Orthotopic Homotransplantation of the Human Liver

Starzl, Thomas E.; Groth, Carl G.; Brettschneider, Lawrence; Penn, Israel; Fulginiti, Vincent A.; Moon, John B.; Blanchard, H; Martin, A. Lynn; Porter, K. A.

doi:10.1097/00000658-196809000-00009

Cited by 628 publications

(197 citation statements)

References 9 publications

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“…By this time, thousands of human kidneys had been successfully transplanted as well as the first livers (17) and hearts (18) (Table 1). None of these organ recipients had overt leukocyte chimerism.…”

Section: The Split Of Organ and Bone Marrow Transplantationmentioning

confidence: 99%

Chimerism and tolerance in transplantation

Starzl

2004

Proc. Natl. Acad. Sci. U.S.A.

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127

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Studies in experimental models (1953)(1954)(1955)(1956)) demonstrated that acquired donor-specific allotolerance in immunologically immature or irradiated animals is strongly associated with donor leukocyte chimerism. Bone marrow transplantation in immune-deficient or cytoablated human recipients was a logical extension (1968). In contrast, clinical (1959) and then experimental organ transplantation was systematically accomplished in the apparent absence of leukocyte chimerism. Consequently, it was assumed for many years that success with organ and bone marrow transplantation involved fundamentally different mechanisms. With the discovery in 1992 of small numbers of donor leukocytes in the tissues or blood of long-surviving organ recipients (microchimerism), we concluded that organ engraftment was a form of leukocyte chimerismdependent partial tolerance. In this initially controversial paradigm, alloengraftment after both kinds of transplantation is the product of a double immune reaction in which responses, each to the other, of coexisting donor and recipient immune systems results in variable reciprocal clonal exhaustion, followed by peripheral clonal deletion. It was proposed with Rolf Zinkernagel that the individual alloresponses are the equivalent of the MHC-restricted T cell recognition of, and host response to, intracellular parasites and that the mechanisms of immune responsiveness, or nonresponsiveness, are governed by the migration and localization of the respective antigens. Elucidation of the mechanisms of nonresponsiveness (clonal exhaustion-deletion and immune ignorance) and their regulation removed much of the historical mystique of transplantation. The insight was then applied to improve the timing and dosage of immunosuppression of current human transplant recipients.

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Section: The Split Of Organ and Bone Marrow Transplantationmentioning

confidence: 99%

Chimerism and tolerance in transplantation

Starzl

2004

Proc. Natl. Acad. Sci. U.S.A.

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127

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“…Heparinized Bypass from June 15-September 6,1982 Twelve patients, nine of whom were adults, underwent liver transplantation using a conventional bypass system that necessitated systemic anticoagulation with heparin. These are the subject of a brief comparison with the current system.…”

Section: Mortality and Survivalmentioning

confidence: 99%

Venous Bypass in Clinical Liver Transplantation

Shaw¹,

Martin²,

Marquez³

et al. 1984

Annals of Surgery

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245

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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 (L T). 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 L T without bypass (NBP), the 57 total BP patients experienced better postoperative renal function (p < 0.001), required less blood use during surgery (p < 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 L T as a service-oriented procedure.T HE DRAMA TIC IMPACT of cyclosporine on survival following liver transplantation has been widely reported. I -4 Yet despite extensive experience with the operation during the preceding 17 years, only a few important technical improvements were reported to have significantly enhanced survival. 3 • 5 -s In fact, during the first 3 years in which cyclosporine was used, mortality related to a difficult intraoperative course remained a disturbing problem. For the most part, these difficulties centered around the anhepatic phase and repeatedly underscored the need for an effective method of venous bypass. The need for the development of new methodology was clearly demonstrated by the severe penalty imposed by the requirement for systemic heparinization during a trial of venous bypass using conventional

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“…The full-size liver grafts were implanted according to the veno-venous bypass technique used routinely by Starzl et al [10]. The standard liver resection technique was used for reduction of the donor livers [11].…”

Section: Methodsmentioning

confidence: 99%

Long-Term Graft Outcome of Pediatric Liver Transplantation in Copenhagen: Analysis of the First 51 Cases

Yamauchi¹,

Yamashita²,

Wettergren³

et al. 2006

Dig Surg

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Background: Graft loss after liver transplantation remains a significant problem, especially in pediatric patients. The aim of this study was to assess our initial series of pediatric liver transplantation and to identify the risk factors that influence graft outcome. Methods: The first 51 transplantations were analyzed retrospectively. All transplantations were stratified into three groups according to graft type (full-size, reduced-size, and living-related-donor graft). Survival data of the grafts were stratified and multivariate analysis conducted with respect to preoperative and surgical factors. Results: Seventeen of all the transplants were full-size grafts and 34 technical-variant grafts (27 reduced-size grafts from cadavers and 7 living-related-donor grafts). The overall graft survival rates were 65, 62 and 53% at 1, 3 and 5 years, respectively. Twenty-three of 51 grafts (45%) were lost. Poor status of the recipients (hospitalization or intensive care unit care before surgery), a retransplanted graft, and a reduced-size graft were independent risk factors for graft failure. With experience, overall graft survival has improved significantly and the differences in graft survival between graft types have disappeared. Conclusions: To improve graft survival after pediatric liver transplantation, the timely referral of potential recipients to the transplant team and employing a meticulous technique during the operation, particularly for the technical-variant graft, are required.

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Orthotopic Homotransplantation of the Human Liver

Cited by 628 publications

References 9 publications

Chimerism and tolerance in transplantation

Chimerism and tolerance in transplantation

Venous Bypass in Clinical Liver Transplantation

Long-Term Graft Outcome of Pediatric Liver Transplantation in Copenhagen: Analysis of the First 51 Cases

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