Indications and successes of intestinal transplantation in children in the 21st century: A retrospective cohort study.

AIMS: To report the results and successes of intestinal transplantation (ITx) in the most active European centres, to emphasize that, although it is a difficult procedure, it should remain a therapeutic option for children with total, definitive and complicated intestinal failure when intestinal rehabilitation fails. METHODS: We retrospectively collected data about all patients less than 18 receiving an ITx from 2010 to 2022 in 8 centres, and outcomes in July 2022. RESULTS: ITx was performed in 155 patients, median age 6.9 years, in 45% for short bowel syndromes, 22% congenital enteropathies, 25% motility disorders, and 15% re-transplantations. Indications were multiple in most patients, intestinal failure-associated liver disease in half. The graft was in 70% liver-containing. At last follow up 64% were alive, weaned from parenteral nutrition, for 7.9 years; 27% had died and the graft was removed in 8%, mostly early after ITx. DISCUSSION: ITx, despite its difficulties, can give a future to children with complicated intestinal failure. It should be considered among the therapeutic options offered to patients with a predicted survival rate lower than that after ITx. Patients should be early discussed within multidisciplinary teams in ITx centres, to avoid severe complications impacting the results of ITx, or even to avoid ITx.

Prediction models of donor arrest and graft utilization in liver transplantation from maastricht-3 donors after circulatory death.

Shortage of organs for transplantation has led to the renewed interest in donation after circulatory-determination of death (DCDD). We conducted a retrospective analysis (2001-2009) and a subsequent prospective validation (2010) of liver Maastricht-Category-3-DCDD and donation-after-brain-death (DBD) offers to our program. Accepted and declined offers were compared. Accepted DCDD offers were divided into donors who went on to cardiac arrest and those who did not. Donors who arrested were divided into those producing grafts that were transplanted or remained unused. Descriptive comparisons and regression analyses were performed to assess predictor models of donor cardiac arrest and graft utilization. Variables from the multivariate analysis were prospectively validated. Of 1579 DCDD offers, 621 were accepted, and of these, 400 experienced cardiac arrest after withdrawal of support. Of these, 173 livers were transplanted. In the DCDD group, donor age < 40 years, use of inotropes and absence of gag/cough reflexes were predictors of cardiac arrest. Donor age >50 years, BMI >30, warm ischemia time >25 minutes, ITU stay >7 days and ALT ≥ 4× normal rates were risk factors for not using the graft. These variables had excellent sensitivity and specificity for the prediction of cardiac arrest (AUROC = 0.835) and graft use (AUROC = 0.748) in the 2010 prospective validation. These models can feasibly predict cardiac arrest in potential DCDDs and graft usability, helping to avoid unnecessary recoveries and healthcare expenditure.

Primum Non Nocere: Organ Donation After Electrocution and Transplantation of Electricity-Damaged Livers: Report of 2 Cases.

Liver transplantation remains the treatment of choice for patients with end-stage liver disease. However, allograft availability continues to be a problem, and extending the criteria for organ acceptance is key. Deceased donors after electrical accidents, as well as electricity-traumatized allografts, are not common but should be considered suitable. This study describes 2 cases of heart-beating organ donors with electrical injury to the liver. In 1 case, the electric shock was the cause of death; in the second case, the injury was caused by defibrillation at organ procurement. Both allografts had sustained sizeable electrical injury, and both resulted in excellent early posttransplant outcomes. These cases demonstrate that electrocution is not a contraindication to donation and that electricity-traumatized allografts may remain transplantable after careful assessment. Education of all staff in the management of such donors can optimize utility of such allografts.

Immunosuppression withdrawal after auxiliary liver transplantation for acute liver failure.

BACKGROUND: The potential for immunosuppression withdrawal is the rationale for auxiliary liver transplantation (AUX) in patients with acute liver failure (ALF). PATIENTS AND METHODS: Forty-four AUX were performed in 28 adults and 16 children with ALF secondary to seronegative hepatitis (n = 20; 45%), paracetamol hepatotoxicity (n = 14; 32%), acute viral hepatitis (hepatitis B virus [HBV] n = 3, Epstein-Barr virus n = 1; 9%), drug-induced hepatitis (n = 3; 7%), autoimmune hepatitis (n = 2; 5%), and mushroom poisoning (n = 1; 2%). All patients fulfilled the King's College Hospital transplant criteria for ALF. After partial hepatectomy, 38 patients received a segmental auxiliary graft and six, a whole auxiliary graft. Immunosuppression was based on calcineurin inhibitors and steroids. RESULTS: Thirty-four patients (77%) are alive after a median follow-up of 30 months (range 4 to 124). Eight adults and two children died of sepsis (n = 6; 14%) at a median interval of 30 days (range 2 to 66), intraoperative cardiac failure (n = 1), brain edema on postoperative day 8 (n = 1), sudden death on day 35 (n = 1), and multiple organ failure associated with HBV recurrence 4 years after transplantation (n = 1). Three patients underwent retransplantation for small-for-size graft syndrome with sepsis on postoperative day 15 (n = 1) and for ductopenic rejection 4 and 15 months after AUX (n = 2). In 10/31 (32%) survivors (6/18 adults and 4/13 children) immunosuppression was completely withdrawn after a median of 19 months. CONCLUSION: Complete immunosuppression withdrawal can be achieved in a significant proportion of patients after AUX for ALF.

Liver transplantation with monosegments.

BACKGROUND: Shortage of size-matched pediatric donors led to the development of surgical techniques to reduce or split livers and thus increase the potential pool of donors. Despite this, neonatal transplantation remains a problem because of the small size of the recipients. Further reduction of the left lateral segment is possible to provide a single segment graft (segment III). We report our experience of transplanting 6 babies using this technique. METHODS: Of 310 children transplanted in our center between October 1989 and March 1998, 6 patients, 2 male and 4 female, median age 37.5 days (range 5 to 92 days), median weight 3.45 kg (range 2.45 to 5.46 kg) were transplanted with a monosegment. The cause of liver failure was neonatal hemochromatosis in 4, retransplantation for hepatic artery thrombosis in 1, and hepatitis B in one. The donor liver was reduced or split to a left lateral segment. Segment II was then resected and discarded before transplantation. RESULTS: Overall, graft and patient survival is 83.3%. Five patients are alive with good graft function at a mean follow-up of 30.4 months (range 8 to 82 months). One child who was transplanted for hepatic artery thrombosis died from sepsis and multiorgan failure 48 hrs after transplant. None of the survivors had vascular or biliary complications. CONCLUSIONS: Monosegment liver transplantation with segment III appears to be a satisfactory option for treating small babies with liver failure.

The use of TachoSil in children undergoing liver resection with or without segmental liver transplantation.

INTRODUCTION: Local haemostatic agents are used for the control of surgical haemorrhage when standard techniques are inadequate, but there are few studies of these products in children. PATIENTS AND METHODS: This was a prospective, open-label study in which children (aged 4 weeks to 6 years) undergoing liver resection with or without segmental liver transplantation were treated with TachoSil, a collagen patch coated with a dry layer of human fibrinogen and human thrombin, if minor (i. e., oozing) or moderate bleeding was present after primary haemostatic treatment. Time to haemostasis after TachoSil application was the primary endpoint. Safety was assessed by adverse events (AEs), including post-operative infections, symptoms of graft rejection and re-operations. RESULTS: Enrolment was stopped early after 16 children had entered the study. 13 children underwent whole liver resection and transplantation and 3 patients underwent segmental resection. Satisfactory haemostasis was achieved in 13 children (81.3%; 95% CI: 61.8-100%) at 3 min and in 1 child at 8 min. Occurrence of AEs was as expected, with most being known complications of the underlying disease, surgical procedure, or use of immunosuppressive medication. No AEs were considered to be related to the use of TachoSil. CONCLUSIONS: The use of TachoSil for haemostasis after primary haemostatic treatment appears to be safe and effective in children undergoing liver resection.

Segmental liver transplantation from non-heart beating donors--an early experience with implications for the future.

We report our experience of pediatric liver transplantation with partial grafts from non-heart beating donors (NHBD). Controlled donors less than 40 years of age with a warm ischemia time (WI) of less than 30 min were considered for pediatric recipients. Death was declared 5 min after asystole. A super-rapid recovery technique with aortic and portal perfusion was utilized. Mean donor age was 29 years and WI 14.6 min (range 11-18). Seven children, mean age 4.9 years (0.7-11), median weight 20 kg (8.4-53) received NHBD segmental liver grafts. Diagnoses included seronegative hepatitis, neonatal sclerosing cholangitis, familial intrahepatic cholestasis, hepatoblastoma, primary hyperoxaluria and factor VII deficiency (n=2). The grafts included four reduced and one split left lateral segments, one left lobe and one right auxiliary graft. Mean cold ischemia was 7.3 h (6.2-8.8). Complications included one pleural effusion and one biliary collection drained percutaneously. At 20 months (10-36) follow-up all children are alive and well with functioning grafts. Donation after cardiac death is a significant source of liver grafts for adults and children with careful donor selection and short cold ischemic times.

Paediatric liver transplantation: the surgical view.

Liver transplantation is the accepted treatment for a wide variety of liver diseases in children. Over the past 10 years a number of innovative surgical techniques have been developed to overcome the shortage of size matched donors particularly in children less than 5 years of age. Graft and patient survival at one year after liver transplantation has continued to improve, and is now over 85% and higher for good risk cases. Complications are relatively common, but provided graft function is satisfactory, long term survival for these children is to be expected. The need for retransplantation has fallen significantly. Causes of early mortality include graft dysfunction and sepsis. Late mortality is due to sepsis, post-transplant lymphoproliferative disease, and non-compliance. Long term survival with good graft function and excellent quality of life is possible for the majority of children undergoing liver transplantation.

Auxiliary partial orthotopic liver transplantation for Crigler-Najjar syndrome type I.

OBJECTIVE: To determine if auxiliary partial orthotopic liver transplantation (APOLT) has the long-term potential to correct the underlying abnormality in Crigler-Najjar syndrome type 1 (CNS1) without the need for total liver replacement. BACKGROUND: Orthotopic liver transplantation has been used successfully to replace the defective enzyme in CNS1. Experimental studies have shown that only 1% to 2% of the normal hepatocyte mass is needed for bilirubin conjugation. If APOLT corrects the underlying metabolic abnormality, it has the advantage of preserving the native liver, which would serve as a "safety net" should the graft fail, and there is the potential for gene therapy in the future with possible withdrawal of immunosuppression. METHODS: Seven APOLT procedures were performed in six recipients with CNS1. Median age at transplantation was 10.5 years. Six transplants were performed as a left auxiliary liver transplant, and one was performed as a right auxiliary liver transplant. Median serum bilirubin level at transplantation was 320 micromol/L. All patients required 12 to 16 hours of phototherapy daily before the transplant to maintain serum bilirubin levels between 250 and 350 micromol/L. RESULTS: Median serum bilirubin level was 50 micromol/L at day 5 after the transplant and 23 micromol/L at a median follow-up of 32 months. In four children, early severe acute rejection developed, requiring conversion to tacrolimus; one underwent a second transplant for chronic rejection and graft atrophy but died from lymphoproliferative disease 6 months after the second transplant. CONCLUSIONS: This report shows that APOLT is technically feasible and provides adequate hepatocyte mass to correct the underlying metabolic abnormality in CNS1.

Differences in tumour growth, tumour cell proliferation and immune function after laparoscopy and laparotomy in an animal model.

BACKGROUND: Clinical and experimental studies have shown that laparoscopy preserves the immune response and can give better clinical results than laparotomy. However, the use of laparoscopy for the treatment of cancer patients is still controversial due to the risk of port-site and haematogenous metastases and increased tumour growth. The purpose of this experimental study was to assess tumour growth and the mechanism of differential tumour behaviour after laparoscopy and laparotomy. METHODS: Seventy-five young, male Wistar rats were randomly assigned to one of two experiments. Experiment 1: 45 animals were inoculated subcutaneously with Walker carcinosarcoma 256 cells and were subdivided into three groups of 15 rats. Control group la was submitted to anaesthesia only, group 1b received carbon dioxide (CO(2)) pneumoperitoneum,while group 1c received a laparotomy. Animals were sacrificed on postoperative day (POD) 7; tumours were excised and weighed to evaluate tumour growth. Nucleolar organiser regions identified by silver staining (AgNORs) were analysed to evaluate cell proliferation. Experiment 2: 30 rats were submitted to the same procedures as before, with ten animals in each group (2a, 2b, 2c), and a delayed-type hypersensitivity response (DTH) was used to evaluate the immune function. RESULTS: The average tumour mass was 1.76 g in group 1a, 2.81 g in group 1b and 4.21 g in group 1c (p < 0.05). The AgNOR expression results were similar in the three groups. The immune function was better preserved in the control group (2a: average inflammatory area on POD1 = 106 mm(2) and on POD2 = 128.18 mm(2)), than in the pneumoperitoneum group (2b: average inflammatory area on POD1 = 79.75 mm(2) and on POD2 = 126.93 mm(2)); the worst results were in the laparotomy group (2c: average inflammatory area on POD1 = 33.33 mm(2) and on POD2 = 61.32 mm(2)).There were significant differences between groups 2a and 2c and between 2b and 2c. CONCLUSION: Laparotomy stimulates a greater tumour growth than CO(2) pneumoperitoneum, but there is no difference in tumour cell proliferation. The cellular immune function is better preserved in animals submitted to CO pneumoperitoneum than in the laparotomized animals. These results suggest a relationship between a weaker immune response and a greater tumour growth.

Liver transplantation for extra hepatic biliary atresia.

Kasai portoenterostomy has transformed the prognosis for children with Extra Hepatic Biliary Atresia (EHBA). However, for children developing end stage liver disease following portoenterostomy, liver transplantation (OLT) is the treatment of choice. Between February 1989 and March 1996, 64 children with EHBA underwent 79 transplants (26 males, 38 females; median age 2.2 years, range 5 months-17 years; median weight 11.4 kg, range 5-65 kg). Of these, 58 (85%) had undergone previous portoenterostomy. Nineteen patients (30%) had gastrointestinal bleeding prior to OLT assessment. Mean serum bilirubin was 229 mumol/liter (range 11-801 muml/liter). Four children had associated polysplenia syndrome. Of the 79 transplants, 30 received whole and 41 reduced-size cadaveric grafts and 9 living related grafts. Eleven patients (17%) died, nine within one month of surgery. Thirteen patients were retransplanted once and one twice. There were 16 vascular complications (10 hepatic artery thrombosis, 3 portal vein thrombosis, 3 venous outflow obstruction) and 10 biliary complications (4 anastomotic leaks, 6 strictures). Ten patients (16%) had bowel perforation following the transplant. The 5 year actuarial patient and graft survival for this group is 84% and 69% respectively with normal physical and mental development in the majority. OLT provides satisfactory treatment for children with EHBA with end stage liver disease with long term survival in the majority.

Split liver transplantation: King's College Hospital experience.

BACKGROUND: The purpose of split liver transplantation is to increase the source of pediatric grafts without compromising the adult donor pool. Early results have been discouraging because of technical complications and selection of poor risk patients. METHODS: The results of a single center experience of 41 split liver transplantations were analyzed. Patient and graft survival and complications related to the technique were analyzed. RESULTS: Patient and graft survival for the whole group was 90% and 88% respectively at a median follow up of 12 months (range 6-70 months). Patient and graft survival for the right lobe graft was 95% and the left lateral segment 86% and 82% respectively. Four patients died, of which two of the patients were first two splits following technical complications. Two others died, one from cerebral lymphoma and the other of multiorgan failure secondary to sepsis. One patient has been retransplanted for chronic biliary sepsis. CONCLUSION: Split liver transplantation has now become an acceptable treatment option for both adult and pediatric recipients with end stage liver disease. Right lobe recipients are not disadvantaged by the procedure. Good results can be achieved with better patient selection and by the use of good quality organs.

Replacement of the retrohepatic vena cava in segmental liver transplantation.

Reduced grafts represent an important technical development in paediatric liver transplantation. The use of a left lateral segment graft has required preservation of the native inferior vena cava to "piggy-back" the graft onto it. We report four children who underwent left lateral segment transplantation with caval replacement using the donor iliac vein because the native retrohepatic inferior vena cava was small, friable or difficult to preserve. There were no caval or hepatic vein complications post-transplant and the donor iliac vein proved to be a satisfactory interpositional graft. The technique offers the advantages of a wider retrohepatic cava avoiding venous outflow or caval obstruction, provides good tissue to suture and is well suited for the triangulation technique of the left hepatic vein.

Bowel perforation after paediatric orthotopic liver transplantation.

Bowel perforation is a well-recognized complication following orthotopic liver transplantation. Of 194 paediatric liver transplantations performed in our hospital, 13 patients (6.7%) developed bowel perforation post-transplantation. Contributory factors included previous operation, steroid therapy and viral infection. The incidence was higher in children who underwent transplantation for biliary atresia after a previous Kasai portoenterostomy. Seven patients (53% of this group) reperforated. Diagnosis may be difficult and a high index of suspicion is needed.

A validated technique for the analysis of biliary bile acid secretion in donor livers prior to transplantation.

Many parameters currently used for the pre-transplant assessment of liver allografts, are not reliable enough in predicting the likelihood of early graft dysfunction or non-function. It is generally accepted that bile secretion is a sign of hepatic function post-transplant and that bile flow shows a close linear relationship to the secretion of bile acids ("apparent choleretic activity"). We have studied bile flow, biliary bile acid concentrations and composition and measured apparent choleretic activity from hepatic bile collected with a new technique under controlled conditions at the time of retrieval from 18 donor livers. More than three samples were collected from each of 13 donors and a total of 65 samples of hepatic bile were analysed. Of these, ten showed typical apparent choleretic activity with a positive slope in the regression line analysis (correlation coefficient of 0.9), validating our collection technique.