Lipiodol and dye at the site of ablation decreases during RFA.

OBJECTIVES: Intrahepatic metastasis is one of the serious complications of radiofrequency ablation (RFA) therapy for hepatocellular carcinoma. The aim of this study was to investigate how liver tissue could be disseminated during the RFA procedure with different devices and protocols in an in vivo porcine model. METHODS: Three pigs underwent RFA procedures using 2 different devices: needles that could be expanded (LeVeen needle) and those that could not (cool-tip needle). A LeVeen needle was used with a single-step full extension method or a stepwise extension method. Before RFA, a mixture of lipiodol and blue dye was injected intrahepatically into a precoagulated area. After the ablation procedure, the specimen was cut to evaluate the amount of dye remaining in the ablated region and the distribution of the dye outside the ablated area. RESULTS: The stepwise extension method resulted in the disappearance of the smallest amount of the dye and lipiodol at the ablation site, compared with the full extension method and cool-tip needle. Dye was found at sites distant from the ablated area in all cases using the cool-tip needle, but in none with the stepwise extension method. CONCLUSIONS: The stepwise procedure using the expandable needle can reduce tumor cell scattering, which can cause intrahepatic metastasis, compared with other methods.

Use of oily contrast medium for selective drug targeting to tumor: enhanced therapeutic effect and X-ray image.

Highly malignant rabbit tumor (VX-2) was implanted at the periphery of the liver in 63 rabbits. Selective delivery of the anticancer agent copoly(styrenemaleic acid) conjugated to neocarzinostatin (SMANCS), which was dissolved in an oil contrast medium (Lipiodol), was performed by injection via the proper hepatic artery. The anticancer effect was also evaluated by various parameters. By using low-kVp X-ray examination of the resected rabbit liver, Lipiodol was found to distribute throughout the entire liver arterial lumina and was retained there for about 24 hr, but disappeared from the normal liver arterial lumina gradually. However, Lipiodol was retained in the tumor tissue and vessels for at least 7 days, whereas it was undetectable in any other organs. A radioactive analogue of Lipiodol, a chloroiodinated fatty acid, was prepared by using [14C]linoleic acid. This analogue was used in the study of the distribution by low-kVp X-ray examination, Sudan III staining, and autoradiography. Lipiodol remained in the tumor vessels as well as the tumor cells. The use of the radioisotope yielded a quantitative profile of Lipiodol accumulation in tumor tissues; approximately 1000 times more at 15 min and 100 times more at 3 days after the injection than that of most other organs or plasma. Its major excretion route appeared to be through the bile and then the feces. The biological activity of SMANCS was also determined and was found to be significant in both tumor and liver even 7 days after injection. No activity was found in any other organ or tissue. The relatively high biological activity of SMANCS in the nontumorous liver adjacent to the tumor may be the result of continuous drug release from SMANCS-Lipiodol in the tumor tissue. By histological examination, massive tumor necrosis and infiltration of the inflammatory cells were found in the rabbits treated with SMANCS-Lipiodol. In the rabbits treated with Lipiodol alone, necrosis of the tumor was only minimal, and no infiltration of inflammatory cells was observed. Survival periods of the treated rabbits (n = 14) were significantly longer than those of controls (n = 10); 23.1 +/- 5.5 (S.D.) days versus 16.1 +/- 2.9 days (p less than 0.005), respectively, even though only one injection was used for this highly malignant tumor. Mean tumor size for both groups at laparotomy was 163.3 +/- 83.0 sq mm and 160.5 +/- 76.5 sq mm, respectively (not significant).(ABSTRACT TRUNCATED AT 400 WORDS)

New model for describing urinary iodine excretion: its use for comparing different oral preparations of iodized oil.

Iodine excretion in urine after oral dosing with iodized oil is influenced by various factors involved in the retention and elimination of iodine by the body. In a study comparing different treatments of severely iodine-deficient schoolchildren from Malawi, a hyperbolic function was found to describe changes in urinary iodine concentration over time more adequately than a simple exponential function. Compared with oil A, comprising ethyl esters of iodized fatty acids, the retention and elimination of iodine from oil B, comprising triacylglycerol esters of iodized fatty acids, were significantly greater. The mean duration of effectiveness of oral iodized oil, based on urinary iodine concentrations > 0.40 mumol/L, was estimated to be 13.7, 9.9, and 52.5 wk for a single dose of iodized oil A (490 mg I), a split dose of iodized oil A (2 x 245 mg I), and a single dose of iodized oil B (675 mg I), respectively. Dividing the dose of oil A into two equal amounts given on consecutive days did not improve its efficacy.

Lipiodol accumulation in hepatic hemangioma. Detection with osmium postfixation.

Lipiodol has been used to increase the detectability of small primary neoplasms in the liver. We report a patient who was found to have lipiodol deposits in the liver one month after intra-arterial injection. The region was resected, under ultrasound control, because of the impression that the lesion was malignant. The specimen contained two small hemangiomas as well as many small dysplastic nodules (adenomatous hyperplasia) in a noncirrhotic parenchyma. To locate the lipiodol deposit in this case, the tissue was radiographed, postfixed in osmium tetroxide, and embedded in paraffin. Black osmium-stained deposits were found within the cavities of the hemangiomas but not in the dysplastic nodules. Most of the deposits were extracellular multivesiculated bodies with a small focus of lipid droplets engulfed by multinucleated foreign-body type giant cells. This report reinforces that hepatic lipiodol retention is not specific for hepatocellular carcinoma. We present, for the first time, the histologic appearance of lipiodol accumulation in an hemangioma. The value of osmium tetroxide postfixation for the detection of lipiodol is also demonstrated.

Effect of particle size on the tissue distribution of iodized emulsified fat following intravenous administration.

Three iodinated fat emulsions were tested by intravenous injection to rats: coarse with a mean size of particles of 7 micrometers, fine with a mean size of 1.3 micrometers, and ultrafine with a mean size of 0.7 micrometers. Iodine content analysis and scintigraphy of radioactive iodinated emulsions show important differences. Coarse emulsion is almost entirely fixed in the liver and the lungs; fine emulsion has a higher relative liver fixation; and ultrafine emulsion has a hepatosplenic fixation of short duration. Degradation of contrast medium is slow with coarse emulsion and very fast with ultrafine emulsion which is responsible for the rising iodine concentration in blood. Fine emulsion is a good compromise between excessive pulmonary fixation of coarse emulsion and high iodine peak in the blood after injections of ultrafine emulsion. The dose of 0.2 ml/kg of fine emulsion gives persistent enhancement of hepatic parenchyma without significant toxicity.

Demonstration of Lipiodol in paraffin sections using a modified silver impregnation technique.

To demonstrate postangiographic Lipiodol (LIP) in hepatocellular carcinoma (HCC) in paraffin sections, direct impregnation of formalin-fixed tissue blocks with silver nitrate (AgNO3) was followed by routine processing. LIP appeared as black globules in the sinusoids. Ninety-four tissue blocks from 13 postangiographic LIP HCCs and 69 from 8 non-LIP HCCs and 4 fatty livers were studied. Seventy-two of 73 negative controls and all positive blocks as seen on soft tissue radiographs (STRs) were correctly coded (specificity 98.6%, sensitivity 100%). Twenty-six of the 44 LIP-negative areas on STRs from LIP cases contained scanty globules of less than 10 microns in diameter. Fatty change gave no positive readings. Thus, modified AgNO3 impregnation is a simple, accurate means of detecting LIP in high-quality paraffin sections suitable for tumor diagnosis and, if applied to postangiographic LIP, ultrasonographically guided liver biopsy, can verify that a biopsy has reached a suspected tumor focus.

Distribution of Lipiodol and evidence for tumor necrosis in hepatocellular carcinoma.

To study the distribution and thromboembolic effect of Ultrafluid Lipiodol, 15 surgically removed hepatocellular carcinomas with selective intraarterial Lipiodol injection 7 to 10 days before surgery and 15 noninjected controls were studied radiologically and histologically. Tissue blocks were processed with an en bloc silver impregnation technique for Lipiodol localization in histologic sections. Lipiodol was distributed evenly in tumors measuring less than 5 cm in diameter and peripherally in tumors measuring 10 cm or more. Lipiodol droplets were mainly extracellular. There was no difference in tumor architecture or in hemorrhage and necrosis scores between Lipiodol-injected cases and negative controls (1.18 versus 0.92). Similarly, in injected cases, no differences were observed between Lipiodol-positive and Lipiodol-negative areas (scores of x-ray Lipiodol-positive versus Lipiodol-negative areas: 1.17 versus 1.36; scores of microscopic Lipiodol-positive versus Lipiodol-negative areas: 1.18 versus 1.14). Lipiodol-negative but hypodense areas examined by x-ray proved to be necrosis or fibrosis with or without viable tumor islands. Lipiodol has no thromboembolic effects. The uneven Lipiodol distribution may account for its failure as a carrier for chemotherapeutic agents in large tumors.

Clinicopathological study on combination therapy consisting of arterial infusion of lipiodol-dissolved SMANCS and transcatheter arterial embolization for hepatocellular carcinoma.

Combination therapy (LpTAE) consisting of arterial infusion of a lipophilic anticancer drug, SMANCS, dissolved in an oily lymphographic agent, lipiodol (LPD), and transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) was studied with special reference to the pathological findings. A total of 32 patients were subjected to surgical resection after LpTAE. The pattern of LPD deposition in the tumor was examined by CT scan (Lipiodol CT, LpCT) at 7 days and/or 1 month after LpTAE. The resected materials were examined radiographically with soft X-rays and histologically. LPD was deposited in tiny daughter nodules with a diameter of less than 5 mm and in tumor thrombi as well as in the main tumors, which showed necrotic change. Part of the LPD flowed out from the main tumor via the drainage vein and was deposited in the capsular invasion, resulting in necrosis. LPD accumulated almost exclusively within the blood spaces of trabecular-type HCC, creating a pattern corresponding to a cast of the tumor vessels, which showed prominent necrosis. On the other hand, LPD was not deposited in scirrhous, compact, or well-differentiated HCC, which showed little or no necrosis. It was demonstrated that LpCT images, which accurately depicted the existence and the extent of LPD deposition and necrosis in the tumor, were useful for precise evaluation of the therapeutic effect. Our findings indicate that LpTAE and LpCT are valuable for the diagnosis and treatment of HCC and should play a central role in systemic therapeutic approaches to this disease.

Tumor targeting by arterial administration of lipids: rabbit model with VX2 carcinoma in the liver.

We previously found that a lipid contrast medium, Lipiodol, remained selectively in liver tumors for a prolonged time after injection via the hepatic artery. We now extend this technique to other lipids including linoleic acid, olive oil, tea seed oil, and medium-chain triglyceride (MCT). MCT is a semisynthetic triglyceride with a lower viscosity than that of the other lipids. Each lipid was mixed with 14C linoleic acid, and the mixture with or without anticancer agent smancs was injected via the proper hepatic artery of rabbits with VX2 carcinoma in the liver. The 14C count in the tumor tissue was always more than 100 times that of the plasma or kidney, and the radioactivity 15 min after injection of MCT was more than 2500 times greater than that of blood plasma. At 24 hr after injection, the radioactivity recovered in the tumor was 4.9-37.0% (average 19.6%) of the dose, which indicated the greatest retention in the tumor tissue; there was rapid clearance from the rest of the body primarily via the bile. Advantages of the administration of lipid-solubilized drugs are: (i) remarkable tumor-selective targeting (a decisive anticancer effect with fewer side effects); (ii) prolonged drug retention (resulting in infrequent administration); (iii) various choices of different fatty acids with various pharmacokinetic characteristics as the carriers of the anticancer agents; and (iv) arterial administration is practicable in most hospitals.

Lipiodol avid liver metastases from adrenocortical carcinoma; prospects for therapy?

A young lady with liver metastases from adrenocortical carcinoma was given a tracer dose of lipiodol into the hepatic artery and her liver metastases were shown to be extremely lipiodol avid. A therapeutic dose of lipiodol I131 was then given. There was not, however, any evidence of response to this treatment.

Lipiodol UF retention in dental sialography.

Lipiodol is a lipid based contrast medium and is very useful in sialography. It gives very fine images and clearly shows the details of the gland. It is viscous and has a relatively high iodine content. However, lipiodol UF drops sometimes remain in the salivary gland and in the adjacent tissues for a long time and may cause irritation. We report a case where lipiodol UF leaked from Stensen's duct and was not resorbed after a period of 70 months.

Lipiodol computerized tomography: how sensitive and specific is the technique in the diagnosis of hepatocellular carcinoma?

Computerized tomography (CT) following the intra-arterial injection of Lipiodol (Lipiodol-CT) was performed on 60 patients suspected of having a hepatocellular carcinoma (HCC). Four main patterns of uptake of the Lipiodol within the liver were seen on CT. Of the 14 well circumscribed lesions with dense homogeneous uptake of Lipiodol, 13 were confirmed to be HCCs. Of the 25 lesions with dense patchy uptake of Lipiodol at the periphery and/or in the centre, 19 were confirmed to be HCCs. In 18 patients, in whom only ill defined faint patchy uptake of Lipiodol was present in the liver, or in whom no hepatic uptake was present at all, only one patient was found later to have an HCC. Of the three hypodense lesions in the liver with no Lipiodol uptake, one was found to be necrotic HCC, one a cholangiocarcinoma and one a regenerative nodule. In the diagnosis of HCC, Lipiodol-CT had an overall sensitivity of 97.1%, an accuracy of 88.3% and a specificity of 76.9%. Of the 34 patients with HCC, only 23 were solitary at diagnosis. The size of the HCCs ranged from 0.8 cm to 11 cm in diameter with the median size at 2.2 cm. Eleven of 34 HCCs (32.3%) were resectable. We conclude that, as part of a screening programme for high risk patients. Lipiodol-CT is useful in the early detection of HCCs. The technique also plays an important role in determining whether the tumour should be resected or managed with chemotherapy. By detecting HCCs while still small, the resectability rate can also be improved.

[In-flow of contrast into the liver--a rare complication during lymphography (author's transl)]. / Kontrastmitteleinschwemmung in die Leber--Eine seltene Komplikation bei der Lymphographie.

A lymphogram is described in which Lipiodol was found to have reached the liver from pelvic lymphatics. The common iliac and para-aortic lymph nodes had been invaded by tumour from a squamous carcinoma and this had produced complete lymphatic obstruction of the normal lymph paths. In addition, there was occlusion of the bifurcation of the iliac veins due to tumour, a finding also described by other authors. The causes for the finding of Lipiodol in the liver are discussed. The pathway by which the Lipiodol had reached the liver from the pelvic lymphatics, and the reaction of the liver parenchyma to the contrast medium, are considered.

[Interference factors in the in vivo diagnosis of the thyroid]. / Störfaktoren bei der In-vivo-Diagnostik der Schilddrüse.

Anamnestic iodine contamination and medication with thyroid drugs were registered in 260 patients of a clinical thyroid care unit and 200 patients of a thyroid doctor's office in the southern German endemic goiter region. We found in the university clinic 54% patients with interfering factors, 30% with iodine contamination and 20% with multiple interferences. In the physician's practice there were 18%, nearly all treated with thyroid hormone. The influence of those factors on thyroidal technetium uptake and the resulting restriction on its diagnostic value is discussed.

Distribution pattern of radioactive labelled lipiodol-UF following intralymphatic application for therapy.

Endolymphatic radiotherapy with 4 mCi32P tri-n-octylphosphate and 1 mCi 131 I triolein LIPIODOL UF has been performed in 75 patients suffering from malignant melanoma of the lower extremity. On the average, 13.3% of the radioactive substance remains in the syringes and connecting tubes. In most patients the radioactive material available for therapeutic irradiation is further reduced due to contamination of operation sheets and swabs (mean: 15.3%). There is, however, still sufficient radioactivity remaining for effective internal irradiation of the lymph nodes. The average radiation dose absorbed by the lymphatic tissue is 90.998 rad. The method is limited by the hazard of radiation damage to the lungs. Almost 80% of these patients had detectable concentrations of radioactivity in the lung fields. The average radiation dose was found to be 299 rad. So far radiation induced fibrosis has bot been observed in this series.

[Lipiodolized angiography in hepatocellular carcinomas. Contribution of iodine-131-labelled lipiodol]. / L'angiographie lipiodolée au cours des carcinomes hépato-cellulaires. Apport du lipiodol marqué à l'iode 131.

Twelve patients with hepatocellular carcinoma and cirrhosis were investigated by Lipiodol injection into the hepatic artery. A CT scan was done 4-6 days later. Lipiodol was retained by hepatic tumors in each case. This method emphasized the extension of the carcinoma and allowed to discover daughter tumors. I131-lipiodol was also injected in 4 of the 12 patients and then its biodistribution was evaluated. At the 6th hour after injection, I131-lipiodol was detected by scintigraphy over the liver (74-91 percent) and over the lungs (9-16 percent) only. The tumor to normal liver pixel count ratio was about 5. These results indicate that there is a preferential arterial blood flow towards the hepatic tumors, and that we can consider a therapeutic use of I131-Lipiodol in hepatocellular-carcinoma.

[Magnetic resonance behavior of lipiodol--an experimental study].

OBJECTIVE: To describe the characteristics of magnetic resonance (MR) signals generated by lipiodol and to assess the influence on MR imaging of hepatoma nodule. METHODS: Pure lipiodol and lipiodol emulsions mixed with 76% urografin in different ratio were imaged by both CT and MR; quantitative T(1) and T(2) measurements of lipiodol were performed. Fourty-one SD rats with transplanted walker-256 sarcoma in liver were randomly divided into six groups: 0.4-0.6 ml lipiodol emulsion was infused via hepatic artery in experimental groups by means of laparotomy under celiac anesthesia. The changes in MRI signal of hepatoma nodule were observed. RESULT: In vitro, iodized oil demonstrated high signal on T(1)-weighted images when performed at 37 degree, but all could be suppressed by the fat saturation sequence, and showed very low signal on T(2)-weighted images. The characteristic of MR signal with ultra fluid lipiodol was different from that of iodized oil (P<0.01), showing short T(1) and long T(2) signal; the high signal on T(1)-weighted images was only partially suppressed by the fat saturation sequence. With descending ratio of lipiodol in emulsion, the signal behavior was gradually similar to urografin (r -0.958, P<0.01). When rats were transarterially infused with emulsion, the intensity of the signal on MRI was nearly the same as that in the control rats, but when lipiodol was injected out of the hepatic artery and accumulated in lymphadenopathy, it demonstrated a signal similar to fat; the high intensity signal was maintained on T(1)-weighted images and T(2)-weighted images. CONCLUSION: There are little changes in MR signal intensity when the lipiodol is accumulated in the tumor nodules. MR behavior of lipiodol is determined by its deposit area.