[Liver transplantation in paediatric patients in the Netherlands; evolution over the past two decades]. / Levertransplantaties bij kinderen in Nederland.

OBJECTIVE: To evaluate the results of the national paediatric liver transplantation programme in the University Medical Centre (UMC) Groningen in the Netherlands during the past two decades. DESIGN: Retrospective cohort study. METHOD: We analysed data from paediatric patients who underwent liver transplantation at UMC Groningen in the period 1995-2016. We compared outcomes from children who had undergone a liver transplantation in the period 1995-2005 (cohort A; n = 126) and in the period 2006-2016 (cohort B; n = 169). We performed a subanalysis in cohort B between liver transplantations with deceased donor livers (n = 132) and living donor liver transplantations (LDLT; n = 37). RESULTS: In cohort A, almost all livers came from deceased donors (99%), whereas in cohort B, 37 LDLTs (22%) were performed. The median age of recipients was significantly higher in cohort A (4.4 vs. 2.5 years; p = 0.015). Postoperative complications were comparable for both cohorts. Re-transplantations within a year after transplantation were more often performed in cohort A than in cohort B (25% vs. 12%; p = 0.004). Following LDLT, there was 2 times (5.4%) an indication for re-transplantation. In cohort B the 5-year survival rate was better than in cohort A (83 vs. 71%; p = 0.014). In cohort B, 5-year survival was higher after LDLT than after transplantation with a deceased donor liver (95 vs. 81%; p = 0.025). CONCLUSION: Outcomes after paediatric liver transplantation in the Netherlands have further improved during the past two decades. With an actuarial 5-year survival of 83% in the most recent cohort, and as high as 95% following LDLT, we can say that the UMC Groningen has a successful national paediatric liver transplant programme.

Outcomes after resection and/or radiofrequency ablation for recurrence after treatment of colorectal liver metastases.

BACKGROUND: Repeat liver resection for colorectal liver metastases (CRLMs) is possible in a limited number of patients, with radiofrequency ablation (RFA) as an alternative for unresectable CRLMs. The aim of this study was to analyse survival rates with these interventions. METHODS: This was a database analysis of patients who underwent first and repeat interventions for synchronous and metachronous CRLMs between 2000 and 2013. Descriptive and survival statistics were calculated. RESULTS: Among 431 patients who underwent resection or RFA for CRLMs, 305 patients developed recurrences for which 160 repeat interventions (resection and/or RFA or ablative radiotherapy) were performed. In total, after 707 first or repeat interventions, 516 recurrences (73·0 per cent) developed, of which 276 were retreated curatively. At the time of first intervention, independent risk factors for death were lymph node-positive primary tumour (hazard ratio (HR) 1·40; P = 0·030), more than one CRLM (HR 1·53; P = 0·007), carcinoembryonic antigen level exceeding 200 ng/ml (HR 1·89; P = 0·020) and size of largest CRLM greater than 5 cm (HR 1·54; P = 0·014). The 5-year overall survival rates for liver resection and percutaneous RFA as first intervention were 51·9 and 53 per cent, with a median overall survival of 65·0 (95 per cent c.i. 47·3 to 82·6) and 62·1 (52·2 to 72·1) months, respectively. CONCLUSION: RFA had good oncological outcomes in patients with unresectable CRLMs. Radiofrequency ablation is progressively more applied with each additional intervention.

Interplay of co-inherited diseases can turn benign syndromes in a deadly combination: haemoglobinopathy and bilirubin transport disorder.

We present a case about a 25-year-old male patient suffering from a rare genetic disorder called Mizuho haemoglobin. He was admitted to the Intensive Care Unit with acute liver and renal failure. During admission he also developed a cardiac tamponade twice. Finally he received a liver transplantation. Hereafter the patient stabilised and his liver and renal functions improved. His symptoms could not be explained solely by his known disease. After searching the literature, similarities between his symptoms and a rare complication of sickle cell disease were found. Molecular diagnostics showed that the patient also suffered from Gilbert's syndrome. Due to his chronic haemolysis, symptoms of this other disease were masked. This stresses the importance of always looking for other causes if symptoms or changes cannot be explained by a known rare disorder.

Staging laparoscopy in patients scheduled for pancreaticoduodenectomy minimizes hospitalization in the remaining life time when metastatic carcinoma is found.

OBJECTIVE: To compare the burden of total hospitalization as a ratio of survival of staging laparoscopy versus prophylactic bypass surgery in patients with unresectable periampullary adenocarcinoma. BACKGROUND: Periampullary adenocarcinoma is an aggressive cancer with up to 35% of the patients at surgery found to be unresectable. Palliative prophylactic surgical bypass versus endoscopic stenting has been addressed by randomized controlled trials, but none reported on the burden of hospitalization. METHODS: From a prospective database all patients with periampullary adenocarcinomas with a preoperative patent biliary stent and absent gastric outlet obstruction, but found unresectable during surgery, were analysed. They underwent a staging laparoscopy only versus prophylactic palliative bypass surgery. In-hospital days of the initial admission as well as all consecutive admission days during the remaining life span were compared both in absolute numbers and as relative impact. RESULTS: The inclusion criteria were met by 205 patients. Of these 131 patients underwent a staging laparoscopy detecting metastases in 21 patients. In 184 laparotomies 54 patients underwent prophylactic palliative bypass surgery for unresectable disease. Median total in-hospital-stay in the Laparoscopy Group was 3 days versus 11 days in the Palliative Bypass Group (p = 0.0003). Patients with metastatic disease found during laparoscopy stayed 3.5% of the remaining life time in hospital vs. 10.0% (p = 0.029) in patients with metastatic disease who underwent bypass surgery. CONCLUSIONS: Staging laparoscopy and early discharge in patients with metastatic peri-ampullary carcinoma resulted in reduced hospitalization, both in absolute number of days and as a rate of survival time.

Risk factors for central bile duct injury complicating partial liver resection.

BACKGROUND: Bile duct injury is a serious complication following liver resection. Few studies have differentiated between leakage from small peripheral bile ducts and central bile duct injury (CBDI), defined as an injury leading to leakage or stenosis of the common bile duct, common hepatic duct, right or left hepatic duct. This study analysed the incidence, risk factors and consequences of CBDI in liver resection. METHODS: Patients undergoing liver resection between 1990 and 2007 were included in this study. Those having resection for bile duct-related pathology or trauma, or after liver transplantation were excluded. Characteristics and outcome variables were collected prospectively and analysed retrospectively. RESULTS: There were 19 instances of CBDI in 462 liver resections (4·1 per cent). One-third of patients with CBDI required surgical reintervention and construction of a hepaticojejunostomy. Resection type (P < 0·001), previous liver resection (P = 0·039) and intraoperative blood loss (P = 0·002) were associated with an increased risk of CBDI. Of all resection types, extended left hemihepatectomy was associated with the highest incidence of CBDI (2 of 9 procedures). CONCLUSION: Patients undergoing extended left hemihepatectomy or repeat hepatectomy were at increased risk of CBDI.

Haemostasis monitoring during sequential aortic valve replacement and liver transplantation.

Despite advances in anaesthesiological and surgical techniques, cardiac surgery in cirrhotic patients remains hazardous. This report outlines our experience with haemostasis monitoring in two consecutive cases of sequential aortic valve replacement and liver transplantation. Clotting disturbances proved to have fatal consequences since one of these patients died following massive lung embolism. The second patient underwent successfully this combined procedure and is in good clinical state 14 months postoperatively. Evaluation and discussion of the coagulation monitoring by the Sonoclot Analyzer in both patients and related therapeutic suggestions for the prevention of thrombotic events are discussed.

Comparison of outcome after pediatric liver transplantation for metabolic diseases and biliary atresia.

UNLABELLED: Metabolic diseases (MD) are the second largest indication group for orthotopic liver transplantation (OLTx) in children after biliary atresia (BA). A better outcome after transplantation can be expected because of a better pretransplant condition and the absence of previous abdominal surgery. To prove this statement, patient survival, graft survival, and morbidity were compared between a group of 24 for MD and 52 for BA consecutively transplanted children. The actuarial one- and five-year patient survival rates for MD were 96% and 84%, and for BA 84% and 70%, respectively (p logrank test = 0.17). Three MD children (13%) and 15 BA children (29%) died. The actuarial one- and five-year graft survival rates for MD were 75% and 58%, and for BA 75% and 64%, respectively (p logrank test = 0.76). Seven MD children (29%) and 11 BA children (21%) were retransplanted. Postoperative bleeding and gastrointestinal complications occurred less frequent (4% vs. 18% and 4% vs. 14%, respectively), whereas biliary complications, viral infections, and acute rejection occurred more frequently (38% vs. 21%, 29% vs. 15%, and 50% vs. 37%, respectively) in MD children. The difference in the incidence of the various postoperative complications between both groups was not statistically significant. The mean ICU and ventilator stay was 7.5 and four days, respectively, in MD children and 16 and 10 days, respectively, in BA children (p = ns). The mean infection, complication, intervention, and retransplantation rate was equal in both groups. CONCLUSION: Mortality and morbidity after pediatric liver transplantation for MD and BA are not different despite the better starting point for children with MD.

Retransplantation of the liver in children.

BACKGROUND: Because of the poor outcome of hepatic retransplantation, it is still debated whether this procedure should be performed in an era of donor organ scarcity. The aim of this study was to analyze outcome of hepatic retransplantation in children, to identify risk factors influencing this outcome, and to assess morbidity and causes of death. METHODS: A series of 97 children after a single transplantation and 34 children with one retransplantation was analyzed. RESULTS: The 1-, 3-, and 5-year survival of children with a retransplantation was 70, 63, and 52%, respectively, compared with 85, 82, and 78%, respectively, for children after a single transplantation (P=0.009). Survival of children with a retransplantation within 1 month after primary transplantation was worse (P=0.007) and survival of children with a late retransplantation was comparable (P=0.66) with single transplantation. In early retransplantations, the Child-Pugh score was higher, donors were older and weighed more, and more technical variant liver grafts were used compared with single transplantations. Biliary atresia and a high Child-Pugh score were associated with decreased patient survival after retransplantation. Sepsis was the most important complication and cause of death after retransplantation. CONCLUSIONS: Retransplantation is a significant event after pediatric liver transplantation. Outcome after hepatic retransplantation in children is inferior compared with single transplantation. This difference is explained by low survival after early retransplantation and can be explained by the poor clinical condition of the children at time of retransplantation, especially in children with biliary atresia, and by the predominant use of technical variant liver grafts in retransplantations.

Prognostic factors for long-term actual patient survival after orthotopic liver transplantation in children.

BACKGROUND: Orthotopic liver transplantation has become the treatment of choice for children with end-stage liver disease. Although results have improved the last decades, still a considerable number of children die after transplantation. The aim of this study was to analyze long-term actual survival and to identify prognostic factors for such survival rates. METHODS: A consecutive series of 66 children receiving transplants who had or could have had a follow-up of at least 5 years was retrospectively analyzed. Actual survival and prognostic factors in relation to patient, donor, and operation related variables were assessed after multivariate analysis. RESULTS: Actual 1-, 3-, and 5-year patient survival was 86%, 79%, and 73%, respectively. A high Child-Pugh (C-P) score or C-P class C, high donor age, high blood loss index, and retransplantation were predictive factors for actual patient survival. A high blood loss index was correlated with biliary atresia, low recipient age and weight, and with previous upper abdominal operations. The duration of stay of the donor at the intensive care unit (ICU) was a predictive factor for retransplantation. CONCLUSIONS: Children with diseases eligible for liver transplantation should be seen early in the course of their disease in a transplantation center. All possible measures should be taken during the transplantation procedure to keep the blood loss at a minimum. Children with biliary atresia deserve special attention in this respect. The choice of donors has implications for survival.

Early vascular complications after pediatric liver transplantation.

Vascular complications have a detrimental effect on the outcome after liver transplantation. Most studies focus exclusively on hepatic artery thrombosis (HAT). The current study analyzed the incidence, consequences, and risk factors for HAT, portal vein thrombosis (PVT), and venous outflow tract obstruction (VOTO) in a consecutive series of 157 pediatric liver transplantations. The overall incidence of vascular complications was 21%. The incidences of HAT, PVT, and VOTO were 10%, 4%, and 6%, respectively. Patient survival after PVT and VOTO and graft survival after HAT and PVT were less compared with survival of grafts without vascular complications. To identify risk factors for vascular complications, factors related to recipient, donor, and surgical techniques were analyzed. A low donor-recipient (D/R) age ratio, long surgical time, and use of the proper hepatic artery of the recipient for arterial reconstruction were risk factors for HAT. Young age, low weight, segmental grafts, and piggyback technique were risk factors for PVT. Fulminant hepatic failure, high D/R age and weight ratios, and use of segmental grafts were related to VOTO. Vascular complications, which occurred in 21% of the pediatric liver transplantations, had a significant impact on patient and graft survival. Size disparity between donor and recipient was an important risk factor for vascular complications, especially in the case of transplantation of segmental grafts. Patient and graft survival might improve by avoiding the identified risk factors.

Predictive factors for portal fibrosis in pediatric liver transplant recipients.

BACKGROUND: Recent histopathological studies showed an unexpected high incidence of pathological changes in asymptomatic survivors after pediatric liver transplantation. The aim of this study was to analyze the occurrence of histological abnormalities, to assess the clinical significance, and to identify predictive factors for these pathological changes. METHODS: The first annual protocol graft biopsies of 84 consecutive liver transplants were analyzed and correlated with concomitant liver function tests. Identification of predictive factors for the histological abnormalities in the biopsies was performed by a multivariate logistic regression analysis. RESULTS: The incidence of portal fibrosis (PF) was 31%. Liver function tests showed except for the albumin level, an increase in the PF group compared with the group without PF. Mean values of alkaline phosphatase and direct bilirubin were 264 U/liter and 3 micromol/liter, respectively, in the normal group, and 435 U/liter and 23 micromol/liter, respectively, in the PF group (P=0.043 and 0.037). Eight of 19 univariantly tested variables were entered into a logistic regression model: cold ischemia time, preservation solution, type of allograft, cytomegalovirus recipient status, type of biliary reconstruction, biliary complications, graft complications, and rejection. A significant positive correlation with PF was found for cold ischemia time, biliary complications, and cytomegalovirus status. Acute rejection showed a negative correlation. CONCLUSIONS: The incidence of PF within 1 year post liver transplantation was 31%. This finding was accompanied by cholestatic liver function test abnormalities. Factors predisposing to PF were a prolonged cold ischemia time, biliary complications, and a positive cytomegalovirus recipient status. Acute rejection seemed to prevent for PF.

Analysis of survival and morbidity after pediatric liver transplantation with full-size and technical-variant grafts.

BACKGROUND: To alleviate the shortage of size-matched whole-donor organs, too-large-for-size cadaveric donor grafts are modified by liver resection techniques. These modifications result in technical-variant liver transplantation (TVLTx). Patient and graft survival rates after TVLTx are considered comparable to those after full-size liver transplantation (FSLTx). However, morbidity after TVLTx is often underexposed. The aim of this study was to analyze the results of FSLTx and TVLTx in terms of patient and graft survival rates and morbidity. METHODS: A consecutive series of 97 primary and elective pediatric liver transplantations performed in a single center was retrospectively analyzed. Forty-seven children had a FSLTx and 50 a TVLTx (38 reduced-size liver grafts and 12 split-liver grafts). The overall median follow-up period was 3.5 years. RESULTS: There were no differences in patient and graft survival rates between FSLTx and TVLTx. However, after TVLTx there was a significantly higher complication rate (1.42 vs. 0.81 after FSLTx). TVLTx is more hampered by biliary complications (30% vs. 17%), expressed by a higher incidence of cholangitis and leakage of bile. These complications led to a significantly higher incidence of sepsis (44% vs. 19%) and a significantly higher intervention rate (0.40 vs. 1.28) after TVLTx. There was no difference in the incidence of retransplantations between FSLTx and TVLTx. CONCLUSIONS: Both FSLTx and TVLTx offer the same prognosis in terms of patient and graft survival rates for children after a primary and elective liver transplantation. However, TVLTx has a higher morbidity.

Analysis of growth in children after orthotopic liver transplantation.

Growth after pediatric liver transplantation is an important factor in determining the quality of life. We collected data on height, skeletal age, and liver function of 45 consecutive pediatric transplant recipients and assessed the influence of primary diagnosis, liver function, and immunosuppressive regimen on their growth. Height and skeletal age were plotted as median standard deviation scores versus years post-transplantation. Growth, in terms of both height and skeletal age, were continuous without catch-up growth. Primary diagnosis was found to have no influence on height and poor liver function had a negative effect on both height and skeletal growth. A higher alternate day prednisolone maintenance dose also had negative effect on skeletal growth. Thus, it can be concluded that a pretransplant lack of growth will not be restored and is an indication for early transplantation in end-stage liver disease, especially in younger children.