Endometrial protection from tamoxifen-stimulated changes by a levonorgestrel-releasing intrauterine system: a randomised controlled trial.

INTRODUCTION: Tamoxifen is currently the most commonly used adjuvant treatment for breast cancer, however, it frequently causes episodes of unscheduled uterine bleeding, which could be associated with proliferative changes of the endometrium, or even endometrial cancer. We aimed to assess whether a levonorgestrel intrauterine system could modulate the uterine responses to tamoxifen. We also aimed to assess women's tolerance of the screening procedures, the insertion, removal, and potential side-effects of the device. METHODS: We did a randomised controlled trial, in which postmenopausal women who had had at least 1 year of adjuvant tamoxifen treatment and who were undergoing regular follow-up for breast cancer were randomly assigned to either endometrial surveillance alone, or endometrial surveillance before and after insertion of the levonorgestrel intrauterine system for 12 months. We assessed tolerance of the surveillance procedures and the device with visual analogue scales. FINDINGS: Baseline assessment showed only benign uterine changes in all women (n=122). Hysteroscopic assessment indicated a uniform decidual response (confirmed histologically in 40 of 41 cases) in all women fitted with the intrauterine system; there were no new polyps in these women and 13% had fewer fibroids than in controls. Both screening procedures and device were well tolerated. There was an excess of bleeding in the women fitted with intrauterine systems but this resolved to a baseline similar to those receiving surveillance only. INTERPRETATION: The levonorgestrel-releasing intrauterine system had a protective action against the uterine effects of tamoxifen. The effectiveness of this device in preventing uterine changes in the endometrium needs to be assessed in the context of decreasing the need for repeated investigations of postmenopausal bleeding in women taking tamoxifen.

Uterine surveillance of asymptomatic postmenopausal women taking tamoxifen.

The aim of this study was to assess the ability of transvaginal sonography (TVS) and office hysteroscopy with sharp curettage to characterize the morphological changes in the uteri of asymptomatic postmenopausal women taking long-term tamoxifen for breast cancer. The overall acceptability of a single-visit screening clinic for these women was also evaluated. Fifty-eight women were recruited from patients undergoing regular follow-up at the Leicester Royal Infirmary for breast cancer. A single-visit clinic was acceptable to 94.8% of these women. Transvaginal sonography detected endometrial thickness of greater than 5 mm in 84.5% of cases, but there was no relationship between total tamoxifen exposure and endometrial thickness. Transvaginal sonography also detected uterine lesions such as fibroids and endometrial cysts in 34.5% of cases. Hysteroscopy detected the latter uterine lesions in 53.4% of cases, with three cases (5.2%) of endometrial polyps also being identified in these women. Sharp curettage sampling of the endometrium produced specimens sufficient for diagnosis in 84.5% of cases; 70.7% of specimens were reported as showing types of 'quiescent' endometrium with 13.8% of specimens showing 'active' endometrium. In the latter group, there was a case of complex hyperplasia detected and also a case with granulomatous endometritis. For each histopathological diagnosis identified, there was a wide range of endometrial thickness recorded by TVS. A single-visit screening clinic involving TVS and hysteroscopy with sharp curettage was acceptable to asymptomatic women taking tamoxifen. However, hysteroscopy was more effective than TVS in detecting endometrial lesions such as polyps, fibroids and cystic areas. Although TVS detected endometrial thickness greater than 5 mm in the majority of cases, there were no malignancies detected and, for each histopathological classification, there was a wide range of endometrial thickness associated. Thus, the isolated use of TVS is insufficient for screening the endometria of these women.

Modulation of cell surface components of human breast cancer cells by retinoic acid: enhanced HLA-DR expression.

The effect of the differentiating agent all-trans-retinoic acid on the expression of components of the milk fat globule membrane and HLA-DR by breast cancer cell lines has been examined. Effects on proliferation were also considered, to determine whether any cell surface changes were related to or independent of proliferation effects. No significant differences were observed in the expression of components detected by the milk fat globule membrane antibodies HMFG1 and HMFG2 over 8 days culture with 10(-7)-10(-9)M retinoic acid for the cell lines MCF-7, T-47 D, ZR-75, MDA-MB-231, and BT-20. In contrast , there was enhanced expression of HLA-DR by two oestrogen receptor-positive cell lines T-47 D and ZR-75 and the oestrogen receptor-negative line MDA-MB-231, with differing sensitivities. These effects were independent of inhibition of proliferation, which was only observed for oestrogen receptor-positive cell lines and for different durations of exposure. The finding of enhanced HLA-DR expression after retinoic acid treatment has not previously been reported and is of interest regarding clinical potential for the induction of tumour immunity.

Histoplasmosis in the acquired immunodeficiency syndrome (AIDS).

This case report describes a 50-year-old man from South America with AIDS who developed disseminated histoplasmosis with focal lymph node involvement. Treatment with ketoconazole was initially successful. Six weeks after cessation of ketoconazole he died of what was thought to be relapse of histoplasmosis.

Histoplasma capsulatum. Isolation from an Australian cave environment and from a patient.

The fungus Histoplasma capsulatum, although commonly found in bat-frequented caves in many countries, has not previously been isolated from that environment in Australia. This report describes the isolation of H. capsulatum from several sources, including cave soil, the organs of mice exposed to the cave environment, and the sputum of a patient clinically diagnosed as having acute pulmonary histoplasmosis after exposure to the cave environment.