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Biliary atresia and the polysplenia syndrome: Its impact on final outcome
Biliary Atresia and the Polysplenia Syndrome: Its Impact on Final Outcome By J. Vazquez, J.C. Ldpez Gutierrez, M. G&mez, M. L6pez-Santamaria, J. Murcia, J. Larrauri, M.C. Diaz, P. Jara, and J.A. Tovar Madrid, Spain • Up to 25% of babies with biliary atresia (BA) bear associated malformations that most often cluster in the polysplenia syndrome (PS). This article examines the impact of associated PS on the final outcome of the authors" BA patients and the necessary modifications of surgical technique during orthotopic liver transplantation (OLT) in these patients. The authors studied 88 consecutive infants with biliary atresia operated upon during the 10-year period between 1984 and 1993. BUiary drainage was provided by a Roux-en-Y hepaticojejunostomy. OLT was performed in 38. Eleven infants (12%) had three or more components of PS: malrotation (11), preduodenal portal vein (11), polysplenia (10), situs inversus (4), absent inferior vena cava (3), cardiac defects (2), and anomalous hepatic artery supply (2). Bile drainage was achieved in 7/11 infants (63% versus 48% for regular BA patients) 5 of whom (45% versus 31%) are jaundice-free with a mean follow-up of 105 months. Three patients received transplants (2 from living-related donor) and are alive and well with normal liver function after a mean follow-up of 35 months. Overall survival was 72% in the BA plus PS and 66% in the BA group (P = not significant [NS]). Results show that long-term bile drainage in these PS patients can be achieved at least as often as in other BA patients (45% versus 31%) (P = NS) and indicate that Kasai operation remains the best initial choice. When OLT becomes necessary, attention to vascular anatomy is required to determine the feasibility of reconstruction. The absence of inferior vena cava may facilitate the implantation and reduce postoperative rena ! dysfunction because the vena cava is not occluded during the anhepatic phase. Copyright © 1995 by W.B. Saunders Company INDEX WORDS: Polysplenia syndrome; biliary atresia; liver transplantation.
XTRAHEPATIC biliary atresia is an obstructive
E anomaly of the extrahepatic biliary system. Its incidence is 1 per 10,000 to 15,000 live births. 1 The
cause of the anomaly, pathogenic mechanisms involved, and moment of production of the lesion are unknown. The incidence of associated malformations is as high as 25% of patients with extrahepatic biliary atresia, 2 suggesting that the disease probably is triggered in utero during organogenesis. The most common multiple malformation syndrome associated with biliary atresia is polysplenia syndrome, described by Helwig. 3 This syndrome consists of polysplenia, intestinal malrotation, absence of the inferior vena cava, situs inversus, preduodenal portal vein, abnormalities of the hepatic artery, and cardiac defects, among other abnormalities. The Kasai operation has been described as having a Journal of Pediatric Surgery, Vol 30, No 3 (March), 1995: pp 485-487
poor prognosis in patients with extrahepatic biliary atresia and polysplenia4; on the other hand, liver transplantation is complex and possibly contraindicated when portoenteroanastomosis fails, s We analyzed the clinical manifestations and outcome of a subgroup of 11 patients with extrahepatic biliary atresia and polysplenia syndrome who were treated using the Kasai operation and liver transplantation. We studied (1) the impact of polysplenia syndrome on the outcome of portoenteroanastomosis, and (2) the need for modifications of the conventional surgical technique of orthotopic liver transplantation in these patients. MATERIALS AND METHODS We reviewed the clinical material of 88 patients with extrahepatic biliary atresia treated over a 10-year period (1983 to 1993). Eleven patients (12.5%) had three or more components of the polysplenia syndrome: 11 malrotation, 11 preduodenal portal vein, 10 polysplenia, 4 situs inversus, 3 absent inferior vena cava, 2 cardiac malformation, and 2 abnormalities of the hepatic artery. Table 1 summarizes the clinical findings from this group of patients. All the patients diagnosed as possible extrahepatic biliary atresia underwent exploratory laparotomy. The Kasai operation was performed if the diagnosis was confirmed by intraoperative cholangiography. If the atresic situation of the gallbladder did not permit cholangiography to be performed, portoenteroanastomosis was established. The biliary plaque (porta hepatis) was identified, and portoenteroanastomosis was done using the Kasai technique. 6 In seven patients, the bilioenteric conduit was exteriorized to the left upper quadrant, below the mesocolon. All ostomies were closed within 12 weeks of operation if cholangitis did not occur. In the immediate postoperative period antibiotics (clindamycin/aminoglycosides) were given prophylactically, as well as phenobarbital and steroids for 5 days, followed by tapering-off of the dose. In cases in which biliary flow was not established, the patient was given a 5-day course of steroids and 15 days of prostaglandin E2 (Prostrin). If biliary flow was not established within the next 3 months of medical treatment, preoperative workup was begun for potential liver transplantation.
From the Department of Pediatric Surgery, Liver Transplant Section, Department of Pathology, and Section of Hepatology, Hospital Infantil "La Paz, "Madrid, Spain. Presented at the 41st Annual International Congress of the British Association of Paediatric Surgeons, Rotterdam, The Netherlands, June 29-July 1, 1994. Address reprint requests to Juan Vazquez, MD, Hospital Infantil "La Paz," Dpto. Cirugia Pediatrica, Seccion Trasplantes Digestivos, P/Castellana, 261, 28046, Madrid, Spain. Copyright © 1995 by W.B. Saunders Company 0022-3468/95/3003-0027503.00/0 485
486
V A Z Q U E Z ET A L
Table 1. Anomalies in 11 Patients With BiliaryAtresia and
T a b l e 2. C l i n i c a l Data and Results in 11 P a t i e n t s W i t h Biliary Atresia
Polysplenia S y n d r o m e
and Polysplenia Syndrome
Case 1
Sex
MR
PVPD
P
AIVC
Sl
CM
AHA
F
+
+
+
-
+
-
-
Age at Operation (d)
BF
Bi (rng/dL)
GOT/GPT (U/L)
LTx
+
0.6
90/154
-
Follow-Up
2
F
+
+
+
-
+
+
-
60
Alive, 6 yr
3
F
+
+
+
+
-
-
-
112
-
18.8
533/266
-
4
M
+
+
+
+
-
-
-
75
-
24
389/209
LDLTx
A l i v e , 12 m o A l i v e , 11 m o
Died
5
F
+
.
+
45
_+
11.1
247/223
LDLTx
6
F
+
+
+
+
-
+
-
72
+
20.2
419/335
LTx
7
F
+
+
+
-
+
-
+
67
+
0.7
146/282
-
8
F
+
+
+
+
-
-
-
60
+
0.3
117/t76
-
Alive, 6 yr
+
1.3
180/345
-
A l i v e , 10 y r
.
.
.
.
Alive, 7 yr A l i v e , 11 y r
9
F
+
+
+
+
-
-
-
44
10
F
+
+
+
-
+
-
-
42
-
11.4
192/190
-
Died
11
F
+
+
+
+
-
-
-
72
+
0.4
223/413
-
A l i v e , 12 y r
132
-
25.4
321/200
-
Died
A b b r e v i a t i o n s : F, f e m a l e ; M, m a l e ; M R , m a l r o t a t i o n ; PVPD, p r e e d u o d e n a l p o r t a l v e i n ; P, p o l y s p l e n i a ; A I V C , a b s e n t i n f e r i o r v e n a c a v a ; SI, situs i n v e r s u s ;
CM, cardiac malformation;
AHA, anomalous
hepatic
A b b r e v i a t i o n s : BF, bile f l o w ; Bi, b i l i r u b i n in s e r u m ; L T x , l i v e r t r a n s p l a n tation; LDLTx, living donor liver transplantation.
artery.
Three patients received liver transplants, one a complete liver transplant and two a segmental liver transplant, from live donors. In the complete liver transplant the absence of the vena cava required distal ligature of the donor retrohepatic vena cava. In the two cases of segmental liver transplantation from live donors, ligature of the retrohepatic vena cava was not necessary because the left lateral liver segment with its hepatic vein draining segments II and III was used. Because of severe portal hypoplasia in two cases ( < 2.5 mm), a wide dissection to the confluence of the mesenteric and splenic veins was performed. In the two segmental liver transplants from live donors, a saphenous vein graft was taken from the donor to lengthen the left portal branch. To arterialize the hepatic segments, a saphenous vein graft was interposed between the left hepatic artery and infrarenal aorta. In all three liver transplants the bile ducts were reconstructed by jejunal bypass using the intestinal loop used previously for Kasai portoenteroanastomosis. Our immunosuppression protocol consisted of a triple therapy of azathioprine, cyclosporine, and corticoids. We used cytomegalovirus prophylaxis consisting of gancyclovir, as well as antibiotic prophylaxis of vancomycin and azactan in the first 48 hours.
The realization of liver transplantation in the absence of a retrohepatic vena cava was not more difficult than conventional transplantation. In the two cases of segmental liver transplantation, there were no disturbances in kidney function because renal venous return flow did not have to be interrupted during the operation (Fig 1). One patient had an episode of corticoid-resistant rejection and required treatment with monoclonal antibodies (OKT3); the histological lesions did not remit completely. On day 21 posttransplantation, the patient presented with a systemic cytomegalovirus infection that was treated with gancyclovir. Deterioration of liver function required a segmental liver
RESULTS
Eight of the 11 patients are alive and well after a follow-up ranging from 30 to 144 months. Of the 8 survivors, 3 had liver transplants and 5 had Kasai portoenteroanastomosis. The 5 patients with satisfactory outcome after the Kasai operation are free of jaundice and have a mean serum bilirubin concentration of 0.6 mg/dL (range, 0.3 to 1.3) after a mean follow-up of 105 months. Table 2 summarizes the clinical findings and results from this group of patients. The three deaths were caused by liver failure secondary to failure to reestablish bile flow after the first operation; two could not have a liver transplant because no liver transplant program existed at our center at the time (before 1986) and one patient died while waiting to receive a graft of suitable size for the patient's weight.
Fig 1. Angiogram of a 16-week-old jaundiced infant showing anomalous drainage through azygous system.
BILIARY ATRESIA & POLYSPLENIA SYNDROME
487
transplant with major blood group incompatibility ( A + / O + ) . The evolution of the new liver transplant was satisfactory, and the patient had normal liver function at the time of release from the hospital. The follow-up has lasted 11 months. The remaining two patients who received liver transplants are well and have normal liver function after follow-up periods of 84 and 12 months. Of the other eight patients, five are well and have normal or almost normal liver function without jaundice. None of them (ages 6, 6, 10, 11, and 12 years) are currently candidates for liver transplantation. We obtained excellent results with the Kasai operation in a group designated as high-risk. The results obtained with the Kasai operation (5/11) in terms of survival without jaundice were superior to those of other biliary atresia series (45% versus 31% for regular biliary atresia patients, P = NS). The patients who were received transplants are alive and well, but the series is too small to draw conclusions. DISCUSSION
The embryological aspects of this multiple malformation have been studied by Davenport 7 and Lilly. 8 According to these investigators, the embryological insult may occur around the fifth week of gestation in the group of patients with biliary atresia and polysplenia syndrome, although the existence of genetic factors cannot be excluded because polysplenia has familial incidence. 9
Our results confirm the opinion held by other investigators that the Kasai operation is an excellent option that yields results that are similar or superior to other operations in patients with biliary atresia. Liver transplantation has become consolidated as an important option when bile flow cannot be restored by portoenteroanastomosis. As other authors have shown, situs inversus, preduodenal portal vein, intestinal malrotation, and the absence of retrohepatic vena cava are not contraindications for this type of therapy. Our results with liver transplantation corroborate this opinion. One factor to consider in this group of patients is that most weighed less than 7 kg and there is a scarcity of donors of an adequate size. Our first experiences with liver transplantation from live donors are reason for hope of resolving these problems. However, the live donor technique entails risks because it involves submitting a healthy subject to a major surgical procedure. Although left lateral segmentectomy is a technique that has minimal risks, this type of transplant compromises a family's emotional stability and has important ethical connotations. To conclude, our data confirm that the Kasai operation is a viable option in patients with extrahepatic biliary atresia and polysplenia. The different modalities of liver transplantation (complete, reduced, or live donor) should be reserved for cases in which an internal biliary fistula cannot be created.
REFERENCES 1. Vhzquez J, Hern~ndez-Cano A, Diez-Pardo J, et al: Estado actual de la atresia biliar. An Esp Pediatr 26:407-409, 1987 2. Chandra RS: Biliary atresia and other structural anomalies in the congenital polysplenia syndrome. J Pediatr 85:649-655, 1974 3. Helwig FC: Multiple spleen combined with other congenital abnormalities. Arch Pathol 8:761-767, 1929 4. Davenport M, Savage M, Mowat A, et al: The biliary atresia-splenic malformation syndrome, in Ohi R (ed): Biliary Atresia. Professional Postgraduate Services, Tokyo, 1991, pp 11-14 5. Colomb K, Mizrahi S, Downes T, et al: Liver transplantation in patients with situs inversus. Transplant Int 6:158-160, 1993
6. Kasai M, Suzuki M: A new operative procedure (hepatic portoenterostomy) for uncorrectable type of the congenital biliary atresia. J Surg 13:733-739, 1959 7. Davenport M, Savage M, Mowat AP, et al: Biliary atresia splenic malformation syndrome: An etiologic and prognostic subgroup. Surgery 113:662-668, 1993 8. Karrer FM, Hall R, Lilly JR: Biliary atresia and the polysplenia syndrome. J Pediatr Surg 26:524-527, 1991 9. Niikawa N, Kohasaka S, Mizumoto M, et al: Familial clustering of situs inversus totalis and asplenia and polysplenia. Am J Med Genet 16:43-47, 1983
XTRAHEPATIC biliary atresia is an obstructive
E anomaly of the extrahepatic biliary system. Its incidence is 1 per 10,000 to 15,000 live births. 1 The
cause of the anomaly, pathogenic mechanisms involved, and moment of production of the lesion are unknown. The incidence of associated malformations is as high as 25% of patients with extrahepatic biliary atresia, 2 suggesting that the disease probably is triggered in utero during organogenesis. The most common multiple malformation syndrome associated with biliary atresia is polysplenia syndrome, described by Helwig. 3 This syndrome consists of polysplenia, intestinal malrotation, absence of the inferior vena cava, situs inversus, preduodenal portal vein, abnormalities of the hepatic artery, and cardiac defects, among other abnormalities. The Kasai operation has been described as having a Journal of Pediatric Surgery, Vol 30, No 3 (March), 1995: pp 485-487
poor prognosis in patients with extrahepatic biliary atresia and polysplenia4; on the other hand, liver transplantation is complex and possibly contraindicated when portoenteroanastomosis fails, s We analyzed the clinical manifestations and outcome of a subgroup of 11 patients with extrahepatic biliary atresia and polysplenia syndrome who were treated using the Kasai operation and liver transplantation. We studied (1) the impact of polysplenia syndrome on the outcome of portoenteroanastomosis, and (2) the need for modifications of the conventional surgical technique of orthotopic liver transplantation in these patients. MATERIALS AND METHODS We reviewed the clinical material of 88 patients with extrahepatic biliary atresia treated over a 10-year period (1983 to 1993). Eleven patients (12.5%) had three or more components of the polysplenia syndrome: 11 malrotation, 11 preduodenal portal vein, 10 polysplenia, 4 situs inversus, 3 absent inferior vena cava, 2 cardiac malformation, and 2 abnormalities of the hepatic artery. Table 1 summarizes the clinical findings from this group of patients. All the patients diagnosed as possible extrahepatic biliary atresia underwent exploratory laparotomy. The Kasai operation was performed if the diagnosis was confirmed by intraoperative cholangiography. If the atresic situation of the gallbladder did not permit cholangiography to be performed, portoenteroanastomosis was established. The biliary plaque (porta hepatis) was identified, and portoenteroanastomosis was done using the Kasai technique. 6 In seven patients, the bilioenteric conduit was exteriorized to the left upper quadrant, below the mesocolon. All ostomies were closed within 12 weeks of operation if cholangitis did not occur. In the immediate postoperative period antibiotics (clindamycin/aminoglycosides) were given prophylactically, as well as phenobarbital and steroids for 5 days, followed by tapering-off of the dose. In cases in which biliary flow was not established, the patient was given a 5-day course of steroids and 15 days of prostaglandin E2 (Prostrin). If biliary flow was not established within the next 3 months of medical treatment, preoperative workup was begun for potential liver transplantation.
From the Department of Pediatric Surgery, Liver Transplant Section, Department of Pathology, and Section of Hepatology, Hospital Infantil "La Paz, "Madrid, Spain. Presented at the 41st Annual International Congress of the British Association of Paediatric Surgeons, Rotterdam, The Netherlands, June 29-July 1, 1994. Address reprint requests to Juan Vazquez, MD, Hospital Infantil "La Paz," Dpto. Cirugia Pediatrica, Seccion Trasplantes Digestivos, P/Castellana, 261, 28046, Madrid, Spain. Copyright © 1995 by W.B. Saunders Company 0022-3468/95/3003-0027503.00/0 485
486
V A Z Q U E Z ET A L
Table 1. Anomalies in 11 Patients With BiliaryAtresia and
T a b l e 2. C l i n i c a l Data and Results in 11 P a t i e n t s W i t h Biliary Atresia
Polysplenia S y n d r o m e
and Polysplenia Syndrome
Case 1
Sex
MR
PVPD
P
AIVC
Sl
CM
AHA
F
+
+
+
-
+
-
-
Age at Operation (d)
BF
Bi (rng/dL)
GOT/GPT (U/L)
LTx
+
0.6
90/154
-
Follow-Up
2
F
+
+
+
-
+
+
-
60
Alive, 6 yr
3
F
+
+
+
+
-
-
-
112
-
18.8
533/266
-
4
M
+
+
+
+
-
-
-
75
-
24
389/209
LDLTx
A l i v e , 12 m o A l i v e , 11 m o
Died
5
F
+
.
+
45
_+
11.1
247/223
LDLTx
6
F
+
+
+
+
-
+
-
72
+
20.2
419/335
LTx
7
F
+
+
+
-
+
-
+
67
+
0.7
146/282
-
8
F
+
+
+
+
-
-
-
60
+
0.3
117/t76
-
Alive, 6 yr
+
1.3
180/345
-
A l i v e , 10 y r
.
.
.
.
Alive, 7 yr A l i v e , 11 y r
9
F
+
+
+
+
-
-
-
44
10
F
+
+
+
-
+
-
-
42
-
11.4
192/190
-
Died
11
F
+
+
+
+
-
-
-
72
+
0.4
223/413
-
A l i v e , 12 y r
132
-
25.4
321/200
-
Died
A b b r e v i a t i o n s : F, f e m a l e ; M, m a l e ; M R , m a l r o t a t i o n ; PVPD, p r e e d u o d e n a l p o r t a l v e i n ; P, p o l y s p l e n i a ; A I V C , a b s e n t i n f e r i o r v e n a c a v a ; SI, situs i n v e r s u s ;
CM, cardiac malformation;
AHA, anomalous
hepatic
A b b r e v i a t i o n s : BF, bile f l o w ; Bi, b i l i r u b i n in s e r u m ; L T x , l i v e r t r a n s p l a n tation; LDLTx, living donor liver transplantation.
artery.
Three patients received liver transplants, one a complete liver transplant and two a segmental liver transplant, from live donors. In the complete liver transplant the absence of the vena cava required distal ligature of the donor retrohepatic vena cava. In the two cases of segmental liver transplantation from live donors, ligature of the retrohepatic vena cava was not necessary because the left lateral liver segment with its hepatic vein draining segments II and III was used. Because of severe portal hypoplasia in two cases ( < 2.5 mm), a wide dissection to the confluence of the mesenteric and splenic veins was performed. In the two segmental liver transplants from live donors, a saphenous vein graft was taken from the donor to lengthen the left portal branch. To arterialize the hepatic segments, a saphenous vein graft was interposed between the left hepatic artery and infrarenal aorta. In all three liver transplants the bile ducts were reconstructed by jejunal bypass using the intestinal loop used previously for Kasai portoenteroanastomosis. Our immunosuppression protocol consisted of a triple therapy of azathioprine, cyclosporine, and corticoids. We used cytomegalovirus prophylaxis consisting of gancyclovir, as well as antibiotic prophylaxis of vancomycin and azactan in the first 48 hours.
The realization of liver transplantation in the absence of a retrohepatic vena cava was not more difficult than conventional transplantation. In the two cases of segmental liver transplantation, there were no disturbances in kidney function because renal venous return flow did not have to be interrupted during the operation (Fig 1). One patient had an episode of corticoid-resistant rejection and required treatment with monoclonal antibodies (OKT3); the histological lesions did not remit completely. On day 21 posttransplantation, the patient presented with a systemic cytomegalovirus infection that was treated with gancyclovir. Deterioration of liver function required a segmental liver
RESULTS
Eight of the 11 patients are alive and well after a follow-up ranging from 30 to 144 months. Of the 8 survivors, 3 had liver transplants and 5 had Kasai portoenteroanastomosis. The 5 patients with satisfactory outcome after the Kasai operation are free of jaundice and have a mean serum bilirubin concentration of 0.6 mg/dL (range, 0.3 to 1.3) after a mean follow-up of 105 months. Table 2 summarizes the clinical findings and results from this group of patients. The three deaths were caused by liver failure secondary to failure to reestablish bile flow after the first operation; two could not have a liver transplant because no liver transplant program existed at our center at the time (before 1986) and one patient died while waiting to receive a graft of suitable size for the patient's weight.
Fig 1. Angiogram of a 16-week-old jaundiced infant showing anomalous drainage through azygous system.
BILIARY ATRESIA & POLYSPLENIA SYNDROME
487
transplant with major blood group incompatibility ( A + / O + ) . The evolution of the new liver transplant was satisfactory, and the patient had normal liver function at the time of release from the hospital. The follow-up has lasted 11 months. The remaining two patients who received liver transplants are well and have normal liver function after follow-up periods of 84 and 12 months. Of the other eight patients, five are well and have normal or almost normal liver function without jaundice. None of them (ages 6, 6, 10, 11, and 12 years) are currently candidates for liver transplantation. We obtained excellent results with the Kasai operation in a group designated as high-risk. The results obtained with the Kasai operation (5/11) in terms of survival without jaundice were superior to those of other biliary atresia series (45% versus 31% for regular biliary atresia patients, P = NS). The patients who were received transplants are alive and well, but the series is too small to draw conclusions. DISCUSSION
The embryological aspects of this multiple malformation have been studied by Davenport 7 and Lilly. 8 According to these investigators, the embryological insult may occur around the fifth week of gestation in the group of patients with biliary atresia and polysplenia syndrome, although the existence of genetic factors cannot be excluded because polysplenia has familial incidence. 9
Our results confirm the opinion held by other investigators that the Kasai operation is an excellent option that yields results that are similar or superior to other operations in patients with biliary atresia. Liver transplantation has become consolidated as an important option when bile flow cannot be restored by portoenteroanastomosis. As other authors have shown, situs inversus, preduodenal portal vein, intestinal malrotation, and the absence of retrohepatic vena cava are not contraindications for this type of therapy. Our results with liver transplantation corroborate this opinion. One factor to consider in this group of patients is that most weighed less than 7 kg and there is a scarcity of donors of an adequate size. Our first experiences with liver transplantation from live donors are reason for hope of resolving these problems. However, the live donor technique entails risks because it involves submitting a healthy subject to a major surgical procedure. Although left lateral segmentectomy is a technique that has minimal risks, this type of transplant compromises a family's emotional stability and has important ethical connotations. To conclude, our data confirm that the Kasai operation is a viable option in patients with extrahepatic biliary atresia and polysplenia. The different modalities of liver transplantation (complete, reduced, or live donor) should be reserved for cases in which an internal biliary fistula cannot be created.
REFERENCES 1. Vhzquez J, Hern~ndez-Cano A, Diez-Pardo J, et al: Estado actual de la atresia biliar. An Esp Pediatr 26:407-409, 1987 2. Chandra RS: Biliary atresia and other structural anomalies in the congenital polysplenia syndrome. J Pediatr 85:649-655, 1974 3. Helwig FC: Multiple spleen combined with other congenital abnormalities. Arch Pathol 8:761-767, 1929 4. Davenport M, Savage M, Mowat A, et al: The biliary atresia-splenic malformation syndrome, in Ohi R (ed): Biliary Atresia. Professional Postgraduate Services, Tokyo, 1991, pp 11-14 5. Colomb K, Mizrahi S, Downes T, et al: Liver transplantation in patients with situs inversus. Transplant Int 6:158-160, 1993
6. Kasai M, Suzuki M: A new operative procedure (hepatic portoenterostomy) for uncorrectable type of the congenital biliary atresia. J Surg 13:733-739, 1959 7. Davenport M, Savage M, Mowat AP, et al: Biliary atresia splenic malformation syndrome: An etiologic and prognostic subgroup. Surgery 113:662-668, 1993 8. Karrer FM, Hall R, Lilly JR: Biliary atresia and the polysplenia syndrome. J Pediatr Surg 26:524-527, 1991 9. Niikawa N, Kohasaka S, Mizumoto M, et al: Familial clustering of situs inversus totalis and asplenia and polysplenia. Am J Med Genet 16:43-47, 1983