E. R. Howard

Biliary atresia: The King's College Hospital Experience (1974–1995)

UNLABELLED The survival experience of 338 infants born with biliary atresia between January 1973 and December 1995 was analyzed. All the infants had their initial surgery at a single UK centre. These infants were divided into three groups based on year of birth; group 1 (1970s, n = 38); group 2 (1980s, n = 182), and group 3 (1990s, n = 118). The data from group 1 were incomplete and selected, and comparisons with the remaining groups were therefore restricted. However, all infants who had been treated since 1980 underwent portoenterostomy or hepaticojejunostomy and were included. RESULTS In the whole cohort there were 89 deaths (26%), 79 children (23%) who underwent liver transplantation and 170 children (50%) who were alive at last follow-up. The 5- and 10-year actuarial survival for group 2 was 50% and 41%, respectively and the 5-year actuarial survival for group 3 was 60%. Overall, 57 children have survived to 10 years after surgery for biliary atresia. There has been a progressive fall in the age at surgery from a median of 77 days in group 1, through 69 days in group 2 to 56 days in group 3 (P < .0001). However, there was no significant difference in outcome to 5 years between the age cohorts (< 40 days, 41 to 60 days, 61 to 99 days, and > or = 100 days; P > .1) for the infants treated since 1980 (n = 200). CONCLUSIONS Portoenterostomy is an effective long-term procedure for biliary atresia in about 40% to 50% of infants. The remaining 50% to 60% will require transplantation mostly within 2 years of age, although there is also a continuing need beyond 5 and 10 years. The age at surgery has limited usefulness as a predictor of survival after portoenterostomy and certainly should not be used to dictate primary treatment.

Choledochal cysts: lessons from a 20 year experience.

Cystic dilatation of the biliary tree is a rare congenital anomaly. To determine mode of presentation, diagnostic pitfalls, and long term outcome after surgery, 78 children (57 girls, 21 boys) with choledochal cyst treated between 1974 and 1994 were reviewed. Anatomical types were: Ic (n = 44), If (n = 28), IVa (n = 4), and V (n = 2); a common pancreaticobiliary channel was identified in 76% patients. Age at presentation ranged from 0-16 (median 2.2) years, six patients being diagnosed by prenatal ultrasonography. Of the 72 patients diagnosed postnatally, 50 (69%) presented with jaundice, associated with abdominal pain in 25 or a palpable mass in three, 13 (18%) presented with pain alone, and two (3%) with a palpable mass. The classic triad of jaundice, pain, and a right hypochondrial mass was present in only four (6%). Four children presented acutely after spontaneous perforation of a choledochal cyst, two presented with ascites and one cyst was discovered incidentally. Plasma and/or biliary amylase values were raised in 30 of 31 patients investigated for abdominal pain; seven had evidence of pancreatitis at operation. In 35 of 67 (52%) patients referred without previous surgery, symptoms had been present for more than one month, and in 14 of them for more than one year, before diagnosis. Delayed referral was due to misdiagnosis as hepatitis (n = 12), incomplete investigation of abdominal pain (n = 6), and failure to note the significance of ultrasonographic findings (n = 10). Two patients referred late died from liver failure. Of the 76 patients with type I or IV cysts, 59 underwent radical cyst excision and hepaticojejunostomy as a primary procedure and 10 as a secondary operation after previously unsuccessful surgery. Sixteen patients have been lost to follow up but most of the remainder are well after a mean period of 4.1 (0.1-13) years. Choledochal cysts are often misdiagnosed, but prognosis is excellent if radical excision is performed.

Antenatal diagnosis of congenital anomalies of the biliary tract

BACKGROUND The accuracy of the technique of antenatal ultrasonography in the diagnosis of congenital bile duct lesions is unknown. METHODS Thirteen patients with proven biliary disease who had abnormal antenatal scans were reviewed. Two infants had type I cystic biliary atresia and one had a noncommunicating segmental dilatation of the bile duct in a type 3 biliary atresia. The remainder had choledochal cysts and included two patients with intrahepatic cysts. The correct diagnosis was made antenatally in only two (15%) cases. Of the remaining patients, seven received a diagnosis of intraabdominal cysts of unknown etiology, three of duodenal atresia, and one ovarian cyst. The median gestational age at the antenatal diagnosis was 20 weeks. RESULTS Jaundice developed in 11 infants, and dilatation of intrahepatic biliary radicals was noted in four of the choledochal cysts. Obstructive jaundice and increasing cyst size were indications for early surgery, and twelve infants underwent a laparotomy at a median age of 4 weeks. During the median follow-up period of 2 years, 12 of the 13 patients have lost their jaundice or remained anicteric. Antenatal diagnosis offers the possibility of early definitive surgery for uncomplicated choledochal dilatation and the chance of improved outcome for surgically treated biliary atresia. An algorithm is suggested for the management of antenatally detected cystic biliary lesions.

Association between HLA and extrahepatic biliary atresia

The etiopathogenesis of extrahepatic biliary atresia (EHBA) remains undefined. There are clinical and pathological suggestions supporting the idea that EHBA could consist of at least two forms: the congenital (embryonic or fetal) and the acquired (perinatal) types. To test the hypothesis that susceptibility to this disease would be influenced by host genetic factors, we studied the human leukocyte antigen (HLA) system in 55 patients with and without major extrahepatic congenital anomalies. We found, especially in those without associated malformations, a significantly higher frequency of HLA-B12, of haplotypes A9-B5 and A28-B35, and of their disequilibrium values, as compared with the 8th International Histocompatibility Workshop controls. This study suggests that immunogenetic factors may play a role in determining susceptibility to EHBA, and the different HLA frequencies in those with and without anomalies lend support to the hypothesis that biliary atresia may be an etiologically heterogeneous disorder.

Endoscopic sclerotherapy in the management of esophageal varices in 61 children with biliary atresia

Sixty-one children who have survived 2.5 years or more after corrective surgery for biliary atresia were prospectively followed by endoscopy. Esophageal varices were detected in 41 patients (67%), 17 of whom (28%) had experienced episodes of variceal hemorrhage. Control of variceal bleeding was achieved by endoscopic injection sclerotherapy in all but one child who died from hemorrhage before the completion of treatment. Complications of the technique comprised episodes of bleeding before variceal obliteration (7), esophageal ulceration (5), and stricture (3). These resolved with conservative management and without long-term sequelae. During a mean follow-up period of 2.8 years after variceal obliteration, rebleeding from recurrent esophageal varices developed in only one child and responded to further sclerotherapy. These results are better than those following surgical procedures for portal hypertension in biliary atresia, and therefore endoscopic sclerotherapy is recommended as the treatment of choice.

Surgical outcome in biliary atresia: etiology affects the influence of age at surgery.

Objective:The exact nature of the relationship between age at Kasai portoenterostomy (KP) for biliary atresia (BA) and outcome is controversial. Methods:Single-center retrospective analysis of consecutive cases (January 1994–December 2005) undergoing KP, using 2 dichotomous measures of outcome (clearance of jaundice to <20 &mgr;mol/L and native liver survival at 2 years post-KP). Outcome was analyzed by age cohort (<30 days, 30–40 days, etc) and cumulatively. Data are quoted as median (interquartile range). Statistical analysis was by extended Fisher r × c analysis. P < 0.05 was regarded as significant. Results:Two hundred twenty-five infants with BA were divided into 3 groups based on possible etiology: isolated BA (n = 177), biliary atresia splenic malformation (BASM) syndrome (n = 28), and cystic BA (n = 23). Three infants had both BASM and a cyst. Age at KP was significantly greater in those with isolated BA [58 (48–61)] compared with both BASM [47 (39–59); P = 0.02] and cystic BA [47 (39–54); P = 0.02]. Overall, 127 (56%) cleared their jaundice and 145 (65%) survived to 2 years with their native liver. Children with isolated BA showed no statistical difference by age cohort for clearance of jaundice (P = 0.75) or for native liver survival (P = 0.14). In contrast, there was a marked detrimental effect of age at KP for both BASM and cystic BA groups (P = 0.02). Conclusion:There is a marked detrimental effect of age at KP on groups with a presumed “developmental” origin, not seen in the majority with isolated BA.

Results of surgical treatment for extrahepatic biliary atresia in United Kingdom 1980-2. Survey conducted on behalf of the British Paediatric Association Gastroenterology Group and the British Association of Paediatric Surgeons.

A postal survey identified 114 infants with biliary atresia (roughly one in 21 000 live births). Biliary operations were performed on 107. Of the 105 infants who were followed up, 35 were free of jaundice at 10 months to 3 1/2 years. Good results occurred most often in those operated on by 12 weeks and were also related to the number of cases operated on in each centre. Only two of 18 infants treated in centres dealing with one case a year were free of jaundice compared with 11 of 38 at centres treating two to five cases a year and 22 of 49 in a centre treating more than five cases a year. Jaundice in an infant of more than 2 weeks associated with yellow urine or pale stools is never physiological and requires urgent investigation to identify causes for which effective treatment may be possible. Identification of suspected cases by 4 weeks of age and a greater concentration of investigative and surgical skills should improve the short term results of surgery and the long term prognosis of biliary atresia.

Angiosarcoma of the liver in children

The clinico-pathological features of four cases of pediatric hepatic angiosarcomas are described. One case was initially diagnosed in infancy and underwent resection of a left-sided benign hemangioendothelioma of the liver. Further resection of a lesion in the right liver was followed by malignant transformation. Primary hepatic resection of the tumor was not possible in three other cases, and all received courses of chemotherapy without significant tumor shrinkage. One child underwent liver transplantation but died 4 months later of immunosuppression complications. The remaining three children died of disseminated malignancy. Histological verification of malignancy was difficult in three cases in which there was discrepancy between the rapid growth of the liver tumor and the microscopic features of benign hemangioendothelioma.

Hemangioendothelioma of the liver in infants

Hemangioendotheliomas are the most common type of hepatic vascular tumors that present in infancy. Eleven infants (nine boys, two girls) were referred for definitive management from 1970 through 1990. Ten were symptomatic, and the majority required intensive medical therapy because of cardiac failure. All were treated surgically. Three underwent partial hepatectomy for unilobar disease, and eight had ligation of the hepatic artery because of bilobar disease. There were two deaths (18%) in the early part of the series. Ligation of the hepatic artery was completely successful in controlling cardiac failure in six infants and was partially successful in one. There are two surgical options for treating symptomatic hepatic hemangioendotheliomata in infancy. Bilobar multifocal disease can be treated successfully by ligation of the hepatic artery; if localized, hemangioendothelioma can be resected, with rapid control of symptoms.

Chemotherapy Effects on Hepatoblastoma: A Histological Study

The histopathological features of hepatoblastoma in 17 patients treated with preoperative chemotherapy were compared with those in 11 patients not subjected to chemotherapy during the same 11-year period. Tumor necrosis was more extensive in patients receiving preoperative chemotherapy. Two tumors, however, were apparently unaffected by chemotherapy. There was no obvious correlation between the extent of necrosis and the number of courses of chemotherapy. There also seems to be no evidence of preferential ablation of a particular morphological type of tumor. The most notable feature in cases treated with chemotherapy was the extensive presence of osteoid. Osteoid was present in 36% of untreated cases, occupying < 5% of the surface area, compared with 82% in the treated group. In seven cases, osteoid occupied > 40% of the surface area. This finding raises speculation about the role of chemotherapy in the maturation of tumors that have an inherent ability to differentiate. A longterm study is needed to clarify the prognostic significance of mature heterologous elements in hepatoblastoma