Neuroendocrine tumors of the small bowels are on the rise: Early aspects and management

Abstract

Neuroendocrine tumors of the small bowel are on the rise. In the US they have increased by 300%-500% in the last 35 years. At the same time their prognosis is much improved. Today, most neuroendocrine tumors (NETs) of the duodenum are detected "incidentally" and therefore recognized at an early stage. Duodenal NETs which are well differentiated, not larger than 10 mm and limited to the mucosa/submucosa can be endoscopically resected. The management of duodenal NETs ranging between 10 and 20 mm needs an interdisciplinary discussion. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is recommended for well-differentiated duodenal NET tumors greater than 20 mm, for localized sporadic gastrinomas (of any size) and for localized poorly differentiated NE cancers. Surgery is recommended for any ileal NET. Advanced ileal NETs with a carcinoid syndrome are treated with long-acting somatostatin analogs. This treatment significantly improves (progression-free) survival in patients with metastatic NETs of the ileum. For optimal NET management, tumor biology, type, localization and stage of the neoplasm, as well as the patient's individual circumstances have to be taken into account.

Keywords: Cancer; Carcinoid; Duodenum; Gastrinoma; Ileum; Jejunum; Multiple endocrine neoplasia.

Figure 1

Epidemiological rise in the frequency of neuroendocrine neoplasms of the small bowel, rectum, stomach or pancreas in the United State. Modified from Modlin et al[1].

Figure 2

Endoscopic images of well-differentiated (G1), small intestinal neuroendocrine tumors. A: 8 mm measuring neuroendocrine tumor (NET) in the duodenal bulb (A1). Endoscopic ultrasound shows the infiltration of mucosa and submucosa (A2). The duodenal NET exhibits a low echogenic pattern on endosonography (EUS); B: Duodenal NET of 21 mm size (B1), the muscularis propria is not infiltrated endosonographically (B2). The tumor shows a low echogenic pattern on EUS. The tumor (B3) shows a good arterial perfusion (by Doppler sonography); C: 10 mm-sized duodenal NET (C1). The chromoendoscopy (with indigo carmine) (C2) and the zoom endoscopy (C3) show an intact villous pattern and a crater-like retraction of the mucosa at the center of the tumor (modified from reference [77]); D: Sporadic gastrinoma of the duodenal bulb; E: Sporadic gastrinoma of the second part of the duodenum; F: Multiple duodenal gastrinomas in a patient with multiple endocrine neoplasia type 1 disease; G: 12 mm-sized NET of the distal ileum. Both tumor localisation and histological diagnosis were established using double balloon enteroscopy[34]. Ileal NETs present multifocally in 26%-30% of patients; H-I: 14 mm-sized NET of the terminal ileum. The primary tumor was located 8 cm proximal to the ileocecal valve. Ileocolonoscopy allowed not only tumor localization, but also histological verification of ileal NET disease (modified from reference [77]).