Proceeding with clinical trials of animal to human organ transplantation: a way out of the dilemma.

The transplantation of porcine organs to humans could in the future be a solution to the worldwide organ shortage, but is to date still highly experimental. Further research on the potential effects of crossing the species barrier is essential before clinical application is acceptable. However, many crucial questions on efficacy and safety will ultimately only be answered by well designed and controlled solid organ xenotransplantation trials on humans. This paper is concerned with the question under which conditions, given the risks involved and the ethical issues raised, such clinical trials should be resumed. An alternative means of overcoming the safety and ethical issues is suggested: willed body donation for scientific research in the case of permanent vegetative status. This paper argues that conducting trials on such bodies with prior consent is preferable to the use of human subjects without lack of brain function.

Fat absorption and metabolism in bile duct ligated rats.

BACKGROUND: Bile excretion is obstructed in children with extrahepatic bile duct atresia (EHBA) resulting in fat malabsorption and disturbed lipid metabolism. AIM: Investigate if the bile duct ligated rat exhibits similar deviations as patients with EHBA under different feeding conditions. METHODS: 6 bile duct ligated Wistar rats and 12 matched paired controls were randomised over 3 feeding groups. Rats were killed 16 or 30 days postsurgery. Faeces, blood and livers were collected. Fat absorption was evaluated, markers for cholestasis and the fatty acid composition of serum phospholipids (PL) and cholesterol esters (CE) were determined. Fatty acid desaturation activities in liver microsomes were measured. RESULTS: Cholestatic bile duct ligated rats have a lower fat absorption coefficient and a lower fraction of 18:2n-6 and 18:3n-3 in serum triglycerides than their controls. This demonstrates that bile duct ligated rats suffer from fat malabsorption. In contrast to the observations in serum triglycerides, 18:2n-6 and 18:3n-3 were not reduced in serum PL and CE of cholestatic rats. Overflow of 18:2n-6 rich biliary PL in the general circulation could contribute to this observation. In agreement with what was found in man, serum PL of cholestatic rats have a higher 16:0/18:0 ratio, increased monoenes and reduced unsaturated fatty acids. However, no differences were observed in microsomal desaturation activities. CONCLUSION: Cholestatic bile duct ligated rats exhibit similar deviations in serum fatty acid composition as found in patients with EHBA, therefore they can be used as a model for this human disease.

High-dose omeprazole in esophagitis with stenosis after surgical treatment of esophageal atresia.

The authors describe 4 children with recurrent stenosis and persistent esophagitis after secondary repair of a long gap esophageal atresia. They underwent an esophageal reconstruction by elongation of the lesser gastric curvature according to Schärli at the age of 11 to 14 months. All had esophagitis grade III to IV (Savary-Miller classification), esophageal stenosis, and failure to thrive. Effective treatment of the esophagitis and prevention of stenosis consisted in high doses of omeprazole (1.9 to 2.5 mg/kg/d). After this treatment, the need for esophageal dilatation disappeared, and nutritional status normalized.

Care of the potential pediatric organ donor.

Although all of this information may create the impression that caring for a potential organ donor is an exceedingly complex task, in the authors' experience, this often is not true, and much energy can--and should--be devoted to the care of the bereaved family. Of crucial importance are the early recognition of brain death and the consequent radical switch of the treatment goal from preservation of the patient's brain and life to preservation of organs for the lives of others. Care for the donor is the natural extension of care for a critically ill or injured patient. During the foregoing discussion, the authors had to stress the absence of sound evidence on many points. Because many reports originate from transplant centers dedicated to a specific organ, gaining a comprehensive view on management options in the ICU further is hampered. Thus, this situation leaves another field in which investigations originating from pediatric intensivists could provide evidence urgently needed to make optimal choices. The next decade should see the thyroid hormone controversy solved by at least one controlled prospective study and the differential applicability of inotropic, vasoactive, or fluid-centered strategies. It seems self-evident that only graft survival and related parameters can form adequate endpoints for future studies.

Arterialization of the portal vein in pediatric liver transplantation. A report of two cases.

Portal vein arterialization (PVA) is an acquired concept in shunt surgery for portal hypertension. This technique, recently described as both a temporary and permanent procedure in adult liver transplantation, is reported by the authors in two cases of pediatric transplantation. The indication was low portal blood flow after reperfusion with poor graft function due to persistence of spontaneous retroperitoneal venous shunts. In both cases described, PVA allowed for satisfactory macroscopic liver reperfusion. The increase in portal blood flow from 150 to 500 ml/min in the second patient enabled the liver to be reperfused correctly and led to successful transplantation. The graft function in both cases improved in the 1st postoperative week, but the 1st patient 2 months after transplantation. Signs of hepatic hyperarterialization occurred in the second patient and this necessitated a dearterialization of the portal vein 2 weeks later. Although the benefit of this procedure appears to be beyond doubt in the immediate post-operative period, we have no data on long-term arterialization. We do think that PVA can be performed in pediatric liver transplantation, but it may need to be done only in special, individual situations when no valid alternative can be proposed, such as in the absence of a mesenteric vein and/or the presence of spontaneous retroperitoneal venous shunts.

Wilms' tumour presenting as a pulmonary embolism.

Wilms' tumour (nephroblastoma) is one of the most common solid malignant tumours in infancy and childhood. In about 40% of cases, invasion of the renal vein is present. Rarely, these tumours extend into the inferior vena cava and right atrium. We discuss a 7-week-old girl who presented with acute massive pulmonary embolism, and was found to have a large tumour of the left kidney. Later on, the diagnosis of Wilms' tumour was confirmed. Wilms' tumour presenting as massive pulmonary embolism is extremely rare; to our knowledge this is the fourth case described in literature. We review the cases previously described, and comment on the diagnostic and therapeutic features of this clinical entity.

The course of shipped livers used as full size, reduced or split grafts.

A total of 110 transplants, 66 in adults (8 retransplants) and 30 in children (6 retransplants) were analysed according to the origin of the graft (shipped n = 39-non-shipped i.e. self procured n = 71) and the way they were transplanted (as full size grafts (FS) n = 82, reduced size grafts (RED) n = 23 or split grafts (SG) n = 5). Twenty-nine transplants were performed for urgent and 81 for elective indications. There was a statistically higher incidence of 2 or more risk factors in the donors that were selfprocured (non shipped) than in donors from shipped livers (p = 0.025). The overall 3 months graft survival was 79.5% for shipped livers versus 69% for non-shipped livers and patients survival was 89.2% versus 79.0% respectively after 3 months and 82.9% versus 74.4% after 40 months. From these results that were analysed with risk factors of the donors, cold ischaemia time and liver function tests in recipients, transplanted for acute and elective indications, it is concluded that shipping of grafts is a practical and safe procedure even if size reduction or the use of SG is intended.

Hepato-venous outflow complications following orthotopic liver transplantation with various techniques for hepato-venous reconstruction in adults and children.

Orthotopic end-to-end cavostomy following liver transplantation was without any complications in 63 cases as compared to latero-lateral cavostomy (14.2%) and the piggy-back technique of partial liver grafts (14.2%). Transjugular catheterangioplasty was a practical and successful treatment for the latter, while reoperation for thrombosis in the latero-lateral anastomosis resulted in lethal pulmonary embolism.

[Liver and liver segment transplantation in adults and children. Experiences with the first 50 cases]. / Leber- und Lebersegmenttransplantation bei Erwachsenen und Kindern. Erfahrungen mit den ersten 50 Fällen.

The experience with 50 liver transplants performed in 42 patients within a 16 months period is reviewed. There were 15 transplantations in 12 children and 35 in 30 adults. The series was analysed regarding the source of transplant, i.e. living related (LR) n = 2 or cadaver (CAD) n = 48, graft size i.e. full size (FS) n = 34, reduced size (RED) n = 12 and split grafts (SG) n = 4. Regarding the preservation time or operating time there was no statistically significant difference between the groups. The overall function rate was 88%, 94% for FS and 73.4% for the remaining partial grafts (RED and SG). The difference was not significant (p = 0.062). Biliary leakage occurred in one (2%) reduced graft. Hepatic artery complications (kinking, intima dissection) were encountered in two (4%) patients receiving a FS. It is concluded that the use of partial liver grafts is a safe procedure to alleviate organ shortage while preservation time and operating time are not prolonged as compared to the transplantation of full size grafts.

Time-space distribution of extrahepatic biliary atresia in The Netherlands and West Germany.

Extrahepatic biliary atresia (EHBA) is an infrequent disease confined to early infancy. Its aetiology is not clear, but an infectious agent has been implicated. Demonstration of a time-space clustering would support this hypothesis. Therefore, we investigated the time-space distribution of all 89 cases of EHBA born in a 10-year period in the Netherlands. We carried out a similar study in West Germany and analysed 130 cases of EHBA, born between 1969 and 1986, from 4 paediatric surgical centres. Analysis of these cases did not reveal any evidence for clustering in specific years or in a specific period of the year. The places of birth of the patients also were randomly distributed over rural areas, villages and towns. Neither did a method to reveal time-space interaction give any support for clustering. This random distribution of patients with EHBA suggests that EHBA could be pathogenetically a heterogeneous disease.

Efficacy of hepatobiliary scintigraphy in the differential diagnosis of neonatal cholestasis and postoperative follow-up after hepatoporto-digestive anastomosis.

In the differential diagnosis of unclear neonatal and infant cholestasis the formerly applied 131-I-Rose Bengal scintigraphy has been widely abandoned in favour of hepatobiliary scintigraphy with 99mTc-labelled IDA derivatives excreted with the bile. Our results in 32 jaundiced children ranging from ages 2 weeks to 32 weeks show a high sensitivity of scintigraphy in proving an occlusion in 92% with a clearly lower specificity of 79%, if based on the demonstration of marked bile in the intestine as the only criterion. Diagnostic accuracy, however, can be further increased in additional criteria such as hepatocellular clearance and patient age are considered. The examination is of equally high importance for post-operative follow-up. Here, scintigraphy is superior to all other imaging procedures in the evaluation of bile flow situations. In 52 examinations of portoenterostomies, the prognostic value can be demonstrated not only with a good coincidence of the scintigraphic data with the bilirubin level, but also with the histological degree of liver fibrosis at the time of operation. Early and late complications of hepatoportojejunostomy can usually be recognised and localised. Since the prognosis of extrahepatic biliary atresia depends on an early operation-presently by means of reconstruction of biliary flow-indications for hepatobiliary scintigraphy must be given more widely and earlier (at the latest in the fourth week of life) in all unclear cases of cholestatic syndrome.