Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables.

We studied 134 patients with differentiated thyroid cancer and pulmonary metastases. All were treated with total or near total thyroidectomy, radioiodine and L-thyroxine. The prognostic value of the following variables in three groups of patients were evaluated by univariate and multivariate analysis: age at diagnosis, sex, histologic type, tumor extension, cervical lymph node metastases, mediastinic metastases, presence of metastases in distant sites other than lungs (multiple distant metastases) and morphological (chest x-rays) and functional (131I uptake) features of lung metastases. Univariate analysis identified patient age (p < 0.0001), morphological and functional features of lung metastases (p < 0.0001), presence of multiple distant metastases (p < 0.0001) and histologic type (p = 0.04) as significant prognostic factors. Multivariate analysis showed only morphological (p = 0.0014) and functional (p < 0.0001) features of lung metastases and the presence of multiple distant metastases (p = 0.01) as significant and independent variables. The data show that early (pre-radiological) scintigraphic diagnosis and 131I therapy of lung metastases appear to be the most important elements in obtaining both a significant improvement in survival rate and a prolonged disease-free time interval in these patients.

Effects of all-trans retinoic acid and interferon alpha in peripheral neuroectodermal tumor cell cultures and xenografts.

Peripheral neuroectodermal tumors (PNET) have an unsatisfactory outcome when treated with standard approaches. Among novel treatments, the use of biological response modifiers has rarely been reported in this group of malignancies. We have previously demonstrated that both all-trans retinoic acid (ATRA) and interferon á (IFNá) can inhibit proliferation of human PNET cells and that ATRA can up-regulate IFNá receptor expression in vitro. In this study we evaluated the anti-tumor effects of ATRA and IFNá in PNET cells in vitro and in a human PNET xenograft model, using CHP100 cells. A synergistic inhibitory effect of ATRA and IFNá was observed on CHP100 cells in vitro. On the contrary, a significant inhibition of tumor growth was observed in mice treated with ATRA alone, whereas neither IFNá nor the combination of ATRA and IFNá, reached a statistically significant anti-tumor effect. Histologic examination of tumors revealed the presence of necrosis upon treatment with IFNá, whereas almost no necrosis, but a more differentiated morphology, confirmed by electron microscopy analysis, was associated with the ATRA containing treatments. Taken together these data show an in vitro and in vivo anti-tumor activity of ATRA in human PNET cells, although no synergism of ATRA and IFNá was observed in our xenograft model.

Histological evaluation of thyroid carcinomas: reproducibility of the "WHO" classification.

AIMS AND BACKGROUND: Thyroid carcinomas display several pathologic features, show different behavior and necessitate different treatment; thus correct classification is mandatory. METHODS: The kappa statistic was used as a measure of agreement in a panel of seven pathologists who reviewed 200 cases of thyroid tumors. RESULTS: Overall agreement was 83% (k = 68). Good agreement was found for anaplastic (k = 0.85) and papillary carcinomas (k = 0.81); agreement for medullary carcinoma was acceptable (k = 0.80), suboptimal for other (k = 0.67), and poor for follicular carcinoma (k = 0.54). CONCLUSIONS: Central pathology review of thyroid carcinomas is recommended when clinical and epidemiologic trials are planned.

Distant metastases in differentiated thyroid cancer: long-term results of radioiodine treatment and statistical analysis of prognostic factors in 214 patients.

Long-term results and statistical analysis of prognostic factors in a series of 214 patients with distant metastases from differentiated thyroid cancer (DTC) are reported here. These 214 were part of a total series of 1457 patients with DTC referred to our center from 1967 to 1987. All patients underwent surgery and 131-I therapy and were treated with TSH suppressive doses of thyroid hormones. After a mean follow-up of 7.3 years including clinical, scintigraphic, radiological and laboratory investigations, 24.4% of patients were alive without disease, 36.5% alive with disease, 1.8% dead without disease and 37.3% dead with disease. One of the main factors influencing the survival in our series was 131-I uptake (RIU) by metastatic tissue. No case of complete remission of disease was observed among patients with nonfunctioning metastases. Another important factor was the site of metastases, patients with bone metastases having the worst prognosis. The patient's age at diagnosis represented another important factor for survival; patients over 40 years, particularly those over 60 years had a bad prognosis. A clear interrelation was found among the factors advanced age, nonfunctioning metastases and bone metastases. Patients with these last clinical features were considered to be at high risk and generally had a fatal outcome. Another significant prognostic factor revealed by univariate analysis was the histologic type. Patients with follicular tumor showed a poorer prognosis in comparison to papillary tumor. When multivariate analysis was applied, the factors age at diagnosis, site of metastases and RIU proved to have a significant influence on survival, but not the histologic type. Lastly, the relative rate of males was higher in the group of patients with metastases in comparison to the whole series of DTC patients. Despite this, the factor sex did not influence survival.

Daily fecundability: first results from a new data base.

This multicenter study has produced a database of 7017 menstrual cycles contributed by 881 women. It provides improved knowledge on length and location of the "fertile window" (identified as of up to 12 days duration) and the patterns and level of daily conception probability. The day of ovulation was identified in each cycle from records of basal body temperature and mucus symptoms. By referencing days of intercourse to the surrogate ovulation markers, estimates of daily fecundability were computed either directly or by the Scwartz model, both for single and multiple acts of intercourse in the fertile window. The relationship between coital pattern and fecundability has been explored. Univariate analysis underlines the significant link with fecundability only of the woman's reproductive history.

Probability of conception on different days of the menstrual cycle: an ongoing exercise.

The design of the European Multicenter Study on the probabilities of conception in different days of the menstrual cycle is reviewed. Some results, based on part of the data, are presented. These can be summarized as follows: a) Estimates of the probabilities of conception are lower than the ones previously reported in the literature; b) A strong effect of the man's age on fecundability was found. No evidence of a similar impact of the woman's age was demonstrated; c) The number of days with 'most fertile' mucus and parity affect fecundability.

Role of bronchoalveolar lavage in predicting survival of patients with human immunodeficiency virus infection.

In this multicenter study, we investigated the prognostic factors that influence the risk of death in patients with human immunodeficiency virus (HIV) infection. Clinical and laboratory indices obtained from 161 HIV-seropositive patients who underwent a detailed morphologic and immunophenotypic evaluation of bronchoalveolar lavage (BAL) and peripheral blood cell populations were retrospectively analyzed. In 155 patients, death occurred within the 48-mo follow-up (mean follow-up: 14.8 mo; range: 1 to 48 mo). In the univariate analysis, the patient's age (> 30 yr), HIV disease status, HIV transmission category, number of opportunistic pathogens isolated from the BAL, percentage of BAL neutrophils, and low number of BAL CD4 T cells were predictive of increased mortality. In contrast, the presence of an alveolitis or an increase in the numbers of alveolar macrophages and CD3 T cells was associated with a decreased mortality. In the multivariate analysis, significant independent predictors were age, risk factor for HIV, and presence of an alveolitis. Furthermore, patients with a low number of BAL CD4 T cells had a particularly poor prognosis while the CD4 T-cell count in the peripheral blood (< 50 cells/mm3 in the majority of our patients) had a negligible effect on predicting survival. Our findings suggest the clinical utility of BAL analysis in patients infected with HIV.