Portacaval shunt for glycogen storage disease and hyperlipidaemia.

Complete portacaval shunt was used to treat 10 patients with glycogen storage disease. A favourable effect was noted on body growth and a number of metabolic abnormalities. More recently, continous night feedings with an intermittently placed gastric tube or through a gastrostomy has been shown to be helpful either before or after portacaval shunts. Such alimentation techniques may eliminate the need for shunts in some patients and be of adjuvant benefit in others. Portacaval shunt was also used for three children who had homozygous Type II hyperlipidaemia. Substantial reductions in serum cholesterol concentration were observed, as well as resorption of xanthomas. Reversal of some cardiovascular lesions has been documented. The benefits of portacaval shunt in these disorders is probably due to the change in the hormone climate of the liver and the whole organism brought about by diversion of the hormone-rich splanchnic venous blood around the liver

The influence of portal blood upon lipid metabolism in normal and diabetic dogs and baboons

It has been reported that hyperlipidemia can be alleviated in human beings with an end to side portacaval shunt. Understanding the mechanism of the effect has important implications, including the possibility of devising other ways of lowering serum lipid levels. In this investigation, the influence of splanchnic venous blood on lipid metabolism was evaluated in dogs and baboons by altering the portal venous inflow to all, or portions, of the liver and by measuring the effects on different end points, including the serum lipid concentrations and the rate of hepatic lipid synthesis. In other studies, analyses have been made regarding the effect of alloxan induced insulinopenia and of total pancreatectomy on these processes. The results indicate that the effect of complete portal diversion upon serum lipids is mainly due to diversion of the hormone rich venous return from the upper splanchnic organs, although the bypass of the nutritionally rich blood returning from the intestines may play a secondary role. Therefore, a reduction of hepatic lipid synthesis is an important, although not necessarily the sole, factor in the antilipidemic influence of portacaval shunt. The effects upon synthesis and blood lipids are due more to the diversion of endogenous hormones than to the bypass of intestinal nutrients. The substances in portal venous blood that subserve hepatic lipid metabolism are presumably largely the same as the hepatotrophic factors which have been described before as profoundly affecting hepatic structure, function, and the capacity for regeneration. These portal blood factors are multiple and interrelated, but the single most important one seems to be insulin

Biliary complications after liver transplantation: With special reference to the biliary cast syndrome and techniques of secondary duct repair

In 93 consecutive cases of orthotopic liver transplantation, there were 24 examples of biliary obstruction and eight of bile fistula formation. Six of the obstructed livers developed biliary cast formation so extensive that the smaller intrahepatic ducts became plugged to an extent that they could no longer have been treated by surgical means. In each of the six cases, the most important causative factor was neglected obstruction of the large bile ducts with the intrahepatic lesions apparently being late and secondary. Stone and/or cast formation also occurred in other obstructed livers in the presence of bile fistulas, but these deposits were limited to the large ducts where they could have been or were removed. Although homograft bile undoubtedly has increased lithogenicity at certain postoperative times, the data from the present study have shown that biliary sludge formation essentially is always associated with defective bile duct reconstruction, and the observations have underscored the urgency with which reoperation must be considered. Techniques of secondary intervention have been described, with emphasis on conversion of cholecystojejunostomy to choledochojejunostomy. This operation has permitted salvage of homografts in eight of nine trials and the survival of seven patients. © 1977

Liver Transplantation for Budd-Chiari Syndrome

Orthotopic liver transplantation was accomplished in a 22-year-old woman dying of the Budd-Chiari syndrome. She is well and has normal liver function 16 months postoperatively. In view of the good early result, it will be appropriate to consider liver replacement for this disease in further well-selected cases. © 1976, American Medical Association. All rights reserved

Infections Complicating Orthotopic Liver Transplantation: A Study Emphasizing Graft-Related Septicemia

In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant. © 1976, American Medical Association. All rights reserved

The effect of diabetes mellitus on portal blood hepatotrophic factors in dogs

Ten nondiabetic dogs were submitted to a procedure called splanchnic division which directed the nutrient rich venous return from the intestines into the left lobes of the liver and the hormone rich pancreatico gastroduodeno splenic venous return into the right lobes. Two mth later, the right lobes had undergone the expected gross and microscopic hypertrophy. Compared with the abnormal shrunken and glycogen depleted hepatocytes of the left lobes, the large and otherwise normal hepatocytes of the right lobes had a higher rate of cell division as judged by microscopic examination, measurements of deoxyribonucleic acid synthesis and the results of autoradiography. Both sides had greater cell replication than in the livers of normal unaltered dogs. The dominance of the right lobes following splanchnic division was almost completely eliminated by the prior creation of alloxan induced diabetes in 4 dogs and by the performance of total pancreatectomy at the same time as splanchnic division in 6 dogs. In these 10 diabetic dogs, which were treated with Sc administered insulin for the 2 mth period of the postoperative study, hepatic lobar and cell size were nearly equal on both sides. By light and electron microscopy, the hepatocytes on both sides had abnormalities, somewhat less pronounced on the right. However, the most active cell division was now transferred to the left lobes. The results with alloxan induced diabetes were similar to those after total pancreatectomy, except that lipid deposits were less on both liver sides in the alloxan experiments, and the glycogen was selectively reduced in the right lobes. The latter finding presumably was due to the continued action of glucagon in dogs made diabetic with alloxan. 12 nondiabetic dogs had a procedure called partial portacaval transposition which directed systemic venous blood from the hindquarters, kidneys and adrenal glands into the left lobes of the liver and the total splanchnic venous return into the right lobes. Two mth later, the degree of relative hypertrophy and hyperplasia of the glycogen rich right lobes was even greater than after splanchnic division, as was the morphologic damage to the left lobar hepatocytes. The degree of right lobar hypertrophy following partial portacaval transposition was reduced but not eliminated by pre existing alloxan induced diabetes in 4 dogs and by concomitant total pancreatectomy in 6 more dogs. The dogs were Sc treated with insulin. Structurally, the hepatocytes on the right side after 2 mth were in better condition than were those on the left, although both were abnormal. The dominance of cell division on the right side was reduced, as judged by standard microscopy and by autoradiography, but there was not a shifting of sides. The biochemical analyses reflected the presence or absence of glucagon. These findings are consistent with the earlier multifactorial hypothesis which holds that portal hepatotrophic factors are mainly interreacting hormones generated by splanchnic organs and delivered straight to the liver and that the hormone interrelationships might have augmented significance because of the high concentration of nutritional substrate in the same venous blood. The observations also substantiate by direct testing the suggestion that insulin is the most important hepatotrophic factor and that it profoundly affects many aspects of liver cell structure, division and function