HCC Nodules Research Articles

153 The predictive value of non-invasive diagnostic tools to detect HCC or pre-malignant dysplastic nodules in patients with advanced cirrhosis and a hepatic mass

153 The predictive value of non-invasive diagnostic tools to detect HCC or pre-malignant dysplastic nodules in patients with advanced cirrhosis and a hepatic mass

MDCT of primary liver malignancies.

One of the major indications for abdominal CT is liver malignancies. Hepatocellular carcinoma (HCe) is the most common primary malignant hepatic neoplasm and its incidence is increasing. The HCC usually occurs as a complication of chronic liver disease and most often arises in patients with hepatic cirrhosis. The detection of HCC in patients with cirrhosis has been considered a technical challenge for CT for a long time, because cirrhosis alters both liver parenchymal characteristics as well as vascularization. Most HCCs are hypervascular lesions that typically enhance during the phase of maximum hepatic arterial enhancement; therefore, such lesions have often been difficult to detect with conventional CT of the liver, in which only portal venous phase imaging was performed because of the long scanning time. During the past decade, the introduction of helical CT technology has opened the door to new approaches to liver imaging. With its short acquisition time, spiral CT allows imaging the entire liver twice, before equilibrium: a hepatic arterial dominant phase and portal venous phase of enhancement [1]. The results of several studies have demonstrated that this biphasic approach to scanning greatly improves the detection of HCC. Because of the vascular nature of these lesions, there is evidence that a higher number of HCC nodules are detected when images are acquired in dual-phase CT compared with portal venous imaging alone [2, 3]. The advent of multidector-row CT (MDCT) has offered considerable advantages; they include improved temporal resolutions, improved spatial resolutions in the z axis, and longer anatomic coverage. As a result, we can scan the abdomen within reasonable breath-hold times which decrease respiratory and motion artifacts and provide higher image quality. Excellent 3D data sets can also be produced with thin collimation improving multiplanar imaging and the ability to perform CT angiography of the liver and mesenteric vessels [4] which can be important in patients candidate for hepatic resection, liver transplantation, or transarterial chemoembolization. In this respect, CT porto-angiography is probably superior to classic angiography. The CT angiography provides a complete picture of complex collateralizations of portal vein in potential liver transplantation recipients (Fig. 1). With the improvement in technology an inevitable evolution in scanning techniques is needed to maximize the benefit of new imaging capabilities. The issues of contrast medium administrations need to be revisited including the optimal timing, the total volume, the rate of administration, and the ideal iodine concentration.

Immunohistochemical assessment of proliferating cell nuclear antigen in primary hepatocellular carcinoma and dysplastic nodules.

A complementary way for the assessment of HCC prognosis is represented by the analysis of molecular markers. Thus, immunohistochemical assessment of proliferation can describe tumor aggressiveness, probability of local recurrence or metastasis potential, being very useful for the assessment of recurrence-free survival and survival until death. The aim of our study was to assess proliferating cell nuclear antigen activity in HCC and dysplastic nodules as compared with surrounding non-neoplasic areas. Immunohistochemical techniques were thus performed on the samples obtained by ultrasound-guided liver biopsies or intraoperative biopsies, in 32 patients with HCC, as well as in 3 patients with dysplastic nodules occurring in liver cirrhosis. Expression of PCNA within extranodular areas of the HCC patients in the absence or presence of cirrhosis, was increasing from 40% to 70%, respectively. PCNA expression further increased within intranodular areas of dysplastic nodules and HCC, to 100% and 96.88%, respectively. A progressive increase of the mean values of PCNA-LI was also observed from extranodular areas without or with cirrhosis, towards intranodular areas of dysplastic nodules and HCC (4.2%, 6.8%, 27.9%, 31.9%, respectively). Dysplastic nodules can thus be considered lesions with a high-proliferation rate, representing an early stage of hepatocarcinogenesis. This supported the current recommendations for borderline hepatocellular nodules identified by ultrasound, which indicate an aggressive treatment similar to malignant lesions. In summary, we demonstrated a progressively increasing rate of cellular proliferation, from extranodular non-neoplasic areas to intranodular areas (dysplastic nodules and HCC), as reflected by an increased expression of proliferating cell nuclear antigen labelling index.

The Factors Related to Local Recurrence after Radiofrequency Thermal Ablation of Hepatic Malignancies : Assessment of Spiral CT Findings

Purpose: To determine the factors that are related to local recurrence after Radiofrequency thermal ablation (RFTA) of hepatic tumors. Materials and Methods: We selected 30 patients with 51 hepatic nodules less than 5 cm in diameter (HCC, n=33; metastasis, n=18) who underwent RF thermal ablation between May 1999 and April 2000. Ablation was defined as 'complete' if immediately post-procedual CT showed that a nodule's margin was completely covered by ablation. Every three months, follow-up CT scans were examined for signs of local recurrence, and a nodule was assessed in terms of its size, the histologic diagnosis, adjacent vessels, perfect ablation (a safety margin of more than 5mm beyond the tumor margin), and whether hyperemia was observed after ablation. Finally, a group in which there was local recurrence (group A, n=15) and another showing no recurrence (group B, n=36) were compared. Results: Mean nodule size in group A and group B was 3.26 and 2.24 cm, respectively. Local recurrence was noted in 7 of 33 HCC nodules (21.2%), and in 8 of 18 (44.4%) which were metastatic. There was recurrence in 9 of 31 nodules with adjacent vessels (29.0%), and in 6 of 20 (30%) without adjacent vessels. In two of 17 perfectly ablated nodules (11.8%) there was local recurrence, but this was observed in 13 of 34 imperfectly ablated nodules (38.2%). Finally, local recurrence was seen in 14 of 36 nodules showing hyperemia (38.9%) but in one of 15 (6.7%) without hyperemia. Using chi-square analysis, it was thus shown that with regard to local recurrence, tumor size, perfect ablation and peritumoral hyperemia were statistically significant factors (p

CT-gesteuerte perkutane intratumorale Chemotherapie mit Cisplatin-/Adrenalin-Gel zur Behandlung inoperabler maligner Lebertumoren

To evaluate prospectively the volumetric changes of tumor and necrosis in unresectable malignant liver tumors and the clinical aspects after CT-guided direct intratumoral administration of a novel cisplatin/epinephrine injectable gel in a clinical phase II study. 8 patients with 17 colorectal liver metastases with a mean volume of 42 ml were treated with a mean of 5.1 injections and 8 patients with 11 HCC nodules (mean volume of 22.1 ml) with a mean of 3.25 treatments with CT-guided local administration of a novel cisplatin/epinephrine gel. This method of administration provides a higher local and lower systemic drug concentration. Volumes of tumor and necrosis prior to and after treatment were measured by computer-generated volumetric analysis. Contrast-enhanced studies verified pretherapeutic tumor necrosis with a value of 12.6% in the metastases and 0.6% in the HCC nodules. Intratumoral drug administration resulted in a necrotic volume of 110% in metastases and 128% in HCC versus the mean initial tumor volume, at least 4 treatments resulted in 122% necrosis in metastases and 130% in HCC. Local therapy control rate for the follow-up to 6 months was 38% and 83.3% for the group of metastases and HCC, respectively. Direct intratumoral injection of a novel cisplatin/epinephrine injectable gel results in an induction of a relevant necrosis in malignant liver tumors, with a substantially higher local therapy control rate for HCC compared to colorectal metastases.

Liver tumors in children and young patients: sonographic and color Doppler findings.

Liver tumors are a relatively rare pathologic condition in children and young patients. The aim of the present study was to categorize the sonographic (US) and color Doppler results of liver tumors in these patients. We retrospectively reviewed the US findings of 23 such cases: malignant tumor (13 cases)-hepatoblastoma (four cases), hepatocellular carcinoma (HCC; four cases), and hepatic metastasis (five cases); benign tumor (10 cases)-hepatocellular adenoma (four cases), focal nodular hyperplasia (two cases), mesenchymal hamartoma (two cases), cystadenoma (one case), and hemangioendothelioma (one case). There was no specific US findings for each tumor type. HCC usually developed on a normal liver and was imaged as multiple nodules. Color Doppler US helped in differentiating multiple metastatic nodules (hypovascular) from multiple HCC nodules (hypervascular). Presence of intratumoral cystic areas was usually suggestive of benign tumors. Follow-up US was useful for detecting small nodules in high-risk groups (congenital biliary atresia, glycogen storage disease). Color Doppler US helped in diagnosing portal thrombus or intratumoral shunt. Although there were no highly specific findings, US and color Doppler results contributed, to a certain degree, to the diagnosis of liver tumors in children and young adults by showing intratumoral cystic areas or vascularity.

Interstitial laser photocoagulation under ultrasound guidance of liver tumors: results in 104 treated patients

Objective: To evaluate the efficacy and complications of interstitial laser photocoagulation (ILP) under ultrasound (US) guidance as a technique for focal ablation of liver tumors in patients with normal and impaired hepatic function. Patients and Methods: A total of 104 patients, 77 with 85 nodules of hepatocellular carcinoma on cirrhosis (29 in Child-Pugh A class, 43 in B e 5 in C class) and 27 patients with hepatic metastases (25 from colon, two from lung carcinoma) underwent ILP under US guidance. Depending on tumor size up to four needles were inserted in the tumor and multiple laser illuminations were performed in one or multiple sessions. Necrosis of the nodules was evaluated with triphasic contrast-enhanced CT. Results: Ninety-four patients underwent a single ILP session and nine patients two sessions. CT showed complete necrosis in 70 out of 85 HCC nodules in 65 treated patients and in 24 out of 31 patients with metastases. Three Child C class patients dropped out the control of efficacy by CT because of severe liver failure associated in one case with transient paralytic ileum. One of these patients died 2 months after treatment. Two patients with metastasis dropped the completion of the treatment because of complication occurred after the ILP session (one paralytic ileum, one gastric haemorrage). Conclusions: ILP under US guidance is effective in inducing complete necrosis in small and large liver tumors. Nevertheless, ILP can cause severe derangement of liver function in patients with advanced cirrhosis.

Dynamic Images for Prediction of Therapeutic Efficacy of Hepatocellular Carcinoma Treated with Transcatheter Oily Chemoembolization

Purpose: To predict the therapeutic efficacy of transcatheter oily chemoembolization(TOCE) in the treatment Materials and Methods: We reviewed the findings of 24 dynamic CT or MR scans examined for the purpose of diagnosis before TOCE, and follow-up CT scans obtained after this procedure. In 24 patients (M:F=20:4) with a mean age of 52.2 years, 43 nodular HCCs with a diameter of 5 cm or less were present. The patients under-went double dynamic CT or MR imaging as one arterial phase 30 seconds after the intravenous injection of contrast media, and this was followed by a delayed phase 5 minutes fter injection. HCCs were then classified as one of four types: Type I, high and low attenuation or intensity during the arterial and delayed phase, re-spectively; Type II, iso- and low; Type III, iso- and high; and Type IV, high and iso-. In addition, we classified the degree of lipiodol accumulation by HCC nodules as either Grade 5 (fullmoon-like lipiodolization), Grade 2 (about 40%), or Grade 1 (about 20%), as seen on follow-up CT scans after TOCE. Results: Type I provided an accuracy of 72.1% considering to more than 50% lipiodol accumulation. However, a single finding demonstrating high atenuation or intensity during the arterial phase gave an accura-cy of 79.1% better than that of Type I. Conclusion: A finding of high attenuation or intensity during the arterial phase, as seen on dynamic CT or MR images, provides the best information about the therapeutic efficacy of HCCs treated by means of with TOCE.

Lewis Y antigen expression in hepatocellular carcinoma. An immunohistochemical study.

The altered expression of the Lewis blood group-related antigens during malignant transformation can be used clinically as a tumor marker or as a prognostic indicator. The Lewis Y (LeY) antigen, which is one of the Type 2 human blood group-related antigens, also is thought to behave as an oncodevelopmental cancer-associated antigen. In this study, the authors examined the association between human LeY antigen expression and the clinicopathologic features of HCC, including its proliferative activity. Forty-six histologically confirmed cases of HCC were studied retrospectively. Liver biopsy specimens from the main tumor of each case were obtained under ultrasonic guidance before treatment was initiated. The formalin fixed, paraffin embedded serial sections were immunostained using a modification of the avidin-biotin-peroxidase complex method, with a primary monoclonal antibody (MoAb) directed against the LeY antigen (BM-1/JIMRO). The relationship between LeY antigen expression and the HCC's proliferative activity was analyzed similarly by immunohistochemical methods using a primary MoAb directed against the Ki-67 antigen (MIB 1). In addition, to clarify the relationship between LeY antigen expression and the histologic heterogeneity within HCC, seven cases of surgically resected HCC also were immunostained. The LeY antigen was detected on the membrane and in the cytoplasm of the cancer cells. Of the 46 HCC cases, 20 (43.5%) expressed the LeY antigen in the tumor cells. There was no correlation between LeY antigen expression and the maximum tumor dimension or the Stage. However, the incidence of LeY antigen-positive cases in poorly differentiated HCCs was found to be significantly higher than that in well or moderately differentiated HCCs (P < 0.01). In resected HCC cases, LeY antigen expression within HCC nodules was frequently greater in the less differentiated tumor than in adjacent differentiated tumor. Moreover, the incidence of LeY antigen expression in alpha-fetoprotein (AFP)-positive (AFP > or = 200 ng/ml) HCC cases was significantly higher than that in AFP-negative (AFP < 200 ng/ml) HCC cases (P < 0.05). Furthermore, the mean value of the Ki-67 labeling index in LeY antigen-positive HCC cases (25.2 +/- 11.3%) was significantly higher than that in LeY antigen-negative HCC cases (9.4 +/- 4.1%) (P < 0.001). These results suggest that LeY antigen expression correlated closely to the dedifferentiation and proliferative activity of HCC.

Growth patterns and interstitial invasion of small hepatocellular carcinoma

Twenty-five cases of small hepatocellular carcinoma (HCC; diameter < or = 30 mm) were evaluated for overall morphologic features and growth patterns. The tumors often showed a well-differentiated, normotrabecular histologic pattern and insidious interstitial invasion, which resembled benign hepatocytes scattered in connective tissues. As the tumor grew, a less-differentiated tumor area became predominant. Portal tracts included in small HCC nodules were quantitatively assessed, revealing that they progressively reduced in number with tumor growth. The tumor margin was often reported to be unclear. The present results indicate that the histologic grade of tumor differentiation, capsular formation, existence of liver cirrhosis and patterns of interstitial invasion are important factors for determining the nature of the margin. The score of argyrophilic nuclear organizer regions (AgNOR) was examined in 5 cases showing typical interstitial invasion with the insidious type. In each case, the AgNOR score of the invading tumor cells was lower than that of tumor cells within the HCC nodules, but higher than benign hepatocytes in cirrhotic parenchyma. It clarified that the growth activity of well-differentiated HCC was rather suppressed upon their interstitial invasion.

Immunohistochemical studies of PIVKA-II in hepatocellular carcinoma by indirect immunofluorescence.

Tissue PIVKA-II was examined in 32 hepatocellular carcinomas and 2 metastatic liver tumors using indirect immunofluorescence, and the results were compared with the size, histological grading and serum PIVKA-II level. The specificity of this method was confirmed by the disappearance of reactivity in PLC/PRF/5 cells after the addition of vitamin K to the culture medium. Positive PIVKA-II staining was observed as a clustered or a single cell pattern only in the HCC nodules, but not in the surrounding cirrhotic tissue. PIVKA-II staining was observed in all HCC groups regardless of histological grade. There was no relationship between PIVKA-II staining and the size of HCC. PIVKA-II was detected immunohistochemically even in small HCC of patients whose plasma PIVKA-II levels were below the detection limit. These results suggest that PIVKA-II production is a specific phenotype of HCC regardless of its histological grading and demonstrate that this immunofluorescent PIVKA-II staining is more sensitive and useful than plasma PIVKA-II assay for the diagnosis of HCC.