Hidehisa Aoyama

Surgical treatment of primary carcinoma of the gallbladder based on the histologic analysis of 48 surgical specimens.

During the past 5 years, extended cholecystectomy and/or more radical procedures, including pancreatoduodenectomy and extended hepatic lobectomy, were performed on 48 patients with carcinoma of the gallbladder in an attempt to cure the disease. It was retrospectively proven from microscopic analysis of the surgical specimens taken from the 48 patients that 28 patients had received curative resections. The 28 consisted of all 4 patients with stage I carcinoma, all 9 with stage II, 6 of 8 with stage III, and 9 of 27 with stage IV. We reached the following conclusions: (1) extended cholecystectomy with resection of the bile duct in the hepatoduodenal ligament is the optimum procedure for patients with stage I and stage II carcinomas, and (2) for patients with stage III carcinoma, more radical procedures, including pancreatoduodenectomy and/or wider resection of the liver, might result in curative resection of the disease. For some patients with stage IV tumors, such as duodenal invasion or direct invasion of the liver, curative resection may be achieved by pancreatoduodenectomy or extended hepatic lobectomy.

Changes in hepatic energy charge, blood ketone body ratio, and indocyanine green clearance in relation to DNA synthesis after hepatectomy

The changes in the energy charge (ATP + 0.5 ADP)/(ATP + ADP + AMP) levels of the remnant liver were studied in relation to changes in the incorporation rate of methyl-3H-thymidine into DNA, the blood ratio of acetoacetate/beta-hydroxybutyrate and indocyanine green (ICG) clearance in 70% hepatectomized rabbits. The energy charge levels of the remnant liver decreased rapidly to 0.767 from 0.856 of normal, despite a marked enhancement of mitochondrial phosphorylative activity, concomitant with the fall in blood ketone body ratio, before a maximal increase of DNA synthesis after hepatectomy. Blood ketone body ratio was correlated with hepatic energy charge (r = 0.696, p less than 0.01). After a maximal increase of DNA synthesis, hepatic energy charge levels and the blood ketone body ratios increased gradually to normal levels, concomitant with a rise in ICG clearance. Energy charge levels of the remnant liver can be evaluated by the blood ketone body ratio.

A biochemical basis for depressed ketogenesis in sepsis.

Several investigators have demonstrated a diminished rate of ketogenesis during inflammatory or infectious states despite the availability of free fatty acids supplied to the liver. The biochemical mechanism for this effect is unknown. Malonyl-CoA has been proposed to be a regulator of ketogenesis. Malonyl-CoA levels are low in states of rapid ketogenesis such as starvation or diabetes and high in states of reduced ketogenesis such as carbohydrate feeding. In the present study, the effect of an intra-abdominal abscess on the level of hepatic malonyl-CoA was investigated in four groups of animals (fed control, sterile inflammation, small chronic septic abscess, large chronic septic abscess). Liver samples were frozen in situ 5 days following the intraperitoneal introduction of a rat-fecal agar pellet inoculated with a known bacterial flora which generated an abscess [sterile inflammatory; B. fragilis 10(8)/ml + E. coli 10(2)/ml (small, 0.8 ml or large, 1.5 ml) abscess pellet]. The level of malonyl-CoA in normal fed rats was 5.0 +/- 0.6 nmol/gm wet wt (n = 9). The malonyl-CoA level was not altered in animals with a sterile inflammation. However, hepatic malonyl-CoA levels were significantly increased in small (10 +/- 1 nmole/gm wet wt) (p less than 0.05; n = 9) or large (12 +/- 1 nmol/gm wet wt) (p less than 0.01; n = 14) septic abscess rats compared to control fed and sterile inflammatory rats. Hepatic ketone bodies (beta-hydroxybutyrate and acetoacetate) did not increase in sepsis over control or sterile inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of Glucose Metabolism by Altered Pyruvate Dehydrogenase Activity. I. Potential Site of Insulin Resistance in Sepsis

Regulation of the pyruvate dehydrogenase (PDH) complex has been demonstrated to be a key mechanism in the control of carbohydrate oxidation and conservation of glucose carbon. The effect of sterile inflammation and chronic sepsis (small and large abscess) on the activity of the PDH complex was examined in liver and skeletal muscle. Sepsis altered the proportion of PDH in the active, dephosphorylated form. In hepatic tissue, sterile inflammation leads to a 2.5-fold increase in the proportion of active PDH complex compared to fed control. The same increase in the proportion of active PDH complex was observed in rats with a small septic abscess. However, when the severity of septic episode was increased, the proportion of active PDH complex decreased relative to sterile inflammation or small septic abscess animals. A different pattern in the response to sterile inflammation and sepsis on the proportion of active PDH complex was observed in skeletal muscle compared to liver. In contrast to liver, sterile inflammation did not alter the proportion of active PDH in skeletal muscle. In addition, sepsis (either small or large septic abscess) resulted in a 3-fold decrease in the proportion of active PDH relative to fed control or sterile inflammatory animals. The decrease in the proportion of active PDH complex in sepsis was associated with a corresponding increase in the skeletal muscle acetyl-CoA/CoA ratio. The mechanism responsible for lowered PDH complex activity may have been due to increased PDH kinase activity, secondary to increased skeletal muscle acetyl-CoA/CoA ratios.

Changes in acetoacetate/β-hydroxybutyrate ratio in arterial blood following hepatic artery embolization in man

Acetoacetate/beta-hydroxybutyrate ratio in the hepatic venous blood was compared to the ratios in arterial blood and peripheral venous blood in hypoxic state following right hepatic artery embolization in 5 patients with liver cancer. Ketone body ratios in right hepatic venous blood were positively correlated with those in arterial blood (r = 0.960, p less than 0.001), but not with those in peripheral venous blood. The free NAD+/NADH ratio of the liver mitochondria, which is reflected by the ketone body ration in hepatic venous blood, can be evaluated by the ketone body ratio in the arterial blood.

Relationship between initial hepatic uptake of indocyanine green and hepatic energy status in hepatectomized rabbits

SummaryThe relationship between initial hepatic uptake of indocyanine green (ICG) and hepatic energy status was studied in about 70% hepatectomized rabbits. At 24 h after hepatectomy, the initial plasma disappearance rate (K) and the maximal removal rate (Rmax) of ICG fell to 27 and 26%, respectively, and the mitochondrial phosphorylative activity was enhanced maximally with a concomitant decrease in the energy charge ((ATP+1/2ADP)/(ATP+ADP+AMP)) level. Afterward, the initial reduction of ICG removal rate was followed by a rapid increase in week 1 and more gradual return to preoperative values by week 6 after hepatectomy. In the early period after hepatectomy (1–7 days), the mitochondrial phosphorylative activity was the higher the smaller the %K value was, while in the late period after hepatectomy (1–6 weeks), the mitochondrial phosphorylative activity remained unchanged irrespective of increasing %K. It is suggested that the mitochondrial phosphorylative activity may be a better guide to evaluate the functional status of the remnant liver than the initial hepatic uptake of ICG, especially in the early period after hepatoctomy.

Lung water accumulation in rats after repeated challenges of a sublethal dose ofE. coli and its relation to the hepatic energy charge

We produced a septic model of rats in which lung water accumulation was developed. The degree of lung water accumulation was then compared with the hepatic energy status because the liver is not only a metabolic central organ but also one of the central organs of the reticulo-endothelial system (RES), and clinically, lung edema in sepsis seems to relate to failure of the RES. Three experimental models were examined to form lung water accumulation, namely: the lethal model, givenE. coli 6.0×106 CFU/g BW, the sublethal model, givenE. coli 2.0×106 CFU/g BW and the repeated sublethal dose injection model, givenE. coli 2.0×106×2 at 12 hour intervals. In the lethal models, the energy charge (EC) of the liver decreased markedly (p<0.001) without recovery and the lung water accumulated (p<0.05). In the sublethal models, EC decreased transiently (p<0.05) and the lung water did not increase. However, when the microbial challenge with a sublethal dose was repeated, the decreases in EC were prolonged and the lung water increased significantly after the second injection (p<0.001) despite a 4.9 per cent mortality during the subsequent 24 hours. It is suggested that when the decrease in liver EC is prolonged, even if it is not fatal, an accumulation of lung water is possible in septic states. This finding may help further analyses of the interrelationship between the lung and the liver in severely infected patients.

Clinical aspects and surgical treatments in patients with anomalous arrangement of the pancreatico-biliary ductal system.

胆管と膵管の合流点が十二指腸壁外に認められる先天性総胆管拡張症ならびに正常な胆管の内腔例103例について共通する臨床症状および治療法を検討した. これらに共通する臨床像は上腹部痛ならびに背部痛であり, 発作時の臨床化学的検査で急性膵障害および胆汁うっ滞型の急性肝障害が大部分の症例に, 同時に認められることである. これは胆管と膵管の「共通の導管」が膵管であろうと考えられるところから, この部分に胆汁の通過などによる後天的な通過障害が生じ, 胆汁, 膵液の膵管内および胆管内への振子様移行現象が起り臨床症状が発生するものと考えられる. したがって胆汁をこの共通の導管部を通さない目的でのbiliary diversionが最も良好な成績であった.