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To clarify the optimal dose of Lipiodol (Andre Guerbet, Aulnay-sous-Bois, France) during Lipiodol-transcatheter arterial embolization (L-TAE) and segmental L-TAE used to treat hepatocellular carcinoma, we studied the relationship between the volume of Lipiodol used during these procedures and the necrosis rates in resected specimens, as well as the correlation with the Lipiodol accumulation pattern based on the computed tomography findings (L-CT) and the volume of Lipiodol in resected and nonresected cases after L-TAE or segmental L-TAE. The L-CT and the dose of Lipiodol injected (mL) were studied correlatively in 198 cases (28 resected cases and 170 nonresected cases; tumor size < or = 5 cm in 52 cases and > 5 cm in 118 cases) that underwent L-TAE and in 80 cases (14 resected cases and 66 nonresected cases, tumor size < or = 5 cm in 52 cases and > 5 cm in 14 cases) that underwent segmental L-TAE. The L-CT was classified into four types: type I, homogeneous accumulation (type Ia, accumulation around the tumor; type Ib, no accumulation around the tumor); type II, partial defect; type III, sporadic accumulation; and type IV, punctate or no accumulation. In the 42 resected cases (L-TAE, 28 cases; segmental L-TAE, 14 cases), type I was seen in 68% (Ib, 100%) of the L-TAE cases and 93% (Ia, 79%; Ib, 14%) of the segmental L-TAE cases. The necrosis rate of the cases with type Ib L-CT was 90% to 100%, and all type Ia cases showed complete necrosis. In the 236 nonresected cases (L-TAE, 170 cases; segmental L-TAE, 66 cases), the volume of Lipiodol injected correlated with the L-CT type. In the L-TAE cases with a tumor size < or =5 cm, the frequency of the injected Lipiodol volume (D) being greater than the tumor diameter (d) (D > or = d) was 90%, and 87% of the cases with D > or = d showed type Ib L-CT. In the group whose tumor diameter (d) was more than 5 cm, the frequency of D > or = d was 25%, and 70% of the cases of D > or = d were type Ib. The frequency of D < d was 75%, and in 13% of these cases the L-CT was type Ib and the maximum dose was approximately 10 mL. In segmental L-TAE using the same dose of Lipiodol as in L-TAE, the frequency of D > or = d was 83%, and 93% of those cases showed type I, including 85% of type Ia. There was a correlation between the L-CT type and the necrosis rate, and type I, especially Ia in segmental L-TAE, showed complete necrosis in almost all cases. In L-TAE, standards for the optimal dose of Lipiodol are thought to be as follows: D > or = d in cases with d < or = 5, and slightly D < d and 10 mL maximally in cases with d > 5. In segmental L-TAE using the same dose of Lipiodol as in L-TAE, enhancement of the therapeutic effect was seen compared with L-TAE. This is surmised to have been because of the higher Lipiodol volume with anticancer agents per unit volume of the tumor in segmental L-TAE.

Purpose: To evaluate the feasibility of combining placement of a transjugular intrahepatic portosystemic shunt (TIPS) and transcatheter hepatic segmental artery chemoembolization with Lipiodol (Seg-Lp-TAE) in patients with cirrhosis, esophagogastric varices, and hepatocellular carcinoma (HCC)., Methods: Five patients with bleeding or large, high-flow esophagogastric varices and HCC were treated by TIPS and Seg-Lp-TAE., Results: The mean portosystemic pressure gradient decreased from 20.8 cm H2O to 7.8 cm H2O after TIPS. The direct portogram and endoscopic examination revealed reduction of varices. At 6 months, one shunt had functionally occluded and could not be reopened; the other TIPS remained functional. Follow-up CT and the changes of alpha fetoprotein indicated effective therapy of Seg-Lp-TAE for HCC. Four patients are in stabile clinical condition at 9, 6, 1, and 1 months after the combined therapy; one died after 14 months due to decompensated liver cirrhosis., Conclusion: The combined therapy of TIPS and Seg-Lp-TAE will become a new interventional approach for patients with HCC and esophagogastric varices.

Purpose: Multivariate analysis was used to study the effectiveness and optimum dose level of Lipiodol (LP) in transcatheter arterial embolization (TAE) of hepatocellular carcinoma (HCC)., Methods: A total of 219 cases of nodular type HCC, with a tumor diameter less than 7 cm, were studied. TAE was performed using both Gelfoam sponge (GS) and LP in 158 cases; in the remaining 61 cases only GS was used., Results: Statistical stepwise variable selection revealed that only LP had a negative T-value, suggesting that LP is a useful factor for prognosis. The most favorable effect on patient prognosis was obtained with an LP dose level (expressed in mm) of 1-1.5 times the absolute value of the tumor diameter (expressed in cm)., Conclusion: A significant difference (p < 0.01, log-rank test) in survival was found between the GS with LP group and the GS only group, using Cox's proportional hazard model.

We developed segmental Lp-TAE, which is transcatheter hepatic sub-subsegmental, subsegmental, or segmental chemoembolization using Lipiodol introduced into the tumor-bearing hepatic sub-subsegment, subsegment, or segment as the target area. A total of 98 patients with nonresectable hepatocellular carcinoma (HCC) undergoing segmental Lp-TAE (Seg-Lp-TAE) were studied, and the relationship between the CT pattern observed after Seg-Lp-TAE (Seg-Lp-CT) and the therapeutic results obtained in those patients was evaluated. Seg-Lp-CT was classified into four types (type I, homogeneous; type II, defective; type III, inhomogeneous; and type IV, only slight accumulation, if any) according to the Lipiodol accumulation pattern observed after Seg-Lp-TAE. The cumulative nonrecurrence rates of type I were higher than those of types II-IV. The cumulative survival rates of type Ia, in which Lp accumulation is also seen around the main tumor, were the highest (93.8% at 1 year, 85.9% at 2 years, 85.9% at 3 years, and 57.3% at 4 years). The cumulative survival rates achieved with Seg-Lp-TAE were 89.2% at 1 year, 69.4% at 2 years, 58.9% at 3 years, 44.0% at 4 years, and 30.2% at 5 years, which were higher than those achieved with conventional Lp-TAE. Seg-Lp-TAE is very useful in the treatment of HCC limited to one sub-subsegment, subsegment, or segment, and it is important to choose sub-subsegmental, subsegmental, or segmental Lp-TAE on the basis of the size and site of the tumor as well as the type and the number of feeding arteries.

To determine the effect of appraising subsegmental or segmental transarterial embolization with Lipiodol mixed with anticancer drugs followed by gelatin particles (Segmental Lp-TAE) on inoperable hepatocellular carcinoma, we examined CT patterns and therapeutic results in 57 patients after Segmental Lp-TAE. Fifty-six tumors including 47 tumors less than 5 cm in size were the nodular type and 1 tumor was the massive type. The mean tumor size was 3.6 cm and the mean amount of Lipiodol was 4.4 ml. Portal veins in the embolized segment were highly visualized by injected Lipiodol on plain film immediately after Segmental Lp-TAE. On the follow-up CT, the size of the tumor with dense Lipiodol accumulation were reduced in all cases, and atrophy of the embolized segment was recognized. Forty-four of the 57 patients are alive, with the longest surviving patient still alive at 4 years and 5 months. Seventeen patients have survived for more than 2 years (direct crude survival rate: 65.0%), with the cumulative survival rates 93.2% at 1 year, 71.6% at 2 years. No recurrence was recognized in 33 of the 41 patients (80.0%) that were followed up for more than 1 year after Segmental Lp-TAE is a useful therapeutic method for hepatocellular carcinoma.

The effectiveness of Lipiodol (iodized oil) in transcatheter arterial embolization (TAE) of hepatocellular carcinoma (HCC) was retrospectively evaluated using statistical analysis. A total of 343 HCC patients who underwent TAE at 5 institutions between 1984 and 1989 were divided into 2 groups: the GS-TAE group underwent TAE with Gelfoam sponge alone, whereas the LP-TAE group was given Lipiodol (LP) immediately before GS-TAE. The statistical T value calculated for the LP-TAE group showed that the administration of LP, the tumor size, intrahepatic metastasis, portal vein infiltration, and serum total bilirubin and alpha-fetoprotein levels significantly (P < 0.01) affected the patients' survival. Both the cumulative survival determined using the Kaplan-Meier model and the cumulative hazard calculated using Cox's proportional hazard model differed significantly (P < 0.01) between the GS-TAE group and the LP-TAE group (log-rank test). These results confirmed the effectiveness of LP used in combination with Gelfoam sponge for TAE of HCC.

We experimentally investigated the pharmacokinetics of adriamycin (ADM) in a similar of transcatheter arterial chemoembolization therapy (TAE) of hepatocellular carcinoma using emulsion of lipiodol (Lp) mixed with ADM followed by gelatin sponge, and the difference resulting from composition and method of preparation of the emulsion as well as behavior after mesenteric arterial injection in rat. In in vitro study, the emulsion with iopamidol (iopamiron 300 : IP) was more stable than with amidotrizoic acid (60% Urografin : UG). The highest stability was found in the mixing ratio of Lp. IP and distilled water at 1 : 0.42 : 0.08. Frequent pumping also made the emulsion more stable. But in optimally composed emulsion, pumping 20 or 50 times made no difference in the stability during 30 min. which may be longer than the time from preparation to injection time of the emulsion in clinical application. After injection of the emulsion into the mesenteric artery which may simulate injection into the hepatic artery in hepatocellular carcinoma, the arterial blood flow was suspended. In the peripheral arteries the emulsion separated into two phases of Lp and ADM solution, forming striped pattern, and Lp embolization of the peripheral artery persisted for over 45 min. while ADM extravasated. These findings suggest that after Lp-TAE, Lp maintains an embolizing effect while ADM penetrates into the surrounding tumor tissue, and that this is an underlying mechanism for the anti-cancer effect of Lp-TAE.

The behavior of an anti-cancer drug consisting of transcatheter hepatic segmental arterial chemoembolization using Lipiodol mixed with an anti-cancer drug followed by gelatin sponge (segmental Lp-TAE: Seg-Lp-TAE) was assessed in comparison to that of the non-segmental Lp-TAE to whole liver (Lp-TAE) by means of Tc-99m pertechnetate (RI). Injection of Lipiodol mixed with Adriamycin and 740 mBq of RI followed by gelatin sponge was carried out from segmental or subsegmental hepatic artery in 12 cases of hepatocellular carcinoma and from proper or right hepatic artery in 11 cases (9 with hepatocellular carcinoma and 2 with metastatic liver tumor). The distribution and retention of RI were studied from the time activity curves of ROIs in tumor and non-tumor area, and scintigrams at 4 and 24 hours after injection. The integral value ratio of tumor to non-tumor was significantly higher in Seg-Lp-TAE, indicating that es the distribution of RI after Seg-Lp-TAE is selective in the segments where tumor exists. In Seg-Lp-TAE, the T1/2 was higher and the count ratio of tumor to non-tumor was significantly higher at 4 hours and even higher at 24 hours after injection. These results suggest that an anti-cancer drug reinforces the effect on tumor with little adverse effect on normal liver in Seg-Lp-TAE, which is more advantageous to the treatment of hepatocellular carcinoma.

Transcatheter hepatic segmental arterial chemoembolization using Lipiodol mixed with an anticancer drug followed by the injection of Gelfoam particles, introduced into the tumor-bearing hepatic segment as the target area (segmental Lipiodol-TAE), was carried out in 54 patients with hepatocellular carcinoma (HCC), 7 of whom were later resected. In 5 of the resected 7 cases, complete necrosis was histologically verified. No death due to HCC was encountered in 47 nonoperated cases, and better therapeutic results were obtained with segmental Lipiodol-TAE. It was concluded that this technique does not adversely affect normal tissues, and it does reinforce the effect of TAE.

The therapeutic results of Lp-TAE (transcatheter arterial embolization with Gelfoam particles preceded by the infusion of a mixture of lipiodol and an anticancer drug via the proper hepatic artery) were evaluated in hepatocellular carcinomas (523 non-resected and 24 resected cases). Excellent therapeutic effects were confirmed not only for the main tumor but also for the daughter nodules by a histological examination of the liver tissues resected after Lp-TAE. The cumulative 1-year, 2-year and 3-year survival rates in the 523 non-resected cases were 60.4%, 42.9% and 28.0% respectively. These survival rates were all higher than those achieved by Gelfoam TAE. The above results suggest the usefulness of Lp-TAE in the treatment of hepatocellular carcinoma.

The detectability of small daughter nodules of hepatocellular carcinoma by computed tomography after hepatic arterial infusion of Lipiodol (iodized oil) and by infusion hepatic angiography was studied in 102 cases. The Lipiodol was selectively accumulated by the tumor. Tumors and small daughter nodules appeared as high-density areas on computed tomography. In 24 cases daughter nodules were identified only by computed tomography. In 50 cases computed tomography demonstrated superior ability to detect the daughter nodules when compared with infusion hepatic angiography. In 21 cases the daughter nodules were detected for the first time in areas other than the main site of the primary tumor. Lipiodol-computed tomography is very effective in the diagnosis of daughter nodules of hepatocellular carcinoma.