Gastrinomas are rare neuroendocrine tumors (NETs) with an incidence of approximately 1 to 2 per million people.1 Excessive gastrin release from these tumors leads to acid hypersecretion in the stomach, causing a multitude of clinical presentations. Patients with gastrinomas will typically complain of abdominal pain, diarrhea, heartburn, gastrointestinal bleeding, and weight loss.2
“Zollinger-Ellison syndrome” (ZES) represents the constellation of symptoms caused by an underlying gastrinoma in addition to the development of severe peptic ulcer disease resulting from acid hypersecretion. Most gastrinomas are found within the “gastrinoma triangle,” which is an anatomic region defined by the confluence of the cystic and common bile duct, the second and third parts of the duodenum, and the neck and body of the pancreas.
Management of gastrinomas can be challenging. Initial management of acute symptoms, such as gastrointestinal bleeding, can be done while performing an esophagoduodenoscopy (EGD). In addition to its therapeutic capabilities, EGD can provide useful diagnostic information: the EGD will often identify multiple ulcers within the stomach, duodenum, and jejunum. If these ulcers are actively bleeding, or have stigmata of recent bleeding, endoscopic interventions can be performed to assist in hemostasis. Potential interventions include injection of epinephrine, cauterization, and/or endoscopic clipping.
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Excess acid may also be apparent with evidence of esophagitis and thickened gastric folds. Most patients with peptic ulcer disease will be placed on acid suppression medications with proton pump inhibitors (PPIs), especially in the event of active or recent bleeding.3 Biopsies are often taken of the stomach and duodenal mucosa to rule out an infection with Helicobacter pylori as an underlying cause of peptic ulcer disease. Biopsies can also be taken from the duodenum to rule out additional causes of diarrhea, such as celiac disease or infectious organisms. If a patient has adequately been treated with PPI therapy and repeat EGD shows persistent ulcers, a gastrinoma should be kept on the differential diagnosis.
While an EGD can assist in the diagnosis and acute management of the sequelae of a gastrinoma, additional workup should be done to confirm the diagnosis and plan the appropriate treatment. Patients should have a fasting gastrin level drawn, ideally off PPI therapy. PPIs can, however, cause elevations in gastrin levels, which may provide false positive results. Gastrinomas can be localized using 1 or a combination of imaging modalities including endoscopic ultrasound, computed tomography, or magnetic resonance imaging of the abdomen and pelvis.
Once localized and the management of acute bleeding is completed, it is important to consider the long-term management of gastrinomas. Patients are typically started on high doses of PPIs for control of hypersecretion of acid. If there is inadequate response to PPIs, octreotide can be added to their regimen, which inhibits gastrin secretion.
If a patient has a solitary, sporadic gastrinoma without evidence of metastases on cross-sectional imaging, she/he should be evaluated for surgical resection with the potential for a cure.4 Gastrinomas in the setting of multiple endocrine neoplasia type 1 syndrome are typically not resection candidates unless the lesions are greater than 2 cm, as these patients are at significantly higher risk of multifocal lesions. Patients who are not surgical candidates can be medically managed as above or can be considered for radiation therapy or chemotherapy, although there are significantly fewer data to support these treatment modalities.
References
- Kulke MH, Anthony LB, Bushnell DL. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas. 2010;39(6):735-52.
- Epelboym I, Mazeh H. Zollinger-Ellison syndrome: classical considerations and current controversies. Oncologist. 2014;19(1):44-50.
- Quatrini M, Castoldi L, Rossi G, Cesana BM, Peracchi M, Bardella MT. A follow-up study of patients with Zollinger-Ellison syndrome in the period 1966-2002: effects of surgical and medical treatments on long-term survival. J Clin Gastroenterol. 2005;39(5):376-80.
- Norton JA, Fraker DL, Alexander HR, Jensen RT. Value of surgery in patients with negative imaging and sporadic Zollinger-Ellison syndrome. Ann Surg. 2012;256(3):509-17.
