Outcome of ABO-incompatible liver transplantation in children with no specific alloantibodies at the time of transplantation.

The shortage of suitable liver donors for children has motivated the use of ABO-incompatible (ABO-I) grafts for transplantation in urgent situations. However, survival after ABO-I liver grafts has been reported at about 30% as compared with 80% in cases of ABO-identical or -compatible liver grafts. This difference has been attributed to antibody-mediated, hyperacute or chronic liver rejection, due to preformed ABO antibodies (alloantibodies). In this study, we report our results with ABO-I livers in children without alloantibodies at the time of transplantation. From January 1988 to June 1993, 143 OLT were performed in 122 children. Eight children received 8 ABO-I liver grafts. Of these, 7 patients were included in the study. All 7 were alloantibody free before OLT. Five children were spontaneously alloantibody free, while in 2 children, the plasma alloantibodies were eliminated before and after transplantation using intravenous infusion of specific blood group antigens of the donor blood group (soluble antigens). Immunosuppression consisted of a triple-drug treatment combining CsA, AZA, and steroids. The follow-up period was between 10 and 48 months. One child died from a surgical complication. Six children survived, but 1 died 10 months later from intestinal obstruction. There were no graft losses and no episodes of hyperacute or chronic rejection. The graft and patient survival rate was 71%. There was a 28% incidence of rejection, but all were mild (requiring steroid boluses only). Our results suggest that the absence of ABO alloantibodies at the time of and after transplantation can protect ABO-I liver grafts against antibody-mediated rejection, whether hyperacute or chronic, and that soluble antigens are effective in eliminating alloantibodies in children.

N-acetylcysteine in pig liver transplantation from non-heart-beating donors.

Lipid peroxidation due to oxygen free radicals (OFR) seems to play a major role in loss of liver graft viability after warm ischemia, preservation, and transplantation. N-acetylcysteine (NAC) is an antioxidant that has a direct effect on OFR, and is also a glutathione precursor, another antioxidant. This study was designed to evaluate the efficacy of NAC in preventing ischemia-reperfusion damage of liver grafts harvested from non-heart-beating donors. Liver transplantation was performed on pigs divided into five groups: group 1 (control group; n=5) received livers from heart-beating donors; livers were subjected to 30 min of warm ischemia in groups 2 (n=3, no NAC) and group 3 (n=3; NAC treatment); warm ischemia time lasted 60 min in groups 4 (n=4; no NAC) and 5 (n=5; NAC treatment). Studied parameters included graft survival for more than 3 days, aspartate aminotransferase plasma levels, liver histology, and hepatic total glutathione concentrations. Graft survival was 100% in groups 1, 2, and 3, 0% in group 4, and 20% in group 5. NAC treatment did not influence initial mean aspartate aminotransferase release which was greater in warm ischemic livers than in controls. NAC treatment had no effect on liver hepatic total glutathione after reperfusion of animals receiving warm ischemic grants. Finally, no effect on liver histology was observed with NAC treatment. Our study suggests that in liver transplantation from non-heart-beating donors, NAC has no effect in both graft viability and lipid peroxidation. The role of OFR in primary dysfunction of transplanted warm ischemic livers remains controversial.

Markers of cellular dysoxia during orthotopic liver transplantation in pigs.

OBJECTIVE: To characterize global, regional, and end-organ markers of cellular dysoxia during orthotopic liver transplantation and early reperfusion in pigs. DESIGN: Descriptive study. SETTING: University hospital research laboratory. ANIMALS AND INTERVENTIONS: 7 fasted, anesthetized, and mechanically ventilated Yorkshire pigs underwent orthotopic liver transplantation. Oxygen consumption (VO2) and oxygen delivery (DO2) were both calculated using standard formulae. Gastric interstitial pH and the gastroarterial partial pressure of carbon dioxide (PCO2) gradient were measured with a gastric tonometer. The following were determined from arterial blood samples: serum lactate to pyruvate ratio, serum 3-hydroxybutyrate to acetoacetate ratio, plasma free fatty acids, and plasma free and total carnitine levels. MEASUREMENTS AND RESULTS: Data were collected 1 h after induction of anesthesia (I), at the end of the anhepatic phase (A), and 1 h after reperfusion (R), Median (range) VO2 values obtained at the specified time points were: I 318 (206-1860), A 210 (152-408), R 330 (214-424) ml/kg per min, respectively (NS); DO2 values were: I 1828 (1382-3259), A 1219 (452-2492), R 1741 (1345-12,071) ml/kg per min, respectively (NS). The lactate to pyruvate ratio, reflecting the redox potential of the cytosol, progressively increased: I 22 (9-46), A 29 (16-68), R 43 (23-55), (p < 0.05). Gastric interstitial pH, as well as the gastroarterial PCO2 gradient values at the specified time points did not reach statistical significance. Levels of ketone bodies (3-hydroxybutyrate+acetoacetate) remained lower than 0.120 mmol/l. The ketone body ratio did not significantly vary over time (NS). Plasma esterified and free carnitine concentrations and free fatty acid values remained within normal limits (NS). Among these markers, the ketone body ratio presented the largest area under the receiver operating characteristic curve as a marker of postoperative mortality, with an inflexion point at 0.9. CONCLUSION: In this study, orthotopic liver transplantation was associated with significant variations over time in the redox potential of the cytosol. Postoperative mortality was, however, related to the redox state of the liver mitochondria. Our data suggest the occurrence of abnormal tissue oxygenation during liver transplantation.

Benign tumors of the liver in children: analysis of a series of 20 cases.

Twenty children were treated for a benign hepatic tumor during a 17-year period. One child was not operated upon but followed since birth for 2 years by ultrasonogram. Mesenchymal hamartoma was found in 8 cases, a solitary cyst in 4, and 3 other cases of hamartomas were without cystic components. Two girls had lesions corresponding to focal nodular hyperplasia; two children had a solitary adenoma. Radical surgical treatment was possible in all 19 operated cases, except one case of focal nodular hyperplasia where a right lobectomy would have been necessary. Ultrasonography and angiography are the main explorations to be undertaken before treatment; preoperative embolization of the main arteries to the tumor was done in five cases, with unquestionable advantage in four of them. No mortality was recorded and results were good with a mean follow-up of 19 months.

Lessons from the first 100 liver transplantations in children at Bicêtre Hospital.

The authors report their experience with 100 liver transplantations at Bicêtre Hospital. From 1988 to 1991, 85 children received a total of 100 liver grafts (mean age, 44.4 months; two thirds were under 3 years of age). Fifty-four percent of the grafts were reduced-size. Cyclosporine, steroids, and azathioprine were used for immunosuppression. The actuarial survival rate at 4 years is 86%. Retransplantation was performed in 14 children (16%). Forty-four patients (49%) had another operation. Biliary complications (17%), hepatic artery thrombosis (HAT) (14%), and hemoperitoneum (14%) were the most frequent surgical complications. Retransplantation was avoided in 50% of the patients who underwent urgent artery revision for thrombotic complications. It appeared that ABO-incompatible were better tolerated in children without ABO alloantibodies at the time of transplantation. The survival rates of ABO-identical, -compatible, and -incompatible liver grafts did not differ (61%, 50%, and 57% respectively). The results suggest that an aggressive policy of reintervention, including retransplantation, is necessary to achieve a satisfactory survival rate and quality of life. Children lacking ABO alloantibodies at the time of transplantation might tolerate ABO-incompatible liver grafts better.

Liver retransplantation in children.

Between January 1988 and December 1993, 132 children received 154 orthotopic liver transplantation (OLT) at Bicêtre Hospital (France). Among them, 18 children underwent two and 2 children underwent three transplants (retransplant rate; 15.2%). Retransplantations were classified into three groups according to the interval between both OLTs: 1 (< 7 days, n = 8), 2 (8 days to 6 months, n = 10) and 3 (> 6 months, n = 4). Each group was compared with a control group whose grafts survived more than 1 week. There were no significant differences regarding age (35 +/- 49, 23 +/- 13, and 33 +/- 15 versus 49 +/- 41 months), cold ischemic time (566 +/- 105, 470 +/- 144, and 476 +/- 58 versus 455 +/- 110 minutes) and reduced size graft ratio (62.5%, 60%, and 75%, versus 58.3%). The causes of graft failure included primary nonfunctioning liver (PNF, n = 8) all in group 1 cases, biliary complications associated with hepatic artery thrombosis (HAT, n = 10; group 2, 6; group 3, 4), chronic rejection (n = 3; group 2, 1; group 3, 2) and three others (uncontrollable acute rejection, fulminant hepatitis, and secondary dysfunction, all in the group 2). The authors were unable to detect the cause of PNF. The overall survival rate after retransplantation was 62.5%, 60.0% and 75%, respectively. To reduce the rate of retransplants and improve the prognosis after OLT, further investigation into the cause of PNF, refinements in the anastomotic technique of the hepatic artery, and also early treatment of HAT are some of the goals to be achieved.

Hepatic artery thrombosis in pediatric liver transplantation.

The incidence of hepatic artery thrombosis was analyzed in a series of 59 consecutive liver transplants performed in 52 children less than 15 years of age at the University of Louvain Medical School, Brussels, from March 1984 to March 1987. This incidence was 17% for the whole series; it was increased in small recipients less than 3 years of age and less than 15 kg (23%) in weight, as well as when the liver was harvested from a small donor less than 15 kg in weight (38%). It was also increased when the donor liver was supplied by more than one artery. This incidence was markedly reduced by arterial revascularization from the aorta, either directly or by interposition of an iliac segment; the reduced-size livers had a much lower incidence of arterial thrombosis (5%) than the whole livers (23%). In the present series, we did not find any argument to support the view that poorly controlled rejection could be implicated in the pathogenesis of arterial thrombosis.

Intrahepatic biliary-enteric bypass for complete extrahepatic biliary obstruction in children.

Intrahepatic biliary-enteric anastomosis is rarely practiced in pediatric surgery. The authors report on two children who have been successfully treated using this method. First described by Longmire and Sandford in 1948, intrahepatic biliary-enteric anastomosis is possible in children. This procedure is only indicated as a last recourse for circumstances in which the extrahepatic biliary tree is completely obstructed.

Pediatric liver transplantation: report on 52 patients with a 2-year survival of 86%.

Between March 1984 and March 1987, 59 orthotopic liver transplantations have been performed in 52 children at the Catholic University of Louvain in Brussels. The actuarial survival was 86% +/- 5 up to 3 years of evolution. The most frequent indication has been chronic hepatic insufficiency (43 patients) mainly because of biliary atresia; seven patients were transplanted for acute hepatic insufficiency and only two for liver tumor. Because of important donor/recipient weight discrepancy, a reduced-size liver was used in 20 occasions either for first or second transplant. No difference in the incidence of major complications were seen between whole liver and reduced size liver transplanted children, with the exception of more frequent subhepatic collections in the first and more hepatic artery thrombosis in the second group. Liver tests, clinical rehabilitation, and survival appear to be equal in the two groups.

Spleno-caval shunt in children using internal jugular vein graft: a case report.

Several techniques for decompression of portal hypertension have been described. The spleno-caval shunt is an easy and safe technique described in adult patients. However, the procedures described in adults are not adapted to children. We report an adaptation of this technique in a child, using the internal jugular vein as an interposition graft for relief of portal hypertension.

[Liver transplantation in children. New experience in a Pediatric Surgery unit. Evaluation of the first 18 months' experience]. / Transplantation hépatique chez l'enfant. Nouvelle activité d'un service de Chirurgie Pédiatrique. Evaluation après dix-huit mois.

The authors report an eighteen month experience with orthotopic liver transplantation (OLT) in children in the Pediatric Department of Hospital Bicêtre in Paris, from January 1988 until July 1989. Thirty-eight OLTs including 4 retransplant operations, were performed in 34 children, aged from 7 months to 13 years, 20 of them under the age of 3 years. Biliary atresia was the indication for 22 children. Twenty-eight donors were children. A reduced-size liver was used in 17 cases. The technique for OLT was based on the description by TE Starzl. Surgical complications led to reoperation in 15 cases, mostly in relation to hepatic artery thrombosis (HAT), which occurred in 7 cases: small donor liver was considered to be one of the causative factors. In all but one case of HAT a retransplant was considered; to date it is has been performed in 3 of these children. Thirty-one children have survived, with a mean follow-up of 8 months, all are at home, except for one child at the time of this report. Liver function tests are normal for 22, and moderately altered for 5. For the four remaining children, retransplant is planned for 3 cases and one child has just been retransplanted. The authors emphasise the fact that OLT in small children requires a specialised pediatric environment, particularly as regards intensive care and nursing.

[Intrahepatic glutathione and oxidative stress in liver transplantation in the pig]. / Glutathion intra-hépatique et stress oxydatif en transplantation du foie chez le cochon.

OBJECT: To determine the loss of endogenous GSH from livers cold-stored and reperfused, using a model of liver transplantation in the pig. MATERIAL AND METHODS: Four female Yorkshire pigs weighing 19 to 40 kg received a liver allograft. Donor livers were cold-stored in the UW solution. Mean cold ischemic time was 6.5 hours. Malondialdehyde (MDA) levels were used as an index of oxidative stress. MDA plasma levels were measured following recipient laparotomy (H0), immediately (H1), and 90 minutes after liver reperfusion (H2). MDA and GSH levels in liver were measured following donor laparotomy (T0), at the end of cold ischemic period (T1), and at 90 minutes following liver reperfusion (T2). RESULTS: Three animals survived. MDA liver levels decreased of 44% between T0 and T1, then increased to 92% at T2. In contrast, in plasma, graft reperfusion was associated with an increase of MDA to 140% of the baseline values which reached 188% at H2. Intrahepatic GSH levels decreased of 49% at T1, then to 72% at T2. CONCLUSION: our study suggests that in liver transplantation: (1) Hepatic GSH is depleted to 49% during cold-storage, and an additional 23% is lost after reperfusion; (2) GSH contained in the UW solution does not prevent the loss of hepatocellular glutathione during preservation and reperfusion; (3) after short periods of cold ichemia, endogenous hepatic GSH may protect against oxydative stress in the transplanted liver.

[Post-traumatic hemobilia. Is selective hepatic artery ligation dangerous?]. / Hémobilie post-traumatique. La ligature sélective de l'artère hépatique est-elle dangereuse?

Selective hepatic artery ligation has traditionally been considered dangerous by some authors in the treatment of traumatic haemobilia. Having observed one case in which this technique was successful in controlling liver haemorrhage, the authors have reviewed the literature. Conditions in which selective hepatic artery ligation can be dangerous are discussed. The safety and effectiveness of this treatment of traumatic haemobilia in normovolemic patients is emphasized.

[Total esophagectomy by stripping without thoracotomy in cancer of the pharynx, esophagus and cardia. 34 cases]. / L'oesophagectomie totale par "stripping" sans thoracotomie dans les cancers du pharynx, de l'oesophage et du cardia. Trente-quatre observations.

Total oesophagectomy by stripping without thoracotomy was performed in 34 cancer patients to reduce operative mortality and morbidity in those with impaired respiratory function. The carcinoma was located in the pharynx in 20 cases, on the cardia in 9 cases and on the lower oesophagus in 5 cases. Reconstruction in the posterior mediastinum was effected with the descending colon in 32 patients. The operative mortality rate was 11.8% and fistulization developed in 20.6% of the cases. Eight patients (26.5%) required post-operative endoscopic dilatation. Ninety per 100 of the patients who survived surgery resumed satisfactory feeding. Thus, these patients with high operative risk who underwent oesophagectomy by stripping without thoracotomy benefited from tumoral excision and normal feeding with results comparable to those of other types of oesophagectomy.

[Rapid liver perfusion in multiple organ procurement in children. For liver transplantation]. / Perfusion rapide du foie, lors du multiprélèvement d'organes chez l'enfant. En vue d'une transplantation hépatique.

We report our experience of the rapid liver flush technique in multiple organ harvesting from donor children. Between January 1988 and May 1989, out of 33 liver transplantations in 30 children, 24 were performed using livers obtained from children. The donors' mean age was 75 months. In every case several organs were removed (24 kidneys, 9 heart-lung blocks, 9 hearts, 1 pancreas). The mean duration of the procedure was 153 minutes. Supernumerary hepatic vessels (6 left and 2 right hepatic arteries) were left intact. Twenty-two hepatic grafts were classified as functional. Two grafts classified as non-functional were responsible for 2 deaths in this series. The rapid liver flush technique seems to be satisfactory in donor children when the following characteristics are taken into account: tendency to haemodynamic instability, small caliber of the vessels and fragility of tissues.

[Transplantation of reduced-size livers in children]. / Transplantation des foies réduits chez l'enfant.

Nowadays, liver reduction techniques make it possible to use livers obtained from adults or adolescents for implantation in children. These techniques have been evaluated by analysis of 100 liver transplantations performed between January 1988 and October 1991 in 85 children. Forty-six full-size grafts implanted in 38 children (group 1) were compared with 54 reduced-size grafts implanted in 47 children (group 2). The overall actuarial survival at 4 years was 86 percent. There was no statistical significant difference between the two groups as regards the rates of death (8 versus 19 percent), reoperation (54 versus 64 percent), retransplantation (15 versus 16 percent), hepatic artery thrombosis (13 versus 15 percent) and graft survival (82 versus 70 percent) respectively. Haemorrhage was significantly more frequent in group 1 than in group 2 (P = 0.04), irrespective of whether transplantation was performed urgently or electively. Using reduced-size livers considerably increases the number of liver grafts available to children. Apart from a greater risk of haemorrhage, the results obtained with reduced-size livers were identical with those obtained with full-size livers.

[Congenital absence of portal vein in a girl with biliary atresia treated with liver transplant]. / Ausencia congénita de vena porta en niña con atresia de vías biliares, sometida a trasplante hepático.

The congenital absence of the portal vein is a rare malformation, which has been generally discovered in association with another anomalies like a cardiac, gastrointestinal or genitourinary defects. With portal hypertension and hepatic cirrhosis, this anomaly is similar to spontaneous porto-systemic derivation, and for that not collateral venous drainage is present. In these patients, total interruption of mesentaric venous drainage during procurement of liver transplant produce a very important bowel and mesenteric edema, which can promote an injert fatal evolution. The authors present the first paediatric liver transplant, in a patient with portal venous agenesia, with de piggy-back technique was done and this complication was obviated, and a review of the literature about this issue is done.

Esophageal varices in chronic intestinal insufficiency in absence of portal hypertension or liver cirrhosis: case report.

We report the case of a 62-year-old man with short-bowel syndrome, referred for intestinal transplantation, who had esophageal varices (EV) due to superior vena cava (SVC) thrombosis. Pretransplantation work-up revealed protein S deficiency. Results of liver function tests were normal. Upper endoscopy showed grade II to III EV in the upper and middle segments of the esophagus. Computed tomography demonstrated thrombosis of the jugular, subclavian, and SVC veins and marked collateral vessels in the chest. Transient elastography yielded normal findings. A liver biopsy specimen showed a normal aspect of the liver, without fibrosis or liver cirrhosis. Presence of EV in a patient with chronic intestinal insufficiency may be related to collateral venous circulation associated with SVC thrombosis in the absence of portal hypertension. In this situation, an isolated intestinal graft is indicated.

Outcome of exfoliative rejection after isolated intestinal transplantation in an adult: case report.

A 34-year-old-man with short-bowel syndrome received an isolated small bowel graft. On postoperative day (POD) 11, ileal biopsy specimen demonstrated mild to moderate rejection that did not respond to corticosteroid bolus therapy. On POD 14, endoscopy and histologic examination revealed exfoliative rejection that was not controlled after 14 days of therapy with thymoglobulin. On POD 95, the patient underwent surgery again because of intestinal obstruction. The graft was removed 6 months after transplantation because of continuous severe abdominal pain with weight loss. After enterectomy, the patient developed multiple-organ failure and died on POD day 8. This case underlines the severity of exfoliative rejection and suggests that early enterectomy be performed when the diagnosis is made, before deterioration of clinical status and development of infectious and nutritional complications.