Yoshiyuki Shimamura

Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma — a comparison of lipiodol-transcatheter arterial embolization with and without Adriamycin (first cooperative study)

SummaryA randomized, controlled clinical trial comparing the use of lipiodol-transcatheter arterial embolization (L-TAE) in the presence versus the absence of Adriamycin (ADR) for the treatment of hepatocellular carcinoma was conducted from August 1988 through September 1989. In all, 125 Japanese hospitals participated in this study and 289 patients were entered in the trial. The patients were randomly allocated into group A (L-TAE) or group B (L-TAE+ADR) by telephone registration. There was no significant difference in background factors between group A and group B. Additional treatment, including repeated TAE or hepatic resection, was given to 189 patients. Among the four endpoints analyzed, the rate of tumor reduction and lipiodol accumulation in the tumor did not significantly differ between the two groups. The 3-year survival values for groups A and B were 33.6% and 34.9%, respectively; the difference was not significant. The serum alpha-fetoprotein level, however, decreased to a significantly greater extent in the group that received ADR than in the group that did not (P<0.05). This result suggests that ADR has some favorable additional effect in L-TAE for the treatment of hepatocellular carcinoma.

Combined peripheral and central chemoembolization of liver tumors. Experience with lipiodol‐doxorubicin and gelatin sponge (L‐TAE)

Patients with primary and a few with secondary liver tumors were embolized through the hepatic artery. Lipiodol and doxorubicin occluded peripherally, which was immediately followed by central embolization with gelatin sponge cubes. Preoperative embolizations were made for diagnostic and possible surgical adjuvant purposes. Extensive postembolization necrosis was common in tumors less than 5 cm in diameter, and tumor markers usually decreased temporarily after treatment. There were moderate side effects of pain, fever and nausea, and an acceptable complication and mortality rate with no deaths after embolization alone. This warrants further research on the method, which also seemed to improve the detection rate for small hepatocellular carcinomas.

A randomized trial of intrahepatic arterial infusion of 4′-epidoxorubicin with Lipiodol versus 4′-epidoxorubicin alone in the treatment of hepatocellular carcinoma

We conducted a prospective randomized trial to evaluate the efficacy of Lipiodol in intrahepatic arterial infusion chemotherapy for patients with hepatocellular carcinoma (HCC). A total of 38 patients with unresectable HCCs and underlying cirrhosis were entered in this trial, and 36 of them were evaluable. Every 4 weeks, 17 patients received 70 mg of 4′-epidoxorubicin (epirubicin) alone (group A), whereas 19 patients received a Lipiodol emulsion containing the same dose of epirubicin (group B) through the hepatic artery. A tumor response (CR+PR) was observed in 12% of group A patients and in 42% of group B patients. The group B patients showed a significantly higher response rate than the group A patients. There was a tendency for an increased duration of survival (P=0.09) in the group B patients. These results suggested that the infusion of the Lipiodol emulsion with epirubicin was more effective than epirubicin alone for the treatment of these patients with HCC.

Clinical and radiologic features of hepatocellular carcinoma originating in the caudate lobe

Five patients with hepatocellular carcinoma in the caudate lobe were evaluated. Computed tomography (CT) scan and/or angiography clearly demonstrated multiple intrahepatic metastases in four (80%), and tumor thrombi in the portal vein in two (40%), and in the inferior vena cava in one. Even though there was no recognizable lung metastasis, metastases were found in the orbita in one patient, and in the ribs and thoracic vertebrae in two patients. Four patients died after a mean period of 5.5 months from the initial diagnosis. The mechanism for early invasion into the vessels and multiple intrahepatic metastases of hepatocellular carcinoma arising from the caudate lobe is discussed.

Focal nodular hyperplasia of the liver : arterial angio-CT and microangiography

To differentiate focal nodular hyperplasia (FNH) from other hepatic tumors, especially hepatocellular carcinoma, we evaluated the hemodynamics of histologically proved FNH in three patients, two by arterial angio-CT and one by microangiography of the resected specimen. These studies demonstrated the centrifugal blood supply of FNH (early filling of central tumor vessels radiating to periphery, and lobulated tumor stains with central low density area in the late phase), which could not be demonstrated by dynamic CT or hepatic angiography. Arterial angio-CT is useful as a further study, when differential diagnosis of FNH is uncertain by other imaging techniques.

Bile duct carcinoma arising from the anastomotic site of hepaticojejunostomy after the excision of congenital biliary dilatation: A case report

A SIGNIFICANT ASSOCIATION between congenital biliary dilatation (CBD) mad hepatobiliary malignancies is well established, t The cause of the association is presumed to be the reflux of pancreatic juice into the bile duct and the accumulation of bile juice in choledochal cyst caused by anomalous un ion of the pancreaticobiliary ductal system. These malignancies arise mostly in the gallbladder and the extrahepatic bile duct. Therefore the standard surgical managemen t of CBD is to excise the whole extrahepatic bile duct and to perform hepaticoenterostomy. We will describe a case of a 60-year-old woman who had undergone cyst excision, cholecystectomy, and Roux-en-Y anastomosis for CBD (Todani s classification type I) 5 years earlier and who suffered from bile duct carcinoma arising in the anastomotic site of hepaticojejunostomy. This is the second reported case of a carcinoma that arose from the anastomotic site of hepaticojejunostomy for CBD.

Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma—a comparison between L-TAE with Farmorubicin and L-TAE with Adriamycin: preliminary results (second cooperative study)

A randomized controlled clinical trial was conducted to compare the use of Farmorubicin (FARM) and Adriamycin (ADR) in Lipiodol transcatheter arterial chemoembolization (L-TAE) as a treatment of hepatocellular carcinoma. In all, 192 hospitals participated, and 415 patients were enrolled in the study during the period from October 1989 through December 1990, and their data were collected. The patients were randomly allocated to group A (FARM) or group B (ADR) by a central telephone registration. Several clinical characteristics were slightly worse in group A than in group B, but there was no statistically significant difference. The actual doses of FARM and ADR were 72 mg/body and 48 mg/body, respectively. Additional treatments, including repeated TAE or surgery, were given to 248 patients. The 1- and 2-year survival rates were 69% and 44% for group A and 74% and 57% for group B, respectively. The difference was marginally significant (P value in the log-rank test, 0.038). When each group of patients was classified into two subgroups, i.e., high-risk and low-risk categories, based on the severity index calculated by the Cox regression model from significant prognostic factors, the ADR subgroup was significantly superior to the FARM subgroup in the low-risk category, but there was no significant difference between the subgroups in the high-risk category. The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction did not show any significant difference between the groups. At the above-mentioned doses, ADR seemed to have efficacy almost the same as or slightly superior to that of FARM in L-TAE for the treatment of hepatocellular carcinoma.

Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma. A comparison of L-TAE with farmorubicin and L-TAE with adriamycin (second cooperative study

SummaryA randomized clinical trial comparing L-TAE with Farmorubicin (FARM) and L-TAE with Adriamycin (ADR) in the treatment of hepatocellular carcinoma was conducted from October 1989 through December 1990. In all, 192 hospitals participated in this study and 117 patients were entered. The patients were randomly allocated to group A (L-TAE+FARM) or group B (L-TAE+ADR). There was no significant intergroup difference in background factors. Additional treatment consisting of repeated TAE or surgery was given to 66 patients. Four factors were analyzed in this study: the percentage of reduction in tumor size, the change in the AFP level, lipiodol accumulation, and survival. None of these factors differed significantly between the two groups. The final evaluation of this study will be based on differences in survival after a long-term follow-up. Toxic effects manifested less frequently in group A than in group B, and the decrease in the platelet count in the peripheral blood was significantly lower in group A than in group B. These results suggest that FARM exerts a more favorable effect than does ADR in the treatment of hepatocellular carcinoma.

Management of Metastatic Liver Cancer

One hundred and twenty-four patients with metastatic liver cancer were treated in National Matsudo Hospital between June 1980 and December 1987. They received multi-disciplinary treatment and 40 of them underwent hepatectomy. The survival rate after hepatectomy for metastatic liver cancer was better than without hepatectomy, but there was no significant difference in the prognoses of gastric and colorectal cancer liver metastases after hepatectomy. The prognosis after hepatectomy was similar between synchronous metastases and metachronous metastases and the survival rate after liver resection was the same for solitary and multiple lesions. These results suggest that surgical reduction of liver metastases is a good treatment. In addition, there was no significant difference between the survival rate of patients with unresectable liver metastases who were treated with transcatheter arterial embolization and with hepatic arterial infusion of an anticancer agent emulsified in a lipid contrast medium.

Juxtacaval liver resections with the use of an internal IVC shunt tube.

Almost one tenth of more than 370 hepatectomies, mostly for tumors, involved resection of major parts of the caudate lobe, subsegment 1. Five of them were for tumors or hemangiomas here, compressing or invading the vena cava; two were for metastases of colorectal cancer located very close to the junctions of the right and middle hepatic veins with the vena cava. We would previously have deemed these tumors unresectable. In these patients the vein was banded above and below the liver, an internal shunt tube placed in preparation for shunting of blood, and the afferent liver blood flow controlled. Control of the vena cava by tightening of the bands was needed in two cases. Tumor-invaded parts of the vein wall were resected in two other cases, in whom the presence of the tube facilitated the resection but the bands did not have to be tightened. The procedure did not cause morbidity and we conclude that tumors close to the vena cava can often be resected without complex vascular exclusion techniques, even when they invade the vein.