Biliary atresia associated with congenital structural anomalies

Biliary Atresia Associated With Congenital Structural By Hirofumi

Tanano,

Toshimichi

Hasegawa,

Hisayoshi Kawahara, Osaka, Japan

Background/Purpose: Although biliary atresia (BA) is rarely associated with other congenital anomalies, the presence of a distinct subgroup of patients with accompanying structural anomalies such as situs inversus, polysplenia, or portal vein anomalies has been postulated. The authors present 7 patients with this association. Methods: 7 (8.0%)

Of 87 patients with BA treated in the past 19 years, have had multiple congenital structural anomalies.

Results: These anomalies included situs inversus in 4, polysplenia in 5, preduodenal portal vein in 5, absent portal vein in 1, absent inferior vena cava in 2, malrotation of the intestine in 5, and congenital heart disease in 3 patients. In these 7 patients, hepatic por-toenterostomy (HPE) was performed at the age from 63 to 158 days with an average of 92 days. The por-ta hepatis was abnormal in position in 1 patient. The connective tissue at the porta hepatis was diminished in 6 patients. Histologically, liver fibrosis was mild in 2 and

A

LTHOUGH BILIARY ATRESIA (BA) is rarely associated with other congenital anomalies, the presence of a distinct subgroup with accompanying structural anomalies such as situs inversus, polysplenia-asplenia, or portal vein anomalies has been postulated.1-8 This subgroup of structural anomalies has been recognized as polysplenia syndrome and constitutes 10% to 25% of cases of BA.le8 BA patients with this association have been assumed to have obliteration of the extrahepatic bile duct caused by defective organogenesis in the early fetal period.2-8 However, exact pathogenesis of this subgroup is still unknown. There are some reports that find the results of Kasai’s hepatic portoenterostomy (HPE) are worse in BA patients with structural anomalies than in patients with BA alone.5 Other investigators have noticed no difference in the outcome for patients with or without associated anomalies.3~7~9 We describe 7 patients with BA and associated congenital structural anomalies and discuss the characteristic clinical aspects of this subgroup of BA patients. MATERIALS

AND

METHODS

Of 87 patients with BA treated at the Department of Pediatric Surgery, Osaka University Medical School from 1979 to 1998, 7 patients (8.0%) had multiple congenital structural anomalies in addition to BA. Four of the patients were boys and 3 were girls. The associated anomalies were identified by radiological, intraoperative, or postmorturn investigatrons. BA was diagnosed by abdominal ultrasonography, study of collected duodenal secretions, and hepatobiliary scintigraphy and was confirmed huma/

of Pediatric

Surgery,

Vol34,

No 11 (November),

1999: pp 1687-1690

Takashi

Sasaki,

Anomalies and Akira

Okada

moderate in 5 patients. Bile excretion was good initially in all patients but gradually diminished in 5 patients. Five patients had multiple episodes of cholangitis, followed by sepsis, liver failure, or cardiac failure and subsequently died at the age from 2 months to 6 years. Of the other 2 patients who underwent HPE recently, 1 is doing well and the other has had one episode of cholangitis. Conclusions: BA in association with other congenital structural anomalies may have a poor prognosis. These patients have poor bile secretion after HPE mainly because of delayed operation. J Pediatr Surg 34:1687-1690. Copyright o 7999 by W.B. Saunders Company. INDEX WORDS: Biliary atresia, lies, situs inversus, polysplenia, preduodenal portal vein.

congenital absent

structural anomainferior vena cava,

by obliteration of the extrahepatic bile duct at operation or by cholangiography. For definitive surgery, the remnant of the gallbladder and the common bile duct was dissected toward the porta hepatis, and the connective tissue including the remnant of the hepatic duct was transected at the porta hepatis. Five patients initially underwent a Kasai’s HPE modified with an external jejunostomy. The other two patients initially underwent a Kasai’s HPE without jejunostomy. We evaluated the initial symptoms, age at the time of diagnosis and operation, morphological findings of the porta hepatis, histopathologic findings of the excised connective tissue, biopsied liver specimens, and the postoperative clinical course of patients with BA with associated anomalies. For quantitative evaluation of the remnant bile ducts included in the connective tissue at the porta hepatis, the macroscopic amount and extent of the connective tissue and its continuity from the obliterated extrahepatic bile duct were observed intraoperatively, and histological measurement of the diameter of the maximum remnant bile duct was performed.

RESULTS

As shown in Table 1, observed anomalies included situs inversus in 4, polysplenia in 5, preduodenal portal vein in 5, absent portal vein in 1, absent inferior vena

From the Department of Pediatric Surgery, Osaka University Medical School, Osaka, Japan. Presented at the 32nd Annual Meeting of the Pacijc Association of Pediatric Surgeons, Beijing, China, May 9-14, 1999 Address reprint requests to Akira Okada, MD, PhD, Department of Pediatric Surgery, Osaka University Medical School, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan. Copyright o 1999 by WB. Saunders Company 0022-3468/99/3411-0024$03.00/O

1688

TANANO

Table 1. Congenital

Structural

Anomalies

With

Biliary

Patient

Situs

POIY-

Preduodenal

NO.

Inversus

splenia

PV

Absent PV

Absent IVC

of the Intestine

-

-

3

+ -

+ -

-

f -

+

-

-

+

4

+

+

+

-

+

5 6

f

+ + +

f + -

+

f -

+ -

-

1 2

7

Abbreviations:

+

IVC, inferior

*Ventricular septal defect. tDouble outlet right ventricle, ductus arteriosus, right-sided *Right-sided aortic arch.

was moderately diminished. In patient 4, the connective tissue was remarkably diminished. Histological examination of the excised connective tissue showed maximum diameter of the remnant bile duct to be greater than 300 pm in 2 (patients 4 and 6), but less than 150 pm in the remaining 5 patients. Histological examination of the biopsied liver showed moderate fibrosis in 5 (patients 1, 2,3,6, and 7) and mild fibrosis in 2 patients. The degree of proliferation of the small bile duct and cholestasis with bile plug was moderate in 4 (patients 2, 5, 6, and 7) and mild in 3 patients. Immediately after HPE, bile excretion was noted in all 7 patients. Thereafter, bile excretion remained good in 2 patients (patients 5 and 7) and their post-HPE minimum total bilirubin was 1.7 and 2.1 mg/dL, respectively. However, patient 5 had repeated ascending cholangitis and then required revision of the HPE twice. Four patients (patients 1, 2, 3, and 6) showed moderate bile flow with bilirubin ranging from 2.0 to 6.0 mg/dL. In patient 4, bile flow gradually diminished, and the lowest bilirubin level was 8.0 mg/dL, and the patient underwent revision of the HPE. Four patients (patients 1,2,4, and 5) had multiple episodes of ascending cholangitis, followed by sepsis and liver failure and subsequently died at the age of 2 months to 6 years. Patient 3 died of congestive heart failure at the age of 3 months. Patient 6 is doing well with final serum total bilirubin level of 3.0 mg/dL. However, patient 7 has had one episode of ascending cholangitis.

Atresia

Malrotation

+ vena

cava; PV, portal

common aortic

Cardiac Anomalies

+* +t +* -

+ + vein.

atrioventricular

canal,

patent

arch.

cava with azygous connection in 2, malrotation of the intestine in 5, and congenital heart disease in 3 patients. The initial symptoms of acholic stool and prolonged neonatal jaundice were noted from 0 days to 8 weeks after birth in the 7 patients. However, the patients were referred to pediatricians from 2 months to 5 months of age. In 2 patients (patients 2 and 3), examination and medical or surgical treatment of cardiac defects were performed before HPE. HPE was performed at the age from 63 to 158 days with an average of 92 days after birth (Table 2). Two patients (patients 2 and 6) underwent HPE after the age of 4 months (128 and 158 days, respectively). From the operative findings, the extrahepatic bile duct was of the noncorrectable type in all 7 patients. Despite association of situs inversus, preduodenal portal vein, or absent portal vein, the porta hepatis was identified in all 7 patients and located in almost normal position in 6 patients. It was abnormally located just below the round ligament in one patient (patient 4; Table 3). Continuity of the connective tissue from the obliterated extrahepatic bile duct was not found in patient 4, but it was present in the other 6 patients. In patient 2, the connective tissue at the porta hepatis was found broadly above the bifurcation of the portal vein and was considered almost normal. However, in 5 patients (patients 1, 3, 5, 6, and 7), the connective tissue was found in a narrow area around either the right or left portal branches, and the amount Table 2. Clinical

DISCUSSION

Among congenital structural anomalies associated with BA, splenic malformation such as polysplenia or asplenia has been known to be the most common.1,2,4-6 The polysplenia syndrome has been proposed as an example to represent distinctive components of the associated anomalies in patients with BA.2,5-7 It also has been reported that BA may have any of other several structural anomalies in addition to polysplenia.7,gJ0 We have used the term congenital structural anomalies instead of polysplenia syndrome to categorize the anomalies commonly associated in patients with BA. In the current Course

and Outcome

Lowest Age at

Patient NCL

Initial-HPE Id)

1 2 3 4

83 128 64 63 71

5 6 7

158 77

Post-HPE Bile SecretIon

ET AL

Post-HPE Serum Bilirubin Level (mg/dL)

Revision of HPE

Outcome (Follow-Up Period)

Moderate

6.0

None

Died (8 wk)

Moderate Moderate Poor Good Moderate Good

4.9 2.0 8.0 1.7 3.0 2.1

None None Once Twice None None

Died Died Died Died Alive Alive

(6 yr) (12 wk) (44 wk) (12 wk) (14 wk) (17 wk)

Cause of Death Hepatic Hepatic

failure failure

Cardiacfailure Hepatic failure Hepatic

failure -

BA AND

CONGENITAL

STRUCTURAL

ANOMALIES

1689

series, polysplenia, preduodenal portal vein, and malrotation of the intestine were the common associated structural anomalies. Although the etiology of BA is still unknown, it is widely presumed to be an inflammatory process involving the extrahepatic bile ducts in the late intrauterine or early neonatal period.7-11 According to many previous reports,1-7 the etiology of BA with congenital structural anomalies has been thought to be different from that in BA alone. Situs inversus, polysplenia, portal vein anomaly, absent inferior vena cava, or cardiac defect results from defective organogenesis at around 5 to 6 weeks of gestation.5-7sgJ0Extrahepatic bile ducts begin to grow from the primordial bud of the intestine at 5 weeks of gestation, followed by normal canalization at 6 weeks.‘* Therefore, etiology of BA with structural anomalies may be a part of defective organogenesis in the early fetal period. The operative outcome of the BA patients with associated anomalies varies according to several reports.3s5-gOf the current 7 patients, five (71.4%) have died. Silveria et al9 stressed that the delay of surgical operation contributed to the poor prognosis of this group of patients. The current patients underwent HPE at the age from 63 to 158 days with an average of 92 days. In one patient who underwent HPE at 128 days, a cardiac operation had been performed before HPE. The patient who underwent HPE at 158 days of age had a subsequent delay in evaluating jaundice. Performance of HPE within 60 days of birth has been shown to be an important positive prognostic factor.13J4 Despite the observation of extensive liver fibrosis at the time of HPE in BA patients with the structural anomalies in the other series8 which may be caused by delay of operation or defective organogenesis in the early fetal period, liver fibrosis was not extensive in any patient of the current series. This is consistent with some other reports.6,7J5 Other anomalies, especially cardiac defects, may have prognostic implications of their own.8 One of our patients with major cardiac defects died of congestive heart failure. Poor outcome is also related to imprecise identification of the porta hepatis during operation.3,g Bile drainage after HPE can be achieved by sufficient excision of the connective tissue or fibrous remnants of the hepatic duct, which usually is located broadly at the porta hepatis and may include minute channels communicating with the intrahepatic ducts.“J6 It is essential to mobilize both the right and left branches of the portal vein and excise all tissue lying above the bifurcation of the portal vein.11J6If the porta hepatis is not identified properly, excision of the connective tissue may be insufficient, and postoperative bile excretion may not be adequate.“J3 In the current series, despite association of situs inversus, preduodenal portal vein or absent portal vein, the porta hepatis was

1690

TANANO

present in all patients. Six were found in the normal location, and 1 was found just below the round ligament. The connective tissue at the porta hepatis was diminished in 6 of 7 patients. Although bile drainage was good immediately after HPE with resection of the connective tissue at the porta hepatis despite unusual anatomy of the porta hepatis, eventually bile flow diminished and jaundice recurred in 6 patients. Accurate detection of the porta hepatis during the operation and excision of the sufficient amount of the connective tissue at the porta hepatis is essential. Therefore, a Kasai HPE should be performed as early as possible, with every effort, instead of primary liver transplantation. Patients with BA with other congenital structural anomalies may have a worse outcome than patients with

ET AL

BA alone. This may be the result mostly of poor bile secretion after HPE caused by delayed operation. Early diagnosis and operation with accurate detection of the porta hepatis and excision of the sufficient amount of the connective tissue at the porta hepatis are important for obtaining good bile excretion. Even technically welldone HPE may not improve the outcome for these complex and difficult patients. ADDENDUM

Since completion of the manuscript, patient 6 died of pulmonary complications associated with intrapulmonary shunt and sepsis, and patient 7 has been listed for liver transplantation.

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