Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors

Abstract

THe treatment of patients with advanced neuroendocrine tumors of the pancreas and duodenum has caused considerable controversy^1-4 for many reasons. first, these tumors are rare, with an incidence of approximately 1 to 2 per million people; therefore, no single investigator or surgeon will have a large amount of experience with them, and prospective randomized studies are not possible.⁵ Second, the pathologic characteristics of these tumors are confusing; pathologists often cannot be certain whether an individual neuroendocrine tumor is benign or malignant, primary or metastatic, or multifocal or unifocal, nor can they always determine the subtype of tumor based on immunohistochemistry (insulinoma, gastrinoma, somatostatinoma, or glucagonoma).⁶ Third, the natural history of these tumors is indolent, so patients may live for years with untreated metastatic disease.⁷ Fourth, 2 distinct life-threatening issues with these tumors require effective treatment: excessive hormonal secretion and the malignant tumoral process.⁴ For example, in patients with malignant gastrinoma or insulinoma, life-threatening symptoms occur as a result of excessive uncontrolled hormone secretion and dissemination of metastases. treatment strategies must be designed to meet both problems; the acid hypersecretion and hypoglycemia must be managed, and the tumor metastases and invasion must be controlled. fifth, neuroendocrine tumors of the pancreas occur both sporadically (noninherited form) and in families (inherited), and the disease process may be very different in the 2 forms.⁸ For example, patients who develop zollinger-ellison syndrome (zes) in the sporadic form have a 40% long-term cure rate with surgery, whereas those who develop the same disease in the setting of multiple endocrine neoplasia type 1 (men 1) have a 0% long-term cure rate. thus, treatment of the same tumor may be different in sporadic vs familial forms. furthermore, some physicians argue that surgery is not indicated even for patients with sporadic zes because treatment of the acid secretion with proton pump inhibitors is outstanding and the surgical cure rate is low.^3,9 Finally, most patients with nonfunctional neuroendocrine tumors initially develop either locally advanced or metastatic tumors, resulting in a more difficult surgical procedure and higher morbidity rate.⁴