Alexandra von Herbay

Real-time imaging with the sonographic contrast agent SonoVue: Differentiation between benign and malignant hepatic lesions

Objective. We investigated the ability of contrast‐enhanced sonography with SonoVue (Altana Pharma, Konstanz, Germany), a sulfur hexafluoride microbubble contrast agent, to reveal differences between benign and malignant focal hepatic lesions. Methods. One hundred twenty‐six lesions in 124 patients with focal hepatic lesions detected by B‐mode sonography (hepatocellular carcinoma, n = 36; metastasis, n = 25; cholangiocellular carcinoma, n = 1; lymphoma, n = 2; focal nodular hyperplasia, n = 9; adenoma, n = 4; regenerative cirrhotic nodule, n = 13; hemangioma, n = 29; and focal hyposteatosis, n = 7) were examined in a prospective study. After intravenous injection of 2.4 mL of SonoVue, the liver was examined continuously for 3 minutes by low–mechanical index pulse inversion sonography. Results. For the discrimination of malignant versus benign liver lesions, SonoVue‐enhanced sonography improved sensitivity from 78% to 100% and specificity from 23% to 92% compared with baseline sonography. Receiver operating characteristic analysis revealed a significant improvement in this discrimination (area under the receiver operating characteristic curve, 0.510 ± 0.054 [SD] at baseline sonography, 0.998 ± 0.003 with SonoVue‐enhanced sonography; P < .001). The following flow patterns in the early phase were diagnosis specific: early central starlike pattern for focal nodular hyperplasia, peripheral globular‐nodular pattern for hemangioma, and diffuse arterial enhancement for malignant lesions. Homogeneous enhancement in the late phase was predictive for benign lesions (P < .001). Conversely, 93% of patients without contrast enhancement in the late phase had malignant lesions (P < .001). Conclusions. SonoVue‐enhanced sonography has greater specificity and sensitivity than baseline sonography for the differentiation of benign and malignant liver lesions.

Low vitamin E content in plasma of patients with alcoholic liver disease, hemochromatosis and wilson's disease

The RRR-alpha-tocopherol (vitamin E) content in plasma from 46 patients with liver diseases and 23 healthy controls was determined by high performance liquid chromatography and electrochemical detection. Patients were divided into three groups: alcoholic liver diseases (n = 17; group A), hemochromatosis (n = 17; group B) and Wilsons disease (n = 12; group C). Lipid-standardized alpha-tocopherol levels were determined to neutralize differences due to hyperlipemia. The ratio of serum vitamin E to serum lipids (cholesterol, triglycerides, phospholipids) was highest in healthy controls and in patients in group A with cirrhosis and normal transaminases and bilirubin. Patients in group A with acute or chronic ethanol intoxication and high bilirubin levels had a 37% lower lipid-standardized vitamin E level than controls. Patients in group B with hemochromatosis, showing high serum iron (> 180 micrograms/dl), a low free iron binding capacity (< 8 mumol/l) and high ferritin-levels (< 450 micrograms/l), had a 34% lower vitamin E/lipid ratio than healthy controls. No significant lowering of the vitamin E/lipid ratio was observed in the other patients in group B. A significant decrease (37%) in the vitamin E/lipid ratio was only detectable in patients with Wilsons disease (group C) showing high free serum copper (> 10 micrograms/dl). The data support a role for free radicals in the pathogenesis of active liver diseases.

Association between duplex Doppler sonographic flow pattern in right hepatic vein and various liver diseases

The aim of this study was to evaluate the association between the Doppler sonographic waveforms in the right hepatic vein and various liver diseases.

Pulse inversion sonography in the early phase of the sonographic contrast agent Levovist: differentiation between benign and malignant focal liver lesions.

Objective. To determine whether examination of focal liver lesions by pulse inversion sonography in the early perfusion phase of the contrast agent Levovist (SH U 508A; Schering AG, Berlin, Germany) enables distinction between benign and malignant lesions. Methods. Seventy‐two patients were examined. The cause of the lesion was confirmed by liver biopsy, computed tomography, or both or by hepatic iminodiacetic acid–enhanced scintigraphy. Forty‐two patients had malignant liver lesions, and 30 had benign liver lesions. After injection of 2 g of Levovist intravenously, analysis of Levovist arrival was performed by the interval delay imaging technique for 60 seconds. Results. The early arrival of Levovist less than 30 seconds after injection was used as an indicator for malignancy and had specificity of 67% and sensitivity of 60% (P < .05). The central starlike fill‐in as a sign for focal nodular hyperplasia had specificity of 100% and sensitivity of 67% (P < .001). The rimlike pattern followed by centripetal fill‐in as a sign for hemangioma had specificity of 100% and sensitivity of 18% (P < .01). In contrast, the early diffuse stippled arrival pattern was found in 60% of malignant lesions and also in 33% of cases of focal nodular hyperplasia and in 1 patient with an adenoma. Conclusions. Analysis of Levovist arrival time cannot distinguish between a malignant or benign lesion in individual cases. However, the central starlike arrival pattern is characteristic of focal nodular hyperplasia.

Diminished Plasma Levels of Vitamin E in Patients with Severe Viral Hepatitis

RRR-alpha-Tocopherol (Vitamin E) was assayed in plasma of 48 patients with viral hepatitis and of 32 healthy controls. In patients with highly elevated serum transaminases (ALT > 100 U/L) vitamin E plasma levels were significantly lower (17.5 +/- 4.8 mumol/L) than in controls (22.7 +/- 4.2 mumol/L, p < 0.01). The vitamin E/lipid ratios (3.12 +/- 0.63 mumol/g) in these patients were 33% lower than those of the controls (4.68 +/- 0.54 mumol/g). The lowered vitamin E levels in patients with acute or chronic viral hepatitis with high activity of disease may be due to free radical-mediated liver injury.

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.

Differentiation Between Benign and Malignant Hepatic Lesions Utility of Color Stimulated Acoustic Emission With the Microbubble Contrast Agent Levovist

Objective. This study was undertaken to determine whether the examination of color stimulated acoustic emission in the late phase of Levovist (SH U 508A; Schering AG, Berlin, Germany) enhancement is helpful in the discrimination between benign and malignant liver lesions. Methods. Fifty‐six patients with focal hepatic lesions were examined. Diagnosis of the lesions was confirmed by liver biopsy, computed tomography, or scintigraphy. Thirty‐one patients had malignant liver lesions: hepatocellular carcinoma (n = 14), cholangiocellular carcinoma (n = 1), metastasis (n = 14), and lymphoma (n = 2). Twenty‐five patients had benign lesions: focal nodular hyperplasia (n = 8), hepatic adenoma (n = 1), focal hyposteatosis or hypersteatosis (n = 6), hemangioma (n = 7), and regenerative cirrhotic nodules (n = 3). After a delay of 5 to 10 minutes without scanning, the liver was examined by color stimulated acoustic emission with a fast sweep of 1 to 3 seconds. Results. All patients with homogeneous color stimulated acoustic emission in the late phase of Levovist enhancement had benign liver lesions (P < .001; specificity, 100%; sensitivity, 68%; positive predictive value, 100%; and negative predictive value, 79%). Eighty‐one percent of the patients with nonenhancing lesions in the late phase surrounded by enhanced liver parenchyma had malignant liver lesions (P < .001; specificity, 72%; sensitivity, 94%; positive predictive value, 81%; and negative predictive value, 90%). Interobserver agreement (weighted κ value) improved from 0.570 ± 0.038 for baseline sonography to 0.918 ± 0.028 for color stimulated acoustic emission sonography. The area under the receiver operating characteristic curves for color stimulated acoustic emission sonography (0.927) was significantly higher than for baseline sonography (0.739; P < .05). Conclusions. Color stimulated acoustic emission in the late phase of Levovist enhancement has a high specificity and sensitivity for differentiation between benign and malignant focal liver lesions.

Color doppler sonography avoids misinterpretation of the "parallel channel sign" in the sonographic diagnosis of cholestasis.

The intrahepatic “parallel channel sign” on gray‐scale sonograms is generally interpreted as representing dilated bile ducts, but it may also be caused by enlargement of intrahepatic arteries. This study was performed to evaluate the incidence of misinterpretation of the parallel channel sign without color Doppler sonography and the characteristics of patients in whom misinterpretation of the parallel channel sign is likely to occur.

Kontrastmittelsonographie der Leber als wegweisende Untersuchung für die Therapieplanung des hepatozellulären Karzinoms

Zusammenfassung.Vorgestellt wird der Fall einer 65-jährigen Patientin mit chronischer Hepatitis C, bei der in der B-Bild-Sonographie eine solitäre Raumforderung < 3 cm im rechten Leberlappen diagnostiziert wurde, welche sich in der histopathologischen Untersuchung des Biopsats als gering differenziertes hepatozelluläres Karzinom (HCC; G3) darstellte. Bei der im Rahmen des Tumorstagings durchgeführten Computertomographie (CT) und der Resovist-Magnetresonanztomographie (MRT) ergab sich in Übereinstimmung mit der B-Bild-Sonographie ein solitärer HCC-Knoten ohne Anhalt für weitere fokale Leberläsionen. Ergänzend erfolgte eine Untersuchung mit dem Ultraschallkontrastmittel Levovist® unter Einsatz der Phaseninversionssonographie in der Spätphase. Aufgrund dieser Kontrastmittelsonographie ließen sich zusätzlich multiple Tumorareale im rechten Leberlappen nachweisen, welche weder im CT noch im Resovist-MRT darstellbar waren. Dieser Kontrastmittelbefund des multifokalen HCC war von therapieentscheidender Bedeutung, da dadurch rechtzeitig erkannt werden konnte, dass aufgrund des multifokalen Befunds eine Lebertransplantation kontraindiziert war. Im Gegensatz dazu wäre die Lebertransplantation bei einem solitären HCC < 3 cm die Therapie der Wahl gewesen. Stattdessen erfolgte eine Hemihepatektomie rechts. Bei der histopathologischen Untersuchung des Leberresektats bestätigte sich der Kontrastmittelbefund des multifokalen HCC.Abstract.In a 65-year-old female patient, B-mode sonography detected a single focal lesion in the right liver lobe with a diameter < 3 cm. Histopathologic examination revealed a low differentiated hepatocellular carcinoma (HCC; G3). Tumor staging was performed by CT (computed tomography) scan and Resovist MRI (magnetic resonance imaging). Both examinations found a single liver lesion without signs of additional focal hepatic lesions. In addition, phase-inversion sonography in the late phase was performed using the ultrasound contrast agent Levovist. This examination of late-phase Levovist uptake detected more than five additional focal hepatic lesions in the right liver lobe, which were invisible by CT scan and Resovist MRI. This finding of multiloculated HCC was very important to decide on the patient’s correct therapy. While liver transplantation is the treatment of choice in single HCC < 3 cm, it is contraindicated in multicentric HCC. In the patient described here, hemihepatectomy of the right liver lobe was performed. The histopathologic examination of the resected liver confirmed the diagnosis of multicentric HCC, which was noninvasively diagnosed only by contrast-enhanced sonography, but not by CT scan or MRI.

Kontrastmittelsonographie der Leber als wegweisende Untersuchung für die Therapieplanung des hepatozellulären Karzinoms*@@@Contrast-Enhanced Sonography Using Levovist is Decisive for Staging and Therapeutic Schedule in Hepatocellular Carcinoma

Zusammenfassung.Vorgestellt wird der Fall einer 65-jährigen Patientin mit chronischer Hepatitis C, bei der in der B-Bild-Sonographie eine solitäre Raumforderung < 3 cm im rechten Leberlappen diagnostiziert wurde, welche sich in der histopathologischen Untersuchung des Biopsats als gering differenziertes hepatozelluläres Karzinom (HCC; G3) darstellte. Bei der im Rahmen des Tumorstagings durchgeführten Computertomographie (CT) und der Resovist-Magnetresonanztomographie (MRT) ergab sich in Übereinstimmung mit der B-Bild-Sonographie ein solitärer HCC-Knoten ohne Anhalt für weitere fokale Leberläsionen. Ergänzend erfolgte eine Untersuchung mit dem Ultraschallkontrastmittel Levovist® unter Einsatz der Phaseninversionssonographie in der Spätphase. Aufgrund dieser Kontrastmittelsonographie ließen sich zusätzlich multiple Tumorareale im rechten Leberlappen nachweisen, welche weder im CT noch im Resovist-MRT darstellbar waren. Dieser Kontrastmittelbefund des multifokalen HCC war von therapieentscheidender Bedeutung, da dadurch rechtzeitig erkannt werden konnte, dass aufgrund des multifokalen Befunds eine Lebertransplantation kontraindiziert war. Im Gegensatz dazu wäre die Lebertransplantation bei einem solitären HCC < 3 cm die Therapie der Wahl gewesen. Stattdessen erfolgte eine Hemihepatektomie rechts. Bei der histopathologischen Untersuchung des Leberresektats bestätigte sich der Kontrastmittelbefund des multifokalen HCC.Abstract.In a 65-year-old female patient, B-mode sonography detected a single focal lesion in the right liver lobe with a diameter < 3 cm. Histopathologic examination revealed a low differentiated hepatocellular carcinoma (HCC; G3). Tumor staging was performed by CT (computed tomography) scan and Resovist MRI (magnetic resonance imaging). Both examinations found a single liver lesion without signs of additional focal hepatic lesions. In addition, phase-inversion sonography in the late phase was performed using the ultrasound contrast agent Levovist. This examination of late-phase Levovist uptake detected more than five additional focal hepatic lesions in the right liver lobe, which were invisible by CT scan and Resovist MRI. This finding of multiloculated HCC was very important to decide on the patient’s correct therapy. While liver transplantation is the treatment of choice in single HCC < 3 cm, it is contraindicated in multicentric HCC. In the patient described here, hemihepatectomy of the right liver lobe was performed. The histopathologic examination of the resected liver confirmed the diagnosis of multicentric HCC, which was noninvasively diagnosed only by contrast-enhanced sonography, but not by CT scan or MRI.