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Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma†

This study prospectively evaluates the accuracy of contrast‐enhanced ultrasound (CEUS) and dynamic magnetic resonance imaging (MRI) for the diagnosis of nodules 20 mm or smaller detected during ultrasound (US) surveillance. We included 89 patients with cirrhosis [median age, 65 years; male 53, hepatitis C virus 68, Child‐Pugh A 80] without prior hepatocellular carcinoma (HCC) in whom US detected a small solitary nodule (mean diameter, 14 mm). Hepatic MRI, CEUS, and fine‐needle biopsy (gold standard) (FNB) were performed at baseline. Non‐HCC cases were followed (median 23 months) by CEUS/3 months and MRI/6 months. FNB was repeated up to 3 times and on detection of change in aspect/size. Intense arterial contrast uptake followed by washout in the delayed/venous phase was registered as conclusive for HCC. Final diagnoses were: HCC (n = 60), cholangiocarcinoma (n = 1), and benign lesions (regenerative/dysplastic nodule, hemangioma, focal nodular hyperplasia) (n = 28). Sex, cirrhosis cause, liver function, and alpha‐fetoprotein (AFP) levels were similar between HCC and non‐HCC groups. HCC patients were older and their nodules significantly larger (P < 0.0001). First biopsy was positive in 42 of 60 HCC patients. Sensitivity, specificity, and positive and negative predictive values of conclusive profile were 61.7%, 96.6%, 97.4%, and 54.9%, for MRI, 51.7%, 93.1%, 93.9%, and 50.9%, for CEUS. Values for coincidental conclusive findings in both techniques were 33.3%, 100%, 100%, and 42%. Thus, diagnosis of HCC 20 mm or smaller can be established without a positive biopsy if both CEUS and MRI are conclusive. However, sensitivity of these noninvasive criteria is 33% and, as occurs with biopsy, absence of a conclusive pattern does not rule out malignancy. These results validate the American Association for the Study of Liver Disease (AASLD) guidelines. (HEPATOLOGY 2007.)

PREVALENCE OF ANTIBODIES TO HEPATITIS C VIRUS IN SPANISH PATIENTS WITH HEPATOCELLULAR CARCINOMA AND HEPATIC CIRRHOSIS

The prevalence of antibodies against hepatitis C virus (HCV) was investigated in 96 patients with hepatocellular carcinoma, 106 patients with liver cirrhosis without evidence of cancer, and 177 controls without liver disease. 75% of patients with hepatocellular carcinoma had HCV antibodies (anti-HCV), a significantly higher proportion than that observed in patients with cirrhosis (55.6%), or controls (7.3%). The prevalence of anti-HCV was significantly higher in patients with alcoholic cirrhosis and hepatocellular carcinoma (76%) than in patients with alcoholic cirrhosis alone (38.7%) whereas in patients with cryptogenic cirrhosis there was no significant difference between those with and without primary liver cell cancer (81.4% and 77.5%, respectively). These results indicate that HCV infection may have a role in the pathogenesis of hepatocellular carcinoma, even in patients with chronic liver disease apparently related to other agents such as alcohol, and that this recently identified hepatitis virus may be found in a large proportion of patients with cryptogenic cirrhosis.

Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma

Outcome predictors in patients with hepatocellular carcinoma (HCC) who are treated with percutaneous ablation are ill defined, and it is unknown if successful therapy is associated with improved survival. In our study, 282 cirrhotic patients with early nonsurgical HCC were treated with percutaneous ablation during a 15‐year period. Single tumors were seen in 244 patients, and 2 to 3 nodules were seen in 38 patients. Initial complete response was achieved in 192 patients and was independently related to the size of the main tumor (P = .015) and tumor stage (P = .0001) (≤2 cm, 96%; 2.1‐3 cm, 78%; >3 cm, 56%; 2‐3 nodules, 46%). At the end of follow‐up, 80 patients presented sustained complete response. The 1‐, 3‐, and 5‐year survival rates were 87%, 51%, and 27%, respectively. The independent predictors of survival were Child‐Turcotte‐Pugh class (P = .0001) and initial complete response (P = .006). Child‐Turcotte‐Pugh class A patients with initial complete response achieved 42% survival at 5 years; this figure increased to 63% in patients with tumors 2 cm or smaller. In conclusion, our results demonstrate that initial complete response to percutaneous ablation is associated with an improved survival in both Child‐Turcotte‐Pugh class A and B patients with nonsurgical HCC. Accordingly, initial complete tumor necrosis should be considered a relevant therapeutic target irrespective of tumor size and liver function. (HEPATOLOGY 2004;40:1352–1360.)

High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: An indication for salvage liver transplantation

Surgical resection and liver transplantation offer a 5‐year survival greater than 70% in patients with hepatocellular carcinoma, but the high recurrence rate impairs long‐term outcome after resection. Pathological data such as vascular invasion and detection of additional nodules predict recurrence and divide patients into high and low risk profile. Based on this, we proposed salvage liver transplant to resected patients in whom pathology evidenced high recurrence risk even in the absence of proven residual disease. From January 1995 to August 2003 we have evaluated 1,638 patients. Resection was indicated in 77 patients, but only 17 (22%) (all cirrhotics, 14 hepatitis C virus+) were optimal candidates for both resection and transplantation. Of them, 8 exhibited a high risk profile at pathology and were offered transplantation. Among the 8 high risk patients, 7 presented recurrence, compared with only 2 of the 9 at low risk (P = .012). Two of the high risk patients refused transplant and developed multifocal disease during follow‐up. The other 6 were enlisted and all but 1 had tumor foci in the explant. Only 1 presented extrahepatic dissemination early after transplant and died 4 months later. The others are free of disease after a median follow‐up of 45 months. Two recurrences were detected in low risk patients, 1 of them being transplanted 18 months after surgery. These data in a small series of patients confirm that pathological parameters identify patients at higher risk of recurrence, which allow them to be listed for liver transplantation without proven malignant disease. In conclusion, this policy is clinically effective and could further improve the outcome of resected patients. (Liver Transpl 2004;10:1294–1300.)

Hepatocellular carcinoma and cirrhosis. Results of surgical treatment in a European series.

OBJECTIVE The authors analyze the outcomes of patients with hepatocellular carcinoma (HCC) and cirrhosis who underwent liver resections. BACKGROUND Liver resection is the best option for HCC arising from hepatic cirrhosis. The experience of Western centers with these patients is shorter than the Asian series. METHODS Forty-eight consecutive patients with cirrhosis and HCC who underwent liver resections were studied after a similar diagnostic and therapeutic process. Survival and cumulative recurrence were calculated according to pathologic findings. RESULTS Factors influencing survival at 3 years were as follows: type of resection, absence of vascular invasion, size of the tumor, absence of satellite nodules, and the number of nodules. Factors influencing the rate of recurrence at 3 years were the presence of vascular invasion and the presence of satellite nodules. Patients with favorable prognostic factors have a good survival rate with an acceptable recurrence rate. CONCLUSIONS Identification of prognostic factors may help in the selection of the appropriate treatment for these patients with HCC and cirrhosis.

Intrahepatic peripheral cholangiocarcinoma in cirrhosis patients may display a vascular pattern similar to hepatocellular carcinoma on contrast-enhanced ultrasound.

The aim of this study was to describe the imaging features by contrast‐enhanced ultrasound (CEUS) of intrahepatic cholangiocarcinoma (ICC) in cirrhosis patients. We registered the CEUS images of cirrhosis patients with histologically confirmed ICC. In all cases magnetic resonance imaging (MRI) was done to confirm the diagnosis and/or staging purposes. A total of 21 patients met all the criteria to be included in the study. The median nodule size was 32 mm. All nodules showed contrast enhancement at arterial phase; in 10 cases it was homogeneous and in 11 cases peripheral (rim‐like). All nodules displayed washout during the venous phases; it appeared during the first 60 seconds in 10 nodules, between 60‐120 seconds in five cases, and in six cases after 2 minutes. Ten nodules (five larger than 2 cm) displayed homogeneous contrast uptake followed by washout and they correspond to the specific pattern of hepatocellular carcinoma according to the American Association for the Study of Liver Diseases criteria. However, none of these lesions displayed washout on MRI. Conclusion: CEUS should not be used as the sole imaging technique for conclusive hepatocellular carcinoma diagnosis and if the MRI does not display the diagnostic vascular pattern, a confirmatory biopsy is mandatory. Hepatology 2010;51:2020–2029

Evaluation of hepatocellular carcinoma using SonoVue, a second generation ultrasound contrast agent: correlation with cellular differentiation

The appearance of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS) in the vascular phase is described and evaluated as to whether the enhancement pattern correlates with the degree of cellular differentiation. One hundred four HCCs were prospectively evaluated with CEUS using coherent-contrast imaging (CCI) and SonoVue with a low mechanical index (<0.2). The enhancement of HCCs in the vascular phase was analyzed according to the degree of pathological differentiation obtained by fine-needle biopsy. In the arterial phase, all HCCs except for four well differentiated ones (96.2%) showed enhancement (P<0.05). Histological differentiation of hypoechoic lesions in the early portal phase (7 HCCs; 16%) significantly differed from hyperechoic (1 HCC; 1%) or isoechoic lesions (87 HCCs; 83.6%) (P<0.05), with a significant probability of a worse differentiation in hypoechoic lesions. Histological differentiation of isoechoic lesions in the late phase (30 HCCs; 28.8%) significantly differed from hypoechoic lesions (74 HCCs; 71.2%) (P<0.05), with a significant probability of a better differentiation in isoechoic lesions. CEUS using CCI and SonoVue revealed enhancement in the arterial phase in >95% of HCCs, with a few well-differentiated cases not being diagnosed due to the absence of enhancement. Echogenicity in the portal and late phases correlated with cellular differentiation.

Treatment of hepatocellular carcinoma with tamoxifen: A double-blind placebo-controlled trial in 120 patients

BACKGROUND & AIMS The progression of hepatocellular carcinoma may be influenced by estrogens. This has offered the rationale for evaluating the therapeutic usefulness of estrogen-receptor blockers; it is being debated whether long-term tamoxifen administration improves survival in patients with this neoplasm. The aim of this study was to assess the efficacy of tamoxifen administration in the treatment of hepatocellular carcinoma. METHODS One hundred twenty patients with this neoplasm who were not suitable for surgery, ethanol injection, or transarterial embolization were included in a placebo-controlled trial and randomized to tamoxifen, 20 mg/day per os, (group A, n = 58) or placebo (group B, n = 62). Patients with terminal diseases were excluded. RESULTS Both groups were similar with regard to sex, age, liver function (Child-Pughs score, 6.5 +/- 1.4 vs. 6.4 +/- 1.4), baseline performance status, and tumor stage. Tamoxifen had no antitumoral effect with no differences in the survival between groups (1- and 2-year actuarial rate: group A, 51% and 27%; and group B, 43% and 29%; P = 0.75), even when stratifying patients according to baseline status. Furthermore, there were no differences in the probability of disease progression (P = 0.46) and baseline performance status maintenance (P = 0.93) during follow-up. CONCLUSIONS Tamoxifen has no efficacy in the treatment of patients with advanced hepatocellular carcinoma.

Importance of Evaluating All Vascular Phases on Contrast-Enhanced Sonography in the Differentiation of Benign from Malignant Focal Liver Lesions

OBJECTIVE Our objective was to evaluate the accuracy of a blood-pool sonographic contrast agent in the late phase compared with the three vascular phases for differentiation between benign and malignant focal liver lesions. SUBJECTS AND METHODS In 152 patients (105 with chronic liver disease), 152 solid focal liver lesions characterized either by fine-needle biopsy or by dynamic CT or MRI were studied. The final diagnoses were metastasis for 24, hepatocellular carcinoma for 75, focal nodular hyperplasia for 13, regenerating or dysplastic nodule for 14, hemangioma for 22, cholangiocarcinoma for two, and another focal liver lesion for two. Real-time sonography was performed after a bolus injection of 2.4 mL of SonoVue, using a low mechanical index (< 0.2). All lesions were evaluated in the arterial, portal, and late phases; classified as benign or malignant; and correlated with final diagnoses. RESULTS For discrimination between malignant and benign focal liver lesions, evaluation of all vascular phases improved the sensitivity from 78.4% to 98% and the accuracy from 80.9% to 92.7%, compared with evaluation of the late phase alone. The increase in accuracy was higher in patients with chronic liver disease (16.3%) than in those without (2.1%). CONCLUSION Evaluation of SonoVue enhancement in all three vascular phases is superior to evaluation of SonoVue enhancement in the late phase alone, especially in patients with chronic liver disease.

Natural history of hepatocellular carcinoma in Spain: Five year's experience in 249 cases

In this study we attempted to define the clinical pattern and prognosis of hepatocellular carcinoma (HCC) patients in Spain. Two hundred and forty-nine patients were included in the study. One hundred and eighty-seven were male and 62 female, with their mean age being 62.5 +/- 0.6 years. The majority of patients (92.8%) had an underlying cirrhosis. In most of the patients, the disease appeared as decompensated liver disease. Only 18.5% of the HCC cases were asymptomatic. Only 8.2% of the cases were HBsAg positive. alpha-Fetoprotein reached diagnostic values in only 37.2% of the patients. Surgical treatment was successfully performed in 14 patients: one underwent orthotopic liver transplantation and the 13 others complete tumor resection. Chemotherapy was administered to 38 subjects, while percutaneous ethanol injection was applied in seven cases. Patients receiving only symptomatic treatment, comprised 76.7%. Survival was related to tumor size and liver function. While the median survival of the whole series was 3.3 +/- 0.4 months, it was 14.5 +/- 2.2 months in patients with preserved liver function and small tumors. These results reflect that in Spain HCC patients are diagnosed at a moderately advanced phase. Since early diagnosis is the only way to increase the proportion of patients suitable for curative treatment, early detection plans are mandatory in the population at risk.