Experience with juvenile polyps in North American children: the need for pancolonoscopy.

We report a recent experience with juvenile polyps (JP) in a large cohort of North American children to determine if a pancolonoscopy (PC) is needed in all children with suspected polyps. We reviewed hospital charts of all patients with JP seen over a 9-yr period (January, 1990-October, 1998). A total of 331 JP were encountered during 195 procedures in 184 patients (64% males, 88% white, mean age 5.93 yr [range 0.42-15.5 yr], median age 4.84 yr). Painless rectal bleeding was the commonest symptom. PC was performed in 42% (82/195) of procedures, and 177 JP were encountered: 54% (97/177) were in the rectosigmoid colon, 14% (24/177) were in the descending colon, and 32% (56/177) were proximal to the splenic flexure (i.e., proximal polyps). Overall, proximal polyps were seen in 37% (31/82) of PC. Only proximal polyps were noted in 12% (10/82) of PC. Five patients were re-endoscoped after an initial limited examination because of continuing symptoms from proximal polyps. All but one of the polyps had typical features of a JP on histological examination. Though most JP are located in the left colon, a PC should be the initial procedure because: 1) 37% of PC revealed proximal polyps, 2) 32% of polyps were located proximal to splenic flexure, 3) persistence of symptoms from missed proximal polyp(s) necessitates a repeat study with attendant risks, and 4) there is a possibility of malignant transformation in an unidentified JP.

Is esophagogastroduodenoscopy necessary in all caustic ingestions?

BACKGROUND: It is unclear whether symptoms alone can identify patients with caustic ingestion who will benefit from esophagogastroduodenoscopy (EGD). The published data are contradictory. The purpose of the current study was to determine the relationship between initial symptoms and EGD findings in patients with caustic ingestion. METHODS: Chart review of all caustic ingestions who underwent EGD during a 4-year period (December 1993 through November 1997). RESULTS: Twenty-eight patients (15 girls; mean age, 2.7 years (range, 0.92-13.33) underwent EGD after caustic ingestion. Fourteen percent (4/28) of patients were asymptomatic, and findings on endoscopy were normal. Another 57% (16/28) had normal endoscopic findings, although all were symptomatic. Twenty-nine percent (8/28) of patients had esophageal injury on EGD, and all were symptomatic. Esophageal injury was graded as 1 (mucosal erythema), 2 (superficial burns; noncircumferential) or 3 (deep burns; circumferential). The injury was grade 1 in three of eight patients and grade 2 in two; all had one symptom each. Grade 3 injury was found in three of eight patients: two had two symptoms (drooling and vomiting, drooling and stridor), and one had one symptom (dysphagia). All patients with grade 3 injury subsequently underwent esophageal dilations. Follow-up information was secured for two of the three patients with grade 1 injury and both patients with grade 2 injury at 34.3 months (range, 24-50) after the ingestion, and all were asymptomatic. Of the 20 patients with absence of esophageal mucosal damage, follow-up data were available for 15 patients at 37.2 months (range, 7-63) after the event and all were well. CONCLUSIONS: All patients with clinically significant injury (grades 2 and 3) were symptomatic at initial assessment. No single symptom or combination of symptoms could identify all patients with esophageal injury. All asymptomatic patients had normal findings on endoscopic examinations. Esophagogastroduodenoscopy seems unnecessary in asymptomatic patients with alleged caustic ingestion. A larger, prospective study would be necessary to unequivocally answer this clinically important question.

Direct measurement of pancreatic enzymes after stimulation with secretin versus secretin plus cholecystokinin.

BACKGROUND: Direct measurement of pancreatic enzymes after administration of pancreatic secretagogues is the gold standard in the assessment of exocrine pancreatic function. Recent experience at the authors' institution showed that endoscopic collection of pancreatic secretions 5, 10, and 15 minutes after intravenous administration of secretin is useful in screening for pancreatic insufficiency. Concomitant administration of intravenous cholecystokinin has been a subject of debate. The purpose of this study was to compare pancreatic enzyme levels after administration of secretin versus secretin plus cholecystokinin and to validate the timing of collection of duodenal fluid. METHODS: A prospective, randomized, double-blind study was conducted from September 1997 through September 1998. Patients scheduled for pancreatic enzyme sampling were randomly assigned to receive intravenous secretin (2 U/kg) plus placebo (group 1) or intravenous secretin (2 U/kg) plus cholecystokinin (0.02 microg/kg [Group 2]). Duodenal fluid was collected 5, 10, and 15 minutes later and placed in dry ice. Samples were measured for the levels of trypsin, amylase, lipase, and chymotrypsin. RESULTS: Twenty patients were assigned to each group. The age range was similar in both groups: 12 months to 16 years, 8 months in group 1 (median, 2.1 years) and 15 months to 13 years, 7 months in group 2 (median, 2.5 years). Group 2 had a greater number of patients with all four enzymes at normal levels during at least one of the time points, 75% versus 50% (P = 0.102). The difference in enzyme levels at the 5-, 10-, and 15-minute collections was statistically significant. For all four enzymes in both groups, values varied from highest to lowest with time (P = 0.0001). The enzyme levels at 10 minutes were close to the enzyme levels at 5 minutes; the lowest values occurred at 15 minutes. CONCLUSIONS: Higher pancreatic enzyme levels were obtained after administration of secretin plus cholecystokinin, although the trend did not reach statistical significance. Pancreatic enzyme levels are highest at 5 and 10 minutes, indicating that collections of duodenal fluid should be completed within 10 minutes of the administration of the secretagogues.

Recurrent abdominal pain in children--a retrospective study of outcome in a group referred to a pediatric gastroenterology practice.

Recurrent abdominal pain (RAP) affects a significant number of children each year. We reviewed our experience over a 2-year period to determine the outcome of patients who were referred for pediatric gastroenterology consultation. We identified 356 patients, 149 (42%) male and 207 (58%) female. All patients underwent a thorough interview and complete physical examination. Patients suspected of having irritable bowel syndrome (IBS) were treated as such without further initial evaluation. Others underwent an initial blood and urine evaluation. When these initial screening studies were negative, additional studies were performed including abdominal ultrasonography, radiography, and/or endoscopy of the upper gastrointestinal (GI) tract if the history suggested a possible diagnosis that could be excluded or confirmed by such tests. There was no identifiable diagnosis in 43.5% of the patients studied. IBS was diagnosed in 25.8% of all patients. Constipation was diagnosed in 3.7%. Miscellaneous causes, including GI mucosal lesions, and renal and pancreatic disorders were found in an additional 27% of patients. In a follow-up survey, more than 70% of the treated respondents were improved (i.e., their RAP had resolved or was markedly improved). We conclude that most children with RAP have a functional disorder. Patients with an organic cause for pain can be identified and treated in a cost-effective manner with carefully planned evaluation.

A comparison of the effect of three sedatives on esophageal sphincters in cats.

BACKGROUND/AIMS: Children 5 years old and younger often require sedation for esophageal motility studies (EMS). At our institution, an intramuscular cocktail of meperidine, promethazine and chlorpromazine (MPC) has been used as the standard sedative for young children undergoing EMS. Administering the intramuscular sedative may, however, be more traumatic to the child than the procedure. Moreover, its effect on esophageal motility is not known and prolonged sedation is common. The aim of this study was to determine the effects of MPC and two orally-administered sedatives on esophageal sphincter function, using the cat model, with a goal to identify a potentially suitable orally-administered sedative for use in young children requiring sedation for EMS. METHODS: We measured upper (UESP) and lower (LESP) esophageal sphincter pressures in 25 cats initially without sedation, and then following sedation with midazolam, chloral hydrate and MPC. The results were compared. RESULTS: All three sedatives significantly decreased LESP compared to the control (p<0.05). Midazolam decreased LESP the most; however, the difference from the other sedatives did not reach statistical significance. All three sedatives decreased UESP, compared to control, but the differences were not statistically significant. Of the two oral sedatives, chloral hydrate had the least effect on the esophageal sphincters although its effect was not statistically different from that of midazolam. CONCLUSIONS: Ethically appropriate studies are needed to determine which oral sedative would be most beneficial for use in sedating children undergoing esophageal motility studies. Until studies can be done, the choice between chloral hydrate and midazolam should be based on the experience and comfort of the attending physician with regard to the potential side effects of the medications.

Constipation in infants and children: evaluation and treatment. A medical position statement of the North American Society for Pediatric Gastroenterology and Nutrition.

BACKGROUND: Constipation, defined as a delay or difficulty in defecation, present for 2 or more weeks, is a common pediatric problem encountered by both primary and specialty medical providers. METHODS: The Constipation Subcommittee of the Clinical Guidelines Committee of the North American Society for Pediatric Gastroenterology and Nutrition has formulated clinical practice guidelines for the management of pediatric constipation. The Constipation Subcommittee, consisting of two primary care pediatricians, a clinical epidemiologist, and pediatric gastroenterologists, based its recommendations on an integration of a comprehensive and systematic review of the medical literature combined with expert opinion. Consensus was achieved through Nominal Group Technique, a structured quantitative method. RESULTS: The Subcommittee developed two algorithms to assist with medical management, one for older infants and children and the second for infants less than 1 year of age. The guidelines provide recommendations for management by the primary care provider, including evaluation, initial treatment, follow-up management, and indications for consultation by a specialist. The Constipation Subcommittee also provided recommendations for management by the pediatric gastroenterologist. CONCLUSIONS: This report, which has been endorsed by the Executive Council of the North American Society for Pediatric Gastroenterology and Nutrition, has been prepared as a general guideline to assist providers of medical care in the evaluation and treatment of constipation in children. It is not intended as a substitute for clinical judgment or as a protocol for the management of all patients with this problem.

Tyrosinemia type 1 should be suspected in infants with severe coagulopathy even in the absence of other signs of liver failure.

Tyrosinemia type l is an inherited metabolic disorder attributable to deficiency of fumarylacetoacetate hydrolase, a terminal enzyme in the degradation pathway of tyrosine. Affected individuals may present with any of a number of signs and symptoms, including failure to thrive, fever, vomiting, diarrhea, hepatomegaly, ascites, jaundice, renal Fanconi syndrome, or conditions such as rickets and hepatocellular carcinoma.1 If untreated, the patient may die of acute liver failure before the second year of life, or from chronic liver failure or hepatocellular carcinoma before the end of the second decade of life.2 Although overt liver failure with coagulopathy may be part of the presentation of tyrosinemia, a significant coagulopathy in the absence of overt signs of liver disease has not been emphasized as a clue to the diagnosis of this condition. We report two tyrosinemic infants who presented with severe coagulopathies and no other signs of liver failure to stress this diagnostic point.

Clinical applications of technetium Tc 99m hexamethyl propylene amine oxime leukocyte scan in children with inflammatory bowel disease.

BACKGROUND: Labeled leukocyte imaging is a helpful diagnostic tool in the detection of inflammation and sepsis. The technetium Tc 99m hexamethyl propylene amine oxime (99mTc HMPAO)-labeled leukocyte scan has been found to be more sensitive than the Indium-111 labeled leukocyte scan in detecting inflammatory bowel disease, with reported sensitivities of 95% to 100%. Experience with the 99mTc HMPAO-labeled leukocyte scan was examined and its clinical applications evaluated in the immediate treatment of patients with inflammatory bowel disease. METHODS: A retrospective chart review was undertaken that included pediatric patients who underwent 99mTc HMPAO-labeled leukocyte scan at the James Whitcomb Riley Hospital for Children. The disease activity of patients with inflammatory bowel disease was assessed. The leukocyte scan was performed according to the manufacturer's specifications, and images were obtained 30 minutes and 2 hours after administration of the radiopharmaceutical. RESULTS: During the period of July 1996 through November 1997, 41 scans were performed in 35 patients. Twenty-nine patients had histologically proven inflammatory bowel disease: 24 with Crohn's disease, 4 with ulcerative colitis, and 1 with indeterminate colitis. Active inflammatory bowel disease was suspected in 24 patients when the leukocyte scan was performed. Twenty of the 24 patients (83% sensitivity) had abnormal findings in leukocyte scans that prompted more aggressive management in 15 (75%). Six of the 15 who were receiving maximum medical therapy underwent surgical resection of severely affected bowel segments, and medical treatment was intensified in the other 9. The remaining 5 patients were receiving optimal medical therapy, instituted at their recent visit, and did not require further medication adjustments. Four of the 24 patients with active inflammatory bowel disease had normal leukocyte scans (17% false-negative rate), 3 of whom were receiving corticosteroid therapy at the time the scans were performed. All of the 11 patients in whom inflammatory bowel disease was in remission and 6 patients who did not have inflammatory bowel disease had normal findings in leukocyte scans (100% specificity). CONCLUSIONS: Although a tissue diagnosis is still recommended, obtained during upper and lower gastrointestinal endoscopic examinations, and contrast radiography of the small bowel for the initial work-up of patients with suspected inflammatory bowel disease, the 99mTc HMPAO-labeled leukocyte scan is a safe and useful diagnostic adjunct for subsequent evaluation of patients known to have inflammatory bowel disease. The results of 99mTc HMPAO-labeled leukocyte scans directly influenced treatment of 75% of the study patients with active inflammatory bowel disease, which included the decision to refer patients for surgical intervention.

Juvenile polyp in esophageal colon interposition.

Esophageal polyps are rare in children, whereas colorectal juvenile polyps are common. An 11-year-old boy with an esophageal colonic interposition for an esophageal stricture secondary to caustic injury was found to have a polypoid mass in the interposed colon. Fiberoptic endoscopic removal with diathermy was performed. Histological examination confirmed it was a juvenile polyp. The occurrence of a polyp in a colon removed from its natural location and serving a different function suggests the possibility that an unknown factor produced by colonic cells play a pivotal role in its development.

Further studies of anti-endomysium and anti-gliadin antibodies in patients with suspected celiac disease.

BACKGROUND: The finding of characteristic small intestinal mucosal abnormalities on histologic examination of a biopsy specimen remains the first requirement for the diagnosis of celiac disease. A reliable and noninvasive test would be ideal for the patient's convenience and for reducing health-care costs. The sensitivity and specificity of anti-gliadin antibodies (AGA-immunoglobulin [Ig] G, AGA-IgA) have been variable; anti-endomysium IgA (EmA-IgA) is more helpful. In an earlier study conducted at the authors' institution, celiac disease was present in 19 patients examined from 1992 to 1995. Anti-endomysium titers were higher than normal in all 19 patients (100%). Total villous atrophy was seen in 14 of 17 biopsy specimens (82%) and subtotal atrophy in 3 (18%). The purpose of the current study was to evaluate further the accuracy of EmA-IgA in diagnosing celiac disease. METHODS: One hundred seven patients were screened for celiac disease between March 1996 and July 1997. The level of EmA-IgA was measured in all patients, and AGA-IgG and AGA-IgA were measured in 104 patients. Forty-six patients underwent endoscopic biopsy of the small bowel, with measurement of disaccharidase enzymes in 45 patients. RESULTS: Five of 46 patients had celiac disease (three boys and two girls; mean age, 5.3 years; 2-9.5 years); one also had cystic fibrosis and another had insulin-dependent diabetes mellitus. All five had marked to complete villous atrophy with crypt hyperplasia and increased serum EmA-IgA (100% sensitivity). None of the remaining patients had increased EmA-IgA (100% specificity). Serum levels of AGA-IgG and AGA-IgA were increased in all four celiac disease patients (100% sensitivity), but they were also high in patients without celiac disease (38% and 92% specificity, respectively), which compromises their diagnostic value. None of the patients confirmed to have celiac disease had IgA deficiency. Abnormal disaccharidase enzyme activities were documented in all five celiac disease patients: severe generalized deficiency (n = 2), moderately severe generalized deficiency (n = 2), and alactasia with moderate deficiency of the alpha-glucosidases (n = 1). CONCLUSIONS: This study confirmed the reliability and accuracy of EmA-IgA in the diagnosis of celiac disease. Small bowel biopsy may be unnecessary in EmA-positive patients in whom celiac disease is suspected.

Expression of inducible nitric oxide synthase (iNOS) mRNA in inflamed esophageal and colonic mucosa in a pediatric population.

OBJECTIVE: Increasing evidence suggests that nitric oxide participates in the pathophysiology of intestinal barrier function/dysfunction and inflammation. Increases in inducible nitric oxide synthase (iNOS) mRNA and protein expression have been observed in colonic mucosal biopsies of adults with inflammatory bowel disease (IBD). It is unclear whether iNOS induction is specific for IBD or a reflection of nonspecific mucosal inflammation. Furthermore, the characteristics of iNOS mRNA expression in pediatric patients with gastrointestinal disorders remains ill-defined. Our objective was to examine the relationship between iNOS mRNA expression and gastrointestinal mucosal inflammation in a pediatric population. METHODS: Esophageal and colonic mucosal biopsies were obtained during endoscopy. Total RNA was isolated from these biopsies and reverse transcription-polymerase chain reaction (RT-PCR) performed (35 PCR cycles) using two 20-bp primers that amplified a predicted 372-bp conserved iNOS mRNA fragment. RESULTS: Biopsies were obtained from 29 children (22 boys; mean age 10.6 yr [range 1.7-16.5 yr]). Endoscopic and histological findings included normal esophageal mucosa (n = 3), esophagitis (n = 10), normal rectal mucosa (n = 2), ulcerative colitis (n = 10), and Crohn disease (n = 4). Evidence of iNOS mRNA was detected by PCR amplification in six of 10 patients with ulcerative colitis and in two of four patients with Crohn disease. However, iNOS mRNA was not amplified in any esophageal biopsy or in rectal mucosa biopsies with normal histology. CONCLUSIONS: These data indicate that upregulation of iNOS mRNA expression in colonic mucosa is a feature of IBD in children. iNOS mRNA expression is not upregulated in esophageal mucosa or in the absence of colonic inflammation. Further studies designed to determine the site- and cell-specificity of iNOS mRNA upregulation in mucosal biopsies from children with IBD may further illuminate the pathophysiology of these disorders.

Vertical lines in distal esophageal mucosa (VLEM): a true endoscopic manifestation of esophagitis in children?

BACKGROUND: We observed an endoscopic abnormally in a group of children with histological esophagitis. We termed this finding "vertical lines in esophageal mucosa" (VLEM). We examined the relationship between the presence of VLEM and significant histologic changes in esophageal mucosal biopsies. METHODS: Between January 1, 1992, and August 31, 1994, the senior author (JFF) performed 255 esophageal biopsies. The procedure reports, available endoscopic photographs, and histology reports were reviewed to establish the endoscopic and histologic appearance of the esophageal mucosa. Intraepithelial cells were counted in a blind review of 42 randomly selected biopsies. RESULTS: The esophageal mucosa had a normal appearance on 160 endoscopic studies (Group 1) and VLEM were the only mucosal abnormalities in 41 endoscopies (Group 2). Histology was normal in 92 of 160 biopsies (57.5%) from Group 1, and 1 of 41 biopsies (2.4%) from Group 2. Most patients in Group 2 had eosinophilic esophagitis (34 of 41, 83%, specificity 0.85, sensitivity 0.5, p > 0.001) which was of moderate to severe intensity (31 of 34, 91.2%, specificity 0.88, sensitivity 0.73, p < 0.001). CONCLUSIONS: Histology usually demonstrated moderate to severe inflammation when VLEM were present. VLEM may be a highly specific endoscopic feature of esophagitis in children.

Hepatic granulomas in children. A clinicopathologic analysis of 23 cases including polymerase chain reaction for histoplasma.

In a 15-year period at the Riley Hospital for Children, granulomas were found in 23 (4%) of a total of 521 liver biopsies. An etiology was identified in 87%: Histoplasma was diagnosed in 15 cases (65%) by polymerase chain reaction (PCR) on paraffin-embedded tissue, serology, and special stains; sarcoidosis was diagnosed in four cases; and schistosomiasis was diagnosed in one case. Serial liver biopsies were available from five patients; granulomas occurred in only one biopsy of the series from each patient. Extrahepatic tissue from six patients contained granulomas, and an etiology for the liver granulomas was identified in all six patients (four histoplasmosis, two sarcoidosis). The extrahepatic tissue from two patients with Histoplasma was diagnostic. We made the following conclusions: that PCR is applicable to archival material and greatly increases the yield of specific infectious diagnoses of liver granulomas compared with conventional diagnostic methods (65 versus 22%); that the infections causing liver granulomas are those that are endemic in a community (e.g., Histoplasma in Indiana); that Histoplasma can coexist with a wide variety of systemic and primary liver diseases; that the likelihood of identifying a cause of liver granulomas is increased if there are extrahepatic granulomas; and that hepatic granulomas may have a limited life span. Treatment of liver granulomas should be determined by the clinical setting and directed at the underlying cause.

Helicobacter pylori infection in recurrent abdominal pain in childhood: comparison of diagnostic tests and therapy.

OBJECTIVE: To determine the role of Helicobacter pylori infection in children with recurrent abdominal pain and the usefulness of serologic tests in screening H pylori infection and monitoring treatment of H pylori-associated gastritis. METHODS: During a 3 year period, we investigated the presence of serum immunoglobulin G (IgG) antibody to H pylori in 456 children using the high-molecular-weight cell-associated protein H pylori enzyme immunoassay kit. Among the 456 children studied, 218 (age range, 3 to 18 years; mean age, 9.5 years) had symptoms of recurrent abdominal pain (RAP syndrome) with or without vomiting, and the remaining 238 (age range, 3 to 18 years; mean age, 9.8 years) had no RAP (non-RAP syndrome). We performed upper gastrointestinal endoscopy on 111 consecutive children of the 218 with RAP syndrome and obtained mucosal biopsies for culture, histologic analysis, CLO test (Delta West, Perth, Australia), and H pylori detection by polymerase chain reaction. RESULTS: Thirty-eight (17.4%) of 218 children in the RAP group and 25 (10.5%) of 238 children in the non-RAP group were seropositive for H pylori. Of the 111 children endoscoped, 95 were found to be negative, and 12 were positive by all five assays. Specimens from 2 children were negative by culture and the CLO test but positive by the other three assays. Specimens from 1 child were negative by histologic analysis but positive by all other tests. The remaining child was positive for anti-H pylori IgG but negative by all of the other four assays. Upper gastrointestinal endoscopy detected 14 children with peptic ulcer disease (9 duodenal ulcer and 5 gastric ulcer) and 12 with antral nodular gastritis. Only 4 of the 14 diagnosed with peptic ulcer were H pylori positive by all five assays, whereas all 12 children with antral nodular gastritis were H pylori positive. Nine of the 12 H pylori-positive children were treated with a combination of bismuth subsalicylate, amoxicillin, and metronidazole for 2 weeks. Sera obtained at 2, 4, and 6 months after treatment from all 9 children showed a decrease in anti-H pylori IgG titer. Three H pylori-infected children who did not receive any treatment served as control children, and their IgG levels remained elevated or increased over time. CONCLUSION: The results from our study indicate that screening for the serum IgG antibody to H pylori is a practical method for diagnosing H pylori infection in children, and that serial measurements of the H pylori IgG antibody are useful for monitoring treatment of H pylori because of its high sensitivity and ease of performance. Only 4 of the 14 children diagnosed with peptic ulcer disease were confirmed to be infected with H pylori, whereas all 12 children with antral nodular gastritis were found to be infected by H pylori. These observations suggest that H pylori infection is more frequently associated with gastritis than with peptic ulcer disease in children, and that H pylori gastritis is a cause of RAP syndrome in children.