[Monitoring of hepatic arterial and venous output after orthotopic liver transplantation in man].
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Biomedical subjects
Publications and source records attributed to D Houssin.
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The development of liver transplantation in man emphasises the need for more work in the field of experimental liver transplantation. For this purpose the model of orthotopic liver transplantation in the rat is very useful but difficult to establish as a safe and reproducible technique. The aim of this study concerning acquisition of the orthotopic liver transplantation model in the rat was to define precise objectives for future investigators. Two investigators without experience in microsurgery each performed 75 orthotopic liver transplantations, which were divided into five consecutive series. In each series survival times of the recipients after transplantation were analysed according to the mean duration of the operative procedure and the mean portal vein clamping time. For each investigator, mean duration of the operative procedure progressively decreased to reach a minimum at the 45th graft. From that time on, the portal vein clamping time became less than 17 minutes and a significant increase in the post operative survival time of the recipient was observed. However it was only from the sixtieth transplantation on, with stable portal vein clamping time but technical mistakes fewer that a high success rate was observed.
We report the case of a young patient with end-stage auto-immune chronic active hepatitis and primary amenorrhea who became pregnant 18 months after orthotopic liver transplantation. She continued an uncomplicated pregnancy on treatment with ciclosporin A and spontaneously gave birth to a full term and healthy child.
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Free intestinal autograft has been recommended for oesophageal reconstruction following total circular pharyngolaryngectomy for cancer. Coloplasty or gastroplasty are commonly used for reconstruction of cervical and thoracic oesophagus. Necrosis of the plasty or anastomotic leakage can occur and may require the resection or reintegration of the pedicled graft into the abdominal cavity. For later reconstruction another pedicled graft may not be feasible and interposition of a free intestinal autograft can be a helpful method. The authors report a case of successful reconstruction of the cervical and thoracic oesophagus by a free ileal autograft, after the initial failure of a right coloplasty in a patient with previous gastrectomy. The free ileal autograft was interposed between the cervical oesophagus and the previous coloplasty repositioned in the lower part of the anterior mediastinum. The vessels of the graft were implanted onto the left common carotid artery and the innominate venous confluent.
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Orthotopic liver allografts in the nonrejecting DA-to-PVG strain combination and in the DA-to-LEW strain combination were studied at various times after transplantation for donor class I and class II MHC expression using immunohistological techniques and quantitative analyses. DA-to-DA isografts were also studied. In the isografts, weak class I induction on hepatocytes and biliary epithelium was noted from day 5, and this persisted to day 15, the last time point examined. In DA-to-PVG allografts, class I induction also appeared on hepatocytes and biliary epithelium from day 5, but was more intense than in the isografts. Nevertheless, the induction was patchy within most grafts, and in some grafts was not prominent. Quantitative absorption analyses demonstrated that the maximum increase in donor class I expression was only 3-fold over the normal liver. In the strong DA-to-LEW combination, class I induction on hepatocytes seemed to appear earlier, beginning at day 3, and was more uniform and intense than in the DA-to-PVG model from day 5. In the isografts, there was no induction of class II antigens on hepatocytes or biliary epithelium at any stage, but from days 5 to 15 there was a marked increase in the number of isolated, class II-positive cells in the hepatic lobule, probably representing class II induction in the Kupffer cells of the isografts. In DA-to-PVG allografts, biliary epithelium became class II-positive from day 5, and this persisted to day 30, the last time point examined. Weak but definite class II induction was seen on some hepatocytes from day 5 through day 30. However, the majority of hepatocytes remained class II-negative. By day 30, there was virtually no donor class II staining the sinusoids, but isolated class II-positive cells of recipient type were seen, the pattern suggesting a replacement of the graft Kupffer cells by recipient Kupffer cells at this stage. By quantitative absorption analysis, donor class II expression in the grafts increased approximately 5-fold. In DA-to-LEW allografts, class II induction was not noticeably different from that seen in the DA-to-PVG model, except that induction of class II antigens on the Kupffer cells possibly appeared earlier in this strain combination.
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Cyclosporine administration in patients with organ transplants may cause cholestasis. In the rat, intraperitoneal administration of cyclosporine, 10 mg/kg, for three weeks did not cause liver function test abnormalities or hepatic histological lesions. However a significant reduction of bile flow and bile acid secretion rates was observed. The fact that reduction of bile flow was related to a decrease of the bile acid-independent flow suggests that cyclosporine-induced cholestasis results from an inhibition of bile acid secretion. Whether this inhibition is caused by the parental molecule or by cyclosporine metabolites needs to be clarified.
The need for liver grafts is critical in countries where brain death is not accepted as a legal criterion for organ retrieval. This experimental study was conducted with nonhuman primates in order to evaluate the feasibility of liver transplantation using a living donor. An original technique was employed to remove the left part of the liver from the donor: transection of the parenchyma was done while the blood flow was kept to the left part of the liver. In the recipients, the graft was placed heterotopically. No blood transfusions were administered to donors or recipients. In spite of a few failures, due to consequences of intraoperative bleeding, several donor operations using this original technique were successful, in the immediate postoperative period as well as several months later. Among the recipients, the large number of early failures suggests that the heterotopic position is probably not the appropriate one and that orthotopic transplantation should be preferred.
This study was conducted to evaluate various methods to reduce the mortality rate following acute portal vein occlusion in rat: systemic heparinization, intravenous saline infusion, enteral antibiotics and simultaneous clamping of the superior mesenteric artery were tested alone or in combination. Each of these treatments improved the survival rate after 45 or 60 min occlusion of the portal vein; combination of all treatments provided better results than each treatment alone. These results indicate that, following acute portal vein occlusion in the rat, several factors cooperate to cause death. The decrease in mean arterial blood pressure during occlusion of the portal vein was correlated with the mortality rate; this correlation was significant in the animals with 45 min occlusion of the portal vein. It appeared in this study that, when used in association, simple therapeutic methods are highly effective in improving the survival rate following acute portal vein occlusion in the rat.
Danazol, an inhibitor of pituitary gonadotropin, has been proposed in the treatment of systemic lupus erythematosus (SLE). We report the case of a female patient with SLE in whom a hepatocellular carcinoma was discovered after 4 years of treatment with danazol. Except for 3 days of hypochondrium pain, there were neither clinical signs of liver tumor nor biological abnormalities. An ultrasonography showed 2 tumors of the liver. At histological examination after surgery, one of the tumors was found to be a benign adenoma, while the other was a well differentiated hepatocellular carcinoma. When longterm danazol therapy is required, ultrasonography may be useful for early tumor detection.
From a practical point of view, the care of a child after liver transplantation comprises 3 periods with decreasing severity: -the first one takes place in the intensive care unit: immunosuppression is started with steroids, azathioprine and cyclosporine and four major complications are sought for and treated: primary graft dysfunction, acute rejection, hepatic artery thrombosis and infection; -the second period takes place in conventional hospital settings: cyclosporine is progressively switched from IV to oral; rejection, cytomegalovirus infection and biliary complications are sought for and treated; -the third period takes place at home: the level of immunosuppression is progressively lowered under biochemical supervision; long-term complications (renal and malignancies) are detected.
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A technique is described for orthotopic liver transplantation in the rat using polyethylene cuffs to re-establish subhepatic cava and portal vascular anastomoses. This procedure reduces the time of portal clamping, an important factor of survival. This technique was found to be reliable with a 72.9% long-term survival (more than 60 days) in an experimental group of 59 iso- and allografts. The method was employed in 212 animals during studies on iso-, allo- and xenografts to evaluate the tolerance and rejection mechanisms in rats of pure strain.