Hidenari Takasan

Ligation of a branch of the portal vein for carcinoma of the liver

Portal branch ligation, a new surgical treatment for unresectable carcinoma of the liver, was performed in twenty patients. All the patients tolerated the procedure, and morbidity and mortality were minimal, even in patients in poor general condition. The responses to ligation differed considerably, but significant palliation was attained in some patients and one survived six years. The effect of portal branch ligation on the tumor appears to be closely related to the degree of tumor vascularity, tumor malignancy, and portal circulatory disturbances such as cirrhosis, portal hypertension, or portal thrombosis. We believe that the present procedure can be recommended for clinical application in some patients with unresectable carcinoma of the liver.

Human liver mitochondria

Abstract Contamination with hemoglobin in human liver mitochondria prepared by the procedure commonly applied to rat liver is unavoidable and a major obstacle to the measurement of cytochromes by (reduced minus oxidized) difference spectra. The washing of sliced liver tissues with Locks solution minimized the contamination with hemoglobin. A systematic method has been presented for quantitatively estimating the respiratory pigments without complete removal of hemoglobin. Phosphorylative activity and respiratory enzyme contents were assayed in the mitochondria prepared from 67 biopsy specimens of normal human liver obtained at operation. The maximal phosphorylation rates were 41.7 nmoles ATP synthesis per mg protein per min at 22° with glutamate plus succinate as substrates (on a protein basis) and 36.6 per second (on a cytochrome a (+ a 3 ) basis, “cytochrome a (+ a 3 )-turnover”). No statistically significant decline in the phosphorylation rates with increasing age could be demonstrated. The cytochrome a (+ a 3 ) concentration was fairly constant during the life span, while there was a significant elevation of cytochrome c + c 1 concentration with increasing age. After 70 years of age the cytochrome c + c 1 level increased 1.6-fold, from 76 to 121 pmoles per mg of mitochondrial protein, as compared with young adults. In the young adult cytochrome c + c 1 concentration did not exceed that of cytochrome a (+ a 3 ). The ratio of cytochrome c + c 1 to cytochrome a (+ a 3 ) increased after 60 years of age, and cytochrome c + c 1 concentration was 1.5 times higher than the cytochrome a (+ a 3 ) concentration after 70 years of age.

Clinical Application of Cytochrome a(+a3) Assay of Mitochondria from Liver Specimens: An Aid in Determining Metabolic Tolerance of Liver Remnant for Hepatic Resection

Measurement of cytochrome a(+a(3)) contents in liver mitochondria was made on 52 biopsy specimens of patients with liver tumor. Patients having higher cytochrome a(+a(3)) contents in mitochondria from remaining liver than those of normal human liver mitochondria could survive well major liver resections whether or not associated with liver cirrhosis. However, patients with cytochrome a(+a(3)) contents less than 0.5 x 10(-10) moles per mg protein showed a high rate of postoperative complication (80%) and death (40%) in spite of minor operation. In routinely used liver function tests such as serum albumin, A/G ratio, SGOT, total bilirubin, prothrombin time, BSP and TTT, there were no significant differences between patients with cytochrome a(+a(3)) contents more than 0.5 x 10(-10) moles per mg protein and those less than 0.5. The results indicate that routine laboratory studies do not have much diagnostic value in estimation of a marked decrease of mitochondrial cytochrome a(+a(3)) contents. It is suggested that the measurements of cytochrome a(+a(3)) of the remnant liver should be done prior to a contemplated major resection.

Role of portal blood on the enhancement of liver mitochondrial metabolism

Abstract Ligation of a branch of portal vein in rabbits resulted in the depression of phosphorylation rates of mitochondria from the lobe affected and the marked enhancement of phosphorylation rates of the mitochondria from the lobe which is not deprived of portal blood, within twelve hours. However, when animals were subjected to side to side portacaval shunt, such characteristic response was not induced by ligation of the portal vein. On the other hand, when the parenchymal cells were damaged by ligation of a branch of the hepatic duct, the enhancement of mitochondrial phosphorylation rates in the unligated part was observed in a compensatory manner parallel with the magnitude of the derangement of mitochondrial function in the ligated part. Such a series of enhancement of mitochondrial metabolism is indicative of an excellent mitochondrial homeostasis for generation of energy. Portal blood plays an important role in the enhancement of mitochondrial phosphorylation rates, suggesting that this blood contains a specific factor that is capable of stimulating oxidative phosphorylation of liver mitochondria and is neither inhibited nor destroyed in systemic circulation. It is suggested that the enhancement and depression of mitochondrial metabolism are due to an alteration of the quantitative balance between the available factor and the number of mitochondria present.

Pancreatoblastoma resected by delayed primary operation after effective chemotherapy

A case of pancreatoblastoma resected successfully after effective chemotherapy is discussed. Preoperative chemotherapy may be useful in patients with advanced unresectable pancreatoblastoma to permit complete resection of the tumor.

Alteration in liver mitochondrial metabolism in a patient with biliary obstruction due to liver carcinoma

Summary In a patient with obstructive jaundice secondary to extrahepatic biliary obstruction due to metastatic cancer of the liver, it was found that the delicate balance for energy production was maintained by the enhancement of mitochondrial metabolism and that a progressive decrease in the contents of cytochromes a(+a 3 ) and b of the liver mitochondria developed with a deterioration of the physical status. The same sequence for energy balance in the liver mitochondria also was observed in the liver of rabbits that had major damage induced by experimental ligation of the left hepatic bile duct.

Metastatic cancer of the liver resulting in obstruction of the extrahepatic bile duct

Abstract A case is described of a sixty-five year old man with metastatic cancer of the liver originating in cancer of the colon. The flow of necrotic tissue into the bile duct resulted in obstructive jaundice.

Relation of phosphorylative capacity of liver mitochondria to cytochrome a(+a3) content.

Abstract The correlation between the cytochrome a(+a 3 )turnover number in phosphorylative capacity and cytochrome a(+a 3 ) content was studied in liver mitochondria from various patients. Mitochondrial function was classified into three types according to the turnover number: (1) normal type (a turnover number of 20 to 35 times per second); (2) enhanced type (a turnover number of 35 to 45 times per second); (3) depressed type (a turnover number of 0 to 20 times per second). In the enhanced type of mitochondrial function, the respiratory control ratio and the P:O ratio were considerably higher than those in the normal type, which suggests that the mitochondria were in the condition enhanced by an increased metabolic load on liver. Conversely, in the depressed type of function the cytochrome a(+a 3 ) content was decreased to less than 0.5 × 10−10molmg of protein, with considerably lower respiratory control and P:O ratios. The mitochondria could not respond to energy needs with a normal acceleration of oxidative phosphorylation. Patients with such depressed mitochondrial function showed a high surgical mortality and complication rate. Our results indicate that considerations of the critical level of cytochrome a(+a 3 ) could provide a biochemical basis for judging the potency of compensatory and regenerative capacities of the liver.

Minimal requirement of the remnant pancreas for protein and DNA synthesis of cultured hepatocytes prepared from pancreatectomized rats

The incorporation of 3H-thymidine and 3H-leucine into the hepatocytes was studied, using cultured hepatocytes prepared from normal and pancreatectomized rats. (1) In the cultured hepatocytes prepared from 80% pancreatectomized rats, the incorporation of 3H-thymidine and 3H-leucine into hepatocytes remained unchanged compared with those of sham-operated controls. In contrast, in those from totally pancreatectomized rats, the incorporation of 3H-thymidine and 3H-leucine decreased to approximately 67% and 37% respectively of sham-operated controls. However, those returned to near normal in the cultured hepatocytes from totally pancreatectomized rats treated by 0.8 IU/kg of insulin. (2) The addition of insulin (10(-4) M) to the culture medium stimulated the incorporation of 3H-thymidine into cultured hepatocytes prepared from normal rats to 148% of controls. The insulin-stimulated incorporation was inhibited by the addition of glucagon to the culture medium. The combined addition of insulin and glucagon did not synergistically act on DNA synthesis. It is suggested that the portal blood insulin in the presence of more than 20% of the pancreas is imperative for maintaining spontaneous regeneration.

Clinicopathological study of 30 resectable hepatocellular carcinoma, particularly on prognostic factors

京大第一外科で最近13年間に切除し得た肝細胞性肝癌30例を用いて,外科病理学的観点より予後因子を検討した.術後1ヵ月以内の死亡6例(手術死亡率,20%)で,肝硬変症を19例(63.3%)に合併していた.占居部位は右葉21例,左葉9例であった.手術術式は拡大右葉切除4例,右葉切除6例,右葉部分切除11例,左葉切除6例,左外側区域切除3例であった.腫瘍占居部位と予後とに相関を認めなかった.我々はO-GTT,肝Mitochondria機能の測定により肝予備力の判定を行っているが,手術死亡率および術後生存期間に関しては硬変肝と非硬変肝との間に明らかな差異を認めなかった.被包を有する20例で2年8.3ヵ月,有さない6例で7.1ヵ月の平均生存期間を得た.又,切除断端と腫瘍との距離が3cm以上有するものを切除断端(-)と規定すると,切除断端(-)11例で3年9ヵ月,切除断端(+)13例で約1年の平均生存期間を得た.A.F.P.産生能と予後とに相関をみないが,Edmondsons gradingと予後とに相関を認めた.以上より,被包の有無,腫瘍より切除断端までの距離と組織学的分化度が肝細胞性肝癌の予後を左右する重要な因子と考えることができる.