A superior approach to organ allocation and donation.

BACKGROUND: Whether the twin aims of alleviating organ shortage and of increasing justice of organ allocation necessarily conflict with each other or can be simultaneously furthered while the autonomy of patients is respected is an important question in organ transplantation. It is shown that very minor reforms of existing schemes of organ allocation could increase the scope for justice, autonomy, and beneficence simultaneously. METHOD: Willingness to donate discriminates between patients of comparable medical status in the elective category by preferring potential donors over nondonors. High urgency patients as well as children have priority over patients in the elective category. The proposed solidarity model can easily be implemented, for example, as a sixth ranking scale added to the existing allocation algorithm of Eurotransplant. RESULTS: 1. More justice and more beneficence. It is excluded that of two recipients of equal medical suitability, a patient who is unwilling to donate is unjustly preferred to one who is willing to donate, whereas enhanced solidarity with donors will increase the number of donations and, thereby, the scope for beneficence. 2. Enhanced involvement of individuals and hospitals. More people are induced to declare actively their willingness to donate which in turn enhances the moral obligation of hospitals to participate in transplantation. 3. Fair treatment of dissenting minorities, local residents, and nonresidents. The solidarity model favors altruistic contributors to the organ pool over noncontributors without discriminating against groups. CONCLUSION: A solidarity rule for organ allocation should be gradually introduced.

The course of untreated acute rejection and effect of repeated anti-CD3 monoclonal antibody treatment in rhesus monkey liver transplantation.

The effect of single and repeated treatment of liver allograft rejection using an anti-CD3 monoclonal antibody (FN18) was studied in a rhesus monkey model. Eight RhLA-mismatched monkeys received initial postoperative immunosuppression with CsA/prednisolone for 28 days. After cessation, acute rejection occurred in all animals (days 28-50). Control animals (n = 3) receiving no rejection treatment developed a chronic progressive rejection and died at days 112-160. In the animals treated with FN18 (n = 5), the first acute rejection was successfully reversed. T lymphocytes were cleared from the peripheral blood and the graft. Increased class I and class II MHC-antigens on hepatocytes were reduced to normal levels within 5 days of treatment. The second rejection treatment remained ineffective in two animals with antiidiotypic antibodies to FN18 but was successful in two animals with a low antimouse response. These four animals survived 160-509 days. The results have a number of implications regarding the course of untreated rejection in human liver transplant recipients and repetitive rejection treatment with monoclonal antibodies.

Arterial ketone body ratio as a predictor of donor liver viability in human liver transplantation.

The viability of the donor liver was assessed with regard to early postoperative survival in human liver transplantations from 40 brain-dead donors at Hannover Medical College and 13 living donors at Kyoto University by measuring the arterial ketone body ratio (AKBR). Of 40 grafts harvested from brain-dead patients in Hannover, 35 survived the first week after operation, but 5 developed initial nonfunction of the transplanted graft within the first week. The mean AKBR values were 1.11 +/- 0.11 for grafts that survived and 0.44 +/- 0.10 for grafts that failed (P < 0.01). The AKBR values of the 5 initially nonfunctioning cases were all below 0.7. Of 13 grafts harvested from the living donors in Kyoto, all survived the first week. The AKBR values of the donors were all above 1.0, with a mean value of 1.87 +/- 0.23. Among all 53 cases, the survival rate of the grafts with AKBR above 0.7 was significantly higher than that of the grafts with AKBR below 0.7 (100% vs. 62%, P < 0.01). No other donor parameters, including age, dose of dopamine administered, and clinical laboratory findings, were significantly related to differences in graft survival rates. AKBR is a useful index for the evaluation of donor liver viability. Grafts used from donors with AKBR of less than 0.7 have a significantly increased risk of early nonfunction. Grafts from donors with AKBR of greater than 1.0 have, in our experience, always been viable after transplantation.

Significance of arterial ketone body ratio measurement in human liver transplantation.

Arterial ketone body ratio (KBR), which reflects the NAD+/NADH ratio of hepatic mitochondria, was measured sequentially in 39 liver transplantations. In 22 cases, KBR was increased to above 0.7 within 6 hr after reperfusion (group A). In 11 cases, restoration of KBR was delayed until the first postoperative day (group B) and in 6 cases, KBR failed to recover (group C). The patients in group A survived liver transplantation without complications. By contrast, morbidity and mortality were significantly higher in groups B and C. In 2 cases in group C, the livers were clinically diagnosed as initially nonfunctioning grafts and the patients underwent retransplantation. Another two died of hepatic failure soon after the operation. It is suggested that delayed recovery of KBR is an early indicator of metabolic overload in the liver allograft, and that a delay exceeding 24 hr may imply the need for retransplantation.

Bile duct injury as a part of diagnostic criteria for liver allograft rejection.

The decisive criterium of acute liver allograft rejection was found to be the presence of the diagnostic triad of acute rejection; ie, the presence of portal inflammatory mixed infiltrates, venous endothelialitis (both portal and central), and bile duct injury. On the basis of the presence of each of the components of the diagnostic triad, criteria for the diagnosis of different degrees of acute rejection were developed, particularly focusing attention on a detailed analysis of bile duct injury. Bile duct injury was shown to be an essential part of the histopathologic changes in all grades of acute rejection in the liver allograft, the grade of severity of bile duct injury correlating to a certain extent with the grade of severity of acute rejection. Our analyses have made it evident that bile duct injury, which most probably occurs earlier in the process of acute rejection than endothelialitis, is a more sensitive parameter than endothelialitis in the diagnosis of acute rejection. Furthermore, our analyses have revealed that bile duct injury in acute rejection is likely to be an irreversible process, depending on the number of episodes of acute rejection that previously occurred. On the other hand, it has become clear from our results that bile duct injury must not be considered to be an absolute histopathologic marker of acute rejection; however, it does have to be judged synoptically in connection with the other components of the diagnostic triad and the changes that the triad cause in the hepatic parenchyma. Additional analyses of the grade of severity of cholostases have shown that the cholostases are, to a certain degree, an accompanying phenomenon of the histopathologic changes characterizing acute rejection rather than a histopathologic change that is as significant as the presence of the components of the diagnostic triad.

Management of severe hepatic trauma by two-stage total hepatectomy and subsequent liver transplantation.

Even today major hepatic trauma remains a formidable surgical challenge with considerable deaths from exsanguination. Apart from conservative operative techniques that allow successful management in most cases, liver transplantation may be indicated in a more severe injury. This is a report on a patient with massive, unsalvageable liver trauma on whom the first two-staged procedure was successfully performed. After total hepatectomy as the first step and a prolonged anhepatic period of more than 14 hours, liver replacement by an allograft was carried out in a second operation. The patient recovered completely from the potentially lethal hepatic trauma and is alive more than 17 months later.

Changes in energy substrates in relation to arterial ketone body ratio after human orthotopic liver transplantation.

BACKGROUND: Changes in energy substrate metabolism, as well as those in arterial ketone body ratio (KBR; acetoacetate/3-hydroxybutyrate), were investigated to follow energy status of hepatic allograft. METHODS: Plasma concentrations of energy substrates were measured immediately after 35 orthotopic liver transplantations in 32 adult patients. RESULTS: Twenty-three patients left the intensive care unit within 1 month (group A), six patients were forced to stay in the intensive care unit longer than 1 month (group B), and the other six grafts failed within 1 month (group C). In group B the KBR was significantly lower than in group A 6 hours after reperfusion of the grafts (0.70 +/- 0.09 vs 1.21 +/- 0.10, mean +/- SEM; p < 0.05). In group C the KBR remained significantly lower than in group A at 6 hours (0.65 +/- 0.04 vs 1.21 +/- 0.10; p < 0.01), on the first postoperative day (0.64 +/- 0.03 vs 1.36 +/- 0.10; p < 0.001), and on the second postoperative day (0.65 +/- 0.02 vs 1.58 +/- 0.11; p < 0.01). Total ketone body concentration (TKB) was significantly higher in group B than in group A at 4 hours (462.9 +/- 105.0 mumol/L vs 201.6 +/- 32.6 mumol/L; p < 0.01), 6 hours (483.4 +/- 102.1 mumol/L vs 125.5 +/- 25.9 mumol/L; p < 0.001), and the first postoperative day (481.1 +/- 196.6 mumol/L vs 123.9 +/- 24.1 mumol/L; p < 0.001). No increase in TKB was observed in group C. CONCLUSIONS: It is suggested that low values in KBR accompanied with low levels of TKB should be regarded as a strong indicator of graft failure and fatty acid oxidation and ketogenic pathways are accelerated to compensate for energy deficits in patients with low values in KBR and high levels of TKB until KBR recovers immediately after orthotopic liver transplantation.

Fat emulsions in parenteral nutrition after liver transplantation: The recovery of the allografts RES function and histological observations.

Following liver transplantation, the effect of post-operative parenteral nutrition with MCT LCT (Medium Chain Triglycerides/Long Chain Triglycerides) fat emulsions on the recovery of allografts RES function was investigated in a randomised prospective study of three groups of patients (group I, n = 14: 50g MCT LCT fats twice weekly, group II, n = 15: 0.7 g/kg body weight per day MCT LCT fats, group III, n = 17: 1.5 g/kg body weight per day MCT LCT fats). RES function was assessed using the (99m)Tc-HSA-MM-Clearance ((99m)Technitium-Human serum albumen-Millimicrosphere-Clearance). There were no statistically significant differences in the recovery of RES function between the groups. A negative effect on RES function as a result of the administration of MCT LCT fat emulsions up to 1.5 g/kg b.w. per day can therefore be excluded. The evaluation of liver biopsies before the administration of fats and at the end of TPN (Total Parenteral Nutrition) showed no evidence, in the 20 patients investigated, of any fatty changes in the liver caused by the infusion of fat.

Liver transplantation in pigs: a model for studying reperfusion injury.

A model of orthotopic liver transplantation in pigs was developed to investigate reperfusion injury of the liver. To have direct access to the liver for organ monitoring a relaparotomy was performed 6 h after revascularization. The details of modification in anesthesia and surgical technique are given. Salient features of the technique include (1) the use of an extremely short cuff of the donor suprahepatic caval vein, (2) the use of a central venous catheter fixed in a hepatic vein, and (3) the use of an aortic graft for standardized arterial reconstruction. Twenty-nine transplantations were performed. The total anesthetic time was 13.28 +/- 1.45 h and the operative time was 10.06 +/- 0.77 h. The animals withstood this long procedure remarkably well.

[General aspects of organ donation]. / Allgemeine Aspekte der Organspende.

The general and surgical aspects of organ donation are of great relevance for every surgeon in every hospital, as potential organ donor situations occur in every intensive care unit. Typical organ donors are patients suffering from intracerebral bleeding. There is no upper age limit. The implementation of a potential organ donor program is the indirect responsibility and task of every hospital in order to serve the patients waiting in the geographical region of the hospital; organs retrieved in another region should be available for patients in that other region. The general aspects of organ donation concern, for example, the question of the legal aspects of brain death and adequate surgical procedures concerning the dignity of the donor. The surgical aspects include a highly standardized technique using only aortal flush at an early stage of the operation without major manipulation of the organs prior to perfusion. The liver and pancreas are removed en bloc and consecutively the kidneys, one by one. This no-touch technique is rapid and safe, especially for atypical hepatic arteries, as all the tissue between the superior mesenteric artery, celiac trunk and minor curvature of the stomach is preserved with liver, irrespective of arterial anomalies.