase and the activity of the active form of glycogen phosphorylase increased gradually from the proliferative phase to the secretory phase and reached a maximum during the midsecretory phase, while the activity of the active form of glycogen synthetase increased slightly. In 30 of the 51 women, the relative distribution of glycogen synthetase and glycogen phosphorylase activities in isolated glands and stromal cells was determined following collagenase digestion of the endometrial specimens. The results indicated that the activities of the active form of glycogen synthetase and glycogen phosphorylase in the isolated glands during the secretory phase were more than threefold and twofold, respectively, greater than those present in the isolated stromal cells and that the levels of these enzymes in the glands and stromal cells changed in parallel with those in the undissociated endometrium observed during the menstrual cycle. In addition, histochemical studies revealed the presence of glycogen phosphorylase activity in both the glands and the stromal cells, whereas the glycogen synthetase activity was present only in the glands. These findings suggest that the stromal cells of the human endometrium as well as the glands may play an important role in the nutrition of the implanting blastocyst.

Hormone dependency of carcinoma of the human endometrium effect of progestogen on glycogen metabolism in the carcinoma tissue

The glycogen content and glycogen synthetase and glycogen phosphorylase levels were studied in tissues of endometrial carcinoma obtained from 30 patients (27 postmenopausal and three premenopausal) before and after administration of progestogen, and the values were compared with those obtained previously from normal endometrial tissue of premenopausal patients. After the patients had undergone an oral glucose tolerance test (OGTT), the progestogen Lyndiol (lynestrenol, 5.0 mg, and mestranol, 0.15 mg) was administered dail for seven days. In 15 cases of well differentiated carcinoma the glycogen content after the progestogen administration, accompanied by a corresponding increase in the glycogen synthetase enzyme levels, was significantly higher (P < 0.005) than that in the initial tissue, whereas in the other 15 cases of less differentiated carcinoma no change was observed. This finding that hormonal stimulus in well differentiated carcinoma leads to a similar effect on glycogen metabolism as in normal endometrium of the proliferative phase of the menstrual cycle, supports the possibility of progestogen therapy for human endometrial cancer.