1976-80 Medecine - Medical School of Louvain, Brussels University site, Belgium 1980-86 Surgery - UCL University Hospital Cliniques St LUC - Brussels, Belgium 1986-87 Paediatric Surgery - Necker Enfants Malades , Paris, France 1987-98 Paediatric Surgery - UCL University Hospital - Brussels, Belgium 1987-98 Liver Transplantation - UCL University Hospital - Brussels, Belgium 1998-03 Paediatric Liver Transplantation - Birmingham Children Hospital, UK 1998-03 Paediatric Liver surgery - Birmingham Children Hospital, UK 1998-03 Paediatric IntestinalTransplantation - Birmingham Children Hospital, UK 2003-07 Abdominal Transplantation and Surgery - UCL - Brussels, Belgium
2007 - Liver Transplantation - Ospedale Pediatrico Bambino Gesu, Rome, Italy 2007 - Paediatric Liver surgery - Ospedale Pediatrico Bambino Gesu, Rome, Italy 2007 - Full Professor of Paediatric Surgery, University of Roma Tor Vergata 2009 - Head of Department of HepatoGastroenterology and surgery, Ospedale Pediatrico Bambino Gesu, Rome, Italy 2010 - Head of Department of Paediatric surgery and Transplantation Centre, Ospedale Pediatrico Bambino Gesu, Rome, Italy
Abstract: A case of liver transplantation for HCC complicating BA in an eight-month old infant is reported. HCC in BA is extremely rare. Screening of AFP and ultrasonographic examination should be performed regularly in patients with secondary biliary cirrhosis for early detection of HCC.
Abstract: Over the last 15 years, various oncology groups throughout the world have used the PRETEXT system for staging malignant primary liver tumours of childhood. This paper, written by members of the radiology and surgery committees of the International Childhood Liver Tumor Strategy Group (SIOPEL), presents various clarifications and revisions to the original PRETEXT system.
Abstract: Cytokine deviation may be a factor contributing to graft acceptance. We analyze, in the context of liver transplantation, circulating cytokine levels and their mRNA precursors in liver biopsy samples to study a putative correlation with early immunologic outcome. Forty primary pediatric liver recipients were submitted to a prospective immune monitoring protocol, including 8 of 40 patients with an early, biopsy-proven acute rejection episode. The 32 patients with graft acceptance showed markedly increased interleukin (IL)-10 blood levels at 2 hours after reperfusion on days 1 and 4 after transplantation as compared with baseline, whereas patients with graft rejection only exhibited increased IL-10 levels at 2 hours. A good correlation was observed between IL-10 peripheral levels and levels ascertained by IL-10 reverse transcriptase-polymerase chain reaction at 2 hours and on day 7. Patients with graft acceptance also showed a decrease in interferon gamma (IFN-gamma) at 1 and 2 hours after reperfusion on days 1, 4, 7, 14, and 28 after transplantation. One patient with graft tolerance who had subsequent immunosuppression withdrawal after posttransplantation lymphoproliferative disease showed a similar intraoperative IL-10 pattern, whereas posttransplantation tumor necrosis factor alpha and IFN-gamma levels greatly decreased. The occurrence of cytokine immune deviation may therefore be related to early graft acceptance in children who receive liver transplants.
Abstract: OBJECTIVE: To report clinical presentation, perioperative outcome, and long-term results of surgical management of congenital intrahepatic bile duct (IHBD) dilatations (including Caroli disease) in a multi-institutional setting. SUMMARY BACKGROUND DATA: Congenital IHBD dilatations are a rare congenital disorder predisposing to intrahepatic stones, cholangitis, and cholangiocarcinoma. The management remains difficult and controversial for bilobar forms of the disease or when concurrent congenital hepatic fibrosis is associated. METHODS: From 1976 to 2004, 33 patients (range 11 to 79 years) were retrospectively enrolled. Disease extent into the liver was unilobar in 26 patients and bilobar in 7 patients (21%). Cholangiocarcinoma, congenital hepatic fibrosis, and intrahepatic stones were present in 2, 10, and 20 patients, respectively. Transplantations or liver resections were performed in 5 and 27 patients, respectively, whereas 1 asymptomatic patient was managed conservatively. RESULTS: Postoperative mortality was nil. Postoperative complications occurred in 16 of 32 operated patients (50%) and additional procedures for residual stones were required in 5 patients. During a median follow-up of 80 months (1 patient being lost for follow-up) no patient developed metachronous carcinoma. Six patients (30%) developed recurrent intrahepatic stones but satisfactory late outcome was achieved in 27 patients (87%). CONCLUSIONS: Partial or total liver resection achieves satisfactory late outcome in congenital IHBD dilatations, when the affection is treated at an early stage and when the extent of liver resection is tailored to intrahepatic disease extent and takes into consideration the presence and severity of underlying chronic liver and renal diseases.
Abstract: Mortality on liver transplantation (OLT) waiting lists has increased dramatically. Until recently, non-heart-beating donors (NHBD) were not considered suitable for OLT, because of a higher risk of primary graft nonfunction (PNF) and biliary strictures. However, recent experimental/clinical evidence has indicated that NHBD-OLT is feasible when the period of warm ischemia is short. PURPOSE: To characterize the results of NHBD-OLT in Belgium, a survey was sent to all Belgian OLT centers. RESULTS: Between January 2003 and November 2005, 16 livers originating from NHBD were procured and transplanted. The mean donor age was 48.8 years, including 9 males and 7 females with mean time of stop-therapy to cardiac arrest being 18 minutes and from cardiac arrest to liver cold perfusion, 10.5 minutes. Mean recipient age was 52.2 years including 12 males and 4 females. Mean cold ischemia time was 7 hours 15 minutes. No PNF requiring re-OLT was observed. Mean post-OLT peak transaminase was 2209 IU/L, which was higher among imported versus locally procured grafts. Biliary complications occurred in 6 patients requiring re-OLT (n = 2), endoscopic treatment (n = 2), surgical treatment (n = 1), or left untreated (n = 1). These tended to be more frequent after prolonged warm ischemia. Graft and patient survivals were 62.5% and 81.3%, respectively, with a follow-up of 3 to 36 months. CONCLUSION: This survey showed acceptable graft/patient survivals after NHBD-LT. The NHBD-liver grafts suffered a high rate of ischemic injury and biliary complications and therefore should be used carefully, namely with no additional donor risk factors, lower risk recipients, and short cold/warm ischemia.
Abstract: Analysing the relevance of soluble CD30 (sCD30) in the bloodstream before and after transplantation may be important for the monitoring of transplant recipients. In this study, 27 patients (15 pediatric liver and 12 adult kidney graft recipients) were investigated. In the liver graft group, the patients who developed acute rejection during the first month (n=9) had a slightly higher sCD30 value on pre-transplantation baseline (day 0) and post-transplantation day 7, when compared to patients with normal graft function (n=6) (day 0: 102(1.6) U/ml versus 118(1.5) U/ml, p=0.52) and (day 7: 69(1.5) U/ml versus 83(1.6) U/ml, p=0.47). Increased serum sCD30 was shown to correlate with increased interleukin-10 circulating levels between day 0 and day 7 (r=0.53; p=0.04), whereas, no correlation could be evidenced between interferon-gamma (IFN-gamma) and sCD30 (r=0.02; p=0.47). Similarly, in the kidney transplantation group, no significant difference was found in sCD30 levels at day 0 in both groups with graft rejection or normal graft function (n=6) (85(1.3) U/ml versus 77(1.6) U/ml, p=0.66), but sCD30 decreased significantly at day 7 post-transplantation from baseline value in the rejection group (n=6) (77(1.6) versus 35(1.4); p=0.02). We conclude that increased serum sCD30 was correlated with increased IL-10 (interleukin-10) circulating levels, but not with IFN-gamma levels in the post-transplantation period. Neither pre-transplantation sCD30 nor sCD30 at day 7 post-transplantation could be correlated with acute rejection in liver graft recipient. The monitoring of sCD30 might constitute a tool to assess the risk of acute rejection in renal transplant but did not appear as a valuable mean for early immunological monitoring in the small group of liver allograft recipients patients analysed in this study.
Abstract: AIM: To describe the outcome of children with intestinal failure referred to Birmingham Children's Hospital (BCH) for consideration of intestinal transplantation (ITx), to determine factors for an adverse outcome and to analyse the impact of post-1998 strategies on survival. Subjects and METHODS: A retrospective analysis was performed of children referred for ITx assessment from January 1989 to December 2003. Children were assessed by a multidisciplinary team and categorised into: (a) stable on parenteral nutrition; (b) unsuitable for transplantation (Tx); and (c) recommended for Tx. To analyse the impact of the post-1998 strategies on survival, a comparison was made between the two eras (pre-1998 and post-1998). RESULTS: 152 children with chronic intestinal failure were identified (63M:89F, median age 10 months (range 1-170)). After assessment, 69 children were considered stable on parenteral nutrition (5-year survival 95%); 28 children were unsuitable for Tx (5-year survival 4%); and 55 children were recommended for Tx (5-year survival 35%, which includes 14 children who died waiting for size-matched organs). Twenty three ITx and nine isolated liver transplants (iLTx) were performed. In a multivariate analysis, the following factors in combination had an adverse effect on survival: the presence of a primary mucosal disorder (p = 0.007, OR ratio 3.16, 95% CI 1.37 to 7.31); absence of involvement of a nutritional care team at the referring hospital (p = 0.001, OR ratio 2.55, 95% CI 1.44 to 4.52); and a serum bilirubin>100 micromol/l (p = 0.001, OR ratio 3.70, 95% CI 1.84 to 7.47). Earlier referral (median serum bilirubin 78 micromol/l in the post-1998 era compared with 237 micromol/l in the pre-1998 era, p = 0.001) may be a contributory factor to improved survival. The strategies of combined en bloc reduced liver/small bowel transplantation and iLTx resulted in fewer deaths on the waiting list in the post-1998 era (2 deaths in post-1998 era v 12 deaths in pre-1998 era). The overall 3-year survival in the post-1998 era (69%) has improved compared with the pre-1998 era (31%; p<0.001) CONCLUSION: The changing characteristics at the time of referral, including earlier referral and innovative surgical strategies have resulted in improved long-term survival of children referred for ITx.
Abstract: Timely access to a living donor (LD) reduced pretransplant mortality in pediatric liver transplantation (LT). We hypothesized that this strategy may provide better posttransplant outcome. Between July 1993 and April 2002, 235 children received a primary LT from a LD (n = 100) or a deceased donor (DD) (n = 135). Demographic, surgical and immunological variables were compared, and respective impact on posttransplant complications was studied using a multivariate analysis. Five-year patient survival rates were 92% and 85% for groups LD and DD, respectively (p = 0.181), the corresponding graft survival rates being 89% and 77% (p = 0.033). At multivariate analysis: (1) type of donor (DD) was correlated with higher rate of artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29% and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection incidence could be correlated with type of donor (DD) (p = 0.001), and immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1) according to the multivariate analysis, LT with LD provided similar patient and graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a lower rate of rejection were observed in group DD; (3) this study confirms the efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor is.
Abstract: Living-related liver transplantation was developed in the context of deceased donor organ shortage, which is particularly acute for pediatric recipients. This retrospective study analyzes the surgical technique and complications in the first 100 pediatric liver transplantation using left segmental liver grafts from living donors, performed at Saint-Luc University Clinics between July 1993 and April 2002. Pre-operative evaluation in donors and recipients, analysis of the surgical technique, and postoperative complications were reviewed. After a median follow-up period of 2526 days, no donor mortality was encountered, with a minimal morbidity and no long-term sequelae. At one and five yr post-transplantation, the actuarial patient survival rates were 94% and 92%, the corresponding figures being 92% and 89% for graft survival. The incidences of portal vein and hepatic artery thromboses, and of biliary complications were 14%, 1%, and 27%, respectively. Living-related liver transplantation in children constitutes an efficient therapy for liver failure to face the increased demand for liver grafts. Donor morbidity was kept to acceptable incidence, and surgical technique in the recipient needs to be tailored to minimize postoperative complications.
Abstract: Portal hypertension leads to a wide variety of complications, which lead to significant morbidity and mortality and are some of the leading reasons for liver transplantation in children with chronic liver disease. Evidence-based approaches to the management of adults with portal hypertension exist and have been comprehensively reviewed in a series of international meetings, including the Baveno meetings. Similar evidence-based approaches for the management of portal hypertension in children do not exist and as such international meetings on portal hypertension have not focused on this problem in children. On October 7, 2005 at The Mount Sinai School of Medicine, a panel of pediatric experts reviewed the most recent Baveno statement and crafted a statement modified with their opinions vis a vis approaches to the management of portal hypertension in children.
Abstract: The 3-year survival after small bowel transplantation (SBTx) has improved to between 73% and 88%. Impaired venous access for parenteral nutrition can be an indication for SBTx in children with chronic intestinal failure. AIM: To report our experience in management of children with extreme end-stage venous access. SUBJECTS: The study consisted of 6 children (all boys), median age of assessment 27 months (range, 13-52 months), diagnosed with total intestinal aganglionosis (1), protracted diarrhea (1), and short bowel syndrome (4), of which gastroschisis (2) and malrotation with midgut volvulus (2) were the causes. All had a documented history of more than 10 central venous catheter insertions previously. All had venograms, and 1 child additionally had a magnetic resonance angiogram to evaluate venous access. Five of 6 presented with thrombosis of the superior vena cava (SVC) and/or inferior vena cava. METHODS: Venous access was reestablished as follows: transhepatic venous catheters (5), direct intra-atrial catheter via midline sternotomy (4), azygous venous catheters (2), dilatation of left subclavian vein after passage of a guide wire and then placing a catheter to reach the right atrium (1), radiological recanalization of the SVC and placement of a central venous catheter in situ (1), and direct puncture of SVC stump(1). Complications included serous pleural effusion after direct intra-atrial line insertion, which resolved after chest drain insertion (1), displacement of transhepatic catheter needing repositioning (2), and SVC stent narrowing requiring repeated balloon dilatation. OUTCOME: Four children with permanent intestinal failure on assessment were offered SBTx, 3 of which were transplanted and were established on full enteral nutrition; the family of 1 child declined the procedure. In the remaining 2 children in whom bowel adaptation was still a possibility, attempts were made to provide adequate central venous access as feeds and drug manipulations were undertaken. One of them received liver and SBTx nearly 3 years after presenting with end-stage central venous access, because attempts to achieve independence from parenteral nutrition had failed. The other child died immediately after a transhepatic venous catheter placement, possibly from a nutritional depletion syndrome as no physical cause of death was found. Direct intra-atrial catheters in transplanted children proved to be adequate for the management of uncomplicated transplantation, although the usual infusion protocol had to be modified considerably, and the lack of access would have been critical if massive blood transfusion had been required during the transplant procedure. CONCLUSION: It was possible to reestablish central venous access in all cases. However, this was time consuming and difficult to assemble a skilled team consisting of one of more: surgeon, cardiologist, interventional radiologist, and transplant anesthetist. Small bowel transplantation is easier and safer with adequate central venous access, and we advocate liaison with an SBTx center at an early stage.
Abstract: Hepatic mesenchymal hamartoma is a rare benign tumour in children. It is often large and centrally located in the liver at diagnosis, making surgical resection difficult; thus non-radical resection has been proposed in the past as acceptable management. However, a literature survey and a case with recurrence associated with cytogenetic anomalies suggest that radical liver surgery (resection with a margin of normal liver parenchyma, as for malignant tumour) should be recommended for mesenchymal hamartoma.
Abstract: Progressive familial intrahepatic cholestasis (PFIC) is a severe cholestatic liver disease of early life often requiring liver transplantation. Organ shortage leads to consider living-related liver transplantation. Because of possible partial metabolic defect in heterozygotes, the use of familial donors might be questionable. We therefore evaluated the safety of this procedure, for both donors and recipients. We compared a series of seven parental-children pairs, having participated in the living related liver transplant program for PFIC between 1994 and 2001, with that of a series of seven parental-children pairs, performed for biliary atresia (BA) during the same period. No primary graft dysfunction was observed. There was no difference in the course of transaminases, gamma-glutamyl transpeptidase and bilirubin levels after transplantation in both donor and recipient series. Thirteen recipients and 14 donors are alive and well 3-10 yr post-surgery. One PFIC recipient died nine months post-orthotopic liver transplantation from sepsis. We conclude that PFIC heterozygote status of the donor does not increase the risk of liver dysfunction in either recipients or donors, with a similar course compared with BA recipients and donors.
Abstract: Intestinal function in children with very short bowel syndrome and related intestinal failure may improve after isolated liver transplantation. An infant with an ultrashort gut, ileo-cecal valve, and whole colon received total parenteral nutrition from the first days of life. Enteral feeding failed because of the progressive dilatation of the jejunal portion and motility disorders. He developed early severe cholestatic liver disease (aspartate transferase 186, alanine transferase 103 U/L, serum bilirubin 8.4 mg/dL) and subsequent liver failure. At 8 months of age, he benefited from isolated liver transplantation (left segment graft from living donor). His early posttransplant evolution was characterized by recovery of oral alimentation, improvement of digestive and absorption functions, but he did not achieve TPN-independence. At 20 months, 50% to 60% of his energy needs were covered by parenteral nutrition and he has satisfactory growth indices (3rd percentile for weight and height), reduced stool volume, and frequency. Isolated liver transplantation allowed, in this particular case, time for further intestinal adaptation thereby avoiding the need for intestinal transplantation early in life.
Abstract: BACKGROUND: Mortality after liver transplantation depends on heterogeneous recipient and donor factors. Our aim was to assess risk of death and to develop models to help predict mortality after liver transplantation. METHODS: We analysed data from 34,664 first adult liver transplants from the European Liver Transplant Registry to identify factors associated with mortality at 3-months (n=21,605 in training dataset) and 12-months (n=18,852 in training dataset) after transplantation. We used multivariable logistic regression models to generate mortality scores for each individual, and assessed model discrimination and calibration on an independent validation dataset (n=9489 for 3-month model and n=8313 for 12-month model). FINDINGS: 2540 of 21,605 (12%) individuals in the 3-month training sample had died by 3 months. Compared with those transplanted in 2000-03, those transplanted earlier had a higher risk of death. Increased mortality at 3-months post-transplantation was associated with acute liver failure (adjusted odds ratio 1.61), donor age older than 60 years (1.16), compatible (1.22) or incompatible (2.07) donor-recipient blood group, older recipient age (1.12 per 5 years), split or reduced graft (1.96), total ischaemia time of longer than 13 h (1.38), and low United Network for Organ Sharing score (score 1: 2.43; score 2: 1.67). However, cirrhosis with hepatocellular carcinoma, alcohol cirrhosis, hepatitis C or primary biliary cirrhosis, donor age 40 years or younger, or less, hepatitis B, and larger size of transplant centre (> or = 70 transplants per year) were associated with improved early outcomes. The 3-month mortality score discriminated well between those who did and did not die in the validation sample (C statistic=0.688). We noted similar findings for 12-month mortality, although deaths were generally underestimated at this timepoint. INTERPRETATION: The 3-month and 12-month mortality models can be effectively used to assess outcomes both within and between centres. Furthermore, the models provide a means of assessing the risk of post-transplantation mortality, giving clinicians important data on which to base strategic decisions about transplant policy in particular individuals or groups.
Abstract: Whereas physiologic jaundice constitutes a common finding in neonates, a few cases present with cholestatic jaundice owing to various pathologic conditions, including extrahepatic biliary obstruction. We report the case of a 2-day-old female neonate presenting with neonatal cholestasis, nonbilious vomiting with pyloric obstruction, and multiple intestinal atresias. A pathognomonic clinicoradiologic triad is described, based on clinical data, plain abdominal x-ray, and ultrasound examination.
Abstract: The recent introduction of the meso Rex bypass raises a possible paradigm shift in the therapeutic approach to extra-hepatic portal vein obstruction (EHPVO). Long-term follow-up of patients with EHPVO has revealed a variety of complications including variceal hemorrhage, hypersplenism, biliopathy, growth/development retardation and neuropsychiatric disease. The meso Rex bypass restores physiologic blood flow to the liver. Thus, when feasible, the meso Rex bypass should be considered in patients with clinically significant manifestations of EHPVO. The opinions of a panel of experts regarding the surgical approach to the management of EHPVO are presented.
Abstract: BACKGROUND: Pediatric End-stage Liver Disease (PELD) score is proposed as an objective tool to prioritize children awaiting liver transplantation (LT), higher PELD being associated with increased pre-LT mortality. This study investigated whether PELD may also impact on post-LT results. METHODS: PELD was retrospectively analyzed in 100 pediatric recipients of a primary LT from living-related (n = 49) or postmortem donors (PMD, n = 51). The main pre-LT diagnosis was biliary atresia (n = 64), hepatic malignancy and fulminant hepatitis cases being excluded. PELD was calculated in all patients at the time of pre-LT assessment. Considering the median delay of 117 days between listing and LT in the PMD subgroup, a second PELD was calculated at the time of LT, allowing the determination of a delta PELD during the waiting period. PMD grafts were allocated using an allocation system taking into account waiting times as well as medical urgency, operative at EuroTransplant. RESULTS: Overall 5-year actuarial patient and graft survivals were 96% and 91%, respectively. PELD at listing (13.3 +/- 9.7) showed a normal statistical distribution. PELD scores at listing and at LT were not found to significantly impact on post-LT outcome (NS). In contrast, higher delta PELD might be associated with lower posttransplant patient survival (p = 0.094). CONCLUSIONS: The results of this retrospective analysis suggest that giving priority to high PELD recipients may not result in worsening post-LT outcome. Accordingly, these data support such "sickest children first" allocation policy, which should contribute to reduce pre-LT mortality without worsening post-LT results and increasing organ waste.
Abstract: Major progress has been achieved during the last decades in the treatment of malignant liver tumors in children, both in chemotherapy and surgical management. Chemosensitivity varies between tumor types, and radical resection remains essential to effect a cure. In tumors extensively involving a normal liver, in a diffuse or multifocal manner, radical resection cannot be accomplished with a partial hepatectomy. This has been the case for some instances of advanced hepatoblastoma and epithelioid hemangioendothelioma. In hepatoblastoma, current experience shows that results of primary liver transplantation with neoadjuvant chemotherapy are excellent with around an 80% 5-to-10-year disease-free survival rate. Epithelioid hemangioendothelioma is very rarely seen in children and may have a more malignant behavior than in adult patients, and liver transplantation may not be the best management option. In nonresectable hepatocellular carcinoma (HCC) developed on an otherwise normal liver, the results of liver transplantation are similarly poor to those obtained in adult patients, except in a few highly selected series fulfilling the Milano criteria. The experience with HCC is still very scarce in children. Incidental HCC associated with chronic liver disease does not seem to impact posttransplant survival. When they are symptomatic, however, indications for transplantation should be very selective regarding tumor size, multi-focality, vascular invasion and distant metastases.
Abstract: In the past 20 yr, a dramatic improvement has been achieved in the outcome of children with hepatoblastoma by combining cisplatin based chemotherapy and surgery. Treatment of patients in the USA is an exception to the rule that all patients should receive neoadjuvant chemotherapy. It is paramount that surgical resection be complete, both macro- and microscopically. Complete tumor resection can be achieved after chemotherapy with a partial hepatectomy when the intrahepatic extent is limited to 1-3 sectors. In multifocal (and solitary) hepatoblastomas invading all four liver sectors, and in centrally located tumors with close proximity to the major veins, the SIOPEL-1 study and an extensive review of the world experience have shown that primary transplantation provides high, long term, disease-free survival rate in the range of 80%. In contrast, the results of rescue transplants for incomplete tumor resection or disease recurrence after partial hepatectomy are disappointing (in the range of 30%). Hazardous attempts at partial hepatectomy in children with extensive hepatoblastoma should be discouraged. Guidelines are provided for early referral of children with extended hepatoblastoma to a transplant surgeon. There is a trend for a better patient survival after living related liver transplantation. Patients who will become candidates to liver transplantation should be treated with chemotherapy following the same protocols as for children undergoing a partial hepatectomy. There is a concern about cumulative nephrotoxicity of calcineurin inhibitors and chemotherapeutic drugs. Recent data suggest that these patients tolerate lower Tacrolimus trough blood levels than those transplanted for non-malignant conditions, without increasing the risk of acute rejection. Due to the rarity of the disease, these children should be treated in specialized centers.
Abstract: The evolution of immunosuppression in pediatric liver transplantation has been characterized by a steady reduction of the immunosuppressive load, including removal of anti-lymphocyte antibodies, with the aim to reduce the incidence of EBV-related post-transplant lymphoproliferative disorders. Acute rejection rates were studied retrospectively over two decades of pediatric liver transplantation, according to the successive immunoprophylactic regimens. 318 primary pediatric liver transplant recipients, included between 1984 and 2004 in successive prospective trials, were analyzed, with respect to the impact of the immunosuppressive protocol on acute rejection occurrence. A progressive decrease of rejection incidences was observed, which corresponded to reduced immunosuppressive load and to transplant eras. Such trend might be related to changing approaches towards acute rejection histology and therapy by transplant clinicians, but also to the stepwise minimization of immunosuppressive protocols, putatively enhancing graft acceptance. We hypothesize that the recent population of liver transplant recipients with low immunosuppression might be more suitable for progressive immunosuppression withdrawal trial, with the aim to reach ultimately operational tolerance.
Abstract: BACKGROUND: The ever increasing number of, especially, adults waiting for a liver transplantation necessitates to develop techniques allowing to extend the available donor liver pool. MATERIALS AND METHODS: Between November 1988 and December 2004, 37 (6.6%) of 559 adults underwent split liver transplantation at Saint-Luc Hospitals. There were 36 were right and one left split procedures; 27 split grafts were obtained ex-situ and 10 in-situ. Results of these series are analysed and compared to literature data of split liver transplantation. RESULTS: Three and 12 months patient survival rates were 89.2% and 78.4% respectively. Five years actuarial patient survival was 75.7%. Early (< 3 months) and late (> 3 months) mortality rates were 10.8% (4 pat.) and 21.6% respectively. Early mortality was significantly higher in case of urgent split liver transplantation (3/5 patients vs. 2/32 elective patients--p 0.001). At present 25 patients are alive, with a mean Karnofsky score of 90%. Three and 12 months graft survival rates were 91.7% and 87.1% respectively. Three and one grafts were lost due to primary and early graft non-function. In-situ split grafts had shorter mean warm, cold, total ischemia and operating times as well as less need for blood transfusion; all these differences were however not statistically significant. Surgical complications occurred in 19 (51%) patients. All but one complication occurred early (< 3 months). There were sixteen biliary complications in 13 (35.1%) patients: 9 anastomotic stenoses, 3 anastomotic and 4 transection margin leakages. Six vascular complications occurred in 6 (15.2%) patients: three arterial and 3 portal vein thromboses. Seven (18.9%) patients had a postoperative bleeding. CONCLUSIONS: Graft and patient survival rates of split liver transplantation can be compared to those of classic liver transplantation. However the care of these patients is demanding due to the high number of technical complications. Results of split liver transplantation must be further improved in order to foster it's more widespread use necessary to overcome the actual shortage of liver allografts.
Abstract: BACKGROUND: We studied, retrospectively, the efficacy to control rejection and long-term safety of liver allograft radiotherapy (RT) performed in 14 children. Long-term safety data were collected with the prospect of possible use of RT in liver cell transplantation (LCT). METHODS: Immune suppression included cyclosporine, azathioprine and prednisone. In case of intractable rejection, low-dose allograft RT was administered daily for 3 days, and short-term efficacy was evaluated by liver enzyme assays and histology. The long-term outcome was compared with that of 122 patients undergone transplantation and who had similar treatment, but no RT. RESULTS: Survival at 15 years was 71.4% vs 69.7% in the comparison group. In the RT group, rejection control was complete in six of 14 children and partial in two, all being alive and well 14-18 years later. Ten of 14 children had follow-up biopsy. Six children had normal histology and four had mild unspecific fibrosis. The long-term follow-up biopsy in the comparison group showed fibrosis in 42 of 85 children. The incidence of complications was similar in both groups. CONCLUSIONS: This series shows that, such a RT regimen appeared to be efficient and safe as a rescue treatment for acute rejection. Provided that further investigations in animal models show a certain benefit of low-dose irradiation around LCT, such a regimen could be proposed in human liver cell transplant programmes.
Abstract: Liver transplantation is just as successful in infants as in older children, but more challenging. This relates to the low weight of the recipients and to their rapidly deteriorating clinical condition (malnutrition and end-stage liver disease) ( J Pediatr 1990;117:205-210; BMJ 1993;307:825-828; Ann Surg 1996;223:658-664; Transplantation 1997;64:242-248; J Pediatr Surg 1998;33:20-23). In addition, higher rates of diaphragmatic complications have been shown to significantly correlate with a younger age ( Transplantation 2002;73:228-232; Transpl Int 1998;11:281-283; Pediatr Transplant 2000;4:39-44), but diaphragmatic hernia has never been reported as a complication of liver transplantation. In this report, 2 patients who developed diaphragmatic hernia after liver transplantation are presented. The possible role of several contributing factors resulting in diaphragmatic hernia is discussed. These factors include (1) diaphragm thinness related to low weight and malnutrition, (2) direct trauma at operation (dissection and diathermy), (3) increased abdominal pressure after transplantation caused by the use of a slightly oversized liver graft, and (4) the medial positioning of the partial liver graft in the abdomen.
Abstract: Liver cell transplantation was performed in a child with urea cycle disorder poorly equilibrated by conventional therapy as a bridge to transplantation. A 14-month-old boy with ornithine transcarbamylase (OTC) deficiency received 0.24 billion viable cryopreserved cells/kg over 16 weeks. Tacrolimus and steroids were given as immunosuppressive treatment while the patient was kept on the pre-cell transplant therapy. Mean blood ammonia level decreased significantly following the seven first infusions, while urea levels started to increase from undetectable values. After those seven infusions, an ammonium peak up to 263 microg/dL, clinically well tolerated, was observed. Interestingly, blood urea levels increased continuously to reach 25 mg/dL, after the last three infusions. Eventually, he benefited from elective orthotopic liver transplantation (OLT) and the post-surgical course was uneventful. We conclude that use of cryopreserved cells allowed short- to medium-term metabolic control and urea synthesis in this male OTC-deficient patient while waiting for OLT.
Abstract: Mutations in the Jagged1 gene, a ligand for the Notch signalling pathway, have been implicated in the pathogenesis of Alagille syndrome (AGS), resulting in bile duct paucity. Recently, a mouse model for AGS suggested that abnormalities of the Notch2 receptor, as well as of Jagged1, may be present. Expression patterns of Notch receptors have not been described in the developing human liver or in paediatric liver. The expression of Notch receptors and ligands was examined in fetal, paediatric normal, and diseased human liver by RT-PCR and immunohistochemistry. RT-PCR showed Notch1-4 mRNA expression to be present. In fetal liver, Notch3 protein was expressed on mesenchymal cells, closely adjacent to ductal plate cells that expressed Jagged1. In paediatric normal liver, Notch1 and Notch2 were present on mature bile duct cells. Notch expression was altered in disease, with distinct differences in AGS from extrahepatic biliary atresia (EHBA) and alpha1-anti-trypsin deficiency (alpha1AT). In AGS, where extensive ductular reaction was present, Jagged1 was expressed on ductular reactive cells (DRCs), along with marked Notch2 and Notch3 staining. Where there was ductular paucity, Notch2 and Notch3 were not expressed on remaining biliary epithelial cells. In EHBA and alpha1AT, Notch receptor expression was not seen on DRCs. Instead, Notch2 and Notch3 were expressed by stromal cells. In all diseases, Notch3 was expressed on neovessels in portal tracts and cirrhotic fibrous septa. In conclusion, Notch3 is expressed in close proximity to Jagged1 at the time of ductal plate formation, suggesting that Notch3 is important for bile duct development. The expression of both Notch2 and Notch3 in AGS on DRCs confirms that these receptors may be important in the pathogenesis of this disease. Further studies are required to investigate the presence of Notch2 and Notch3 at other periods in liver development and to clarify the role of Notch signalling in paediatric cholestases.
Abstract: A novel application of the implantable Port-a-Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation.
Abstract: Hepatic epithelioid haemangio-endothelioma (HEHE) is an endothelium-derived tumour of low-to-medium grade malignancy. It is predominantly seen in adults and is unresponsive to chemotherapy. Liver transplantation is an accepted indication when the tumour is unresectable. Hepatic epithelioid haemangio-endothelioma is very rare in children and results after transplantation are not reported. The aim of this study is to review the experience of three European centres in the management of HEHE in children. A retrospective review of all paediatric patients with HEHE managed in three European centres is presented. Five children were identified. Four had unresectable tumours. The first had successful resection followed by chemotherapy and is alive, without disease 3 years after diagnosis. One child died of sepsis and one of tumour recurrence in the graft and lungs 2 and 5 months, respectively, after transplant. Two children who had progressive disease with ifosfamide-based chemotherapy have had a reduction in clinical symptoms and stabilisation of disease up to 18 and 24 months after the use of platinum-based chemotherapy. HEHE seems more aggressive in children than reported in adults and the curative role of transplantation must be questioned. Ifosfamide-based chemotherapy was not effective. Further studies are necessary to confirm if HEHE progression in children may be influenced by platinum-based chemotherapy.
Abstract: BACKGROUND: Before 1999, infants born in the UK with suspected biliary atresia were investigated in regional centres, and, if confirmed, a Kasai operation was done there. Since 1999, all infants with suspected biliary atresia in England and Wales, UK, have been referred to one of three designated centres where both the Kasai operation and liver transplantation (if necessary) could be done. METHODS: We assessed clearance of jaundice (bilirubin <20 micromol/L) as an early outcome in all cases of biliary atresia referred from one of the three centres. We then estimated survival using the Kaplan-Meier method with endpoints of liver transplantation or death. FINDINGS: 148 infants with biliary atresia were treated between January, 1999, and June, 2002. A primary portoenterostomy was done in 142 (96%) infants and a primary liver transplant in five (3%). One child died before any intervention. Early clearance of jaundice after portoenterostomy was achieved in 81 of 142 (57%) infants. Liver transplantation was done in 52 (37%) of those undergoing portoenterostomy. 13 (9%) infants died. Of the 135 children who survived, 84 (62%) still have their native liver and 51 (38%) had transplantation. The median follow-up of survivors was 2.13 (range 0.5-4.1) years. The overall 4-year estimated actuarial survival was 89% (95% CI 82-94). The 4-year estimated actuarial survival with native liver was 51% (42-59%). INTERPRETATION: Our early results suggest that surgical outcome can be improved by centralisation of care to supra-regional centres.
Abstract: The Paediatric Liver Transplant Program at Saint-Luc University Clinics constitutes a substantial single centre experience, including 667 transplantations performed between March 1984 and April 2003, and the history of this program reflects the tremendous progress in this field since twenty years. Liver transplantation in children constitutes a considerable undertaking and its results depend on multiple, intermingled risk factors. An analysis of the respective impact of several surgical and immunological parameters on patient/graft outcome and allograft rejection after paediatric liver transplantation showed a significant learning curve effect as well as the respective impact of pre-transplant diagnosis on survival and of primary immunosuppression on the rejection incidence. The introduction of living related liver transplantation in 1993 not only permitted to provide access to liver replacement in as many as 74% more candidate recipients, but also resulted in better graft survival and reduced retransplantation rate. The results of a recent pilot study suggest that steroid avoidance is not harmful, and could even be beneficial for paediatric liver recipients, particularly regarding growth, and that combining tacrolimus with basiliximab (anti-CD25 chimeric monoclonal antibody) for steroid substitution appears to constitute a safe alternative in this context. The long-term issues represent the main future challenges in the field, including the possibility of a full rehabilitation through immunosuppression withdrawal and tolerance induction, the development of adolescence transplant medicine, and the risk of early atherogenesis in the adulthood.
Abstract: Congenital intrahepatic arterioportal fistula (APF) is a rare condition. In most cases, the symptoms and complications develop during infancy. We report here the incidental finding of a large and solitary congenital APF in a 13-year-old boy, with subsequent related clinical complications. At angiography, an APF connecting the left hepatic artery and the left branch of the portal vein (PV) was demonstrated with reversed flow in the left and main PV. The fistula was successfully occluded, in a single embolisation session, using an Amplatzer occlusion device. This was associated with immediate restoration of normal hepatopetal flow in the PV and followed by resolution of the clinical signs of portal hypertension. This patient is the oldest child with congenital intrahepatic APF to be reported. We emphasise the interest of using a large device (Amplatzer) to occlude a solitary large APF in a single session and, more importantly, to avoid other possible complications related to embolisation.
Abstract: Bile ducts of Luschka (also called supravesicular ducts) are small bile ducts in the gallbladder bed. Although they do not drain any liver parenchyma, they can be a source of bile leak or biliary peritonitis after cholecystectomy in both adults and children, as shown in this case report. As a reminder, variations of biliary anatomy in the gallbladder bed and cholecysto-hepatic triangle of Calot, are reviewed.
Abstract: Recent findings have increased our understanding of the molecular mechanisms involved in the pathogenesis of hepatoblastoma and their relationship to the molecular pathology of familial adenomatous polyposis (FAP). Here, we describe hepatoblastoma in siblings who share a gene mutation for FAP inherited from their father. This observation confirms the link between these diseases and has implications for future molecular research. We also raise the question; should other members of 'at-risk' families be screened following a new diagnosis of either hepatoblastoma or FAP?
Abstract: BACKGROUND/PURPOSE: In children with portal vein (PV) thrombosis, hepatopetal portal flow can be restored by an innovative surgical procedure, the meso-portal-bypass (MPB), if the umbilical portion of the intrahepatic left PV and the superior mesenteric vein are patent. This is associated with resolution of symptoms related to extrahepatic portal hypertension (EHPH). However, no data are available yet on intrahepatic hemodynamic changes after MPB. The aim of this study was to evaluate morphologic adaptation and flow characteristics of the intrahepatic PV branches (ihPVb) after MPB. METHODS: Prospective follow-up Doppler scans of the ihPVb were performed at 0.5 to 1, 3 to 6 and 12 months after MPB in 13 consecutive patients (2000-2002) and compared with preoperative findings. RESULTS: Only small ihPVb were detected preoperatively on Doppler in 8 of 13 cases. Postoperatively (median follow up 12; range, 6 to 24 months), all 13 patients had patent MPB with hepatopetal flow, and ihPVb were easy to detect with satisfactory vessel diameters and flow velocities. CONCLUSIONS: The preoperatively small ihPVb increase rapidly in diameter and hepatopetal flow velocity in patients benefiting from MPB. This correlates well with progressive resolution of their symptoms related to EHPH and reflects rapid adaptation of ihPVb.
Abstract: Combination of cyclosporine (CsA) and tacrolimus immunosuppression post-liver transplantation (LT) and the chemotherapeutic drugs used to treat hepatoblastoma (HB), are nephrotoxic. We aimed to determine the severity and duration of nephrotoxicity in children following LT for unresectable HB. We reviewed all children undergoing LT for unresectable HB at the Liver Unit, Birmingham Children's Hospital, UK, from 1991 to July 2000. Thirty-six children undergoing LT for biliary atresia, matched for age and sex, were selected as controls to compare pre- and post-LT renal function. Renal function was determined by estimation of glomerular filtration rate (eGFR) derived from plasma creatinine using Schwartz's formula. Twelve children with HB (mean age of diagnosis 33 months) who underwent LT (mean age 47 months) and 36 controls (mean age of LT 34 months) were studied. CsA was the main immunosuppressive drug used in each group. The median eGFR before, and at 3, 6, 12, 24 and 36 months after LT in HB group was significantly lower than controls (93 vs. 152, 66 vs. 79, 62 vs. 86, 66 vs. 87, 64 vs. 94, 53 vs. 90 mL/min/1.73 m2, respectively; 0.01 < p < 0.03). The reductions in the median eGFR of both the HB group and controls before and at 36 months after LT were 49 and 41%, respectively. At 36 months after LT, there was a trend for partial recovery of the eGFR in the controls but not in the HB group. Children who underwent LT for unresectable HB had renal dysfunction before transplantation that persisted for 36 months after LT.
Abstract: BACKGROUND/PURPOSE: Extensive intestinal aganglionosis is rare. The diagnosis and treatment are known to be difficult and it had been considered to be fatal. The aim of this study was to review our experience with children with extensive intestinal aganglionosis. METHODS: Retrospective analysis was conducted in patients referred to the intestinal transplantation unit since 1993. Presentation and outcome were analysed looking at 2 groups who had either undergone previous subtotal intestinal resection (group I) or no or limited resection (group II). RESULTS: Eight children were selected (3 patients in group I and 5 in group II). Group I was remarkable in that patients all were referred early in age with progressing liver failure. Parents of one patient refused to accept transplantation as treatment, and he died one month later. Two noncirrhotic patients were maintained in the parenteral nutrition programme and currently progress well with enteral feedings. The other 5 patients underwent transplant, and 4 of 5 are alive after transplantation with a mean follow-up of 22.2 months (range 0.4 to 63.6). CONCLUSIONS: Subtotal resection of intestine at the time of diagnosis must be avoided. Conservative management with parenteral nutrition may be associated with long-term good outcome. Small bowel transplant may open new perspective in the management of patients with end-stage liver disease.
Abstract: Grafts for split liver transplantation can be prepared in situ during the retrieval operation, or ex situ on the back table. The in situ technique has theoretical advantages because it minimizes the cold ischemic time and allows excellent hemostasis at the cut surface. However, in situ liver division prolongs the retrieval procedure, may precipitate hemodynamic instability in the donor, and may cause logistical difficulties for some centers. This report is a single-center analysis comparing results of ex situ liver division (group I: 1992-97; and group II: 1998-2001) before and after a new protocol for liver graft division was introduced in our center. Eighty-nine split liver transplants (SLT) were reviewed retrospectively. Vascular complications were less common in group II (3.3% vs. 20%; p = 0.04), and 1-year graft survival increased from 59% to 78% (p = 0.03). Since 1998, 1-year graft survival of SLT has been similar to that of conventional liver graft transplantation in our center (78% and 74%, respectively). In conclusion, good results can be achieved from splitting livers ex situ and this procedure should be considered when the in situ technique is not feasible.
Abstract: Stem-like cells have been identified in liver that are able to differentiate in vivo and in culture to biliary epithelial cells (BEC), hepatocytes and oval cells. The growth factors/cytokines and signal pathways required for the differentiation processes are beginning to be evaluated. There is increasing evidence to suggest that these stem-like cells may originate from both the bone marrow population or from a precursor remnant from liver embryogenesis, as they share many of the same markers (CD34, c-kit, CD45). Most recently, it has been shown that a population of progenitor cells can copurify with mesenchymal bone marrow cells and differentiate under specific culture conditions to form both hepatic epithelial and also endothelial cells. The interaction of haemopoietic and mesenchymal stem cells needs further evaluation. The close association of ductular reactive cells and neovessels in end-stage cholestatic liver diseases and the relation to Jagged/Notch signalling pathway may be important in the regulation of stem cells to form both biliary epithelial and endothelial cells.
Abstract: BACKGROUND: Children with small or hypoplastic portal veins represent a challenge for liver transplantation. Graft loss of up to 70% has been reported in these patients in the past. A variety of techniques has been used in both cadaveric and living related transplants in an effort to overcome this problem. Variability arises as to whether to use a vascular graft and where on the portal system to attach the graft. METHOD: We present our usage of a simple and straightforward interposition iliac vein allograft fashioned in a manner to achieve large anastomotic cross-sectional area on the confluence of the superior mesenteric/splenic veins. The procedure also overcomes problems of graft vein/portal vein size mismatch in the cases where liver and vein grafts are procured from much larger donors. RESULTS: A total of 14 children presented with hypoplastic portal vein (diameter<5 mm), of a total of 30 consecutive patients requiring cadaveric liver transplants, and benefited from this technique. Median recipient age was 10.5 months. Revascularization times ranged from 22 to 43 min with a mean of 33 min. All patients are alive and well at a mean follow-up of 329 days (10 months). All liver grafts are well and functioning. No portal vein problem was detected. CONCLUSION: Results from this technique are clearly encouraging. Because portal vein hypoplasia is a common problem in pediatric transplant candidates, we believe this alternative technique is of interest and should be added to the transplant surgeon's armamentarium.
Abstract: BACKGROUND: Liver transplantation now is proposed for managing selected hepatoblastoma cases. Indications are not yet well defined. METHODS: The case records of 34 children with hepatoblastoma treated over a period of 10 years (1991 to 2000) were reviewed retrospectively. RESULTS: All patients benefited from preoperative chemotherapy. Twenty patients underwent major hepatic resections. Twelve patients, in absence of residual metastasis, underwent liver transplant because the tumour remained unresectable after chemotherapy. Two patients who presented with recurrence after a right hepatectomy, benefited from transplant as a second option. Two other patients did not undergo surgery because of widespread disease or resistance to chemotherapy. Disease-free survival rates were 95% after surgical resection, 100% when primary transplant was performed in patients with good response to chemotherapy, 60% after transplantation in patients with poor response to chemotherapy, 50% in patients with transplant as second option, and 0% in patients not undergoing surgery. CONCLUSIONS: Transplantation is a potentially curative option for unresectable hepatoblastoma when chemosensitive (decrease in alpha-fetoprotein and decrease in tumour size). In this context, also favourable cases with good response but difficult resections with doubtful margins of resection may best be proposed for primary transplantation. Patients with recurrent or resistant disease are not good candidates.
Abstract: The procurement of left-lateral-segment grafts from living donors for transplantation in children is performed by retaining only the left branches of the artery and veins. New techniques and the implementation of microsurgery in the transplant operation made this procedure a successful approach. However, controversy persists about using such an approach for division of liver grafts from cadaveric donors, and many teams prefer retaining the main arterial trunk with the left split graft, with or without the main portal vein trunk. Since 1998, in our center, when a donor-liver graft is divided we prefer retaining the main vessels with the right split graft if graft vascular anatomy is favorable. After 1998, 40 liver grafts from cadaveric donors were divided, and all divisions were performed ex situ. This experience was retrospectively reviewed to compare the outcome of left split grafts prepared for implantation with the left vasculature only (group A), or with the main arterial supply (group B). A single vascular complication occurred (one hepatic artery thrombosis in group B). Three patients died (one in group A and two in group B) and three other grafts were lost (one in group A and two in group B). One-year and 3-year graft survival rates were 94% and 86% in group A, and 83% and 83% in group B, respectively (not significantly [NS] different). We conclude that left split grafts can be safely transplanted with the left vascular supply only, provided that division is guided by careful anatomical evaluation and that vascular reconstructions are adequate.
Abstract: BACKGROUND: Anatomy of the left hepatic vein (LHV) was studied in a series of 53 consecutive cadaveric liver grafts that were divided for transplantation. METHODS: All divisions were performed ex situ and provided a left split graft with only the LHV as the hepatic outflow. The anatomy was categorized into three types: (A) single LHV trunk, (B) two veins closely merging toward the median hepatic vein, or (C) a double outflow. RESULTS: Direct implantation of the graft was performed in type A and was possible in type B after simple plasty of the ostia to create a single orifice. In type C, a venous jump graft could be interposed at bench work to allow direct anastomosis into the recipient. There were no related complications, except one type A case with late outflow obstruction. CONCLUSION: Liver division can be performed safely in liver grafts with variant LHV anatomy, if appropriate techniques for reconstruction are used. Also ex situ liver division has the advantage of allowing a detailed anatomic evaluation before dividing LHV: reconstruction can be performed ex situ, allowing a single-step direct anastomosis in the recipient, thus shortening suturing time.
Abstract: BACKGROUND/PURPOSE: Nonoperative management of blunt liver trauma may delay diagnosis of related biliary complications leading to delayed surgical intervention and related morbidity. The aim of this study was to see whether technetium (tc) 99 trimethylbromo-im-indolacetic acid (TBIDA) nuclear scan would allow noninvasive early diagnosis of bile leak and pre-emptive management. METHODS: Retrospective analysis of the patient records and radiologic investigations of 7 patients admitted between April 1998 and December 2000 with "major" blunt liver trauma (parenchymal fracture of less than 4 cm on computed tomography [CT] scan or involving porta hepatis) and various types of biliary complications. Patients with or without early TBIDA diagnosis were compared. RESULTS: There were 7 patients. The first 2 patients were treated conventionally without TBIDA, and late diagnosis was associated with further related problems (sepsis, life-threatening hemorrhage in both cases) and prolonged hospital stay. The subsequent 5 consecutive patients benefited from early diagnosis (TBIDA scan, 2 to 4 days after trauma), and preemptive management was done (tailored to each case). There was no further or related morbidity. All 7 patients currently are alive and well. CONCLUSIONS: A TBIDA nuclear medicine scan was efficient in providing an early diagnosis of biliary leakage, thus, allowing adequate preemptive management. In turn, this may have helped avoid related added morbidity compared with cases of late diagnosis. Early TBIDA scan should be performed routinely when the initial CT scan confirms liver trauma graded as "major."
Abstract: BACKGROUND: Neonates and small infants represent less than 5% of paediatric candidates for liver replacement. Most cases present under urgent conditions and receive grafts from large donors. Surgical techniques must be adapted for adequate graft preparation, vascular reconstruction, and abdominal closure. METHODS: Technical aspects and outcome of 15 liver transplantations in infants weighing less than 5 kg performed at our unit were analysed retrospectively. RESULTS: Liver transplantation was performed under urgent or highly urgent condition in 13 cases. Reduced or split liver grafts were used in all cases (median donor to recipient weight ratio, 9), including a monosegmental graft in 2 cases. In 10 cases, vascular reconstruction was done using a vascular conduit (5, 4, and 1 for artery, portal, and hepatic veins, respectively) and a delayed closure of the abdomen was necessary in 7 children. Postoperative complications were as follows: thrombosis of hepatic artery (n = 1) or portal vein (n = 1), gastrointestinal haemorrhage (n = 2), intraperitoneal bleeding (n = 1), biliary stricture (n = 2), septicaemia (n = 1). Two infants died of brain damage with a functioning graft. One child underwent retransplant for chronic rejection. CONCLUSIONS: Overall, survival rate is 60% (median follow-up, 34 months), which compares favourably with older patient groups when case mix is comparable.
Abstract: A 16-y-old boy who had undergone bone marrow transplantation for relapsed acute lymphoblastic leukaemia developed liver cirrhosis and refractory ascites, which did not respond to salt restriction, diuretics and abdominal paracentesis. Liver transplantation was not feasible because of poor nutritional status, pre-existing renal dysfunction and uncertainty about the prognosis of his leukaemia. The patient underwent a successful transjugular intrahepatic portosystemic shunt (TIPS), with immediate resolution of ascites, enabling cessation of diuretics and improvement in nutritional status. At 24 mo following TIPS there has been no re-accumulation of ascites. CONCLUSION: TIPS may have a role in the management of refractory ascites secondary to liver cirrhosis in selected children.
Abstract: BACKGROUND: The shortage of suitable donors for transplantation is a worldwide problem. The use of cadaveric donors with bacterial meningitis may be associated with an increased risk of sepsis. We report the results of orthotopic liver transplantation (OLT) from 33 such donors between 1989 and 1999. METHODS: The hospital records of recipients from cadaveric donors with meningitis (study group) were retrospectively reviewed and compared with matched recipients from cadaveric donors dying from causes other than meningitis (recipient-matched control group). RESULTS: A total of 34 recipients underwent 21 whole, 10 reduced, and 3 split liver transplants from 33 cadaveric donor livers with bacterial meningitis. The donor meningitis pathogens were Neisseria meningitidis (n=14), Streptococcus pneumoniae (n=4), Haemophilus influenzae (n=1), Streptococcus species (n=2), and unknown (n=12). Twenty-seven patients had an elective OLT and seven patients had an emergency OLT. Adequate antimicrobial therapy before organ procurement and after transplant was administrated. The mean posttransplant follow-up was 37 months (range: 1 day-106 months). There was no difference in recipient and graft survival rates between the study and the recipient-matched groups. In the study group, there were no infectious complications caused by the meningeal pathogens. Overall patient survival rates were 79%, 76%, 72%, and 72% at 1, 6, 12, and 60 months, respectively. Graft survival was 77%, 70%, 65%, and 65% at 1, 6, 12, and 60 months, respectively. The survival rate in elective cases was significantly better than emergency cases (P<0.05). CONCLUSION: Liver transplantation from donors with bacterial meningitis is a safe procedure provided both donors and recipients receive adequate antimicrobial therapy.
Abstract: BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare condition in which deficiency of the liver enzyme alanine:glyoxylate aminotransferase leads to renal failure and systemic oxalosis. Combined liver-kidney transplantation (LKT) is recommended for end-stage renal failure (ESRF) in adults, but management of infants and young children is controversial. We retrospectively reviewed six children who underwent LKT for PH1. METHODS: The median age at diagnosis was 1.8 years (range 3 weeks to 7 years). Two children presented with severe infantile oxalosis at 3 and 9 weeks, five patients had ESRF with nephrocalcinosis and systemic oxalosis, (median duration of dialysis 1.3 years), and one had progressive chronic renal failure. Four children underwent combined LKT, one child staged liver then kidney, and one infant had an isolated liver transplant. The median age at transplantation was 8.9 years (range 1.7-15 years). RESULTS: Overall patient survival was four out of six. The two infants with PH1 and severe systemic oxalosis died (2 and 3 weeks post-transplant) due to cardiovascular oxalosis and sepsis. The other four children are well at median follow-up of 10 months (range 6 months to 7.4 years). No child developed hepatic rejection and all have normal liver function. Renal rejection occurred in three patients. Despite maximal medical management, oxalate deposits recurred in all renal grafts, contributing to graft loss in one (one of the infants who died), and significant dysfunction requiring haemodialysis post-transplant for 6 months. CONCLUSIONS: LKT is effective therapy for primary oxalosis with ESRF but has a high morbidity and mortality rate in children who present in infancy with nephrocalcinosis and systemic oxalosis. We feel that earlier LKT, or pre-emptive liver transplantation, may be a better therapeutic strategy to improve the outlook for these patients.
Abstract: BACKGROUND: The critical shortage of size-matched donor organs for infants and small children in need of combined liver and intestinal transplantation has lead to long waiting times and a high risk of dying before transplantation. Utilizing grafts from larger donors could alleviate this problem, but using larger composite grafts in small children has been challenging and unsuccessful in the past. METHODS: We conducted a pilot study for evaluating the results of transplanting into small recipients a composite graft (reduced-size liver and whole small bowel, including duodenum and pancreas head) procured from large donors. Liver size reduction was performed ex situ using the extrahilar approach, which leaves the liver hilum untouched. Straightforward implantation of the graft was performed by simple, two-step vascular anastomoses. The preservation of the donor duodenum in continuity with the combined graft avoided the need for biliary reconstruction, thus preserving maximal bowel length for gut continuity restoration in the recipient. RESULTS: Two children, weighing 7.6 and 9.8 kg, respectively, underwent transplantation of a composite graft procured from donors weighing 35 kg. Their waiting time (68 and 97 days, respectively) was shorter compared with our previous experience with conventional techniques. Both are currently alive and well, at home and on full enteral feeds, 15 and 11 months after transplantation, respectively. CONCLUSION: This new technique has extended the range of possible donors for small candidates waiting for combined grafts and was successful in two patients. It should be considered for small recipients in the future.
Abstract: BACKGROUND: Absence of the portal bifurcation is exceptional and characterized by an absent extrahepatic portal vein bifurcation, the right portal vein only being at the porta hepatis. There is no extraparenchymal left portal vein. This may represent a problem in liver splitting, reduction, and living related transplantation. METHOD: A case was encountered during reduction of a cadaveric liver allograft to a left lateral segmental graft from a 40-kg cadaveric donor to a 15-kg recipient. The portal venous inflow was reconstructed with a vein graft via a novel extrahilar approach to the left portal vein at the umbilical fissure. RESULTS: This graft was used successfully in a 3-year-old child requiring transplantation for a failed Kasai operation for extrahepatic biliary atresia. The child is now well, 1 year posttransplant, after an uneventful postoperative course with good portal flow within the graft. CONCLUSION: The situation of an absent left portal vein extrahepatic course should not preclude splitting or reduction procedures. The innovative technical solution, we propose, should add to the armamentarium of the liver transplant surgeon contemplating a left lateral segmental graft for the paediatric liver transplant recipient.
Abstract: STUDY DESIGN: Between July 1993 and March 1997, 110 children were listed for primary elective liver transplantation with cadaveric (Cad: n = 68) or living-related (LR: n = 42) donors. Pregraft mortality, post-transplant survival, and surgical and immunologic complications were retrospectively compared in both groups. RESULTS: The pregraft mortality rate was 10 (15%) of 68 versus 1 (2%) of 42 in the Cad and LR groups, respectively (P =.049). Postliver transplantation 1-year patient and graft survival rates were 87% and 75% in the Cad group (n = 49) versus 92% and 90% in the LR group (n = 41), respectively (NS). The incidence of post-transplant complications was as follows: hepatic artery thrombosis (Cad: 16%; LR: 0%, P =.020), portal vein thrombosis (Cad: 8%; LR: 2%, NS), and biliary complications (Cad: 14%; LR: 34%, P =.044). The overall incidence of acute rejection was similar in both groups; however, a lower incidence of acute rejection occurred in LR graft recipients treated with tacrolimus. CONCLUSIONS: The introduction of an LR donor liver transplantation program allowed a significant decrease in the pretransplant mortality rate, with a consequent overall improvement in patient survival compared with the Cad series. The incidence of biliary complications was higher in the LR series, whereas better human leukocyte antigen matching in this subgroup did not result in a lower rejection incidence.
Abstract: The incentive to develop intrafamilial living related liver transplantation (LRLT) originated from the shortage of cadaveric organ supply. We report our experience with LRLT in 63 children during 1993-1998 in the frame of a protocol approved by the Ethics Committee of our Institution. During this period, 152 potential intrafamilial (mostly parental) donors were evaluated; 44 (28.5%) were excluded because of surgical (n = 4), medical (n = 39) or psychosocial reason (n = 1). Out of 108 who matched all medical, surgical and psychological criteria of selection, 45 did not underwent living donation because their child received a cadaveric graft (n = 22; LRLT was their second option) or because one of the parents who had both been selected was chosen [by the surgical team because of more favourable anatomy (n = 8) or by mutual agreement between the two parents (n = 5)]. Sixty-three living donors (36 mothers, 24 fathers, one grand mother, one aunt and one uncle) underwent procurement of the left lobe (n = 52), the left lobe extended to part of segment IV (n = 8) or a left hepatectomy (n = 3) without mortality or any serious morbidity. Their median hospital stay was 7 days (range: 6-12); full physical rehabilitation and normalization of liver tests were usually obtained within three weeks. Their psychological follow-up did not disclose any longstanding serious sequellae. The median age of the recipients was 13 months (range 5-189); 30 were younger than one year at the time of transplant. Their median weight was 8.1 kg (range: 4.3 to 60); 36 had an actual weight under 10 kg. Fifty-two received an ABO identical and 11 received an ABO compatible transplant. The native liver diseases were similar to common data in children, with biliary atresia being the most frequent indication (74.6%). The median weight of the graft was 260 gr (range: 138-680) with a median ratio between the graft weight and the recipient body weight of 3.17% (range: 0.75-8.08). All grafts were implanted orthotopically with semi-microvascular reconstruction of the hepatic vein, portal vein and hepatic artery [end to end anastomosis in 58 (2 arteries were reconstructed in 7 patients) and interposition of an iliac arterial allograft from the infrarenal aorta in 5]. Base line immunosuppression consisted of a triple drug regimen including steroids, Azathioprine and either Cyclosporine-Sandimmun (n = 9), Cyclosporine Microemulsion formulation-Neoral (n = 13) or Tacrolimus-Prograft (n = 41). Biopsy-proved acute rejection was treated with intravenous bolus of steroids; steroid-resistant acute rejection was treated by a switch from Cyclosporine to Tacrolimus or addition of Mycophenolate-Mofetil (Cellcept) in Tacrolimus treated patients. Actuarial patient survival was 91.8% and 89.6% after LRLT at one and five years post-transplant, respectively, and 87.5% and 82.8% at one and five years, respectively, in 90 patients who received a cadaveric graft during the same interval. Actuarial graft survival was 91.8% and 84.1% after LRLT at one and five years, respectively, and 76.4% and 73.3% at one and five years, respectively, after cadaveric transplants. Vascular thrombosis was observed in 9.5% of the patients (arterial thrombosis: 1.6%; portal thrombosis: 7.9%) without graft loss. Biliary complications were observed in 26.9% (bile leak from cut surface in 3.1%, anastomotic stricture in 22.2% and intrahepatic stricture in 1.5%); two patients died from septic shock possibly related to uncompletely relieved anastomotic stricture; all other biliary complications were successfully treated either conservatively or surgically. The incidence of acute rejection was 90.9% in 22 patients with Cyclosporine-based immunosuppression; acute rejection was corticoresistant in 50%. It was 46.3% in 41 patients with Tacrolimus-based immunosuppression (64% with Prograft in capsules and 18.7% with Prograft in granules); no acute rejection was corticoresistant. (ABSTRACT TRUNCATED)
Abstract: BACKGROUND: Arterial or venous homografts are frequently implanted for vascular reconstruction in orthotopic liver transplantation (OLT). When fresh vascular homografts (VH) from the same donor were not available, VH from another donor preserved at 4 degrees C in Terasaki (Ter) solution (modified lymphocyte culture medium) were used. METHODS: The clinical results after implantation of Ter-stored VH versus fresh VH in the revascularization of pediatric OLT were studied retrospectively. Short- and long-term follow-up of vascular patency was carried out by doppler ultrasonography in each case. A histological and bacteriological study of nonimplanted VH stored at 4 degrees C in saline (Sal), Ter and University of Wisconsin (UW) solutions for various time periods (days 0-28) was also undertaken. RESULTS: Between 1989 and 1996, 21 iliac arteries and 21 iliac veins preserved in Ter solution (mean preservation time: 8 days; range 1-26) and 100 fresh VH (68 arteries and 32 veins) (preservation time: 8 hr, range 4-21) were used in pediatric OLT. Thrombosis rates were 0 of 21 for stored arteries vs. 7 of 68 (10%) for fresh arteries (NS) and 3 of 21 (14%) for stored veins vs. 3 of 32 (9%) for fresh veins (NS). Actuarial graft survival rates were similar in both groups. Histological analysis of stored, nonimplanted VH invariably showed endothelial destruction within 24-48 hr after procurement. The bacteriological study showed contamination rates of 14 of 25 (56%) for Sal-stored VH, 5 of 25 (20%) for UW, and 1 of 19 (5%) for Ter (Sal vs. UW and Sal vs. Ter: P<0.01; UW vs. Ter: NS). CONCLUSIONS: Ter-preserved cadaveric VH could be safely used in OLT despite early destruction of endothelium.
Abstract: Primary cricopharyngeal achalasia (a = absence, chalasia = relaxation) is a rare cause of swallowing disorders in newborns. Two cases are reported which were successfully treated by a myotomy of the cricopharyngeal muscle. A thorough history is essential in differential diagnosis as well as observation of the feeding infant. Presence of anatomical obstruction to swallowing and existence of neurological defects should be ruled out. Cineradiography with lateral views by an experienced radiologist is the best diagnostic technique. Esophageal manometry may provide information regarding other esophageal dyskinetic problems. However, these studies are difficult to perform in neonates and infants. Endoscopy may be helpful to exclude vocal cord paralysis or mechanical obstruction. Balloon dilatation has been reported as being successful in several reports; however no comparison of efficacy has been made in any series between dilatation of the upper esophagus and surgical myotomy which remains in our mind, the optimal treatment of cricopharyngeal achalasia.
Abstract: INTRODUCTION: Retransplantation is a rescue operation in orthotopic liver transplantation. Its appropriateness has been questioned on medical, economical and also on ethical grounds. MATERIAL AND METHODS: During the period february 1984-december 1997, 54 (14.5%) of 372 adult patients were retransplanted; three (0.8%) of them had two retransplantations. Indications were graft dysfunction [(primary non function (8x) and early dysfunction (14x in 13 patients)], immunological failure [acute (9x in 8 patients) and chronic (9x) rejection], technical failure [(hepatic artery thrombosis (5x in four patients), allograft decapsulation (1x), ischaemic biliary tract lesions (6x)] and recurrent viral allograft disease [HBV (4x) and HCV (1x)]. RESULTS: Five year actuarial patient survival after retransplantation was 70.8%, which was identical to this of non retransplanted patients (72%). Early (< 3 mo) mortality was significantly lower in elective procedures (9.1%--2/22 pat. vs 34.4%--11/32 pat. in urgent procedures--p < 0.05). Mortality was highest in the graft dysfunction (23.8%, 5/21 pat.) and immunological failure (41%, 7/17 pat.) groups. Five of six patients retransplanted for rejection, whilst being on renal support, and two of three patients retransplanted urgently twice died of infectious complications. All patients retransplanted because of recurrent allograft disease were long-term (> 3 mo) survivors. Both HBV-infected patients died of allograft reinfection 7 months later; the two HBV-Delta infected patients were, free of infection, 44 and 6 months after retransplantation under HBV-immunoprophylaxis. Length of hospitalisation after primary transplantation and retransplantation were identical (median of 16 days--range 11 to 40 vs 14 days (range 7 to 110). Economical study during the period 1990-1995 showed that costs of the first hospitalization of primary transplantation and of retransplantation could be equalized during the period 1994-1995 as a consequence of the more frequent use of elective retransplantation (median 1.3 million BF, range 720,988 to 8,887,145 vs 1.1 million BF, range 943,685 to 1,940,409). CONCLUSIONS: Hepatic retransplantation is a successful safety net for many liver transplant patients. Every effort should be made to do this intervention electively under minimal immunosuppression. In case of immunological graft failure and hepatic artery thrombosis retransplantation must be done early in order to avoid infectious complications; the same holds for ischaemic biliary tract lesions which cannot be cured by interventional radiology. Retransplantation for recurrent benign disease should be restricted to those diseases which can be effectively treated by (neo- and) adjuvant antiviral therapy.
Abstract: OBJECTIVE: To achieve hepatic portal revascularisation and decompression of extrahepatic portal hypertension in children with cavernoma and obstruction caused by idiopathic portal vein thrombosis. DESIGN: Selected cases. SETTING: Teaching hospitals. Belgium and Italy. SUBJECTS: 11 children who weighed between 5.9 and 54 kg (2 emergencies) with symptomatic extrahepatic portal hypertension. INTERVENTION: Interposition of venous autograft between the superior mesenteric vein and the distal (umbilical) portion of the left portal vein. MAIN OUTCOME MEASURES: Improvements in symptoms and endoscopic appearance after operation. RESULTS: 2 bypasses had to be redone because they stenosed; all 11 were patent at the time of writing (median follow-up 6 months, range 1-32 months). CONCLUSION: The bypass effectively relieved symptoms of extrahepatic portal hypertension by restoring normal hepatic portal blood flow.
Abstract: Between 1984 and 1997, a total of 444 children (< 15 years) received an orthotopic liver transplant (OLT) at Saint-Luc University Clinics. Biliary atresia constituted the indication for OLT in 304 cases (68%). Median age (range) at OLT was 2.1 years (0.3-14.5). 177 children (40%) received a whole liver graft, 184 (41%) a reduced-size graft, 26 (6%) a split liver graft, whereas a living-related donor graft was used in 57 children (13%). Most grafts were ABO-identical or -compatible, in 395 cases (89%) and 40 (9%), respectively. Overall actuarial patient survivals at one and five years were 85% and 81%. The overall retransplantation rate was 19%. The results of uni- and multivariate statistical analyses showed a significant impact of year of transplantation (learning curve effect), with a 15% improvement of patient survival between the 1984-7 and the 1995-7 periods (p < 0.002). Results differed according to the indications for OLT, the best survivals being recorded for familial cholestasis, the worst for liver tumor (p = 0.004). Five year patient survival was significantly better after elective OLT (82%), when compared to highly urgent OLT (63%) (p < 0.001). Patient survivals were comparable in the children receiving primary cyclosporin-A microemulsion or tacrolimus immunosuppression, which were significantly higher than in the historical group treated with cyclosporin-A. No impact of the age at OLT, type of graft and ischemic time could be reported. In conclusion, this series illustrates the progressive improvements introduced in our pediatric liver transplant program between 1984 and 1997, including the technical variants allowing pediatric OLT using adult donors as well as the introduction of new immunosuppressive strategies.
Abstract: OBJECTIVE: To evaluate the impact of standardized operative and peri-operative care on the outcome of liver transplantation in a single center series of 395 adult patients. METHOD AND MATERIAL: Between February 1984 and December 31, 1998, 451 orthotopic liver transplantations were performed in 395 adult patients (> or = 15 years) at the University Hospitals St-Luc in Brussels. Morbidity and mortality of the periods 1984-1990 (Gr I--174 pat.) and 1991-1998 were compared (Gr II--221 pat.). During the second period anti-infectious chemotherapy and perioperative care were standardized and surgical technique changed from classical orthotopic liver transplantation with recipients' vena cava resection (and use of veno-venous bypass) towards liver implantation with preservation of the vena cava (without use of bypass). Immunosuppression was cyclosporine based from 1984 up to 1996 and tacrolimus based during the years 1997 and 1998. Immunosuppression was alleviated during the second period due to change from quadruple to triple and even double therapy and due to the introduction of low steroid dosing and of steroid withdrawal, once stable graft function was obtained. Indications for liver grafting were chronic liver disease (284 pat--71.9%), hepatobiliary tumor (52 pat--13.2%), acute liver failure (40 pat--10.1%) and metabolic disease (19 pat--4.8%). Regrafting was necessary because of graft dysfunction (21 pat), technical failure (12 pat), immunological failure (18 pat) and recurrent viral allograft disease (5 pat); three of these patients were regrafted at another institution. Follow-up was complete for all patients with a minimum of 9 months. RESULTS: Actuarial 1, 5 and 10 years survival rates for the whole group were 77.9%, 65.7% and 58.3%. These survival rates were respectively 77.3%, 69.7%, 62.5% and 73.2%, 59.6% 51.4% for benign chronic liver disease and acute liver failure; those for malignant liver disease were 80.6%, 44.3% and 36.7%. Early (< 3 months) and late (> 3 months) posttransplant mortalities were. 14.4% (57 pat) and 21.2% (84 pat). Early mortality lowered from 20% in Gr I to 9.4% in Gr II (p < 0.02); this was due to a significant reduction during the second period of bacterial (99/174 pat.--56.9% vs 82/221 pat.--37.1%), fungal (14 pat.--8% vs 7 pat.--3.2%) and viral (87 pat.--50% vs 49 pat.--22.2%) infections (p < 0.05) as well as of perioperative bleeding (92 pat.--52.9% vs 39 pat.--17.6%--p < 0.001). Late mortality remained almost identical throughout the two periods as lethal outcome was mainly caused by recurrent allograft diseases, cardiovascular and tumor problems. Morbidity in these series was important considering that almost, half of the patients had a technical complication, mostly related to bleeding (131 pat--33.2%) and biliary problems (66 pat--16.7%). Retransplantation index was 1.1 (54 pat.--14%). Early retransplantation mortality was 24%; it lowered, although not yet significantly, during the second period (8/25 pat.--32% vs. 5/29 pat.--17.2%). CONCLUSION: Despite a marked improvement of results, liver transplantation remains a major medical and surgical undertaking. Standardization of operative and perioperative care, less haemorraghic surgery and less aggressive immunosuppression are the keys for further improvement.
Abstract: The pharmacokinetics of intravenous and oral tacrolimus was assessed in paediatric liver transplant patients at two centers in Europe. Sixteen patients, age 0.7 to 13 years, participated in the study; 12 patients were evaluable for intravenous pharmacokinetics, and 16 for oral. Intravenous tacrolimus was given as a continuous 24 h infusion (mean 0.037+/-0.013 mg/kg/day), and oral tacrolimus was given in 2 doses per day (mean 0.152+/-0.015 mg/kg). Whole blood samples for the intravenous pharmacokinetic profile were taken before initiation of the first infusion, 4, 8, 12 and 24 h post-infusion, and every 24 h thereafter until intravenous administration was discontinued. During the 12 h wash-out period between intravenous and oral administration, samples were taken every 3 h. Samples for the oral pharmacokinetic profile were taken immediately before the first oral dose and 0.5, 0.75, 1, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-administration. Non-compartmental procedures were used to characterise the pharmacokinetic parameters. Mean estimates for clearance and terminal half-life were 2.3+/-1.2 ml/min/kg and 11.5+/-3.8 h, respectively, following intravenous tacrolimus. The mean bioavailability of oral tacrolimus was 25+/-20%. A strong correlation was observed between AUC and trough whole blood levels of tacrolimus (r=0.90). The clearance was approximately 2-fold higher than that previously observed in adults; this could explain the higher dosage requirements in children.
Abstract: BACKGROUND/PURPOSE: Performing a pyloromyotomy through a supraumbilical skin fold incision will leave an almost invisible scar and therefore has definitive cosmetic advantages. This alternative approach may be related to technical difficulties in delivering a large pyloric tumor when compared with the conventional pyloromyotomy through a right upper quadrant incision. However, in situ (intraabdominal) myotomy can help overcome this inconvenience. METHODS: Of 122 cases of infantile hypertrophic pyloric stenosis operated on between January 1990 and August 1996, 29 underwent a pyloromyotomy performed intraabdominally through the umbilical route. The medical records of these babies were reviewed. RESULTS: Twenty-three boys and six girls (median age, 30 days; range, 17 to 70 days) underwent surgery. The median hospital stay was 2.5 days. There were two intraoperative technical complications (small mucosal perforation) and one postoperative wound complication (abcess formation) requiring local drainage. CONCLUSIONS: In situ pyloromyotomy through the umbilical route is an elegant alternative in cases of a large pyloric tumor.
Abstract: BACKGROUND/AIMS: Bacterial infections complicate the course of up to 80% of pediatric liver transplant recipients, and in some cases, neutropenia, surgical complications and/or antibiotic resistance prevent successful control of sepsis. The aim of the present study was to evaluate the safety and efficacy of granulocyte macrophage colony stimulating factors (GM-CSF) in treating neutropenia following pediatric orthotopic liver transplantation. METHODS: Among a cohort of 430 pediatric orthotopic liver transplantation recipients, 13 children (12 months to 15 years, median 2 years, 10 males) received 15 courses of GM-CSF, 5 microg x kg(-1) x d(-1) subcutaneously, during their post-transplant course. In nine cases, the initial neutrophil count was below 1000/mm3. Ten patients were infected. Three received GM-CSF for severe sepsis without neutropenia. The mean duration of treatment was 16.3 days (range 4-49). RESULTS: In all but one neutropenic patient the neutrophil count increased above 1500/mm3 and the mean neutrophil count increased from 1392+/-1912/mm3 (range 130-7170, median 640) to 4508+/-2459/mm3 (range 350-9630, median 4390) (p<0.01). Only one neutropenic patient (FK506 related) failed to respond to treatment. No rejection episode was induced by treatment, no side effects were noted, and patients with sepsis were cured. CONCLUSION: In these patients, GM-CSF was safe, it achieved a significant increase in neutrophilic count, and was beneficial in patients with severe bacterial infections. This compound may prevent infectious complications in neutropenic patients and may benefit patients with severe sepsis with or without neutropenia.
Abstract: Due to the shortage of size-matched liver donors, relatively oversized liver grafts (even after ex situ volume reduction) are frequently used for liver transplantation in children. This was recently observed when livers from large, living related donors were procured for transplantation in very small recipients. Given that abdominal hyperpressure can compromise vascular flow in the new graft, primary closure of the abdomen was delayed by temporary Silastic prosthetic closure in selected cases. The new technique was original in that the skin was closed, avoiding fluid loss and reducing the risk of infections reported with other techniques, and in that reoperation allowed for a delayed, but primary-type, closure (fascia and skin) that resulted in an esthetically correct aspect. Over a period of 7 years, 330 pediatric liver transplantations were performed, and delayed prosthetic closure was achieved successfully and safely in 47 cases. The present report outlines this clinical experience.
Abstract: BACKGROUND: Decompression of extrahepatic portal hypertension by directly bypassing the thrombosed portal vein has never been reported in cases of children with idiopathic (or neonatal) portal vein obstruction and cavernoma. METHODS: Seven children (15 years or younger) with portal vein obstruction requiring surgical decompression (urgently in two cases), and in whom preoperative Doppler had shown that the intrahepatic portal branches were hypoplastic but free of thrombus, were included in a pilot study. The cavernoma was bypassed by interposing a venous jugular autograft between the superior mesenteric vein and the distal portion of the left portal vein. Patients received follow-up using routine clinical parameters, upper gastrointestinal endoscopy, and Doppler ultrasound. RESULTS: The mesenterico-portal bypass restored a direct (physiological) hepatopetal portal flow. The operation resulted in effective portal decompression as demonstrated by decrease of the pressure gradient, rapid regression of clinical signs of portal hypertension, and definitive control of bleeding. CONCLUSIONS:This study shows that direct bypassing of portal cavernoma is possible and results in effective portal decompression. Restoration of the hepatic portal flow is a major advantage compared with conventional surgical shunting procedures. This new technique is potentially applicable to two thirds of children with portal vein thrombosis and should be considered when shunting procedures are indicated.
Abstract: BACKGROUND: When compared with cadaveric grafts (Cad), the potential advantages of pediatric orthotopic liver transplantation (OLT) from living-related (LR) donors may include better graft quality, shorter ischemic time, appropriate preparation of the recipient, and better immunologic compatibility. METHODS: The aim of this study was to analyze early hepatocyte, endothelial, and bile duct cell injury following pediatric OLT using LR (n=15) or uncomplicated Cad reduced-size (n=10) grafts. Median (range) total ischemic times were 190 min (105-261) versus 760 min (418-948) in LR and Cad groups, respectively (P<0.001). RESULTS: The post-OLT cytolytic profile, assessed daily during the first 7 days using both plasma glutamate-pyruvate transaminase and serum alpha-glutathione S-transferase, showed significantly higher levels of both parameters for the 10 uncomplicated Cad cases when compared with the 15 LR grafts (P<0.001). The evaluation of hepatic endothelial cell function during the first week after OLT, using serum hyaluronic acid levels, suggested lower endothelial injury in the LR grafts, when compared with the Cad grafts (P=0.059). Bile duct cell injury, as assessed using plasma gamma-glutamyl transferase levels, was similar in both groups, with a progressive increase at the end of the first week after OLT, which was correlated with a similar incidence of early acute rejection in both groups (80% in the LR group vs. 62% in the Cad group, NS). CONCLUSION: (1) The hepatocellular and endothelial cell damage was reduced after OLT with LR grafts, which may be related to shorter ischemic time when compared with Cad grafts; (2) the putative immunologic advantage for LR grafts was not confirmed in terms of incidence of acute rejection.
Abstract: MESENTERICO-LEFT INTRAHEPATIC PORTAL VEIN SHUNT: Original technique to treat symptomatic extrahepatic portal hypertension. OBJECTIVE: Revascularization of the intrahepatic portal system as decompressive surgery for chronic extrahepatic portal hypertension. SUMMARY BACKGROUND DATA: In patients with extrahepatic portal hypertension (portal trunk thrombosis in presence of a normal liver), shunt surgery is indicated when patient is bleeding from varices at a site not accessible for the endoscopist. Although surgical portal decompression is an efficient procedure, there is a risk of depriving the liver from the splanchnic venous flow and a risk of developing porto-systemic shunt related side effects. METHOD: A shunt was created between the superior mesenteric vein and the umbilical portion of the left portal vein. This technique allows to bypass the thrombosed portion of the portal vein but avoiding dissection of the cavernoma in the liver hilum and related risk of intraoperative hemorrhage. RESULTS: The procedure was successfully performed in one adult patient considered unshuntable in view of classic surgical procedures and in whom sclerotherapy was unsuccessful. This operation achieved an effective decompression of the splanchnic venous system. CONCLUSION: Rerouting the venous splanchnic flow through the liver was possible. It had the major physiological advantage of restoring the normal hepatic vascularization. It also avoided putting the patient at risk of developing porto-systemic shunt related side effects. This option should be considered when shunt procedures are indicated in patients with extrahepatic portal hypertension.
Abstract: Between 1984 and 1996, the authors performed 499 liver transplants in 416 children less than 15 years old. The overall patient survival at 10 years was 76.5%. It was 71.3% for the 209 children grafted in 1984-1990; 78.5% for biliary atresia (n = 286), 87.3% for metabolic diseases (n = 59), and 72.7% for acute liver failure (n = 22). The 5-year survival was 73.6% for the 209 children grafted in 1984-1990 and 85% for the 206 grafted in 1991-1996. Scarcity of size-matched donors led to the development of innovative techniques: 174 children who electively received a reduced liver as a first graft in our center had a 5-year survival of 76% while 168 who received a full-size graft had a survival of 85% (NS). Results of the European Split Liver Registry showed 6-month graft survival similar to results obtained with full-size grafts collected by the European Liver Transplant Registry. Extensive use of these techniques allowed the mortality while waiting to be reduced from 16.5% in 1984-1990 to 10% in 1991-1992. It rose again to 17% in 1993, leading the authors to develop a program of living related liver transplantation (LRLT). The legal and ethical aspects are analyzed. Between July 1993 and October 1997, the authors performed 53 LRLTs with 90% survival. In elective cases, a detailed analysis was made of the 45 children listed for LRLT between July 1993 and March 1997 and the 79 registered on the cadaveric waiting list during the same period. Mortality while waiting was 2% and 14.5% for the LRLT and cadaveric lists, respectively. The retransplantation rate was 4.6% and 16.1% for LRLT and cadaveric transplants, respectively. Overall post-transplant survival was 88% and 82% for children who received a LRLT or a cadaveric graft, respectively. Overall survival from the date of registration was 86% and 70% (P < 0.05) for LRLT or cadaveric LT respectively. The 2-year post-transplant survival in children less than 1 year of age at transplantation was 88.8% and 80. 3% with a LRLT or cadaveric graft, respectively; patient survival after 3 months post-transplant was 95.8% and 91.9% for stable children waiting at home, 93.7% and 93.7% in children hospitalized for complications of their disease, and 89.5% and 77.7% for children hospitalized in an intensive care unit at the time of transplantation for children who received a LRLT or cadaveric graft, respectively. It is concluded that LRLT seems to be justified for multidisciplinary teams having a large experience with reduced and split liver grafting.
Abstract: Encouraging results of alternative techniques used for liver transplantation in children (liver reduction) and the persistent lack of a sufficient number of cadaver donors has favored the development of living related donor liver transplantation. This program, which began after a long preparative period concerning the ethical questions involved, has included 32 children during the first 30 months. Results have been excellent. All children who underwent elective transplantations (n = 18) are still living. Among the 14 patients whose condition required hospitalization before transplantation, 86% have survived. Vascular complications and graft loss due to primary dysfunction or chronic rejection have been reduced, but 22% of the patients have biliary stenosis. In the donors, there has been no severe complication or sequelae. Use of related living donor livers has increased the number of grafts available for children on the waiting list for cadaver livers. The resulting gain in waiting time has also reduced the risk of death before transplantation. In our experience, the combination of the two transplantation programs using living donors and cadaver livers has had a positive impact on global management of children referred for liver transplantation, whatever the option chosen by the parents.
Abstract: The influence of the implantation technique on the outcome was studied prospectively in a series of 116 consecutive adult patients undergoing primary liver transplantation during the period January 1991-June 1994. Thirty-eight patients (32.8%; group 1) underwent classical orthotopic liver transplantation (OLT) with replacement of the recipient's inferior vena cava (R-IVC) and with venovenous bypass (VVB). Thirty-nine patients (33.56%) had a piggy-back OLT with preservation of the R-IVC (group 2); bypass was used in 17 of them (43.6%) because of poor hemodynamic tolerance of R-IVC occlusion. Thirty-nine patients (33.6%) had OLT without VVB and with side-to-side cavocaval anastomosis (group 3). The three techniques were performed irrespective of the anatomical situation and of the status of the recipient at the time of transplantation. The following parameters were assessed in all patients: implantation time, blood product use, morbidity (e.g., hemorrhagic, thoracic, gastrointestinal, neurological, and renal complications), and outcome. Thirty-one patients underwent detailed intraoperative hemodynamic assessment. The early (< 3 months) post-transplant mortality of 10.3% (12/116 patients) was unrelated to the implantation technique. Group 3 had a significantly shorter mean implantation time, a reduced need for intraoperative blood products, and a lower rate of reoperation due to intra-abdominal bleeding. After excluding two immediate perioperative deaths and eight patients requiring early retransplantation because of primary nonfunction, the frequency of immediate extubation was significantly higher in group 3. Detailed hemodynamic assessment did not show a difference between 6 group 1 patients and 17 group 3 patients, indicating that partial lateral clamping of the IVC fulfills the function of venous bypass. Similar results were obtained in 6 group 2 patients who did not have IVC occlusion. Cavocaval OLT has become our preferred method of liver implantation. It allows the transplantation to be performed without VVB, regardless of the anatomical situation and of the condition of the patient at the time of transplantation. Moreover, it avoids all of the potential complications and costs of VVB.
Abstract: Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests taken during i.v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively, and the bioavailabilities were 22% and 21% for the first and last NEO doses. A large interpatient variability was observed. This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability.
Abstract: BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a life-threatening condition the incidence of which in pediatric solid organ transplantation may be related to the immunosuppressive load. It has been suggested that tacrolimus, a new and potent immunosuppressor, causes an increased incidence of this syndrome. METHODS: The incidence, early signs, and risk factors for lymphoproliferative disease were reviewed in a cohort of 89 pediatric liver transplant recipients treated with tacrolimus. RESULTS: Eighteen patients (20%) developed a PTLD-16 concomitant to a primary Epstein-Barr virus (EBV) infection and 2 with previous immunity against EBV. Three additional patients had preliminary signs of PTLD concomitant to primary EBV infection, but did not develop individualized lymphoid masses. Six patients died (6.7% of all tacrolimus-treated patients). Mean tacrolimus blood level during the 3 months preceding EBV infection reached 11.8+/-1.8 ng/ml in PTLD patients versus 9.4+/-3.4 ng/ml in non-PTLD patients (0.05<P<0.1). Previous OKT3 or antithymocyte globulin treatment was also significantly associated to PTLD. There was no association with age, rejection episodes, steroid-resistant rejection, prior cytomegalovirus infection, HLA mismatch, living donor or cadaveric organ transplantation, United Network for Organ Sharing status at the time of orthotopic liver transplant, and primary or rescue tacrolimus treatment. A significant increase of total gamma-globulin level occurred in PTLD patients, and mono/oligoclonal production was significantly associated to PTLD. CONCLUSION: In EBV-infected pediatric liver transplant recipients, use of OKT3 or antithymocyte globulin and high tacrolimus blood levels are risk factors for a significant increase in the incidence of PTLD. An increase in total gamma-globulin level and appearance of mono/oligoclonal immunoglobulin production are the major preliminary signs of the syndrome.
Abstract: The aim of this study was to analyze the influence of technical problems resulting from splanchnic venous anomalies on the outcome of orthotopic liver transplantation. From February 1984 until December 1995, 53 (16.3%) of 326 adults underwent consecutive transplantations whilst having acquired anomalies of the splanchnic veins. These consisted of portal vein thrombosis (n = 32, 9.8%), thrombosis with inflammatory venous changes (phlebitis; n = 6, 1.8%) and alterations related to portal hypertension surgery (n = 15, 4.6%). Because of major changes in surgical technique, i.e., eversion instead of blind venous thrombectomy, immediate superior mesenteric vein approach in cases of extended thrombosis, and piggyback implantation with preservation instead of removal of the inferior vena cava, patients were divided into two groups: those who underwent transplantation during the period February 1984 to December 1990 (group 1) and those transplanted between January 1991 and December 1995 (group 2). Surgical procedures to overcome the anomalies consisted of venous thrombectomy (n = 26), implantation of the donor portal vein at the splenomesenteric confluence (n = 5) or onto a splenic (n = 1) or ileal varix (n = 1), interposition of a free iliac venous graft between recipient superior mesenteric vein and donor portal vein (n = 9), and interruption of surgical portosystemic shunt (n = 13). All patients had a complete follow-up. The 1- and 5-year actuarial patient survival rates were similar in patients with (n = 53) and without (n = 273) splanchnic venous abnormalities (75.5% vs 78.1% and 64.3% vs 66.9%, respectively). Early (< 3 months) post-transplant mortality was 24.5% (13/53 patients). Mortality was highest in the portal vein thrombophlebitis group (5/6, 83.3%), followed by the portal hypertension surgery group (5/15, 33.3%) and the portal vein thrombosis group (3/32, 9.4%). Technical modifications significantly reduced mortality in group 2 (10.3%, 3/29 vs 41.7%, 10/24 patients in group 1; P < 0.05) as well as the need for re-exploration for bleeding (13.8%, 4/29 patients in group 2 vs 15/24, 62.5% in group 1; P < 0.01). Mortality directly related to bleeding was also significantly lowered (1/29, 3.4% in group 2 vs 9/ 24, 37.5% in group 1; P < 0.01). We conclude that liver transplantation can be safely performed in the presence of splanchnic vein thrombosis and previous portal hypertension surgery.
Abstract: Two cases of gastroduodenal outlet obstruction caused by arteriomesenteric compression in children who have cerebral palsy are reported. Clinical symptoms of gastrointestinal obstruction include recurrent postprandial nausea and vomiting, upper abdominal distension, and pain. In such patients, multiple predisposing factors can contribute to the development of arteriomesenteric compression, including marked weight loss, supine position, and severe scoliosis. Upper gastrointestinal x-rays using barium contrast allow diagnostic confirmation. In our experience, this cause of acute gastroduodenal outlet obstruction may usually resolve after conservative treatment using a jejunal feeding tube passed beyond the compression, left lateral positioning, and renutrition.
Abstract: During the period from 1972 to 1992, 59 children received surgical treatment at the University of Louvain Medical School for biopsy-proven Hirschsprung's disease (HD). The extent of aganglionosis was as follows: short segment restricted to the rectosigmoid or descending colon (n = 44, 75%); long segment (n = 9,15%); ultra-short segment (n = 3, 5%); unknown length because of death without autopsy (n = 3, 5%). The median age at operation was 7 months for short-segment disease compared with 14 months for those with long-segment disease. Surgical procedures used for short-segment disease were Swenson with colostomy (n = 16), Swenson-Pellerin without colostomy (n = 27), Duhamel (n = 1), and for long-segment disease were Martin (n = 3), Swenson-Deloyers (n = 2), Swenson-Boley (n = 2) and ileostomy only in = 2). Lynn's sphincteromyotomy was performed in the three ultra-short cases. There were six deaths (10%) at a median age of 86 days (range, 28 to 1545 days), three had long-segment disease, and the others were not classified because of death before curative surgery. Enterocolitis (EC) was the most common cause of death (five cases) and was also the major source of morbidity after curative surgery (12 of 44, 27%) in short-segment patients, three of seven (43%) in long-segment patients. The functional success of the procedure was evaluated in 70% of the surviving patients (37 of 53; mean follow-up, 8.7 years; range, 1.2 to 21.5), using a novel semiquantitative scoring system, specifically designed for children who have HD. This system assesses normal stool evacuation, abdominal distention, soiling, and severe incontinence. The results were compared with those from a population of 39 healthy children and adolescents and demonstrated progressive improvement in function during childhood and adolescence (P = .04) for patients treated for short-segment disease. However, function was found to be consistently poorer in all age groups when compared with healthy controls (5 to 10 years, P < .01; 10 to 15 years, P < .05; > 15 years, P < .01).
Abstract: The oral bioavailability of Sandimmun can be impaired by cholestasis, external biliary diversion, and diarrhea. We report two cases of pediatric liver transplant recipients who experienced chronic rejection and diarrhea secondary to proximal bowel resection. These conditions resulted in poor oral absorption of Sandimmun; the children were converted to the new oral microemulsion formulation Neoral, which significantly improved oral absorption, allowing intravenous cyclosporine weaning and patient discharge. Comparative pharmacokinetic studies were performed in both cases, and the relative Neoral/Sandimmun bioavailabilities were 32.9 and 5.4, respectively. Accordingly, Neoral may constitute to good alternative to ensure the effectiveness of oral cyclosporine administration, particularly in liver-transplanted children with severe cholestasis or shortened small bowel.
Abstract: In vitro glucuronidation was studied in liver microsomes from two patients with Crigler-Najjar type I (CN-I) disease and compared with the activity measured in microsomes prepared from six control human livers. The UDP-glucuronosyltransferase (UGT) activity was determined toward the following substrates: 4-nitrophenol, propofol, (-)-morphine (formation of the 3-glucuronide), and diflunisal (formation of the phenolic and acyl glucuronides). Glucuronidation of 4-nitrophenol was reduced in one of the CN-I livers (CN-I No. 1) (0.9 nmol min(-1)mg(-1)) and normal in the other CN-I liver (CN-I No. 2) (3.5 nmol min(-1) mg(-l)) compared to the control livers (5.6 +/- 29 nmol min(-1) mg(-1)), mean +/- S.D.). Propofol glucuronidation was not detectable (i.e. less than 0.100 nmol min(-l) mg(-1) in the CN-I No. 1 liver and normal in the CN-I No. 2 liver (1.78 nmol min(-1) mg(-1) against 1.52 +/ 0.72 nmol min(-l) mg(-) in the control livers). The glucuronidation of (-)-morphine to the 3-glucuronide and the formation of the phenolic and acyl glucuronides of diflunisal were normal in both CN-I livers compared to the control livers. Our results show that CN-I patients are heterogeneous regarding UGT activity toward the phenolic substances 4-nitrophenol and propofol.
Abstract: A prospective trial was conducted in 129 recipients of primary liver transplantation, to compare induction immunosuppression using triple drug therapy (cyclosporine, steroids, and azathioprine; group 1, n = 42), versus triple drug therapy with a 10-day course of OKT3 (group 2, n = 44) or of the anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 (group 3, n = 43). Two-year actual patient survival rates were 64%, 79%, and 93% in groups 1, 2, and 3, respectively (1 vs. 2, NS; I vs. III, P = 0.003; 2 vs. 3, NS). Up to 2 years after transplantation, 18%, 44%, and 53% of the grafts in groups 1, 2, and 3, respectively, had not experienced steroid-resistant acute rejection (1 vs. 2, P = 0.002; 1 vs. 3, P = 0.007; 2 vs. 3, NS). The overall incidence of chronic rejection was 4%. OKT3 therapy, but not LO-Tact-1, significantly increased the incidence of cytomegalovirus infections (P = 0.019). In conclusion, immunoprophylaxis with LO-Tact-1 seemed to provide a liver graft acceptance rate at least as satisfactory as that with OKT3, without an increase in the incidence of infections.
Abstract: BACKGROUND: Open surgery is the standard approach for splenectomy in hematologic disorders, but a few cases of successful laparoscopic splenectomy have been reported. METHODS: Thirty-one patients (18 adults, group 1; and 13 children, group 2) underwent laparoscopic splenectomy. Indications for surgery included idiopathic thrombocytopenic purpura (25 patients), congenital spherocytosis (4 patients), and hemolytic anemia (2 patients). In 97% of the patients the diameter of the spleen was less than 15 cm.RESULTS: Laparoscopic splenectomy was successful in 94% of the patients; conversion to open surgery was mainly related to hemorrhage. Accessory spleen was found in 39% in group 1 and 8% in group 2. Two adults received intraoperative autotransfusion. Postoperative morbidity was minimal. The median postoperative stay was 3 days (range, 2 to 12 days) in group 1 and 2 days (range, 2 to 5 days) in group 2. CONCLUSIONS: Laparoscopic splenectomy is safe in both adults and children. Adequate selection of patients (small-size spleen, splenic destruction on preoperative scanning of platelets), appropriate preparation in patients with idiopathic thrombocytopenic purpura (immunoglobulin G), and meticulous surgical technique (with routine opening of the gastrocolic ligament to search for accessory spleen) are key factors in obtaining the same long-term results as with open surgery.
Abstract: Calcification within active post-transplantation lymphoproliferative disorders has, to our knowledge, never been described. We report the case of a 14-month-old boy who presented 4 months after orthotopic liver transplantation with a primary calcification in a lymphoproliferative nodule involving the hepatic graft. This calcification was detected by routine ultrasonography, visible on plain radiographs, and the post-transplantation lymphoproliferative disorder was histologically proved.
Abstract: OBJECTIVE: Results from clinical pharmacokinetic studies of propofol indicate that this i.v. anaesthetic agent may undergo significant extrahepatic glucuronidation. We have investigated whether glucuronidation of propofol takes place in the kidney and/or the gut wall. First, propofol concentrations were measured in arterial (radial artery) and portal venous blood of 12 cirrhotic patients with trans internal jugular porto-systemic shunting (TIPSS). RESULTS: In 7 of the 12 patients arterial propofol concentrations were higher than portal venous concentrations. In the remaining patients, propofol concentrations were higher in the portal vein than the radial artery. Since an additional study in 5 patients anaesthetized with propofol while undergoing cholecystectomy showed propofol and an acid-labile conjugate of it in bile, it is difficult to interpret the results in patients with TIPSS due to the possibility of enterohepatic cycling. Next, in vitro studies with human liver (n = 5), kidney (n = 5) and small intestinal (n = 5) microsomes showed that all three tissues were capable of forming propofol glucuronide. Vmax for propofol glucuronidation was approximately 3 to 3.5 times higher in kidney (5.56 nmol.min-1.mg-1 protein) than liver (1.80 nmol.min-1.mg-1 protein) and small intestine (1.61 nmol.min-1.mg-1 protein). CONCLUSION: Based on these in vitro results, it is concluded that extrahepatic glucuronidation in the small intestine and especially in the kidney may contribute to the overall glucuronidation of propofol in man.
Abstract: Paediatric orthotopic liver transplant recipients may develop chronic hepatitis after surgery. To investigate the role of hepatitis C virus in this pathology a cohort of 249 paediatric orthotopic liver transplant recipients was studied. Sixteen children (6.4%) were found to have chronic hepatitis C virus hepatitis after orthotopic liver transplantation. All but one of them had serum transaminase values which were persistently raised two to eight times the upper limit of normal. Thirteen were positive for both serology and serum hepatitis C virus RNA. Serum hepatitis C virus RNA detection occurred five to 33 months before hepatitis C virus antibodies. Liver tissue hepatitis C virus RNA and hepatitis C virus core antigen were detected in five. In one patient, tissue hepatitis C virus core antigen was detected when other tests for hepatitis C were negative. Two patients had positive human cytomegalovirus serum antibodies and RNA before transplantation. Although serum hepatitis C virus RNA was not detected after transplantation, serum enzyme immunosorbent assay and tissue core antigen were still detectable in both patients. In another child, serum hepatitis C virus RNA was positive and hepatitis C virus core antigen was found on a liver biopsy specimen but antihepatitis C virus antibodies were negative as well as liver hepatitis C virus RNA. No patient developed severe liver disease or cirrhosis during a follow up of up to 72 months. It is concluded that hepatitis C virus is a significant cause of morbidity after paediatric orthotopic liver transplantation. Diagnosis cannot rely on serological testing only. The patients remained stable on follow up, but longer prospective histological studies remain necessary to establish prognosis.
Abstract: The shortage of liver grafts results in the fact that 8% of potential recipients die before receiving a graft. Liver graft division has therefore been proposed to maximize the current available liver graft pool. However, the question of benefit or additional risk for the recipient that this technique might carry remains unanswered. The European Split Liver Registry was opened in March 1993 and reviewed retrospectively the clinical experience obtained at nine European centers regarding the use of split liver transplants, during the five year period from March 1988 to March 1993. From 50 donor livers, 100 grafts were prepared: 2 grafts were discarded and the other 98 were transplanted in 53 children (2 times in 3 children) and 42 adults (2/42 in heterotopic position). Sixty-three grafts were implanted in an urgent recipient (half of whom had acute hepatic failure). Portal vein thrombosis, hepatic artery thrombosis, biliary complications, and retransplantation rates were 4%, 11.5%, 18.7%, and 18.7%, respectively. Most of these complications were unrelated to the technique itself. Actual 6-month graft survivals of elective and urgent orthotopic transplants were 80% and 61.3% in children, and 72.2% and 55.6% in adults; actual 6-month patient survival rates for similar groupings were 88.9% and 61.1%, and 80% and 67.7%, respectively. Similar rates are reported after conventional transplants in Europe. It is concluded that split liver transplantation is an efficient transplant technique that benefits both urgent patients who otherwise could have died before getting a graft in time and elective patients.
Abstract: Two siblings presented with neonatal cholestasis and early liver insufficiency. The older was admitted for end-stage cirrhosis with severe hypoglycemia and had long-term successful liver transplant at the age of 15 months. The second child presented a similar neonatal history of cholestasis, hypoglycemia, hyperlactacidemia, liver insufficiency and progressive cirrhosis. Extensive work-up excluded all known causes of neonatal cholestasis. Gluconeogenesis was found normal following alanine and fructose infusion. Repeated hypoglycemia with early post-prandial hyperlactacidemia led us to investigate the mitochondrial respiratory chain enzyme activities. Selective defects of complexes I, III and IV, coded by mitochondrial DNA, were detected in liver tissue of this patient and on preserved frozen tissue from his sibling, whilst normal activities were found in liver tissue samples from control patients with end-stage liver diseases. No extrahepatic manifestations were found. We conclude that liver deficiency of mitochondrial respiratory chain enzymes may cause liver disease in neonates, associated with hypoglycemia and post-prandial hyperlactacidemia. The disease is cured by liver transplantation.
Abstract: The feasibility and safety of laparoscopic splenectomy were evaluated in a prospective multicenter study of 50 patients operated on for idiopathic thrombocytopenic purpura (ITP) (n = 31), hereditary spherocytosis (n = 6), hemolytic anemia (n = 4), Hodgkin's disease or lymphoma staging (n = 5), benign splenic tumors (n = 3), and wandering spleen (n = 1). Conversion to laparotomy was required in 10%. An accessory spleen was routinely searched for, although the lesser sac was opened during surgery in only 10%; the overall incidence was 14%. Hospital mortality was 2% and postoperative morbidity 22%. Postoperative hospital stay and home rehabilitation were improved when exclusively laparoscopic splenectomy was performed. In ITP patients, at a mean follow-up of 8.2 months, 8 patients (27%) had recurrence of thrombocytopenia, which was transient in 7% and permanent in 20%. Laparoscopic splenectomy is feasible and safe when performed in selected patients by expert laparoscopic surgeons. Adequate selection of patients and routine, careful search for accessory spleen are critical. The recurrence rate (20%) for ITP was high at 8.2 months, and this factor is the major limitation of laparoscopic splenectomy at present.
Abstract: This paper describes a quick procedure for cadaveric liver graft retrieval during multiple organ harvesting. The technique is based on minimal preliminary dissection, absence of in situ direct portal perfusion, and en bloc removal of the liver and pancreas, with an aortic patch encompassing the coeliac trunk and superior mesenteric artery. The results of 110 pediatric liver transplantations with 109 organs harvested using this technique are reported. There were no graft harvesting injuries. The liver graft primary nonfunction rate was 4.5% (5/110). The 3-month retransplantation rate was 10%. The actual patient survival rates were 93% at 3 months and 90% at 1 year; actual graft survival rates were 85.5% and 78%, respectively. The technique described was at least as safe as conventional procedures. A major advantage of the procedure is its flexibility, which allows for the easily combined procurement of other organs (whole pancreas and intestine).
Abstract: Hyperbilirubinemia in Crigler-Najjar disease type I (CN) can be partially controlled by daily phototherapy, but these children remain at permanent risk of developing brain damage due to kernicterus. Because liver transplantation is the only available curative treatment for liver-based inborn errors of metabolism, orthotopic liver transplantation (OLT) was performed in six patients with CN. Mean age at surgery was 52.5 months (range 27 to 100). Despite a mean daily phototherapy of 12.4 +/- 0.8 hr, mean bilirubin of the 6 patients was 388 microM/L (range 175 to 703) before OLT; one of them was also being treated with tin-protoporphyrin. All 6 had elevated AST/ALT, ranging from 1.4 to 6 times upper normal values. Complications occurred in three patients after OLT, including miliary tuberculosis in one, graft rejection and retransplantation in one, and hepatic artery thrombosis in one. All patients survive with normal serum bilirubin level (follow up 6 to 116 months). Four have normal enzymes on post-OLT follow-up (30 to 95 months), follow a normal education program, and have a normal social life. One recently transplanted patient has progressively normalizing liver function tests 6 months after OLT. One patient transplanted at 8 y.o. (now 116 months post-OLT) has moderate neurological delay due to pretransplant kernicterus, and posttransplant chronic persistent hepatitis. Our series shows that OLT cures hyperbilirubinemia in CN patients, with an excellent survival prospect. The procedure should be decided upon before neurological sequelae occur, since these persist after transplantation.
Abstract: Current methods for accessory liver transplantation in the rat require a high degree of microsurgical expertise and long training before success is achieved. We present a simpler method of arterialized accessory liver transplantation using the cervical vessels for revascularization of the transplanted liver with the cuff technique, which is useful for studies of liver preservation, reperfusion injury, and liver regeneration. After classical 70% hepatectomy is performed on the graft, the right common carotid artery is anastomosed to the donor aorta, the distal right external jugular vein is anastomosed to the donor portal vein, and the proximal right external jugular vein is anastomosed to the donor supradiaphragmatic inferior vena cava. The skin is not closed over the cervically transplanted liver (CTL). This method was used 30 times for periods of up to 6 h with a 90% success rate. CTL structure and function, as revealed by histology, bile flow rates, biliary bilirubin concentrating capacity, membrane potential, enzyme activity and distribution, have shown the CTL to be a structurally normal and metabolically active graft. In conclusion, the cervical approach to arterialized accessory liver transplantation is simple, and should prove useful for studies of liver preservation, reperfusion, regeneration, physiology, and toxicology.
Abstract: Twenty-three pediatric liver transplant recipients (median age 3.9 years) were converted from cyclosporine A-based immunosuppression to FK506 for uncontrollable acute rejection (AR; n = 16), chronic rejection (n = 4), or predominantly nonspecific hepatitis (n = 3). Of these, 19 had received poly- or monoclonal anti-T lymphocyte antibodies either for AR prophylaxis or therapy before FK506 conversion. Full clinical and histologic responses to FK506 therapy were observed in 11/16 cases of AR compared with 0/7 cases of non-AR indications (P = 0.006). Acute FK506 toxicity included renal dysfunction in 12/23 children (52%), neurological disorders in 7/23 (30%), and isolated hyperkalemia in 2/23 (9%), with a poor correlation with the corresponding FK506 trough plasma level. Moreover, a significant impairment of glomerular filtration rate was recorded in the 12 children who received FK506 treatment for more than 6 months (P = 0.002). FK506 therapy had to be definitively withdrawn in 6 cases (fatal infections: n = 4; persistent tremor: n = 1; reason unrelated to FK506: n = 1). Five children developed a lymphoproliferative syndrome (LPS), leading to death in 3 cases despite cessation of the immunosuppressive therapy; in the other 2 patients, LPS was controlled, and the children were successfully retransplanted for chronic rejection under FK506. The occurrence of Epstein-Barr virus primary infection under FK506 therapy was found to constitute a significant risk factor for LPS (P = 0.027). In summary, full response to FK506 conversion was observed in 69% of uncontrollable AR cases; however, 74% and 22% of this probably over-immunosuppressed population experienced major adverse events and LPS under FK506 therapy, respectively.
Abstract: A 4-year-old child referred for acute jaundice following percutaneous needle biopsy of the liver underwent hepatobiliary scintigraphy. Although all conventional liver tests suggested preservation of hepatocyte function, the tracer uptake in the liver appeared dramatically reduced at scintigraphy and the blood pool activity did not decrease significantly until the end of the study. Visualization of the bile ducts indicated, however, that the tracer was taken up by the hepatocyte and further excreted into the biliary tree. There was no tracer pooling in the biliary tree although no bowel activity was observed, even on delayed images. The association of persistent blood pool activity, bile duct visualization without tracer pooling, and nonvisualization of the bowel was caused by a continuous recirculation of the tracer from the biliary tree into the bloodstream. The presence of a biliovenous fistula was further proven by percutaneous transhepatic cholangiography performed 24 h later. Since 1975, only 16 cases of bilhemia have been reported. To the best of our knowledge the scintigraphic pattern of this rare but life-threatening complication has not previously been reported.
Abstract: Two 10-year and 11-year-old children with oesophageal and gastric varicose haemorrhage unresponsive to medical treatment and repeated endoscopic sclerotherapy underwent percutaneous transjugular intrahepatic portosystemic shunting (TIPSS). A newly developed introducing system was used. The procedure was performed to avoid the increased risk of emergency liver transplantation in children with hepatic failure. Immediately after the procedure bleeding stopped and the patient's condition improved. Ascites disappeared and liver function improved. The stent shunt was shown to be patent by angiography and Doppler ultrasound for a follow up period of more than 1 year. CONCLUSION: TIPSS may be of benefit in children with severe portal hypertension. It allows control of intractable bleeding, and stabilizes the patients preparing them for subsequent elective orthotopic liver transplantation.
Abstract: BACKGROUND: Split liver grafting has not gained wide acceptance mainly because of different vascular and biliary technical problems. STUDY DESIGN: A new technique of right split liver transplantation is described. The piggyback implantation technique, using wide side-to-side cavocavostomy overcomes problems encountered when sharing the superhepatic vena cava cuff between two livers and obtains optimal drainage of venous allograft outflow, thus avoiding extensive bleeding at the transection margin. RESULTS: This technique was successfully used in two adult recipients. CONCLUSIONS: Piggyback transplantation using wide side-to-side cavocavostomy allows easy and safe implantation of the right split liver allograft.
Abstract: Biliary atresia is the most frequent cause of chronic cholestasis in infants. When left untreated, this condition leads to death from liver insufficiency within the first 2 yr of life. The modern therapeutic approach consists of a sequential strategy with Kasai portoenterostomy as a first step and, in case of failure, liver transplantation. After portoenterostomy, no more than 20% to 30% of patients will live jaundice-free into adulthood. Illness in another third will be palliated, and these patients have extended survival, delaying liver transplantation to later childhood (2 to 15 yr). The remaining 30% to 40% will not benefit from the Kasai operation and will die of liver failure in infancy. The annual need of liver transplantation for biliary atresia is one case per million people. This indication represents 35% to 67% of the reported series of pediatric liver transplantation and between 5% and 10% of the indications for liver transplantation, all ages included. Approximately four of five children transplanted for biliary atresia will become long-term survivors with good physical and mental development; recurrence of the disease after transplantation has not been observed. Because most candidates are young children (< 3 yr) of small size (< 10 kg), there is a shortage of size-matched donors (which has been alleviated by the use of innovative techniques such as reduced and split livers). The resulting redistribution of the adult donor liver pool is ethically justified by the equal quality of the results after transplantation of a full-size or partial graft.
Abstract: Due to developments in surgical techniques and organ preservation, the shipping of renal and extrarenal organs is becoming increasingly more frequent. During the period from 1 January 1991 to 31 December 1992, 39 of 180 (21%) implanted liver allografts were shipped to our center by local harvesting teams. The fact that each of nine livers (23.1%) presented with minor and major (vascular and parenchymatous) problems stresses the need for better surgical training and standardization in procurement techniques. The introduction of a liver allograft feedback report could be an easy way to perform quality control.
Abstract: The outcome after liver transplantation when grafts were retrieved from the donor by the classical aortic and portal cooling (APC) method was compared with the outcome when exclusively aortic in situ perfusion (AC) was used. Retrospectively, 163 donor hepatectomies performed over a 20-month period were reviewed to analyze overall graft (APC n = 78, AC n = 85) and patient outcome. The global graft and patient survival rates were not significantly lower in the APC group, except for 3-month graft survival (APC 72%, AC 87%; P = 0.015). However, this could be unrelated to the technique. In a subgroup of 140 cases (APC n = 64, AC n = 76), a more detailed analysis was performed. Populations of donors and recipients were similar. The graft injury and the immediate graft function were not significantly different between both groups. A multivariate analysis shows that low donor weight (P = 0.007), donor hypernatremia (P = 0.014), and in situ portal perfusion (P = 0.045) were significant determinants of a higher postoperative peak of glutamic pyruvic transaminase. In summary, in this series, routine human liver procurement using exclusive aortic perfusion seemed to be at least as safe as using a combined aortic and portal perfusion technique. This simplified method may also represent some advantages for combined pancreas and intestinal harvesting in the future.
Abstract: OBJECTIVE: To evaluate the strategy of a combined diagnostic and therapeutic approach in children with intra-abdominal organ injury following blunt abdominal trauma. DESIGN: Retrospective clinical study. SETTING: Pediatric intensive care unit of an university hospital. PATIENTS: 38 children with documented intra-abdominal injury. INTERVENTION: Initial non-surgical treatment by a team of pediatric intensivists, radiologists and surgeons. MEASUREMENTS AND RESULTS: Physical examination, oriented blood and urine tests, plain abdominal film, abdominal ultrasound (US) and computed tomography (CT) with contrast. US documented intra-abdominal fluid in 30 and initial organ lesion in 14 out of 31 patients evaluated. Abdominal CT demonstrated the precise organ lesion in 34 out of 36 patients examined with solid organ lesion. Early laparotomy was needed in 7 because of severe shock, pneumoperitoneum and ruptured diaphragm, and delayed surgery in 6 patients. All 38 patients regained a normal life. CONCLUSIONS: The stepped diagnostic approach combined with initial non-surgical treatment by a team provided accurate diagnosis and appropriate treatment. Abdominal US, by demonstrating free intra-abdominal fluid is very sensitive to detect patients with intra-abdominal organ injury, CT scan with contrast is needed to give precise information of specific organ lesions.
Abstract: The wide application of liver transplantation in children is hampered by the shortage of size-matched pediatric donors; this results in high mortality rate on the waiting list, a long waiting time, worsening of the clinical condition of the waiting patient, deterioration of the overall results, and an increase in the cost. Reduced-size liver transplants have been shown to be a safe way to alleviate the shortage of size-matched organs. We have retrospectively analyzed the impact of the reduced-size liver transplants on the waiting list and the results in a consecutive series of 314 transplants performed in 261 children over an 8-year period (1984-1991). Among these 314 grafts, 160 (51%) were innovative techniques including 86 reduced livers (stricto senso), 66 partial livers (with preservation of the recipient vena cava), and 8 split livers. Such an extensive use of these technical variants allowed a sharp decrease in the waiting list mortality: from 14.9% between 1984 and 1989 to 6.6% in 1990 and 5% in 1991; the corresponding figures for infants registered under the age of 1 year were 25%, 13.3%, and 8.3%, respectively. Results obtained with a full-size graft or a technical variant were similar regarding surgical complications (with a significantly lower incidence of arterial thrombosis for the reduced transplants), graft loss, and patient survival. The 5-year survival of the whole group was 78.1% without any significant difference regarding type of transplant, indications (with the best results: 89.4% 5-year survival obtained in 41 children grafted for metabolic diseases), or age (the 5-year survival was 82.2% for the 41 infants transplanted under the age of 1 year, 78.9% for the 124 children transplanted between 1 and 3 years, and 81.3% for the 96 children transplanted between 6 and 15 years). This series of reduced-size liver transplants, which is the largest worldwide single institutional experience, confirms that the extensive use of reduced transplants in children is safe; this study also shows that innovative techniques, including the split liver, allow a drastic decrease of the waiting list mortality of candidates in the pediatric age range without alterations of the results.
Abstract: A prospective trial was conducted to assess the efficacy of induction immunosuppression with antilymphocyte monoclonal antibodies in 129 primary liver transplant patients who were randomly divided into three groups according to immunosuppression during the first 10 days post-OLT: triple drug therapy only (TDIS: cyclosporine, steroids, azathioprine) (group I: n = 42); TDIS with a 10-day course of OKT3 (group II: n = 44); and LO-Tact-1 (anti-IL-2 receptor mAb) (group III: n = 43). Biopsy-proved acute rejection (AR) was treated using the same biopsy-guided protocol in the 3 groups. One-year patient survival rates were 67%, 84%, and 93% in groups I, II, and III, respectively (I vs. II, NS; I vs. III, P = 0.001; II vs. III, P = 0.044). Incidences of AR were studied in the subgroup of 100 patients who were exposed to the risk of developing rejection, with an overall rate of 89% during the first 3 months post-OLT, similar in the 3 groups. However, incidences of steroid-resistant rejection diagnosed during the 10 first days post-OLT were 54%, 24%, and 34% in groups I, II, and III and 46%, 26%, and 11%, respectively, during the 10-90 days interval. Sixteen patients with CMV had received OKT3, whereas the 5 remaining CMV cases had not (P = 0.019). In summary: (1) mAbs did not modify crude incidence of AR; (2) in the early period (< 10 days), TDIS immunoprophylaxis combined with OKT3 was more efficient than TDIS alone; (3) when compared with groups I and II, LO-Tact-1 apparently better prevented steroid-resistant rejection during the 10-90 days post-OLT; (4) OKT3 significantly increased incidence of CMV infection. In conclusion, TDIS with LO-Tact-1 seemed to achieve the better risk-benefit ratio in induction immunosuppression after OLT.
Abstract: The serum monoethylglycinexylidide (MEGX) level 15 min (t15) after i.v. administration of lidocaine (1 mg/kg) in liver donors was retrospectively correlated with graft outcome and early hepatic function. Among the 35 orthotopic liver transplants studied, 4 recipients had to be retransplanted within 10 days post-OLT because of early graft nonfunction or dysfunction, and 3 recipients died, with a median (range) donor MEGX t15 (ng/ml) of 100 (86-119) and 169 (146-182), respectively. The remaining 28 OLT patients living with functioning grafts had a donor MEGX of 87 (18-245). No significant correlations could be found between donor MEGX t15 and recipient mean and peak glutamic-oxaloacetic and -pyruvic transaminases, total serum bilirubin, or mean and minimum prothrombin time values studied from day 1 to day 5 post-OLT. Moreover, categorization of donors using the MEGX t15 cut-off point of 80 ng/ml could not predict liver graft quality, as previously suggested. In summary, MEGX t15 in liver donors correlated neither with graft outcome nor with early functional parameters. Accordingly, the MEGX test should not be used as an isolated discriminatory evaluation for organ utilization.
Abstract: The authors report their experience of liver transplantation for metastatic tumor in 6 patients. Although good palliation can be offered with prolonged survival in some patients, secondaries of the liver remain the poorest indication for liver transplantation. A prospective multicentric study would be needed to evaluate the usefulness of post-transplantation chemotherapy.
Abstract: Orthotopic liver transplantation (OLT) has been proposed to treat patients with type IV glycogenosis because of early progressive cirrhosis. Reports have shown absence of disease progression in other organs after OLT and even regression of cardiac amylopectin infiltration in one case. We describe a 15-month-old child in whom a liver transplant was performed for type IV glycogenosis. There were no clinical signs of extrahepatic disease before OLT. Nine months later, the patient developed progressive cardiac insufficiency and died from cardiac failure. Because of massive amylopectin deposits, decreased myofibrils in cardiac cells, and exclusion of other causes of cardiac failure, death was attributed to amylopectionosis. Our observation contrasts with the Pittsburgh experience and suggests that cardiac amylopectionosis may progress after OLT.
Abstract: Since the first laparoscopic cholecystectomy performed in 1987 by Philippe Mouret in Lyon (France), there has been a real revolution in the field of visceral surgery: more and more operations are performed by this mini-invasive surgical method: lithiasis of the common bile duct, Nissen and Heller procedure, truncal vagotomies, abdominal and thoracic, supra-selective vagotomies, hernia, appendectomy, band sections during intestinal occlusion, resection of the colon and rectum, oesophagectomies ... In Belgium, more than 3,000 cholecystectomies have been listed in a national registry in which the modalities and complications of this laparoscopic approach have been scrutinized. During the years to come, there will be an important technological development which will make this procedure easier, safer and quicker. Consequences of this new approach cannot completely be foreseen but there are some drawbacks: possible simplification of well established surgical techniques in order to facilitate the laparoscopic approach, causing a deterioration of the long term results, teaching and training difficulties for young and older surgeons, very costly equipment.
Abstract: The influence of ABO-compatibility was reviewed in 70 emergency orthotopic hepatic transplantations (OHT) performed at our institution in 60 highly urgent recipients between February 1984 and March 1989. Thirty-eight were ABO-identical (Id); 16, compatible (Comp), and 16, incompatible (Inc) transplants, respectively. The three groups did not differ statistically with respect to the indications, the adult/child ratio and the proportions of first OHT and retransplantations. Graft survival rates of ABO-Id, ABO-Comp and ABO-Inc OHT at one year were 47, 38 and 19 per cent, respectively (p less than 0.02). Incidences of perioperative mortality, arterial thrombosis and irreversible rejection were slightly (although not significantly) higher in the ABO-Inc group. Retransplantation rates were 19, 7 and 36 per cent in the ABO-Id, Comp and Inc groups, respectively. Patient survival rates at one year were 59 per cent for the ABO-Id group versus 43 per cent for both ABO-Comp and Inc combinations (NS). The results of this series of highly urgent OHT confirm that graft survival is lower with ABO-Inc livers; their use should be strictly considered as a short term life-saving procedure. Improvement of patient survival after a first urgent ABO-Inc OHT may require an aggressive policy of retransplantation.
Abstract: An acute or fulminant adenovirus hepatitis developed in 5 of 224 pediatric patients who were recipients of orthotopic liver transplants. All had received prednisolone, azathioprine, and cyclosporine as basal immunosuppression, and four received monoclonal (OKT3) or polyclonal (antithymocyte globulin) antibodies for steroid-resistant rejection episodes. These patients initially had high fever and a worsening condition for a mean of 73 days after transplantation (range 44 to 140 days). Results of biochemical tests showed very high serum levels of lactate dehydrogenase. Aspartate aminotransferase values were always markedly more elevated than those of alanine aminotransferase. Two patients had severe leukopenia. Results of histologic studies of the liver showed extensive areas of confluent necrosis and targetlike hepatocyte nuclei. Typical intranuclear viral inclusions were observed on electron microscopy. Adenovirus was cultured in all patients and in two relatives. Two patients died of liver failure; others recovered after cessation of immunosuppression. We conclude that adenovirus hepatitis can be fatal in liver transplant recipients. There is no specific treatment, and immunosuppression must be discontinued.
Abstract: Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in children. The polysplenia syndrome anomalies, which occur in approximately 10% of children with biliary atresia, may represent special difficulties at liver transplantation. We have reviewed our experience with this syndrome in 116 children with biliary atresia who underwent liver transplantation between March 1984 and December 1989. The main features of the polysplenia syndrome, which included absence of the inferior vena cava, preduodenal portal vein, midgut malrotation, aberrant hepatic artery, and situs inversus, were encountered in 12 of the 116 children (10.3%). Severe portal vein hypoplasia (3.5 mm or smaller) was also present in 7 of these children. Eight patients received a complete and four received a reduced liver graft. The vascular anomalies increased the technical difficulty of OLT but could be surmounted, although they did contribute to the peroperative death of one child. The 1-month survival rate was 83% for the 12 children with features of the polysplenia syndrome and 88% for the other 92 children with biliary atresia alone.
Abstract: 10 children who died suddenly during liver transplantation were found at necropsy to have extensive obstruction of small lung vessels by platelet aggregates. In 7 of these patients pulmonary artery pressure changes before death were consistent with acute obstruction of the pulmonary vascular bed. Platelet aggregates were not strikingly increased in blood vessels in other tissues. No single obvious cause for these unusual histological findings could be identified, although the presence of intravascular catheters, perioperative blood and platelet concentrate transfusions, and cellular debris from the liver forced into the circulation during surgery might predispose to platelet aggregation.
Abstract: The development of pediatric liver transplantation is considerably hampered by the dire shortage of small donor organs. This is a very sad situation because in most experienced centers, liver replacement can offer a long-term hope of survival of more than 70% in a growing variety of pediatric liver disorders. The reported experience with 54 reduced-size grafts on a total of 141 transplants performed in 117 children between 1984 and 1988 demonstrates that the technique of reduced-size liver transplantation not only allows long-term survival but, in fact, offers the same survival hope with the same quality of liver function, regardless of the child's age and clinical condition. The prominent feature of our experience with the reduced liver concerns its deliberate use for elective cases. Seventy-seven per cent of the 30 children who electively received a reduced liver were alive 1 year after transplantation, as were 85% of the 62 children who received a full-size graft. There is no difference in the long-term survival rate of patients who received elective grafts, which is in the range of 75% with both techniques.
Abstract: Of 139 children who received an orthotopic liver transplant in our center between March 1984 and July 1989, a total of 17 patients (12%) had transplants before their first birthday (mean age 10.3 months; range 8 to 11). The mean weight was 7.3 kg (range 5.2 to 13). Nine retransplantations were performed in five children because of primary nonfunction (three children), hepatic artery thrombosis (four), or rejection (two). A reduced donor liver was used for 11 of 26 transplants. Baseline immunosuppression included cyclosporine, prednisone, and azathioprine with OKT3 or anti-thymocyte globulin for steroid-resistant rejection episodes. Survivors were discharged after a mean hospital stay of 47 days (range 22 to 87), and nonsurvivors died within a mean of 40 days (range 0 to 120). The 1 year actuarial survival rate was 64.7%, in comparison with 75.8% in the whole series. One patient died perioperatively, two died from primary nonfunction, one from adenovirus infection, two from rejection, and one from bone marrow aplasia. Eighteen rejection episodes, of which 11 were steroid resistant, occurred in 11 patients. Our series shows that liver transplantation can be successful in this age group.
Abstract: Extreme scarcity of small pediatric donors makes a search necessary for technical variants to benefit infants and small children from the larger group of potential adolescent and adult donors. Three such technical variants are available for orthotopic transplantation. The reduced-size graft allows a weight ratio between donor and recipient of up to 4 to 6. The segmental graft allows transplantation of segments of livers from adult donors into infants and small children of up to a weight ratio of 8 to 9. The technique of the split liver, whereby one single donor liver is divided in such a way as to obtain two viable grafts for transplantation into two different recipients, is the most recent technical variant used to increase the flexibility of liver replacement and maximize the use of the donor liver pool. We report herein our two first cases of split liver with transplantation in four different recipients, with two long-term survivors. The described technique can also be useful in urgent adult transplantation.
Abstract: The children's liver transplantation program at the University of Louvain Medical School in Brussels has been organized with a multidisciplinary pediatric approach. The age distribution of the first 139 patients transplanted between March 1984 and June 1989 is characterized by the distinct preponderance of infants and small children (62.5% younger than 3 years, 16 younger than 1 year). Biliary atresia unalleviated by the Kasai portoenterostomy or its modifications was the single most frequent indication (101 cases) followed by the heterogenous group of metabolic diseases (17 cases). Two children underwent combined liver and kidney transplantation. A prominent feature of this series is the routine use of the reduced-size liver (40% of the 171 grafts) to alleviate the shortage of size-matched pediatric donors. The actuarial survival rate of the 139 children was 75.8% at 1 year and 72.4% at 2 years and thereafter. For patients who received 1 graft electively, the 1-year survival rates were 85.2% and 92.5% for those who received a full-size or a reduced-size liver with the same proportion (83%) of long-term surviving patients having normal liver tests. Long-term survival rates were not influenced by age, except for infants younger than 1 year with 62.4% surviving at 1-year posttransplantation. This latter group included a vast majority (14 of 16) of severely debilitated biliary atresia cases in preterminal condition. Graft loss from rejection was kept at a low rate of 5.2% (acute in 5-2.9% and chronic in 4-2.3%).
Abstract: Stenosis of the suprahepatic inferior vena caval anastomosis is a rare but serious vascular complication after liver transplantation. It may cause significant obstruction to venous drainage from the allograft liver and result in the Budd-Chiari syndrome with massive ascites and pleural effusion causing respiratory compromise. The authors report two such cases in which percutaneous transluminal angioplasty (PTA) of the stenotic anastomosis was performed. This nonsurgical approach resulted in resolution of ascites, pleural effusion, and respiratory distress in both patients. They conclude that PTA is a therapeutic alternative with minimal risk compared with surgical repair or retransplantation and should be considered the initial treatment of choice in selected patients.
Abstract: This report reviews the results of some paediatric surgical departments and points out the unsolved problems in biliary atresia disease. The authors conclude that a 5-year survival rate of 60% may be achieved in long-term follow-up, but a complete cure is observed only in 30%. Children who develop a cirrhosis and portal hypertension without or in spite of bile flow can benefit only by liver transplantation. As a result of long-term clinical experience conditions are defined that should be taken in consideration in the surgical treatment of bile duct atresia. In respect of liver transplantation the disadvantages of an external bile draining fistula to prevent cholangitis, an extensive mobilisation of the liver for HPE procedure, and the disadvantages of reoperation are discussed. By avoiding these disadvantages liver transplantation procedure will be facilitated and a 1-2 year survival rate of 80% may be achieved.
Abstract: Pediatric liver transplantation in Europe has expanded rapidly during the last four years. The survival rate of the 254 children less than 15 years recorded in the European Registry on December 31, 1987 was 68% at one year and 61% at three years; nineteen centers have contributed to this activity, of which 11 had performed less than 5 cases each while two thirds of the experience was concentrated in three centers (Brussels, Cambridge, Hannover). The results obtained in the first 100 children (65% were younger than 3 years) who received a liver graft at the University of Louvain Medical Center in Brussels between March 1, 1984 and July 31, 1988 are reported. The survival rates (79% at one year and 73% at three year) which do not differ with regard to the age, the indication of the technical modalities (whole liver or reduced size livers) are strongly influenced by the clinical condition (84% vs 50% at one year in elective and emergency transplantations respectively). One third of the 122 grafts transplanted by the authors were reduced livers harvested from older and often adult donors. This technique provides results of equal quality and does not entail an increased rate of technical complications; on the contrary, the incidence of arterial thrombosis has been significantly reduced. Transplantation of a reduced size liver is safe and should be recommended even in elective conditions, in view of the dire shortage of small pediatric donors.
Abstract: 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.
Abstract: The authors analyse the records of 60 children who had a failed Kasaï procedure and were referred for liver transplantation between 1984 and 1986. By the end of 1987, 45 had been transplanted, eight had died before transplantation, four had been excluded while three were still waiting for a potential donor. Actuarial survival at 2 and 3 years of the 30 children with a follow-up greater than one year is 79 +/- 8%. Nowadays, the surgical therapy of biliary atresia should include liver replacement. The original porto-enterostomy (one Roux-en-Y loop, no stoma) according to Kasaï should remain the first surgical procedure performed under 8 weeks by a trained surgeon. Good long-term results can be expected in 30 to 40%. In case of straight failure, liver replacement should be recommended in early age and, in case of delayed failure, before the age of 6 to avoid chronic disabling.
Abstract: An inquiry among surgical residents and recently formed surgeons was set up at two major university centers. The information was gathered from 72 departments with an officially accepted surgical training program. Major shortcomings were noted at both the theoretical and practice levels. The global impression of the recently trained surgeons shows moderate enthusiasm. The pedagogic value of several accredited surgical training programs must be questioned. A global evaluation at the end of the training program is also deemed indispensible. The strictly surgical curriculum of the surgeons recently trained in Belgium is totally insufficient when compared to that of those trained abroad. Suggestions to improve the surgical training program as a whole are given in detail.
Abstract: In a 9 month-old infant, who displayed an epileptic seizure, the Brain CT-Scan shows a ventricular enlargement and a bilateral pericerebral effusion, associated with a left parieto-temporal arterio-venous malformation. Angiogram reveals a small angioma shunting the blood flow from the left middle cerebral artery into the lateral sinus. Intracranial pressure, recorded with a fontanellar transducer, is borderline. The angioma is excised and the operation, during which the subarachnoid location of the pericerebral effusion is confirmed, is followed by gradual subsiding of the internal and external hydrocephalus, that was caused by enhancement of the pressure in the venous sinuses. This case belongs to an infantile form of Benign Intracranial Hypertension, in which CT-Scan has to be interpreted cautiously, to avoid the pitfall of a wrong diagnosis of brain atrophy.
Abstract: Liver transplantation has become a clinical therapeutic modality for end stage liver diseases. The results achieved in children are better than in adults: in T.E. Starzl unique experience in Pittsburgh, USA, the survival rate at one and four years are 75 and 70% respectively. Complete rehabilitation of these children can nowadays be expected. Between March 1984 and June 1985, 8 children received an orthotopic liver transplantation at the University of Louvain Medical School in Brussels, Belgium; one child received two transplantations after acute and irreversible rejection of a first ABO incompatible graft. The indications were biliary atresia in five (polysplenia in one), biliary hypoplasia in one, alpha-1-antitrypsine deficiency in one and Crigler-Najjar syndrome type I in one. The age of the patients at the time of liver replacement was 12 to 18 months in four, 8 to 13 years in four. Six patients are alive after 17, 14, 12, 10, 3 and 3 months; the two youngest children deceased during the first postoperative month. The Kaplan-Meyer one year survival rate is 75%; all surviving children are in excellent clinical condition with a normal liver function. The 9 transplanted livers were harvested from multiorgan cerebral death donors with the exception of one neonate whose liver alone was removed; 4 were retrieved locally, the five others were offered by foreign hospitals through the organ procurement agencies (Eurotransplant, France-Transplant, U.K. Transplant). Due to appropriate logistics with air flight transportation of the harvesting team when indicated, the total ischaemia time was kept below 6 hours in every case. Two small children underwent a left lobe orthotopic transplantation after ex vivo right trisegmentectomy of the liver retrieved from an older donor with one long term survival. The indications for liver transplantation in children are end-stage liver diseases consisting of a) cholestatic diseases among which the most frequent is biliary atresia after unsuccessful Kasai procedure followed by familial cholestasis (Byler syndrome) and the paucity of the intrahepatic bile ducts of the syndromatic (Alagille syndrome) or non syndromatic type. b) the metabolic diseases resulting either in cirrhosis with liver failure (alpha-1-antitrypsin deficiency, Wilson disease, glycogen storage disease type I and IV, protoporphyria) or in extrahepatic complications of enzymatic deficiency of an otherwise normally functioning liver (Crigler-Najjar syndrome type I, familial hypercholesterolemia and perhaps oxalosis). c) the hepatocellular diseases either chronic with cirrhosis of various origin or acute, eg. toxic hepatitis.(ABSTRACT TRUNCATED AT 400 WORDS)
Abstract: Verneuil's disease is classically described as a chronic hidradenitis suppurativa of the apocrine sweat glands of the skin. It is characterized by the formation of recurrent abscesses of the subcutaneous tissues at the level of areas containing apocrine sweat glands. Extensive chronic inflammatory lesions of skin and subcutaneous tissues can evolve in multiple fistula. Occurrence in the perianal region is rather frequent (32% according to Goligher), but the lesions are often misdiagnosed. Fistula-in-ano are rare. When such is the case, fistula-in-ano are the consequences of a long evolution of the disease, the extension of the superficial lesions in the muscles of the anal sphincters or inappropriate surgical treatment. Five cases having undergone iatrogenic lesions are reported. Diagnosis is mainly a clinical one and has to be confirmed by pathological examination. Treatment is surgical and can bring healing if wide excisions of perianal lesions are conducted in single or multiple stages.
