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MR imaging patterns of gadolinium retention within liver neoplasms.

BACKGROUND: To determine the spectrum of appearances of gadolinium retention within cholangiocarcinoma (CCA) and other liver neoplasms. METHODS: Two hundred ten patients underwent hepatic magnetic resonance imaging (MRI) at 1.5 T with precontrast T1- and T2-weighted spin-echo (SE) images and delayed Gd-DTPA- or gadoteridol- (0.1 mmol/kg) enhanced T1-weighted SE images. Postcontrast images were evaluated for lesions suspicious for tumors, and lesion signal intensity was characterized as homogeneously or heterogeneously hypo-, iso-, mildly hyper-, or markedly hyperintense to liver. Data from 94 patients with benign or malignant neoplasms are presented. RESULTS: Imaging demonstrated 237 malignant neoplasms (121 hepatocellular carcinoma [HCC], 26 CCA, 17 colon carcinoma metastases, 73 other tumors) and 28 benign neoplasms (22 hemangioma, six focal nodular hyperplasia [FNH]). One hundred forty malignant lesions appeared as homogeneous postcontrast (29 hypointense, 75 isointense, 17 mildly hyperintense, 19 markedly hyperintense) and 97 as heterogeneous (15 isointense, 50 mildly hyperintense, 32 markedly hyperintense). Malignant lesions showing homogeneous, mildly or markedly hyperintense signal intensity postcontrast included 10 CCA, seven HCC, six epithelioid hemangioendothelioma, eight neuroendocrine tumor metastases, three adenocarcinoma metastases of unknown origin, and one breast carcinoma metastasis. Hemangiomas appeared as homogeneous postcontrast in 19 lesions (six isointense, one mildly hyperintense, 12 markedly hyperintense) and as heterogeneous in three lesions (markedly hyperintense). FNH appeared as homogeneous postcontrast in one lesion (isointense) and as heterogeneous in five lesions (one isointense, four mildly hyperintense). CONCLUSION: Homogeneous gadolinium retention on delayed postcontrast images of malignant hepatic neoplasms is seen in a high percentage of CCA lesions and less commonly with other neoplasms.

Contrast Media↗

Benign and malignant liver neoplasms: some new etiologic associations.

Several agents have recently been implicated in the development of benign and malignant liver neoplasms. Recognition of their possible role by the primary care physician may prevent serious consequences to patients exposed to these agents, which include oral contraceptives, androgens, hepatitis virus, and vinyl chloride.

Androgens↗

Using multidetector CT for preoperative vascular evaluation of liver neoplasms: technique and results.

OBJECTIVE: The purpose of our study was to evaluate the performance of CT angiography using multidetector CT (MDCT) for preoperative vascular evaluation in candidates who were scheduled for liver neoplasm resection. SUBJECTS AND METHODS: Forty-two consecutive subjects with malignant liver tumors scheduled for resection were studied with multiphase MDCT. The first 22 subjects underwent both multiphase MDCT angiography and catheter angiography before surgery. The subsequent 20 subjects underwent only preoperative CT angiography. Postprocessing was performed, and the images were analyzed for the depiction of arterial, portal vein, and hepatic vein anatomy and for the identification of important vascular variants. The postprocessing findings were compared and correlated with the findings from catheter angiography (22/42) or intraoperative sonography (42/42) and surgery (42/42). RESULTS: Arterial anomalies were detected on the images of 17 of 42 patients, including a replaced right hepatic artery in five, replaced left hepatic artery in six, accessory right and left hepatic arteries in two, common trunk for the celiac and superior mesenteric arteries in one, and early bifurcation of the celiac artery in one. In 22 patients in whom catheter angiography confirmation was available, the number of arteries and almost all the significant anomalies were correctly identified on CT angiography (accuracy, 97%; sensitivity, 94%; specificity, 100%). In the subset of 20 patients who underwent MDCT angiography without catheter angiography confirmation, all clinically relevant information was provided by CT angiography. The portal and hepatic vein anatomy and the relationships of the liver tumors to the neighboring venous structures were shown on CT. CONCLUSION: Multidetector CT provides valuable preoperative information about hepatic vascular architecture and can be used as a noninvasive alternative to catheter angiography before oncologic liver surgery.

Adult↗

The impact of intraoperative ultrasonography on surgery for liver neoplasms.

To analyze the effect of IOUS on surgical decision making, we performed a retrospective study of 45 patients who had exploratory laparotomy and IOUS for liver neoplasms. Preoperative lesion detection was compared with intraoperative findings. The effect of IOUS on the choice of surgical procedure was analyzed. Preoperative imaging detected 67% of lesions, 78% when combined with surgical inspection and palpation, and 97% were recognized by IOUS. Surgery was modified in 23 of 45 cases (51%); 19 of those 23 cases (83%) were based on IOUS findings alone. IOUS demonstrated superior lesion detection over noninvasive preoperative liver imaging, and IOUS significantly affected surgical decision making.

Adult↗

Benign liver neoplasms.

A variety of benign focal liver lesions are easily characterized with currently available imaging techniques and contrast agents. The most common benign liver lesions, such as hemangioma, bile duct cyst, and FNH, reveal characteristic cross-sectional imaging features that allow an accurate diagnosis. For atypical variants and more uncommon lesions, including HCA, angiomyelioma, infantile hemagioendothelioma, and mesenchymal hamartoma, integration of clinical data can often help in the interpretation of imaging studies. Finally, for the remaining lesions, such as hepatic adenomatosis, the imaging findings may not be specific enough to negate the need for a tissue biopsy.

Adenoma↗

Hypomethylation of the rat glutathione S-transferase pi (GSTP) promoter region isolated from methyl-deficient livers and GSTP-positive liver neoplasms.

DNA methylation at the 5-position on the cytosine ring in CpG dinucleotides (CpG sites) appears to play an important role in regulating gene expression. In general, there is an inverse relationship between promoter CpG site methylation and the potential for transcription. Thus, changes in DNA methylation density may lead to altered levels of proteins such as glutathione S-transferase pi (GSTP), which is frequently used as a marker to detect hepatocellular foci and neoplasms in the rat. In the present study, the level of CpG methylation in the rat GSTP promoter region was determined in bisulfite-treated DNA isolated from control (untreated) rat livers, chemically induced, GSTP-positive rat liver neoplasms, and methyl-deficient rat livers that contained numerous GSTP-positive foci after administration of a defined diet deficient in folate and choline and low in methionine (0.18%). Eight cytosines between -235 and + 140 in the GSTP promoter region were methylated in a site-specific manner in GSTP-negative control liver, whereas these same sites were hypomethylated in all four chemically-induced, GSTP-positive neoplasms. Similarly, all CpG sites were unmethylated in methyl-deficient liver DNA within 3 weeks of the rats receiving the methyl-deficient diet, and they remained unmethylated throughout the 36-week treatment period. Five of the eight CpG sites are located within consensus sequences for the DNA binding proteins Spl and E2F. This indicates at least one possible mechanism that could potentially lead to transcriptional activation of GSTP in hepatocellular foci and neoplasms during rat hepatocarcinogenesis. These findings suggest that methylation of critical cytosines within the promoter region rather than all CpG-associated cytosines may be a determining factor in regulation of GSTP expression.

Animals↗

CT-guided percutaneous ethanol injection with disposable curved needle for treatment of malignant liver neoplasms and their metastases in retroperitoneal lymph nodes.

AIM: To explore the feasibility of computed tomography (CT)-guided percutaneous ethanol injection (PEI) using a disposable curved needle for treatment of malignant liver neoplasms and their metastases in retroperitoneal lymph nodes. METHODS: CT-guided PEI was conducted using a disposable curved needle in 26 malignant liver tumors smaller than 5 cm in diameter and 5 lymph node metastases of liver cancer in the retroperitoneal space. The disposable curved needle was composed of a straight trocar (21G) and stylet, a disposable curved tip (25 G) and a fine stylet. For the tumors found in deep sites and difficult to reach, or for hepatic masses inaccessible to the injection using a straight needle because of portal vein and bile ducts, the straight trocar was used at first to reach the side of the tumor. Then, the disposable curved needle was used via the trocar. When the needle reached the tumor center, appropriate amount of ethanol was injected. For relatively large malignant liver tumors, multi-point injection was carried out for a better distribution of the ethanol injected throughout the masses. The curved needle was also used for treatment of the metastasis in retroperitoneal lymph nodes blocked by blood vessels and inaccessible by the straight needle. RESULTS: All of the 26 liver tumors received 2 or more times of successful PEI, through which ethanol was distributed throughout the whole tumor mass. Effect of the treatment was monitored by contrast-enhanced multi-phase CT and magnetic resonance imaging (MRI) examinations three months later. Of the 18 lesions whose diameters were smaller than 3 cm, the necrotic change across the whole mass and that in most areas were observed in 15 and 3 tumors, respectively. Among the 8 tumors sizing up to 5 cm, 5 were completely necrotic and 3 largely necrotic. Levels of tumor seromarkers were significantly reduced in some of the cases. In 5 patients with metastases of liver cancer in retroperitoneal lymph nodes who received 1 to 3 times of PEI, all the foci treated were completely necrotic and smaller demonstrated by dynamic contrast-enhanced CT or MRI 3 months later. CONCLUSION: CT-guided PEI using a disposable curved needle is effective, time-saving and convenient, providing an alternative therapy for the treatment of malignant liver tumors and their retroperitoneal lymph node metastases.

Adult↗

Differential expression of drug metabolizing enzymes in primary and secondary liver neoplasm: immunohistochemical characterization of cytochrome P4503A and glutathione-S-transferase.

The question whether expression of drug metabolizing enzymes in human liver is altered by liver neoplasm remains controversial; however, the ability or unability of tumour cells to metabolize certain drugs may be important for developing therapeutic strategies. We therefore investigated the abundance and localization of two classes of drug metabolizing enzymes [cytochrome P4503A (CYP3A) and pi-type glutathione-S-transferase] by means of immunohistochemistry (standard ABC technique) in patients with hepatocellular carcinoma (HCC, n = 16) and with liver metastasis from adenocarcinoma (n = 53) in comparison to normal controls (n = 5). The distribution of CYP3A in normal liver samples showed a characteristic pattern of four to five layers of stained hepatocytes surrounding the central vein. Eleven out of 16 cases of HCC showed expression of CYP3A; staining was less intense than in normal liver and zonation was completely lost. In contrast, only 5 out of 53 samples of metastasis stained positively for CYP3A. The difference between primary and secondary neoplasm was statistically significant (chi-square, P < 0.0001). Pi-type glutathione-S-transferase (GST) stained positively in 9 out of 16 HCC and in 48 out of 53 cases of liver metastasis (chi-square, P < 0.01) indicating a higher percentage of immunostaining in liver metastasis. In summary, we observed differences in the abundance and distribution pattern of CYP3A and GST between primary and secondary neoplasma of human liver and in comparison to normal controls. In combination with established methods these data may contribute to the establishment of reliable test systems for distinguishing primary from secondary liver tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Immunohistochemical assessment of human microsomal epoxide hydrolase in primary and secondary liver neoplasm: a quantitative approach.

1. Epoxide hydrolases form an enzyme family involved in the metabolism of a variety of xenobiotics including cytostatic drugs and carcinogens. Whether human microsomal epoxide hydrolase--one of the main members of the epoxide hydrolase family--is expressed in neoplasia of the liver has been the subject of a controversial discussion. 2. We therefore developed a quantitative immunohistochemical assay and monitored epoxide hydrolase expression in hepatocellular carcinomas (HCC, n = 20), cholangio-cellular carcinomas (CCC, n = 2) and liver metastases (n = 57) of tumours of various origins, and compared the expression intensities and patterns to normal liver tissue. 3. In normal liver tissue microsomal epoxide hydrolase displays expression of the constitutive type with non-zonal staining of all hepatocytes. 4. When using a quantitative immunohistochemical approach statistically significant differences in microsomal epoxide hydrolase expression were observed between normal tissue, hepatocellular carcinoma and liver metastases (mean optical density 2.35, 1.63 and 0.21 respectively, p = 2.9, 6.3 and 18.9). These data indicate differential expression in different types of liver neoplasm. 5. As microsomal epoxide hydrolase is involved in metabolism of different xenobiotics our findings may have implications for tumour progression.

Aged↗

Feasibility study of an ultrasound contrast agent (levovist) in color Doppler imaging of liver neoplasms.

The purpose of this study was to determine the efficacy of using an ultrasound contrast agent (levovist) to enhance the color Doppler imaging of liver neoplasms. Thirty patients with hepatic tumors were enrolled in this study. After intravenous administration of levovist, the color Doppler signals of normal hepatic vessels were enhanced. In various hepatic tumors, the different patterns of tumor vascularity were observed, which had not been demonstrated in conventional non-contrast color Doppler imaging. In 11 of 16 patients with hepatocarcinoma, additional color Doppler signals were observed in the central part of the tumors. On the contrary, 3 patients with metastatic liver lesions the enhanced color Doppler signals appear only at the peripheral of tumors. A typical rim-like color enhancement was seen in 2 of the 3 cases. In six patients with hepatic hemangiomas contrast-enhanced color Doppler imaging demonstrated the blood vessels at the margin of the neoplasms. Contrast-enhanced color Doppler imaging improves the visualization of the hepatic neoplasm vascularity. This technique holds great promise for detecting small liver tumors and differentiating hepatic neoplasms.

Adult↗

Repeated hepatic arterial infusion chemotherapy using an implanted port system in patients with unresectable malignant liver neoplasms: significant factors affecting early hepatic arterial occlusion.

The purpose of this study was to identify significant factors affecting early hepatic arterial occlusion in patients who received repeated hepatic arterial infusion chemotherapy using an implanted port system. Eighty-five patients with unresectable liver neoplasms who underwent implantation of the port system were studied. Arterial infusion chemotherapy was performed every 1-4 weeks. Arterial occlusion was evaluated by hepatic arteriography performed via the port every 3 months. Twenty variables were analyzed using univariate and multivariate analyses to identify significant factors affecting early hepatic arterial occlusion. Hepatic arterial occlusion was found in 25.9% (22/85) of the patients. Thirteen of them experienced early arterial occlusion within 6 months. The mean survival period was significantly worse in patients who experienced early arterial occlusion than those who did not (16 months vs. 26 months, p<0.05). In the multivariate analysis, the following 3 variables had independent value for early arterial occlusion; i). diameter of the common hepatic artery, ii). gender, and iii). previous systemic chemotherapy. Early arterial occlusion affects therapeutic effects and survival in patients who undergo arterial infusion chemotherapy with an implanted port. Factors demonstrated here are important to classify patients at risk of early hepatic arterial occlusion.

Adult↗

Hepatic xenobiotic metabolizing enzymes in two species of benthic fish showing different prevalences of contaminant-associated liver neoplasms.

English sole (Parophrys vetulus) and starry flounder (Platichthys stellatus) are closely related benthic fish which show substantial differences in prevalences of contaminant-associated hepatic neoplasms and putatively preneoplastic foci of cellular alteration when captured from estuaries containing a variety of organic chemical contaminants, including polycyclic aromatic hydrocarbons (PAH) and chlorinated hydrocarbons. Because PAH are strongly implicated as causative agents in the etiology of these lesions, several of the hepatic enzymes involved in activation and detoxication of PAH were studied in these two species. Hepatic aryl hydrocarbon hydroxylase (AHH), epoxide hydrolase (EH), and glutathione S-transferase (GST) activities were measured in animals sampled from both contaminated and reference areas. English sole, the species showing higher prevalences of contaminant-associated hepatic lesions, had higher (1- to 2-fold) hepatic activities of AHH and lower activities of EH (0.8-fold) and GST (1.8-fold) than those of starry flounder, regardless of site of capture. These results are largely consistent with increased activation and decreased detoxication of PAH by English sole in comparison to starry flounder. Both laboratory and field data suggested that the observed species differences in enzyme activities were constitutive and not related to differential exposure to contaminants. There were also substantial differences between these species with respect to expression of GST isoenzymes, in that starry flounder expressed two highly anionic GST isoenzymes which did not correspond to any GST isoenzymes expressed in English sole liver; a previous study in an elasmobranch fish showed that an anionic GST was most active toward PAH oxides. These differences in enzyme activities and isoenzyme profiles suggest a toxicological basis which may help to explain, at least in part, the differences in prevalences of contaminant-associated liver neoplasms between these two species.

Animals↗