Bronchioalveolar cell carcinoma: radiologic appearance and dilemmas in the assessment of response

Bronchioalveolar cell carcinomas (BACs), a subset of primary lung adenocarcinomas, are uncommon. Histologically, they are a diverse group of malignancies. The diagnosis is restricted to adenocarcinomas that grow in a lepidic manner and that have no stromal, vascular, or pleural invasion. Their histologic diversity leads to varied radiologic manifestations that are often indistinguishable from those of other primary non-small-cell lung cancers (NSCLC). However, typical manifestations, many of which can be attributed to lepidic growth, have been reported. Radiologic manifestations include a solitary peripheral pulmonary nodule, airspace disease, and multiple nodules and a combination of these findings can be present in a single patient. The most common manifestation, a solitary pulmonary nodule, is usually indistinguishable from other primary NSCLC. However, pseudocavitation and air bronchograms within the nodule can be useful in suggesting the correct diagnosis. In addition to aiding in the diagnosis of BAC, radiologic imaging is an important component in the evaluation of the therapeutic efficacy of treatment; serial measurements of tumor size before and after treatment are commonly used to assess response. However, BACs that are consolidative or ground-glass in nature present challenges in tumor-response determination. Other imaging modalities, such as positron emission tomography scanning, may prove helpful in assessing the metabolic response to therapy but have yet to be proven effective.     

Health promotion evaluation: focus on "healthy cities"

Since the Healthy City movement is a health promotion strategy, an update study was carried out to put into context the health promotion evaluation debate stressing the principles to be considered in an evaluation initiative and in the problematic of Health Cities projects. A literature review of "Healthy Cities" was conducted. A typology based on of Healthy Cities papers found in MEDLINE, LILACS and published in the "Health Promotion International" between 1985 and 2000 was proposed taking into consideration the main focus of each paper. Articles on evaluation were analyzed in more details according to stressing methods, research tools, indicators, study results, and critical appraisal of their models. Finally, it is highlighted initiatives that would come close to the principles of "Health Promotion" and adopt evaluation as a tool for building up capabilities and the empowerment of community groups involved with Healthy Cities initiatives.     

Estrogen deficiency accelerates progression of glomerulosclerosis in susceptible mice

Estrogen deficiency may contribute to the development and progression of glomerulosclerosis in postmenopausal women. The responsiveness to estrogens could be controlled by genetic traits related to those that determine the susceptibility to glomerular scarring. This study was undertaken to determine whether the intensity of the sclerotic response was modified by the estrogen status in sclerosis-prone ROP Os/+ mice. Ovariectomized ROP Os/+ mice developed more severe renal dysfunction and glomerulosclerosis than intact, ie, estrogen sufficient age-matched female mice. Ovariectomized ROP Os/+ exhibited increased accumulation of extracellular matrix, predominantly of laminin, and a marked distortion of the glomerular architecture. We found an increase in macrophage infiltration in the mesangium of ovariectomized ROP Os/+. Estrogen deficiency decreased glomerular estrogen receptor expression in ROP Os/+ mice, which we had previously found to be low in the parental ROP strain. Thus, although physiological estrogen levels in young ROP Os/+ mice could not prevent the development of glomerulosclerosis, estrogen deficiency accelerated the progression of glomerular scarring in this mouse strain. This suggests that estrogen replacement will slow but not prevent the progression of glomerulosclerosis. It underscores the importance of the genetic composition of individuals that determines the susceptibility to diseases as well as the response to treatment.     

Brain metastases with an unknown primary: a clinical perspective

A review of 43 patients with cerebral metastases, an unknown primary, and no other sites of metastases is presented. 27/43 (62.7%) had solitary metastases and 37.2% (16/43) had multiple metastases. Surgical treatment involved complete resection in 30.2%, subtotal resection in 37.2% and biopsy alone or no surgical procedure in the remainder. 39/43 patients underwent whole brain irradiation with the majority receiving 3000–4000 rads/10–20 fractions. Overall survival was 52% at six months and 20% at one year, and was significantly better in patients with solitary as opposed to multiple metastases (p < 0.03). A failure analysis including autopsy data demonstrates that (28/41) 68.3% of patients died of progressive intracranial disease without extracerebral metastases. Implications for treatment strategies are discussed.     

Interobserver and intraobserver variability in measurement of non-small-cell carcinoma lung lesions: implications for assessment of tumor response.

PURPOSE: Response of solid malignancies to therapy is usually determined by serial measurements of tumor size. The purpose of our study was to assess the consistency of measurements performed by readers evaluating lung tumors. MATERIALS AND METHODS: The study group was composed of 33 patients with lung tumors more than 1.5 cm. Bidimensional (BD) and unidimensional (UD) measurements were performed on computed tomography (CT) scans according to the World Health Organization (WHO) criteria and the Response Evaluation Criteria in Solid Tumors (RECIST), respectively. Measurements were performed independently by five thoracic radiologists using printed film and were repeated after 5 to 7 days. Inter- and intraobserver measurement variations were estimated through statistical modeling. RESULTS: There were 40 tumors with an average size of 1.8 to 8.0 cm (mean, 4.1 cm). Analysis of variance showed a significant difference (P <.05) among readers and among the measured nodules for UD and BD measurements. Interobserver misclassification rates were more than intraobserver misclassification rates using either progressive disease or response criteria. The probability of misclassifying a tumor with the WHO criteria or RECIST was greatest with interobserver measurements when criteria for progression (43% BD, 30% UD) were used and lowest with intraobserver measurements when criteria for response (2.5% BD, 3.0% UD) were used. In addition, interobserver misclassification rates were more than intraobserver misclassification rates for both regular and irregular tumors. CONCLUSION: Measurements of lung tumor size on CT scans are often inconsistent and can lead to an incorrect interpretation of tumor response. Consistency can be improved if the same reader performs serial measurements for any one patient.     

Alternative Animal and Non-Animal Models for Drug Discovery and Development: Bonus or Burden?

Mammalian models have served as a basis for R&D over the past decades. Nevertheless, these models are expensive, laborious, may yield results that cannot always be translated into the human in vivo situation and, more recently, have reverberated great social and ethical dilemmas. Hence, the prospect of changes in the global scientific scenario and the Three Rs principle (Reduction, Replacement and Refinement) have encouraged the development of alternative methods to the use of mammals. Despite the efforts, suitable alternative tests are not available in all areas of biomedical research, as regulatory acceptance requires time, prior validation and robust financial and scientific investment. In this perspective, we aim to shed light on the concepts, challenges and perspectives for implementation of innovative alternative animal and non-animal methods in scientific research. The applicability and meaningfulness of invertebrate animal models, in silico analysis and reverse pharmacology are discussed, among other aspects of relevance in today’s scenario. Overall, the use of alternative models, including Artemia salina (brine shrimp), Caenorhabditis elegans (roundworm), Danio rerio (zebra fish), Drosophila melanogaster (fruit fly), Galleria mellonella (greater waxmoth) and in silico modelling, increased 909% from 1990 to 2015, as compared to 154% of conventional mammals in the same period. Thus, technological and scientific advancements in the fields of toxicology and drug development seem to have diminished the need for mammalian models. Today, however, mammals still remain critically indispensable to provide – in most cases –reliable data subsidizing and validating translation into the clinical setting.