Daniele Alberti

Size reduction of the donor liver is a safe way to alleviate the shortage of size-matched organs in pediatric liver transplantation.

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 childs 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.

Direct bypassing of extrahepatic portal venous obstruction in children: A new technique for combined hepatic portal revascularization and treatment of extrahepatic portal hypertension

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.

Split-liver transplantation eliminates the need for living-donor liver transplantation in children with end-stage cholestatic liver disease.

Background. End-stage cholestatic liver disease (ESCLD) is the main indication for liver replacement in children. Pediatric cadaver–organ-donor shortage has prompted the most important evolutions in the technique of liver transplantation, in particular living-donor liver transplantation (LDLT) and split-liver transplantation (SLT). Methods. Between November 1997 and June 2001, 127 children with ESCLD were evaluated for liver transplantation, and 124 underwent 138 liver transplantations after a median time of 40 days. Causes of liver disease were congenital biliary atresia (n=96), Alagille’s syndrome (n=12), Byler’s disease (n=8), and other cholestatic diseases (n=8). Results. Ninety (73%) patients received a split-liver graft, 28 (23%) a whole liver, and 6 (4%) a reduced-size liver. Overall 2- and 4-year patient survival rates were 93% and 91%, respectively; the 2- and 4-year graft-survival rates were 84% and 80%, respectively. In split-liver recipients, 4-year patient and graft-survival rates were 91% and 83%, respectively; these were 93% and 78%, respectively, in whole-liver recipients and 67% and 63%, respectively, in reduced-size liver recipients. Retransplantation rate was 11%, whereas mortality rate was 8%. Overall incidence of vascular and biliary complication were 16% and 27%, respectively. Conclusions. SLT can provide liver grafts for children with ESCLD with an outcome similar to the one reported following LDLT, eliminating mortality while they are on a transplantation wait list. The need for pediatric LDLT should be reevaluated and programs of SLT strongly encouraged and supported at a national and international level.

Treatment of extrahepatic portal hypertension in children by mesenteric-to-left portal vein bypass: a new physiological procedure

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.

Feasibility and Efficacy of Transjugular Intrahepatic Portosystemic Shunt (tips) in Children

Objectives: Transjugular intrahepatic portosystemic shunt (TIPS) is a valuable tool in managing complications of severe portal hypertension (PH) in adults. In children, TIPS is regarded as a temporary and technically demanding procedure. We report the first paediatric series of TIPS and review its feasibility and efficacy in children. Methods: Children with severe PH that is unresponsive to nonselective &bgr;-blockers and endoscopic treatment were considered candidates for TIPS placement with an expanded polytetrafluoroethylene-covered Viatorr stent graft. Indications were cirrhotic PH, noncirrhotic PH, and portal vein thrombosis, in both native and transplanted livers. Results: Thirteen children were selected for TIPS between 2005 and 2010. The indications were bleeding in 8 (61.5%) and ascites in 5 (38.5%). TIPS was successfully placed in 11 children, median age 9.8 years (range 2.2–18) and median weight 30 kg (11.5–96). Two patients had a portal cavernoma and 3 had received split liver transplantation. Following TIPS, the portosystemic gradient decreased to 10 mmHg (5–15 mmHg) (P < 0.00001); PH complications resolved in 10 of 11 patients (91%); no patient developed clinical encephalopathy; and 3 patients required a TIPS revision. All of the shunts were patent at last follow-up (20.4 months, range 0.2–67) in 7 or liver transplantation (6 months, 1.5–33) in 4. Conclusions: Our results suggest that TIPS is feasible and effective in children with ascites or gastrointestinal bleeding unresponsive to medical and endoscopic treatment. TIPS should become part of the armamentarium that is used to manage PH complications in children, both in native livers and in transplanted grafts, as a bridge to transplantation and for long-term management.

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.

Adenomyomatosis of the Gallbladder in Childhood

Adenomyomatosis of the gallbladder (ADMG) is defined as an acquired disease characterized by localized or diffuse hyperplastic extensions of the mucosa into, and often beyond, the thickened gallbladder muscular layer (Rokitansky-Aschoffs sinuses). In recent years, attention has been drawn to its malignant potential. The occurrence of ADMG has never been reported in children. The authors report the case of a 5-year-old boy with symptomatic ADMG, who was successfully treated by laparoscopic cholecystectomy.

Results of a Stepwise Approach to Extrahepatic Portal Vein Obstruction in Children

Background: The management of extrahepatic portal vein obstruction (EHPVO) in children is controversial. We report our experience with a prospective evaluation of a stepwise protocol based on severity of portal hypertension and feasibility of mesoportal bypass (MPB). Methods: After diagnosis, children with EHPVO underwent surveillance endoscopies and received nonselective &bgr;-blockers (NSBBs) or endoscopic variceal obliteration (EVO) when large varices were detected. In patients who failed NSBBs and EVO, we considered MPB as first-line and shunts or transjugular intrahepatic portosystemic shunt (TIPS) as second-line options. Results: Sixty-five children, median age 12.5 (range 1.6–25.8), whose age at diagnosis was 3.5 (0.2–17.5) years, were referred to our unit. Forty-three (66%) had a neonatal illness, 36 (55%) an umbilical vein catheterisation. Thirty-two (49%) presented with bleeding at a median age of 3.8 years (0.5–15.5); during an 8.4-year follow-up period (1–16), 43 (66%) had a bleeding episode, 52 (80%) were started on NSBBs, 55 (85%) required EVO, and 33 (51%) required surgery or TIPS. The Rex recessus was patent in 24 of 54 (44%), negatively affected by a history of umbilical catheterisation (P = 0.01). Thirty-four (53%) patients underwent a major procedure: MPB (13), proximal splenorenal (13), distal splenorenal (2), mesocaval shunt (3), TIPS (2), and OLT (1). At the last follow-up, 2 patients died, 53 of 57 (93%) are alive with bleeding control, 27 of 33 (82%) have a patent conduit. Conclusions: Children with EHPVO have a high rate of bleeding episodes early in life. A stepwise approach comprising of medical, endoscopic, and surgical options provided excellent survival and bleeding control in this population.

Microemulsion formulation of cyclosporine in pediatric liver transplantation.

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.

Esophageal atresia: pre and post-operative management

Esophageal atresia is a relatively common congenital malformation occurring in 1:3000-4500 live births. Improvement in surgical, anesthetic and neonatal care has achieved a survival rate near 100% in infants weighing over 1500g and having no major cardiac problem. To achieve these outcomes, as well as a good surgical technique, careful preoperative management (early diagnosis, investigation of associated anomalies, suction of the upper pouch, prevention and treatment of gastric and bowel distension) and accurate postoperative care (postoperative analgesia and ventilation, management of trans-anastomotic and chest tube, prevention, early recognition and treatment of complications) are mandatory.