Lens culinaris agglutinin-reactive alpha-fetoprotein and protein induced by vitamin K absence II are potential indicators of a poor prognosis: a histopathological study of surgically resected hepatocellular carcinoma.

BACKGROUND: We histopathologically examined Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) and protein induced by vitamin K absence (PIVKA) II-positive HCC to clarify the efficacy of these markers for predicting a poor prognosis. METHODS: Serum AFP-L3 and PIVKA II was measured in 110 HCC patients. AFP-L3 was measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting, and PIVKA II by using a high-sensitivity kit. The growth type, capsule formation, capsule infiltration, portal vein invasion, intrahepatic metastasis and histological tumor grade were evaluated pathologically. RESULTS: Thirty-eight (35%) HCC patients were AFP-L3-positive, and 63 (57%) were PIVKA II-positive. In AFP-L3-positive HCC, the frequencies of an infiltrative growth type (positive : negative = 66% : 42%, P = 0.027) and a poorly differentiated type (positive : negative = 32% : 6%, P < 0.001) were significantly higher than in AFP-L3-negative HCC. In PIVKA II-positive HCC, the frequencies of an infiltrative growth type (positive : negative = 62% : 28%, P < 0.001), vascular invasion (positive : negative = 63% : 26%, P < 0.001), and intrahepatic metastasis (positive : negative = 38% : 4%, P < 0.001) were significantly higher than in PIVKA II-negative HCC. In both AFP-L3- and PIVKA II-positive HCC, the frequency of a poorly differentiated growth type was significantly higher than in HCC positive for either AFP-L3 or PIVKA II or HCC negative for both AFP-L3 and PIVKA II (both positive : either positive : both negative = 37% : 12% : 0%; P = 0.014, P < 0.001, respectively). CONCLUSIONS: AFP-L3 was related to progression from moderately differentiated to poorly differentiated HCC, whereas PIVKA II was more specific to vascular invasion. PIVKA II is therefore likely to be a useful indicator of vascular invasion.

Value of fusing PET plus CT images in hepatocellular carcinoma and combined hepatocellular and cholangiocarcinoma patients with extrahepatic metastases: preliminary findings.

BACKGROUND/AIMS: This study aimed to evaluate the usefulness of (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) and PET plus computed tomography (CT) fusion images for the detection of extrahepatic metastases of hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (combined HCC/CC). METHODS: Twenty-one patients with HCC and combined HCC/CC were enrolled in the study from December 2004 to February 2005. In all patients, PET and CT of the chest to pelvis region were performed. The sensitivity of PET plus CT fusion images was compared with the sensitivity of PET, CT, and bone scintigraphy. RESULTS: In 14 patients, a total of 58 extrahepatic metastases were diagnosed. The detection rate of PET plus CT fusion images, PET, CT, and bone scintigraphy was 98.2% (57 of 58 metastases), 89.6% (52 of 58 metastases), 91.2% (52 of 57 metastases), and 68.7% (11 of 16 bone metastases), respectively. No extrahepatic metastases were detected in the other seven patients. The detection rate of PET was 10/18 (55.6%) for intrahepatic lesions of HCC and combined HCC/CC. CONCLUSIONS: The fusion of PET plus CT images is useful in detecting extrahepatic metastases in HCC and combined HCC/CC patients.

Clinicopathological study of scirrhous hepatocellular carcinoma.

BACKGROUND AND AIMS: Scirrhous hepatocellular carcinoma (SHCC) is characterized by diffuse fibrosis of the tumor, however, its clinicopathological features are not fully clarified. This study aimed to clarify the clinicopathological features of SHCC. METHODS: Among 546 consecutively resected HCC without preoperative anticancer therapies, 25 SHCC were selected for the study and compared with 521 cases without scirrhous as the control. RESULTS: SHCC accounted for 4.6% of cases. On diagnostic imagings, SHCC was frequently misdiagnosed as cholangiocarcinoma (CC), combined HCC-CC or metastatic carcinoma. Overall survival rate was significantly higher than the control. The average (+/-SD) tumor size of SHCC was 3.4 +/- 1.8 cm without significant difference to the control. The majority of SHCC (88%) were located close to the liver capsule. SHCC was characterized by stellate fibrosis (84%), no encapsulation (100%), no necrosis and hemorrhage (100%), intratumoral portal tracts (80%), remarkable lymphocyte infiltration (84%), clear cell change (84%), and hyaline bodies (52%). The number of alpha-smooth muscle actin-positive myofibroblast-like cells (activated stellate cells) in the tumor was about three times more than that in the control. Regarding the developmental mechanism of scirrhous change, a close correlation with unique tumor location and activation of stellate cells was suggested. CONCLUSIONS: SHCC presents with characteristic clinicopathological features and the recognition of SHCC is important for both clinicians and pathologists.

Expression of vascular endothelial growth factor-C in human hepatocellular carcinoma.

BACKGROUND/AIMS: Vascular endothelial growth factor-C (VEGF-C) is thought to be an important factor in tumor angiogenesis/lymphangiogenesis, but its role in hepatocellular carcinoma (HCC) has not yet been fully investigated. METHODS: We immunohistochemically examined VEGF-C expression in surgically resected tissues of 90 HCC. RESULTS: In the 78 HCC with a single histological grade, VEGF-C expression was significantly stronger in poorly differentiated HCC than in well- (P=0.003) or moderately differentiated HCC (P=0.0002). A 'nodule-in-nodule' case presented VEGF-A expression in the well-differentiated component and VEGF-C expression in the moderately-poorly differentiated component. According to nodular diameter, VEGF-C expression was significantly higher in nodules of 3.0 cm or larger (P=0.0263). Extrahepatic metastases seen in seven cases expressed VEGF-C. In 20 of the 28 cases who were able to be followed up, the frequency of intrahepatic recurrence tended to be higher and extrahepatic metastasis was significantly higher in the cases who had VEGF-C expression in the tumor casts of the intrahepatic portal/hepatic vein branches than other cases without the expression (P=0.0139). Disease-free survival time tended to be shorter in cases with VEGF-C expression in tumor casts of the portal/hepatic vein than in those without VEGF-C expression (P=0.053; log-rank test). CONCLUSIONS: VEGF-C expression is related to the progression of HCC, and VEGF-C expression in tumor casts of the intrahepatic portal/hepatic vein is considered to be a factor indicating recurrence/metastasis sites.

Pathomorphological study on small nodular lesions in hepatitis C virus-related cirrhosis.

We examined pathomorphologically small nodular lesions in hepatitis C virus-related cirrhosis (type C cirrhosis). Small nodular lesions seen in the non-cancerous areas of 128 consecutively resected hepatocellular carcinomas (HCCs) associated with type C cirrhosis were selected for the study. From these, 18 large regenerative nodules (LRNs), 14 low-grade dysplastic nodules (LDNs), 10 high-grade DNs (HDNs), and 12 well-differentiated HCCs were detected. The diameters of HDN (11.7+/-4.3 mm) and well-differentiated HCC (12.3+/-3.5) were significantly larger than those of LRN (8.1+/-1.0) and LDN (8.6+/-2.7). Fatty change was not seen in LRNs and LDNs, while it was found in 4 HDNs (40%) and 8 well-differentiated HCCs (75%). Iron deposits were found in 2 LRNs (11%), 5 LDNs (36%), and 3 HDNs (30%), but not in the well-differentiated HCCs. The number of Kupffer cells in LDN and HDN was increased compared with that in the surrounding regenerative nodules. Cell density and the degree of neovascularization were well correlated with the progression from DN to HCC. The lack of neovascularization supports the concept that LRN has no neoplastic potency and can be regarded as the morphologic marker in the differentiation of LRN from DN.

Unique hypervascular nodules in alcoholic liver cirrhosis: identical to focal nodular hyperplasia-like nodules?

BACKGROUND/AIMS: Currently, focal nodular hyperplasia (FNH)-like nodules in cirrhotic liver is spotlighted. Unique hypervascular nodules mimicking FNH-like nodule in alcoholic liver cirrhosis were clinicopathologically clarified. METHODS: Six resected and six biopsy cases of small hypervascular nodules found in alcoholic cirrhosis were studied clinicopathologically. RESULTS: All cases were male and consumed 90-150 g/day of ethanol for longer than 20 years, and hepatitis virus markers were negative. The nodules, 9-21 mm in diameter, were detected by ultrasonography during follow-up of alcoholic cirrhosis, and showed hypervascularity on angiography. Six patients were diagnosed as hepatocellular carcinoma and six were as hyperplastic nodule by biopsy, and the former six cases received partial hepatectomy. All of the resected nodules were completely or incompletely encapsulated. Histologically, all resected and biopsy nodules showed moderate increase of cell-density with an irregular trabecular pattern, and scar-like fibrosis with anomalous blood vessels, and unpaired arteries. All nodules showed marked or mild iron deposits in hepatocytes and/or kupffer cells, and a diffuse capillarization of the sinusoids. CONCLUSIONS: The nodules in the present series seem to fall in the same category as FNH-like nodules in cirrhotic liver, and should be taken account in screening programs including patients with alcoholic cirrhosis.