Fibrolamellar variant of hepatocellular carcinoma does not have a better survival than conventional hepatocellular carcinoma--results and treatment recommendations from the Childhood Liver Tumour Strategy Group (SIOPEL) experience.

PURPOSE: Fibrolamellar hepatocellular carcinoma (FL-HCC) and conventional hepatocellular carcinoma (HCC) cases in two consecutive paediatric HCC trials were analysed to compare outcome and derive treatment implications. PATIENTS AND METHODS: Data of 24 FL-HCC (24% PRETEXT IV) and 38 HCC (42% PRETEXT IV) cases from SIOPEL-2 and -3 (1995-1998, 1998-2006) were analysed. Patients were treated according to SIOPEL-2 and -3 high-risk protocol (carboplatin+doxorubicin alternating with cisplatin; seven preoperative, three postoperative cycles) or with primary surgery followed by chemotherapy as indicated. RESULTS: Thirteen of 24 FL-HCC (54%) and 32/38 HCC (84%) were initially treated with chemotherapy. Eight FL-HCC (33%) and five HCC patients (13%) had primary surgery. Partial response was observed in 31% of FL-HCC versus 53% of HCC patients (p=0.17). Complete resection was achieved in ten FL-HCC and seven HCC patients (p=0.08). Three-year event free survival (EFS) was 22% for FL-HCC versus 28% for HCC. Overall survival (OS) was not significantly different at 3 years follow up (42% for FL-HCC versus 33% for HCC, p=0.24). EFS/OS Kaplan-Meier curves did not differ significantly, with median follow up of 43 (FL-HCC) and 60 (HCC) months. No significant correlation was found between potential prognostic factors and OS. In the entire cohort nine out of 23 (39%) patients with complete resection or orthotopic liver transplantation versus 34/39 (87%) without successful surgical treatment, died. CONCLUSIONS: Long-term OS in FL-HCC and HCC is similar. With low response rates, complete resection remains the treatment of choice.

Histological and immunohistochemical revision of hepatocellular adenomas: a learning experience.

Light has been shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA) recognizing HNF1 α -inactivated HCA (H-HCA), inflammatory HCA (IHCA), and ß -catenin-activated HCA (b-HCA). We reviewed retrospectively our surgical HCA series to learn how to recognize the different subtypes histopathologically and how to interpret adequately their immunohistochemical staining. From January 1992 to January 2012, 37 patients underwent surgical resection for HCA in our institution. Nine had H-HCA (25%) characterized by steatosis and loss of L-FABP expression; 20 had IHCA (55.5%) showing CRP and/or SAA expression, sinusoidal dilatation, and variable inflammation; and 1 patient had both H-HCA and IHCA. In 5 patients (14%), b-HCA with GS and ß -catenin nuclear positivity was diagnosed, two already with hepatocellular carcinoma. Two cases (5.5%) remained unclassified. One of the b-HCA showed also the H-HCA histological and immunohistochemical characteristics suggesting a subgroup of ß -catenin-activated/HNF1 α -inactivated HCA, another b-HCA exhibited the IHCA histological and immunohistochemical characteristics suggesting a subgroup of ß -catenin-activated/inflammatory HCA. Interestingly, three patients had underlying vascular abnormalities. Using the recently published criteria enabled us to classify histopathologically our retrospective HCA surgical series with accurate recognition of b-HCA for which we confirm the higher risk of malignant transformation. We also underlined the association between HCA and vascular abnormalities.

Long term survival in two children with rhabdomyosarcoma of the biliary tract.

BACKGROUND: Due to low incidence, rhabdomyosarcoma (RMS) of the biliary tract poses numerous complex management problems especially in diagnosis and local therapy. PATIENTS: The two presented patients were diagnosed by biopsy, performed by laparotomy and endoscopic retrograde cholangiopancreatography (ERCP) respectively. Nearly complete tumor regression was achieved by chemotherapy and irradiation according to the CWS-protocol. Subsequent radical resection followed directly in one patient and after local relapse in the other. Both patients are in remission 13 resp. 4 years after diagnosis with a good quality of life. CONCLUSIONS: Even in well responding biliary rhabdomyosarcomas, surgery after chemotherapy and radiotherapy seems to be necessary. Adjuvant chemotherapy should be continued after hepatic lobectomy.

Living-related versus deceased donor pediatric liver transplantation: a multivariate analysis of technical and immunological complications in 235 recipients.

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.

Isolated liver transplantation in an infant with ultrashort gut.

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.

Orthotopic liver transplantation from a living-related donor in an infant with a peroxisome biogenesis defect of the infantile Refsum disease type.

Peroxisomal biogenesis defects include a number of severe neurodevelopmental disorders, among which infantile Refsum disease (IRD) occupies the mildest end of the spectrum. Although high docosahexaenoic acid (DHA) and low phytanic acid diets can correct some of the biochemical defects, they have not consistently altered the progressive course of the disease. We carried out orthotopic liver transplantation (OLT) in a mildly symptomatic 6-month-old infant who was a sibling of a severely neurologically impaired older sister. After transplantation the clinical course of this young child appeared much improved by comparison to her older sister. She walked alone at 4 years, had acceptable social interaction and had a noticeable recovery of audition. After transplantation her biochemical parameters were significantly improved: phytanic acid and very long-chain fatty acid (VLCFA) serum concentrations decreased. Abnormal bile acids disappeared from plasma. Although the OLT did not result in a cure of the disorder, the clinical and biochemical results suggest that OLT should be considered in mildly symptomatic patients.

The paediatric liver transplantation program at the Université catholique de Louvain.

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.

Adult liver transplantation at UCL: update 2002.

The authors present the results of a single centre study of 587 liver transplants performed in 522 adults during the period 1984-2002. Results have improved significantly over time due to better pre-, peri- and post-transplant care. One, five, ten and fifteen year actuarial survivals for the whole patient group are 81.2; 69.8; 58.9 and 51.2%. The high incidence of de novo tumors (12.3%), of cardiovascular diseases (7.5%) and of end-stage renal function (3.6%) should be further incentives to tailor the immunosuppression to the individual patient and to direct the attention of the transplant physician to the long-term quality of life of the liver recipient.

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.

Risk-adapted treatment for childhood hepatoblastoma. final report of the second study of the International Society of Paediatric Oncology--SIOPEL 2.

SIOPEL 2 was a pilot study designed to test the efficacy and toxicity of two chemotherapy (CT) regimens, one for patients with hepatoblastoma (HB) confined to the liver and involving no more than three hepatic sectors ('standard-risk (SR) HB'), and one for those with HB extending into all four sectors and/or with lung metastases or intra-abdominal extra hepatic spread 'high-risk (HR) HB'. SR-HB patients were treated with four courses of cisplatin (CDDP), at a dose of 80 mg/m(2) every 14 days, delayed surgery, and then two more similar CDDP courses. HR-HB patients were given CDDP alternating every 14 days with carboplatin (CARBO), 500 mg/m(2), and doxorubicin (DOXO), 60 mg/m(2). Two courses of CARBO/DOXO and one of CDDP were given postoperatively. Between October 1995 and May 1998, 77 SR-HB (10 of whom were actually treated with the HR protocol) and 58 HR-HB patients were registered and all 135 could be evaluated. Response rates for the entire SR-HB and HR-HB groups were 90% (95% CI 80-96%) and 78% (95% CI 65-87%), and resection rates were 97% (95% CI 87-99%) and 67% (95% CI 54-79%) including several children undergoing liver transplantation. For SR-HB patients, 3-year overall and progression-free survivals were 91% (+/-7%) and 89% (+/-7%) and for the HR-HB group 53% (+/-13%) and 48% (+/-13%), respectively. The short-term toxicity of these regimens was acceptable, with no toxic deaths. A treatment strategy based on CDDP monotherapy and surgery thus appears effective in SR-HB but, despite CT intensification, only half of the HR-HB patients are long-term survivors. For SR-HB patients, the efficacy of CDDP monotherapy and the CDDP/DOXO ('PLADO') combination are now being compared in a prospective randomised trial (SIOPEL 3).

Liver transplantation for hepatoblastoma: results from the International Society of Pediatric Oncology (SIOP) study SIOPEL-1 and review of the world experience.

BACKGROUND: For hepatoblastoma (HB) that remains unresectable by partial hepatectomy after chemotherapy, total hepatectomy with orthotopic liver transplantation (LTX) has been advocated as the best treatment option. The role of LTX in the overall management of HB is still, however, unclear. PROCEDURE: The results of LTX from the first study of HB by the International Society of Pediatric Oncology, SIOPEL-1, were analyzed. In addition, the world experience of LTX for HB was extensively reviewed. Twelve patients in the SIOPEL-1 study underwent a LTX. Median (range) follow-up at Dec. 31, 2001 was 117 months (52-125) since LTX. RESULTS: Overall survival at 10 years post-LTX was 85% for the seven children who received a "primary LTX" and 40% for the 5 children who underwent a "rescue LTX" after previous partial hepatectomy. In the world experience (147 cases), the overall survival rate at 6 year post-LTX was 82% for 106 patients who received a "primary LTX" and 30% for 41 patients who underwent a "rescue LTX." Multivariate analysis of patients undergoing primary LTX showed that only macroscopic venous invasion had a significant impact (P-value: 0.045 with a hazard ratio of 2.96) on overall survival. CONCLUSIONS: Orthotopic LTX has added a new dimension to the treatment of HB unresectable by partial hepatectomy. Because of the rarity of the disease and to optimize results, children with extensive HB should be treated in centers with surgical expertise in pediatric major liver resection and LTX, in close collaboration with pediatric oncologists, radiologists, and histopathologists.

Fifteen years single center experience in the management of progressive familial intrahepatic cholestasis of infancy.

Recent advances in genetics and in physiopathology of bile composition and excretion have clarified the understanding of progressive familial intrahepatic cholestasis (PFIC). The aim of the present study is to review the experience of our center in terms of diagnosis, management and outcome of 49 pediatric PFIC patients, belonging to the three classical subtypes described. We analyse the clinical, biological, and histological patterns and review the response to the medical and surgical treatment and the global outcome. The only clinical difference between the different subtypes of PFIC patients was the intensity of pruritus. Serum gamma-glutamyltransferase (GGT) and liver histology allowed to differentiate PFIC III from PFIC I and II patients. High levels of biliary bile acids in 2 low-GGT patients was associated with favourable outcome. Response to ursodeoxycholic acid (UDCA) varies from patient to patient and was not associated to a particular subtype of PFIC. In five patients of this cohort, external biliary diversion was performed without improvement. Transplantation is indicated whenever medical treatment fails to restore normal social life, growth and well being of the child and it is associated with excellent survival (> 90%).

Pediatric liver transplantation for biliary atresia: results of primary grafts in 328 recipients.

PURPOSE: The purpose of this study was to assess the overall results of recipients undergoing transplantation for biliary atresia (BA), according to age, surgical techniques, and transplant eras, and to identify the prognostic factors affecting outcome. METHODS: Between 1984 and 2000, 328 pediatric recipients with BA who underwent orthotopic liver transplantation (OLT) were reviewed. Median age at OLT was 1.5 years (range, 0.4-14.5 years). Kasai hepatoportoenterostomy (KHPE) had been previously performed in 285 (87%) children. Regarding surgical techniques, 125 (38%) children received a whole-liver graft, 128 (39%) received a reduced-size graft, 16 (5%) received a split-liver graft, and 59 (18%) received a living-related (LR) donor graft. RESULTS: Overall actuarial patient survivals were 87%, 83%, and 81% at 1, 5, and 10 years, respectively. One-year patient survivals in children undergoing transplantation at the different age ranges were 85% (under 1 year), 86% (1-3 years), 83% (3-6 years), 100% (6-10 years), and 100% (beyond 10 years) (not significant). One-year patient survivals for the different transplant eras were 75% (1984-1988), 85% (1989-1992), 93% (1993-1996), and 98% (1997-2000) (P=0.0001). Multivariate analysis demonstrated that pretransplant recipient weight (P=0.004), indication for OLT (P=0.083), and age at OLT (P=0.024) predicted patient survival. The type of baseline calcineurin inhibitor (tacrolimus) and the age at OLT (beyond 6 years) were significantly associated with a better graft survival. CONCLUSIONS: Best results in children undergoing transplantation beyond 6 years indicate the importance of performing a KHPE as the first therapeutic step in BA; innovative surgical techniques, particularly LR donor graft, allowed successful transplantation in infants with early failure of KHPE.

History of pediatric liver transplantation. Where are we coming from? Where do we stand?

The history of pediatric liver transplantation cannot be dissociated from one man, Thomas E. Starzl, whose pioneer efforts contributed more than anyone else to what has become a routinely successful clinical procedure. During the pre-cyclosporine era, the pediatric experience was confined nearly exclusively in Denver: first attempt in 1963, first success with survival beyond one year in 1967, cumulative experience with 84 pediatric cases in the pre-cyclosporine era (1967-1979) with a 2-year patient survival rate of 30%. The stampede for the development of other liver transplant centers came with the introduction of cyclosporine in the early eighties. Besides Pittsburgh, seven centers (Brussels, Cambridge and Hanover in Europe; Boston, Dallas, UCLA, Minneapolis in USA) had performed up to 1986 at least 20 pediatric liver transplants each with a long-term (>1 year) patient survival rate ranging between 57% and 83%. At the moment, a long-term patient survival rate in excess of 90% in elective patients -including infants - is commonly obtained in experienced centers. The shortage of size matched liver donors which was responsible for a high death rate on the cadaveric waiting list stimulated the development or technical innovations based on the segmental anatomy of the liver: reduced ('cutdown') liver graft, split graft and living liver transplantation. Challenging technical aspects in the recipient have been solved in order to reduce the incidence of surgical complications like outflow obstruction, arterial and portal thrombosis, and biliary problems. The indications of liver transplantation have been refined; regarding biliary atresia, which is the most frequent indication, a consensus has developed to propose a sequential strategy with a single attempt at hepatoportoenterostomy followed, when it fails, by liver transplantation. Some contra-indications accepted in the past are not currently valid with better understanding of the pathophysiology and/or increased clinical experience; such is the case of the hepatopulmonary syndrome. A major progress in preoperative management has been achieved through a multidisciplinary approach, particularly regarding nutrition and control of portal hypertension-related bleeding and ascites. Perioperatively, liver transplantation has derived benefit from the expertise of anesthetists managing babies with serious conditions and increased experience of the transplant surgeons regarding the knowledge of all the technical modalities, good strategy, technical skills and meticulous control of bleeding. It is well-recognized that children require more immunosuppression than adults. As in adults, the first breakthrough came with the introduction of cyclosporine which more than doubled the one-year patient survival rate. The next advance during the last decade was afforded by FK 506 - Tacrolimus which allows steroid withdrawal with the first year post-transplant in most patients. Besides its efficacy in reducing the incidence of rejection and absence of cosmetic side-effects, the steroid-sparing effect of Tacrolimus is of utmost importance to preserve the growth potential of children. The use of OKT-3 both for induction and treatment of rejection has been abandoned nearly universally because its use, cumulated with other immunosuppressants, resulted in a high incidence of lymphoproliferative disorder. In contrast, anti-IL2-receptor monoclonal antibodies, will most likely gain an increasing place in induction, with the availability of chimeric or humanized preparations. The side-effects of immunosuppression can endanger both the quality of life and the life expectancy; they are a special source of concern in pediatric recipients whose survival can be expected to be more than a few decades. Children would benefit most from the development of a marker able to identify the patients who have developed graft acceptance, allowing complete wearing of immunosuppression. Also they would benefit most from research protocols of tolerance induction. Since the vast majority of liver-transplanted children will have a reasonably normal life expectancy, the focus should be switched to their long-term rehabilitation and the assessment of their quality of life when they reach adulthood.

Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group.

PURPOSE: To improve survival and reduce operative morbidity and mortality in children with primary epithelial liver tumors by using preoperative chemotherapy, as well as to collect information on the epidemiology, natural history, and prognostic factors. PATIENTS AND METHODS: Forty children with hepatocellular carcinoma (HCC) were registered onto the Group for Epithelial Liver Tumors International Society of Pediatric Oncology's first study from January 1990 to February 1994. The outcome could be analyzed in 39 of those patients. Disease was often advanced at the time of diagnosis; metastases were identified in 31% of the children and extrahepatic tumor extension, vascular invasion, or both in 39%. Multifocal tumors were common (56%). Thirty-three percent of tumors were associated with hepatic cirrhosis. All but two patients received preoperative chemotherapy (cisplatin and doxorubicin). RESULTS: Partial response was observed in 18 (49%) of 37 patients; there was no response or progression in the remainder. Complete tumor resection was achieved in 14 patients (36%). Twenty patients (51%) never became operable. Overall survival at 5 years was 28%, and event-free survival was 17%. Most deaths resulted from tumor progression (26 of 28). Presence of metastases and pretreatment extent of disease system grouping at diagnosis had an adverse influence on overall survival in multivariate analysis. CONCLUSION: Survival for pediatric HCC patients is significantly inferior to that for children with hepatoblastoma. Complete tumor excision remains the only realistic chance of cure, although it is often prevented by advanced disease. The presence of metastases is the most potent predictor of poor prognosis. A prospective worldwide cooperation in the field of pediatric HCC should be encouraged to look for novel therapeutic concepts.

Unusual evolution of an Epstein-Barr virus-associated leiomyosarcoma occurring after liver transplantation.

We report the case of a child who developed, 2 yr after orthotopic liver transplantation (OLTx) for biliary atresia, a multi-focal hepatic tumor with lymphonodular metastases, identified as an Epstein-Barr virus (EBV)-associated leiomyosarcoma. Chemotherapy was given without tumor response. Subsequently, slow growth of the tumor was observed. Immunosuppression was tapered and stopped 9 yr after transplantation. At the present time, 12 yr after the discovery of the first hepatic lesions, the patient is alive and completely symptom-free, the abdominal masses are stable, and liver function tests are completely normal. Smooth muscle tumors are increasingly recognized in children with various immunodeficiencies occurring after organ transplantation. This unusual evolution of a clinically aggressive tumor into a stable disease after restoration of immunity confirms that the immune status of the patient is a crucial factor.

Elevated right ventricular pressures are not a contraindication to liver transplantation in Alagille syndrome.

BACKGROUND: Elevated right ventricle pressure resulting from pulmonary artery stenoses may affect outcome and survival after liver transplantation in patients with Alagille syndrome. METHODS AND RESULTS: Between 1984 and 1997, among 444 pediatric liver transplant recipients, 17 had liver transplantation for Alagille syndrome (mean age 3.5 years, range 1.2-13 years), mainly because of poor quality of life with intractable pruritus, and failure to thrive. All patients had pulmonary artery stenosis. In 10 patients considered to have elevated RV pressure on ECG and/or Doppler-echocardiography, a cardiac catheterization was performed before liver transplantation. Mean RV systolic pressure was 55 mmHg (median 49.5 mmHg, range 35-98 mm Hg), mean RV to left ventricular systolic pressure ratio 0.53 (median 0.53, range 0.29-0.78) with a ratio above 0.5 in 6 patients (median 0.66, range 0.5-0.8). All patients underwent successful liver transplantation. Five patients died 1 to 9 months after transplantation from noncardiac causes. In two of them, cardiac catheterization before transplantation showed a RV to left ventricular pressure ratio of 0.51 in one and 0.37 in the second. In the three others, echocardiography before transplantation estimated RV pressures below 0.5 systemic pressures. At follow-up (median 6 years, range 1.5-15 years), liver tests were normal in all, none complained of pruritus and body weight was normalized in 70%. None of the patients presented cardiac symptoms, arrhythmias, or worsening of their cardiac status. CONCLUSIONS: Liver transplantation can be performed safely in children with Alagille syndrome, even in the presence of elevated right ventricular pressure.

Sacrococcygeal teratoma: results of a retrospective multicentric study in Belgium and Luxembourg.

Eighteen patients, operated upon for sacrococcygeal teratoma in 7 different centres in Belgium and Luxembourg between 1992 and 1996, were reviewed. From an epidemiological point of view, this series compares very well to others. Although excellent results were obtained, with all patients surviving, some imperfection in diagnosis, timing of delivery and of operation, and in operative technique was observed. Therefore, it is stated that for optimal treatment of sacrococcygeal teratoma to be achieved, these cases should be treated in just a very few centres of neonatal surgery.