Antral Duplication Cyst: A Cause of Hypergastrinemia, Recurrent Peptic Ulceration, and Hemorrhage

Abstract

Antral duplication cyst of the stomach is rare and may appear as an abdominal mass, gastric outlet obstruction, or gastrointestinal hemorrhage(1,2). We report an unusual case of a noncommunicating antral duplication cyst lined by antral mucosa that caused hypergastrinemia, recurrent peptic ulceration, and upper gastrointestinal bleeding, beginning in the patient at 2 weeks of age. Similar cases have been reported before but none with documented hypergastrinemia. CASE REPORT A 16-month-old, female infant was seen in our institution for recurrent episodes of hematemesis and melena. The first episode occurred at 2 weeks of age when an endoscopic examination at a local hospital showed multiple gastric ulcers. No further workup was done, and treatment with ranitidine was begun. Between 2 weeks and 16 months of age, the patient had occasional vomiting with a small amount of blood and was treated with ranitidine intermittently by her physician. The current episode of gastrointestinal bleeding started 2 days before admission. Physical examination revealed a pale, young child who was developmentally delayed, with mild esotropia. She weighed 9.1 kg (10th percentile), was 77 cm in height (25th percentile), and had a head circumference of 47 cm (10th percentile). Vital signs were stable except for tachycardia (160 bpm). Her abdomen was soft, without organomegaly. Her stools were melanotic and tested positive for occult blood. Laboratory studies showed hemoglobin of 6.4 g/dl. with normal indices; platelets 422,000/mm3; and WBC 15,900/mm3. The patient was transfused with packed red blood cells to reach a hemoglobin of 10.2 g/dl. The serum electrolytes, calcium, phosphorus, liver enzymes, and coagulation levels were normal. The patient underwent EGD, which revealed severe exudative esophagitis, with no active bleeding and normal-appearing gastric and duodenal mucosa. Rapid urease test for Helicobacter pylori on the antral mucosa was negative. Prolonged pH monitoring for 16 hours showed significant acid exposure to the distal esophagus (fraction of time that pH was <4 = 15%), wherein gastric pH stayed less than 3 more than 94% of the time. Scintigraphic scan using 180 ml of formula for 2 hours showed frequent gastroesopahageal reflux with normal gastric emptying (half-life of 100 minutes). The patient was treated with 2 mg/kg ranitidine three times daily, 250 mg sucralfate three times daily, and 0.2 mg/kg cisapride three times daily. After 8 weeks, ranitidine was decreased to 2 mg/kg nightly, and sucralfate was discontinued. The developmental delay was investigated with urine and serum amino acid screen, blood chromosomal analysis, urine for mucopolysaccharide screen, and computed axial tomography of the head. All results were normal. The patient experienced two more episodes of upper gastrointestinal bleeding at 20 and 21 months of age, requiring blood transfusions. She had been receiving 2 mg/kg ranitidine nightly. Endoscopic examination showed a duodenal bulb ulcer. Serum gastrin level at 20 months of age was 646 pg/ml while the patient was receiving 2 mg/kg ranitidine nightly. Continuous recording showed that gastric pH stayed at less than 2 throughout 20 hours, during which the patient was receiving continuous intravenous 5 mg/kg ranitidine per day. When ranitidine infusion was increased to 10 mg/kg per day the gastric pH stayed at less than 2 for 91% of the 23-hour recording time, suggesting acid hypersecretion. A secretin stimulation test (2 units/kg) did not increase the serum gastrin level from the baseline level, whereas a twofold increase was noted at 30 minutes, with meal stimulation test using 240 ml of Pediasure (Ross Pharmaceuticals, Columbus, OH, U.S.A.). Serum parathyroid and thyroid stimulation hormone levels were normal. Computed axial tomography of the abdomen using contrast revealed a 7 × 22 mm cyst with low-density content at the gastric antrum at its inferior wall. Single photon emission computed tomographic imaging of the abdomen, using indium-111 octreoscan, yielded negative results for gastrinoma. An abdominal exploration at 22 months of age revealed antral thickening, but a cyst was not appreciated. Antrectomy with Billroth II gastrojejunostomy and truncal vagotomy were then performed. The serum gastrin level on the 10th day after surgery was 40 pg/ml. On the 11th day, gastric pH stayed at or above 5 more than 90% of the recording time of 21 hours, suggesting significant inhibition of acid secretion. The patient did well with no recurrence of gastrointestinal bleeding during a postoperative followup of 12 months. The gastrin levels at 5 and 8 months after surgery were 44 pg/ml, and 50 pg/ml, suggesting effective control of the hypergastrinemic state. The patient receives a regular diet and is given 3 mg/kg ranitidine at bedtime. PATHOLOGIC FINDINGS The resected surgical specimen consisted of a 10 × 3 × 2 cm segment of stomach, including a short segment of the attached duodenum. Approximately 0.5 cm from the pyloric margin, a 2-cm cyst containing 1 ml of clear fluid was embedded in the posterior lateral wall (Fig. 1). There was gastric erosion in the proximal portion of the stomach and a small hemorrhagic area of the mucosa at the duodenal margin. Histologic study of the antrum demonstrated normal glands and normal lamina propria, with a few scattered plasma cells and eosinophils. In contrast, the antral mucosa of the duplication cyst demonstrated unusually high foveolae. The lamina propria was almost acellular with no inflammatory cells. In the muscular wall of the duplication and in the normal muscularis propria, there was ectopic pancreas with normal distribution of islets. Immunoperoxidase localization of gastrin and somatostatin cells demonstrated scattered positive cells in the deep glands in both the antrum and duplication. The number of gastrin and somatostatin cells were counted along measured lengths of mucosa, 4 mm or 5 mm long, similar to findings in Annibale et al (3). Gastrin cells were 61/mm in the mucosa and 162/mm in the duplication. Somatostatin cells were 53/mm in the mucosa and 30/mm in the duplication. Scattered somatostatin cells, but no gastrin cells, were demonstrated in the islet tissue in the ectopic pancreas. DISCUSSION Gastric duplication cysts are rare in children, accounting for only 4% to 8% of all alimentary tract duplications (4,5). They are usually spherical or tubular cysts in the greater curvature of the stomach and may not communicate with the gastric lumen (4). Although they are usually lined with enteric mucosa, they may have gastric mucosa. Gastric duplication cysts usually become symptomatic before 2 years of age, either from the mass effect or from peptic ulceration and hemorrhage. Communicating cysts may hemorrhage into the gastrointestinal tract, whereas closed cysts may hemorrhage into the cyst or may perforate. Cases of gastric duplication cysts with symptoms of hemoptysis (6), rectal bleeding (7), and recurrent pancreatitis(8) have been reported. Our patient had an antral duplication with an antral mucosal lining. Such cysts are rare, accounting for 2.2% of all gastric duplications(1,2). They may manifest as an epigastric mass gastric outlet obstruction and may mimic pyloric stenosis. Symptoms appeared in our patient at a uniquely early age (2 weeks old), with recurrent peptic ulceration of the stomach and duodenum associated with hypergastrinemia. In normal situations, acid in the gastric lumen acts directly on the somatostatin cells to stimulate the release of somatostatin, thereby preventing gastrin release by a paracrine mechanism. In an alkaline or neutral environment, there is suppression of somatostatin release resulting in increased gastrin release(9). In our patient, because the extopic antral mucosa was not communicating with the gastric lumen and lacked parietal cells, there was no hydrogen ion feedback inhibition of gastrin release. We postulate that this resulted in continued secretion of gastrin from the ectopic antral mucosa, which overflowed into the systemic circulation and resulted in gastric acid hypersecretion. A similar mechanism has been proposed in retained gastric antrum syndrome after partial gastrectomy with Billroth II surgery(10) and in a 10-month-old infant with a hyperplastic antral polyp that prolapsed into alkaline duodenum with consequent hypergastrinemia and hemorrhage (11). The serum gastrin level fell after surgery, which excluded the diagnosis of a gastrinoma in the pancreas. Ectopic pancreatic tissue was present in the duplication but did not have abnormal gastrin cell proliferation. The anatomy in this case demonstrated an increased gastrin to somatostatin ratio in the noncommunicating duplication cyst, similar to findings reported in cases with antral gastrin cell hyperfunction (3). This effect is probably related to trophic activity of unopposed secretion of gastrin from lack of local hydrogen ions. However, the normal ratio of gastrin to somatostatin cells in the antrum excludes the diagnosis of antral gastrin cell hyperfunction. Our patient had a computed axial tomographic scan in which imaging suggested a cyst. However, because the cyst was not appreciated at surgery and there was uncertainty about the mechanism of the hypergastrinemia, vagotomy and antrectomy with Billroth II gastrojejunostomy were performed to control hypergastrinemia. This procedure, as expected, eliminated the patient's hypergastrinemia. However, if our hypothesis is true, removing only the cyst should have eliminated the hypergastrinemia. This case demonstrates that gastric antral duplication cyst should be considered in the diagnosis of unexplained hypergastrinemia and peptic ulceration in childhood.FIG. 1: . Mucosal surface of the resected gastric antrum. The duplication cyst has been cut open at the left, revealing the thick muscularis and hollow cavity. The scale is 1 mm between lines.