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Cholelithiasis in infancy: Resolution of Gallstonesin three of four infants
C h o l e l i t h i a s i s in Infancy: Resolution of Gallstones in Three of Four Infants By Nabil N. Jacir, Kathryn D. Anderson, Martin Eichelberger, and Philip C. Guzzetta Washington, DC 9 Cholelithiasis in infancy is believed to be a rare finding. It is also held that all cholelithiasis in infancy has a predisposing factor such as hemolysis, prolonged fasting, congenital abnormality of the biliary tree, or the administration of T P N and is associated with severe morbidity and mortality. In the last three years, four infants at our hospital have been found on real-time ultrasonography to have gallstones. Their ages ranged from 3 weeks to 6 months. One patient had a hemolytic disease but the finding of cholelithiasis in the other three patients was incidental. A repeat sonogram in the infant with hemolysis three months after initial recognition and one day before scheduled cholecystectomy revealed spontaneous resolution of the gallstones. This led us to a conservative approach in the other three patients. T w o more infants had spontaneous resolution of their gallstones and one child, n o w aged 16 months, is thriving with a persistent asymptomatic gallstone visible on sonogram. 9 1986 by Grune & Stratton, Inc.
administered. An abdominal sonogram at four days of age was normal. Hepatitis antigen, G6PD, alpha 1 antitrypsin, and T O R C H (toxoplasmosis, rubella, cytomegalovirus, hepatitis, and herpes) levels were normal, except for a herpes titer of 1 to 64. At six weeks of age, H I D A scan revealed intrahepatic cholestasis with patent extrahepatic biliary ducts. Repeat of the abdominal sonogram revealed cholelithiasis (Fig 1). Two weeks later, the total bilirubin had fallen to 3.9 mg percent, and repeat sonogram again confirmed gallstones. Three weeks later, the bilirubin was 3.4 mg percent total, 0.8 direct, and S G O T was 200. A percutaneous liver biopsy was performed. The biopsy revealed "cholestasis, giant cell transformation, and portal fibrosis." The child was scheduled for elective cholecystectomy, because of the persistence of gallstones. On admission for surgery at 14 weeks of age, the child was noted to be anicteric for the first time, and the bilirubin was 0.4 mg percent. The child was asymptomatic and feeding well, stools were normal in color. Sonogram revealed no evidence of gallstones (Fig 2), and surgery was cancelled. Repeat sonograms 2 weeks and 6 months later were also normal. All liver function studies have returned to normal and the child is developing and growing normally.
INDEX W O R D : Cholelithiasis.
Case 2
H O L E L I T H I A S I S in infancy is rare. ~ s A number of conditions that occur in the neonatal period predispose to the development of cholelithiasis. These include congenital abnormalities of the biliary tract, hemolysis, prolonged fasting and TPN administration, use of diuretics, and diseases of the terminal ileum. ~'4-7 In addition, phototherapy, use of umbilical vein catheters, infection, and the use of antibiotics have been implicated in the development of gallstones) Cholelithiasis in infancy is usually associated with severe morbidity and mortality. Perforation of the biliary tract and peritonitis are among the reported complications) The conventional approach to cholelithiasis has, therefore, primarily been surgical, and cholecystectomy has been recommended. 9 In the last 3 years, we have found gallstones in four infants undergoing abdominal ultrasound. Since the finding was incidental in 3 of the 4 infants and repeat sonography has shown disappearance of the stones in all but one of the infants, we present this report and suggest a conservative approach to cholelithiasis in the asymptomatic infant.
C
CASE REPORTS Case I A full-term black female had moderate hepatosplenomegaly, tachypnea, and rales at birth. The child's blood type was B positive and the mother was O negative. Bilirubin rose to 22.4 mg percent total, 14.2 mg percent direct. Phototherapy and phenobarbital were
Journal of Pediatric Surgery, Vo121, No 7 (July), 1986: pp 567-569
A three-week-old white male presented with a four-day history of projectile vomiting. Perinatal history was unremarkable. Physical examination was within normal limits. Blood count, serum electrolytes, and urinalysis were normal. Sonography of the upper abdomen showed a pyloric enlargement consistent with hypertrophic pyloric stenosis. Also noted within the gallbladder was mobile echogenic material that exhibited acoustic shadowing. The infant underwent pyloromyotomy with no attempt at exploring the gallbladder. Recovery was uneventful. Four months later, a repeat sonogram showed normal gallbladder, bile ducts, and pylorus. The infant is doing well.
Case 3 A two-week-old white female presented with vomiting since birth. Perinatal history was unremarkable. Physical exam was within normal limits. Her blood count, blood chemistry, and urinalysis were all normal. Sonography of the upper abdomen revealed a normal pylorus but a mobile tiny echogenic focus was seen in the gallbladder. An upper GI series revealed gastroesophageal reflux with no other abnormalities. The infant did very well on medical management of her gastroesophageal reflux. Follow-up ultrasonography at three months of age was normal.
From the Children's Hospital National Medical Center, Washington, DC. Presented at the 34th Annual Meeting o f the Surgical Section o f the American Academy o f Pediatrics, San Antonio, Texas, October 19-20, 1985. Address reprint requests to Nabil N. Jacir, MD, Children~ Hospital National Medical Center, I I 1 Michigan Ave, NW, Washington, DC 20010. :e'~1986 by Grune & Stratton, Inc. 0022-3468/86/2 107-0002503.00/0
567
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JACIR ET AL
Fig I. The gallbladder has mobile echogenic material causing acoustic shadowing.
Case 4 A six-month-old black male presented with a history of intermittent vomiting and constipation since the age of 2 months. Physical exam was normal. A plain film of the abdomen revealed calcification in the right upper quadrant. An upper GI showed gastroesophageal reflux. Sonography of the upper abdomen showed the calcification to be a mobile gallstone in the gallbladder. The patient improved dramatically on medical treatment for his reflux, and improved from the third percentile to the 50th percentile in weight. Sonography at one year of age showed the persistence of a single gallstone. The child is asymptomatic and thriving. DISCUSSION
Cholelithiasis in childhood, and particularly in infancy, is uncommonly recognized) -3 It is also thought that cholelithiasis in infancy is associated with severe morbidity and mortality. In a series of ten neonates with cholelithiasis collected and reported by Brill et al, half of these patients had perforation of the gallbladder or common bile duct. 2 Several underlying conditions appear to predispose to cholelithiasis, including hemolytic anemias with the increased hepatic excretion and congenital abnormalities of the biliary tract. Cholelithiasis is also associated with
Fig 2.
Normal gallbladder with no evidence of gallstones.
administration of TPN and furosemide, prolonged fasting, and the use of phototherapy. ''4'8 Ileal resection or ileal disease that interrupts the enterohepatic circulation of bile salts are also incriminated in the development of cholelithiasis.6 Other predisposing conditions are the use of umbilical vein catheters, infection, and antibiotics. The finding of cholelithiasis was incidental in 3 of our 4 patients. Only one patient (Case 1), had an increase in bilirubin. Wooley et al ~~ report a 2% incidence of jaundice in babies with hypertrophic pyloric stenosis; however, patient 2 was anicteric, although he had hypertrophic pyloric stenosis. The other two patients had gastroesophageal reflux. Therefore, 3 of our 4 patients were completely asymptomatic with respect to the bilary tree, and had no known predisposing factor to develop cholelithiasis. As ultrasonographic examination of the upper abdomen gains popularity for initial screening in infants with vomiting, more cases of cholelithiasis probably will be encountered in infants who have no symptoms referable to the bilary tree. Gallstones are seen as echogenic material on ultrasonography, which exhibits acoustic shadowing, unlike sludge, which does not show acoustic shadowing, l~ Hematomas and polyps in the wall of the gallbladder are echogenic but do not exhibit acoustic shadowing and are, usually, immobile. Food particles and feces within the gallbladder lumen in patients with biliary enteric surgical anastomosis or fistula can exhibit acoustic shadowing) ~ All of our patients exhibited acoustic shadowing and, therefore, they met the ultrasonographic criteria for the diagnosis of cholelithiasis. Spontaneous resolution of cholelithiasis occurred in 3 of our 4 patients. The gallstones disappeared at age three and a half months in patient no. 1, at age 4 months in patient no. 2, and at age 3 months in patient no. 3. The calcific gallstone in the infant who presented with vomiting at age six months (Case 4) persisted. This infant is asymptomatic and thriving, with a persistent gallstone one year after initial diagnosis. A follow-up sonogram is recommended at 4 to 6 months. The natural history of cholelithasis in infants is unclear. In the young infant, who is asymptomatic in the absence of clinical and radiologic evidence of bilary tract disease, cholecystectomy would appear to be indicated, only after a reasonable delay to see if the gallstones will disappear spontaneously. We are not sure whether the child who still has a calcified stone at the age of 18 months should be subjected to cholecystectomy in the absence of symptoms. We plan repeat sonograms at 4- to 6-month intervals in the other three infants. Close follow-up of the fourth patient is also planned.
CHOLELITHIASlS IN FOUR INFANTS
569
REFERENCES
I. Whitington PF, Black DD: Cholelithiasis in premature infants treated with parenteral nutrition and furosemide. J Pediatr 97:647649, 1980 2. Brill PW, Winchester P, Rosen MS: Neonatal cholelithiasis. Pediatr Radiol 12:285-288, 1982 3. Boyle R J, Sumner TE, Vollery FM: Cholelithiasis in a 3week-old small premature infant. Pediatr 71:967-969, 1983 4. Moosa A: Cholelithaisis in childhood. J R Coil Surg Edinb 18:42-46, 1973 5. Pearson HA: Sickle cell syndrome and other hemoglobinopathies, in Miller D, Bachman R, McMillon C (eds): Blood Diseases of Infancy and Childhood. St Louis, Mosby, 1984, pp 413-414 6. Pellerin D, Bertin P, Nihoul-Fekete C, et al: Cholelithiasis and ileal pathology in childhood. J Pediatr Surg 10:35-41, 1975
7. CaUahan J, Hailer JO, Cacciarelli AA, et al: Cholelithiasis in infants: Association with total parenteral nutrition and furosemide. Radiology 143:432-439, 1982 8. McDonagh AF: Phototherapy: A new twist to bilirubin. J Pediatr 99:909-91 I, 1982 9. flays DM: Biliary tract and liver, in Holden, Ashcraft (eds): Pediatric Surgery. Philadelphia, Saunders, 1980, pp 525-526 10. Woolley MM, Felsher BF, Asch M J, et al: Jaundice, pyloric stenosis and hepatic glucuronyl transferanse. J Pediatr Surg 9:359363, 1974 I1. Durrell CA, Vincent LM, Mittelstaedt CA: Gallbladder ultrasonography in clinical context. Seminar Ultra CT MB 5:316317, 1984
administered. An abdominal sonogram at four days of age was normal. Hepatitis antigen, G6PD, alpha 1 antitrypsin, and T O R C H (toxoplasmosis, rubella, cytomegalovirus, hepatitis, and herpes) levels were normal, except for a herpes titer of 1 to 64. At six weeks of age, H I D A scan revealed intrahepatic cholestasis with patent extrahepatic biliary ducts. Repeat of the abdominal sonogram revealed cholelithiasis (Fig 1). Two weeks later, the total bilirubin had fallen to 3.9 mg percent, and repeat sonogram again confirmed gallstones. Three weeks later, the bilirubin was 3.4 mg percent total, 0.8 direct, and S G O T was 200. A percutaneous liver biopsy was performed. The biopsy revealed "cholestasis, giant cell transformation, and portal fibrosis." The child was scheduled for elective cholecystectomy, because of the persistence of gallstones. On admission for surgery at 14 weeks of age, the child was noted to be anicteric for the first time, and the bilirubin was 0.4 mg percent. The child was asymptomatic and feeding well, stools were normal in color. Sonogram revealed no evidence of gallstones (Fig 2), and surgery was cancelled. Repeat sonograms 2 weeks and 6 months later were also normal. All liver function studies have returned to normal and the child is developing and growing normally.
INDEX W O R D : Cholelithiasis.
Case 2
H O L E L I T H I A S I S in infancy is rare. ~ s A number of conditions that occur in the neonatal period predispose to the development of cholelithiasis. These include congenital abnormalities of the biliary tract, hemolysis, prolonged fasting and TPN administration, use of diuretics, and diseases of the terminal ileum. ~'4-7 In addition, phototherapy, use of umbilical vein catheters, infection, and the use of antibiotics have been implicated in the development of gallstones) Cholelithiasis in infancy is usually associated with severe morbidity and mortality. Perforation of the biliary tract and peritonitis are among the reported complications) The conventional approach to cholelithiasis has, therefore, primarily been surgical, and cholecystectomy has been recommended. 9 In the last 3 years, we have found gallstones in four infants undergoing abdominal ultrasound. Since the finding was incidental in 3 of the 4 infants and repeat sonography has shown disappearance of the stones in all but one of the infants, we present this report and suggest a conservative approach to cholelithiasis in the asymptomatic infant.
C
CASE REPORTS Case I A full-term black female had moderate hepatosplenomegaly, tachypnea, and rales at birth. The child's blood type was B positive and the mother was O negative. Bilirubin rose to 22.4 mg percent total, 14.2 mg percent direct. Phototherapy and phenobarbital were
Journal of Pediatric Surgery, Vo121, No 7 (July), 1986: pp 567-569
A three-week-old white male presented with a four-day history of projectile vomiting. Perinatal history was unremarkable. Physical examination was within normal limits. Blood count, serum electrolytes, and urinalysis were normal. Sonography of the upper abdomen showed a pyloric enlargement consistent with hypertrophic pyloric stenosis. Also noted within the gallbladder was mobile echogenic material that exhibited acoustic shadowing. The infant underwent pyloromyotomy with no attempt at exploring the gallbladder. Recovery was uneventful. Four months later, a repeat sonogram showed normal gallbladder, bile ducts, and pylorus. The infant is doing well.
Case 3 A two-week-old white female presented with vomiting since birth. Perinatal history was unremarkable. Physical exam was within normal limits. Her blood count, blood chemistry, and urinalysis were all normal. Sonography of the upper abdomen revealed a normal pylorus but a mobile tiny echogenic focus was seen in the gallbladder. An upper GI series revealed gastroesophageal reflux with no other abnormalities. The infant did very well on medical management of her gastroesophageal reflux. Follow-up ultrasonography at three months of age was normal.
From the Children's Hospital National Medical Center, Washington, DC. Presented at the 34th Annual Meeting o f the Surgical Section o f the American Academy o f Pediatrics, San Antonio, Texas, October 19-20, 1985. Address reprint requests to Nabil N. Jacir, MD, Children~ Hospital National Medical Center, I I 1 Michigan Ave, NW, Washington, DC 20010. :e'~1986 by Grune & Stratton, Inc. 0022-3468/86/2 107-0002503.00/0
567
568
JACIR ET AL
Fig I. The gallbladder has mobile echogenic material causing acoustic shadowing.
Case 4 A six-month-old black male presented with a history of intermittent vomiting and constipation since the age of 2 months. Physical exam was normal. A plain film of the abdomen revealed calcification in the right upper quadrant. An upper GI showed gastroesophageal reflux. Sonography of the upper abdomen showed the calcification to be a mobile gallstone in the gallbladder. The patient improved dramatically on medical treatment for his reflux, and improved from the third percentile to the 50th percentile in weight. Sonography at one year of age showed the persistence of a single gallstone. The child is asymptomatic and thriving. DISCUSSION
Cholelithiasis in childhood, and particularly in infancy, is uncommonly recognized) -3 It is also thought that cholelithiasis in infancy is associated with severe morbidity and mortality. In a series of ten neonates with cholelithiasis collected and reported by Brill et al, half of these patients had perforation of the gallbladder or common bile duct. 2 Several underlying conditions appear to predispose to cholelithiasis, including hemolytic anemias with the increased hepatic excretion and congenital abnormalities of the biliary tract. Cholelithiasis is also associated with
Fig 2.
Normal gallbladder with no evidence of gallstones.
administration of TPN and furosemide, prolonged fasting, and the use of phototherapy. ''4'8 Ileal resection or ileal disease that interrupts the enterohepatic circulation of bile salts are also incriminated in the development of cholelithiasis.6 Other predisposing conditions are the use of umbilical vein catheters, infection, and antibiotics. The finding of cholelithiasis was incidental in 3 of our 4 patients. Only one patient (Case 1), had an increase in bilirubin. Wooley et al ~~ report a 2% incidence of jaundice in babies with hypertrophic pyloric stenosis; however, patient 2 was anicteric, although he had hypertrophic pyloric stenosis. The other two patients had gastroesophageal reflux. Therefore, 3 of our 4 patients were completely asymptomatic with respect to the bilary tree, and had no known predisposing factor to develop cholelithiasis. As ultrasonographic examination of the upper abdomen gains popularity for initial screening in infants with vomiting, more cases of cholelithiasis probably will be encountered in infants who have no symptoms referable to the bilary tree. Gallstones are seen as echogenic material on ultrasonography, which exhibits acoustic shadowing, unlike sludge, which does not show acoustic shadowing, l~ Hematomas and polyps in the wall of the gallbladder are echogenic but do not exhibit acoustic shadowing and are, usually, immobile. Food particles and feces within the gallbladder lumen in patients with biliary enteric surgical anastomosis or fistula can exhibit acoustic shadowing) ~ All of our patients exhibited acoustic shadowing and, therefore, they met the ultrasonographic criteria for the diagnosis of cholelithiasis. Spontaneous resolution of cholelithiasis occurred in 3 of our 4 patients. The gallstones disappeared at age three and a half months in patient no. 1, at age 4 months in patient no. 2, and at age 3 months in patient no. 3. The calcific gallstone in the infant who presented with vomiting at age six months (Case 4) persisted. This infant is asymptomatic and thriving, with a persistent gallstone one year after initial diagnosis. A follow-up sonogram is recommended at 4 to 6 months. The natural history of cholelithasis in infants is unclear. In the young infant, who is asymptomatic in the absence of clinical and radiologic evidence of bilary tract disease, cholecystectomy would appear to be indicated, only after a reasonable delay to see if the gallstones will disappear spontaneously. We are not sure whether the child who still has a calcified stone at the age of 18 months should be subjected to cholecystectomy in the absence of symptoms. We plan repeat sonograms at 4- to 6-month intervals in the other three infants. Close follow-up of the fourth patient is also planned.
CHOLELITHIASlS IN FOUR INFANTS
569
REFERENCES
I. Whitington PF, Black DD: Cholelithiasis in premature infants treated with parenteral nutrition and furosemide. J Pediatr 97:647649, 1980 2. Brill PW, Winchester P, Rosen MS: Neonatal cholelithiasis. Pediatr Radiol 12:285-288, 1982 3. Boyle R J, Sumner TE, Vollery FM: Cholelithiasis in a 3week-old small premature infant. Pediatr 71:967-969, 1983 4. Moosa A: Cholelithaisis in childhood. J R Coil Surg Edinb 18:42-46, 1973 5. Pearson HA: Sickle cell syndrome and other hemoglobinopathies, in Miller D, Bachman R, McMillon C (eds): Blood Diseases of Infancy and Childhood. St Louis, Mosby, 1984, pp 413-414 6. Pellerin D, Bertin P, Nihoul-Fekete C, et al: Cholelithiasis and ileal pathology in childhood. J Pediatr Surg 10:35-41, 1975
7. CaUahan J, Hailer JO, Cacciarelli AA, et al: Cholelithiasis in infants: Association with total parenteral nutrition and furosemide. Radiology 143:432-439, 1982 8. McDonagh AF: Phototherapy: A new twist to bilirubin. J Pediatr 99:909-91 I, 1982 9. flays DM: Biliary tract and liver, in Holden, Ashcraft (eds): Pediatric Surgery. Philadelphia, Saunders, 1980, pp 525-526 10. Woolley MM, Felsher BF, Asch M J, et al: Jaundice, pyloric stenosis and hepatic glucuronyl transferanse. J Pediatr Surg 9:359363, 1974 I1. Durrell CA, Vincent LM, Mittelstaedt CA: Gallbladder ultrasonography in clinical context. Seminar Ultra CT MB 5:316317, 1984