Site-independent prognostic value of chromosome 9q loss in primary gastrointestinal stromal tumours

Although the significance of tumour site for estimating malignant potential in gastrointestinal stromal tumours (GISTs) has recently been recognized, site-specific genetic patterns have not to date been defined. This study examined 52 c-kit-positive primary GISTs (with a mean follow-up of 42.3 months in 51 cases) from three different locations (35 gastric, 12 small intestinal, and five colorectal) using comparative genomic hybridization (CGH). In general, tumour site correlated with key prognostic factors, including tumour size, mitotic rate, proliferative activity, and probable malignant potential. Furthermore, several DNA copy number changes showed a site-dependent pattern. These included losses at 14q (gastric 83%, intestinal 35%; p = 0.001), losses at 22q (gastric 46%, intestinal 82%; p = 0.02), losses at 1p (gastric 23%, intestinal 88%; p = 1 x 10(-5)), losses at 15q (gastric 14%, intestinal 59%; p = 0.002), losses at 9q (gastric 14%, intestinal 53%; p = 0.006), and gains at 5p (gastric 11%, intestinal 53%; p = 0.002). These data demonstrate strong site-dependent genetic heterogeneity in GISTs that may form a basis for subclassification. Prognostic evaluation of DNA copy number changes identified losses at 9q as a site-independent prognostic marker associated with shorter disease-free survival (p = 0.03) and overall survival (p = 0.002). Furthermore, 9q loss also appeared to carry prognostic value in predicting overall survival for patients with advanced or progressive GISTs (p = 0.003).     

Biological and clinical significance of cytogenetic abnormalities in low-risk and high-risk gastrointestinal stromal tumors

We report cytogenetic findings in 19 c-Kit-positive gastrointestinal stromal tumors (GISTs) that represent a heterogenous group of mesenchymal neoplasms with respect to site, histology, and biologic behavior. All of the GISTs (5 low-risk, 11 high-risk, 3 recurrences) displayed clonal chromosomal aberrations; 15 were hypo- to near-diploid, and 4 were near-triploid and hypotetraploid. The most common abnormalities were loss of chromosomes 14 and/or 22, demonstrated in 14 GISTs irrespective of site or predominant phenotype. Ten cases (2 low-risk, 5 high-risk, 3 recurrences) were characterized by loss of both chromosomes 14 and 22, 2 cases (1 low-risk, 1 high- risk), by loss of chromosome 14; and 2 high-risk cases, by loss of chromosome 22. Additional chromosomal aberrations occurred preferentially in high-risk and recurrent GISTs, including loss of 9p and 1p in 8 cases each, loss of 15 in 6 cases, loss of 3p in 5 cases, loss of 13q and 10q in 4 cases each, loss of 19 in 3 cases, and complete or partial gains of chromosomes 5 and 4 in 2 cases each. More significantly, 5 of 6 patients with clinically aggressive GISTs, including 2 recurrences and 3 metastasing GISTs, were additionally characterized by loss of 9p; four of these had additional loss of chromosomes 1p and 15. The presented results herein indicate that loss of chromosome 14 and/or 22 is an early change in GIST tumorigenesis irrespective of site or differentiation, whereas malignant transformation and progression of GISTs appear to be associated with an increasing incidence of additional secondary aberrations.     

Beta-oxidation of 1-[14C]-17-[131I]-iodoheptadecanoic acid following intracoronary injection in humans results in similar release of both tracers

Radioiodine labelled 17-iodo-heptadecanoic acid (IHA) is used for non-invasive study of myocardial metabolism in coronary heart disease and cardiomyopathy. Yet in the interpretation of in vivo myocardial tracer kinetics, it is controversial whether the intracellular degradation of IHA or the removal of iodide across cellular membranes is the rate-limiting step in iodide release from the myocardium. In five patients undergoing coronary sinus catheterization, a mixture of about 40 kBq of [¹²³I] NaI was injected into the left coronary artery. During the following 15-min period, frequent blood samples were taken from the aorta and the coronary sinus. In the aqueous phase of the venous blood, ¹⁴CO₂ and inorganic ¹³¹I appeared nearly in parallel, with a peak time of 4–5 min. Moreover, as shown by the AV difference, there was no significant back diffusion of IHA and no significant non-specific deiodination detectable over the period of observation. There was myocardial retention of inorganic iodide (¹²³I) injected into the left coronary artery. The data strongly support the premise that lipid turnover through -oxidation is the rate-limiting step in the externally measured release of iodide after IHA injection, provided that recirculating inorganic radioactive iodide is corrected for. In addition, 15 volunteers were studied using [¹¹C]palmitic acid and [¹²³I]IHA using PET and dynamic planar camera scintigraphy with iodide correction. There was no significant difference between the mean values of the elimination half-times, and also no significant correlation between half-times of both fatty acids for single individuals.     

Aneurysm of the membranous septum causing outflow obstruction of the venous ventricle in corrected transposition of the great arteries

A 58 year-old man with clinical and hemodynamic evidence of subpulmonic stenosis was admitted to our hospital. Angiography revealed corrected transposition of the great arteries and an aneurysm of membranous ventricular septum (AVS) that protruded into the venous outflow tract, causing severe subpulmonic obstruction during systole. The diagnosis was confirmed at surgery, and successful repair of the aneurysm was performed. This was an unusual case because the AVS caused such severe obstruction that the venous ventricular pressure was elevated to a value equal to the systemic level.     

Diagnostische Genauigkeit der Dual-energy-CT-Angiographie bei Patienten mit Diabetes mellitus

Die Radiologie - Die periphere arterielle Verschlusskrankheit (PAVK) ist eine wesentliche Komplikation des Diabetes mellitus und stellt aufgrund ausgeprägter Gefäßverkalkungen eine...     

123I]-phenylpentadecanoic acid uptake in patients with dilated cardiomyopathy

BACKGROUND: The rate constant for global fatty acid influx (k(1)) was studied in 12 male patients with dilated cardiomyopathy (DCM). METHOD: 10 normal subjects served as controls. 201-Thallium (201TI) and [123I]-phenyl-pentadecanoic acid (IPPA) were administered during bicycle exercise under fasting conditions. RESULTS: All patients showed non-homogeneous tracer uptake defects for 201TI and IPPA. k(1) was significantly higher in DCM patients than controls. k(1) showed significant inverse correlation between cardiac index, left-ventricular ejection fraction, left-ventricular enddiastolic pressure and echocardiographic left-ventricular ejection fraction. CONCLUSION: We presume that an increased regional rate constant of IPPA influx into the myocardial tissue in patients with DCM reflects a compensatory mechanism of altered myocardium.     

Establishment and characterization of two distinct malignant mesothelioma cell lines with common clonal origin

We describe two newly established malignant mesothelioma (MM) cell lines derived from a pleural effusion of a male. One cell line, designated as MM-Z03E, reveals an epithelioid cobblestone morphology, while the second one, designated as MM-Z03S and subcloned after in vivo selection, exhibits a sarcomatoid storiform growth pattern. Both cell lines showed the immunologic profile characteristic for MM (i.e., expression of cytokeratin, CK18, calretinin, and vimentin in both phenotypes). Cytogenetics, multicolor fluorescence in situ hybridization, comparative genomic hybridization, and oligonucleotide array CGH were performed on both cell lines. Aberrations shared by both cell lines included chromosomal losses of 1q34 approximately qter, 4, 9p, 10p, 13, 14, 16q, 18, and 22, as well as a complex structural aberration involving chromosome 17. Aberrations exclusive to MM-Z03E included gains of 3q11q27 and 5p, while gain of 9q and losses of 3q27qter, 11q, and 18 in MM-Z03S were exclusive to MM-Z03E. Both cell lines were able to develop solid transplant tumors in nude mice within 16 weeks, and immunophenotyping of tumor xenografts revealed an overall retained expression profile of the markers used. Remarkably, one xenograft from MM-Z03E revealed overexpression of p53 and widely invasive growth. In conclusion, both cell lines are useful in vivo and in vitro model systems to study the underlying genetic mechanisms of biphasic differentiation in MM, which can be of certain value considering the increasing relevance of assessing MM tumor biology for the clinical management of this disease.