Biomedical subjects
Publications and source records attributed to S Iwatsuki.
A girl aged 6 years 9 months with severe heart disease secondary to homozygous familial hypercholesterolaemia underwent orthotopic cardiac transplantation and her liver was replaced with the liver of the same donor. In the first 10 weeks after transplantation serum cholesterol fell to 270 mg/dl from preoperative concentrations of more than 1000 mg/dl.
Post-transplant lymphomas or other lymphoproliferative lesions, which were usually associated with Epstein-Barr virus infections, developed in 8, 4, 3, and 2 recipients, respectively, of cadaveric kidney, liver, heart, and heart-lung homografts. Reduction or discontinuance of immunosuppression caused regression of the lesions, often without subsequent rejection of the grafts. Chemotherapy and irradiation were not valuable. The findings may influence policies about treating other kinds of post-transplantation neoplasms.
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Pancreaticoduodenal transplantation was performed with cyclosporine and steroid immunosuppressive therapy in 10 mongrel dogs that had pancreaticoduodenectomy. There was an average animal survival of 50.6 days and an average duration of normoglycemia of 41.8 days. We suggest that pancreaticoduodenal transplantation, which was abandoned as a clinical procedure 10 years ago, be reconsidered for clinical application.
A total of 42 patients who had failed prior renal transplantation underwent repeat cadaveric transplantation using cyclosporin A and low dose steroid immunosuppression. Patient survival at 1 year was 100 per cent. Over-all graft survival was 83 per cent at 1 year, which was significantly better than had been obtainable previously in this high risk group. Repeat cadaver transplantation with cyclosporin A is safe and offers those who have failed previous transplantation an opportunity for existence free of dialysis.
A venous bypass technique (BP) that does not require the use of systemic anticoagulation is used routinely at our institution in all adult patients during the anhepatic phase of liver transplantation (LT). Complete cardiopulmonary profiles were obtained in a subset of 28 consecutive cases. During the anhepatic phase while on bypass, mean arterial pressure, central venous pressure, and pulmonary arterial wedge pressure were maintained at prehepatectomy levels. Oxygen consumption fell secondary to a decrease in temperature and the removal of the liver. Consequently, cardiac index fell without an increase in arterial-venous O2 content difference, reflecting adequate tissue oxygenation. Compared with 63 patients in a previous series given LT without bypass (NBP), the 57 total BP patients experienced better postoperative renal function (p less than 0.001), required less blood use during surgery (p less than 0.01), and had better survival 30 days after LT. The equivalency of 90-day survival in these groups results from the lack of effect of BP on the long-term survival of patients considered at high risk for metabolic reasons. BP patients at high risk for technical considerations, however, survived LT whereas NBP patients did not. BP offers other advantages important in establishing LT as a service-oriented procedure.
Twelve dogs had transplantation of almost the entire small intestine in the orthotopic location; immunosuppression was with cyclosporine and prednisone. Half the dogs had survival of at least one month, and a third lived for at least four months. Two of the animals are still living after 550 and 555 days. Maintenance of nutrition, and absorption of D-xylose and fat were better than in control animals with an iatrogenic short gut syndrome, but distinctly worse than that of normal dogs.
Computerized tomography (CT) of liver is used in oncologic practice for staging tumors, evaluating response to treatment, and screening patients for hepatic resection. Because of the impact of CT liver scan on major treatment decisions, it is important to assess its accuracy. Patients undergoing liver transplantation or resection provide a unique opportunity to test the accuracy of hepatic-imaging techniques by comparison of findings of preoperative CT scan with those at gross pathologic examination of resected specimens. Forty-one patients who had partial hepatic resection (34 patients) or liver transplantation (eight patients) for malignant (30 patients) or benign (11 patients) tumors were evaluable. Eight (47%) of 17 patients with primary malignant liver tumors, four (31%) of 13 patients with metastatic liver tumors, and two (20%) of 10 patients with benign liver tumors had tumor nodules in resected specimens that were not apparent on preoperative CT studies. These nodules varied in size from 0.1 to 1.6 cm. While 11 of 14 of these nodules were less than 1.0 cm, three of 14 were greater than 1.0 cm. These results suggest that conventional CT alone may be insufficient to accurately determine the presence or absence of liver metastases, extent of liver involvement, or response of hepatic metastases to treatment.
Techniques have been developed which permit removal of the kidneys, liver, heart and other organs from the same donor without jeopardy to any of the individual grafts. The guiding principle is avoidance with all organs of warm ischemia. This is achieved by carefully timed and controlled infusion of cold solutions into anatomic regions, the limits of which are defined by preliminary dissection.
During a 24-month period (May 1981 to May 1983), 47 pediatric patients (ranging in age from 7 months to 18 years) underwent orthotopic liver transplantation using cyclosporine and prednisone. Major indications were biliary atresia/hypoplasia, and metabolic liver disease. Thirty-two of 138 patients evaluated for the procedure died prior to transplantation. Thirty patients are alive from 6 to 29 months later including 7/15 patients who required retransplantation. Twenty-one of 32 patients are alive at 1 year following initial transplantation. All 30 survivors are clinically well and living at home; only one has an abnormal bilirubin level. Serious, life-threatening medical and surgical complications were common during the early months following transplantation. With one exception, deaths and major rejection episodes occurred early (before 120 days). All survivors are relieved of the stigmata of chronic liver disease, and many have demonstrated catch-up growth. Liver transplantation is an effective treatment for end-stage pediatric liver disease.
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Whole cadaveric pancreata were transplanted to the pelvic extraperitoneal location in four patients with diabetes who previously had undergone successful cadaveric renal transplantation. One graft was lost within a few hours from venous thrombosis but with patient survival. The other three are providing normal endocrine function after two and a half, 11 and 12 months. The exocrine pancreatic secretions were drained into the recipient jejunum through enteric anastomoses. Because mucosal slough of the graft duodenum and jejunum in two patients caused a protein losing enteropathy and necessitated reoperations, we now do the pancreatic transplantation with only a blister of graft duodenum large enough for side-to-side enteroenterostomy. The spleen has been transplanted with the pancreas mainly for technical reasons, and this technique should have further trials in spite of the fact that delayed graft splenectomy became necessary in two recipients to treat graft induced hematologic complications.
During the course of performing 123 consecutive orthotopic liver transplantations in a two year period, a total of 220 livers were encountered (123 donors and 97 recipient organs), 24 of which had inadequacies or anomalies of hepatic arterial supply which required modifications of the basic techniques of arterial reconstruction. The various methods used to deal with these various situations are described herein. The use of vessel grafts from the donor has proved quite satisfactory over a number of years. The routine procurement of various vessel grafts can provide a multiplicity of options for arterial reconstruction, only a few of which have been mentioned herein.
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End-to-side portacaval shunts were carried out in three children with the liver disease of alpha-1-antitrypsin deficiency and complications of portal hypertension. Their clinical courses have been stable for 3 1/2 to almost 7 years. Postoperative liver biopsy material from two of the patients showed the typical histopathological changes caused by portal diversion, as well as an apparent reduction in the quantity of alpha-1-antitrypsin particles in the hepatocytes. The metabolic changes caused by portal diversion have apparently created a more favourable equilibrium between the synthesis and excretion of the abnormal alpha-1-antitrypsin.
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One hundred fifty liver resections were performed with an operative mortality rate of 4%. Indications for liver resections were 43 primary liver malignancies, 43 metastatic liver tumors, and 64 benign liver diseases. The 3-year actuarial survival rate after treatment of primary liver malignancy was 56%, and that after treatment of metastatic liver tumors was 66%. All but one of 59 patients with benign disease who survived operation were alive without development of late symptoms or complications.