Recent standardization of treatment strategy for pancreatic neuroendocrine tumors

Abstract

Recent advances in localization techniques, such as the selective arterial secretagogue injection test (SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors (PNET). For patients with sporadic functioning PNET, curative resection surgery has been established by localization with the SASI test using secretin or calcium. For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1 (MEN 1) which are usually multiple and sometimes numerous, resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test. As resection surgery of PNET has increased, several important pathological features of PNET have been revealed. For example, in patients with Zollinger-Ellison syndrome (ZES), duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma, and in patients with MEN 1 and ZES, gastrinomas have been located mostly in the duodenum, and pancreatic gastrinoma has been found to co-exist in 13% of patients. Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation. The most important prognostic factor in patients with PNET is the development of hepatic metastases. The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit. The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.

Figure 1

Schema of the selective arterial secretagogue injection test. Results of the selective arterial secretagogue injection (SASI) test in a patient with Zollinger-Ellison syndrome. In this patient, serum immunoreactive gastrin (IRG) at 40 s after the injection of 30 units of secretin rose only after injection into the gastroduodenal artery. Thus, it was diagnosed that the gastrinoma(s) was located in the upper part of the pancreas and/or the duodenum. Gastr.duod.a: Gastroduodenal artery; Spl.a.: Splenic artery; Superior mesenteric a.: Superior mesenteric artery.

Figure 2

Numerous mucosal gastrinomas in the duodenum. Mucosal tumors with depression (arrows).

Figure 3

A cluster of G cells in hyperplasia of duodenal Brunner’s glands in a patient with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome.