Pancreatic neuroendocrine tumors: gastrinoma
What is the medical management of gastrinoma and ZES?
The approach to the treatment of patients with gastrinoma and ZES has undergone an evolution over the last fifty years. Initially, effective therapy consisted of aggressive surgery including total removal of the stomach. The goal of surgery was to remove the organ responsible for the increased acid production in an attempt to manage the debilitating and often life threatening ulcer disease. In the modern era, medical treatment of elevated gastric acid secretion is the mainstay of therapy. The H2 antagonists (cimetidine, ranitidine, famotidine) alone or in combination with anticholinergic agents (probanthine, isopropamide) and the substituted benzimidazole (omeprazole), which functions as an inhibitor the secretion of acid, have been used successfully in the long-term treatment of patients with ZES. Symptom relief does not always reflect the effectiveness of anti-acid secretion therapy. Most studies have demonstrated that in order to assess the adequacy of therapy, gastric acid secretion must be measured while the patient is taking the medication.
Patients with ZES often require higher doses of acid reducing medications compared to patients with peptic ulcer disease or gastro-esophageal reflux. The long-term use of these higher doses of H2 antagonists and omeprazole has proven not only effective but also safe.
The increased gastric acid secretion seen in ZES patients must be controlled because most patients will not be cured following surgical exploration. If acid hypersecretion is controlled, patients have an excellent quality of life; however, long-term prognosis is being increasingly determined by the malignant nature of the gastrinoma. As many as 90% of gastrinomas may be malignant and therefore, it is important to consider surgical therapy directed at the primary and metastatic disease if feasible in patients with sporadic ZES. Metastatic disease is often to the liver and can be managed with surgical resection, regional infusions or radiofrequency ablation. For isolated liver metastases not amenable to these approaches without evidence of extra-hepatic disease, a liver transplant may be considered based on the slow growing (indolent) nature of these tumors.
Systemic therapies beyond those directed at the control of acid secretion have had limited utility. Somatostatin receptor directed therapies such as octreotide and radiolabled-octreotide have been used with variable results. Systemic chemotherapies such as cisplatin and adriamycin have also been tried with limited success. The mainstay of management remains surgical removal or debulking when possible and the use of acid controlling medications to control symptoms.