PURPOSE: To determine the relative frequency, incidence, and locations of metastases of hepatocellular carcinoma (HCC), correlate extrahepatic metastatic disease with intrahepatic tumor staging, and determine the computed tomographic (CT) manifestations of HCC metastases. MATERIALS AND METHODS: CT findings in 403 consecutive patients with HCC at our institution since 1992 were reviewed retrospectively. One hundred forty-eight patients with extrahepatic metastatic HCC were identified, and the locations, sizes, and attenuation and enhancement characteristics of the lesions were recorded. RESULTS: A majority (128 [86%] of 148) of patients with extrahepatic HCC foci had either intrahepatic stage IVA tumor (112 [76%] patients) or an intrahepatic stage III tumor (16 [11%] patients) at the occurrence of metastases. The most frequent site of the first detectable metastasis was the lung (58 [39%] patients). Tabulation of all extrahepatic metastatic sites showed the most common to be the lung in 81 (55%) patients, the abdominal lymph nodes in 60 (41%) patients, and the bone in 41 (28%) patients. CONCLUSION: The lung, abdominal lymph nodes, and bone are the most common sites of extrahepatic metastatic HCC. Most extrahepatic HCC occurs in patients with advanced intrahepatic tumor stage (stage IVA). Incidental extrahepatic lesions at CT in patients with stage I or II intrahepatic HCC are unlikely to represent metastatic HCC.

Adolescent↗

PubMed2000

Prognostic significance of arterial phase CT for prediction of response to transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma: a retrospective analysis.

OBJECTIVE: The purpose of this study was to use hepatic arterial phase helical CT to assess tumor vascularity and predict the likelihood of response to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. MATERIALS AND METHODS: Helical CT findings for 57 patients with hepatocellular carcinoma were classified into one of three patterns of vascularity on the basis of the degree of tumor or liver enhancement during the hepatic arterial phase. Cases in which hypervascular lesions predominated were classified as a type 1 pattern. Cases in which hypovascular lesions predominated were classified as a type 2 pattern. Patients were classified as responders or nonresponders on the basis of the changes of tumor size revealed on CT after three transcatheter arterial chemoembolization treatments. RESULTS: We classified the 57 patients as 37 responders (65%) and 20 nonresponders (35%). A statistically significant correlation between the type 1 hypervascular pattern and response to transcatheter arterial chemoembolization was seen; conversely, the type 2 hypovascular pattern correlated with nonresponse to transcatheter arterial chemoembolization (chi-square = 7.85, p = 0.02). Patients classified as responders lived significantly longer than those classified as nonresponders with 12-, 24-, and 36-month survival rates of 90%, 67%, and 36%, respectively, for responders and 70%, 17%, and 10%, respectively, for nonresponders. CONCLUSION: We found that patients who responded to transcatheter arterial chemoembolization had prolonged survival (p < 0.01). Response correlated closely with tumor vascularity as shown on hepatic arterial phase helical CT.

Antineoplastic Agents↗

PubMed2000

Detection of vascular complications after liver transplantation: early experience in multislice CT angiography with volume rendering.

OBJECTIVE: Our objective was to investigate the usefulness of three-dimensional multislice CT angiography for the evaluation of liver transplant recipients presenting with clinical or sonographic findings suggestive of hepatic vascular complications. CONCLUSION: Our early results indicate that three-dimensional multislice CT angiography with volume rendering can reveal common and potentially lethal vascular complications in patients who have undergone liver transplantation.

Aneurysm↗

PubMed1999

Expression of the human hepatocyte growth factor cDNA in primary cultures of rat hepatocytes.

Hepatocyte growth factor (HGF) and epidermal growth factor (EGF) are primary mitogens for hepatocytes in culture. hepatocytes express the HGF-receptor MET but not HGF itself. To investigate the influence of autocrine HGF expression on the proliferative potential of hepatocytes, primary cultures were submitted to retrovirus-mediated transduction of the human hgf (huHGF) cDNA. Expression of the transduced cDNA revealed a minimum 2-fold increase in HGF-mRNA, whereas expression of the Escherichia coli beta-galactosidase gene remained even. Estimation of huHGF copy numbers showed there was a minimum 4-fold increase, suggesting an increase in the population of transduced cells. Immunoprecipitation of excreted huHGF and growth bioassays proofed that HGF was present and functional. HGF is excreted into the medium and therefore, by diffusion, available to transduced and non-transduced cells. The increase in huHGF-transduced cells suggests that the autocrine pathway as opposed to the paracrine pathway, which are both present at the same time, confers a growth advantage to these cells.

Animals↗

PubMed1997

Expression of HGF and cMet in the developing and adult brain.

Hepatocyte growth factor (HGF) was recently recognized as a potential neurotrophic factor in the developing brain. We studied expression of HGF and its receptor using Northern blot analysis and in situ hybridization for mRNA and double immunofluorescent laser confocal microscopy. HGF and cMet messages were abundant in the hippocampus of both human and rat brains. In this region, both messages were localized in the neuronal layer. Segregation of HGF predominantly in the hippocampal CA3-4 and cMet in CA1 supports the hypothesis that HGF may mediate important neurotrophic functions in both developing and adult brains.

Animals↗

PubMed1996

Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium.

Mature adult parenchymal hepatocytes, typically of restricted capacity to proliferate in culture, can now enter into clonal growth under the influence of hepatocyte growth factor (scatter factor) (HGF/SF), epidermal growth factor (EGF), and transforming growth factor alpha (TGFalpha) in the presence of a new chemically defined medium (HGM). The expanding populations of hepatocytes lose expression of hepatocyte specific genes (albumin, cytochrome P450 IIB1), acquire expression of markers expressed by bile duct epithelium (cytokeratin 19), produce TGFalpha and acidic FGF and assume a very simplified morphologic phenotype by electron microscopy. A major change associated with this transition is the decrease in ratio between transcription factors C/EBPalpha and C/EBPbeta, as well as the emergence in the proliferating hepatocytes of transcription factors AP1, NFkappaB. The liver associated transcription factors HNFI, HNF3, and HNF4 are preserved throughout this process. After population expansion and clonal growth, the proliferating hepatocytes can return to mature hepatocyte phenotype in the presence of EHS gel (Matrigel). This includes complete restoration of electron microscopic structure and albumin expression. The hepatocyte cultures however can instead be induced to form acinar/ductular structures akin to bile ductules (in the presence of HGF/SF and type I collagen). These transformations affect the entire population of the hepatocytes and occur even when DNA synthesis is inhibited. Similar acinar/ductular structures are seen in embryonic liver when HGF/SF and its receptor are expressed at high levels. These findings strongly support the hypothesis that mature hepatocytes can function as or be a source of bipotential facultative hepatic stem cells (hepatoblasts). These studies also provide evidence for the growth factor and matrix signals that govern these complex phenotypic transitions of facultative stem cells which are crucial for recovery from acute and chronic liver injury.

Adult↗

PubMed1996

Pulsatile perfusion system for ex vivo investigation of biochemical pathways in intact vascular tissue.

We have constructed and performed initial validation of an innovative perfusion system that allows exposure of intact segments of vascular tissue to realistic physiological and hemodynamic environments ex vivo. Computer-controlled opening and closing of an in-line gate valve allows generation of arterial pressure waveforms. The control algorithm predicted resultant pressure waveforms with a high degree of accuracy (Pearson correlation coefficient > 0.97). To document vascular homeostasis ex vivo, vasomotor bioassays and morphological studies were performed. The bioassays consisted of injecting epinephrine (2 x 10(-3) mg/ml) into the perfusion system followed by acetylcholine (100 microM) while concurrently measuring vessel diameter with a laser micrometer, significant vasomotion was measured for canine carotid arteries (n = 4) bioassayed after 1, 24, and 48 h of perfusion (P < 0.03). Additionally, human saphenous vein segments were perfused for 24 h (n = 4) and viewed with laser confocal scanning microscopy and transmission electron microscopy; photomicrographs show typical vascular morphology. We conclude that the vascular perfusion system described herein is well suited for investigating the response of intact vascular tissue to hemodynamic variables.

Acetylcholine↗

PubMed1995

Fusion of immunoscintigraphy single photon emission computed tomography (SPECT) with CT of the chest in patients with non-small cell lung cancer.

In non-small cell lung cancer (NSCLC), accurate staging is critical in deciding between potentially curative surgery and palliative treatment. Image registration, or fusion, combines the unique functional information provided by SPECT imaging with the excellent anatomic detail offered by computed tomography (CT) or magnetic resonance imaging to better characterize the information provided by each separate modality. In this study, we explored the role of fusion of immunoscintigraphy SPECT with CT in the staging of NSCLC. We fused chest CT with 99mTc-labeled IMMU-4 anti-carcinoembryonic antigen Fab' antibody fragment SPECT in 14 patients with NSCLC using a landmark-based algorithm. The algorithm's accuracy was a measure from the center-to-center distance and the percentage overlap of two regions of interest: one drawn on CT and warped onto SPECT, the other drawn directly on the SPECT. We found that the average center-to-center distance was 1.3 +/- 0.8 pixels. Average overlap was 46 +/- 20%. CT-SPECT fusion helped differentiate tumor from normal blood pool, necrotic areas within viable tumor, tumor recurrence from scar, and malignant lymphadenopathy from hyperplasia. We conclude that fusion of CT and SPECT augments the information provided by each separate modality. Future clinical applications of fusion in NSCLC staging using immunoscintigraphy appear promising.

Adult↗

PubMed1990

Crystallization and preliminary X-ray study of rat Clara cell 10,000 Mr protein.

Single crystals of Clara cell 10,000 Mr protein have been grown by vapour diffusion in the presence of ammonium sulphate. The space group is P4(1)32 or P4(3)32 with unit cell dimension a = 156.9 A. Crystals diffract to about 3.8 A resolution.

Animals↗