Junnosuke Kojima

Treatment of hepatocellular carcinoma by transcatheter arterial embolization combined with intraarterial infusion of a mixture of cisplatin and ethiodized oil

The therapeutic effectiveness of transcatheter arterial embolization (TAE) with intraarterial infusion of cisplatin/ethiodized oil mixture in treatment of resectable and unresectable hepatocellular carcinoma was compared with TAE with intraarterial infusion of doxorubicin mixed with and without ethiodized oil. The series included 97 patients with unresectable hepatocellular carcinoma and 40 patients with resectable hepatocellular carcinoma. With TAE using doxorubicin infusion, a partial response of the tumor was seen in only 11%, and the 2-yr survival was calculated to be only 5%. Histologic examination of the specimens obtained by hepatectomy also showed that this treatment was relatively ineffective in daughter tumor and portal tumor thrombi. In contrast, TAE with infusion of cisplatin/ethiodized oil mixture significantly increased the rate of partial response (38%), and significantly prolonged the 2-yr survival (45%). Histologically this treatment gave severe necrosis in daughter tumors (69%) and tumor thrombi (78%) as well as main tumor (75%). This treatment was significantly better than TAE with doxorubicin and ethiodized oil infusion in terms of the tumor regression and histologic responses of main tumor and portal vein tumor thrombi, but not in terms of the 2-yr survival. However, 2 patients (8%) died within 4 wk of the latter treatment, whereas no deaths were reported after the former treatment. Therefore, TAE combined with intraarterial infusion of cisplatin/ethiodized oil mixture may be a safe and useful treatment modality for hepatocellular carcinoma.

Regional therapy in the management of intrahepatic recurrence after surgery for hepatoma.

The significance of regional therapy against the intrahepatic recurrence for hepatocellular carcinoma (HCC) was evaluated. During the past 6 years, 101 patients who had radical operations for HCC (liver cirrhosis, 75%; chronic hepatitis, 22%) were followed. Forty-seven patients (47%) had recurrences; the liver was the site of first recurrence in 43 patients and distant site recurrence in four patients. In the patients where the liver was the recurrent site, 33 patients (77%) received regional therapies for an aggregate total of 60 times. Transcatheter arterial chemoembolization was chosen as the first preferred therapy against recurrence in the liver in 30 of 33 patients (91%). Postrecurrence survival of the patients treated with regional therapy was significantly better than disease-free survival (p less than 0.001). Disease-free survival after surgery, postrecurrence survival, and postsurgery survival were compared in the patients treated with regional therapy and untreated patients. Fifty per cent survival after recurrence of the treated patients was 27 months, and that of the untreated patients was 3 months. Postrecurrence survival (p less than 0.001) and postsurgery survival (p less than 0.01) of the treated patients were significantly better than those of the untreated patients. To obtain successful long-term survival after surgery for the cirrhotic patients with HCC, it is necessary to repeat active regional therapies against the recurrent liver.

A pre-operative chemoembolization therapy using lipiodol, cisplatin and gelatin sponge for hepatocellular carcinoma

SummaryThe significance of pre-operative transcatheter arterial chemoembolization therapy using lipiodol, cisplatin and gelatin sponge (Gelfoam) for the prevention of the recurrence of hepatocellular carcinoma (HCC) was evaluated. On the 103 patients who underwent radical operations for HCC with a tumor size less than 10 cm, 52 patients received no pre-operative therapy (group C), and 51 patients received pre-operative chemoembolization using lipiodol, a chemotherapeutic agent and Gelfoam. Of these 51 patients, 37 patients received a combination of lipiodol, cisplatin and Gelfoam (group A), while the remaining 14 patients received lipiodol, adriamycin and Gelfoam (group B). The disease-free survival rates after surgery were compared between group A, group B and group C. The 2-year disease-free survival rates in group A, group B and group C were 72%, 46% and 54%, respectively. These rates therefore suggest that pre-operative chemoembolization using lipiodol, cisplatin and Gelfoam is a useful method to prevent the recurrence of HCC after surgery.

Recent advances in ultrasonographic diagnosis of hepatocellular carcinoma

The diagnostic accuracy of ultrasonography (US) for hepatocellular carcinoma (HCC) was estimated by checking against the regional cancer registry, and also the clinical features, major therapy, and prognosis of HCC cases diagnosed by initial US were examined for the two periods of 1980 and 1984. The number of patients with HCC was 83 of 4442 in 1980 and 86/3393 in 1984. As for the detectability of the tumor, the sensitivity improved from 94.0% to 96.5%. Regarding the ability to confirm the detected tumor to be HCC, the sensitivity improved from 53.0% to 68.6% without decrease in the specificity of 99.9%. The size and number of nodules were more accurately diagnosed in 1984, and cases with small (⩽4 cm) single nodule increased from 2% to 9%. Active therapy was performed in more cases and the 2‐year survival rate increased from 9% to 20%. The remarkable improvement was achieved in the diagnostic accuracy of US for HCC during 4 years from 1980 to 1984.

Electrophoretic fractionation of serum γ-glutamyl transpeptidase in human hepatic cancer

Abstract Serum γ-glutamyl transpeptidase from patients with various hepatobiliary diseases was fractionated by polyacrylamide gradient gel slab electrophoresis to study the specific patterns of γ-glutamyl transpeptidase fractions in hepatic cancer. On zymograms of normal serum γ-glutamyl transpeptidase, a total of 10 fractions was observed. Additionally, fractions I′, I″ and II′ were recognized in sera from hepatocellular carcinoma patients. Among these, fraction I′, which migrated slightly, but significantly, slower than fraction I was the most specific; it was found in 55% of the hepatocellular carcinoma patients. Fractions I″ and II′ were also relatively specific, each was observed in about 29% of these patients. Fractions V to IX were observed in few hepatocellular carcinoma cases. Fraction I′ is thought to be a hepatoma-related fraction, highly specific for the serum of hepatocellular carcinoma patients. Fractions I″ and II′ were also thought to be hepatoma-related fractions of 7-glutamyl transpeptidase. We suggest that fractions I′, I″ and II′ may be useful in the diagnosis of hepatocellular carcinoma.

Glycylproline dipeptidyl aminopeptidase and γ-glutamyl transpeptidase in human hepatic cancer and embryonal tissues

Changes of glycylproline dipeptidyl aminopeptidase (GPDA) and gamma-glutamyl transpeptidase (gamma-GTP) activities and their subcellular distributions were compared in human hepatic cancer and embryonal tissues. The activity of GPDA in cancer tissues was significantly higher than that found in healthy liver, though there were no significant differences between fetal and adult livers. The placenta, however, had the highest GPDA activity. The activity of gamma-GTP, on the other hand, was increased significantly not only in cancer tissues but also in live tissues adjacent to the tumor, and it was higher in the fetal liver but much lower in the placenta. Subcellular distribution of GPDA was also different from that of gamma-GTP in cancer tissues, especially after postmortem changes. These results suggest the possibility that GPDA has carcinoembryonic characters similar to gamma-GTP, but the mechanisms, whereby serum activities of these two enzymes were increased in hepatocellular carcinoma patients, are different from each other.

Changes in the cellular glycosaminoglycans of cultured mastocytoma cells induced by sodium butyrate

The effect of sodium butyrate on the cellular glycosaminoglycans of cultured mastocytoma p-815-4 cells was investigated using enzymic digestion, electrophoresis, nitrous acid degradation, and sequential partition fractionation. The average cellular glycosaminoglycan content of mastocytoma p-815-4 cells grown in the presence of 2 mM sodium butyrate was ten times as much as that of the control p-815-4 cells. Approximately 90% of the glycosaminoglycans isolated from the control cells and 70% from the butyrate-treated cells were found to be chondroitin 4-sulfate by enzymic digestion. The remainders were chondroitinase ABC-resistant. Hyaluronic acid and dermatan sulfate were not detected in either control cells or butyrate-treated cells. The chondroitinase ABC-resistant fraction of glycosaminoglycans from butyrate-treated cells showed a molar ratio of sulfate to uronic acid of more than 2.0, and provided some physicochemical properties characteristic to reference bovine lung heparin.

Carcinoembryonic proteins in gastric carcinoma metastatic to the liver

SummaryTwo cases of liver metastases from gastric carcinoma are described in which the simultaneous occurrences of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carcinoplacental alkaline phosphatase (CPALP) were demonstrated in the sera and tumor tissues. AFP was detected not only in the tumor tissues but also in the liver tissue adjacent to the tumor, while the other 2 carcinoembryonic proteins were not detected in the non cancerous liver tissues. The characteristics of CPALP in Case 1 were almost similar to the Nagao isoenzyme, based on enzyme tests involving L-leucine, L-phenylalanine and EDTA inhibitions, heat-stability and Michaelis constant, except for electrophoretical slower moving, while that in Case 2 were identical to variant type CPALP (Warnock).

Prediction of sustained response to interferon alpha therapy with serum soluble interleukin 2 receptor levels in patients with chronic hepatitis C

Abstract It is difficult to predict sustained response to interferon alpha therapy for patients with chronic hepatitis C. Loss of serum hepatitis C viral RNA (HCV-RNA) and normal serum alanine aminotransferase (ALT) level at the end of treatment do not necessarily mean sustained response. Relapses are very common. In this study, serum levels of soluble interleukin 2 receptor (sIL-2R, an indicator of immune response) were investigated to see if they are helpful to predict sustained response. We studied consecutive twenty patients with chronic hepatitis C who had HCV-RNA negativity and normal ALT levels at the end of interferon alpha therapy. Total doses of interferon ranged from 288 million units (MU) to 480MU. Serum HCV-RNA sequences were examined before and at the end of treatment by nested polymerase chain reaction (PCR) using primers to the 5′ noncoding region. Serum sIL-2R levels were also measured before and at the end of treatment using enzyme-linked immunoassay. Eight of twenty (40%) patients were sustained responders and the rest of the patients (60%) relapsed (partial responders). Serum sIL-2R levels in sustained responders decreased (−96.2 ± 45.2 IU/l), whereas partial responders showed increase in serum sIL-2R levels (81.3 ± 50.5 IU/l). The difference in sIL-2R changes between sustained responders and partial responders was significant (P

A quantitative study on distortion of hepatic lobular architecture in needle biopsy specimens obtained from alcoholics

アルコール多飲者の肝生検標本のうち,アルコール性肝炎に特徴的といわれる所見に乏しくかつ線維化がほとんどない程度から一部のグ鞘間またはグ鞘・中心静脈間にbridgingの形成をみる程度までの組織像を有する例において,グ鞘域の分布の偏りが対照とした非アルコール多飲群のそれよりも大きいことを見出した.このグ鞘域の分布の偏りはある種の小葉構造の歪みを表わすと考えられるがこの歪みの程度の数量的表現を試みた.これによりアルコール群(46標本)では線維化が同程度の非アルコール群(33標本)に比し小葉の歪み度が有意に大きいことが分り(P<0.001),アルコール多飲者の肝組織像の一つの特徴と考えられた.又組織の線維化の程度の数量化も試み歪み度との関連を検討したが,アルコール群では歪み度と線維化度の間に有意の相関を認め(p<0.01),非アルコール群では相関を認めなかった.