Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Lack of effect of aspartame or of L-phenylalanine on photically induced myoclonus in the baboon, Papio papio

The effects of large doses of L-phenylalanine and of aspartame on seizure susceptibility and severity have been assessed in baboons Papio papio from Senegal which show photosensitive epileptic responses similar to primary generalised epilepsy in man. L-Phenylalanine, 50, 150 or 450 mg/kg, or aspartame, 300 or 1000 mg/kg, were administered orally. Peak plasma L-phenylalanine concentrations of approximately 2000 mumoles/l occurred 1-4 h after the highest dose of L-phenylalanine or aspartame. The plasma L-phenylalanine to large neutral amino acid ratio increased approximately 30-fold at this time. Compared with water administration there were no changes in epileptic responses 1-5 h after either treatment. In this primate model of epilepsy acute increases in plasma phenylalanine concentration are neither pro- nor anticonvulsant.     

Coxankylometer nach Prof. C. Heine in Innsbruck

Ohne Zusammenfassung (Hierzu Tafel VIII.)     

PR35THE INCIDENCE OF NON‐MELANOMA SKIN CANCER IN NEW ZEALAND

Background It is estimated that skin cancers cost $33 million per annum to the New Zealand healthcare system. Basal cell carcinoma and squamous cell carcinoma are the commonest types of non melanoma skin cancers (NMSCs). Anecdotal evidence indicates that there has been a doubling in the incidence of NMSCs in New Zealand over the last decade. Because of the high incidence mandatory reporting of NMSCs to the National Cancer Registry is not required. This lack of accurate data has led to poor health care policies and strategies including funding and workforce planning. Aims The aims of this study are to (1) present the latest statistics on NMSCs in New Zealand, including the incidence across different regions over the last decade, patient demographics, anatomic distribution of NMSCs, incidence and sites of metastasis, and disease‐specific survival; to (2) the histopathology of NMSCs, including surgical margins, histologic grade, and perineural, lymphatic, and vascular invasion; and (3) the relative role of different faculties treating NMSCs. Method This project has been approved by the multi‐centre ethics committee. A retrospective review was conducted from patients’ histology records from public and private pathology laboratories within defined catchment areas. Criterion for analysis is a confirmed diagnosis of NMSC treated surgically. A Microsoft Access database is created that will facilitate subsequent data retrieval and analysis. Results and Conclusion It is hoped that this up‐to‐date data will form the framework for the development of sound and sustainable healthcare policies of management of NMSCs including management strategies and workforce planning, and research direction on this common disease.     

Alterations in glucose transporter proteins in alcoholic liver disease in the rat.

We used the intragastric feeding rat model for alcoholic liver disease to investigate alterations in glucose transporter isoforms GLUT 1 and GLUT 2 in response to different dietary fats and ethanol. Six groups of rats (three rats/group) were fed ethanol or dextrose with either saturated fat, corn oil, or fish (menhaden) oil. All control animals were pair fed the same diets as ethanol-fed rats except that ethanol was isocalorically replaced by dextrose. In all animals, the following were assessed: pathological changes in the liver, immunohistochemical and Western blot analysis of GLUT 1 and GLUT 2 isoforms, and glycogen distribution. The most severe pathological changes were seen in fish oil/ethanol fed rats, moderate changes were seen in the corn oil/ethanol group and no changes were observed in the dextrose-fed or saturated fat/ethanol groups. In the groups of rats showing pathological liver injury (corn oil/ethanol and fish oil/ethanol), the depletion in liver glycogen was accompanied by decreased GLUT 2 expression and increased GLUT 1 expression. A decrease in glycogen and GLUT 2 expression was also seen in the fish oil/dextrose-fed rats. We hypothesize that the shift in glucose transporters from GLUT 2 to GLUT 1 probably reflects a compensatory response to attenuated gluconeogenic activity and to meet the increased intracellular demand for glucose. This demand for glucose in the presence of depleted glycogen may serve to provide a source for ATP synthesis in the centrilobular zone where hypoxia occurs secondary to ethanol metabolism.     

Orbital hydatid cysts: Report of four cases

Hydatid cysts of central nervous system are rare and comprise only 2% to 3% of all hydatid cysts reported. Orbital localization is very uncommon and has been reported less than 1 % of all hydatid diseases. The primary treatment of hydatid disease is surgical. The most important complication of the surgical treatment is secondary hydatidosis due to spillage of the cyst contents. Because of the difficulties of the orbital localization, total extirpation of the cysts without rupture is almost impossible. Preventing spontaneous rupture of the cysts during surgery and postoperative antihelmintic treatment should be taken into consideration in these cases.This study includes four cases who underwent surgery for orbital hydatid cysts. Radiological characteristics, operative technique and postoperative medical therapy are discussed.