Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up.

OBJECTIVES: Levonorgestrel (LNG), delivered locally into the uterine cavity has a profound effect on the endometrium. The aim of the study was to use a LNG intrauterine system to treat non-atypical and atypical endometrial hyperplasia in women and to evaluate the long-term cure (remission) rate. METHODS: Each of the 20 women in the study, of whom eight were diagnosed with atypical hyperplasia, received a LNG-IUS, releasing 20 microg LNG/day. The study is a non-comparative study with long-term follow-up (range 14-90 months). RESULTS: All women developed a normal endometrium, except one asymptomatic woman with atypical hyperplasia who still had focal residual non-atypical hyperplasia at 3 years follow-up in the presence of a thin (< 4 mm) endometrium. CONCLUSION: Continuous intrauterine delivery of LNG appears to be a promising alternative to hysterectomy for the treatment of endometrial hyperplasia and could enhance the success rate when compared with other routes of progestagen administration as well as intrauterine progesterone delivery. The significant reduction of the PR expression observed during treatment with the LNG-IUS appears to be a marker for the strong antiproliferative effect of the hormone at a cellular level resulting in an inhibition of estrogen bioactivity and endometrial suppression.

Endometrial safety after 5 years of continuous combined transdermal estrogen and intrauterine levonorgestrel delivery for postmenopausal hormone substitution.

OBJECTIVE: To investigate endometrial histology and thickness of the endometrium after long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (LNG) in postmenopausal women. DESIGN: A 5-year non-comparative prospective clinical trial. SUBJECTS: Out of 182 symptomatic postmenopausal women using estrogen substitution therapy (EST) combined with a novel T-shaped LNG-releasing intrauterine system (Femilis Slim LNG-IUS), to prevent endometrial proliferation and bleeding, only those women (n=102) who used two consecutive LNG-IUSs, were isolated with the aim to study the long-term effects on the endometrium. The mean age of the women was 57 years (range 47-71). The majority of women received percutaneous 17beta estradiol, 1.5mg daily, or an equivalent dose by patch or orally, on a continuous basis. MAIN OUTCOME MEASURES: Endometrial histology and ultrasonographic evidence of endometrial suppression, after a period of approximately 5 years of use. The mean duration of use of the regimen was 70 months (range 25-98). RESULTS: The dominant endometrial histologic picture was that of inactive endometrium characterized by glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found. On transvaginal ultrasound, this corresponds with a thin endometrium (< or = 5 mm). CONCLUSION: The results of this 5-year study in 102 postmenopausal women using EST demonstrates that the LNG-IUS effectively opposes the estrogenic effect on the endometrium resulting in strong suppression during the entire period of EST. Due to its high efficacy and absence of systemic effects on organ tissues (e.g., breasts), target delivery in the uterine cavity could be a preferred route to administer a progestagen in women using EST.

Endometrial safety with a low-dose intrauterine levonorgestrel-releasing system after 3 years of estrogen substitution therapy.

OBJECTIVE: To evaluate the pharmacodynamic effects of a novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), on the endometrium in 24 postmenopausal women using estrogen substitution therapy (EST) to suppress climacteric symptoms. DESIGN: A 3-year non-comparative prospective clinical trial. SUBJECTS: The treatment with the FibroPlant-LNG intrauterine system (IUS), releasing 14 microg of LNG per day, was part of a regimen for estrogen substitution therapy in symptomatic postmenopausal women to prevent endometrial proliferation and bleeding. The majority of women received percutaneous 17 beta estradiol, 1.5 mg daily, or an equivalent dose by patch or orally, on a continuous basis. OUTCOME MEASURES: Menstrual pattern, endometrial histology and ultrasonographic evidence of endometrial suppression, after 3 years of use. RESULTS: The endometrial histology specimen showed profound endometrial suppression with glandular atrophy and stroma decidualization in all women. On transvaginal ultrasound, this corresponds with a thin endometrium (<5 mm) and clinically with a "bleed-free" menstrual pattern or amenorrhoea. CONCLUSION: The results of this 3-year study in 24 postmenopausal women using EST suggest that the FibroPlant-LNG IUS is effective in causing strong suppression of the endometrium during the entire period of EST. Target delivery in the uterine cavity could be the preferred route of administering a progestin to oppose estrogen stimulation of the endometrium.

Anechoic halo in solid liver tumors: sonographic, microangiographic, and histologic correlation.

The origin of the sonographic halo sign in liver metastases was studied after autopsy in 33 livers with macroscopic tumoral involvement. For 20 lesions a detailed comparison of findings from high-resolution 7.5- and 10-MHz sonography, microangiography, and histology was carried out. Histologic study focused on the tumor periphery and its relationship to the adjacent liver parenchyma. In particular, the type of tumor infiltration, the presence or absence of peritumoral fibrosis, and the degree of liver cell compression were assessed. In all but two cases the halo was extratumoral and was caused by peritumoral liver cell compression. In the remaining two cases the halo was tumoral and was caused by irregular fibrosis or vascularization.

A case of histiocytosis X-central type. Histological, immunohistochemical and electronmicroscopical analysis.

We report a case of Histiocytosis X (HX) associated with a high bone marrow and peripheral blood monocytosis in a 70 yr-old man. The histiocytic clusters in the skin showed the characteristics of epidermal Langerhans cells (LC): positivity for OKT6, OKIa1, ATP-ase and presence of Birbeck granules. Histiocytes in all other locations showed positivity for OKM1, OKIa1, acid P-ase and absence of Birbeck granules. The circulating monocytes were also negative for OKT6 and ATP-ase and lacked Birbeck granules. From these data we assume that the proliferation of monocytes in the bone marrow was the primary event, resulting in the release of large numbers of circulating monocytes and histiocytic proliferation in various tissues. These histiocytes acquired differing characteristics according to the microenvironment in which they underwent their final maturation. In the skin they differentiated into cells presenting the morphological, enzyme-and immunohistochemical characteristics of LC.

Biochemical and histochemical analysis of steroid hormone binding sites in human primary breast cancer.

Mammary carcinoma tissue from 514 primary breast cancer patients were all biochemically and histochemically analyzed for both estrogen receptors and progesterone receptors. The dextran-coated charcoal (DCC) method measured the ER and PR as defined by Scatchard analysis, ligand competition experiments and target organ specificity. The ligands, estradiol-6-carboxymethyloxime-BSA-fluoresceine isothiocyanate and hydroxyprogesteronehemisuccinate-BSA-tetramethylrhodamine isothiocyanate, used for histochemistry, did not bind to either ER or PR and were mainly bound to the membrane fraction of isolated breast cancer cells. Fluorescence was not specifically inhibited by estrogens or progestogens. In addition, "estrogenic" always coincided with "progestogenic" fluorescence. The binding of the fluoresceine compounds to tissue slides depended on the large steroid hormone substitution on the bovine serum albumin molecule. Clinical parameters, known to be related to ER and PR did not correlate with the histochemical results. The observations indicated the impossibility of specific steroid receptor detection by the histochemical method. Therefore, up to the present, evaluation of hormone dependency and prognosis in human breast cancer cannot be based on this approach.

Correlation of sonographic patterns in liver metastases with histology and microangiography.

Thirty-three livers with microscopic metastatic involvement were studied at autopsy by high resolution real time ultrasound at 7.5 and 10 MHz. Eighteen lesions with different sonographic appearances were selected for further microangiographic and histologic analysis. Tumor vascularity was assessed on microangiography. The anatomic pathologic study included both the evaluation of the microscopic and histologic appearances.

[Comparative microangiographic and histological study of hepatic metastases. Possible implications in the phenomena of contrast medium uptake in x-ray computed tomography of the neoplastic liver]. / Etude comparative microangiographique et histologique des métastases hépatiques. Implications possibles dans les phénomènes de captation de contraste en tomodensitométrie du foie néoplasique.

A comparative study using microangiographic and histologic techniques was realized in 43 metastatic livers, totaling 109 lesions. Three different types of tumor vascularization could be recognized. In 30 lesions, residual vessels could be identified. They constitute the only vascular elements in most of the hypervascular lesions studied. On histology, these vessels corresponded to preserved hepatic arterial branches and portal radicles. 79 lesions appeared hypervascular. In 51 lesions, hypervascularity was due to tortuous irregular vessels, corresponding at microscopy to dysplastic capillaries clearly lined with endothelial cells. On the contrary, in 28 metastases, microangiographies showed amorphous contrast uptake. In these cases the contrast was found in large intercellular spaces without endothelial lining, suggesting free interstitial circulation. These observations suggest that the morphology and the dynamic of CT in liver metastases must be influenced by the arterial or portal venous nature of the different vessels. Furthermore, the extravascular diffusion should be function of the type of tumor circulation. If this circulation is confined to real vessels, diffusion will be function of the structure of the walls of these vessels. On the contrary, if the intratumoral circulation is of the free interstitial type, diffusion will be absent and mixing will occur because of the continuity of vascular and interstitial spaces.

The histology of eccrine poromas: a study of 14 cases.

A histological study of 14 eccrine poromas in 14 different patients was conducted and the results correlated with the clinical data. Histologically, an eccrine poroma is an easily recognizable epithelial skin tumor. Three morphological variants can be identified: a benign, a premalignant or dysplastic, and an invasive, malignant form. These tumors hardly have a typical clinical appearance. Symptoms such as bleeding, pain and itching are suggestive of a possible malignant transformation. There seems to be a predilection for localization on the limbs and the head. Most of the lesions occur in patients above the age of 60. It is noteworthy that these tumors, at least those of the face, occur on actinically damaged areas.