Gastric metaplasia: a frequently overlooked feature of duodenal biopsy specimens in untreated celiac disease.

BACKGROUND: Duodenal gastric metaplasia is rarely reported in untreated celiac disease, although it is seen in 60% to 100% of duodenal biopsy specimens in nonceliac patients with histologic duodenitis. The low incidence could represent underreporting, a decreased incidence in pediatric patients generally, or the more distal sampling site that is customary for most biopsy specimens that are obtained to diagnose celiac disease. It could also be a unique feature of the inflammatory reaction that characterizes this disease. The purpose of this study was to examine the incidence of gastric metaplasia in duodenal specimens from children with untreated celiac disease with special reference to patient age and biopsy site. METHOD: Formalin-fixed paraffin-embedded specimens of duodenal mucosa were selected from the pathology department's archival material. Sections were either stained histochemically or by immunochemical methods, according to an antigen-retrieval protocol. Forty-four duodenal specimens from untreated patients with celiac disease (n = 22) and control subjects of similar age with normal histology (n = 22) were examined. Ten of each were obtained during upper endoscopy from the proximal duodenum (proximal site) and 12 of each by Crosby capsule near the ligament of Treitz (distal site). RESULTS: All specimens from patients with celiac disease exhibited marked villous atrophy. None had been noted to have gastric metaplasia during routine examination of sections stained by hematoxylin and eosin. Fifteen (68%) of 22 of the celiac specimens and 2 of 22 (9%) control specimens contained gastric metaplasia, identified as patches of gastric-type cells containing MUC5AC (gastric mucin), pS2 (gastric trefoil factor) and neutral (periodic acid-Schiff-positive) mucin. Five of the seven celiac specimens that had no metaplasia showed increased numbers of goblet cells expressing gastric markers. The incidence of gastric metaplasia was not different for endoscopic (70%) or capsule (67%) specimens. Sixty-eight percent (7/11) of patients aged less than 3 years had gastric metaplasia. CONCLUSION: The presence of gastric metaplasia has been previously underreported in celiac disease specimens. Detection would be improved by the routine use of period acid-Schiff/ alcian blue staining. The incidence of gastric metaplasia in celiac disease is not significantly influenced by biopsy site or age at time of the biopsy.

Management of fibrosing pancreatitis in children presenting with obstructive jaundice.

BACKGROUND: Children with fibrosing pancreatitis are conventionally treated surgically to relieve common bile duct (CBD) obstruction caused by pancreatic compression. Residual pancreatic function has not been formally tested in these patients. AIMS: To evaluate the usefulness of non-surgical temporary drainage in children with fibrosing pancreatitis and to assess pancreatic function after resolution of their CBD obstruction. PATIENTS: Four children (1.5-13 years; three girls). METHODS AND RESULTS: Abdominal sonography and computed tomography revealed diffuse enlargement of the pancreas, predominantly the head. The CBD was dilated due to compression by the head of the pancreas. Pancreatic biopsy specimens obtained in three patients showed notable acinar cell atrophy and extensive fibrosis. Cystic fibrosis was excluded. No other cause of pancreatitis was identified. Pancreatic tissue from one patient contained viral DNA sequences for parvovirus B19 detected by polymerase chain reaction; serum IgM to parvovirus was positive. Three patients had temporary drainage of the CBD and one patient underwent a choledochojejunostomy. Serial imaging studies revealed resolution of the CBD obstruction with reduction in pancreatic size. Exocrine pancreatic function deteriorated. Three patients developed pancreatic insufficiency within two to four months of presentation. The fourth patient has notably diminished pancreatic function, but remains pancreatic sufficient. None has diabetes mellitus. CONCLUSIONS: Temporary drainage of the CBD obstruction is recommended in fibrosing pancreatitis in children along with close monitoring of the clinical course, before considering surgery.

Advances in the diagnosis and treatment of gastroesophageal reflux disease.

Pathophysiology and treatment of gastroesophageal reflux (GER) in children have often been extrapolated from studies in adult patients. Fortunately, many groups are now addressing GER specifically in relation to children. Abnormalities in gastrointestinal motility are described in gastroesophageal reflux GER, and there are several new studies looking at this issue in infantile GER. An international working group has put together recommendations for management of infantile GER. The results of a large pediatric study using omeprazole and a review of the use of the prokinetic cisapride in pediatrics are summarized. Several papers review recent experiences with laparoscopic fundoplication. New diagnostic modalities used to investigate GER in infants and children are discussed. These studies aid in both our understanding of possible pathogenesis of GER as well as treatment of the young patient with GER.

Changes in gastric emptying in early postnatal life.

OBJECTIVE: To study the pattern of gastric emptying in very premature infants and to determine whether there are changes with postnatal age and the ability to tolerate feedings. METHODS: Sequential ultrasound measurements of the gastric antral cross-sectional area were obtained in 32 infants (mean gestational age, 26 +/- 1 weeks) before and after feeding for 2 hours. Studies were carried out after initiation of feedings, when full feedings were received, and at 32 weeks. Infants classified as feeding intolerant (n = 9) were also studied when feedings were restarted. Gastric emptying was assessed by the time taken for antral cross-sectional area to reach maximal value and to decrease to half the maximal increment (half-antral clearance). RESULTS: Delayed antral distention was observed at the time of the initial study in both feeding-tolerant (8 of 23) and feeding-intolerant (8 of 9) infants; however, there were significant differences in times for maximal antral distention (p < 0.002) and half-antral clearance (p < 0.006) between the feeding-tolerant and feeding-intolerant infants. By the time of full feedings, the feeding-intolerant infants showed immediate gastric emptying but still had a longer half-antral clearance time (p < 0.01). By 32 weeks, all infants had immediate antral distention and a more mature curvilinear pattern of gastric emptying. CONCLUSIONS: Knowledge of these different patterns of gastric emptying in very premature infants may lead to the development of more rational feeding strategies.

Joubert syndrome with congenital hepatic fibrosis: an entity in the spectrum of oculo-encephalo-hepato-renal disorders.

Joubert syndrome is an autosomal recessive inherited condition characterized by agenesis or hypoplasia of the cerebellar vermis, retinal dystrophy, chorioretinal colobomata, oculomotor abnormalities, episodic hyperpnea, ataxia, and mental retardation. Congenital hepatic fibrosis has not previously been described in Joubert syndrome. We report two unrelated children with Joubert syndrome and hepatosplenomegaly. On histopathological examination, both had congenital hepatic fibrosis. Both were also found to have congenital medullary cystic disease of the kidneys. Joubert syndrome appears to be one of a spectrum of congenital malformation syndromes involving the central nervous system, eye, liver and kidneys.

Gastrointestinal complications of gastrocystoplasty.

The cases are reported of five children with chronic renal failure who underwent gastrocystoplasty for a variety of urological disorders. Gastrocystoplasty comprises the transplantation of a vascularised segment of stomach to the bladder to form an augmented neobladder. The patients had gastrointestinal complications after the operation, including considerable weight loss in all five patients, accompanied by marked failure to thrive in four of the five patients, and food aversion, feeding intolerance, dumping syndrome, delayed gastric emptying, and oesophagitis in two patients. Three of the five patients developed severe abdominal pain and haemorrhagic cystitis secondary to gastric acid secretion in the neobladder from the transplanted gastric pedicle. Nutritional and pharmacological interventions were used to manage the gastrointestinal problems. Explanations are offered for the pathophysiology of the observed complications of gastrocystoplasty. It is believed that the use of this procedure in infants and children, particularly those with chronic renal failure and uraemia, warrants caution until successful long term follow up and experience with this procedure have been reported.

The T84 human colonic adenocarcinoma cell line produces mucin in culture and releases it in response to various secretagogues.

The T84 colonic adenocarcinoma cell line, which has been used extensively as a model for studies of epithelial chloride secretion, also produces mucin and secretes it in culture. Electron microscopy of fixed sections of cultured cells, along with Immunogold labelling with an antibody to human small intestine (SI) mucin, revealed the presence of goblet-like cells with mucin-containing secretory granules. The mucin was of high molecular mass, had an amino acid composition similar to that of purified human SI and colonic mucins, and competed effectively with SI mucin for binding to the anti-(SI mucin) antibody. A sensitive solid-phase immunoassay specific for intestinal mucins was developed and used to measure mucin secretion by T84 cells. Cultures were treated for 30 min at 37 degrees C with a number of agents known to cause chloride secretion by T84 cell monolayers and the amount of mucin appearing in the medium was measured. Carbachol (1 mM), A23187 (10 microM), prostaglandin E1 (PGE1) (1 microM) and vasoactive intestinal polypeptide (VIP) (0.1 microM) all stimulated mucin release, but histamine (1 mM) had no effect. Whereas VIP is reported to stimulate chloride secretion more strongly than carbachol, it was less effective than carbachol in stimulating mucin secretion. Phorbol 12-myristate 13-acetate (PMA) (0.1-10 microM) also stimulated mucin release strongly, implicating a responsive protein-kinase C-dependent pathway. Additive secretory responses were obtained with combined stimulation by VIP (10 nM-1 microM) and carbachol (1 mM). Responses to stimulation with A23187 (1-10 microM) together with PMA (10 nM-10 microM) suggest that cytosolic Ca2+ concentration is a modulator of PMA activity.

Inhibition of mucin secretion in a colonic adenocarcinoma cell line by DIDS and potassium channel blockers.

The factors which influence the exocytosis of mucins are not well characterized. Since the physical properties of mucins may be affected significantly by the co-secretion of electrolytes and water, we studied the relationship between ion movement and mucin secretion in T84 cells, a human colonic adenocarcinoma cell line which has been well characterized with respect to apical chloride secretion. Secretion of mucin was assessed by immunoassay of mucin appearing in the medium within 30 min of stimulation. Cells were grown on plastic in DMEM/Ham's F12 medium and experiments were carried out at 70% confluence. Mucin secretion was stimulated by the calcium ionophore A23187, or A23187 plus vasoactive intestinal polypeptide. Stimulated mucin secretion was not affected by loop diuretics (furosemide (1 x 10(-3) M) or bumetanide (1 x 10(-4) M)), with or without the addition of ouabain (5 x 10(-5) M) and amiloride (1 x 10(-5) M), making it unlikely that transcellular chloride movements in necessary for mucin secretion. However, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; (1 x 10(-5) and 5 x 10(-5) M) and three potassium channel blockers BaCl2 (1 x 10(-3) and 5 x 10(-3) M), tetraethylammonium chloride (1 x 10(-2) M) and quinine (5 x 10(-4) M) inhibited mucin secretion. A DIDS-sensitive chloride channel or chloride/bicarbonate exchanger and a Ca2(+)-dependent potassium channel may play important roles in mucin secretion. Since plasma membranes are sparingly permeable to DIDS, the DIDS-sensitive site is likely to be on the apical plasma membrane, perhaps at an initiation locus for exocytosis.

Late gastrointestinal bleeding and protein loss after distal small-bowel resection in infancy.

Four children who underwent extensive small-bowel resection in infancy developed recurrent iron deficiency anemia due to gastrointestinal bleeding between 4 and 12 years later. The initial resections were required for multiple ileal atresia (n = 2) and gastroschisis (n = 2). Three patients have had melena and one had persistently guaiac-positive stools. Three patients had protein-losing enteropathy, and in one there was persistent hypoalbuminemia. Colonoscopy identified circumferential ulcerative lesions at the surgical anastomosis (n = 2) and at laparotomy another patient had well-defined linear ulcers close to the surgical anastomosis. Histology demonstrated focal ulceration with chronic inflammation, but did not show granulomata, crypt abscesses, or malignancy. Multiple imaging procedures and gastroduodenoscopy failed to identify an alternative bleeding source. Medical therapy including iron, antacids, sucralfate, H2 antagonists, and cholestyramine was ineffective. Two patients have undergone anastomotic resection. One experienced symptomatic recurrence 4 months after surgery. Repeat colonoscopy found ulceration at the new anastomosis with similar histology. The other patient remains asymptomatic 7 months postsurgery. Recurrent gastrointestinal hemorrhage due to anastomotic ulceration, of unknown etiology, appears to be a late complication of small-bowel resection in infancy.