Net of the duodenum and proximal jejunum D44.9

The neuroendocrine tumors of the duodenum and proximal ileum (acronym "NET of the dodenum and proximal jejunum") are also known under various terms such as carcinoid, islet cell tumor or gastrinoma, among others. These terms are used to indicate the respective preferred localisation (islet cell tumour) or the pattern of secretion (gastrinoma with the hypersecretion of gastrin).

There are 5 types of benign neuroendocrine tumors of the duodenum and proximal jejunum:

Gastrin-positive tumor (proximal duodenum)

• Functionally active gastrin-positive tumour (gastrinoma) of the proximal duodenum, sporadically or MEN-1-associated (D44.8) - about 65% of duodenal NETs (Zollinger-Ellison syndrome)
• Functionally inactive serotonin-positive tumor
• Functionally active serotonin-positive tumor
• Functionally inactive somatostatin-positive tumor (Ampulla Vateri) with or without neurofibromatosis type 1 (NF1 - Q85.1)
• Furthermore the:
• Gangliocytic paraganglioma (periampullary)

Highly differentiated neuroendocrine carcinoma (NEK):

• Functionally active gastrin-positive carcinoma (gastrinoma), sporadic or MEN-1 associated
• Functionally inactive somatostatin-positive carcinoma (Ampulla Vateri) with or without neurofibromatosis type 1 (NF1)
• Functionally inactive or active (with carcinoid syndrome) carcinoma
• Malignant gangliocytic paraganglioma

Approximately 30% of small bowel tumors are NETs, which preferentially occur in the distal small bowel. At the time of diagnosis, a locally confined growing tumor can be expected in 29%, regional lymph node metastases in 41%, and distant metastases in 30% (Modlin IM et al. 2007).

In principle, all GEP-NETs originate from the neuroendocrine cells of the gastroenteropancreatic (GEP) system. This endocrine cell system and its tumors are characterized by the expression of cell type-specific peptide hormones (e.g. gastrin) and various other peptides. neurotransmitters such as synaptophysin and chromogranin-A. The increased secretion of these hormones leads to diagnostically groundbreaking hypersecretion syndromes (e.g. flush symptoms) with corresponding clinical symptoms. Duodenal NETs consist of gastrinomas in about 65% of cases and somatostatinomas in about 15% of cases.

The functionally active duodenal gastrinomas occur either sporadically or associated with MEN-1. The MEN-1-associated gastrinomas usually occur multiple times and are usually not larger than 1.0 cm. They are predominantly located in the proximal duodenum. Despite their small size and their limited extension to the duodenal mucosa and submucosa, duodenal gastrinomas often have nodal metastases at the time of diagnosis. Liver metastases occur relatively late.

Non-functional duodenal NETs (rare) include prognostically favourable and unfavourable tumours. They are highly differentiated and behave benignly if they do not cross the submucosa. If they are poorly differentiated (NEKs), advanced metastasis is often already present at the time of diagnosis.

The duodenal somatostatinomas (about 15% of all duodenal NETs) are preferably located in the area of the papilla vateri or periampullary. They do not develop somatostatinoma syndrome (diabetes, cholelithiasis and diarrhoea). Duodenal somatostatinomas are often associated with neurofibromatosis type I. It is not uncommon for a double-sided pheochromocytoma to occur simultaneously. If they infiltrate the muscularis propria, they are potentially malignant. Fines are characterized by glandular patterns with psammoma bodies.

The poorly differentiated (G3) neuroendocrine carcinomas of the duodenum (NEKs) are mostly found periampullary or directly in the area of the papilla Vateri. Their proliferation rate is usually well over 20% (G3).

A special feature are the duodenal gangliocytic paragangliomas, which occur in the vicinity of the Papilla Vateri and generally behave benignly despite a size > 2 cm and infiltration of the Muscularis propria.

Well differentiated, non-functional NETs of the duodenum, which are restricted to the mucosa/submucosa, have a diameter of up to 1cm, show a low proliferative activity (Ki-67<2%, G1) and do not grow angioinvasively, can be called NET without risk factors. They can be resected endoscopically.

Duodenal NETs with angioinvasion or a proliferation rate >2% or infiltration of the deep submucosa or a size of >2cm are primarily operated.

Duodenal gastrinomas (any size, poorly differentiated (G3) neuroendocrine carcinomas) as well as sporadic, often periampullary somatostatin-producing duodenal NETs of >1-2cm are operated primarily.

The gangliocytic paragangliomas of the duodenum can be successfully removed endoscopically up to a size of 3.0 cm (Park SJ et al. 2014).

The timing and extent of surgery should be determined according to patient characteristics (age, comorbidity, etc.) and patient preferences.

Non-functional MEN1-pNEN ≤1cm should generally not be resected.

Non-functional MEN1-pNEN > 2cm, which are suspected in imaging to have lymph node metastasis (diffuse distant metastasis should be excluded) without significant co-morbidity should normally be resected.

MEN1-NF-pNEN between 1 and 2cm: surgery as well as close monitoring possible.

Depending on the initial tumor stage, the rate of affected lymph nodes, grading, primary tumor localization, lymph and blood vessel invasion, there is a varying but relevant risk of recurrence. Late recurrences, occasionally after more than 10 years after resection, can occur. Most recurrences occur as remote metastasis. Meaningful prospective randomized studies comparing adjuvant treatment with a follow-up strategy are not available, i.e. a possible benefit of adjuvant therapy compared to follow-up and initiation of therapy in case of recurrence is not proven (AWMF guideline).

Neuroendocrine tumors of the duodenum are now detected 5 to 10 times more frequently than 35 years ago. Today they are often diagnosed "en passant" in the course of an esophagogastroduodenoscopy.

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