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Image of the Month—Diagnosis
Arch Surg. 2003;138:914.
Answer: Zollinger-Ellison Syndrome
Figure 1. Hypertrophic folds within the body of the stomach, and a normal antrum.
Figure 2. Duodenum and proximal jejunum revealing multiple ulcers.
Gastrinomas are rare neuroendocrine tumors that secrete gastrin, producing severe peptic ulcer or even jejunal ulcer disease. Zollinger and Ellison1 were the first to attribute marked peptic ulcer disease in association with gastric acid hypersecretion and tumors of the pancreas. The discovery of gastrin in the 1960s helped further delineate the pathophysiology.2
Gastrinomas are the most common malignant pancreatic islet cell tumors. The incidence is rare, occurring in 0.1 to 3 million individuals per year.3 About 25% are associated with inherited familial disorders, such as multiple endocrine neoplasia type 1, and the remainder are sporadic. The incidence among patients with peptic ulcer disease is 0.1%; however, this approaches 1% in patients with recurrent disease.2 Sixty percent are malignant, of which 25% are especially virulent and grow rapidly.3-4 Ninety percent are located within the gastrinoma triangle, defined as the junction of the cystic duct and common bile duct superiorly, the second and third portions of the duodenum inferiorly, and the junction of the neck and body of the pancreas medially.2
Patients typically have symptoms of epigastric pain, heartburn, dysphagia, or diarrhea. The mean age at onset is 50 years (range, 7-90 years), with a male-female predominance of 2:1. Ninety percent of patients have peptic ulceration, and 10% to 15% also have distal duodenal and jejunal ulcers.3 Hypertrophic gastric folds within the proximal stomach are caused by gastrin stimulation. Forty percent of patients have secretory watery diarrhea associated with significant malnutrition and weight loss. About 20% of patients will have diarrhea as their sole complaint. Ten percent will have evidence of severe reflux by endoscopy and can exhibit strictures of the esophagus.3
A fasting serum gastrin level is the initial screening test for gastrinoma. A level greater than 100 pg/mL (47.7 pmol/L) indicates hypergastrinemia, and a level greater than 1000 pg/mL (477 pmol/L) is pathognomonic. Our patient's gastrin level was 1120 pg/mL (534.2 pmol/L). The secretin stimulation test can distinguish gastrinoma from other sources of hypergastrinemia.
Localization studies historically have been poor. Ultrasound, computed tomography, and angiography have sensitivities of 21%, 59%, and 68%, respectively, and specificities of 92%, 95%, and 94%.2 To date, the most accurate test is somatostatin receptor scintigraphy (sensitivity, ~90%; specificity, ~100%),3, 5 which localized the tumor to an isolated area at the descending duodenum and head of the pancreas.
Treatment of Zollinger-Ellison syndrome is controversial. Historically, surgical cure rates for gastrinoma excision have been poor, with only a 5% success rate, and total gastrectomy has been the treatment of choice.2 The advent of powerful acid-suppressing medications has prompted some authors to recommend medical therapy alone.6 Mortality from complications of severe ulcer disease has dramatically dropped, owing to these medical regimens.7 However, tumor size and risk of rapid growth, with a 60% potential for malignancy, confer a much greater risk of mortality.3-4,7 Patients with sporadic gastrinomas without evidence of metastatic disease should be offered surgical exploration. Although surgery is seldom curative for patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1, liver metastasis may be preventable and overall survival, prolonged.3
Surgical exploration involves full abdominal exploration, focusing in the gastrinoma triangle. Intraoperative ultrasound, intraoperative endoscopic transillumination, and longitudinal duodenotomy can help identify small tumors.3-4 Most tumors can be enucleated but may require extensive resection if the tumor is larger than 2 cm. Regional lymph nodes should also be removed for histologic evaluation. Our patient had a 1 cm-gastrinoma resected from the wall of the second portion of the duodenum. An enlarged local node was negative for metastatic disease. Immediate cure rates are 14% to 58%, and long-term cure rates are between 31% and 81%. The 5- and 10-year survival rates for resection of sporadic gastrinomas are 100% and 95%, respectively.3-4
AUTHOR INFORMATION
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Corresponding author and reprints: James C. Hebert, MD, University of Vermont, Fletcher House, 111 Colchester Ave, Burlington, VT 05401 (e-mail: james.hebert{at}vtmednet.org).
REFERENCES
1. Zollinger RM, Ellison EH. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg. 1955;142:709-728.
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2. Howard TJ, Passaro E. Gastrinoma: new medical and surgical approaches. Surg Clin North Am. 1989;69:667-681.
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3. Dolan, JP, Norton JA. Neuroendocrine tumors of the pancreas and gastrointestinal tract and carcinoid disease. In: Norton JA, Bollinger RR, Chang AE, et al, eds. Surgery: Basic Science and Clinical Evidence. New York, NY: Springer; 2001.
4. Norton JA, Fraker DL, Alexander HR, et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med. 1999;341:635-644.
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5. Alexander HR, Fraker DL, Norton JA, et al. Prospective study of somatostatin receptor scintigraphy and its effect on operative outcome in patients with Zollinger-Ellison syndrome. Ann Surg. 1998;228:228-238.
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6. Hirschowitz BI. Clinical course ofnonsurgically treated Zollinger-Ellison syndrome. Front Gastrointest Res. 1995;23:360-371.
7. Yu F, Venzon DJ, Serrano J, et al. Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing Zollinger-Ellison syndrome. J Clin Oncol. 1999;17:615-630.
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SECTION EDITOR: GRACE S. ROZYCKI, MD
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