Duodenal neuroendocrine tumors (d-NETs): challenges in diagnosis and treatment

Duodenal neuroendocrine tumors (d-NETs) represent 2% of all gastroenteropancreatic neuroendocrine neoplasms. Approximately 40 to 60% of patients at the time of diagnosis have metastases to regional lymph nodes and 10% have liver metastases. D-NETs are mostly incidentally discovered during upper gastrointestinal endoscopy as solitary lesions confined to the mucosa and submucosa. The majority of d-NETs are non-functional, but 10% are gastrinomas and less than 4% present with typical carcinoid syndrome. Measurement of serum gastrin and chromogranin A and screening for the MEN-1 syndrome is mandatory in all patients, while 5-HIAA should be measured only in case of typical symptoms. Magnetic resonance imaging (MRI) may be used to assess tumor spread and to detect primary tumor. Endoscopic ultrasound should be routinely used only for patients who are candidates for endoscopic treatment. Approximately 50% of patients have positive findings on somatostatin receptor scintigraphy (SRS), which should be used only in patients with metastatic disease. Treatment of d-NETs is controversial. Further studies are mandatory in order to detect patients who would benefit from radical surgery, which is associated with high mortality and morbidity rates. Current knowledge suggests that all tumors larger than 20 mm in diameter, sporadic gastrinomas and all periampulary dNETs must undergo radical surgery. Endoscopic mucosal resection is treatment of choice for G1 d-NETs smaller than 20 mm confined to submucosa. Transduodenal surgical resection may be used for patients with d-NETs invading muscularis propria. Additional surgical interventions are recommended after endoscopic treatment in case of G1 or G2 d-NETs with positive margins, G2 or G3 histological grading, invasion into muscular layer or in case of lymphovascular invasion. In case of metastatic disease, cytoreductive surgery should be considered as it improves overall 5-year survival rates. Somatostatin analogs may be used for G1 and G2 tumors, while cisplatin and etopozide should be used for G3 d-NETs. Everolimus may be effective for patients with G2 d-NETs. Peptide receptor radionuclide therapy may be used for patients with positive SRS and progressive disease.