Toshio Fukazawa

Effect of EFA deficiency on lipid transport from liver

Studies are reported of the effect of an essential fatty acid (EFA) deficiency on synthesis of triglycerides (TG) and phospholipids (PL) and secretion of these compounds by livers of male Sprague-Dawley rats. Animals were fed a semipurified diet containing corn oil or hydrogenated coconut oil (HCO) as the sole source of fat or no fat from weaning to 20 weeks of age. Liver function of the animals in each group was compared by an isolated liver perfusion technique with perfusates containing erythrocytes and linoleate, and in vivo experiments via tail vein injection of palmitate-3H. Perfusion experiments showed that an EFA deficiency reduced the ability of the liver to secrete TG and PL. Accumulation of TG in the liver and its diminished secretion into the blood of EFA deficient animals were demonstrated by in vivo experiments with palmitate-3H. The rate of conversion of linoleate to arachidonate and synthesis of PL was greater in livers of EFA deficient rats than in the control, corn oil fed animals. The results suggest a relationship of EFA metabolism to lipid transport.

Three-dimensional organization of the hepatic microvasculature in Hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemic fibrovascular dysplasia. Although hepatic vascular shunts are often observed in HHT, the responsible pathological mechanism is unknown. This issue was addressed by performing a 3-dimensional reconstruction study of the hepatic microvasculature of an HHT-involved liver in a 79-year-old woman. Clinical observation revealed high-output congestive heart failure and hepatic encephalopathy due to arteriovenous and portovenous shunts, respectively. Angiography revealed tortuous dilation of hepatic arterial branches and intrahepatic arteriovenous shunts. The 3-dimensional analysis of the autopsy liver revealed focal sinusoidal ectasia, arteriovenous shunts through abnormal direct communications between arterioles and ectatic sinusoids, and portovenous shunts due to frequent and large communications between portal veins and ectatic sinusoids. Type 1 HHT was suggested by the lack of endoglin immunoreactivity in the liver. The 3-dimensional reconstruction study of hepatic microvasculature was successful in identifying the pathological changes responsible for the intrahepatic shunts in HHT.

Biosynthesis of protein relative to the accumulation of fat in the liver of EFA deficient rats

Effect of an essential fatty acid (EFA) deficiency in the rat on the incorporation of leucine-14C and glucosamine-14C into serum and liver protein are reported. Weanling male rats of the Sprague-Dawley strain were raised on a fat-free diet for 10–12 weeks and then switched to diets supplemented with 10% corn oil or 10% hydrogenated coconut oil. Leucine-14C or glucosamine-14C was injected into the tail veins of the animals of each group. At selected intervals up to 120 min after the injections, the animals were sacrificed and the radioactivity of the liver and serum proteins was measured. The levels of triglyceride (TG) in the serum and the liver were also determined. Less radio-activity was incorporated into the serum β-lipoprotein (β-LP) fraction of the hydrogenated coconut oil than the corn oil fed animals injected with leucine-14C, but no differences were observed in the incorporation of radioactivity into the liver protein and both albumin and globulin fractions of the serum of these groups of animals. In the similar experiments with glucosamine-14C less radioactivity was incorporated into the β-LP fraction of the serum and into the smooth endoplasmic reticulum of the liver in the hydrogenated coconut oil (EFA deficient) than the corn oil fed animals. Time course studies also indicated that less radioactivity was incorporated into the β-LP fraction than into the albumin and globulin fractions of the serum of the hydrogenated coconut oil group. These findings suggest that an EFA deficiency results in an impairment of the synthesis or release of lipoprotein.

Hepatocellular carcinoma arising in an elderly male with primary biliary cirrhosis

We report the case of an elderly male with asymptomatic primary biliary cirrhosis (PBC) who developed a hepatocellular carcinoma (HCC). The 89-year-old man, who was otherwise healthy, was admitted for investigation of mild hepatic dysfunction, which had been detected during a routine physical check-up. Serum chemistry, positive anti-mitochondrial antibody (M2) and liver biopsy results led to a diagnosis of PBC. Three years later, at age 92, computed tomography (CT) and ultrasound scans of his abdomen revealed a large hepatic tumour, which was confirmed on liver biopsy to be HCC. The tumour ruptured 3 months after diagnosis and the patient was successfully stabilized by coil embolization of his right hepatic artery. We believe that, to date, this is the oldest reported patient to have had interventional radiology for the management of HCC.

Early carcinoma of the distal second part of the duodenum treated by wedge resection.

A case of early carcinoma of the distal second part of the duodenum, in a 74-year-old man, is presented. Endoscopic retrograde cholangiopancreatography was performed for diagnosis of a common bile duct stone. During this procedure, small elevated lesions were found incidentally in the distal second part of the duodenum, and the histologic examination of a biopsy specimen showed adenocarcinoma. The lesions were removed by wedge resection, and pathologic examination revealed duodenal carcinoma limited to the lamina propria. Although carcinoma of the duodenum, other than of the ampulla of Vater region, is very rare, it is sometimes possible to detect asymptomatic early tumors. However, this requires careful observation of the entire duodenal mucosa, including that of the distal duodenum, at duodenoscopy.

Change of liver weight in the elderly.

60歳以上の高齢者における肝重量の加齢的変化につき, 肝重量に影響を及ぼす病的因子を可及的に除外した剖検582例 (男性291例・女性291例) を対象として, 定量的に検討した.肝重量および肝重量体重比はいずれも加齢と共に減少した. 肝重量および肝重量体重比はいずれも肥満の影響を受け, 肥満者では前者は高く, 後者は低値を示した. 肥満度別に検討しても肝重量および肝重量体重比は逐齢的に減少した. 男女の比較では同じ年齢では, 女性は肝重量は低い傾向を示したが, 肝重量体重比は高い傾向を示し, 肥満度別の検討でも同様の結果であった.

Extreme right lobar atrophy of the liver : A rare complication of autoimmune hepatitis

Lobar atrophy is a rare morphologic change of the liver. We describe a 73-year-old woman with mild liver dysfunction and history of Sjögrens syndrome who had right hepatic lobar atrophy. Serum biochemistry levels were as follows: albumin, 4.5 g/dl; total bilirubin, 1.0 mg/dl; alanine aminotransferase, 25 international units/l; aspartate aminotransferase, 27 international units/l; alkaline phosphatase, 333 international units/l; and gamma-glutamyl transpeptidase, 332 international units/l. Serological data were as follows: rheumatoid factor, 27.9; anti-nuclear antibody, 1:640; and antismooth muscle antibody, 1:80. Viral markers for hepatitis B were all negative. Anti-hepatitis C virus (anti-c-100) was negative. Portal hypertension developed thereafter, and the patient died of hepatic failure at age 76. Postmortem examination revealed autoimmune hepatitis with moderate fibrosis, portal vein thrombus, and complete obstruction of the right hepatic duct due to hepatolithiasis. Terminal hepatic failure resulted from combination of decreased hepatic volume due to the right lobar atrophy, exacerbation of autoimmune hepatitis in the remnant left hepatic lobe, decreased portal venous blood flow due to thrombosis, portal hypertension, and cholangitis with hepatolithiasis. This is the first reported case of hepatic lobar atrophy due to autoimmune hepatitis. From a clinical standpoint, patients with hepatic lobar atrophy, even if asymptomatic, should be followed up with careful attention to progression of liver diseases, portal hypertension, and biliary complications.

Lipoprotein patterns in hepato-biliary diseases

アガロースゲル電気泳動法を用いて,肝,胆道疾患におけるリボ蛋白像を観察し,各リボ蛋白分画の脂質染色性と移動度の差から9型に分類した.非代償性肝硬変の多くはpre-β帯が消失し,α,β帯の減少したA型を示した.慢性肝炎ではpre-βがβに連続したB型を示した.閉塞性黄疸,急性肝炎で,総ビリルビン,血中胆汁酸の著明な増加のみられた症例はα帯が消失し,幅広いβ帯のみが泳動されるL型を示した. 一般にリボ蛋白泳動後,デンシトメトリーにより得られたα%はアポA濃度と相関が見られたが,幅広く濃染したα帯を示すM型の2例でアポA濃度はむしろ低下していた. 経過を追って観察した急性肝炎症例では症状の改善に伴ってpre-β帯が出現した.又細いβ帯のみ泳動されるA-L型をとった症例は予後不良であった. リポ蛋白像の観察は肝,胆道疾患の診断,予後の判定に有用な指標になると考えられた.

Cholelithiasis in the Aged

胆石症は加齢とともに増加傾向があり, 近年高齢者人口の増加とともに臨床的に重要な疾患とされている. 今回著者らは, 老人医療施設の剖検例で, 高齢者の胆石症について検討したので報告する. 対象は浴風会病院 (東京) の1962年～1973年7月の11年半の60歳以上の剖検例1070例で, 男375例, 女695例である.1) 胆石発生頻度は, 60歳以上の高齢者では18.8%であり, 男13.9%, 女21.4%であった. 年齢別では, 60歳代男2.4%, 女24.5%, 70歳代男17.4%, 女18.8%, 80歳代男11.9%, 女21.1%, 90歳代男20.0%, 女31.3%であった.2) 胆石所在部位は, 95%が胆嚢内であった. 胆嚢外結石は18.9%の症例にみられた.3) 胆石の種類はビリルビン系石が多くみられ, コレステロール系石とビリルビン系石の比は, 男で1:4.3, 女で1: 9.2であった.4) 胆石症の3主徴である発熱, 黄疸, 疼痛を認めた症例は, 胆嚢内胆石の場合, 男でそれぞれ32.5%, 10.0%, 30.0%であり, 女では20.0%, 10.4%, 30.4%であった. silent stone は, 男52.5%, 女58.4%認められた. 胆嚢外胆石の場合, 発熱, 黄疸, 疼痛は男でそれぞれ41.7%, 25.0%, 41.7%, 女で37.5%, 12.5%, 54.2%認められた. silent stone は男50.0%, 女41.7%存在した.5) 胆石症例の死亡前の主な臨床診断は, 男女とも中枢神経系, 循環器系, 呼吸器系の疾患であり, 胆道系疾患は男で23.1%, 女で21.5%であった. 胆石症と診断された症例は男で9.6%, 女で8.7%であった.6) 胆石症が直接死因となった症例は, 男で7.7%, 女で4.7%みられた.7) 胆石症に胆嚢癌の合併は, 女で2.1%みられた. 胆嚢癌の胆石保有率は女で60%であった.