19, 5-7 (1975)
in Pig Liver Transplantation DONG K. KIM, M.D., RICARDO J. LAVARELLO, M.D., PAUL P. ROSEN, M.D., AND JOSEPH G. FORTNER, M.D. Laboratory ofSurgical Memorial Sloan-Kettering
Research and Department of Pathology, Cancer Center, New York, New York 10021
Submitted for publication November 15. 1974
nerves. Heineke-Mikulicz pyloroplasty was performed following vagotomy. Poland-China pigs, 3-4-months-old, of either sex, weighing 15-20 kg, were operated upon. A total of 29 orthotopic liver transplantations were performed according to the modified technique of others [3, 61. Animals were divided into control (no vagotomypyloroplasty, 15 pigs) and vagotomy (vagotomy-pyloroplasty, 14 pigs) groups in an alternating way. Anesthesia was done by Pentothal sodium induction and halothane (0.5-l %) maintenance. Postoperatively, intravenous fluids were given for 2-3 days, after which Purina pig chow was started. Immunosuppressive treatment was not given. Blood was analyzed twice weekly for electrolytes, CBC, LDH, GOT, bilirubin, alkaline phosphatase, total protein and albumin. Autopsy was performed when the recipient pig died.
Morphophysiological similarities of the livers of the pig and human make the pig an ideal model for the study of liver transplantation. Frequent gastric ulcers after transplantation, however, are troublesome. Although vagotomy-pyloroplasty prevents pig gastric ulcer very effectively , peculiarities of the pig anatomy hinder its application. The present communication reports a simple method for vagotomy and its results in pig liver transplantation. MATERIALS AND METHODS Because there is no subdiaphragmatic segment of the esophagus or diaphragmatic hiatal ring in pigs, vagotomy by conventional approach through the abdomen is difficult to perform. The technique reported here involves transdiaphragmatic truncal vagotomy by entering the periesophageal pleural sac through the abdomen (Fig. 1). The periesophageal pleural sac is a closed cavity in the mediastinum. Most of its wall is formed by the parietal pleura, but the diaphragm around the esophagogastric junction contributes part of its inferior border. Hence, this sac could be entered through an incision at the diaphragm made just above the esophagogastric junction without producing pneumothorax. Two vagal trunks along the esophagus are readily accessible in the sac. Care must be taken, however, not to perforate the wall of the periesophageal pleural sac where vagal trunks are densely adhered. To avoid this mishap, vagus nerves were crushed by clamping and ligated with heavy silk without an attempt to resect the
RESULTS Only the pigs that survived 4 days or longer after transplantation produced gastric ulcer. In the control group, nine pigs survived 4 or more days, and all of them developed gastric ulcer. The ulcers involved the cardia-lesser curvature of the stomach in five, the greater curvature in two, and the antrum in two pigs. The ulcers were massive in size, being an average of 5 x 10 cm in diameter, and penetrated the muscular layers of the stomach, except in two pigs where the ulcers were superficial and without complication. All seven penetrated ulcers produced a fatal complication: Massive GI 5
Copyright o 1975 by Academic Press, Inc. All rights of reproduction in any form reserved.
19, NO. I, JULY
FIG. I. Anatomy of the periesophageal pleural diaphragm at the esophagogastric junction anteriorly.
sac and the vagus nerves. Note an incision made to the
bleeding in five (survival in days, 6, 6, 9, 11 and 27) and gastric perforation in two pigs (survival in days, 14 and 16). Of two pigs with superficial ulcer, one died of liver necrosis after 4 days, and the other was sacrificed 335 days after transplantation. In the vagotomy group, eight pigs survived 4 days or longer, but only one pig produced gastric ulcer. This pig died of GI bleeding and allograft rejection on the 330th posttransplant day. Of the other pigs, four died of pneumonia (survival in days, 6, 8, 12 and 30), one of liver abscess (31 days), one of volvulus of the small bowel (13 days), and one of rejection (9 days). Rejection was diagnosed on the basis of ruling out other causes of death and histologic findings of mononuclear cell infiltration in the hepatocytes and subendothelial thickening of the small hepatic vessels. There was also scattered focal necrosis of the hepatocytes in one pig that survived 9 days. No correlation was seen between the incidence of gastric ulcer and the degree of liver function derangement. DISCUSSION Frequent gastric ulcers after liver transplantation in pigs were reported by others [ 1, 41, but the incidence of gastric ulcer in con-
trol pigs of this study seems exceptionally high. On the other hand, it is remarkable to observe the rarity of gastric ulcer in vagotomized pigs, suggesting a highly effective role for vagotomy-pyloroplasty in preventing gastric ulcer after liver transplantation. Gastric ulcers were found to be frequent in rapidly growing young pigs (2). Norton et al.  reported 100%incidence of gastric ulcer in piglets (6-12 kg) of 8-12 weeks of age, stressed by hemorrhage of 40% blood volume. They also observed that the adult pigs (40-60 kg) similarly stressed produced no gastric ulcer. Pigs in the current study were relatively young, 1416weeks-old, and weighed 15-20 kg. This young age of the pigs might explain the high incidence of gastric ulcer in this study. It is conceivable that young pigs, due to their prematurity, might have a weak area in the gastric barrier against ulcerogenic effect. The massivenessof pig gastric ulcer is also suggestivethat the weak area of the stomach was ulcerated as a whole. CONCLUSION Vagotomy-pyloroplasty, by use of described techniques, prevents gastric ulcer very effectively, and no technical complication is observed. Based on these ob-
servations, it would seem best to avoid a young pig.or to perform vagotomy-pyloroplasty routinely in pig liver transplantations.
ACKNOWLEDGMENTS We thank Dr. R. Csurny, Mr. S. Denecko, Mr. R. Barters, Mr. A. Carreras, Mr. A. Torres, Mr. R. Torres, and Mrs. A. F. Zaki for their technical assistance.
REFERENCES 1. Belzer, F. 0.. May, R., Berry, M. N., Phil, D., and Lee, J. C. Short term preservation of porcine livers. J. Surg. Res. 10:55, 1970. 2. Blood, D. C., and Henderson, J. A. Veterinary
Medicine, 3rd Ed., p. 874. Williams and Wilkins, Baltimore, MD, 1968. Came, R. Y., Yoffa, D. E., White, H. J. O., and Maginn, R. R. A technique of orthotopic liver transplantation in the pig. Br. J. Surg. 55:203, 1968. Caine, R. Y., White, H. J. O., Yoffa, D. E., Maginn, R. R., Binns, R. M., Samuel, J. R. and Molina, V. P. Observations of orthotopic liver transplantation in the pig. Br. Med. J. 2:478, 1967. Norton, L., Nolan, P., Sales, J. E. L., and Eiseman, B. A swine stress ulcer model. Ann. Surg. 176:133, 1972. Terblanche, J., Peacook, J. H., Bowes, J., and Hobbs, D. E. F. The technique of orthotopic liver transplantation in the pig. J. Surg. Rex 8:151, 1968.