Air emboli in human donor liver.
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Biomedical subjects
Publications and source records attributed to M J Slooff.
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BACKGROUND AND METHODS: The records of 118 patients who had hepatic resections for colorectal liver metastases were analyzed retrospectively. RESULTS: The patient group, from 15 institutions in The Netherlands, was found to have a 5-year actuarial survival rate of 21% and a 5-year actuarial disease-free survival rate of 19%. The postoperative mortality rate was 7.6%. In the remaining group, the morbidity rate was 34.7%. A number of factors were examined that were reported to be of prospective significance in other studies. In the multivariate proportional hazard model of Cox, the number of metastases (P = 0.001) and the amount of perioperative blood loss (P = 0.002) were related significantly to disease-free survival. A factor that may be considered a contraindication to resection is the presence of extrahepatic disease (whether nodal or visceral), even if resectable. CONCLUSIONS: Although the actual benefit of resection is limited, and it is associated with considerable morbidity, surgical therapy offers some patients a chance for cure. It is a valid expectation that improvement in techniques and a proper understanding of hepatic anatomy will improve the safety and efficacy of hepatic resections in the future. Future research should focus on defining better selection criteria and on study of the value of adjuvant treatment modalities.
Isolated hepatocytes are a valuable tool to study liver functions. Suitable methods to preserve the isolated cells with good maintenance of viability and functions are crucial to extend experiments with hepatocytes from a single isolation over 2 or more consecutive days. We investigated whether University of Wisconsin (UW) solution, which was designed to preserve organs for transplantation, is also suitable for preservation of isolated rat hepatocytes. Viability, as determined by Trypan blue exclusion and reduction of the tetrazolium 3(4,5-dimethyl-thiazoyl-2-yl)2,5 diphenyltetrazolium bromide to a purple formazan, morphological appearance using electron microscopy, ATP levels and uptake and storage of three model drugs ([3H]vecuronium, [3H]taurocholic acid and [3H]ouabain) were determined directly after isolation and after 22 hr of storage in UW solution at 0-4 degrees. The present study shows that cold storage of rat hepatocytes for 22 hr in UW can be performed without significant loss of viability and with maintenance of proper morphology, cellular ATP and transport functions. In contrast, after storage in Krebs-Henseleit buffer the normal morphology, ATP content and transport functions were strongly affected. These results imply that hepatocytes from a single isolation and stored in UW solution can be used for experiments on 2 consecutive days.
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We investigated the influence of Eurocollins (EC) and University of Wisconson solution (UW) on prognostic factors for graft survival after pediatric liver transplantation. The 1-year graft survival was studied for 30 patients in which 38 transplantations were performed between 1982 and 1988. We preserved 19 grafts in EC and the other 19 grafts in UW solution. For grafts preserved in EC, the median preservation time was 5 h compared to 10.8 h for grafts preserved in UW solution (P < 0.01). Graft survival at 1 year was equivalent in both groups (63%). No significant differences were observed between the two groups for the following variables: patient diagnosis, child-pugh score, age, operative time, anhepatic phase, blood loss, morbidity, ICU stay, donor age and graft survival. Multivariate analysis indicated that in the EC group anhepatic phase, blood loss and preservation time were significant predictors of graft survival whereas in the UW group, none of these factors appeared to be significant. We concluded that UW was superior to EC solution in pediatric liver transplantations because it allowed longer preservation times, the length of the anhepatic phase was less important and the tolerance for blood loss seemed to be extended.
A group of individuals who had granted or refused permission to have organs removed from a decreased relative for transplantation were interviewed. Organ donation was found to be a very delicate subject: the request for organ donation often comes unexpectedly and most relatives are not aware of the wishes of the decreased (donor codicil), which complicates the decision process. Some of the relatives who refused regretted their decision later. Remorse was also encountered in the group who gave their permission, although positive feelings were more common. The position of the member of staff who asks for permission is complicated. Suggestions are presented to improve the procedure.
Analysis of quality-of-life effects is part of the current technology assessment of the Dutch orthotopic liver transplant-program. Data are collected by means of computer-assisted interviewing, including one interview before transplantation and annual follow-up interviews. Data on psychiatric morbidity are obtained from medical records. This article shows preliminary results of a cross-sectional analysis of data collected from 1987 to 1989. Eighty-eight measurements were obtained from 46 adult patients (response rate 82%). Pretransplant scores suggest major restrictions on all domains of life, especially a low amount of energy. After transplantation all indicators show improvement, although the level of the general population is not always attained. Improvement of subjective quality of life is more marked, possibly due to euphoria at surviving the hazardous procedure. Psychiatric events occurred only infrequently. We conclude that orthotopic liver transplantation contributes positively to the quality of life of surviving patients. In addition, computer-assisted interviewing proved to be a feasible survey technique, even when very ill patients were involved.
A case of primary squamous cell carcinoma in a pre-existing hepatic cyst is presented. A review of the literature suggests that this rare type of liver tumor tends to arise from solitary, nonparasitic cysts, lined with squamous epithelium. Effective therapy is not available, the prognosis is grave.
Transport systems involved in uptake and biliary secretion of bile salts have been extensively studied in rat liver; however, little is known about these systems in the human liver. In this study, we investigated taurocholate (TC) transport in canalicular and basolateral plasma membrane vesicles isolated from 15 human livers (donor age 6-64 yr). ATP stimulated the uptake of TC into both canalicular and basolateral human liver plasma membrane vesicles (cLPM and blLPM, respectively). Considerable interindividual variations in the transport velocity were observed in the different membrane preparations used: 9.0 +/- 1.3 (mean +/- SEM, n = 17; range 1.6-18.0) and 9.3 +/- 2.0 (range 1.1-29.8) pmol TC.mg protein-1.min-1 at 1.0 microM TC for cLPM and blLPM, respectively. TC transport was temperature sensitive and showed saturation kinetics with a high affinity for TC (Km 4.2 +/- 0.7 microM and 3.7 +/- 0.5 microM for cLPM and blLPM, respectively). Transport was dependent on the ATP concentration and saturable (Km 0.25 +/- 0.03 mM, n = 3). Neither nitrate, which reduces membrane potential, nor the protonophore FCCP strongly inhibited ATP-dependent TC transport, indicating that membrane potential and proton gradient are not involved in this process. TC transport was significantly inhibited by the classical anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate (250 microM) and the glutathione conjugate S-(2,4-dinitrophenyl)glutathione (100 microM). In conclusion, high affinity ATP-dependent TC transport is present in human liver at both the canalicular and the basolateral sides of the hepatocyte.
A method is described for the isolation of subfractions from human liver plasma membranes, enriched in canalicular domains (cLPM) and basolateral domains (blLPM), respectively, and the results are compared to those obtained with rat liver. The studies were performed in 18 human livers. The cLPM (isolated at densities 1.103-1.127 for human and 1.036-1.127 for rat cLPM) from human as well as rat liver showed a lower density than the blLPM (1.141-1.161 for human and 1.151-1.172 for rat blLPM). Human and rat blLPM were characterized by increased levels of (Na+/K+)-ATPase (relative enrichment 33 and 21, respectively). Both human and rat cLPM showed high specific activities of leucine aminopeptidase; relative enrichment factors were 42 and 31, respectively. Mg(2+)-ATPase and alkaline phosphatase, specific canalicular enzymes in rat liver, were only slightly enriched in the cLPM of human liver, which indicates that these enzymes are not suitable as marker enzymes for human liver cLPM. Both cLPM and blLPM of human and rat origin were only slightly contaminated with mitochondria, lysosomes, Golgi membranes and endoplasmic reticulum. Total recoveries of cLPM and blLPM were 0.02 mg protein/g liver each for the human membrane preparations, compared to 0.07 and 0.16 mg protein/g liver for the membranes prepared from rat liver. Analysis of membrane fluidity revealed that the human liver cLPM were more rigid than blLPM (mean difference in fluorescence polarization PDPH 0.024). They contained more cholesterol (0.43 vs. 0.30 mumol/mg protein) and phospholipids (0.54 vs. 0.39 mumol/mg protein, respectively), which was compatible to rat liver plasma membrane fractions. This study shows that besides similarities, there are several differences between human and rat liver plasma membrane fractions.
Since 1982, the liver transplantation team of the University Hospital of Groningen has been carrying out transplantations in children. This article focuses on the experiences of the parents of 19 children who have undergone transplantation. An interview and two questionnaires were used to collect the data. Data concerned children's physical and psychosocial functioning and their daily behaviour. Five older children also filled in two questionnaires. In general, parents were positive about their child's functioning. When the interviews were analysed at an individual level, several problems were reported, however. These problems did not fall within one specific domain. As a consequence, the questionnaires did not show any significant differences between these children and a matched control group of healthy children. The parents of the children aged 1-3 yr were more positive about their children's functioning than the parents of the children aged 4-12 yr. The positive results should be assessed in the light of children's functioning before transplantation: when compared with pre-transplantation problems, present problems are of little significance.
In 45 liver transplant recipients, the value of weekly monitoring of cytomegalovirus (CMV) antigenemia for early diagnosis of active CMV infection was compared with serology and rapid viral isolation. Active CMV infection occurred in 23 patients. The sensitivities of the antigenemia assay and serology (of blood) and rapid viral isolation (from blood or urine) were 96%, 96%, 57%, and 70%, respectively. First diagnostic results of these methods were obtained a median of 25, 36, 31, and 49 days, respectively, after transplant. CMV infection was symptomatic in 20 patients; antigenemia was present at the onset of disease in 13 of these. Maximum CMV antigenemia levels were higher in patients with severe disease than in those with mild or asymptomatic infection. CMV antigenemia is a sensitive, early, quantitative marker of active CMV infection after liver transplantation.
In a clinical setting, the effect of Eurocollins (EC) and University of Wisconsin solution (UW) on liver grafts were studied in the early reperfusion phase of liver transplantation. Blood samples were drawn before and after declamping of the portal vein in a group of 11 transplants with EC-perfused livers, and a group of 12 transplants with UW-perfused livers. Parenchymal damage was assessed by the LDH, AST, and ALT, and purine degradation by measuring the uric acid levels. Metabolic function was determined by the serum bile acids and the plasma amino acids, i.e. (valine + leucine + isoleucine)/(phenylalanine + tyrosine) ratio. Donor and pretransplant recipient parameters were almost identical. The cold ischemia time of both groups differed significantly. The results show the following: a significant difference between both the LDH and the uric acid levels in the two groups was revealed, with a smaller increase of the LDH levels and no increase of the uric acid levels in the UW group. Metabolic activity, as measured from the bile acids and the amino acid profile in the peripheral blood, was identical in both groups. We conclude that both EC-stored and UW-stored liver grafts show immediate metabolic function after reperfusion. The amount of metabolic function was equal in both groups, notwithstanding longer cold ischemia time in the UW group. In addition, more parenchymal damage occurred in the EC group.
The prospects for patients who survive the first year after liver transplantation are discussed. The 10-year survival for these patients is more than 80%. The quality of life is good, as measured on self-assessment scales. Pregnancy is possible. The main side-effects of drugs concern osteoporosis (corticosteroids), deterioration of renal function (cyclosporine), and de novo malignancies. Recurrence of original disease is at present of clinical importance for Budd-Chiari syndrome and hepatitis B and D. Recurrence of primary biliary cirrhosis is still under discussion.
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To examine the effectiveness of liver transplantation (LTx) for the treatment of primary biliary cirrhosis (PBC) the actual survival of 30 PBC patients who received liver grafts was compared with predictions of what survival would have been without transplantation. Three models, based on Cox' regression analysis, were used. Two models were derived from survival of PBC patients in drug trials and the third from cirrhotic patients who did not receive transplants. Observed and expected survival were compared for a follow-up time of 7 years. After 1 year the difference in favour of LTx was small, but after 5 years survival with LTx exceeded all predicted survival probabilities without LTx. After 3 years every year of follow-up added about 0.3 years to expected survival gain per transplanted patient, resulting in 1.5 to 2.3 life-years gained at 7 years' follow-up, depending on the model used. The benefit was greatest for patients in Child-Pugh classes B and C. The consistency between the three models in their predictions supports the validity of the use of predictive models in the indirect assessment of LTx.