Verhandlungen der Deutschen Gesellschaft für Pathologie
-
Verh Dtsch Ges Pathol · Jan 2004
Review Comparative Study[Left ventricular assist devices (LVAD): optional treatment alternative to cardiac transplantation?].
Left ventricular assist devices (LVAD) are used to "bridge" patients with end-stage heart failure until transplantation of a donor heart can be performed ("bridge to transplantation"). However, LVAD support sporadically results in improved cardiac function, and heart transplantation is not necessary even after removal of LVAD in a subset of patients ("bridge to recovery"). Additionally, LVAD appears to be an optional treatment alternative to heart transplantation in patients with contraindication for organ replacement ("destination therapy"). ⋯ LVAD lead to lowered cardiac pressure and volume overload followed by decreased ventricular wall tension, reduction of cardiomyocyte hypertrophy, improved coronary perfusion and a decrease of chronic ischemia in the myocardium. Improved coronary flow and myocardial perfusion as well as decreased ventricular wall tension may serve as a possible explanation for changes of the molecular systems involved in the development of chronic cardiac insuffiency. This review focuses on the roles of apoptosis, heme-oxygenase-1 (HO-1), Metallothionein (MT) and the transcription factor NFkkappaB in chronic heart failure after mechanical circulatory support.
-
Verh Dtsch Ges Pathol · Jan 2007
[Colorectal serrated adenoma: diagnostic criteria and clinical implications].
More than 40 years ago Morson (1962) coined the paradigm that adenomas are the main precursors of colorectal carcinoma (CRC) whereas hyperplastic polyps are "non-neoplastic" lesions without cancer risk. Later-on (1988) this was supported by Vogelstein's molecular adenoma-carcinoma progression model with APC mutations being a key-initiating molecular event (classic adenoma-carcinoma pathway). In 1992 a new molecular mechanism, the mutator pathway of CRC was discovered in HNPCC patients. ⋯ Today four categories of serrated lesions can be delineated: (i) the most frequent classic hyperplastic polyp (HP, 80-90%), followed by (ii) sessile serrated adenoma (SSA, 15-20%) and (iii) by the rare traditional serrated adenoma (TSA, < 1%). Whereas HPP are benign, SSA are probably slowly progressing lesions and TSA as well as SSA with APC-type adenomatous atypias (iv. mixed SSA) indicate increased cancer risk. Molecularly serrated polyps seem to share a defect in apoptosis caused by either K-ras or BRAF gene mutation leading to CpG island methylation (CIMP) affecting MLHI (--> MSI type CRC) or non-MMR oncogenes (--> MSI-L or MSS type serrated CRC, Mäkinen 2007).
-
Verh Dtsch Ges Pathol · Jan 2000
ReviewMolecular aspects of adhesion-epigenetic mechanisms for inactivation of the E-Cadherin-mediated cell adhesion system in cancers.
E-Cadherin and its undercoat proteins, alpha- and beta-Catenins, which connect cadherins to actin filaments and establish firm cell-cell adhesion, act as an invasion suppressor system. It was demonstrated that transcriptional inactivation of E-Cadherin expression occurred frequently in tumor progression, and that E-Cadherin expression in human cancer cells was regulated by CpG methylation around the promoter region. In diffusely infiltrating cancers, mutations were found in the genes for E-Cadherin and alpha- and beta-Catenins. ⋯ Regulation of the E-Cadherin-mediated cell adhesion system by tyrosine phosphorylation of beta-Catenin is important in determining the biological properties of human cancers. Tumor cells are dissociated throughout the entire tumor masses of diffuse-type cancers, whereas those of solid tumors with high metastatic potentials are often focally dissociated or dedifferentiated at the invading fronts. Thus, both irreversible and reversible mechanisms for inactivating the E-Cadherin-mediated cell adhesion system well correspond to the pathological features of human cancers.
-
While most colorectal polyps can be classified as either adenomas (AD) or hyperplastic polyps (HP), approximately 5 % have some of the features of these lesions but are distinguishable from both. These lesions include sessile serrated adenoma or polyp (SSP), mixed polyp (MP), and traditional serrated adenoma (SA). These relatively recently described entities account for only about 3%, 1% and 1% of colorectal polyps respectively. ⋯ Finally, a simple working nomenclature for the diagnostic reporting of colorectal polyps is suggested. In this system, MPs and SAs are combined as 'serrated polyps with dysplasia'. It is likely that the recognition and diagnosis of serrated polyps of the colorectum will assume increasing importance in the coming years and that their complex morphology and molecular heterogeneity will present interesting challenges for pathologists, scientists and clinicians.