Insulin, glucagon, and insulin/glucagon mixtures have been infused for four days into the left portal vein of dogs after portacaval shunt. In the left but not the right liver lobes, insulin alone reduced atrophy, preserved hepatocyte ultrastructure, and trebled cell renewal. Glucagon alone had no effect. In small doses, glucagon did not potentiate the action of insulin and in large doses it may have reduced the insulin benefit. These studies explain the development of the previously mysterious Eck fistula syndrome, provide clues about in-vivo cell growth control by hormones, and suggest new lines of inquiry about the pathogenesis and/or treatment of several human disease processes.

Summary4 days after portacaval shunt, the livers of normal dogs had pronounced atrophv and other structural abnormalities. These changes were greatly reduced in the left liver lobes, but not in the right, by a constant infusion to the left portal vein of insulin in non-hypoglyczmic doses. These experimental findings should have implications in clinical medicine.ISTRODl:CTIOS DURING the past ten years we have developed evidence that substances, termed hepatotrophic factors, in the portal venous blood of dogs can profoundly influence liver function as well as the size, internal structure, chemical composition, and dividing capability of the hepatocytes. 1 -' In most of these experiments, techniques were exploited that permitted comparative study of two portions of the same liver which were given different kinds of portal venous inflow under diabetic or non-diabetic conditions. The concept emerged that manifold hepatic processes are controlled or influenced by hormones that are generated by splanchnic organs and delivered straight to the liver, with a presumably augmented significance because of the episodically high concentrations of nutrient substrate in the same blood. 2 -' Insulin has' been identified as the most important of these undoubtedly multiple portal hepatotrophic constituents. 2·~ If the foregoing conclusions were correct, the ztiology METHODSEight normal mongrel dogs averaging about 19 kg had large side-ta-side portacaval shunts (group I)_ The shunts were made completely diverting by ligating the right and left portal branches at their origin. Thirteen more dogs of approximately the same weight had the same procedure except that the tip of a fine infusion catheter was placed into the tied-off left portal branch and led outside to a small finger pump that was incorporated into a light body cast. A pump infusion of regular insulin diluted in heparinised physiological saline was started, using volumes that never exceeded 21 ml/day. The thirteen test dogs were divided into two subgroups of nine (group 2) and four (group 3) on the basis of the insulin dose that was given (see accompanying table). Ten normal dogs in our laboratory had morning blood-sugars of 61·1-!9·2 (S.D.) mg/dl. The nine test dogs receiving the larger dose of insulin for 4 days had 30 morning blood-sugar concentrations that were 64·8± 13·0 (S.D.) mg/dl. The four dogs treated with low insulin doses had 13 sugar determinations of 71·2,:8·4 (S_D.) mg/dl. All dogs were on an ad-libitum diet from the 1st postoperative day onward.The experiments lasted 4 days_ Their design permitted an evaluation of any direct protective effect of insulin upon the left lobar hepatic tissues as well as a judgment whether insulin which passed through the left lobes without being consumed or degraded had a spillover effect upon the right side after recirculation. Histopathological end-points were used. The size of the hepatocytes was determined on hzmatoxylin-and-eosin-stained sections by a method previously described. l In essence, the technique cORsists in ...

The purpose of this report is to describe some unusual manifestations that followed a very extensive hepatectomy (85 to 90 per cent) and to comment about the less than complete degree of regeneration that occurred postoperatively. Case ReportA nineteen year old girl had undergone exploration one week prior to admission because of a huge mass that occupied all of the upper abdomen and which, as indicated by liver scan ( Figure 1, left), replaced much of the liver. Tissue diagnosis of a well differentiated hepatoma was made from the previous exploration. Measurement of alpha fetoprotein was negative. For some months she had had severe abdominal pain that was eventually demonstrated to be due to hemorrhage into the tumor. A selective celiac arteriogram demonstrated a single hepatic artery. (Figure 1, right.) Although the entire arterial blood supply appeared to be involved in tumor, an attempt at resection was decided on.The procedure was carried out May 10, 1972, through a bilateral subcostal incision. The right hepatic artery, portal vein, and hepatic duct were ligated and divided. Branches of the left main hilar structures passing to the medial segment of the left lobe were cut, leaving only the lateral segment connected. The right and middle hepatic veins and all the small hepatic veins entering the inferior vena cava from the caudate lobe were sacrificed so that only the left hepatic vein remained. The lateral segment of the left lobe was smaller than usual, constituting approximately 15 per cent of the normal liver mass. Part of this segment had to be excised to remove the tumor, which extended to the left of the falciform ligament. The remaining hepatic fragment was thought to represent between 10 and 15 per cent of a normal liver. The excised specimen weighed 2,100 gm and had areas of hemorrhage within the tumor. It was examined histologically in five university departments of pathology noted for their special interest in liver disease. All consultants described the well-differentiated features of the neoplasm. Two diagnoses of hepatocellular adenoma were made, but three of the consultants classified the lesion as a hepatoma (hepatocarcinoma).After resection was completed, the residual fragment felt tense, a condition that was aggravated by efforts to cover the raw liver edge with the falciform ligament or omentum. Consequently, the raw surface was left open. The large right subphrenic cavity was extensively drained. The operation required nine hours and 5,500 ml of blood. Postoperative ventilatory support was provided for the first five hours. The patient was completely disoriented for three days but then suddenly became lucid.Requests for reprints should be addressed to Thomas E. Starzl, MD. Department of Surgery, University of Colorado Medical Center, 4200 East Ninth Avenue, Denver, Colorado 80220. NIH Public Access Author ManuscriptAm J Surg. Author manuscript; available in PMC 2010 October 25. Serious abnormalities in liver function, including jaundice, did not clear until the third week. (Figure 2) A...