Valentina Ravetta

Contrast-Enhanced Versus Conventional and Color Doppler Sonography for the Detection of Thrombosis of the Portal and Hepatic Venous Systems

OBJECTIVE We conducted a prospective study to compare sonography, color Doppler sonography, and contrast-enhanced sonography for the detection and characterization of portal and hepatic vein thrombosis complicating hepatic malignancies. SUBJECTS AND METHODS Three hundred sixteen patients with biopsy-proved hepatic tumors were studied at baseline and 3 months later with sonography, color Doppler sonography, and contrast-enhanced sonography. Thrombosis was defined as the presence of intraluminal echogenic material at sonography, absence of intraluminal color signals at color Doppler sonography, and presence of nonenhancing intraluminal area at contrast-enhanced sonography. Thrombi were considered malignant if they displayed continuity with tumor tissue at sonography, intrathrombus color signals at color Doppler sonography, and enhancing signals at contrast-enhanced sonography, both having arterial waveforms at Doppler spectral examination. Definitive diagnoses were obtained by sonographically guided biopsy except for thrombi displaying at conventional sonography unequivocal continuity with tumor tissue. RESULTS Thrombosis was detected in 79 (25.0%) of 316 patients at baseline and in 83 (26.3%) of 316 patients after 3 months. Eighty-one (97.6%) of the 83 thrombi were malignant. Definitive diagnosis was performed by imaging in 60 (72.3%) of the 83 cases and by biopsy in 23 cases (27.7%). For thrombus detection, contrast-enhanced sonography displayed significantly higher sensitivity than color Doppler sonography (p = 0.004) and borderline superiority over sonography (p = 0.058). For thrombus characterization, contrast-enhanced sonography was significantly more sensitive than color Doppler sonography (p < 0.0005) and conventional sonography (p = 0.02). CONCLUSION Contrast-enhanced sonography is superior to sonography and color Doppler sonography for the detection and characterization of portal and hepatic vein thrombosis complicating hepatic malignancies.

Repeated radiofrequency ablation for management of patients with cirrhosis with small hepatocellular carcinomas: A long‐term cohort study

In most patients with cirrhosis, successful percutaneous ablation or surgical resection of hepatocellular carcinoma (HCC) is followed by recurrence. Radiofrequency ablation (RFA) has proven effective for treating HCC nodules, but its repeatability in managing recurrences and the impact of this approach on survival has not been evaluated. To this end, we retrospectively analyzed a prospective series of 706 patients with cirrhosis (Child‐Pugh class ≤B7) who underwent RFA for 859 HCC ≤35 mm in diameter (1‐2 per patient). The results of RFA were classified as complete responses (CRs) or treatment failures. CRs were obtained in 849 nodules (98.8%) and 696 patients (98.5%). During follow‐up (median, 29 months), 465 (66.8%) of the 696 patients with CRs experienced a first recurrence at an incidence rate of 41 per 100 person‐years (local recurrence 6.2; nonlocal 35). Cumulative incidences of first recurrence at 3 and 5 years were 70.8% and 81.7%, respectively. RFA was repeated in 323 (69.4%) of the 465 patients with first recurrence, restoring disease‐free status in 318 (98.4%) cases. Subsequently, RFA was repeated in 147 (65.9%) of the 223 patients who developed a second recurrence after CR of the first, restoring disease‐free status in 145 (98.6%) cases. Overall, there were 877 episodes of recurrence (1‐8 per patient); 577 (65.8%) of these underwent RFA that achieved CRs in 557 (96.5%) cases. No procedure‐related deaths occurred in 1,921 RFA sessions. Estimated 3‐ and 5‐year overall and disease‐free (after repeated RFAs) survival rates were 67.0% and 40.1% and 68.0 and 38.0%, respectively. Conclusion: RFA is safe and effective for managing HCC in patients with cirrhosis, and its high repeatability makes it particularly valuable for controlling intrahepatic recurrences. (HEPATOLOGY 2011)

Low-density lipoprotein oxidation in essential hypertension.

Objectives: To investigate the occurrence of enhanced low-density lipoprotein (LDL) oxidation as an additional factor promoting atherosclerosis progression in hypertensive patients. Design: The oxidation of plasma LDL was investigated in a group of untreated patients with mild-to-moderate essential hypertension without clinically evident target organ damage and in a group of control subjects. Methods: LDL oxidation was evaluated as both the susceptibility to oxidation in vitro and the presence of plasma anti-oxidized LDL antibodies (as an index for oxidation in vivo). Results: LDL from hypertensive subjects exhibited enhanced susceptibility to oxidation in vitro as revealed by early and accelerated generation of conjugated dienes after exposure to CuSO4. Vitamin E concentration in LDL from hypertensive subjects was slightly but significantly decreased and its efficiency in protecting LDL from oxidation was impaired. Furthermore, a higher plasma anti-oxidized LDL titre was found in hypertensive patients. Subclass analysis revealed that the contemporary presence of hypercholesterolaemia did not significantly modify either the increased susceptibility of LDL to oxidation or the presence of plasma anti-oxidized LDL antibodies detected in hypertensive patients. Moreover, no correlation was found between LDL oxidation parameters and blood pressure values. Conclusions: LDL from hypertensive patients is more susceptible to oxidation in vitro and is more promptly oxidized in vivo. These findings suggest a possible participation of LDL oxidation in promoting and accelerating the atherosclerosis that often develops in hypertensive patients.

Presence of autoantibodies against oxidatively modified low-density lipoprotein in essential hypertension: a biochemical signature of an enhanced in vivo low-density lipoprotein oxidation.

Objective We have previously reported that low-density lipoproteins (LDL) isolated from patients with essential hypertension are more susceptible to in vitro oxidation than lipoproteins isolated from normotensive control subjects. In the present study we investigated the occurrence of in vivo LDL oxidation in hypertensive patients. Design The presence of antioxidatively modified LDL autoantibodies was taken as a suitable index of in vivo LDL oxidation because, after oxidative modifications, LDL express antigenic epitopes that elicit an immune response. The antibody titres were measured in plasma from untreated patients with newly diagnosed essential hypertension. Methods An enzyme-linked immunosorbent assay method was employed, using native LDL, Cu2+-oxidized LDL and malondialdehyde-derivatized LDL (MDA-LDL) as antigens. Human serum albumin and MDA human serum albumin were also used to monitor cross-reactivity with other oxidized molecules. The antibody titre was expressed as the ratio between anti-modified and anti-native antigen absolule values. Results The patients with essential hypertension had an antibody ratio significantly higher than control subjects with respect to anti-Cu2+-oxidized LDL immunoglobulins G and M, and with respect to anti-MDA-LDL immunoglobulins G and M. A significant positive correlation was found between anti-MDA-LDL and anti-Cu2+-oxidized LDL antibody titres. The anti-MDA human serum albumin antibody titre was not different in the two groups of palients. An inverse correlation was detected between the anti-MDA-LDL immunoglobulin M titre and the age of the patients. Conclusions The results obtained are consistent with the view that, during the early phases of hypertension development, LDL undergo in vivo oxidation that is mirrored by the generation of autoantibodies against epitopes of oxidized LDL. The oxidation process appears specific for LDL and might be relevant both for the progression of hypertension and for the development of the atherosclerosis that often complicates hypertension itself.

Contrast-enhanced ultrasonography and spiral computed tomography in the detection and characterization of portal vein thrombosis complicating hepatocellular carcinoma

The aim was to compare the performances of contrast-enhanced (CE) ultrasonography (US) and spiral computed tomography (CT) in the detection and characterization of portal vein thrombosis complicating hepatocellular carcinoma (HCC). We studied 50 patients with HCC who had biopsy-proven portal vein thrombi that had been detected with US and color Doppler US. Thirteen of the thrombi involved the main portal trunk and 37 the segmental branches. CEUS and CT were performed within a week of thrombus biopsies. For each imaging technique, diagnoses of thrombosis (present/absent) and thrombus nature (malignancy/benignancy) were made by experienced readers under blinded conditions and compared with pathological findings to determine accuracy rates for thrombus detection and characterization. Forty-four of the 50 thrombi were pathologically diagnosed as malignant and the remaining six were benign. CEUS detected 50/50 (100%) thrombi and correctly characterized 49/50 (98%). CT detected 34/50 (68%) thrombi and correctly characterized 23 of these 34 (68%). CEUS outperformed CT in terms of both thrombus detection (P < 0.0001) and characterization (P = 0.0001). CEUS appears to be significantly superior to CT for detection and characterization of portal vein thrombosis complicating HCC, and it should be considered in the staging of these tumors.

Abdominal spilled stones: ultrasound findings

Laparoscopic cholecystectomy (LC) is the treatment of choice for uncomplicated symptomatic gallstones. Spillage of stones due to gallbladder rupture has been reported in up to 33% of all LCs, but clinical sequelae caused by dropped gallstones are uncommon. We recently observed two patients with retained stones after LC. Correct diagnosis was made by abdominal ultrasonography (US) in both cases. In the first patient, who presented with fever, malaise, and weight loss 18 months after LC, abdominal US revealed hypoechoic focal lesions containing hyperechoic images with posterior shadowing of the liver and spleen. US-guided aspiration biopsies of these lesions yielded purulent material, and the injection and aspiration of saline solution provoked rolling movements of the hyperechoic images. Laparotomy confirmed the diagnosis of abscess-containing spilled gallstones. In the second patient, multiple hyperechoic images with posterior shadowing were observed in the Morison pouch during a routine US examination. The diagnosis of retained stones was consistent with the history of gallstone spillage during LC performed 2 months previously and was confirmed by computed tomographic findings of hyperdense images in the Morison pouch. The patient was asymptomatic, and treatment was thus deferred. Our experience suggests that US can be very useful in the detection of gallstones spilled during LC.

Plasminogen activator inhibitor-1 and carotid intima-media thickening in patients with newly detected primary hypertension.

Objective To investigate the correlation between ultrasonographically evaluated intima-media thickness (IMT) of common carotid artery (CCA) and cardiovascular risk factors for subjects with newly detected, uncomplicated and untreated primary hypertension. Methods The study population consisted of 200 subjects (123 men and 77 women, aged 46±7.5 years). Blood pressure was measured in the clinical setting and by 24 h noninvasive ambulatory monitoring. Fasting levels of blood glucose, plasma lipids and lipoproteins, fibrinogen and plasminogen activator inhibitor (PAI)-1 were measured. Ultrasound examination included measurement of far-wall intima-media complex of CCA and morphologic evaluation of occurrence of plaques in carotid and femoral bifurcations. Results The prevalence of greater than normal IMT (mean IMT ≥ 0.80 mm) was 22%. Significant univariate correlations to the dichotomy between normal and greater than normal mean IMT were detected for age, smoking, level of LDL cholesterol, level of PAI-1 and total ultrasonographic score. Multivariate logistic regression analysis confirmed the associations between greater than normal mean IMT and plasma concentrations of LDL cholesterol and PAI-1 as well as total ultrasonographic score. Conclusion Greater than normal IMT of CCA was more strictly related to other cardiovascular risk factors than it was to blood pressure and was strongly associated with the occurrence of atherosclerotic plaques in carotid and femoral arteries. The role of PAI-1 in intima-media thickening that is emerging suggests that fibrinolytic balance is an important determinant of vessel-wall homeostasis in hypertensive patients.

Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules

Background & Aims. The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned for the risk of false positive diagnosis in case of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS LI-RADS) classifying lesions at risk for HCC investigated by CEUS. Aim of the present study was to validate this LI-RADS scheme for the diagnosis of HCC. Methods. A total of 1006 nodules in 848 patients with chronic liver disease at risk for HCC collected in 5 Italian centers were retrospectively analyzed. Nodules were classified as LR-5, (HCC) if ≥ 1 cm with arterial phase hyperenhancement, and late washout (onset ≥60 seconds after contrast injection) of mild degree. Rim enhancement and/or early and/or marked washout qualified lesions as LR-M (malignant, but not specific for HCC). Other combinations qualified lesions at intermediate risk for HCC (LR-3) or probable HCC (LR-4). Diagnostic reference standard was CT/MRI diagnosis of HCC (=506) or histology (n=500). Results. Median size was 2 cm. Of 1006 nodules, HCC were 820 (81%), cholangiocarcinoma 40 (4%), regenerative nodules (±dysplastic) 116 (11%). The LR-5 category (52% of all nodules) was 98.5% predictive of HCC, with no risk of misdiagnosis for pure cholangiocarcinoma. Sensitivity for HCC was 62%. All LR-M nodules were malignant and the majority of non-hepatocellular origin. Over 75% of cholangiocarcinomas were LR-M. The LR-3 category included 203 lesions (HCC 96=47%) and the LR-4 202 (HCC 173=87%). Conclusions. The CEUS LI-RADS class LR-5 is highly specific for HCC, enabling its use for a confident non invasive diagnosis.BACKGROUND & AIMS The use of contrast enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC) in cirrhosis was questioned because of the risk of a false positive diagnosis in cases of cholangiocarcinoma. The American College of Radiology has recently released a scheme (CEUS Liver Imaging Reporting and Data System [LI-RADS®]) to classify lesions at risk of HCC investigated by CEUS. The aim of the present study was to validate this LI-RADS scheme for the diagnosis of HCC. METHODS A total of 1,006 nodules from 848 patients with chronic liver disease at risk of HCC were collected in five Italian centers and retrospectively analyzed. Nodules were classified as LR-5, (HCC) if ≥1 cm with arterial phase hyperenhancement, and late washout (onset ≥60 s after contrast injection) of mild degree. Rim enhancement and/or early and/or marked washout qualified lesions as LR-M (malignant, but not specific for HCC). Other combinations qualified lesions at intermediate risk for HCC (LR-3) or probable HCC (LR-4). Diagnostic reference standard was CT/MRI diagnosis of HCC (n = 506) or histology (n = 500). RESULTS The median nodule size was 2 cm. Of 1,006 nodules, 820 (81%) were HCC, 40 (4%) were cholangiocarcinoma, 116 (11%) regenerative nodules (±dysplastic). The LR-5 category (52% of all nodules) was 98.5% predictive of HCC, with no risk of misdiagnosis for pure cholangiocarcinoma. Sensitivity for HCC was 62%. All LR-M nodules were malignant and the majority of non-hepatocellular origin. Over 75% of cholangiocarcinomas were LR-M. The LR-3 category included 203 lesions (HCC 96 [47%]) and the LR-4 202 (HCC 173 [87%]). CONCLUSIONS The CEUS LI-RADS class LR-5 is highly specific for HCC, enabling its use for a confident non-invasive diagnosis. LAY SUMMARY This is a retrospective study of approximately 1,000 focal lesions at risk for hepatocellular carcinoma (HCC). Herein, we demonstrate that the refined definition of the typical contrast enhanced ultrasound pattern of HCC introduced by the Liver Imaging Reporting and Data System (LI-RADS®) practically abolishes the risk of misdiagnosis of other malignant entities (e.g. cholangiocarcinoma) for HCC with negligible reduction in sensitivity. These data support the use of contrast enhanced ultrasound to diagnose HCC in cirrhosis.

Structural changes in the heart and carotid arteries in hypertensive patients associated with cardiovascular risk factors

Objective To estimate the relationship between structural changes in the heart and in the carotid arteries in hypertensives and to analyze the correlations between these structural changes and cardiovascular risk factors. Methods We studied 76 subjects (39 men and 27 women, mean age 45 ± 7 years) with mild-to-moderate untreated and uncomplicated hypertension. All of the subjects underwent ambulatory blood pressure monitoring, M-mode echocardiography for evaluation of their left ventricular mass and B-mode high-resolution ultrasonography to determine their carotid arterial wall thickness. Results The mean intimal plus medial thickness of the common carotid artery was found to be related significantly and independently to the left ventricular mass indexed by the body surface area. In multivariate analysis, age and the high-density lipoprotein cholesterol level were related strongly to the intimal plus medial thickness, whereas the clinic systolic blood pressure, average night-time systolic blood pressure and glycemia were the most important determinants of the left ventricular mass index. Logistic regression analysis suggested that the thickness of the posterior left ventricular wall was a stronger predictor of the carotid intima-medial thickness than were age and the high-density lipoprotein cholesterol level. Conclusion The carotid wall thickness and left ventricular mass of hypertensives are related independently; nevertheless the main determinants of structural cardiac and vascular changes are probably different. The mean intima-media thickness of the common carotid artery in mild-to-moderate untreated and uncomplicated hypertensive patients was related significantly and independently to the left ventricular wall thicknesses. Age and the high-density lipoprotein cholesterol level were the most important determinants of the mean intima-media thickness, whereas the clinic systolic blood pressure, average night-time systolic blood pressure and glycemia were strongly related to the left ventricular mass index.

The Prognosis of Patients with Liver Metastases from Colorectal Cancer still Depends on Anatomical Presentation more than on Treatments.

BACKGROUND The best management of liver metastases from colorectal cancer is still debated and little is known about the true impact of treatments on survival. MATERIALS AND METHODS The study involved 122 patients (77 males), aged 64.0 ± 11.0 years (range: 27.8-86.1) at diagnosis of liver metastatization (synchronous in 59). All underwent chemotherapy and at least one procedure of radiofrequency ablation; 53 also had partial hepatic resections. Demographics, tumor characteristics and survival outcomes from liver metastatization were analyzed with univariate and multivariate techniques. This analysis was performed also taking into account relative survival as the best estimate of specific survival. RESULTS The analysis with observed survival selected the categorized number of involved lymph nodes in the colorectal specimens as the only statistically significant predictor, while the analysis with relative survival also showed site of the primary tumor (above the sigmoid colon or otherwise) and number of liver metastases as significant factors. The standardized mortality ratio was 9.673 (95% CI: 7.668-11.663) and a total of 201.85 years of life were lost in comparison with the survival of the reference population. CONCLUSIONS The computation of relative survival – better than observed survival – selected a more adequate number of predictors, making investigation of even limited series of patients with confounding factors reliable. The finding that prognosis was mainly dependent on the anatomical presentation of the primary tumor and of liver metastases – instead of treatments – could explain the still contrasting opinions on the role of the available therapies in this field.