Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Outcomes of 17,137 pregnancies in 2 urban areas of Ukraine

OBJECTIVES: Frequent terminations of pregnancy and high rates of fetal loss have been reported, but not confirmed, in the former eastern bloc. A census of pregnancies in Ukraine, a former eastern bloc country, was conducted to determine the rates of these events. METHODS: All pregnancies registered in 2 urban areas were enumerated. During a 19-month period between 1992 and 1994, 17,137 pregnancies and their outcomes were recorded. RESULTS: Sixty percent of the pregnancies were voluntarily terminated, generally before the 13th week. In pregnancies delivered at 20+ weeks, fetal mortality was 29 per 1000, nearly 5 times the rate among Whites in the United States. There was a greater proportion of very early deliveries (20-27 weeks) in Ukraine, as well as higher death rates at all gestational ages. Perinatal mortality was estimated to be 35 per 1000, about 3 times the US rate. CONCLUSIONS: This is believed to be the first study in the former eastern bloc to ascertain all of the clinically recognized pregnancies in a specified period and to determine their outcomes. The data document elevated reproductive risks in a former Soviet state.     

The incidence of deep venous thrombosis after arthroscopic knee surgery

We retrospectively reviewed the records of 2050 arthroscopic knee surgeries performed at The Orthopedic Specialty Hospital from January 1993 to December 1994. The number of clinically detected deep venous thromboses, with confirmation by duplex ultrasonography, was determined. Prospectively, preoperative and postoperative duplex ultrasonographic images were completed on 239 patients divided into 2 groups: those undergoing nonligament, intraarticular arthroscopic surgery (N = 131) and those undergoing arthroscopically assisted ligament surgery and extraarticular or osteotomy surgery (N = 108). For the retrospective study, the incidence of deep venous thrombosis was 0.24%. Prospectively, seven total deep venous thromboses were identified (rate, 2.9%), with five being identified within 8 days of surgery in asymptomatic patients (rate, 2.1%). There were no statistically significant associations or correlations between the development of deep venous thrombosis and patient personal data or surgical variables, respectively. The difference in the rate of deep venous thrombosis between the two prospective groups was not statistically significant; however, patients who had more invasive surgery tended to be at higher risk for developing deep venous thrombosis. A cost-benefit analysis did not support the routine use of duplex ultrasonography to detect deep venous thrombosis in patients undergoing arthroscopic knee surgery.     

Exploring linkage for alcoholism using affection status and quantitative event related potential phenotypes

Using genome-scan data from the Collaborative Study on the Genetics of Alcoholism (COGA), we compared results of linkage analyses using a qualitative alcoholism phenotype to results of linkage analyses using event related potential (ERP) quantitative phenotypes, and compared our results to the results of Reich et al. [1998] and Begleiter et al. [1998]. We describe a general and simple strategy for identifying regions of the genome which may harbor genes involved in alcohol dependence which takes into consideration the results of both the affection status and ERP linkage analyses.     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

     

T lymphocytes in patients with Down's syndrome.

Individuals with Down's syndrome (DS) are thought to have abnormalities in their immune system, and a tendency to infection and malignancy. Studies to quantify the number of T lymphocytes in the peripheral blood of 82 unselected institutionalized patients (50 DS, 27 controls matched for sex and age, 2 chronic lymphocytic leukemic, 2 acute leukemic, and 1 Hodgkin's disease) were conducted. The numbers of circulating T cells in DS patients did not differ significantly from the control group, and were in the upper limits of normality. Number of "avid" T cells, however, were significantly higher in the DS than in the control group. The blastogenic response of the T cells to mitogen was significantly depressed. The data did not exclude the existence of qualitative abnormalities. Except for DS patients with congenital heart disease, those older than 15 years were not more prone to upper respiratory infections than other institutionalized mentally retarded patients.