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The route, distribution and clearance of intraarterially administered Lipiodol in the liver has been the subject of much speculation. The hepatic microcirculation was therefore studied by in vivo microscopy after injection of Lipiodol into the hepatic artery and the portal vein in rats. After intraarterial injection, Lipiodol rapidly entered the portal branches through arterio-portal communications. Lipiodol also passed through the sinusoids from the portal into the hepatic veins and then into the systemic circulation. Sinusoidal congestion occurred when the oil droplets filled the liver microcirculation and resolved as the oil was cleared. It is of clinical significance to note the passage of the oil into the systemic circulation after arterial injection.

Iodinated lipid emulsions are highly efficient macrophage imaging agents. Nevertheless, none of them has been accepted for clinical use because of adverse reactions. We have tested a new iodinated lipid emulsion, Intraiodol. The size and surface properties of the particles of this emulsion are similar to those of Intralipid which in turn closely resemble the naturally occurring chylomicrons. Using computed tomography (CT) of the rabbit liver as well as vital microscopy and electron microscopy of the rat liver we found that Intraiodol has low efficiency as a liver-specific contrast medium because its particles are predominantly taken up by the hepatocytes and to a less extent by the Kupffer cells, as is Intralipid. The low efficiency of Intraiodol could be fully compensated by an increase in dosage without any significant effect on sinusoidal blood flow. This in turn suggests that the likelihood of release of toxic mediators (and thereby related adverse reactions from activated macrophages) is reduced. We believe that this new way of delivering iodinated lipid particles to the liver represents an important advance in the search for a non-toxic lipid emulsion for CT of the liver.

Iodinated lipid emulsions have been shown to have great potential as site specific contrast media for the liver and spleen. Because of unacceptable adverse reactions none of these emulsions has been adopted for clinical use. In an attempt to find an explanation for these adverse reactions we tested three iodinated lipid emulsions, EOE-13, AG 60.99 and AG 66.18. The following models were used: Computed tomography (CT) of the rabbit liver, in vivo microscopy and electron microscopy of the rat liver. The emulsions contained particles of different sizes and were used in varying doses. We found that the larger the emulsion particles, the more likely they were to be taken up by the Kupffer cells and thereby the higher the opacification of the liver achieved at CT. We also observed changes in the microcirculation of the liver when the emulsions were given in doses required to secure satisfactory opacification of the liver at CT. The main changes were 1) a marked increase in the size of the Kupffer cells, and 2) damage to the sinusoidal endothelium, both contributing to sinusoidal congestion. These changes strongly suggest activation of the macrophages and this in turn probably results in the release of toxic mediators. We suspect that the adverse reactions observed in patients when using iodinated lipid emulsions are due to these toxic mediators.

A new iodinated lipid emulsion, Intraiodol, for which animal studies have indicated better tolerance than for other iodinated lipid emulsions, was tested in 15 patients with malignant lesions, and in one patient with focal nodular hyperplasia. Repeated CT scans of the liver and spleen and blood tests were performed for 24 hours after intravenous injection of Intraiodol. The uptake of Intraiodol in the liver (peak mean 28.6 HU) was higher than in the spleen (peak mean 21.8 HU). The uptake of Intraiodol in malignant lesions was minimal (peak mean 2.8 HU). The detection rate of hepatic lesions was equal to or better than that achieved by US, CT, and/or CT angiography. However, liver uptake of Intraiodol was low in 2 patients with severe fatty infiltration. Intraiodol produced vascular enhancement up to one hour after injection since it was eliminated slowly from the circulation. The observed adverse reactions consisted of temporary metallic taste in 5 of the patients, fever and exacerbation of back pain in one patient, and transient thrombocytopenia in one patient. Alkaline phosphatase increased (17%, p<0.01) only at two hours, and erythrocyte count (6%, p<0.05) at 24 hours after injection. Our initial results indicate diagnostic advantages of Intraiodol without serious adverse reactions. Further clinical studies are required to confirm these findings.

After hepatic artery embolization with Gelfoam®powder in five rabbits, two colors of Microfil®(silicone rubber solution) were perfused into the aorta and the portal vein to study hepatic microcirculation under a dissection microscope. In three of the animals, many intrahepatic arterial branches and portions of the hepatic sinusoids were perfused with the arterial Microfil (orange color), whereas in the other two animals no orange Microfil was found in the liver. In the three animals, occlusions of the hepatic artery were random in distribution and often segmental, and arteries as small as 50 µm in diameter were involved. In the latter group, levels of arterial occlusion could not be evaluated. Microcollaterals developed through the capsular artery, peribiliary arterial plexus, and vasa vasora of the portal vein.

Angiography and computed tomography (CT) were performed in 96 patients before laparotomy for an intended liver resection. of these, 73 patients underwent liver resection, from a local excision to a trisegmentectomy. The accuracy of angiography in tumor localization was 77 per cent when the results were compared with the findings at laparotomy and from resected specimens. With CT the accuracy was 85 per cent. In 47 patients an analysis of the number of tumor nodules was possible. There were 76 nodules, and 42 (55) were correctly identified by angiography and 58 (76) by CT. Thirty-four tumor nodules were not seen at angiography, with the majority of these situated in the left liver lobe. At CT, 18 nodules were not observed, about equal numbers in right and left lobes. Five lesions thought to be present at angiography (9 at CT), could not be verified upon inspecting the resected specimens. Neither angiography nor CT seems to be reliable enough for an accurate prediction of resectability of liver tumors prior to laparotomy.

Sixty computed tomographic angiographic (CTA) examinations of the liver were performed with contrast injection into the coeliac axis. Data from both an arterial and a portal venous phase were recorded. In 41 patients it was possible to compare the results of CTA with palpation of the liver during laparotomy. The results from CTA and laparotomy were the same in 35 patients (85%). In one patient CTA disclosed verified liver lesions not diagnosed at laparotomy. There were 2 false negative and 3 false positive CTA examinations. In the remaining 19 patients, a clinical follow-up period of at least 6 months was used to evaluate the results of CTA. In the 7 patients in whom CTA showed benign lesions or a normal liver parenchyma, the clinical follow-up revealed no evidence of tumour growth in the liver.References

BackgroundOrthograde percutaneous isolated hepatic perfusion (IHP) techniques using balloon occlusion catheters are relatively simple and facilitate repeated therapy, but they result in higher rates of leakage from the perfusion circuit into the systemic circulation. Therefore, a feasible protocol for percutaneous IHP with less leakage is required.PurposeTo investigate hemodynamic changes in rat liver and tumor during retrograde-outflow isolated hepatic perfusion (R-IHP) with aspiration from the portal vein (PV).Material and MethodsAnimal experiments were approved by the Animal Experiment Ethics Committee of Lund University. Eighteen rats underwent R-IHP after laparotomy and catheterization of the PV and hepatic artery (HA). The HA, inferior vena cava (IVC), and PV were ligated, and flow through the suprahepatic IVC was controlled with a suture loop. The rats were divided into two groups to examine blood flow during R-IHP. Four rats (group 1) underwent arteriography via the HA with and without R-IHP, and 14 rats (group 2) were inoculated with tumor and examined by in vivo fluorescence microscopy of liver and tumor during R-IHP.ResultsIn group 1, hepatic arteriography during R-IHP confirmed arterioportal communication in all four rats, with the PV acting as an outflow tract. In vivo fluorescence microscopy in group 2 showed strong enhancement of tumors, and no blood supply from the portal venules to the tumors was seen in any of the 14 rats. Blood flow in the major portion of the hepatic lobules was stopped and the percentage of enhanced area was significantly lower in the normal hepatic lobules than in the tumors (P < 0.0001).ConclusionWe confirmed reversal of blood flow concomitant with good perfusion of the liver tumor and with reduced perfusion of normal liver parenchyma during R-IHP.