Objective: The aim of this study was to compare the value of contrast-enhanced ultrasonography (CEUS) with standard B-mode ultrasound (US) for diagnosis of splenic lymphoma involvement.Methods: From 04/2005 to 10/2008 n = 250 lymphoma patients were investigated by standard B-mode US. A homogeneous splenic echotexture was found in 199 patients (79%). To clarify the benefit of CEUS in this group a pilot series was performed with 16 of the 199 lymphoma patients. All patients with an abnormal splenic echotexture on standard B-Mode US (n = 51) including focal hypoechoic splenic lesions (n = 41) and an inhomogeneous splenic texture (n = 10) were studied by CEUS. CEUS data were retrospectively evaluated. The diagnoses included indolent lymphoma (n = 27), aggressive lymphoma (n = 14), and Hodgkin's disease (n = 10). Number and size of lesions were determined by B-mode US and CEUS. The visualisation of splenic lymphoma involvement by CEUS in comparison to B-mode US was classified as worse, equal, or better.Results: All patients with a homogeneous spleen on B-mode US(n = 16) had no visible focal lesions on CEUS. Study patients with focal lesions (n = 41) had a hypoechoic (n = 22) or isoechoic (n = 19) enhancement during the arterial phase, and a hypoechoic enhancement during the parenchymal phase (n = 41). The visualisation of focal splenic lymphoma was equal (n = 32), better (n = 6), or worse (n = 3). In all study patients with an inhomogeneous spleen on B-mode US (n = 10) no focal lesions were found by CEUS and the value of CEUS therefore was classified as worse.Conclusion: CEUS has no clear advantage for diagnosis of splenic lymphoma involvement. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Background: CpG islands methylation is the main epigenetic modification found in human tumors leading to transcriptional silencing of certain tumor suppressor genes. Reacquisition of p16/ CDKN2A tumor suppressor gene expression by 5-aza-2'-deoxycytidine results in concurrent growth inhibition of neuroendocrine pancreatic tumor cells. However, the growth suppressive effects of 5-aza-2'-deoxycytidine is unlikely to be solely attributable to the restored p16/ CDKN2A function, but rather a consequence of re-expression of additional genes silenced by de novo methylation. In an effort to validate DNA methylation as an important mechanism in neuroendocrine tumorigenesis and metastatic spread, we attempted to isolate methylation-specific transcripts in neuroendocrine pancreatic tumor cells. Methods: Differentially expressed methylation-associated genes were identified by cDNA-representational difference analysis (cDNA-RDA). Differential expression was confirmed by semi-quantitative RT-PCR using insert specific primers. Results: We identified 48 differently expressed gene fragments and methylation-associated expression was confirmed by semi-quantitative RT-PCR. 52,3% (25 of 48) showed elevated expression levels after 5-aza-2'-deoxycytidine treatment, whereas 47.7% revealed lower expression levels. 7 fragments showed homology to genes with unknown function. Interestingly, 5-aza-2'-deoxycytidine treatment led to re-expression of cofillin whereas matriptase expression levels were significantly lower. Both genes have been associated with metastastic spread and tissue invasion. The other differentially expressed genes play an unknown role in the course of neuroendocrine tumorigenesis. Conclusion: DNA methylation appears to be an important molecular mechanism in the process of neuroendocrine pancreatic tumorigenesis and metastatic spread. The definition of DNA methylation patterns associated with neuroendocrine pancreatic tumors might open up the potential for a new sensitive diagnostic tool and might serve as a new antitumor target. Copyright (C) 2007 S. Karger AG, Basel and IAP.

Objective. Second‐generation contrast agents have shown spleen‐specific uptake. The aim of this study was to investigate the ability of contrast‐enhanced sonography (CES) to demarcate splenic lesions in patients with pain in the left upper quadrant (LUQ) and an inhomogeneous splenic texture. Methods. From October 2003 to July 2005, 31 consecutive patients with pain in the LUQ and splenic inhomogeneity on B‐mode sonography were studied by CES using a second‐generation contrast agent (SonoVue; Bracco SpA, Milan, Italy). The following data were retrospectively evaluated: extent of enhancement (EE) of the spleen and focal splenic lesions was determined and classified, with the EE of surrounding tissue used as an in vivo reference. Focal splenic lesions were classified after CES as round or wedge shaped, solitary or multiple, and anechoic, hypoechoic, or hyperechoic. Results. The EE of the spleen after CES was anechoic (n = 1), hypoechoic (n = 1), or hyperechoic (n = 29). In 16 of 31 patients, focal lesions were seen after CES. The EE of the lesions was anechoic (n = 11) or hypoechoic (n = 5). Lesions were solitary (n = 6) or multiple (n = 10) and round (n = 5) or wedge shaped (n = 11). Final clinical diagnoses of splenic abnormalities were no specific diagnosis (n = 13), complete autosplenectomy (n = 2), splenic lymphoma (n = 5), and splenic infarction (n = 11). The CES diagnoses were confirmed by computed tomography (n = 21), scintigraphy (n = 2), magnetic resonance imaging (n = 1), and clinical follow‐up (n = 7). Conclusions. In patients with pain in the LUQ and splenic inhomogeneity, CES enables visualization of splenic abnormalities in more than 50% of the patients; in this group, splenic infarction was the most common diagnosis.

OBJECTIVE:Transpulmonary sonography contrast agents, in conjunction with contrast-specific imaging techniques, are increasingly accepted in clinical use for diagnostic imaging of several organs. Anatomically, the lung is characterized by dual blood sources, supplied from both the pulmonary and bronchial arteries. Contrast-enhanced sonography enables us to determine whether the pulmonary or the bronchial arteries are the source of blood to lung lesions, depending on the time to enhancement and the extent of enhancement after contrast agent application.CONCLUSION:This article reports our first experience with transcutaneous contrast-enhanced sonography for the diagnosis and differential diagnosis of peripheral lung lesions.

Many important articles about fat distribution disorders within the liver have been published in the 1980s and 1990s. However, the diagnostic dilemma of distinguishing diffuse or focal fat distribution disorders especially from malignant neoplasmas persists and is still of clinical relevance. Rare and more common sonographic patterns can be subdivided according to their echogenicity, location, quantity, shape and boundaries by B-mode sonography. The knowledge of the characteristic sonographic patterns of diffuse and focal fat distribution disorders within the liver avoids in most cases costly and more invasive diagnostic procedures. Depending on clinical background in individual cases confirmation of diagnosis of focal fatty liver disease is necessary.

Many important articles about fat distribution disorders within the liver have been published in the 1980s and 1990s. However, the diagnostic dilemma of distinguishing diffuse or focal fat distribution disorders especially from malignant neoplasmas persists and is still of clinical relevance. Rare and more common sonographic patterns can be subdivided according to their echogenicity, location, quantity, shape and boundaries by B-mode sonography. The knowledge of the characteristic sonographic patterns of diffuse and focal fat distribution disorders within the liver avoids in most cases costly and more invasive diagnostic procedures. Depending on clinical background in individual cases confirmation of diagnosis of focal fatty liver disease is necessary.

Die Lunge ist durch eine duale Gefäßversorgung charakterisiert. Die Existenz einer bronchial-arteriellen Versorgung wurde bereits im 2. Jahrhundert von Galen vermutet. Angiographische Studien zeigen, dass unterschiedliche Lungenläsionen eine unterschiedliche Gefäßversorgung aufweisen. Mithilfe der Farbdopplersonographie können Lungenarterien durch Ortslage, Flussrichtung und quantitative Spektralkurvenanalyse klassifiziert werden. Dieser Artikel will die Pathophysiologie sowie Grundlagen der Farbdopplersonographie von Lungengefäßen darstellen.

regulation by these two isoforms.Conclusion: DNA replication is regulated by licensing proteins.The MCM2 protein has been found to have a novel isoform.These two isoforms are reciprocally related during senescence and proliferation.We conclude there is a molecular switch between these two isoforms that will dictate the rate of DNA replication during senescence versus proliferation.

Human MAGE and GAGE genes encode tumor-specific antigens presented by HLA I molecules recognized on tumor cells by cytolytic T lymphocytes. To determine if pancreatic cancer patients would be suitable for MAGE-or GAGE-based immunotherapy, the expression frequency of MAGE-A1, -A2, -A3, -A4, -A6 and GAGE1-8 genes was assessed in 15 pancreatic tumor cell lines and 23 pancreatic tumor specimens using reverse transcription-polymerase chain reaction (RT-PCR). In 67% of the cell lines at least one of the MAGE-A genes was detected, 53% revealed concomitant expression of two or more genes. GAGE1–8 expression was detected in 47% of the cell lines. In the primary pancreatic tumors, MAGE-A analysis revealed exclusive MAGE-A1 and MAGE-A2 gene expression in 26 and 30% of the specimens, respectively, independent from clinicopathologic factors. Treatment of MAGE-A expression-negative pancreatic tumor cells with the demethylating agent 5-aza-2′-deoxycytid-ine could activate MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4 and GAGE transcription suggesting silencing due to promoter methylation. Interestingly, a metastatic lesion to the liver revealed concomittant expression of MAGE-A1, -A2, -A3 and -A6 consistent with a more pronounced genome-wide hypomethylation in metastases. Therefore, a subset of pancreatic cancer patients could be eligible for active, specific immunotherapy directed against MAGE-A antigens and demethylating agents could increase the number of candidate patients.

Functional inactivation of the Rb and p53 pathways appears to be a rite of passage for all cancerous cells. However, p53 and Rb alterations are rare events in neuroendocrine gastroenteropancreatic (GEP) tumors. The CDKN2 locus on chromosome 9p21 sits at the nexus of both pathways harboring tumor suppressor genes, which restrain cell growth by affecting the function of pRb and p53. Therefore, we analyzed the implication of their inactivation in 37 primary neuroendocrine GEP tumors and two cell culture models. RT-PCR analysis revealed loss of expression of at least one of the tumor suppressor genes CDKN2A/p16, CDKN2B/p15, and CDKN2D/p14 with distinct genetic profiles, most frequently in nonfunctional pancreatic tumors (57%) and small intestinal carcinoids (44%), and less commonly in insulinomas (30%) and gastrinomas (22%). DNA analysis and methylation-specific PCR attributed loss of expression to either homozygous deletion or 5'CpG island hypermethylation. 5-Aza-2-deoxycytidine treatment reversed CDKN2A/p16 and CDKN2B/p15 silencing with concurrent growth restraint. Thus, tumor suppressor genes localized in the 9p21 gene cluster are specific targets of inactivation in neuroendocrine GEP tumors, and demethylating agents might hold promise for selective therapy.