A. P. Barreiros

Contrast-Enhanced Ultrasonography With SonoVue Differentiation Between Benign and Malignant Lesions of the Spleen

Objective. We investigated the ability of contrast‐enhanced ultrasonography with SonoVue (Bracco SpA, Milan, Italy), a sulfur hexafluoride microbubble contrast agent, to reveal differences between benign and malignant focal splenic lesions. Methods. In a prospective study we investigated 35 lesions in 35 patients (24 male and 11 female; mean age ± SD, 54 ± 15 years) with focal splenic lesions detected by B‐mode ultrasonography. After intravenous injection of 1.2 to 2.4 mL of SonoVue, the spleen was examined continuously for 3 minutes using low–mechanical index ultrasonography with contrast‐specific software. The final diagnosis was established by histologic examination, computed tomography, or magnetic resonance imaging. Results. In 14 patients, the splenic lesions were malignant (metastasis, n = 6; non‐Hodgkin lymphoma, n = 6; and Hodgkin lymphoma, n = 2). In 21 patients, the focal splenic lesions were benign (ischemic lesion, n = 6; echogenic cyst, n = 5; abscess, n = 4; hemangioma, n = 3; hematoma, n = 1; hemophagocytosis syndrome, n = 1; and splenoma, n = 1. Typical findings for benign lesions were 2 arrival patterns: no contrast enhancement (neither in the early nor in the parenchymal phase; P < .05) and the beginning of contrast enhancement in the early phase followed by contrast enhancement in the parenchymal phase 60 seconds after injection. In contrast, the combination of contrast enhancement in the early phase followed by rapid wash‐out and demarcation of the lesion without contrast enhancement in the parenchymal phase (60 seconds after injection) was typical for malignant lesions (P < .001). Conclusions. Contrast‐enhanced ultrasonography is helpful in the differentiation between benign and malignant lesions of the spleen.

Contrast-enhanced ultrasound for imaging of adrenal masses.

PURPOSE The number of incidentally discovered adrenal masses is growing due to the increased use of modern high-resolution imaging techniques. However, the characterization and differentiation of benign and malignant adrenal lesions is challenging. This study aimed to evaluate contrast-enhanced ultrasound for the characterization of adrenal masses. MATERIALS AND METHODS We studied 58 patients with adrenal masses detected with computed tomography, magnetic resonance imaging, or ultrasound. 7 patients had bilateral adrenal lesions. Contrast-enhanced ultrasound was performed using high-resolution ultrasound (3.5 - 7 MHz) and intravenous injection of 2.4 ml SonoVue. The contrast enhancement pattern of all adrenal lesions was documented. RESULTS The 18 malignant adrenal tumors were significantly larger at the time of diagnosis compared to the 40 benign lesions (p < 0.03). The majority of benign adrenal lesions (37 / 40) had a nonspecific type of contrast enhancement (24 / 40) or a peripheral to central contrast filling (13 / 40) described as the iris phenomenon. Similar findings were observed in malignant adrenal tumors: most malignant lesions also showed nonspecific (6 / 18) or peripheral to central contrast filling (9 / 18). Peripheral to central contrast filling had 50 % sensitivity (26 - 74 %) and 68 % specificity (51 - 81 %) for indicating malignancy. CONCLUSION Contrast-enhanced ultrasound facilitates the visualization of vascularization even in small adrenal masses, but it does not help to distinguish malignant and benign lesions.

A systems biology perspective on cholangiocellular carcinoma development: Focus on MAPK-signaling and the extracellular environment

BACKGROUND/AIMS Multiple genes have been implicated in cholangiocellular carcinoma (CCC) development. However, the overall neoplastic risk is likely associated with a much lower number of critical physiological pathways. METHODS To investigate this hypothesis, we extracted all published genetic associations for the development of CCC from PubMed (genetic association studies, but also studies associating genes and CCC in general, i.e. functional studies in cell lines, genetic studies in humans, knockout mice etc.) and integrated CCC microarray data. RESULTS We demonstrated the MAPK pathway was consistently enriched in CCC. Comparing our data to genetic associations in HCC often successfully treated by a multityrosine kinase inhibitor, sorafenib, we demonstrated a similar overrepresentation of MAPK. In contrast, most cancer-related genetic studies focusing on genes related to transcription and cell cycle control, we consistently found genes coding for products in the extracellular environment to be significantly enriched. Thus, CCC must be regarded as developing in the context of an altered extracellular environment. CONCLUSIONS Our study suggests the liver microenvironment holds essential functions and structures key to CCC progression. Furthermore, we identified the MAPK signaling pathway consistently enriched, pointing towards a critical role in CCC development. These data may provide a rationale for treatment of CCC with sorafenib.

Nitric Oxide Promotes Resistance to Tumor Suppression by CTLs

Many human tumors express inducible NO synthetase (NOS2), but the roles of NO in tumor development are not fully elucidated. An important step during tumor development is the acquisition of apoptosis resistance. We investigated the dose-dependent effects of endogenously produced NO on apoptosis using ecdysone-inducible NOS2 cell lines. Our results show that short-term NOS2 expression enhances CD95-mediated apoptosis and T cell cytotoxicity dose dependently. Furthermore, we could show that during chronic exposure to NO, besides the primary cytotoxic NO effect, there is selection of cell clones resistant to NO that show cross-resistance to CD95-induced apoptosis and the killing by CTLs. We propose that NO production could initially act as an autocrine suicide or paracrine killing mechanism in cells undergoing malignant transformation. However, once failed, the outcome is fatal. NO promotes tumor formation by enhancing the selection of cells that can evade immune attack by acquiring apoptosis resistance.

Neues zur Sonographie in der Gastroenterologie (Teil 2)

ZusammenfassungIm vorliegenden zweiten Teil wird die endoskopische Kontrastmittelsonographie diskutiert, die eine Anwendung in Bereichen ermöglicht, die dem herkömmlichen transabdominellen Ultraschall nicht zugänglich sind. Des Weiteren wird die Anwendung von Ultraschallkontrastmitteln in extravaskulärer oder kavitärer Form präsentiert. Das Manuskript endet mit der Darstellung von elastographischen Verfahren, die als perkutane, aber auch endoskopische Verfahren verfügbar sind.AbstractIn the presented second part of the manuscript contrast-enhanced endoscopic ultrasound is discussed which allows the application of contrast-enhanced ultrasound in areas which are not accessible by transabdominal ultrasound. Furthermore, the extravascular application of contrast agents will be presented. The manuscript ends with a focus on the description of elastography techniques which can be used percutaneously but are also available in endoscopic procedures.