Khalid Sharif

Biliary atresia in England and Wales: results of centralization and new benchmark

INTRODUCTION Biliary atresia (BA) is a rare, potentially life-threatening condition of the newborn presenting with conjugated jaundice. Typically, it is treated by an initial attempt to restore bile flow (the Kasai portoenterostomy [KP]) as soon as possible after diagnosis and, if this fails, liver transplantation. Since 1999, the treatment of BA has been centralized to 3 centers in England and Wales able to offer both treatment options. The aim of this study was to review the outcome of this policy change and provide a national benchmark. METHODS The management of all infants born within England and Wales during the period January 1999 to December 2009 was assessed using 3 key performance indicators such as median time to KP, percentage clearance of jaundice (≤20 mol/L) post-KP, and 5- and 10-year native liver and true survival estimates. Data are quoted as median (range), and P < .05 was considered significant. RESULTS A total of 443 infants had confirmed BA; and of these, most were isolated BA (n = 359), with 84 having other significant anomalies (but predominantly BA splenic malformation syndrome). Four infants died before any biliary intervention. Kasai portoenterostomy was performed in 424 infants (median age, 54 [range 7-209] days), and a primary liver transplant was performed in 15. Clearance of jaundice post-KP was achieved in 232 (55%). There were 41 deaths, including 4 (10%) without any intervention, 24 (58%) post-KP usually because of end-stage liver disease and mostly on a transplant waiting list, and 13 (32%) post-LT usually because of multiorgan failure. Overall, the 5- and 10-year native liver survival estimates were 46% (95% confidence interval [CI], 41-51) and 40% (95% CI, 34-46), respectively. The 5- and 10-year true patient survival estimates were 90% (95% CI, 88-93) and 89% (95% CI, 86-93), respectively. Outcome was worse for those with other anomalies (lower clearance of jaundice post-KP [43% vs 57%; odds ratio, 1.7; 95% CI, 1.04-2.8]; P = .02) and an increased mortality overall (eg, at 5 years, 72 [95% CI, 64-83] vs 94 [95% CI, 91-96]; χ(2) = 33; P < .0001). CONCLUSIONS National outcome measures in BA appear better than those from previously published series from comparable countries and may be attributed to centralization of surgical and medical resources.

Mesoportal bypass for extrahepatic portal vein obstruction in children: close to a cure for most!

AIM Extrahepatic portal vein obstruction (EPVO) is a common cause of portal hypertension in children and can lead to life-threatening bleeding, thrombocytopenia, and coagulation disorders. Mesoportal bypass (MPB) restores normal physiologic portal flow to the liver and corrects portal hypertension. There is, however, little long-term outcome data after MPB. The aim of our study was to analyze the long-term outcome after MPB in children. METHODS Retrospective single-center review of all MPB with more than 5-year follow-up was performed in children between 1998 and 2003. RESULTS Thirty children underwent MPB, which was successful in 29. Long-term follow-up is available for 24. Median age at the time of bypass was 8.5 years (range, 0.4-14.2 years). Material used for bypass was as follows: left internal jugular vein (n = 20), recanalized umbilical vein (n = 2), gastric vein, and a large colic vein (n = 2). Median time since MPB is 8 years (range, 5.3-8.8 years). One MPB using recanalized umbilical vein thrombosed at 4 months but was successfully refashioned using Gortex. One MPB with left internal jugular vein was thrombosed at 1 year after cardiac surgery. Overall, 23 of 24 children have a patent bypass and resolution of portal hypertension. All showed an decrease in spleen size. Recurrent blood flow in the cavernoma with secondary increase in spleen size occurred in 5 children (median time, 3.4 years after MPB). Further evaluation of these 5 revealed no recurrence of portal hypertension. CONCLUSION The MPB provides long-term correction of portal hypertension owing to EPVO. Where technically feasible, MPB is the preferred surgical procedure for treatment of EPVO.

Improved outcome of referrals for intestinal transplantation in the UK

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 µmol/l (p = 0.001, OR ratio 3.70, 95% CI 1.84 to 7.47). Earlier referral (median serum bilirubin 78 µmol/l in the post-1998 era compared with 237 µmol/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.

Management of end-stage central venous access in children referred for possible small bowel transplantation.

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.

Management of hepatic epithelioid haemangio-endothelioma in children: what option?

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.

Congenital, solitary, large, intrahepatic arterioportal fistula in a child: management and review of the literature.

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.

Phenotypic variation and long-term outcome in children with congenital hepatic fibrosis.

Background and Objective: Congenital hepatic fibrosis (CHF) and Caroli syndrome are frequently associated with renal cystic diseases. They have a variable clinical course, and the natural history is not well defined despite molecular advances. Our study describes the clinical manifestations and long-term outcome in children with this disorder. Methods: A retrospective case review of children with CHF at a single centre diagnosed on the basis of clinical features, radiological and endoscopic evidence of portal hypertension (PHT), and compatible histopathological findings. Children were categorised based on hepatic phenotype—group 1 (Caroli syndrome) and group 2 (CHF). Hepatobiliary as well as renal manifestations were recorded at presentation, and their evolution followed up until transplant or last follow-up. Results: There were 40 children (22 boys) with a median age of 1.3 years at clinical presentation. Fourteen of 40 (35%) children presented in the neonatal period with primarily renal disease, of whom 11 (78%) had Caroli syndrome (P = 0.02). Significant PHT with oesophageal varices was seen in 86%, with no difference in the incidence of gastrointestinal bleeding and varices between Caroli syndrome and CHF. Cholangitis developed in 10 of 40 (25%) and was more common in the Caroli syndrome group (P = 0.009). A higher proportion of children with Caroli syndrome developed chronic kidney disease (CKD) stage 3 and above as compared with CHF (85% vs 42%; P = 0.007). Twelve of 21 (57%) and 8 of 19 (42%) children in the Caroli syndrome and CHF groups required either combined liver-kidney or isolated liver transplant, with the most common indication for renal transplantation being end-stage renal disease (CKD5d) with or without advanced PHT or cholangitis. All 14 (100%) children with neonatal presentation developed CKD5d and required combined liver-kidney transplant before 14 years of age, whereas 77% of children presenting beyond the neonatal period survived without liver-kidney transplant (P < 0.001). Neonatal presentation was the best predictor of the need for transplant. Conclusions: Caroli syndrome is more likely to present in the neonatal period and these patients are more likely to develop CKD5d. CKD stage 3 or above with recurrent cholangitis is more common in Caroli syndrome presenting beyond the neonatal period and adds to the significant morbidity in these patients. Children presenting in the neonatal period have a more severe phenotype and should be considered early for combined liver-kidney transplant.

Staged abdominal closure after small bowel or multivisceral transplantation.

Sheth J, Sharif K, Lloyd C, Gupte G, Kelly D, de Ville de Goyet J, Millar AJ, Mirza DF, Chardot C. Staged abdominal closure after small bowel or multivisceral transplantation. 
Pediatr Transplantation 2012: 16: 36–40.

Impact of Change in the United Kingdom Pediatric Donor Organ Allocation Policy for Intestinal Transplantation

Background. Graft availability remains a problem in pediatric intestinal transplantation (IT), with most children waiting being less than 10 kg weight. In November 2004, wait-listed children in the United Kingdom were prioritized nationally to receive pediatric donor organs to improve donor availability for IT. We aimed to evaluate the impact of this change on the recipient population. Methods. Data regarding pediatric donor organ availability and allocation were accessed from the National Transplant database. Recipient demographics and outcomes were recorded from the Liver Unit database. Between 2001 and 2006, there were 228 pediatric donors in the United Kingdom (nonheart-beating donors were excluded), of which 39 livers were allocated to emergency super-urgent liver candidates. A total of six isolated intestine and 21 liver-intestine transplants (15 reduced size, six full grafts) were performed in the same period. Results. Since January 2001, there has been a progressive reduction in overall pediatric organ donation. Increasing awareness about IT has resulted in a significant increase in number of small bowel organs being offered (71.8% vs. 19.5%), although this has been associated with an increase in referrals for transplantation. Despite an increase in number of IT being performed (2.6 vs. 7.7 mean transplants per year), waiting list mortality still remains high in smaller children (<10 kg weight). No mortality was observed in larger children and in candidates for isolated IT. Conclusions. The new prioritization of the national pediatric donor allocation favoring IT has resulted in an increased number of procedures, without an impact on waiting list mortality for small children.

The role of endoscopic ultrasound for evaluating portal hypertension in children being assessed for intestinal transplantation.

Intestinal transplant is an established treatment of irreversible intestinal failure, unless complicated by advanced intestinal failure-associated liver disease, when liver-bowel transplant may be necessary. Finding at least moderate hepatic fibrosis or gastroesophageal varices (GOV) at oesophago-gastroduodenoscopy (OGD) has been an indication for combined transplantation. Endoscopic ultrasound (EUS) is a sensitive method for detection of GOV. We hypothesized that EUS would detect early GOV and decrease the need for liver biopsy. Sixteen children, median age 13 months (range, 7-88), being assessed for intestinal transplant underwent simultaneous OGD and EUS. In 9 of 16 patients the results of OGD and EUS were concordant, that is, both positive (2) or both negative (7) for GOV. In seven patients, GOV were only identified by EUS. Liver biopsy was avoided in four of these cases. EUS is superior to OGD for detecting GOV in children with intestinal failure-associated liver disease and results in fewer liver biopsies being necessary.