Contrast enhanced ultrasound of splenic lymphoma involvement.

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.

Identification of methylation-associated gene expression in neuroendocrine pancreatic tumor cells.

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 semiquantitative 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 metastatic 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.

Transcutaneous contrast-enhanced sonography of peripheral lung lesions.

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.

Contrast-enhanced sonography for differential diagnosis of an inhomogeneous spleen of unknown cause in patients with pain in the left upper quadrant.

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.

Second-generation sonographic contrast agent for differential diagnosis of perisplenic lesions.

OBJECTIVE: On contrast-enhanced sonography, second-generation contrast media have shown a spleen-specific uptake of the microbubble contrast agent. To date, there is little data about the diagnostic value of contrast-enhanced sonography in perisplenic lesions. CONCLUSION: In patients with a perisplenic tumor of unknown cause, contrast-enhanced sonography enables the diagnosis or exclusion of accessory spleens.

Contrast-enhanced sonography of the lung for differential diagnosis of atelectasis.

OBJECTIVE: Because of the absence of air in atelectatic tissue, sonography allows visualization of lung atelectasis and may characterize pulmonary and bronchial arterial vascularity by contrast-enhanced sonography (CES). METHODS: Thirty consecutive patients with obstructive atelectasis (OA) (n = 17) and compression atelectasis (n = 13) were retrospectively studied by CES using a second-generation sulfur hexafluoride contrast agent (SonoVue [BR1]; Bracco SpA, Milan, Italy). The following CES parameters were evaluated: (1) time to enhancement (TE) of the contrast agent after intravenous application was determined and classified as short TE and delayed TE (short TE, < or =6 seconds; versus delayed TE, >7 seconds); and (2) extent of enhancement (EE) was evaluated during the arterial phase (2-30 seconds) and the parenchymal phase (1-5 minutes): the EE of pleural lesions was determined in comparison with splenic enhancement and classified in reduced EE versus marked EE. RESULTS: All 13 patients with compression atelectasis had a short TE and a marked EE during arterial and parenchymal phases. In the remaining 17 patients with OA, 10 patients had a short TE and 7 patients had a delayed TE. The EE during both phases was reduced in 5 patients and marked in 3. Nine of 17 patients with OA had different EE during arterial and parenchymal phases. CONCLUSIONS: Compression atelectasis is characterized by CES with a short TE and a marked EE, indicating patent pulmonary arterial vascularization. In patients with OA, a variable CES pattern is found. With regard to only the TE, a delayed TE implies OA. This indicates a shifting of pulmonary vascularization to bronchial arterial vascularization in these patients.

Contrast-enhanced sonography for differential diagnosis of pleurisy and focal pleural lesions of unknown cause.

BACKGROUND: Ultrasound enables the visualization of pleural-based lesions with a poor correlation to specific pathology. At this time, there are no data about the diagnostic value of contrast-enhanced sonography (CES) in pleural lesions. METHODS: From August 2004 to January 2005, 25 consecutive patients with clinical symptoms of pleurisy and focal pleural lesions of unknown origin seen on B-mode ultrasonography were prospectively studied by CES. The lesions were diagnosed as pleuropneumonia (n = 12), pulmonary embolism/infarction (n = 7), malignant lymphoma (n = 2), pleural metastasis (n = 2), granuloma (n = 1), and unknown cause (n = 1). The diagnosis of the lesions was confirmed by contrast-enhanced CT scanning (n = 20), scintigraphy (n = 3), and follow-up (n = 2). Time to the enhancement of the contrast agent was determined. The CES patterns were evaluated during the arterial phase (ie, 2 to 30 s) and the parenchymal phase (ie, 1 to 5 min). The extent of the enhancement of pleural lesions was classified using normal liver tissue as an in vivo reference (absent, hypoechoic, isoechoic, hyperrechoic, or mixed echogenicity). RESULTS: In 20 patients, an enhancement of the pleural lesion was seen. All 12 patients with pleuropneumonia had a short time to enhancement (between 1 and 6 s), and a marked enhancement (isoechoic/hyperechoic) during the arterial and parenchymal phase. In the remaining 13 patients with other diagnoses than pleuropneumonia, 5 patients had no enhancement and 8 patients had a delayed time to enhancement (> 6 s). The extent of the enhancement was reduced (hypoechoic/anechoic) in 12 of 13 patients during the arterial and parenchymal phases. CONCLUSION: In patients with pleurisy and pleural lesions of unknown cause that were found sonographically, CES enables the diagnosis or exclusion of pleuropneumonia.

Pictorial review: sonographic patterns of diffuse and focal fatty infiltration of the liver: differential diagnosis to metastatic liver disease.

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.

Expression spectrum and methylation-dependent regulation of melanoma antigen-encoding gene family members in pancreatic cancer cells.

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'-deoxycytidine 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.