Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma

AIM To evaluate whether pathologically early hepatocellular carcinoma(HCC) exhibited local tumor progression after radiofrequency ablation(RFA) less often than typical HCC.METHODS Fifty pathologically early HCCs [tumor diameter(mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter(mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion(namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrastenhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method.RESULTS During the follow-up period for the 50 pathologically early HCCs, 49(98%) of the nodules did not exhibit local tumor progression. However, 1 nodule(2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46(24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0%(7/187), 16.0%(30/187), 21.9%(41/187) and 24.6%(46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test(P = 0.002). CONCLUSION The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs.

Diagnostic efficacy of gadoxetic acid-enhanced MRI for hepatocellular carcinoma and dysplastic nodule

AIM:To evaluate the relationship between the signal intensity of hepatobiliary phase images on gadoxetic acid-enhanced magnetic resonance imaging(MRI)and histological grade.METHODS:Fifty-nine patients with 82 hepatocellular lesions were evaluated retrospectively.Hepatobiliary phase images on gadoxetic acid-enhanced MRI were classified into 3 groups:low,iso or high.Angiographyassisted computed tomography(CT)findings were also classified into 3 groups:CT during arterial portography,and CT hepatic arteriography:A:iso,iso or low;B:slightly low,iso or low;;and C:low,high.We correlated angiography-assisted CT,hepatobiliary phase findings during gadoxetic acid-enhanced MRI and histological grades.Furthermore,correlations between MRI findings and histological grade for each hemodynamic pattern were performed.Correlations among radiologicaland pathological findings were statistically evaluated using the chi-square test and Fisher's exact test.RESULTS:There was a significant correlation between histological grade and hemodynamic pattern(P<0.05).There was a significant correlation between histological grade and signal intensity in the hepatobiliary phase(P<0.05)in group A lesions.There was no significant correlation between histological grade and signal intensity in the hepatobiliary phase in group B or C lesions(P>0.05).CONCLUSION:Signal intensity in the hepatobiliary phase correlated with histological grade in the lesions that maintained portal blood flow,but did not correlate in lesions that showed decreased or defective portal blood flow.

Establishment of a real-time PCR for quantifying transforming growth factor beta1 in blood of hepatocellular carcinoma patients

Background: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor and early detection is of the utmost importance. Transforming growth factor β1 (TGF-β1) message RNA (mRNA) has been reported to be elevated in HCC patients using Northern blotting. However, little work has been done about the detection of TGF-β1 mRNA levels in peripheral blood of patients with HCC using the real-time polymerase chain reactions (PCR) method. Objective: To assess the prognostic value of quantitative levels of TGF-β1 mRNA in peripheral blood of patients with HCC, and to investigate the relationship between the expression of TGF-β1 mRNA in peripheral blood and many diagnostic and pathological factors. Methods: We developed an optimized Taqman real-time PCR to quantify TGF-β1 mRNA in peripheral blood of 53 patients with HCC and 44 healthy volunteers. In addition, blood was collected from patients with HCC for measuring levels of total bilirubin (TBil), prealbumin, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltranspeptidase (GGT), alpha-L-fucosidase (AFU), alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), viral load and platelet counts. Statistical analysis was performed using the SPSS software system (SPSS 10.0). Results: In real-time PCR, fluorescence was detectable in all blood specimens from patients with HCC and healthy volunteers. The levels of TGF-β1 mRNA expression in patients with HCC were significantly higher compared to that in healthy volunteers (P<0.000 1), suggesting an association of the activated TGF-β1 gene transcription with hepato- carcinogenesis. Patients with HCC were divided into 2 groups according to their TGF-β1 mRNA above (group A, n=28)or below (group B, n=25) the mean level. Statistical results demonstrated that TGF-β1 mRNA expression level was correlated with patients age, serum levels of CEA, CA19-9 and viral copy number (P<0.05). Conclusion: Although this is a small sample size pilot study these findings imply that quantitative measurement of TGF-β1 mRNA level in peripheral blood may be a complementary serologic marker of HCC.

Intraarterial and intravenous contrast enhanced CT and MR imaging of multi-step hepatocarcinogenesis defining the early stage of hepatocellular carcinoma development

Liver cancer is the second leading cause of cancer deaths in men worldwide,and the 6th and 7th cause of cancer deaths in men and women in developed countries.70%-90%of primary liver cancer is hepatocellular carcinoma.Hepatitis B or C viruses and chronic inflammation due to alcohol intake are the main risk factors for hepatocellular carcinoma.One of the key approaches for the early detection of hepatocellular carcinoma is to understand the specific imaging findings of liver nodules in the multi-step hepatocrcinogenesis process.In this article,we review the imaging findings of multistep hepatocarcinogenesis,with a focus on the early detection of malignant,cirrhotic nodules with CT and MRI.

Contrast-enhanced ultrasound with sulphur-hexafluoride in diagnosis of early HCC in cirrhosis

Contrast-enhanced ultrasound(CEUS)with pure blood stream contrast agents allow the study of blood supply of focal liver lesions and especially of hepatocellular carcinoma(HCC)in cirrhosis.Its sensitivity and specificity in diagnosis of small tumors is very high.This review summarizes the recent results on CEUS with SonoVue,which is one of the second generation contrast agents,in the diagnosis of early HCC in cirrhosis emphasizing its increasing role in routine clinical practice.

Liver carcinogenesis: diagnostic and clinical aspects of preneoplastic nodules

In multistep hepatocarcinogenesis,sizable lesions can precede the development of hepatocellular carcinoma(HCC).These lesions are currently classified as low grade(LG)-and high grade(HG)-dysplastic nodules.Following international guidelines recommending the surveillance of cirrhotic patients,a growing number of 1-2 cm hepatocellular nodules are recognized including early hepatocellular carcinoma(eHCC)and DN the latter accounting for as many as 70%of nodules<1 cm.HG-DN are currently considered the most advanced HCC precursors.The histological diagnosis of low-grade dysplastic nodule(LG-DN),high-grade dysplastic nodule(HG-DN)and eHCC in small liver biopsies requires a comprehensive stepwise morphological and immunocytochemical approach.By imaging the differential diagnosis among these lesions is a challenge.According to vascular enhancement at dynamic computed tomography(CT)or magnetic resonance imaging(MRI)these precursors are classified as hypo-vascular/indeterminate nodules even though distinction between LG-DN and HG-DN is almost impossible.The introduction of gadoexetic acid-enhanced MRI has represented an extremely important advance in this field allowing a better differentiation of dysplastic lesions from eHCC and progressed HCC.Additional MRI features as diffusion-weighted imaging further improved diagnostic accuracy of imaging.According to Liver Imaging Reporting and Data System(LI-RADS),either CT/MRI or Contrast-Enhanced Ultrasound LI-RADS,the dysplastic lesions should be categorized as LR-3 or LR-4.Natural history of these lesions confirmed that HCC can develop from HG-DN but which nodule and when it will undergo malignant transformation is not predictable.The search and validation of radiological and tissue markers able to select lesions more prone to HCC development,is currently underway.Whether and how HG-DN should be ablated or closely followed up is currently debated.