The feasibility of hepatic homotransplantation has been clearly established in principle inasmuch as several animals are still alive almost 3 years after complete hepatectomy and liver replacement. Both orthotopic and auxiliary operations are complicated surgical techniques. Nevertheless, the results in dogs are comparable to those which can be obtained with homotransplantation of the kidney.In man the problem is more difficult. In patients who have a need for such operations, there is invariably a metabolic disorder more complex than that caused by renal failure. In addition, the new organ must function efficiently from the beginning since its complete functional failure leads to death within a few hours. There is no recourse to an artificial liver to maintain life until the reversal of an injury which is caused by either ischemia or rejection.Nevertheless, research of several kinds may soon make possible the successful use of hepatic transplantation procedures for the definitive treatment of human liver disease as exemplified by the reports in this symposium concerning new techniques of organ preservation, histocompatibility analysis, and immunosuppression.

UNTIL last year, the kidney was the only organ which had been transplanted with subsequent significant prolongation of life. There had been nine reported attempts at orthotopic liver transplantation; seven in Denver 2 2 + 2 3 and one each in Bostonle and P a r i~.~ Two of these patients had succumbed within a few hours after operat i~n ,~, 22 and none had lived for longer than 23 days.This dismal picture has changed within the last 9 months, inasmuch as seven consecutive patients treated with orthotopic liver transplantation from July 23, 1967 to March 17, 1968 all passed through this previously lethal operative and postoperative period. Three of the recipients are still alive after 9, 23$, and 1 months; the others died after 2, 3%, 454, and 6 months. MethodsThe Recipients. Summary information for the seven patients is given in Table 1. Their ages were 13 months to 16 years. Six were females. The indications for transplantation, which had been established by earlier explorations at other hospitals, were

No abstract

UNTIL last year, the kidney was the only organ which had been transplanted with subsequent significant prolongation of life. There had been nine reported attempts at orthotopic liver transplantation; seven in Denver 2 2 + 2 3 and one each in Bostonle and P a r i~.~ Two of these patients had succumbed within a few hours after operat i~n ,~, 22 and none had lived for longer than 23 days.This dismal picture has changed within the last 9 months, inasmuch as seven consecutive patients treated with orthotopic liver transplantation from July 23, 1967 to March 17, 1968 all passed through this previously lethal operative and postoperative period. Three of the recipients are still alive after 9, 23$, and 1 months; the others died after 2, 3%, 454, and 6 months. MethodsThe Recipients. Summary information for the seven patients is given in Table 1. Their ages were 13 months to 16 years. Six were females. The indications for transplantation, which had been established by earlier explorations at other hospitals, were

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 ...