Small cell carcinoma of the gall-bladder with intestinal metaplastic epithelium

A case of small cell carcinoma of the gall-bladder Is described. lmmunohistochemically, the tumor cells were positive for chromogranin A, synaptophysin and neuronspecific enolase, which suggests that they derived from neuroendocrine cells. The overlying and surroundlng epithelium of the tumor showed intestinal metaplasia including goblet cells, pseudopyloric glands, Paneth's cells, and chromogranin A and synaptophysin-positive endocrine cells. Definite adenocarcinoma was absent. The endocrine cells in the epithellum were more numerous In the vicinity of the tumor. The present case supports the supposition that endocrine cell tumor (including small cell carcinoma) of the gall-bladder may develop from endocrine cells of the intestinal metaplastic lesion.     

Jejunal endocrine tumour composed of somatostatin and gastrin cells and associated with duodenal ulcer disease

Summary A case of malignant endocrine tumour of the jejunum, associated with severe duodenal ulcer is described. The tumour and a local metastasis were examined by immunohistochemistry and found to contain abundant somatostatin-immunoreactive cells together with less numerous cells displaying gastrin immunoreactivity. This is to our knowledge the first case of intestinal somatostatinoma. The presence of gastrin cells in the tumour may explain the ulcer diathesis.     

PULMONARY ADENOMA AND ENDOCRINE CELL HYPERPLASIA IN SYRIAN GOLDEN HAMSTER TREATED WITH 4-NITROQUINOLINE 1-OXIDE

Chronic effects of 4-nitroquinoline 1-oxide (4 NQO) on the lungs of Syrian golden hamsters were studied. 4 NQO was subcutaneously injected weekly for 3 weeks at a dose of 20 mg/kg body weight. The animals were sacrificed at the 65th and 80th experimental weeks. Two cases of pulmonary adenomas were demonstrated in the 10 4 NQO-treated animals at the 80th week, and the tumor cells contained cytoplasmic lamellar inclusion bodies. In a previous study, we reported 4 NQO- induced pulmonary endocrine cell hyperplasias in the 4 NQO-treated hamster after the 20th experimental week (Jpn. J. Cancer Res., 77,1986). In the present study, 12 pulmonary endocrine cell hyperplasias were recognized in serial sections of the 24 treated animals. The hyperplastic lesions showed positive immunoreactivity to calcitonin. The hyperplastic lesion did not develop to pulmonary endocrine cell neoplasm. ACTA PATHOL JPN 38 : 1097∼1104, 1988.     

Cyclical use of tamoxifen and high-dose medroxyprogesterone acetate in advanced estrogen receptor positive breast cancer

Summary One-hundred and seventy patients with estrogen receptor positive (10 pmol/g protein) advanced breast cancer have been treated in a prospective randomized study either with continuous tamoxifen 30 mg × 1 daily (TAM), or with TAM 30 mg × 1 daily for 8 weeks alternating with medroxyprogesterone acetate 500 mg × 2 daily for 8 weeks (TAM/HD-MPA). The response rate was 62% in the group treated with cyclic TAM/HD-MPA versus 41% in the TAM alone group (p = 0.02). There was no significant difference in duration of remissions or survival.     

Diagnosis and surgical treatment of multiple endocrine neoplasia

Background Multiple endocrine neoplasia (MEN) is relatively rare. But more patients could be found by detailed examination. We discuss the diagnosis and surgical treatment of MEN. Methods The clinical data of 95 MEN cases were retrospectively analyzed. There were 30 cases of MEN1 including 19 cases from 6 families. The MEN1 gene mutation was detected in 81.48% of cases admitted after 1997. There were 22 cases of primary hyperparathyroidism (PHPT), 10 cases of enteropanceatic tumor including 9 cases of insulinoma, 15 cases of pituitary adenoma, 9 cases of adrenal adenoma, 2 cases of thymic carcinoid. Two patients had 4 glands involved, 3 patients had 3 glands involved, 16 patients had 2 glands involved, and 6 patients had only one gland involved. Three patients had neither clinical symptoms nor biochemical changes, and was diagnosed by MEN1 gene mutation. Six patients presented with nephrolithasis and 6 patients had impaired pancreatic endocrine function. There were 60 cases of MEN2a and 5 cases of MEN2b. 58 cases of MEN2a belongs to 19 kindreds. All MEN2a patients but one presented RET gene mutation in codon 634, and all MEN2b cases had mutation in codon 918. 48 cases of MEN2a had thyroid masses with elevated calcitonin levels. 27 patients had pheochromocytoma including 12 cases of multiple loci and 5 malignancy. 13 patients presented with hyperparathyroidism. 5 MEN2b patients had medullary thyroid carcinoma and mucosal ganglioneuromatosis with Marfanoid. Among them, 3 patients had bilateral pheochromocytoma. Results In MEN1, subtotal parathyroidectomy was performed in 12 patients with PHPT and one patient received parathyroid adenoma enucleation. Insulinomas were enucleated in 4 patients. Two patients underwent thymus tumor extirpation. Total thyroidectomy with bilateral dissection of regional lymph nodes was performed in 16 patients with MEN2a and nodule enucleation was performed in 9 patients. Twenty two MEN2a patients underwent pheochromocytoma enucleation including bilateral adrenal resection in 10 cases. 5 MEN2b patients underwent total thyroidectomy with bilateral lymph node dissection. Among them, 3 cases underwent bilateral adrenal operations. Conclusions MEN varies in symptoms. Germline mutation test is helpful in establishing a diagnosis. Surgical management should be aimed at the improvement of life quality in MEN1 and prevention of the fetal tumors in MEN2.     

Analysis of the factors influencing the quality of life of patients with advanced or recurrent breast cancer

To investigate the factors influencing the quality of life (QOL) of Japanese patients with advanced or recurrent breast cancer, a newly developed QOL questionnaire, The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD), was answered by 23 patients, and a multiple regression analysis was performed. The demographic and medical factors relating to the overall QOL score and to the four categories of the QOL-ACD, namely (1) activity, (2) physical condition, (3) psychological condition, and (4) social relationships, were analyzed. The results indicated that skin metastasis, a heavier body weight, and bone metastasis had a strong negative influence on the overall QOL scroe, whereas endocrine therapy, the existence of a primary lesion, and more extensive first surgery had a strong positive influence on it. With regard to the analysis of the four categories, endocrine therapy was found to be positively related to all four categories. The multiple correlation coefficient (R) between the estimated overall QOL score and the observed overall QOL score was about 0.77. The results of this analysis showed that endocrine therapy can improve the QOL of patients with advanced or recurrent breast cancer, and that the QOL-ACD questionnaire could prove extremely useful for predicting the QOL of individual patients and for aiding clinicians in deciding on the most appropriate type of therapy for each patient.     

长期饮酒对男性生殖系统功能影响

目的探讨饮酒对男性生殖系统的损害及其机理。方法选择45名男性饮酒者和9名慢性酒精中毒者为研究对象,以15名不吸烟不接触毒物的男性为对照组。结果长期大量饮酒和酒精中毒者血清中T和CS水平下降,而LH和FSH水平升高;精浆和精子中LDH,LDH-x和G-6PD活力下降,以LDH-x下降为敏感;精子数量和活动精子年均降低,精子畸形率及异常精液检出率均升高。上述各指标与对照组比较差异均有高度显著性（P＜0.01）。结论长期饮酒可损害男性生殖系统功能。     

空蝶鞍综合征20例的临床和MRI分析

分析２０例空蝶鞍综合征（ＥＳＳ）的ＭＲＩ表现和其中１６例的内分泌改变。结果１６例ＥＳＳ均有内分泌功能异常。ＭＲＩ表现有蝶鞍充满长Ｔ＿１和长Ｔ＿２的脑脊液;垂体受压至鞍底,冠状位呈“锚”状,矢状位呈“新月”状;垂体柄延长。结果表明ＥＳＳ常具有内分泌功能紊乱,ＭＲＩ对ＥＳＳ具有特征性诊断意义。     

The microanatomy of canine islets of Langerhans: implications for intra-islet regulation

Summary In recent years models for the internal (intra-islet) regulation of hormone secretion have been proposed to explain how different islet cells might regulate each other by means of their respective secretory peptides. Models that emphasize the importance of a directed intra-islet blood flow and sequence of perfusion of islet cells rely on a certain type of islet microanatomy and vascular supply. The experimental studies underlying these models have partly been performed in dogs. To extend the incomplete morphological knowledge of the canine endocrine pancreas both canine islets of Langerhans and extrainsular cells have been analysed in immunostained serial semithin (0.5 m) sections. In addition to their occurrence within islets of Langerhans, all endocrine cell types are also found at extrainsular sites (about 9% of all endocrine cells) where they are distributed in different quantities among the epithelial lining of exocrine acini or excretory ducts and the connective tissue. There are continuous transitions from single extrainsular cells to small mono-and polycellular cell groups to islets. In a comprehensive analysis of whole islets, including computer-assisted three-dimensional reconstructions, the size, shape and vascularization of the islets as well as their cellular composition and the microtopology of islet cells have been studied. We have found marked intra-and inter-islet heterogeneities of the parameters investigated that are not compatible with concepts of a uniform and directed vascular perfusion of the various islet cell populations. Instead, their paracrine regulation may occur primarily via hormonal secretion into the intercellular spaces or vascular hormonal delivery to adjacent cells.     

UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay.

The fact that certain ultraviolet (UV) filters used in cosmetics display estrogenic activity prompted us to study potential actions on androgen receptors (AR) in the human breast carcinoma cell line MDA-kb2, which expresses functional endogenous AR and glucocorticoid receptors (GR) and is stably transfected with a luciferase reporter plasmid. Dihydrotestosterone (DHT), methyltrienolone (R1881), methyltestosterone, danazol, and androstenedione increased luciferase activity, with EC50 values between 0.11 nM (R1881), 0.14 nM (DHT), and 73.5 nM (androstenedione). DHT-induced luciferase gene expression was inhibited by nonsteroidal antiandrogens, hydroxyflutamide, flutamide, bicalutamide, and vinclozolin. In contrast, the steroidal AR agonist/antagonist cyproterone actetate showed agonistic activity in the absence and presence of DHT, which was not blocked by hydroxyflutamide and thus seems not to be mediated by AR. GR-mediated activation of luciferase by dexamethasone was 100 times less potent than DHT and was not antagonized by hydroxyflutamide. The cell line was used for screening of UV filters, benzophenone-3 (Bp-3), benzophenone-4, 3-benzylidene camphor, 4-methylbenzylidene camphor, butyl-methoxy-dibenzoylmethane, homosalate (HMS), octyl-dimethyl-PABA, and octyl-methoxycinnamate. Two of these, Bp-3 and HMS, antagonized DHT-induced AR activation below cytotoxic concentrations, with IC50 of 5.57 10-6 M (HMS) and 4.98 10-6 M (Bp-3). None of the eight UV filters displayed agonistic activity when tested alone, but high concentrations of Bp-3 induced an increase of luciferase activity in the presence of dexamethasone, which was not blocked by hydroxyflutamide or the estrogen antagonist, ICI 182,780. These data indicate that the UV filters Bp-3 and HMS possess antiandrogenic activity in vitro in addition to estrogenic activity.