Bile Duct Patterns in the Hilar Region of the Liver in Two Cases of Biliary Atresia By Eiichi Deguchi, Jun Yanagihara, and Naomi lwai
Kyoto, Japan 0 Bile duct patterns in the hilar region of the liver were demonstrated in two autopsy cases of biliary atresia by three-dimensional graphic reconstructions. In one case, jaundice had completely disappeared after successful hepatic portojejunostomy. However, at the age of 4 months, this patient died of cardiac failure caused by endocardial cushion defect. The histological reconstruction of this case showed that there were large patent bile ducts, 150 pm to 400 pm in diameter. and plenty of bile ductules surrounding the large ducts to form networks. The other patient died of hepatic failure at the age of 9 months. In this case, only a few large ducts ended in bile lakes that did not connect with the portojejunostomy. and only a few ductules were found around the large ducts. These results indicate that the existence of networks of bile ductules and the patency of large bile ducts at the porta hepatis contribute to good postoperative bile excretion. 0 1990 by W.B. Saunders Company. INDEX WORDS: Biliary atresia.
T
HE PROGRESS of surgery for biliary atresia has made it possible for most patients to attain adequate biliary excretion, but there are still some patients in whom the results are unsatisfactory.’ For the achievement of postoperative bile excretion, the presence of a patent bile duct at the porta hepatis is necessary. There have been some reports2d that describe histological changes of the bile ducts in the hilar region of the liver, but only a few have mentioned the fine structures of the intrahepatic bile ducts in the hilar region in patients having biliary atresia and good bile excretion. MATERIALS AND METHODS
Autopsy liver specimens were obtainedfrom two patients with biliary atresia, treated by hepatic portojejunostomy with a simple Roux-en-Y anastomosis at the Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan. The sex and age of the patients, the type of extrahepatic bile duct, and the postoperative course are listed in Table 1. Postoperative bile excretion was good in case 1, and resulted in the complete disappearance of jaundice. However, at the age of 141 days, this patient died of cardiac failure due to an endocardial cushion defect and patent ductus arteriosus. In case 2, postoperative bile excretion was poor, and at the age of 28 1 days this patient died of hepatic failure. At the time of autopsy, the liver was carefully removed together with the tissues of the porta. hepatis and fixed in 10% formalin. After fixation, the hepatic portojejunostomy region of the liver was cut into S-mm serial slices tbat were embedded in ordinary paraffin. One slice from each case was selected for further investigation. One hundred 5-Frn serial sections were prepared and stained with hematoxylin and eosin. For the graphic reconstruction, Takahashi’s5 method was
Journal of Pediatric Surgery, Vol 25, NO 3 (March), 1990: pp 307-310
used. An area of approximately 2 mm* was chosen arbitrarily in a slide from a set of serial sections. The area was projected onto a sheet of tracing paper at a magnification of x 80, and the boundaries of all the bile ducts and ductules were carefully traced. The procedure was repeated for each of the serial sections. The drawings, placed one upon another in series, were examined, and the three-dimensional structure of the biliary duct system was analyzed. The results of these observations were presented in a stereogram. RESULTS
Clinical Courses Case 1. His mother was in good health during the pregnancy. Birth weight was 2,970 g. Jaundice persisted after the period of neonatal jaundice. Surgery was performed on the 58th day of life. Total serum bilirubin was 17.1 mg/dL, and direct bilirubin was 15.5 mg/dL. The type of extrahepatic bile duct was III-c,-v. This patient also had cardiac anomalies (an endocardial cushion defect and patent ductus arteriosus), situs inversus, and intestinal malrotation. Hepatic portojejunostomy with a simple Roux-en-Y anastomosis was performed. Postoperative bile excretion was excellent, and the total serum bilirubin had decreased to 0.6 mg/dL 3 weeks after the operation. However, he died of cardiac failure on the 83rd postoperative day. Case 2. The first of male twins, his mother was in good health during the pregnancy. Birth weight was 3,600 g. Jaundice continued after the period of neonatal jaundice. Surgery was performed on the 59th day of life. Total serum bilirubin was 10.4 mg/dL, and direct bilirubin was 10.0 mg/dL. The type of extrahepatic bile duct was III-b,-v. Hepatic portojejunostomy with a simple Roux-en-Y anastomosis was performed. Postoperative bile excretion was good at first and the total serum bilirubin decreased to 6.7 mg/dL. However, after the 50th postoperative day, the level gradually rose and it became more than 10 mg/dL. Despite two more hepatic portojejunostomy operations, serum bilirubin continued to be high. On the 222nd postoperative day, he died of hepatic failure.
From the Division of Surgery, Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan. Date accepted: October 7.1988. Address reprint requests to Eiichi Deguchi, MD, Division of Surgery, Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602. Japan. 8 1990 by W.3. Saunders Company. 0022-3468/90/2503-0008$03.00/0
307
DEGUCHI, YANAGIHARA, AND IWAI
308
Tabla 1. Types of Extrahepatic Bila Duct and Postoperstive Course of the Two Patients A*& Case NO.
1
sex
Male
Tvpaof ExtrMi Eii
Ill-c,-U
Duct
opmtim
(daw) 58
Ascending
chdan&is -
ReolMauX -
Age at Autopsy
(Cause of Death) 141 days (Cardiacfailure)
2
Male
111-b,+
59
-
2
281 days
Associated Anomelv Congenitalheartdisease(ECD, PDA) situs inversus Intestinal malrotation -
(Hepatic failure)
Bile Duct Pattern in the Hilar Region of the Liver of a Biliary Atresia Patient With Excellent Bile Excretion Figure 1 shows the histological appearance of the porta hepatis of case 1. Postoperative bile excretion was excellent and there were no signs of cholangitis. A large bile duct, 200 pm in diameter opening into the lumen of the portojejunostomy can be observed. Many bile ducts and ductules are present in the fibrotic tissue at the porta hepatis.
In the vicinity of the porta hepatis, there are several large bile ducts, 150 pm to 400 pm in diameter, around which are some bile ductules (Fig 2). Figure 3 shows a three-dimensional microscopic bile duct system in the vicinity of the porta hepatis, reconstructed from slides from case 1. The pattern of the bile duct system is complicated and irregularly arranged, but the ducts and ductules are in close communication with each other and form networks. These networks of bile ductules are more prominent between the parenchyma and the large ducts.
Fig 1. Case 1. Photomicrograph of hepatic portojejunostomy region. Arrow indicates a large bile duct, 200 pm in diameter, that opens into the free lumen of the hepatic portojejunostomy. (H&E. originsi magnification x4D.j
Fig 2. Case 1. Photomicrograph of hilar region of the liver. There are two large bile ducts, 400 firn in diameter, surrounded by several bile ductules. (H&E, original magnification x40.1
BILE DUCT PATTERNS IN THE HLAR REGJON OF BA
Fig 3. Case 1. Graphic reconstruction of bile ducts in the hilar region. Patent large ducts and plenty of bile ductules connect with each other to form Retworks.
Bile Duct Pattern in the Hilar Region of the Liver of a Biliary Atresia Patient With Poor Bile Excretion In case 2, postoperative bile excretion was poor and jaundice continued. Hepatic insufficiency was the main cause of death. The microscopic appearance of the bile duct system in the vicinity of the porta hepatis is shown in Fig 4. There is a small bile duct, approximately 100 pm in diameter, that opens into a bile lake that has no connection with the lumen of the hepatic portojejunostomy. There are only a few bile ducts and ductules. Figure 5 is a microscopic reconstruction of the bile duct system at the porta hepatis of case 2. It shows a single small bile duct and only a few bile ductules that end abruptly and do not form a network.
Fig 4. Case 2. Photomicrograph of hliar rsglon of the liier. A small bile duct, 100 pm in diameter, open8 into a bile lake (5). However, few ductules are seen around the bile ducta. (H&E, original magnification x40.)
DISCUSSION
For the achievement of good postoperative bile excretion in patients with biliary atresia, microscopic patency of the ducts in the porta hepatis and an opening into the lumen of the hepatic portojejunostomy are necessary. Retrograde cholangiography and resin-cast cannot demonstrate the fine structures of the bile ductules. Histological reconstruction is the only technique that meets the requirements. Several reports have described the histopathological changes of the bile duct systems in the porta hepatis in biliary atresia. 2-4However, very few have presented the three-dimensional structure of the bile ducts and ductules around the porta hepatis. Our graphic reconstruction method shows that the most important factors in the achievement of good bile excretion after hepatic portojejunostomy are (1) opening of a patent bile duct into the lumen of the hepatic portojejunostomy; (2) ducts at least 200 pm in diameter; and (3) the presence of dense networks of ductules between the ducts and the hepatic parenchyma. These
Fig 5. Case 2. Graphic reconstruction of bile ducts in the hiler region. The bile duct is small, end very few bile ductules or networks can be seen.
DEGUCHI, YANAGIHARA,
310
networks between the bile duct and bile ductules in the porta hepatis are similar to those that surround interlobular bile ducts in the peripheral portal tracts.6 The present study indicates that preservation of the main draining routes, not only in the peripheral portal tracts but also in the vicinity of the porta hepatis, is the key to the successful treatment of biliary atresia. These results also indicate that the presence of abundant networks between the ducts and ductules in the vicinity of the porta hepatis correlates well with postoperative bile excretion. The patients in the present study lived for 4 months
AND IWAI
and 9 months, respectively. The difference in their ages may account for the absence of networks of ductules in the porta hepatis in case 2. Chandra et al’ studied the histological changes in the extrahepatic bile duct and found that “the majority of patients older than 12 weeks had obliteration of the ductal remnants.” The age of the patient may also be an important factor in the obliteration of the biliary duct system in the porta hepatis. Therefore, as the results of our study suggest, early initial surgery or early reoperation, if necessary, is particularly important in the treatment of biliary atresia.
REFERENCES 1. Suruga K, Miyano T, Arai T, et al: A study of patients with long-term bile flow after hepatic portoenterostomy for biliary atresia. J Pediatr Surg 20:252-255,1985 2. Miyano T, Suruga K, Tsuchiya H, et al: A histopathological study of the remnant of extrahepatic bile duct in so-called uncorrectable biliary atresia. J Pediatr Surg 12:19-25, 1977
3. Gautier M, Moitier G, Odievre M: “Uncorrectable” extrahepatic biliary atresia: Relationship between intrahepatic bile duct pattern and surgery. J Pediatr Surg 15:129-132,198O
4. Chiba T, Kasai M, Sasano N: Histopathological studies on intrahepatic bile ducts in the vicinity of porta hepatis in biliary atresia. Tohoku J Exp Med 118: 199-207, 1976 5. Takahashi T: Three-dimensional morphology of the liver in cirrhosis and related disorders. Virchows Arch [A] 37297-l 10.1978 6. Ohi R, Kasai M, Takahashi T: lntrahepatic biliary obstruction in congenital bile duct atresia. Tohoku J Exp Med 99:129-140, 1969 7. Chandra RS, Altman RP: Ductal remnants in extrahepatic biliary atresia: A histopathologic study with clinical correlation. J Pediatr 93:196-200,1978
Kyoto, Japan 0 Bile duct patterns in the hilar region of the liver were demonstrated in two autopsy cases of biliary atresia by three-dimensional graphic reconstructions. In one case, jaundice had completely disappeared after successful hepatic portojejunostomy. However, at the age of 4 months, this patient died of cardiac failure caused by endocardial cushion defect. The histological reconstruction of this case showed that there were large patent bile ducts, 150 pm to 400 pm in diameter. and plenty of bile ductules surrounding the large ducts to form networks. The other patient died of hepatic failure at the age of 9 months. In this case, only a few large ducts ended in bile lakes that did not connect with the portojejunostomy. and only a few ductules were found around the large ducts. These results indicate that the existence of networks of bile ductules and the patency of large bile ducts at the porta hepatis contribute to good postoperative bile excretion. 0 1990 by W.B. Saunders Company. INDEX WORDS: Biliary atresia.
T
HE PROGRESS of surgery for biliary atresia has made it possible for most patients to attain adequate biliary excretion, but there are still some patients in whom the results are unsatisfactory.’ For the achievement of postoperative bile excretion, the presence of a patent bile duct at the porta hepatis is necessary. There have been some reports2d that describe histological changes of the bile ducts in the hilar region of the liver, but only a few have mentioned the fine structures of the intrahepatic bile ducts in the hilar region in patients having biliary atresia and good bile excretion. MATERIALS AND METHODS
Autopsy liver specimens were obtainedfrom two patients with biliary atresia, treated by hepatic portojejunostomy with a simple Roux-en-Y anastomosis at the Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan. The sex and age of the patients, the type of extrahepatic bile duct, and the postoperative course are listed in Table 1. Postoperative bile excretion was good in case 1, and resulted in the complete disappearance of jaundice. However, at the age of 141 days, this patient died of cardiac failure due to an endocardial cushion defect and patent ductus arteriosus. In case 2, postoperative bile excretion was poor, and at the age of 28 1 days this patient died of hepatic failure. At the time of autopsy, the liver was carefully removed together with the tissues of the porta. hepatis and fixed in 10% formalin. After fixation, the hepatic portojejunostomy region of the liver was cut into S-mm serial slices tbat were embedded in ordinary paraffin. One slice from each case was selected for further investigation. One hundred 5-Frn serial sections were prepared and stained with hematoxylin and eosin. For the graphic reconstruction, Takahashi’s5 method was
Journal of Pediatric Surgery, Vol 25, NO 3 (March), 1990: pp 307-310
used. An area of approximately 2 mm* was chosen arbitrarily in a slide from a set of serial sections. The area was projected onto a sheet of tracing paper at a magnification of x 80, and the boundaries of all the bile ducts and ductules were carefully traced. The procedure was repeated for each of the serial sections. The drawings, placed one upon another in series, were examined, and the three-dimensional structure of the biliary duct system was analyzed. The results of these observations were presented in a stereogram. RESULTS
Clinical Courses Case 1. His mother was in good health during the pregnancy. Birth weight was 2,970 g. Jaundice persisted after the period of neonatal jaundice. Surgery was performed on the 58th day of life. Total serum bilirubin was 17.1 mg/dL, and direct bilirubin was 15.5 mg/dL. The type of extrahepatic bile duct was III-c,-v. This patient also had cardiac anomalies (an endocardial cushion defect and patent ductus arteriosus), situs inversus, and intestinal malrotation. Hepatic portojejunostomy with a simple Roux-en-Y anastomosis was performed. Postoperative bile excretion was excellent, and the total serum bilirubin had decreased to 0.6 mg/dL 3 weeks after the operation. However, he died of cardiac failure on the 83rd postoperative day. Case 2. The first of male twins, his mother was in good health during the pregnancy. Birth weight was 3,600 g. Jaundice continued after the period of neonatal jaundice. Surgery was performed on the 59th day of life. Total serum bilirubin was 10.4 mg/dL, and direct bilirubin was 10.0 mg/dL. The type of extrahepatic bile duct was III-b,-v. Hepatic portojejunostomy with a simple Roux-en-Y anastomosis was performed. Postoperative bile excretion was good at first and the total serum bilirubin decreased to 6.7 mg/dL. However, after the 50th postoperative day, the level gradually rose and it became more than 10 mg/dL. Despite two more hepatic portojejunostomy operations, serum bilirubin continued to be high. On the 222nd postoperative day, he died of hepatic failure.
From the Division of Surgery, Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan. Date accepted: October 7.1988. Address reprint requests to Eiichi Deguchi, MD, Division of Surgery, Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602. Japan. 8 1990 by W.3. Saunders Company. 0022-3468/90/2503-0008$03.00/0
307
DEGUCHI, YANAGIHARA, AND IWAI
308
Tabla 1. Types of Extrahepatic Bila Duct and Postoperstive Course of the Two Patients A*& Case NO.
1
sex
Male
Tvpaof ExtrMi Eii
Ill-c,-U
Duct
opmtim
(daw) 58
Ascending
chdan&is -
ReolMauX -
Age at Autopsy
(Cause of Death) 141 days (Cardiacfailure)
2
Male
111-b,+
59
-
2
281 days
Associated Anomelv Congenitalheartdisease(ECD, PDA) situs inversus Intestinal malrotation -
(Hepatic failure)
Bile Duct Pattern in the Hilar Region of the Liver of a Biliary Atresia Patient With Excellent Bile Excretion Figure 1 shows the histological appearance of the porta hepatis of case 1. Postoperative bile excretion was excellent and there were no signs of cholangitis. A large bile duct, 200 pm in diameter opening into the lumen of the portojejunostomy can be observed. Many bile ducts and ductules are present in the fibrotic tissue at the porta hepatis.
In the vicinity of the porta hepatis, there are several large bile ducts, 150 pm to 400 pm in diameter, around which are some bile ductules (Fig 2). Figure 3 shows a three-dimensional microscopic bile duct system in the vicinity of the porta hepatis, reconstructed from slides from case 1. The pattern of the bile duct system is complicated and irregularly arranged, but the ducts and ductules are in close communication with each other and form networks. These networks of bile ductules are more prominent between the parenchyma and the large ducts.
Fig 1. Case 1. Photomicrograph of hepatic portojejunostomy region. Arrow indicates a large bile duct, 200 pm in diameter, that opens into the free lumen of the hepatic portojejunostomy. (H&E. originsi magnification x4D.j
Fig 2. Case 1. Photomicrograph of hilar region of the liver. There are two large bile ducts, 400 firn in diameter, surrounded by several bile ductules. (H&E, original magnification x40.1
BILE DUCT PATTERNS IN THE HLAR REGJON OF BA
Fig 3. Case 1. Graphic reconstruction of bile ducts in the hilar region. Patent large ducts and plenty of bile ductules connect with each other to form Retworks.
Bile Duct Pattern in the Hilar Region of the Liver of a Biliary Atresia Patient With Poor Bile Excretion In case 2, postoperative bile excretion was poor and jaundice continued. Hepatic insufficiency was the main cause of death. The microscopic appearance of the bile duct system in the vicinity of the porta hepatis is shown in Fig 4. There is a small bile duct, approximately 100 pm in diameter, that opens into a bile lake that has no connection with the lumen of the hepatic portojejunostomy. There are only a few bile ducts and ductules. Figure 5 is a microscopic reconstruction of the bile duct system at the porta hepatis of case 2. It shows a single small bile duct and only a few bile ductules that end abruptly and do not form a network.
Fig 4. Case 2. Photomicrograph of hliar rsglon of the liier. A small bile duct, 100 pm in diameter, open8 into a bile lake (5). However, few ductules are seen around the bile ducta. (H&E, original magnification x40.)
DISCUSSION
For the achievement of good postoperative bile excretion in patients with biliary atresia, microscopic patency of the ducts in the porta hepatis and an opening into the lumen of the hepatic portojejunostomy are necessary. Retrograde cholangiography and resin-cast cannot demonstrate the fine structures of the bile ductules. Histological reconstruction is the only technique that meets the requirements. Several reports have described the histopathological changes of the bile duct systems in the porta hepatis in biliary atresia. 2-4However, very few have presented the three-dimensional structure of the bile ducts and ductules around the porta hepatis. Our graphic reconstruction method shows that the most important factors in the achievement of good bile excretion after hepatic portojejunostomy are (1) opening of a patent bile duct into the lumen of the hepatic portojejunostomy; (2) ducts at least 200 pm in diameter; and (3) the presence of dense networks of ductules between the ducts and the hepatic parenchyma. These
Fig 5. Case 2. Graphic reconstruction of bile ducts in the hiler region. The bile duct is small, end very few bile ductules or networks can be seen.
DEGUCHI, YANAGIHARA,
310
networks between the bile duct and bile ductules in the porta hepatis are similar to those that surround interlobular bile ducts in the peripheral portal tracts.6 The present study indicates that preservation of the main draining routes, not only in the peripheral portal tracts but also in the vicinity of the porta hepatis, is the key to the successful treatment of biliary atresia. These results also indicate that the presence of abundant networks between the ducts and ductules in the vicinity of the porta hepatis correlates well with postoperative bile excretion. The patients in the present study lived for 4 months
AND IWAI
and 9 months, respectively. The difference in their ages may account for the absence of networks of ductules in the porta hepatis in case 2. Chandra et al’ studied the histological changes in the extrahepatic bile duct and found that “the majority of patients older than 12 weeks had obliteration of the ductal remnants.” The age of the patient may also be an important factor in the obliteration of the biliary duct system in the porta hepatis. Therefore, as the results of our study suggest, early initial surgery or early reoperation, if necessary, is particularly important in the treatment of biliary atresia.
REFERENCES 1. Suruga K, Miyano T, Arai T, et al: A study of patients with long-term bile flow after hepatic portoenterostomy for biliary atresia. J Pediatr Surg 20:252-255,1985 2. Miyano T, Suruga K, Tsuchiya H, et al: A histopathological study of the remnant of extrahepatic bile duct in so-called uncorrectable biliary atresia. J Pediatr Surg 12:19-25, 1977
3. Gautier M, Moitier G, Odievre M: “Uncorrectable” extrahepatic biliary atresia: Relationship between intrahepatic bile duct pattern and surgery. J Pediatr Surg 15:129-132,198O
4. Chiba T, Kasai M, Sasano N: Histopathological studies on intrahepatic bile ducts in the vicinity of porta hepatis in biliary atresia. Tohoku J Exp Med 118: 199-207, 1976 5. Takahashi T: Three-dimensional morphology of the liver in cirrhosis and related disorders. Virchows Arch [A] 37297-l 10.1978 6. Ohi R, Kasai M, Takahashi T: lntrahepatic biliary obstruction in congenital bile duct atresia. Tohoku J Exp Med 99:129-140, 1969 7. Chandra RS, Altman RP: Ductal remnants in extrahepatic biliary atresia: A histopathologic study with clinical correlation. J Pediatr 93:196-200,1978
