Liver transplantation from elderly donors.
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Biomedical subjects
Publications and source records attributed to D Castaing.
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Despite the availability of whole-blood cyclosporine assays, the different responses of individual patients to its administration after transplantation continue to pose clinical problems, particularly with respect to toxicity. Fifty-seven recipients of first orthotopic liver transplants were studied between January 1992 and July 1992. Initial immunosuppression was carried out with azathioprine, methylprednisolone and cyclosporine, at a dose of 1 mg/kg/day adjusted to achieve blood levels between 400 and 600 ng/ml. Cyclosporine levels were measured 12 hr after the start of intravenous administration and correlated with the occurrence of toxic complications. Twelve patients experienced toxic complications in the first 7 days after orthotopic liver transplantation. These were neurological in six patients (of whom four also had kidney failure) and renal complications in the other six patients. All complications were reversed by reducing or stopping administration of cyclosporine. We noted excellent correlation between the occurrence of complications and cyclosporine whole-blood levels (p < 0.0001) despite the fact that levels did not exceed the therapeutic range. However, no correlation was observed between toxicity and cumulative dosage. In this study we were able to demonstrate that a standardized dose of cyclosporine does not prevent the occurrence of toxic side effects even when cyclosporine whole-blood levels are subsequently maintained in the therapeutic range. This highlights the importance of the first dose of cyclosporine and consequent early postoperative blood levels and indicates that these problems are unlikely to be overcome until a method of predicting individual requirements can be established in clinical practice.
The dramatic development of liver transplantation compared to a relative shortage of donors has brought a renewed interest to xenotransplantation. Because of anatomical and immunological compatibilities, nonhuman primates are the most appropriate donors. The aim of this work was to analyze the different problems of a baboon-to-man liver xenotransplantation. Thirty baboons bred in a French Primatology Center were studied. The analysis of anatomical, microbiological, and immunological data showed that only 8 baboons out of 30 were suitable as donors for xenotransplantation. Considering these data and the ethical issues, the actual feasibility of xenotransplantation programs is discussed.
Two hundred and ninety-one patients with hepatocellular carcinoma were treated by chemoembolization (CE), using ethiodized oil, doxorubicin, and a gelatin sponge. Patients with thrombosis of either the portal vein or a main branch were excluded. The mortality rate in the first 2 months after treatment was 7% in noncirrhotic patients, 2.8% in patients with class A cirrhosis, 8% in patients with class B cirrhosis, and 37% in patients with class C cirrhosis. The tumor diameter remained the same in 55.3% of patients, was reduced by up to 50% in 20% of the patients, was reduced by more than 50% in 7.3% of the patients, and almost completely disappeared in 1.8% of the patients. The diameter of the tumor increased in 15.6% of patients. Forty-three patients underwent a resection or transplantation after chemoembolization. Histologic examination of the specimens revealed significant necrosis of the tumor. The long-term survival rate at 2 years was 49% for class A cirrhotics, 29% for class B cirrhotics, and 9% for class C cirrhotics. Complications included cholecystitis (10%), vasculitis (14%), renal decompensation (13%), an increase in ascites (14%), and jaundice (12%). Chemoembolization is an effective and safe initial treatment for hepatocellular carcinoma. It is effective in producing tumor necrosis and reducing the size of the tumor. Improvement in survival was noted when patients who underwent chemoembolization were compared with an historical series of untreated patients, and resection and transplantation are kept as options.
The effect of storage temperature on early graft function following liver transplantation was investigated by analyzing the results following transplantation during three periods in which different techniques for graft storage were used. The techniques involved ice-packing (period 1), storage in a standard operating room refrigerator without ice-packing (period 2) and storage in an accurately controlled refrigerator without ice-packing (period 3). In period 2 there was a significantly higher incidence of histological lesions, primary non-function and retransplantation compared to periods 1 and 3. It was concluded that this was due to inaccurate control of the standard refrigerator in period 2, thus allowing the temperature of the graft to increase, while in periods 1 and 3 the graft temperature was kept close to 4 degrees C by ice-packing and accurate refrigerator control, respectively. These results demonstrate that accurate control of storage temperature is important in terms of subsequent graft function. This may become more important as storage times are progressively increased with the use of UW solution.
A patient with undiagnosed cirrhosis presented with massive haematuria 16 years after augmentation colonoplasty. Portal hypertension (PHT) was responsible for a portocaval collateral circulation with vesical varices detected by low pressure endoscopy performed between episodes of haematuria. A very similar case was published in 1991. Surgical haemostatis with partial or total resection of the colonoplasty was only temporarily effective in our patient, who subsequently underwent liver transplantation due to repeated episodes of hepatic encephalopathy. No recurrence of haematuria was observed six years after the diversion. This rare cause of haematuria must be considered in view of the widespread use of intestinal conduits in urology: a dozen cases have been reported after transileal cutaneous ureterostomy, occurring an average of 3 years after the operation. Direct treatment of the varices, either by surgical devascularisation or resection or be endoscopic laser sclerosis or coagulation, is only temporarily effective. Treatment of the PHT appears to be the most effective measure in the long term: beta-blockers administered in the absence of episodes of haematuria or portal by-pass surgery in the case of failure.
In the last four years, 551 liver transplantations have been performed at the Paul Brousse center, for a total of 840 liver transplantations performed from 1984 to 1992. Several changes have been observed in the field of liver transplantation in the past years. The field of immunosuppression was marked mainly by the advent of FK506 as a preventive treatment of rejection and as a treatment of cortico-resistant rejection. Results are still under analysis. From the surgical viewpoint, the main modification was the advent of UW solution, which extends cold ischemic time. However, our policy was to maintain the cold ischemic time at less than 12 hours. Primary indications for liver transplantations have changed with an increase in the rate of patients transplanted for cirrhosis related to hepatitis virus infection: from 24% in the period 1984-1988 to 42% in the period 1989-1992. The difference was due mainly to HCV-related cirrhosis, which increased from 8% to 20%. Alcoholic cirrhosis was a rare indication in the period 1989-1992 (3.4%); however, it was an increasing indication in the last 2 years. In order to improve the long-term results, major attention was given to the recurrence of initial liver disease. In patients transplanted for HBsAg-positive liver disease, long-term passive anti-HBs immunoprophylaxis was administered, which reduced the rate of HBV recurrence in patients without HBV replication before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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A modification of the technique of liver transplantation by the face-à-face venacavaplasty is described and the use in four patients reported. This technique enables livers with a small vena cava to be inserted in an anatomic fashion and should help increase the use of such grafts where disparity between vessel size exists.
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Gallbladder cancer is the most common malignant tumor of the biliary tract, but its early diagnosis is uncommon. The use of ultrasonography has increased the detection of benign gallbladder tumors, and the premalignant potential of gallbladder adenomas is now undisputed. Adenomyomatosis of the gallbladder has recently been suggested to have malignant potential, and we report a case of adenocarcinoma of the gallbladder occurring in localized adenomyomatosis that was successfully treated by radical curative surgery. The more rigorous use of ultrasonography and a more aggressive approach to "benign" polypoid lesions of the gallbladder may represent the best way of achieving early diagnosis and cure in gallbladder cancer.
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Intraoperative echography helps both in the detection of the tumor and in the assessment of the vascular and biliary anatomy. The experience reported here was gained with 114 carcinomas in cirrhotic livers, 46 carcinomas in normal livers, 330 cases of metastases to the liver and 55 benign tumors. Ultrasound has modified the surgical prediction in 10 to 30% of all cases, according to the group.
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