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Contemporary Management of Biliary Atresia
Symposium on Pediatric Surgery
Contemporary Management
of Biliary Atresia Thomas R. Weber, M.D.,*andJay L. Grosfeld, M.D.t
The term "biliary atresia" refers to an obliterative process of unknown etiology involving the extrahepatic bile ducts, resulting in severe neonatal obstructive jaundice. These lesions were previously divided into "correctable" and "uncorrectable" forms, based on the anatomy involved and the assumed success rate after surgical repair. These terms now seem obsolete, since the introduction of hepatic portoenterostomy by Kasai, which has resulted in many long-term survivors even among the "uncorrectable" types. Much remains to be learned about this disease, but great advances have been made by a number of investigators over the last 15 years to improve the survival of these infants.
HISTORICAL BACKGROUND The first clinical and autopsy description of infants with biliary atresia is credited to John Thompson, a physician at the Royal Hospital for Sick Children, Edinburgh, in 1892.7 In 1916, Holmes described a number of variants of biliary atresia based on necropsy findings and predicted that 16 per cent of these infants could be cured by biliary-enteric anastomosis. This figure proved to be reasonably accurate until recently." Scattered reports of successful repair of some forms of biliary atresia, primarily those associated with choledochal cyst or patent common hepatic duct, appeared between 1940 and 1960. The dismal outlook for these infants was further emphasized by a survey of the members of the Surgical Section, American Academy of Pediatrics in 1966,11 which reported that less than 7 per cent of 843 infants with biliary atresia seen between 1954 and 1964 lived beyond early childhood. These early dismal reports gave further encouragement to those physicians who were reluctant to refer children for exploration and attempted repair. 15 In 1968, Kasai" published his remarkable series of patients with biliary atresia repaired by high transection of atretic ducts and hepatoportoenterostomy reconstruction. In that and subsequent publications, Kasai has shown that long-term survival can be achieved with portoenterostomy, and as a consequence the dismal outlook for these children has been markedly improved. From the Section of Pediatric Surgery, Department of Surgery, Indiana University School of Medicine and the James Whitcomb Riley Hospital for Children, Indianapolis, Indiana
*Assistant Professor of Pediatric Surgery tProfessor and Director, Section of Pediatric Surgery, and Surgeon-in-Chief Surgical Clinics of North America-Vol. 61, No.5, October 1981
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Surgeons in the United States began performing the Kasai procedure in the early 1970s. As experience was gained with the procedure in this country, improved survival rates were reported. 3 , l o, 13 The increasing survival is also undoubtedly due to earlier referral of the jaundiced infant for evaluation and therapy. There have been a number of modifications in the reconstructive phase of the hepatoportoenterostomy, primarily, once again, from the Japanese experience. 7 These modifications have been necessitated by the high risk of cholangitis in these infants after portoenterostomy. 14 Unfortunately, none of these changes has been uniformly successful in eliminating this complication. The operative approaches to these infants will be discussed more thoroughly later.
EVALUATION OF THE JAUNDICED INFANT Jaundice is a common occurrence in newborn infants, primarily premature infants or those with concomitant disorders such as sepsis, bowel obstruction, or respiratory distress. The so-called "physiologic" jaundice of infancy, resulting from immaturity of the intrahepatic conjugating mechanisms of bilirubin, causes indirect or unconjugated hyperbilirubinemia. This is generally short lived and has no permanent sequelae if treated aggressively with phototherapy and exchange transfusion, if necessary. The infant with jaundice persisting for more than three weeks usually has a "mixed" type of hyperbilirubinemia, with both unconjugated and conjugated forms, indicating a degree of cholestasis. These infants must be suspected of having a pathologic process and should be thoroughly investigated. The causes of jaundice in the latter infants can be divided broadly into "medical" and "surgical" categories. The most common disorders associated with jaundice in these two groups are as follows: SURGICAL CAUSES MEDICAL CAUSES Biliary atresia Infectious Biliary hypoplasia Cytomegalovirus Choledochal cyst Rubella virus Perforation of extrahepatic bile duct Herpes virus Inspissated bile plug Hepatitis A, B, non-A, and non-B Toxoplasmosis Syphilis Genetic disorders Galactosemia Congenital fructose intolerance Alpha.-antitrypsin deficiency Cystic fibrosis Neimann-Pick disease Polysplenia syndrome Alagelle syndrome Miscellaneous conditions Hemolytic disease Bacterial sepsis Pyelonephritis Hyperalimentation Congenital bowel obstruction (intestinal atresia, etc.) Congestive heart failure Hypothyroidism
CONTEMPORARY MANAGEMENT OF BILIARY ATRESIA
1081
A few cases of biliary atresia have been associated with confirmed neonatal viral hepatitis and certain metabolic conditions such as alpha.santitrypsin deficiency, but in general, surgical and medical disorders do not coexist in the same infant. The preoperative differentiation between medical and surgical causes of jaundice in infants is highly desirable but, unfortunately, is not always possible. Numerous new radiographic and blood studies enthusiastically reported throughout the past 10 years have invariably proved to be nonspecific for the detection of biliary atresia. There remain a few necessary screening studies to differentiate medical from surgical jaundice in infancy, but it should be emphasized that no single study or combination of studies can make that distinction every time. The work-up for neonatal jaundice is as follows: Blood and serum studies Complete blood count Blood type, Coombs test Bilirubin, total and direct Coagulation screen Serum protein electrophoresis, alpha.-antitrypsin level Thyroid function (T3,T4) Liver function Hepatitis A and B surface antigens TORCH screen (toxoplasmosis, rubella, cytomegalovirus, herpes) Renal functions Radiologic studies Chest x-ray 99Tc = PIPIDA scan 131I = rose bengal excretion (optional) Liver ultrasonography ' Urine studies Urinalysis Urine culture, for bacteria and cytomegalovirus Sweat chloride level Stool color and consistency
When these routine screening tests have been exhausted and no specific disorder has been identified, the infant with clay-colored stools and evidence of obstruction on radioisotopic hepatic excretion scans should then undergo surgical exploration without undo delay. The surgical approach to the jaundiced infant is covered later, but one important point needs to be emphasized. These procedures should be performed at tertiary pediatric centers by surgeons knowledgeable in the operative approach of the infant biliary tree. Attempts at cholangiography or portal dissection to "make the diagnosis" with plans to then transfer the child to another center for portoenterostomy should be condemned. A second operative procedure puts the child at needless risk and is invariably made more difficult by the presence of vascular adhesions. Indeed, in many large series of portoenterostomy patients, the major source of operative mortality is reoperation."
OPERATIVE THERAPY FOR BILIARY ATRESIA The infant is explored through a transverse incision in the right upper quadrant. The incision is kept small at first, to expose only the liver and gallbladder. If a gallbladder is present, a small catheter is threaded into its lumen and a cholangio-
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gram performed with 25 per cent Hypaque. Usually two films are taken in rapid succession, the second after manual compression of the distal common bile duct to attempt to produce retrograde flow of contrast into the intrahepatic biliary tree. At no time should excessive force be utilized to inject the contrast or should clamps of any kind be used to occlude the common duct, as the biliary tree is small and fragile in the infant and may be damaged or perforated. If contrast is demonstrated in the intrahepatic biliary tree and flows into the duodenum (Fig. 1), a liver biopsy is performed and the operative procedure terminated. On the other hand, if the gallbladder is totally absent, is found to be only a fibrotic mass without a lumen, or contrast cannot be demonstrated in the intrahepatic bile ducts (Fig. 2), a diagnosis of biliary atresia can be assumed and portal dissection begun. The peritoneum overlying the portal triad is opened, and the cystic duct-eommon bile duct junction is identified. Liberal use is made of the electrocautery to divide the dilated lymphatics in this region, as this seems to reduce postoperative bilious ascites. Right and left hepatic arteries are identified and encircled with tapes so that these structures can be carefully preserved. The common hepatic duct is then identified and dissection is continued toward the liver. This structure is invariably found to be a fibrous band, which on histologic examination has no lumen. High in the porta hepatis, where the portal vein branches into right and left divisions, the obliterated common hepatic duct enlarges to form a fibrous mass, which probably represents the obliterated right and left hepatic ducts (Fig. 3A). This fibrous mass must be gently dissected away from the portal vein and transected at the liver surface (Fig. 3B). This usually results in minor hemorrhage that can be controlled with pressure. Use of the electrocautery or suture ligature at this level should be avoided because of the risk of occluding the microscopic ducts. The cut fibrous mass is submitted for frozen histologic examination. The pres-
Figure 1. Intraoperative cholangiogram performed by injection of contrast material through the gallbladder. Note the flow of dye into the intrahepatic ducts, and distally into the duodenum, thus eliminating biliary atresia as the cause of jaundice in this infant.
CONTEMPORARY MANAGEMENT OF BILIARY ATRESIA
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Figure 2. Cholangiogram performed intraoperatively in an infant with jaundice. The contrast material flowed easily into the duodenum, but not into the liver. This confirmed the diagnosis of biliary atresia, and Kasai portoenterostomy was successful in establishing bile flow.
ence of ductal structures lined by biliary epithelium within the fibrous mass is evidence that the dissection is sufficient. If no biliary ductules are found on frozen section, higher transection of atretic ducts, at times even extending deep into liver substance, is necessary, utilizing frozen section control at each level. Intestinal reconstruction of the biliary tree can be accomplished in several ways (Fig. 3C). In general, a Roux-en- Y jejunal loop is utilized, with exteriorization of the biliary limb as a "biliary ostomy" (Fig. 4). This allows collection of bile into an external ostomy bag, with intestinal refeeding of the bile performed by insertion of a small soft catheter into the more distal ostomy. An alternative approach is the formation of a straight jejunal conduit from liver to skin without a "refeeding" loop (Fig. 5), but these children can develop serious fluid and electrolyte problems postoperatively because of lost bile, which cannot be returned, and thus this technique has been largely abandoned. Both of these techniques allow quantification and biochemical study of the bile produced and probably decrease to some extent the incidence of ascending cholangitis postoperatively. The biliary ostomy is exteriorized through a separate stab wound incision in the right upper quadrant. Placement of soft Penrose drains about the anastomosis completes the operative procedure. These drains are usually removed within one week. Most investigators advocate leaving the exteriorized loop intact for 18 to 24 months until a vigorous flow of bile (500 to 1000 ml per day) is present. At that time a simple end-to-end anastomosis of the ostomies is performed.
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Figure 3. A, Dissection of the porta hepatis in the Kasai procedure. The gallbladder and obliterated common hepatic duct have been reflected upward after transection of the common bile duct. Note the widening of the hepatic duct into a fibrous mass at the division of the portal vein. B, The portal vein is reflected downward, and the fibrous mass transected at the liver surface (dashed line). The mass is sent for frozen section to determine the presence of microscopic ducts. C, 'Portoenterostomy is performed after frozen section confirmation of the presence of ductules. The sutures are placed outside of the margin of the transection to prevent occlusion of the ducts.
RESULTS, COMPLICATIONS, AND PROGNOSIS The results of hepatic portoenterostomy can be measured in several ways. First, 70 to 80 per cent of the children will drain bile from the biliostomy, usually within 7 to 10 days postoperatively, although it may take up to several weeks. Secondly, approximately 60 per cent of infants will become anicteric, usually within several months after the hepatoportoenterostomy procedure. Finally, long-term survival may be achieved in 30 to 50 per cent of infants (Table 1). Several factors have been found to be important in determining frequency and volume of bile flow, and thus overall survival. The age of the infant at the time of operation seems to be important, with those infants under three months of age having the highest success rate. 13 Indeed, one to two months seems to be the ideal
* Figure 4. Portoenterostomy reconstruction utilizing a Roux-en-Y jejunal loop. The loop has been divided and exteriorized as a "biliostomy" allowing excreted bile to be collected in an external ostomy device (Suruga technique). The bile is refed through the second ostomy orifice.
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CONTEMPORARY MANAGEMENT OF BILIARY ATRESIA
Figure 5. An alternative method for biliary drainage consists of a straight segment of jejunum from liver to abdominal wall, allowing drainage of bile into an ostomy device (Sawaguchi technique).
age for exploration. The size of the ductules has likewise been found to directly correlate with bile flow, with ducts greater than 150 microns having a better prognosis." A recent study from our institution has shown that a high level of alkaline phosphatase in the bile, measured at one to two weeks postoperatively, is a very early indicator of successful bile drainage (Fig. 6).16 This seemed to be an even more reliable sign than bilirubin excretion in the early postoperative period and even appeared to correlate with survival. These data are somewhat preliminary and must await long term follow-up for confirmation. For the infant that does not drain bile after the first operation, or drains very small amounts of bile, reoperation and higher transection of atretic ducts may offer some hope for improved bile flow. In our own series;" and another previously reported.i a few infants have benefited from higher transection of ducts several weeks to months after the initial operation. Especially gratifying are the results of reoperation in infants who drained bile initially but who then stop. 16 We have found mechanical obstruction of the biliary jejunal loop, calculus sludge at the hepatoen-
Table 1.
Results of Hepatoportoenterostomy (Recent Series) PER CENT
INVESTIGATOR
Kasai et al. 7 Suruga et al. 7 Sawaguchi et al. 7 Altman 3 Weber et al. 16
WITH BILE
PER CENT
PERIOD
NO. OF PATIENTS
FLOW
JAUNDICE-FREE
1971-1977 1972-1977 1967-1977 1972-1978 1976--1979
67 58 90 43 17
89% 89% 63% 67% 82%
55% 70% 40% 42% 58%
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120
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40
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0
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500
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.SURVIVORS
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2
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WEEKS POST OPERATIVE Figure 6. Clearance of alkaline phosphatase and bilirubin into bile after Kasai procedure, calculated using serum and bile levels of these substances, and bile volume. Note statistically significant differences between survivors and nonsurvivors at 1, 4 and 12 weeks for alkaline phosphatase clearance, and at 4 and 12 weeks for bilirubin clearance.
terostomyanastomosis, and recurrent fibrosis, all of which may respond to reoperation. It is clear that very close patient follow-up is mandatory for early diagnosis and operative therapy of these potential complications. The problem of postoperative cholangitis has received much attention, both clinically'? and experimentally, 8 without adequate resolution. Decrease in the volume of bile output, increasing serum bilirubin levels, fever, and lethargy are the most common signs and symptoms of this complication. Cholangitis can. occur anytime after the operative procedure but seems most prevalent in the first 12 to 18 months postoperatively. The therapy for cholangitis consists of admission to the hospital and the immediate institution of intravenous broad-spectrum antibiotics (gentamycin and ampicillin) after obtaining appropriate cultures of bile and blood. Irrigation of the biliostomy loop with antibiotic solutions has not been helpful in our experience. Prophylactic antibiotics (trimethoprim-sulfamethoxazole) have been utilized in
CONTEMPORARY MANAGEMENT OF BILIARY ATRESIA
."
1087
the postoperative period in an attempt to reduce the incidence of cholangitis, with equivocal results. It was hoped that exteriorization of the biliary loop would decrease the incidence of cholangitis; however, this has not been completely successful. The biliary loop becomes colonized with bacteria, primarily gram-negative organisms, very early after the Kasai procedure," and this undoubtedly plays a role in recurrent infections. Once bile flow is vigorous, usually at 18 to 24 months of age, the incidence of cholangitis decreases and the biliostomy is closed. Cholangitis is still possible, however, and thus close observation and repeat liver function studies are mandatory. Retrograde contrast study through the biliary ostomy should be performed in all cases of recurrent cholangitis, as an occasional infant will have partial obstruction of the loop. Portal hypertension is not an uncommon development after an hepatoportoenterostomy procedure, even in those infants with excellent bile flow. Continuing cirrhosis has been shown to occur after successful portoenterostomy, 4 and this frequently leads to portal hypertension and variceal hemorrhage. Various shunting procedures have been utilized in these children;' with good success in stopping the hemorrhage. Undoubtedly this complication will become more prevalent as many more of these children survive for more than four years. The Kasai procedure has been performed for the past 20 years in Japan; indeed, there are survivors that are now over 20 years of age. 7 However, only recently have continued refinements in the operative technique and preoperative and postoperative care been utilized, thus resulting in survival rates in the 50 per cent range. 3,5 Future improvement in survival would seem to depend on earlier operation, better understanding of the disease process, improved control of cholangitis postoperatively, and aggressive reoperation in those infants who have poor bile drainage or who stop draining bile.
SUMMARY The outlook for the infant with biliary atresia has improved considerably over the past 15 years since the introduction of hepatoportoenterostomy by Kasai, Survival rates of 50 per cent are now possible as a result of earlier operation and close follow-up for the detection of the serious complications that may occur. Further improvements in survival will undoubtedly result from increased understanding of the basic disease process involved.
REFERENCES 1. Altman, R. P.: Portal decompression by interposition mesocaval shunt in patients with biliary atresia. J. Pediatr. Surg., 11:809, 1976. 2. Altman, R. P.: Results of reoperations for correction of extrahepatic biliary atresia. J. Pediatr. Surg., 14:305, 1979. 3. Altman, R. P.: The portoenterostomy procedure for biliary atresia: A five year experience. Ann. Surg., 188:351, 1978. 4. Altman, R. P., Chandra, R., and Lilly, J. R.: Ongoing cirrhosis after successful portoenterostomy in infants with biliary atresia. J. Pediatr. Surg., 10:685, 1975. 5. Altman, R. P., and Lilly, J. R.: Technical details in the surgical correction of extrahepatic biliary atresia. Surg. Gynec. Obstet. 140:953, 1975. 6. Chandra, R. S., and Altman, R. P.: Ductal remnants in extrahepatic biliary atresia: A histopathologic study with clinical correlation. J. Pediatr., 93:196, 1978.
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7. Hays, D. M., and Kimura, K.: Biliary Atresia: The Japanese Experience. Cambridge, Harvard University Press, 1980. 8. Hirsig, J., Kara, 0., and Rickham, P. P.: Experimental investigations into the etiology for cholangitis following operation for biliary atresia. J. Pediatr. Surg., 13:55, 1978. 9. Hitch, D. C., and Lilly, J. R.: Identification, quantification, and significance of bacterial growth within the biliary tract after Kasai's operation. J. Pediatr. Surg., 13:563, 1978. 10. Hitch, D. C., Shikes, R. H., and Lilly, J. R.: Determinants of survival after Kasai's operation for biliary atresia. J. Pediatr. Surg., 14:310, 1979. 11. Izant, R. J., Akers, D. R., Hays, D. M., et al.: Biliary atresia survey. Presented at the 35th Annual Meeting, American Academy of Pediatrics, Chicago, October 1966. 12. Kasai, M., Kimura, S., Asakura, Y., et al.: Surgical treatment of biliary atresia. J. Pediatr. Surg., 3:665, 1968. 13. Lilly, J. R.: Surgical jaundice in infancy. Ann. Surg., 186:549, 1977. 14. Lilly, J. R., and Hitch, D. C.: Postoperative ascending cholangitis followingportoenterostomy for biliary atresia: Measures for control. World J. Surg., 2:581, 1978. 15. Thaler, M. M., and Gellis, S. S.: Studies in neonatal hepatitis and biliary atresia. Am. J. Dis. Child., 116:257, 1968. 16. Weber, T. R., Grosfeld, J. L., and Fitzgerald, J. F.: Prognostic determinants after hepatoportoenterostomy for biliary atresia. Am. J. Surg., 141:57, 1981. Department of Surgery James Whitcomb Riley Hospital for Children Indianapolis, Indiana 46223
Contemporary Management
of Biliary Atresia Thomas R. Weber, M.D.,*andJay L. Grosfeld, M.D.t
The term "biliary atresia" refers to an obliterative process of unknown etiology involving the extrahepatic bile ducts, resulting in severe neonatal obstructive jaundice. These lesions were previously divided into "correctable" and "uncorrectable" forms, based on the anatomy involved and the assumed success rate after surgical repair. These terms now seem obsolete, since the introduction of hepatic portoenterostomy by Kasai, which has resulted in many long-term survivors even among the "uncorrectable" types. Much remains to be learned about this disease, but great advances have been made by a number of investigators over the last 15 years to improve the survival of these infants.
HISTORICAL BACKGROUND The first clinical and autopsy description of infants with biliary atresia is credited to John Thompson, a physician at the Royal Hospital for Sick Children, Edinburgh, in 1892.7 In 1916, Holmes described a number of variants of biliary atresia based on necropsy findings and predicted that 16 per cent of these infants could be cured by biliary-enteric anastomosis. This figure proved to be reasonably accurate until recently." Scattered reports of successful repair of some forms of biliary atresia, primarily those associated with choledochal cyst or patent common hepatic duct, appeared between 1940 and 1960. The dismal outlook for these infants was further emphasized by a survey of the members of the Surgical Section, American Academy of Pediatrics in 1966,11 which reported that less than 7 per cent of 843 infants with biliary atresia seen between 1954 and 1964 lived beyond early childhood. These early dismal reports gave further encouragement to those physicians who were reluctant to refer children for exploration and attempted repair. 15 In 1968, Kasai" published his remarkable series of patients with biliary atresia repaired by high transection of atretic ducts and hepatoportoenterostomy reconstruction. In that and subsequent publications, Kasai has shown that long-term survival can be achieved with portoenterostomy, and as a consequence the dismal outlook for these children has been markedly improved. From the Section of Pediatric Surgery, Department of Surgery, Indiana University School of Medicine and the James Whitcomb Riley Hospital for Children, Indianapolis, Indiana
*Assistant Professor of Pediatric Surgery tProfessor and Director, Section of Pediatric Surgery, and Surgeon-in-Chief Surgical Clinics of North America-Vol. 61, No.5, October 1981
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Surgeons in the United States began performing the Kasai procedure in the early 1970s. As experience was gained with the procedure in this country, improved survival rates were reported. 3 , l o, 13 The increasing survival is also undoubtedly due to earlier referral of the jaundiced infant for evaluation and therapy. There have been a number of modifications in the reconstructive phase of the hepatoportoenterostomy, primarily, once again, from the Japanese experience. 7 These modifications have been necessitated by the high risk of cholangitis in these infants after portoenterostomy. 14 Unfortunately, none of these changes has been uniformly successful in eliminating this complication. The operative approaches to these infants will be discussed more thoroughly later.
EVALUATION OF THE JAUNDICED INFANT Jaundice is a common occurrence in newborn infants, primarily premature infants or those with concomitant disorders such as sepsis, bowel obstruction, or respiratory distress. The so-called "physiologic" jaundice of infancy, resulting from immaturity of the intrahepatic conjugating mechanisms of bilirubin, causes indirect or unconjugated hyperbilirubinemia. This is generally short lived and has no permanent sequelae if treated aggressively with phototherapy and exchange transfusion, if necessary. The infant with jaundice persisting for more than three weeks usually has a "mixed" type of hyperbilirubinemia, with both unconjugated and conjugated forms, indicating a degree of cholestasis. These infants must be suspected of having a pathologic process and should be thoroughly investigated. The causes of jaundice in the latter infants can be divided broadly into "medical" and "surgical" categories. The most common disorders associated with jaundice in these two groups are as follows: SURGICAL CAUSES MEDICAL CAUSES Biliary atresia Infectious Biliary hypoplasia Cytomegalovirus Choledochal cyst Rubella virus Perforation of extrahepatic bile duct Herpes virus Inspissated bile plug Hepatitis A, B, non-A, and non-B Toxoplasmosis Syphilis Genetic disorders Galactosemia Congenital fructose intolerance Alpha.-antitrypsin deficiency Cystic fibrosis Neimann-Pick disease Polysplenia syndrome Alagelle syndrome Miscellaneous conditions Hemolytic disease Bacterial sepsis Pyelonephritis Hyperalimentation Congenital bowel obstruction (intestinal atresia, etc.) Congestive heart failure Hypothyroidism
CONTEMPORARY MANAGEMENT OF BILIARY ATRESIA
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A few cases of biliary atresia have been associated with confirmed neonatal viral hepatitis and certain metabolic conditions such as alpha.santitrypsin deficiency, but in general, surgical and medical disorders do not coexist in the same infant. The preoperative differentiation between medical and surgical causes of jaundice in infants is highly desirable but, unfortunately, is not always possible. Numerous new radiographic and blood studies enthusiastically reported throughout the past 10 years have invariably proved to be nonspecific for the detection of biliary atresia. There remain a few necessary screening studies to differentiate medical from surgical jaundice in infancy, but it should be emphasized that no single study or combination of studies can make that distinction every time. The work-up for neonatal jaundice is as follows: Blood and serum studies Complete blood count Blood type, Coombs test Bilirubin, total and direct Coagulation screen Serum protein electrophoresis, alpha.-antitrypsin level Thyroid function (T3,T4) Liver function Hepatitis A and B surface antigens TORCH screen (toxoplasmosis, rubella, cytomegalovirus, herpes) Renal functions Radiologic studies Chest x-ray 99Tc = PIPIDA scan 131I = rose bengal excretion (optional) Liver ultrasonography ' Urine studies Urinalysis Urine culture, for bacteria and cytomegalovirus Sweat chloride level Stool color and consistency
When these routine screening tests have been exhausted and no specific disorder has been identified, the infant with clay-colored stools and evidence of obstruction on radioisotopic hepatic excretion scans should then undergo surgical exploration without undo delay. The surgical approach to the jaundiced infant is covered later, but one important point needs to be emphasized. These procedures should be performed at tertiary pediatric centers by surgeons knowledgeable in the operative approach of the infant biliary tree. Attempts at cholangiography or portal dissection to "make the diagnosis" with plans to then transfer the child to another center for portoenterostomy should be condemned. A second operative procedure puts the child at needless risk and is invariably made more difficult by the presence of vascular adhesions. Indeed, in many large series of portoenterostomy patients, the major source of operative mortality is reoperation."
OPERATIVE THERAPY FOR BILIARY ATRESIA The infant is explored through a transverse incision in the right upper quadrant. The incision is kept small at first, to expose only the liver and gallbladder. If a gallbladder is present, a small catheter is threaded into its lumen and a cholangio-
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WEBER AND JAY
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GROSFELD
gram performed with 25 per cent Hypaque. Usually two films are taken in rapid succession, the second after manual compression of the distal common bile duct to attempt to produce retrograde flow of contrast into the intrahepatic biliary tree. At no time should excessive force be utilized to inject the contrast or should clamps of any kind be used to occlude the common duct, as the biliary tree is small and fragile in the infant and may be damaged or perforated. If contrast is demonstrated in the intrahepatic biliary tree and flows into the duodenum (Fig. 1), a liver biopsy is performed and the operative procedure terminated. On the other hand, if the gallbladder is totally absent, is found to be only a fibrotic mass without a lumen, or contrast cannot be demonstrated in the intrahepatic bile ducts (Fig. 2), a diagnosis of biliary atresia can be assumed and portal dissection begun. The peritoneum overlying the portal triad is opened, and the cystic duct-eommon bile duct junction is identified. Liberal use is made of the electrocautery to divide the dilated lymphatics in this region, as this seems to reduce postoperative bilious ascites. Right and left hepatic arteries are identified and encircled with tapes so that these structures can be carefully preserved. The common hepatic duct is then identified and dissection is continued toward the liver. This structure is invariably found to be a fibrous band, which on histologic examination has no lumen. High in the porta hepatis, where the portal vein branches into right and left divisions, the obliterated common hepatic duct enlarges to form a fibrous mass, which probably represents the obliterated right and left hepatic ducts (Fig. 3A). This fibrous mass must be gently dissected away from the portal vein and transected at the liver surface (Fig. 3B). This usually results in minor hemorrhage that can be controlled with pressure. Use of the electrocautery or suture ligature at this level should be avoided because of the risk of occluding the microscopic ducts. The cut fibrous mass is submitted for frozen histologic examination. The pres-
Figure 1. Intraoperative cholangiogram performed by injection of contrast material through the gallbladder. Note the flow of dye into the intrahepatic ducts, and distally into the duodenum, thus eliminating biliary atresia as the cause of jaundice in this infant.
CONTEMPORARY MANAGEMENT OF BILIARY ATRESIA
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Figure 2. Cholangiogram performed intraoperatively in an infant with jaundice. The contrast material flowed easily into the duodenum, but not into the liver. This confirmed the diagnosis of biliary atresia, and Kasai portoenterostomy was successful in establishing bile flow.
ence of ductal structures lined by biliary epithelium within the fibrous mass is evidence that the dissection is sufficient. If no biliary ductules are found on frozen section, higher transection of atretic ducts, at times even extending deep into liver substance, is necessary, utilizing frozen section control at each level. Intestinal reconstruction of the biliary tree can be accomplished in several ways (Fig. 3C). In general, a Roux-en- Y jejunal loop is utilized, with exteriorization of the biliary limb as a "biliary ostomy" (Fig. 4). This allows collection of bile into an external ostomy bag, with intestinal refeeding of the bile performed by insertion of a small soft catheter into the more distal ostomy. An alternative approach is the formation of a straight jejunal conduit from liver to skin without a "refeeding" loop (Fig. 5), but these children can develop serious fluid and electrolyte problems postoperatively because of lost bile, which cannot be returned, and thus this technique has been largely abandoned. Both of these techniques allow quantification and biochemical study of the bile produced and probably decrease to some extent the incidence of ascending cholangitis postoperatively. The biliary ostomy is exteriorized through a separate stab wound incision in the right upper quadrant. Placement of soft Penrose drains about the anastomosis completes the operative procedure. These drains are usually removed within one week. Most investigators advocate leaving the exteriorized loop intact for 18 to 24 months until a vigorous flow of bile (500 to 1000 ml per day) is present. At that time a simple end-to-end anastomosis of the ostomies is performed.
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Figure 3. A, Dissection of the porta hepatis in the Kasai procedure. The gallbladder and obliterated common hepatic duct have been reflected upward after transection of the common bile duct. Note the widening of the hepatic duct into a fibrous mass at the division of the portal vein. B, The portal vein is reflected downward, and the fibrous mass transected at the liver surface (dashed line). The mass is sent for frozen section to determine the presence of microscopic ducts. C, 'Portoenterostomy is performed after frozen section confirmation of the presence of ductules. The sutures are placed outside of the margin of the transection to prevent occlusion of the ducts.
RESULTS, COMPLICATIONS, AND PROGNOSIS The results of hepatic portoenterostomy can be measured in several ways. First, 70 to 80 per cent of the children will drain bile from the biliostomy, usually within 7 to 10 days postoperatively, although it may take up to several weeks. Secondly, approximately 60 per cent of infants will become anicteric, usually within several months after the hepatoportoenterostomy procedure. Finally, long-term survival may be achieved in 30 to 50 per cent of infants (Table 1). Several factors have been found to be important in determining frequency and volume of bile flow, and thus overall survival. The age of the infant at the time of operation seems to be important, with those infants under three months of age having the highest success rate. 13 Indeed, one to two months seems to be the ideal
* Figure 4. Portoenterostomy reconstruction utilizing a Roux-en-Y jejunal loop. The loop has been divided and exteriorized as a "biliostomy" allowing excreted bile to be collected in an external ostomy device (Suruga technique). The bile is refed through the second ostomy orifice.
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CONTEMPORARY MANAGEMENT OF BILIARY ATRESIA
Figure 5. An alternative method for biliary drainage consists of a straight segment of jejunum from liver to abdominal wall, allowing drainage of bile into an ostomy device (Sawaguchi technique).
age for exploration. The size of the ductules has likewise been found to directly correlate with bile flow, with ducts greater than 150 microns having a better prognosis." A recent study from our institution has shown that a high level of alkaline phosphatase in the bile, measured at one to two weeks postoperatively, is a very early indicator of successful bile drainage (Fig. 6).16 This seemed to be an even more reliable sign than bilirubin excretion in the early postoperative period and even appeared to correlate with survival. These data are somewhat preliminary and must await long term follow-up for confirmation. For the infant that does not drain bile after the first operation, or drains very small amounts of bile, reoperation and higher transection of atretic ducts may offer some hope for improved bile flow. In our own series;" and another previously reported.i a few infants have benefited from higher transection of ducts several weeks to months after the initial operation. Especially gratifying are the results of reoperation in infants who drained bile initially but who then stop. 16 We have found mechanical obstruction of the biliary jejunal loop, calculus sludge at the hepatoen-
Table 1.
Results of Hepatoportoenterostomy (Recent Series) PER CENT
INVESTIGATOR
Kasai et al. 7 Suruga et al. 7 Sawaguchi et al. 7 Altman 3 Weber et al. 16
WITH BILE
PER CENT
PERIOD
NO. OF PATIENTS
FLOW
JAUNDICE-FREE
1971-1977 1972-1977 1967-1977 1972-1978 1976--1979
67 58 90 43 17
89% 89% 63% 67% 82%
55% 70% 40% 42% 58%
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WEEKS POST OPERATIVE Figure 6. Clearance of alkaline phosphatase and bilirubin into bile after Kasai procedure, calculated using serum and bile levels of these substances, and bile volume. Note statistically significant differences between survivors and nonsurvivors at 1, 4 and 12 weeks for alkaline phosphatase clearance, and at 4 and 12 weeks for bilirubin clearance.
terostomyanastomosis, and recurrent fibrosis, all of which may respond to reoperation. It is clear that very close patient follow-up is mandatory for early diagnosis and operative therapy of these potential complications. The problem of postoperative cholangitis has received much attention, both clinically'? and experimentally, 8 without adequate resolution. Decrease in the volume of bile output, increasing serum bilirubin levels, fever, and lethargy are the most common signs and symptoms of this complication. Cholangitis can. occur anytime after the operative procedure but seems most prevalent in the first 12 to 18 months postoperatively. The therapy for cholangitis consists of admission to the hospital and the immediate institution of intravenous broad-spectrum antibiotics (gentamycin and ampicillin) after obtaining appropriate cultures of bile and blood. Irrigation of the biliostomy loop with antibiotic solutions has not been helpful in our experience. Prophylactic antibiotics (trimethoprim-sulfamethoxazole) have been utilized in
CONTEMPORARY MANAGEMENT OF BILIARY ATRESIA
."
1087
the postoperative period in an attempt to reduce the incidence of cholangitis, with equivocal results. It was hoped that exteriorization of the biliary loop would decrease the incidence of cholangitis; however, this has not been completely successful. The biliary loop becomes colonized with bacteria, primarily gram-negative organisms, very early after the Kasai procedure," and this undoubtedly plays a role in recurrent infections. Once bile flow is vigorous, usually at 18 to 24 months of age, the incidence of cholangitis decreases and the biliostomy is closed. Cholangitis is still possible, however, and thus close observation and repeat liver function studies are mandatory. Retrograde contrast study through the biliary ostomy should be performed in all cases of recurrent cholangitis, as an occasional infant will have partial obstruction of the loop. Portal hypertension is not an uncommon development after an hepatoportoenterostomy procedure, even in those infants with excellent bile flow. Continuing cirrhosis has been shown to occur after successful portoenterostomy, 4 and this frequently leads to portal hypertension and variceal hemorrhage. Various shunting procedures have been utilized in these children;' with good success in stopping the hemorrhage. Undoubtedly this complication will become more prevalent as many more of these children survive for more than four years. The Kasai procedure has been performed for the past 20 years in Japan; indeed, there are survivors that are now over 20 years of age. 7 However, only recently have continued refinements in the operative technique and preoperative and postoperative care been utilized, thus resulting in survival rates in the 50 per cent range. 3,5 Future improvement in survival would seem to depend on earlier operation, better understanding of the disease process, improved control of cholangitis postoperatively, and aggressive reoperation in those infants who have poor bile drainage or who stop draining bile.
SUMMARY The outlook for the infant with biliary atresia has improved considerably over the past 15 years since the introduction of hepatoportoenterostomy by Kasai, Survival rates of 50 per cent are now possible as a result of earlier operation and close follow-up for the detection of the serious complications that may occur. Further improvements in survival will undoubtedly result from increased understanding of the basic disease process involved.
REFERENCES 1. Altman, R. P.: Portal decompression by interposition mesocaval shunt in patients with biliary atresia. J. Pediatr. Surg., 11:809, 1976. 2. Altman, R. P.: Results of reoperations for correction of extrahepatic biliary atresia. J. Pediatr. Surg., 14:305, 1979. 3. Altman, R. P.: The portoenterostomy procedure for biliary atresia: A five year experience. Ann. Surg., 188:351, 1978. 4. Altman, R. P., Chandra, R., and Lilly, J. R.: Ongoing cirrhosis after successful portoenterostomy in infants with biliary atresia. J. Pediatr. Surg., 10:685, 1975. 5. Altman, R. P., and Lilly, J. R.: Technical details in the surgical correction of extrahepatic biliary atresia. Surg. Gynec. Obstet. 140:953, 1975. 6. Chandra, R. S., and Altman, R. P.: Ductal remnants in extrahepatic biliary atresia: A histopathologic study with clinical correlation. J. Pediatr., 93:196, 1978.
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L.
GROSFELD
7. Hays, D. M., and Kimura, K.: Biliary Atresia: The Japanese Experience. Cambridge, Harvard University Press, 1980. 8. Hirsig, J., Kara, 0., and Rickham, P. P.: Experimental investigations into the etiology for cholangitis following operation for biliary atresia. J. Pediatr. Surg., 13:55, 1978. 9. Hitch, D. C., and Lilly, J. R.: Identification, quantification, and significance of bacterial growth within the biliary tract after Kasai's operation. J. Pediatr. Surg., 13:563, 1978. 10. Hitch, D. C., Shikes, R. H., and Lilly, J. R.: Determinants of survival after Kasai's operation for biliary atresia. J. Pediatr. Surg., 14:310, 1979. 11. Izant, R. J., Akers, D. R., Hays, D. M., et al.: Biliary atresia survey. Presented at the 35th Annual Meeting, American Academy of Pediatrics, Chicago, October 1966. 12. Kasai, M., Kimura, S., Asakura, Y., et al.: Surgical treatment of biliary atresia. J. Pediatr. Surg., 3:665, 1968. 13. Lilly, J. R.: Surgical jaundice in infancy. Ann. Surg., 186:549, 1977. 14. Lilly, J. R., and Hitch, D. C.: Postoperative ascending cholangitis followingportoenterostomy for biliary atresia: Measures for control. World J. Surg., 2:581, 1978. 15. Thaler, M. M., and Gellis, S. S.: Studies in neonatal hepatitis and biliary atresia. Am. J. Dis. Child., 116:257, 1968. 16. Weber, T. R., Grosfeld, J. L., and Fitzgerald, J. F.: Prognostic determinants after hepatoportoenterostomy for biliary atresia. Am. J. Surg., 141:57, 1981. Department of Surgery James Whitcomb Riley Hospital for Children Indianapolis, Indiana 46223