Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis.

BACKGROUND: Needle biopsy of a suspicious liver lesion could guide management in the setting of equivocal imaging and serology, although it is not recommended generally because there is the possibility of tumour dissemination outside the liver. The incidence of needle track seeding following biopsy of a suspicious liver lesion is ill-defined, however. METHODS: A systematic review and meta-analysis of observational studies published before March 2007 was performed. Studies that reported on needle tract seeding following biopsy of suspicious liver lesions were identified. Lesions suspected of being hepatocelleular cancer (HCC) were considered. Data on the type of needle biopsy, diagnosis, incidence of needle track seeding duration to seeding, follow-up and impact on outcome were tabulated. RESULTS: Eight studies identified by systematic review on biopsy of HCC were included in a meta-analysis. The pooled estimate of a patient with seeding per 100 patients with HCC was 0.027 (95% confidence interval (CI) 0.018 to 0.040). There was no difference whether a fixed or random effects model was used. Q was 4.802 with 7 degrees of freedom, p = 0.684; thus the observed heterogeneity was compatible with variation by chance alone. The pooled estimate of a patient with seeding per 100 patients per year was 0.009 (95% CI 0.006 to 0.013), p = 0.686. CONCLUSIONS: In this systematic review we have shown that the incidence of needle tract tumour seeding following biopsy of a HCC is 2.7% overall, or 0.9% per year.

Homogenization of Mammalian tissues.

Satisfactory homogenization of a tissue is a necessary prerequisite to any fractionation schedule. A detailed protocol is given for rat liver because of the widespread use of this tissue. Although this technique should be broadly applicable to any soft tissue and to any subsequent fractionation procedure, there are certain tissues and applications that require either minor or extensive modification. Some of these points are addressed in the Notes section.

N-benzylimidazole for preparation of S9 fraction with multi-induction of metabolizing enzymes in short-term genotoxicity assays.

To evaluate the usefulness of N-benzylimidazole (BI) as an inducer with wide spectrum detection of precarcinogens in short-term bioassays, hepatic levels of cytochrome P-450 (CYP) and mutagenic activation of various carcinogens in Wistar and Sprague-Dawley rats orally treated with BI and BI plus ethanol or acetone were compared with those in the same strains of rats treated with 3-methylcholanthrene (MC), phenobarbital (PB) and polychlorobiphenyls (PCB). Immunoblot analyses for microsomal CYP proteins revealed a marked induction by BI in the levels of CYP1A1, CYP2B1 and constitutive CYP1A2 (approximately 11-fold), 2B2 (approximately 21-fold), 2E1 (1.5-fold) and 3A2 (4-fold) in rats of both strains. These levels were comparable with those induced by MC and PB, but were less than the CYP1A1/2 and 2B1 levels induced by PCB, while CYP2B2 was at the same level. In contrast, the level of CYP2E1 was clearly higher in BI-treated rats. The combinations of BI and acetone or ethanol specifically induced CYP2E1 (4-fold) and 2B1 (1.7-fold) levels when compared with BI alone in Wistar rats. The combined treatments also elevated mutagenic activities of eight heterocyclic amines (HCAs), aflatoxin B(1) (AFB(1)), benzo[a]pyrene and 2-aminofluorene in strain TA98 up to 14.3-, 5.1-, 2.8- and 2.1-fold above the untreated group, respectively, and those of five N-nitrosamines in strain TA100 up to 19.1-fold. Induction of specific CYP species responsible for activation of HCAs, AFB(1) and N-nitrosamines was confirmed by application of several CYP inhibitors. In addition, BI induced activities of both MC- and PB-inducible UDP-glucuronyltransferases towards 4-nitrophenol and testosterone. These results demonstrate that BI has a bifunctional action, with wide spectrum induction of phase I and II enzymes, and combined treatment with ethanol or acetone would be a pertinent inducer for metabolic enzymes in in vitro bioassays, the potential being comparable with or superior to other typical ones.

Detection, characterisation and purification of a murine liver factor capable of desensitising towards the lethal activity of tumour necrosis factor.

Tumour necrosis factor (TNF) is a major mediator in septic shock and several inflammatory diseases such as hepatitis. Galactosamine (GalN) sensitises experimental animals for TNF and the combination TNF/GalN leads to a lethal inflammatory hepatitis. We describe that a single injection of lipopolysaccharide (LPS), interleukin-1 (IL-1) or TNF can desensitise against the lethality induced by TNF/GalN, but also against changes in metabolic parameters such as hypothermia and transaminase release, in a dose responsive way. We also describe the desensitising capacity of a component present in Mouse Liver Extract (MLE). The MLE desensitises mice against the effects of TNF/GalN in a dose responsive way. The activity of the MLE is heat labile and does not involve LPS, TNF, IL-1 or TNF soluble receptors. We describe partial and complete purification of the factor. Partially pure material protects mice against all changes induced by TNF/GalN. The protection is dose dependent and heat labile and also possible in endotoxin-hyporesponsive C3H/HeJ mice. The pure material protects against lethality, hypothermia and AST release and it appears as a heat labile protein of relative molecular weight of 70 kDa probably with a break down product of 35 kDa.

Purification and physical-chemical characterization of hepatic stimulator substance.

Hepatic stimulator substance is a liver growth stimulator derived from the hepatocyte cytosol of weanling or regenerating adult rat livers. The present paper reports the almost 9,000-fold purification of hepatic stimulator substance with an approximately 100,000-fold increase in specific growth stimulator activity. Purification steps included heating at 95 degrees C for 15 min, 40% cold ethanol precipitation, passage over Procion Red HE3B, DEAE cellulose and Sephadex G75 columns and gel filtration and reverse-phase fast protein liquid chromatography techniques. As little as 27 ng per ml of the purest material produced a 2-fold stimulation in the standard HTC cell activity assay. Further studies indicate that hepatic stimulator substance is a highly negatively charged protein and that disulfide bonds or a complex tertiary structure are not essential to its activity. Hepatic stimulator substance is stable over a wide range of pH's and temperatures. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver stain revealed 1 major band at 12,400 daltons and 1 minor band at 17,500 daltons.

Roles of phospholipid and detergent in soluble protein activation of squalene epoxidase.

"Soluble protein factor" (SPF) from hog liver stimulates hepatic microsome-associated squalene epoxidase in the presence of phosphatidylglycerol or phosphatidylserine. When SPF and phosphatidylglycerol are preincubated for 30 min at 37 degrees C before addition to the epoxidase system, this stimulation is abolished. On Sephadex chromatography of the protein--phospholipid mixture, both components appear in the void volume, whereas SPF alone is retarded on the column. These results suggest formation of a SPF--phosphatidylglycerol complex. Treatment of the complex with Tween 80 restores the stimulatory effects of SPF on squalene epoxidase. The stimulation of microsomal squalene epoxidase by SPF was abolished by pretreatment of the membrane with low concentrations of deoxycholate or by solubilizing the enzyme with Triton X-100, implying that an intact membrane system is required for SPF sensitivity. SPF has been purified 1200-fold from hog liver.

Regulation of human lymphocyte function by a soluble extract from normal human liver.

The blastogenic and DNA synthetic response of human peripheral blood lymphocytes (PBL) to phytohemagglutinin (PHA) and allogeneic cells can be inhibited by a nontoxic aqueous extract (LEx) of normal human liver. LEx reversibly inhibits the activation of PBL by PHA, arrests ongoing DNA synthesis, and limits the duration of the DNA synthetic response to PHA at concentrations as low as 0.7 to 1.5 microgram LEx protein/culture. In contrast, human T lymphocyte E rosette formation is unaffected by LEx concentrations in excess of 900 microgram/culture. LEx has been partially purified by ultracentrifugation, ammonium sulfate precipitation, and molecular exclusion chromatography and appears to be a heat labile protein with a m.w. of approximately 65,000 and an isoelectric point of approximately 4.08. LEx is distinct from other previously described human immunoregulatory molecules and is potentially releasable in vivo from injured or necrotic liver cells. Because of its potency and anatomic distribution LEx may potentially modulate immunopathogenetic events responsible for assorted inflammatory and neoplastic liver diseases.