Barrett's esophagus in three children after antileukemia chemotherapy.

Barrett's esophagus, a columnar metaplasia of the lower esophagus that is usually associated with gastroesophageal reflux (GER), was found in three children on long-term antileukemia chemotherapy. Two of the children had been on a standard acute lymphoblastic leukemia (ALL) maintenance protocol with 2 to 3 years of methotrexate and 6-mercaptopurine administration. The third child received daunorubicin, cytosine arabinoside, and 6-thioguanine for treatment of acute myelogenous leukemia (AML). None of the patients had clinical or pathologic evidence of GER disease. We propose that the Barrett's esophagus in these patients did not result from the usual peptic esophagitis, but rather from chemotherapy-induced esophageal mucosal injury.

Radiographic findings in children and young adults with Barrett's esophagus.

The upper-gastrointestinal examinations of 32 patients (mean age, 11 years) with histologically proven Barrett's esophagus were reviewed to evaluate the radiologic findings in children. All patients had symptoms of chronic gastroesophageal reflux and/or esophagitis, including atypical findings such as aspiration pneumonia, seizures, and failure to thrive. Fourteen patients had other diseases that might predispose them to abnormal esophageal motility and gastroesophageal reflux. Twenty-five patients had single-contrast and seven patients had double-contrast examinations. Four patients had normal single-contrast studies; 24 had gastroesophageal reflux; 12 had strictures; 10 had esophageal ulcers; and only four had hiatal hernias. The most notable difference between the results of endoscopy and the upper-gastrointestinal studies was the rate of detection of esophageal ulcers. Ten of the patients with single-contrast studies had ulcers seen at endoscopy but not shown radiologically. No specific radiologic signs of Barrett's esophagus were found, although most of our patients had abnormal upper gastrointestinal studies.

How useful is the barium enema in the diagnosis of infantile Hirschsprung's disease?

We studied the usefulness of the barium enema to rule out Hirschsprung's disease (congenital megacolon) in the evaluation of infants with constipation. Results from barium enemas in 58 constipated infants and children who underwent rectal suction biopsies to rule out aganglionosis were evaluated in retrospect for the presence of a transition zone, delayed evacuation of barium, and colonic anatomic abnormalities. As expected, the presence of a transition zone was most accurate in predicting Hirschsprung's disease. Eighty percent of infants with aganglionosis had a roentgenographic transition zone, while 20% did not. Twenty-nine percent of infants with a suspected roentgenographic transition zone did not have aganglionosis. Delayed evacuation of barium was a poor predictor of aganglionosis. The presence of delayed evacuation of barium did not improve the accuracy of the transition zone to predict Hirschsprung's disease. Barium enemas did not reveal any additional colonic anatomic defects other than a transition zone to account for constipation in our study group. These results demonstrated that the barium enema is not a specific enough screening procedure to rule out Hirschsprung's disease in the unobstructed infant. Rectal suction biopsy is diagnostic and should be performed as the procedure of choice in those infants suspected of having Hirschsprung's disease.

Caustic injuries to the esophagus in children.

The ingestion of caustic chemical agents, usually accidentally by children, produces a wide range of injuries from minor mouth burns to necrosis of the esophagus and stomach. The type of agent, amount, concentration, and duration of exposure are the determining factors. The treatment for the average burn is fairly well standardized, but the serious injuries require prompt recognition of complications and appropriate therapy to prevent more serious complications.

Treatment and prognosis of symptomatic gallbladder disease in patients with cystic fibrosis.

Twenty-four (3.6%) of 670 patients with cystic fibrosis seen over a 25-year period developed symptomatic gallbladder disease. Only four patients were less than 16 years old. Four patients presented with unusual problems, including one with acute cholangitis and two with atonic gallbladder, one of whom required cholecystectomy. Another patient was found to have cholangiocarcinoma of the gallbladder when an exploratory laparotomy was performed to investigate biliary obstruction. Twenty patients had cholelithiasis, 15 of whom underwent cholecystectomy. Only one patient had substantial pulmonary difficulties postoperatively. Patients who presented with classic biliary colic had no further symptoms after cholecystectomy. One patient developed intrahepatic stones 6 years later and required a choledochoduodenostomy. As the pulmonary status of most cystic fibrosis patients will eventually deteriorate, we recommend that serious consideration be given to performing a cholecystectomy as soon as practical after the diagnosis of symptomatic cholelithiasis. Our experience indicates that surgery can be performed safely unless pulmonary status is already extremely compromised and the patient is in overt respiratory failure.

Pharmacokinetic determination of ranitidine pharmacodynamics in pediatric ulcer disease.

The pharmacokinetics and pharmacodynamics of ranitidine were evaluated during three methods of administration in 12 children ranging in age from 3.5 to 16 years with documented gastric or duodenal ulcer disease. First, a continuous intravenous infusion of ranitidine was administered to determine the serum concentration necessary to suppress gastric acid secretion by at least 90%. From these data a therapeutic dose of ranitidine was calculated and administered on separate days via the intravenous bolus and oral routes. Half-life, volume of distribution, and clearance values for ranitidine were the same after intravenous bolus and oral doses (1.8 vs 2.0 hours, 2.3 vs 2.5 L/kg, and 794.7 vs 788.0 ml/min/1.73 m2, respectively). The bioavailability of ranitidine given orally averaged 48%. Serum ranitidine concentrations necessary to inhibit gastric acid secretion by at least 90% ranged between 40 and 60 ng/ml for all children studied. No adverse clinical or biochemical effects were observed in any child during the 6 weeks of orally administered treatment. Endoscopic reevaluation after 6 weeks indicated complete healing of initial ulcers.

Multifocal osteonecrosis in adolescents with Crohn's disease: a complication of therapy?

Three adolescents with severe Crohn's ileocolitis developed osteonecrosis after receiving intravenous corticosteroids and parenteral nutrition, including 10% lipid infusion. Each had achieved clinical remission with therapy. However, several months following completion of therapy, each developed arthralgias and arthritis of weight-bearing and non-weight-bearing joints. Roentgenographic evaluation revealed osteonecrosis involving multiple joints. Osteonecrosis may result from the interference with blood flow to bone and has been produced in animals by infusion of lipid solutions and administration of corticosteroids. We report these cases of osteonecrosis as a probable complication of corticosteroid and lipid infusion in adolescents treated for severe Crohn's disease.

Ileal atresia with long-segment Hirschsprung's disease in a neonate.

A newborn female had ileal atresia without mesenteric continuity associated with a small, shortened colon but without "malrotation." After correction by an ileocolostomy the infant remained obstructed, requiring an ileostomy at 24 days; subsequently, at 13 months, a Martin-Duhamel operation was done. since associated anomalies are uncommon in each of these conditions, since no cause and effect relationship has been developed, and since no prior survival has been clearly documented, this report is important. The recommendation of distal bowel biopsy is stressed to establish an early diagnosis and, thereby, correct treatment.

Barrett's esophagus in children: a consequence of chronic gastroesophageal reflux.

It is widely acknowledged that Barrett's esophagus in adults is an acquired condition resulting from prolonged gastroesophageal reflux. Barrett's esophagus is rare in childhood, even though gastroesophageal reflux occurs commonly in the pediatric age group. When a columnar-lined esophagus is present in children, it is often regarded as a congenital anomaly rather than as a consequence of chronic gastroesophageal reflux. Over a 5-yr period (1978-1982), we retrospectively studied Barrett's esophagus in children 19 yr of age or younger who were evaluated for gastroesophageal reflux and whose symptoms warranted esophagoscopy and esophageal biopsy. Esophageal biopsies were performed on 103 patients with gastroesophageal reflux. Thirteen children (age range, 8 mo-19 yr) had Barrett's esophagus, for a prevalence of 13%. Gastroesophageal reflux was documented in these children by upper gastrointestinal radiographs or pH monitoring. Radiographs demonstrated esophageal stricture in 5 of the 13 children; none had hiatal hernia. Children presented with symptoms suggestive of gastroesophageal reflux and esophagitis: vomiting, abdominal pain, odynophagia, dysphagia, and heartburn. All children had a past history of excessive regurgitation during infancy. Histologically, three types of columnar epithelium were present: gastric fundic type (11 patients), junctional-type columnar epithelium reminiscent of gastric cardia (7 patients), and specialized columnar (metaplastic intestinal) type (2 patients). We believe that Barrett's esophagus is more common in children than had previously been appreciated. In these children, we suggest that the distal columnar-lined esophagus resulted from chronic gastroesophageal reflux and is not a congenital anomaly.

Importance of early ileostomy closure to prevent chronic salt and water losses after necrotizing enterocolitis.

Six infants with necrotizing enterocolitis were discharged after periods of prolonged hospitalization (two to nine months) with intact ileostomies. Their initial hospitalization was complicated by feeding difficulties, chronic diarrhea, sepsis, rickets, and developmental delay. All were rehospitalized within three months, with severe acidosis and dehydration after a presumed viral-type illness. Each had large-volume ileostomy output, which was rich in electrolytes and bicarbonate. A prolonged recovery phase (two to eight months) again was punctuated with episodes of diarrhea, problems in starting oral feeding, and sepsis. After reanastomosis of the remaining bowel, no infant has had a similar life-threatening episode. It is speculated that the infants' recurrent "salt-and-water-losing states" are secondary to either an anatomic or functional loss of the colon. This problem appears to be a poorly recognized sequela of bowel surgery and necrotizing enterocolitis, and early reanastomosis of discontinuous bowel should be of benefit.

High incidence of pulmonary symptoms in infants evaluated for esophageal disease.

Of 62 children (1-24 months of age) evaluated for esophageal disease, 22 were found to have pulmonary symptoms of apnea, pneumonia, wheezing, cyanosis, cough and stridor. Upper gastrointestinal series showed free gastroesophageal reflux in 10 of 22 infants; 3 were thought to have stricture. Acid-reflux test was positive in 13 of 15 and correlated with the presence of esophagitis in 12. In addition to esophagitis, endoscopic examination found two foreign bodies and an esophageal stricture unrecognized during fluorescopy. Endoscopic grasp biopsy was inadequate in most infants for the histologic evaluation of esophagitis. However, suction biopsy correlated well with endoscopically diagnosed esophagitis. In infants where medical therapy failed and symptoms were life-threatening, a Nissen fundoplication resulted in excellent resolution of symptoms. In children who present with prolonged and often life-threatening symptoms, esophageal dysfunction should be evaluated by rigorous testing.