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High-dose omeprazole in esophagitis with stenosis after surgical treatment of esophageal atresia
High-Dose Omeprazole in Esophagitis With Stenosis After Surgical Treatment of Esophageal Atresia By Ste´phanie Van Biervliet, Myriam Van Winckel, Eddy Robberecht, and Ilse Kerremans Ghent, Belgium
The authors describe 4 children with recurrent stenosis and persistent esophagitis after secondary repair of a long gap esophageal atresia. They underwent an esophageal reconstruction by elongation of the lesser gastric curvature according to Scha¨rli at the age of 11 to 14 months. All had esophagitis grade III to IV (Savary-Miller classification), esophageal stenosis, and failure to thrive. Effective treatment of the esophagitis and prevention of stenosis consisted
in high doses of omeprazole (1.9 to 2.5 mg/kg/d). After this treatment, the need for esophageal dilatation disappeared, and nutritional status normalized. J Pediatr Surg 36:1416-1418. Copyright © 2001 by W.B. Saunders Company.
C
13 months. Oral feeding was started 20 days later. Three months later esophagitis grade II according to Savary-Miller was diagnosed by esophagoscopy and treated with ranitidine, 18 mg/kg/d. Despite these measures, evolution to esophagitis grade IV and stenosis developed. Nasogastric tube feeding was necessary to maintain body weight. In view to persistent esophagitis, therapy was changed to omeprazole (OM) 1.15 mg/kg/d. The esophagitis persisted until the OM dose was increased to 2.5 mg/kg/d. The body mass index (BMI) before repair was 97% of median BMI for age and gender. The BMI fell to 78% and increased again to 92% of BMI for age and gender, under treatment with high-dose omeprazole.
HILDREN with long gap esophageal atresia (EA) can be treated by elongation of the lesser gastric curvature.1 Stenosis of the anastomosis and reflux oesophagitis, however, remains a frequent complication of this procedure. Recurrent dilatation and need for tube feeding impairs the quality of life of these patients. This report describes how high doses of omeprazole (OM) do control the esophagitis and the secondary stricture formation. Ranitidine or lower dose OM, however, had no impact on the course of these complications.
Case 2
CASE REPORTS We describe 4 patients with long gap EA at birth (neonatal gap length ⬎ than 3 cm). Primary repair was impossible, so a cervical esophagostomy and gastrostomy were performed soon after birth. Oral feeding was started soon after the primary intervention to enable the development of normal oral motor capacities.2 Feeding reflexes were maintained by regular administration of oral food, drained through the cervicostomy. The first year of life, the children were fed by the gastrostomy tube. Reanastomosis according to Scha¨rli1 was performed at about 1 year of life. However, severe gastroesophageal reflux disease (GERD) and esophageal stricture, compromising normal feeding, followed this intervention.
Case 1 A boy, born at term, weighing 2.700 kg (⬍P10), with a length of 48 cm (P10), after an uneventful pregnancy, underwent a cervical esophagostomy and gastrostomy at day 2, because of a long gap EA without tracheoesophageal fistula (TEF). Besides a single left kidney, no other congenital malformations were present. Anastomosis was performed at
From the Departments of Pediatrics and Pediatric Surgery, University Hospital Ghent, Belgium. Address reprint requests to Ste´phanie Van Biervliet, Department of Paediatric Gastroenterology, University Hospital Ghent, De pintelaan 185, Ghent, B9000, Belgium. Copyright © 2001 by W.B. Saunders Company 0022-3468/01/3609-0021$35.00/0 doi:10.1053/jpsu.2001.26388 1416
INDEX WORDS: Esophageal atresia, esophagitis, omeprazole, translocation 46,XY,t(4;7;14)(q21;q31.2;q24.3).
A boy, born at term after an uneventful pregnancy, weighing 2.800 kg (⬍P10) with a length of 50 cm (⬍P30), had a long gap EA with a distal TEF, an external hydrocephaly, polydactily of the right hand, and an abnormal thumb on the left hand. A complex translocation 46,XY,t(4;7; 14)(q21;q31.2;q24.3) was diagnosed. Cervical esophagostomy, gastrostomy, and ligation of the fistula were performed at day 2. The hydrocephalus compensated spontaneously, but neuromotor evolution was slightly retarded. Anastomosis was performed at the age of 14 months. Oral feeding was started 8 days later. After 2 months an esophagoscopy was performed because of food refusal. A grade 2 esophagitis without stenosis was diagnosed for which 18 mg/kg/d ranitidine was given. One month later he had a stricture of the anastomosis, and the esophagitis was still present. Therapy was switched to OM (1.25 mg/kg/d). In this period, supplementary nasogastric tube feeding was started because of weight loss. Because of persistent esophagitis and recurrent stenosis, the OM dose was increased to 2.5 mg/kg/d. On this dose, the esophagitis healed within a few weeks. Nevertheless, continuous overnight tube feeding still is necessary 1 year after surgery) because of failure to thrive and chronic diarrhea caused by a dumping syndrome, a current problem in the treatment of EA.3 The BMI decreased from 93% before correction, to 75% of BMI after repair. After treatment with OM it increased again to 85%.
Case 3 A girl, born at term, weighing 2.5 kg (⬍P10), with a length of 48 cm (P10), after an uneventful pregnancy had a long gap EA without TEF. She underwent a cervical esophagostomy and gastrostomy the day after she was born. She received normal oral feeding together with tube feeding. Anastomosis was performed at the age of 14 months. Seven
Journal of Pediatric Surgery, Vol 36, No 9 (September), 2001: pp 1416-1418
ESOPHAGITIS AFTER ESOPHAGEAL ATRESIA
1417
days later oral feeding was started. One month later progressive feeding difficulties suggested a stenosis, confirmed by endoscopy. After dilatation a fulminant grade 4 esophagitis was seen, for which OM (1.2 mg/kg/d) was given. She needed dilatation twice a month. Because of persistent weight loss caused by insufficient food intake, a new gastrostomy was performed to enable supplementary gastric tube feeding. Six months after the intervention, in view of a persistent grade 3 esophagitis, the OM dose was increased to 2.3 mg/kg/d. The esophagitis healed, and the need for dilatation decreased. The last dilatation took place 9 months after the correction. Supplementary tube feeding could be stopped one year after the surgery. The BMI decreased from 99% before correction, to 80% of BMI after repair. After treatment it increased to 89%.
Case 4 A boy, born at term after an uncomplicated pregnancy, weighing 3 kg (P10), with a length of 48 cm (P10), underwent a primary repair for his EA with TEF at day 2. A second-look operation was done after 9 days, because of a persisting pneumothorax. There was a disruption of the primary anastomosis. A cervical esophagostomy and gastrostomy was then performed. The reanastomosis at the age of 11 months was difficult. He started oral feeding after 14 days. One month after the correction, oral feeding became impossible. An almost complete stenosis of the anastomosis developed. A gastrostomy was necessary. OM, 1.1 mg/kg/d was started 4 months after surgery for a grade 4 esophagitis. In view of the persisting esophagitis, the OM dose was increased to 1.9 mg/kg/d. Oral food intakes gradually improved. The gastrostomy was removed 1 year after surgery. The BMI decreased from 91% before to 75% of BMI after repair. After treatment it increased to 89%.
DISCUSSION
Gastric transposition (GT) has become a reliable surgical treatment option.4 Despite the fact that oral-motor and sensory functions and deglutition reflexes were developed normally before restoration of the esophageal continuity,2,5 progressive feeding difficulties occurred in our patients after anastomosis according to Scha¨rli.1 These were caused by esophagitis and stricture formation. Anastomotic strictures commonly occur after EA repair. Factors that predispose to development of anastomotic strictures include ischemia, excess tension, anastomotic leak or dehiscence, 2-layer anastomosis, and, most frequently, GERD.6 Normal esophageal transport function is a complex mechanism that depends on effective esophageal motility, timely relaxation an contractil-
ity of the lower oesophageal sphincter, the mean intralumenal pressure in the stomach, and the gastric emptying.7 More than one of these factors are abnormal in the child with EA. These 4 patients all suffered from a long gap EA. Their postoperative problems were mainly caused by GERD, esophagitis, and stricture of the anastomosis. The most important problem we were confronted with, was the severe and resistant esophagitis. The Scha¨rli procedure is reported to induce acid reflux in the remaining esophagus and the intrathoracic portion of the stomach.1 In Scha¨rli’s original report, however, none of his patients had esophagitis. Later reports describe, however, the regular occurrence of benign strictures.9 In two of our patients the initial anti-acid treatment was high-dose ranitidine, because OM is not registered for children in Belgium. Neither this treatment nor the low OM doses of 1.1 to 1.25 mg/kg/d were able to control the esophagitis, despite the fact that the starting dose of OM already was well above the advised 0.7 mg/kg/d.10 By titrating therapy to clinical efficacy, several months were lost before the esophagitis was finally cured. The effective dose was 1.9 to 2.5 mg/kg/d, which is within the range reported in the pediatric literature (0.7 to 3.3 mg/kg/d).10,11 We did not observe adverse effects. As observed in adults,12 the strictures disappeared once the esophagitis was cured. At this moment, 18 to 24 months after surgical repair, all children are still treated with high dose OM. It is unclear for how long this treatment will be necessary. Because the anatomic situation does not change, life-long treatment might be necessary. Insufficient oral intake and failure to thrive necessitated tube feeding in all our patients. From this experience we would conclude that during the postrepair period, tube feeding is mandatory to maintain a good nutritional status. Therefore, we suggest maintaining a gastrostomy in the immediate postoperative period.8 We would propose to use high-dose omeprazole directly after a surgical repair of long gap EA, because of the high risk of severe GERD.13,14
REFERENCES 1. Scha¨rli AF: Esophageal reconstruction by elongation of the lesser gastric curve. Pediatr Surg Int 11:214-171, 1996 2. Cavallaro S, Pineschi A, Freni G, et al: Feeding troubles following delayed primary repair of esophageal atresia. Eur J Pediatr Surg 2:73-77, 1992 3. Bergmeijer JH, Hazebroek FW: Prospective medical and surgical treatment of gastroesophageal reflux in esophageal atresia. J AM Coll Surg 187:153-157, 1998 4. Davenport M, Hosie GP, Tasker RC, et al: Long term effects of gastric transposition in children: A physiological study. J Pediatr Surg 31:588-593, 1996 5. Moreno-Villares J, Galiano-Segovia MJ, Martin-Ferrer M: Alter-
ationes de la conducta alimentaria en pacientes que precisarion nutricion enteral durante el primer ano de vida. (Changes in feeding behavior of patients who had received enteral nutrition during the 1st year of life). Nutr Hosp 13:90-94, 1998 6. Beasley SW: Esophageal atresia and tracheoesophageal fistula, in Oldham KJ, Colombani PM, Foglia RP (eds): Surgery in infants and children: Scientific principles and practice. Philadelphia, PA, Lippincett-Raven Publishers, 1997, pp 1032-1033. 7. Fonkalsrud EW, Ament ME: gastroesophageal reflux in childhood. Curr Probl Surg 33:1-70, 1996 8. Moriarty KP, Jacir NN, Harris BM, et al: Transanastomotic feeding tubes in repair of esophageal atresia. J Pediatr Surg 31:53-54, 1996
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9. Macksood DJ, Blane CE, Drongowski RA, et al: Complications after gastric transposition in children. Can Assoc Radiol J 48:259-264, 1997 10. Walters JK, Zimmermann AE, Souney PF, et al: The use of omeprazole in pediatric population. Ann Pharmacother 32:478-480, 1998 11. Gunasekaran TS, Hassal EG: Efficacy and safety of omeprazole for severe gastroesophageal reflux in children J Pediatr 123:148-54, 1993
VAN BIERVLIET ET AL
12. Marks RD, Richter JE, et al: Omeprazole v. H2 receptor antagonist in treating patients with peptic stricture and esophagitis. Gastroenterology 106:907-915, 1994 13. Hassall E: Wrap session: Is the Nissen slipping? Can medical treatment replace surgery for severe gastroesophageal reflux disease in children? Am J Gastroenterol 12:43-49, 1998 14. Stal JM, Gregor JC, et al: A cost-utility analysis comparing omeprazole with ranitidine in the maintenance therapy of peptic esophageal stricture. Can J Gastroenterol 12:43-49, 1998
The authors describe 4 children with recurrent stenosis and persistent esophagitis after secondary repair of a long gap esophageal atresia. They underwent an esophageal reconstruction by elongation of the lesser gastric curvature according to Scha¨rli at the age of 11 to 14 months. All had esophagitis grade III to IV (Savary-Miller classification), esophageal stenosis, and failure to thrive. Effective treatment of the esophagitis and prevention of stenosis consisted
in high doses of omeprazole (1.9 to 2.5 mg/kg/d). After this treatment, the need for esophageal dilatation disappeared, and nutritional status normalized. J Pediatr Surg 36:1416-1418. Copyright © 2001 by W.B. Saunders Company.
C
13 months. Oral feeding was started 20 days later. Three months later esophagitis grade II according to Savary-Miller was diagnosed by esophagoscopy and treated with ranitidine, 18 mg/kg/d. Despite these measures, evolution to esophagitis grade IV and stenosis developed. Nasogastric tube feeding was necessary to maintain body weight. In view to persistent esophagitis, therapy was changed to omeprazole (OM) 1.15 mg/kg/d. The esophagitis persisted until the OM dose was increased to 2.5 mg/kg/d. The body mass index (BMI) before repair was 97% of median BMI for age and gender. The BMI fell to 78% and increased again to 92% of BMI for age and gender, under treatment with high-dose omeprazole.
HILDREN with long gap esophageal atresia (EA) can be treated by elongation of the lesser gastric curvature.1 Stenosis of the anastomosis and reflux oesophagitis, however, remains a frequent complication of this procedure. Recurrent dilatation and need for tube feeding impairs the quality of life of these patients. This report describes how high doses of omeprazole (OM) do control the esophagitis and the secondary stricture formation. Ranitidine or lower dose OM, however, had no impact on the course of these complications.
Case 2
CASE REPORTS We describe 4 patients with long gap EA at birth (neonatal gap length ⬎ than 3 cm). Primary repair was impossible, so a cervical esophagostomy and gastrostomy were performed soon after birth. Oral feeding was started soon after the primary intervention to enable the development of normal oral motor capacities.2 Feeding reflexes were maintained by regular administration of oral food, drained through the cervicostomy. The first year of life, the children were fed by the gastrostomy tube. Reanastomosis according to Scha¨rli1 was performed at about 1 year of life. However, severe gastroesophageal reflux disease (GERD) and esophageal stricture, compromising normal feeding, followed this intervention.
Case 1 A boy, born at term, weighing 2.700 kg (⬍P10), with a length of 48 cm (P10), after an uneventful pregnancy, underwent a cervical esophagostomy and gastrostomy at day 2, because of a long gap EA without tracheoesophageal fistula (TEF). Besides a single left kidney, no other congenital malformations were present. Anastomosis was performed at
From the Departments of Pediatrics and Pediatric Surgery, University Hospital Ghent, Belgium. Address reprint requests to Ste´phanie Van Biervliet, Department of Paediatric Gastroenterology, University Hospital Ghent, De pintelaan 185, Ghent, B9000, Belgium. Copyright © 2001 by W.B. Saunders Company 0022-3468/01/3609-0021$35.00/0 doi:10.1053/jpsu.2001.26388 1416
INDEX WORDS: Esophageal atresia, esophagitis, omeprazole, translocation 46,XY,t(4;7;14)(q21;q31.2;q24.3).
A boy, born at term after an uneventful pregnancy, weighing 2.800 kg (⬍P10) with a length of 50 cm (⬍P30), had a long gap EA with a distal TEF, an external hydrocephaly, polydactily of the right hand, and an abnormal thumb on the left hand. A complex translocation 46,XY,t(4;7; 14)(q21;q31.2;q24.3) was diagnosed. Cervical esophagostomy, gastrostomy, and ligation of the fistula were performed at day 2. The hydrocephalus compensated spontaneously, but neuromotor evolution was slightly retarded. Anastomosis was performed at the age of 14 months. Oral feeding was started 8 days later. After 2 months an esophagoscopy was performed because of food refusal. A grade 2 esophagitis without stenosis was diagnosed for which 18 mg/kg/d ranitidine was given. One month later he had a stricture of the anastomosis, and the esophagitis was still present. Therapy was switched to OM (1.25 mg/kg/d). In this period, supplementary nasogastric tube feeding was started because of weight loss. Because of persistent esophagitis and recurrent stenosis, the OM dose was increased to 2.5 mg/kg/d. On this dose, the esophagitis healed within a few weeks. Nevertheless, continuous overnight tube feeding still is necessary 1 year after surgery) because of failure to thrive and chronic diarrhea caused by a dumping syndrome, a current problem in the treatment of EA.3 The BMI decreased from 93% before correction, to 75% of BMI after repair. After treatment with OM it increased again to 85%.
Case 3 A girl, born at term, weighing 2.5 kg (⬍P10), with a length of 48 cm (P10), after an uneventful pregnancy had a long gap EA without TEF. She underwent a cervical esophagostomy and gastrostomy the day after she was born. She received normal oral feeding together with tube feeding. Anastomosis was performed at the age of 14 months. Seven
Journal of Pediatric Surgery, Vol 36, No 9 (September), 2001: pp 1416-1418
ESOPHAGITIS AFTER ESOPHAGEAL ATRESIA
1417
days later oral feeding was started. One month later progressive feeding difficulties suggested a stenosis, confirmed by endoscopy. After dilatation a fulminant grade 4 esophagitis was seen, for which OM (1.2 mg/kg/d) was given. She needed dilatation twice a month. Because of persistent weight loss caused by insufficient food intake, a new gastrostomy was performed to enable supplementary gastric tube feeding. Six months after the intervention, in view of a persistent grade 3 esophagitis, the OM dose was increased to 2.3 mg/kg/d. The esophagitis healed, and the need for dilatation decreased. The last dilatation took place 9 months after the correction. Supplementary tube feeding could be stopped one year after the surgery. The BMI decreased from 99% before correction, to 80% of BMI after repair. After treatment it increased to 89%.
Case 4 A boy, born at term after an uncomplicated pregnancy, weighing 3 kg (P10), with a length of 48 cm (P10), underwent a primary repair for his EA with TEF at day 2. A second-look operation was done after 9 days, because of a persisting pneumothorax. There was a disruption of the primary anastomosis. A cervical esophagostomy and gastrostomy was then performed. The reanastomosis at the age of 11 months was difficult. He started oral feeding after 14 days. One month after the correction, oral feeding became impossible. An almost complete stenosis of the anastomosis developed. A gastrostomy was necessary. OM, 1.1 mg/kg/d was started 4 months after surgery for a grade 4 esophagitis. In view of the persisting esophagitis, the OM dose was increased to 1.9 mg/kg/d. Oral food intakes gradually improved. The gastrostomy was removed 1 year after surgery. The BMI decreased from 91% before to 75% of BMI after repair. After treatment it increased to 89%.
DISCUSSION
Gastric transposition (GT) has become a reliable surgical treatment option.4 Despite the fact that oral-motor and sensory functions and deglutition reflexes were developed normally before restoration of the esophageal continuity,2,5 progressive feeding difficulties occurred in our patients after anastomosis according to Scha¨rli.1 These were caused by esophagitis and stricture formation. Anastomotic strictures commonly occur after EA repair. Factors that predispose to development of anastomotic strictures include ischemia, excess tension, anastomotic leak or dehiscence, 2-layer anastomosis, and, most frequently, GERD.6 Normal esophageal transport function is a complex mechanism that depends on effective esophageal motility, timely relaxation an contractil-
ity of the lower oesophageal sphincter, the mean intralumenal pressure in the stomach, and the gastric emptying.7 More than one of these factors are abnormal in the child with EA. These 4 patients all suffered from a long gap EA. Their postoperative problems were mainly caused by GERD, esophagitis, and stricture of the anastomosis. The most important problem we were confronted with, was the severe and resistant esophagitis. The Scha¨rli procedure is reported to induce acid reflux in the remaining esophagus and the intrathoracic portion of the stomach.1 In Scha¨rli’s original report, however, none of his patients had esophagitis. Later reports describe, however, the regular occurrence of benign strictures.9 In two of our patients the initial anti-acid treatment was high-dose ranitidine, because OM is not registered for children in Belgium. Neither this treatment nor the low OM doses of 1.1 to 1.25 mg/kg/d were able to control the esophagitis, despite the fact that the starting dose of OM already was well above the advised 0.7 mg/kg/d.10 By titrating therapy to clinical efficacy, several months were lost before the esophagitis was finally cured. The effective dose was 1.9 to 2.5 mg/kg/d, which is within the range reported in the pediatric literature (0.7 to 3.3 mg/kg/d).10,11 We did not observe adverse effects. As observed in adults,12 the strictures disappeared once the esophagitis was cured. At this moment, 18 to 24 months after surgical repair, all children are still treated with high dose OM. It is unclear for how long this treatment will be necessary. Because the anatomic situation does not change, life-long treatment might be necessary. Insufficient oral intake and failure to thrive necessitated tube feeding in all our patients. From this experience we would conclude that during the postrepair period, tube feeding is mandatory to maintain a good nutritional status. Therefore, we suggest maintaining a gastrostomy in the immediate postoperative period.8 We would propose to use high-dose omeprazole directly after a surgical repair of long gap EA, because of the high risk of severe GERD.13,14
REFERENCES 1. Scha¨rli AF: Esophageal reconstruction by elongation of the lesser gastric curve. Pediatr Surg Int 11:214-171, 1996 2. Cavallaro S, Pineschi A, Freni G, et al: Feeding troubles following delayed primary repair of esophageal atresia. Eur J Pediatr Surg 2:73-77, 1992 3. Bergmeijer JH, Hazebroek FW: Prospective medical and surgical treatment of gastroesophageal reflux in esophageal atresia. J AM Coll Surg 187:153-157, 1998 4. Davenport M, Hosie GP, Tasker RC, et al: Long term effects of gastric transposition in children: A physiological study. J Pediatr Surg 31:588-593, 1996 5. Moreno-Villares J, Galiano-Segovia MJ, Martin-Ferrer M: Alter-
ationes de la conducta alimentaria en pacientes que precisarion nutricion enteral durante el primer ano de vida. (Changes in feeding behavior of patients who had received enteral nutrition during the 1st year of life). Nutr Hosp 13:90-94, 1998 6. Beasley SW: Esophageal atresia and tracheoesophageal fistula, in Oldham KJ, Colombani PM, Foglia RP (eds): Surgery in infants and children: Scientific principles and practice. Philadelphia, PA, Lippincett-Raven Publishers, 1997, pp 1032-1033. 7. Fonkalsrud EW, Ament ME: gastroesophageal reflux in childhood. Curr Probl Surg 33:1-70, 1996 8. Moriarty KP, Jacir NN, Harris BM, et al: Transanastomotic feeding tubes in repair of esophageal atresia. J Pediatr Surg 31:53-54, 1996
1418
9. Macksood DJ, Blane CE, Drongowski RA, et al: Complications after gastric transposition in children. Can Assoc Radiol J 48:259-264, 1997 10. Walters JK, Zimmermann AE, Souney PF, et al: The use of omeprazole in pediatric population. Ann Pharmacother 32:478-480, 1998 11. Gunasekaran TS, Hassal EG: Efficacy and safety of omeprazole for severe gastroesophageal reflux in children J Pediatr 123:148-54, 1993
VAN BIERVLIET ET AL
12. Marks RD, Richter JE, et al: Omeprazole v. H2 receptor antagonist in treating patients with peptic stricture and esophagitis. Gastroenterology 106:907-915, 1994 13. Hassall E: Wrap session: Is the Nissen slipping? Can medical treatment replace surgery for severe gastroesophageal reflux disease in children? Am J Gastroenterol 12:43-49, 1998 14. Stal JM, Gregor JC, et al: A cost-utility analysis comparing omeprazole with ranitidine in the maintenance therapy of peptic esophageal stricture. Can J Gastroenterol 12:43-49, 1998