Takeshi Oriyama

Do the tumor cells of hepatocellular carcinomas dislodge into the portal venous stream during hepatic resection

Background. The current study was undertaken to investigate whether or not tumor cells are dislodged into the portal venous stream during hepatic resection for hepatocellular carcinomas.

Intrahepatic metastases in hepatocellular carcinoma: the role of the portal vein as an efferent vessel.

The mechanism and pathogenesis of the high frequency of intrahepatic metastasis in hepatocellular carcinoma (HCC) has not yet been elucidated. Two hundred and thirty one tumors (⩽ 5 cm in diameter) of resected specimens of HCC were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens selected at random from the 231 tumors. The most frequent site for tumor spread in HCC was capsular invasion followed by extracapsular invasion, vascular invasion, and finally intrahepatic metastasis. There was a strong statistical correlation between the presence of intrahepatic metastasis and the frequency of vascular invasion (correlation coefficient = 0.998). Radiopaque material injected directly into 23 resected tumors entered only the portal vein in 17 tumors and into both the portal and hepatic veins in six tumors. In all eight patients with unresectable lesions, radiopaque media injected percutaneously into tumor nodules flowed only into the portal vein. These findings suggest that tumor spread in HCC progresses from capsular invasion to intrahepatic invasion and that the portal vein may act as an efferent tumor vessel.

Microwave Coagulonecrotic Therapy for Hepatocellular Carcinoma

Abstract. The present study reports on the usefulness of microwave coagulonecrotic therapy (MCT) as a treatment option for hepatocellular carcinoma (HCC) with poor hepatic reserve. From June 1992 to March 1995, MCT using a microwave electrode was employed on 8 patients using laparoscopic control and 19 with the open method, and wedge resection (Hx) was applied to the 23 patients. All patients had HCC with poor hepatic reserve. Radiation output was 100 watts with a mean radiation duration of about 30 minutes. The severity of liver dysfunction and the regional characteristics of the tumor (tumor size, multiplicity, portal invasion, tumor depth) were comparable between the MCT and Hx groups. The operative time was significantly shorter for the MCT group than the Hx group. The mean blood loss was 1570 ml in the Hx group but negligible in the MCT group. There was no operative mortality in the MCT group in contrast to 4.3% (1 of 23) in the Hx group. Complications were observed in 11.1% (3 of 27) and 34.8% (8 of 23), respectively, for the MCT and Hx groups. The postoperative total bilirubin had lower values and the start of diet was earlier in the MCT group than the Hx group. The 3-year crude and disease-free survival rates were 86% and 44%, respectively, for patients who underwent MCT, which were comparable to 75% and 14% for those with Hx. MCT can achieve long-term results equivalent to those obtained by wedge resections, but it is less invasive and technically easier. Therefore it can be an alternative option in place of limited resection for HCC with poor hepatic reserve.

Pathologic and Radiographic Studies of Intrahepatic Metastasis Hepatocellular Carcinoma; The Role of Efferent Vessels

The efferent vessel of hepatocellular carcinoma (HCC) and the mechanism and pathogenesis of the high frequency of intrahepatic metastasis in HCC has not yet been clarified. Three hundred ninety-three resected specimens of HCC were examined for tumor thrombosis in the portal vein and the hepatic vein: 231 tumors ≤5 cm in diameter were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens and by percutaneous infusion of radiopaque media into tumor nodules in 8 patients. The mode of tumor spread in HCC progressed from capsular invasion to extracapsular invasion, then to vascular invasion, and finally to intrahepatic metastasis. There was a strong statistical correlation between the presence of intrahepatic metastasis and portal vein thrombosis (p<0.05, R=0.998). Radiopaque material injected directly into 23 resected tumors entered only the portal vein in 17 tumors and into both the portal and hepatic veins in 6 tumors. In all 8 patients with unresectable lesions, radiopaque media injected percutaneously into tumor nodules flowed only into the portal vein. These findings suggest that intrahepatic invasion by HCC may occur through the portal vein as an efferent tumor vessel.

Progression of hepatocellular carcinoma as reflected by nuclear DNA ploidy and cellular differentiation

BACKGROUND/AIMS Intratumor heterogeneity of DNA ploidy within a single hepatocellular carcinoma is not well understood. The present study was designed to examine the histologic distribution of intratumor DNA ploidy in hepatocellular carcinomas of different growth types in relation to cell differentiation. METHODS Twenty patients (16 men and four women; mean age, 60.2 years) with hepatocellular carcinoma (mean diameter, 4.3 cm) were studied. One hundred and twenty-seven samples from different sites of each tumor were analyzed by determination of the nuclear DNA content and histological examination. RESULTS The DNA ploidy was heterogeneous in nine (45%) of the 20 tumors. Five tumors had a mixture of diploid and aneuploid regions, and the remaining four consisted of aneuploid regions with different DNA indices. There was no significant difference in patient characteristics between the heterogeneous and homogeneous groups. A significant correlation was found between tumor growth type and the incidence of heterogeneity. Only 16% of single nodular carcinomas without intratumor septal formation exhibited heterogeneity, while single nodular tumors with septal formation or confluent multinodular tumors were associated with high incidences of different DNA ploidy patterns or DNA indices. There was no aneuploidy in well-differentiated foci, while aneuploidy was frequently found in moderately or poorly differentiated foci (incidences of 67% and 74%, respectively). CONCLUSIONS Heterogeneity of DNA ploidy may develop along with changes in growth pattern and cell dedifferentiation or by confluence of nodules originating from different tumor cell clones.

Multivariate analysis of liver regenerative capacity after hepatectomy in humans

Many factors affect liver regeneration after partial hepatectomy; however, those factors that are essential for regulation of liver regeneration in humans are not known. Using multiple regression analysis we conducted a study to determine essential factors involved in the speed of liver regeneration after hepatectomy. The subjects were 59 patients who underwent hepatic resection between January 1980 and December 1991. A regression equation for predicting regeneration speed (Y; cm3/day) during the 1st postoperative month was obtained by stepwise forward multiple regression analysis, using 11 explanatory parameters (Xi). The regeneration speed and the resection ratio (%; indicating the magnitude of resection) were calculated based on a computed tomography (CT) scan volumetric study. The degree of liver fibrosis, expressed as the fibrotic index (%), was morphometrically determined in Azan-Mallory stained sections. Of the 11 explanatory parameters, the resection ratio and the fibrotic index had a significant simple correlation with Y. The following regression equation was obtained: Y (cm3/day)=−1.1+3.7 × resection ratio −5.4 × alkaline phosphatase −3.7 × fibrotic index +1.2× total bilirubin −2.6 × glutamic pyruvic transaminase (multiple correlation coefficient, 0.82). We found that the extent of resection and the degree of fibrosis, as well as alkaline phosphatase, total bilirubin, and glutamic pyruvic transaminase, contributed to the speed of regeneration after partial hepatectomy.

A report of resected mesenchymal hamartoma of the liver in adult.

我々は,検診にてCA19-9の軽度上昇を指摘され,超音波にて偶然発見された成人の肝間葉性過誤腫を経験したので報告する.症例は47歳の女性である.超音波やCTにて肝のS6より肝外性に発育する大きさ7cmの腫瘍を認め,腫瘍は充実性の部分と嚢胞性の部分にて構成されていた.血管造影では腫瘍全体に濃染像が見られた,良性腫瘍を最も疑ったが,悪性腫瘍も否定できず手術を施行した.切除標本では大きさ7.5cm×7.5cmの境界明瞭で光沢のある充実性腫瘍で,内部に大小の嚢胞を認めた.組織像では主に豊富な線維結合織よりなり,その間に大小の血管あるいはリンパ管や,小胆管の増生を認めた.現在,術後3年であるが,再発兆候はない.肝間葉性過誤腫の本邦報告例は64例であり,このうち15歳以下の小児例が52例と大部分を占め,成人例はわずか12例に過ぎない.小児例では腫瘍の発育速度は早く,成人例では発育速度は緩慢であるも悪性腫瘍との鑑別も困難で,共に切除が第一選択の治療である.悪性化や転移例はなく予後良好であるが,3例の再発例があり注意を要する.

In vivo subcellular elemental dynamics in liver graft: With special reference to effect of non-selective endothelin receptor antagonist, TAK-044, on the graft injury

Background: No data are available concerning the in vivo subcellular dynamics of elements in liver grafts and the effect of endothelin receptor antagonist, TAK-044, against graft injury. Methods: Liver transplantation was performed in porcine under active veno-venous bypass. The grafts stored in chilled preservation solution were recirculated following reflush with lactated Ringers solution with or without TAK-044 (10 mg/kg). Cold and warm ischemic times of the grafts were comparable between the two groups. Elements (Na, K, Cl, Ca, P and S) were measured in three fractions of cytoplasm, mitochondria and nucleus by electron probe X-ray microanalysis for the graft biopsy specimens obtained at various time from donor laparotomy to 1 week after liver grafting. Liver functions also were compared between the two groups. Results: In both groups, concentration of each element changed in parallel among the three subcellular fractions and their changes were less marked in the nucleus. In the control group, there were significant increases in cytoplasmic Na and Cl after portal reperfusion and in cytoplasmic and mitochondrial Ca after hepatic artery reperfusion. These were accompanied by K and mitochondrial S decreases without a statistical significance. In the TAK group, such postreperfusion elemental alterations were significantly suppressed and early deterioration of the liver functions was alleviated, as compared with the control group. Conclusion: A supplemental use of TAK-044 in a rinse solution before reflush contributed to stability of subcellular elements after reperfusion and better preservation of early graft function.

Dynamics of serum and tissue alkaline phosphatase activity after hepatectomy in normal and cirrhotic rat liver

Abstract To investigate the pathogenesis of bile stasis after partial hepatectomy in the cirrhotic liver, the activity of alkaline phosphatase in serum and liver tissue, as well as morphologic changes in the bile canaliculi, were compared between cirrhotic and normal rats. In the normal rats, and cirrhotic rats produced by intraperitoneal thioacetamide injection, blood and liver specimens were obtained before and 2, 7, and 14 days after 70% partial hepatectomy. Serum and liver tissue alkaline phosphatase (ALPase) activity, liver weight, and electron histochemical changes in the bile canaliculi and microvilli were assessed. The normal rats showed rapid regeneration and marked elevation in the serum hepatic and tissue ALPase with a peak on day 2. This was associated with the maximal bile canalicular dilation and increased pericanalicular lipid vesicles, but without the microvilli destruction. These changes were normalized by 14 days after hepatectomy. In contrast, in the cirrhotic rats, regeneration and elevation in the serum and tissue ALPase were delayed, and higher total bile acidemia persisted. The bile canaliculi with ectasia before hepatectomy underwent no further dilation, and was associated with marked destruction of the microvilli and weakened ALPase in the bile canalicular membrane. The pericanalicular lipid vesicles was sparse. Persistent cholestasis in the remnant cirrhotic liver after hepatectomy is closely linked to the morphologic derangement and ALPase activity in the intra- and peri-bile canalicular area, and serum ALPase is useful as an index monitoring bile secretory capacity of the remnant liver.

Indication Criteria of Hepatectomy for Hepatocellular Carcinoma Based on Long-Term Result

The current study reports what patients with hepatocellular carcinoma can get a potential cure and good quality of life from hepatectomy based on the long-term results. 504 hepatectomized patients from 1973 through 1992 were used. The survival rate of curative resections was 24% at 10 years in contrast to 0% at 7 years. Crucial factors determining curability and prognosis were degree of portal invasion (Vp) and intrahepatic metastasis (IM), and nuclear DNA content (diploidy vs. aneuploidy). No Vp and IM were found in 72% of 66 patients who survived more than 5 years, and diploidy HCCs accounted for 89% of them. Single nodular type of HCC less than 5 cm in size and well reserved liver functions allowing a wide resection, in whom are definite indication of hepatectomy.