Ryuji Mizumoto

Primary carcinoma of the liver

Abstract Seventy-six patients with histologically proved primary cancer of the liver, including fifty-seven with hepatocellular carcinoma, fifteen with cholangiocellular carcinoma, and four with a mixed type, were admitted and treated at the First Surgical Clinic, Kyoto University Medical School during the twenty-two year period from 1951 to 1973. The symptoms, physical signs, and laboratory findings in these patients were reviewed. Of seventy-one patients with surgical exploration, twenty-three (32 per cent) underwent hepatic resection, eight had ligation of the portal branch, seven had ligation of the hepatic artery, and thirty-three had exploratory laparotomy alone. The final diagnosis in the remaining five patients was established by autopsy or percutaneous needle biopsy. Twenty-eight of fifty-seven patients with hepatocellular carcinoma (49 per cent) also clearly had cirrhosis of the liver. Of ten patients with cirrhosis who underwent hepatic resection, two died from hepatic coma within two months, two showed a delayed recovery of liver function after hepatic lobectomy, but the remaining six patients survived with no remarkable changes after segmental resection or procedures of lesser magnitude and one of them was well for seventeen years and five months after left lateral segmentectomy until he was killed in a traffic accident. Operative mortality in all patients who underwent hepatic resection was 9 per cent, and the one year, three year, and five year survival rates were 43, 22, and 13 per cent, respectively. For patients with nonresectable cancer, ligation of one of the main portal branches supplying the main tumor showed some improvement in their prognosis.

Orthotopic partial hepatic transplantation in dog

Based on the simple anatomy that the venous blood from the left half of the liver is drained by the single left hepatic vein in the dog, the left half of the donor liver was transplanted orthotopically in the space after left hepatic lobectomy of the recipient. Since this technique does not require complete occlusion of either the caval vein or the portal vein, external shunts are unnecessary. Furthermore there is no anhepatic phase during the transplantation procedure and consequently the surgical invasion to the recipient is minimal. Partial liver transplantation using the technique described has thus many advantages. Of the animals transplanted one survived 39 days after the orthotopic partial hepatic transplantation with 70 per cent hepatectomy of the recipient, and the other survived 10 days after total hepatectomy.

Histochemical studies on fat absorption in the jejunal mucosa after total pancreatectomy in dog.

Abstract Histologic and histochemical changes in the jejunal mucosa were investigated to clarify the pathogenesis of the disturbances of digestion and absorption and the effect of estrogen on absorption after total pancreatectomy in dogs. Histologic Changes . The crypts of Lieberkuhn in the jejunal mucosa were slightly lengthened, but a decrease in the absorptive surface due to villous atrophy was not observed after total pancreatectomy. Fat Absorption . The jejunal epithelium contained little or no Sudan-positive material in normal dogs fasting 24 hours, but lipid droplets stained with Sudan III were sometimes found in the absorptive epithelium and occasionally in the central lacteals in pancreatectomized dogs treated with insulin alone. When estrogen was administered together with insulin, lipid droplets were not observed in the epithelial cells or central lacteals, as in the control dogs. After oral administration of olive oil or oleic acid, absorbed lipid droplets were not observed in the jejunal mucosa of dogs treated with insulin alone after total pancreatectomy, but when estrogen was administered together with insulin, numerous lipid droplets appeared in the jejunal mucosa after oral administration of oleic acid, although olive oil was not absorbed. After the administration of medium chain triglycerides, a few lipid droplets were found in the absorptive epithelium at the tip of the villi, but estrogen did not have any effect on absorption. Changes of Enzyme Activity . Adenosine triphosphatase, alkaline phosphatase, and succinic dehydrogenase activities decreased markedly in the absorptive epithelium in dogs treated with insulin alone after total pancreatectomy. When estrogen was administered together with insulin after total resection of the pancreas, the activities of these enzymes in the epithelial cells were restored to normal. The results reported here show (1) that there is not only a disturbance in fat digestion but a definite impairment in fat absorption after total pancreatectomy, (2) that the disturbance in fat absorption can be attributed to the decreased activity in the epithelium of such enzymes as adenosine triphosphatase, alkaline phosphatase, and succinic dehydrogenase, and (3) that the activities of these enzymes are restored by estrogen administration, accompanied by an improvement in the absorption of fatty acids.

Resectability and regeneration of liver in postsinusoidal block

To study resectability and regeneration of cirrhotic liver, hemodynamic changes following partial hepatectomy were observed in dogs with presinusoidal block caused by ligation of the portal vein or with postsinusoidal block caused by ligation of the hepatic veins after portacaval anastomosis, since cirrhosis of the liver in man is mainly of postsinusoidal block occasionally accompanied by presinusoidal block. With a presinusoidal block, resection of 50 per cent liver was tolerated well, but with postsinusoidal block only less than 30 per cent could be resected. Thus the functional reserve of the liver with postsinusoidal block seems to be much less than that of presinusoidal block. After major hepatic resection the weight of the remnant liver with a dual blood supply increased markedly, while with a postsinusoidal block it increased slightly and with a presinusoidal block there was no change. Histometric studies showed that regeneration was prominent in the remnant liver with a dual blood supply, slight with a postsinusoidal block, and even less with a presinusoidal block.Thus, the liver with a postsinusoidal block possesses more extensive regenerative capacity but shows much lower resectability than with a presinusoidal block. Therefore, the resectability of the liver associated with cirrhosis seems to be more closely related to its functional reserve capacity than to its regenerative capacity.

Panel Discussion: Treatment of acute pancreatitis

The purpose of this report is to study the conservative t reatment of acute pancreatitis in early stage and period of convalescence. Tile subjects are 120 cases of acute pancreatitis; 47 cases confirmed operatively and 73 cases diagnosed clinically. Results are as follows: 1) The extent of the involvement of pancreas appeared to parallel the t ime that has elapsed before t reatment with fluid and electrolytes transfusion. I t is suggested that inadequate treatment during 48 hours from onset may aggravate not only symptoms of patients, but also impairment of the pancreas itsself. 2) The dosis of trypsin-inhibitor during 48 hours was sixty thousands units of Trasylol per one liter 0ftransfusion fluid in sever cases with a good course. A large dosis of trypsin-inhibitor, therefore, may be effective on acute pancreatitis, provided that sufficient transfusion is put into practice. 3) In the majori ty of cases who was given even a small amount of l iquid food within the first 48 hours, the patient s condition obviously deteriorated. Any case who had taken only a little during 4 days, appeared to have a high risk to be worsen. Complete starvation is the most important in the treatment over this period. 4) Therapy in early period of 10 severe cases with a good course was complete starvation with gastric suction, adequate transfusion (mean value: 3190ml/day), and sufficient dosis of trypsin-inhibitor (mean value: 260,000 Trasylol units/day) and antibiotics (mean value: 5 g of Cephalothin/

Survival of both donor and recipient in partial hepatic transplantation of dog

Since an immunologically related graft with minimal ischemic damage could be prepared from a living and related donor and regenerative capacity of the donor liver would be expected to rapidly make good the loss of tissue, partial liver transplantation might be an ideal method for the transplantation of this single organ. In this study the left half of the donor liver was transplanted after the removal of the left kidney of the recipient. Survival of the donor, the remanant liver of which was supplied only with the portal blood after 70 per cent hepatectomy was achieved. One each of the donors and the recipients survived more than one month after the partial liver transplantation.

Effect of hepatic circulation on bile-metabolism in canine liver

We collected separately the bile (A, B, C-) by duodenal tube from normal adults and patients with hepatobiliary tracts. H . G . H . contents of each bile and serum were determined by radioimmunoassay. The Dialysis, Dilution test and Recovery test as a preliminary procedure for determination of bile H. G. H. volume presented no effects on H. G. H. determination. The mean serum H. G. H. values were as fcdlow: Normal adult (32 cases) 1.724-0.14 mug/ml, acute hepatitis (8) 4 .18 i0 .88 , Chr. activ, hepatitis (18) 2 .37• hepatic cirrhosis (24) 5.09-40.70 (p<0.05) , hepatoma (8) 7 .9• congestion of liver (4) 4 .65 i0 .45 . The value in acute hepatitis and hepatic cirrhosis was significantly higher when compared with normal adults. The mean bile H. G. H. values were as follow: (only B-bile described) Normal adult 303.6-427.1 mug/ml , (Bile/Serum ratios. 146.5-4-17.5), acute hepatitis 199.8 4-33.0, (80.4-4-23.9) ,Chr. activ, hepatitis 291.84-72.9, (137.2-4-40.6), hepatic cirrhosis 215.74-22.5 (63.4• The value in acute hepatitis and hepatic cirrhosis was significantly lower than those of normal adults, thus there same with low bile/serum ratios. From this fact it is assumed that one mechanism responsible for the high serum H. G. H. value in acute hepatitis and hepatic cirrhosis patients is disturbance in the transfer o f H . G. H. in serum to bile in the presence of an impaired liver.

Peptic ulcer and protective mechanism of the gastric and duodenal ulcer

In this paper, results of histoenzymatological studies on the regenerating mucosa of the clamping and clamping-cortisone ulcer in rats are reported. In this study, beta-glucuronidase and acid phosphatase were stained with Azo-dye. In normal animal, these two enzymes were localized in the middle layer of the mucosa. After making the clamping ulcer, the activities of beta-G increased and reached a maximum at the 2nd ulcer week, especially in the marginal zone of ulcer, and then decreased. In the C-C ulcer rat, a delay of two weeks in reaching a maximum was observed compared with that of the C ulcer rat. Ac-P activities increased also after making the ulcer. However, a delay of one week in reaching a maximum was seen, compared with that of beta-G in the C ulcer and a delay of two weeks in the C-C ulcer. At the Ist ulcer week in the C ulcer, the margin of the damaged mucosa rolled down and the mucous neck ceils were implanted into the connective tissue which developed just above interrupted muscularis mucosa. The undifferentiated cells developed from the cells implanted and formed an epithelial ingrowth in the marginal connective tissue. These cells showed strong activities of beta-G and Ac-P. The immature mucous neck cells and mature cells were formed from these undifferentiated cells and they extended toward the surface of the ulcer. At the 3rd or 5th week, the surface of the ulcer was covered by the regenerated mucosal cell layer. Lower part of the regenerated mucosa showed positive activities of beta-G and Ac-P, but upper part of it did not show any activities. It means that the upper part of the regenerated mucosa is consisted of the mature or differentiated ceils which came from the immature cells in the lower part. On the other hand, in the C-C ulcer, epithelial implantation and epithelial ingrowth were imcomplete at the early stage of healing and extention of the regenerated ceils toward the surface of the ulcer was inhibited by strong development of the connective tissue in the middle stage of healing. Therefore, marked retardation of healing resulted in the C-C ulcer. From these findings, it was strongly suggested that failure of the implantation and epithelial ingrowth in the early stage of the ulcer might cause a prolongation of healing of ulcer.

Studies on the development of acute pancreatitis

About ten years ago, we observed that phospholipase C, the same as a-toxin of Clostridium welchii, is commonly demonstrated in the liver and it plays an important role as a lethal factor after ligation of the hepatic artery of dogs. Furthermore we have also observed that activity of phospholipase C increases in the ischemic liver caused by experimentally bile induced pancreatitis and this may be sometimes one of causes of death in the pancreatitis. And we confirmed that there is abundantly the other phospholipase, phospholipase A, in the pancreas tissue and juice. Following above studies, the role of phospholipase A has been investigated in etiology and pathophysiology of acute pancreatitis. Pathogenesis of an interstitial edema through the pancreatic duct, which is important as the primary stage of pancreatitis, could be divided into mechanical factor and chemical factor. Since we have observed that activated pancreatic enzyme injected into the pancreatic duct, such as trypsin or phospholipase A, can not induce pancreatitis if the injected pressure is too low or if the injected volume is under 0.3cc/Kg body weight, and that physiological saline can not induce pancreatitis even if the injected pressure is high or the injected volume is over 0.3cc/Kg body weight, therefore we have confirmed that on the development of acute pancreatitis it needs both factors, mechanical and chemical. This is also confirmed by our observation that the protective barrier* of the pancreatic duct epithelium stained by Alcian Blue is well preserved and pancreatitis has not been developed two months or more after ligation of the pancreatic duct alone in rabbit.

Studies on phospholipase a in dogs of experimental acute pancreatitis

The fu r t he r exper imental analysis by Zn 65 was per formed to criticize those clinical resul ts more accurately. The ra t io of the radioact ivi ty of pancreas to other organs was the highest in 96 hours a f te r in t ravenous injection of 50 9c Zn 65 into dogs. The Zn 6~ concentrat ion per mg of protein was high in microsomal f rac t ion at the beginning when the largest amount of Zn 65 was dis tr ibuted in microsomal supernatant . The dog pancreat ic juice a f te r DEAE-cellulose column showed five protein peaks among which the last appear ing smal l peak showed the h ighes t specific radioactivi ty of zinc. On these clinical and exper imenta l resul ts some addit ional considerat ions were discussed.