gastroenteropancreatic neuroendocrine tumours (NETs)

Gastroenteropancreatic NETs may be classified into non-functioning tumours, which have no hormone-related clinical features, and functioning tumours, which cause symptoms due to peptide and hormone release. 

In all NETs, presenting features may include non-specific symptoms such as:

-pain (which may be intermittent and present for many years), Pain may be due to local tumour invasion,

-nausea and vomiting,

-anaemia due to intestinal blood los

Most gastroenteropancreatic NETs are non-functioning and present with
mass effects of the primary tumour or metastases (usually liver).

A high index of suspicion is needed to identify patients, and diagnosis is often delayed for several years, often made as an incidental finding at surgery or during radiological

1-Non-functioning gastroenteropancreatic NETs:

Usually asymptomatic

Gastric and rectal NETs are often diagnosed coincidentally at endoscopy, or may be the source of anaemia.

2-Functioning gastroenteropancreatic NETs:
Because GNETs are of neuroendocrine origin, they may secrete various peptides and hormones. Most of these tumours produce several hormones , but very few are associated with clinical syndrome. Symptoms depend on the peptide hormone released.

Carcinoid syndrome

These originate from the enterochromaffin cells (APUD cells) of the intestine. They make up 10% of all small bowel neoplasms, the most common sites being in the appendix, terminal ileum and the rectum. It is often difficult to be certain histologically whether a particular tumour is benign or malignant. Clinically most carcinoid tumours are asymptomatic until metastases are present. 10% of carcinoid tumours in the appendix present as acute appendicitis, the inflammation being secondary to obstruction. Surgical resection of the tumour is usually performed.

Carcinoid syndrome occurs in only 5% of patients with carcinoid tumours and only when there are liver metastases.The bioactive product is secreted directly into the hepatic vein bypassing inactivation by the liver. Clinical features: Spontaneous or induced bluish-red flushing,without sweating predominantly on the face and neck(70%). Gastrointestinal symptoms consist of : intermittent abdominal pain(40%), and recurrent watery diarrhoea(50%). Cardiac abnormalities are found in 50% of patients and consist of pulmonary stenosis or tricuspid incompetence. Examination of the abdomen reveals hepatomegaly.

The tumours secrete a variety of biologically active amines and peptides, including serotonin (5 -hydroxytryptamine; 5-HT), bradykinin, histamine, tachykinins and prostaglandins.

The diarrhoea and cardiac complications are probably caused by 5-HT itself, but the cutaneous flushing is thought to be produced by one of the kinins, such as bradykinin, which is known to cause vasodilatation, bronchospasm and increased intestinal motility.

Diagnosis and treatment

-Role out MEN1, MEN2 and NF1 -Ultrasound examination confirms the presence of liver secondary deposits. -Chromogranin A is the only general marker for NETs -The major metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), is found in high concentration in the urine. -Octreascan-octreotide scintigraphy can identify the primary tumour and secondaries in 80%.

Octreotide and lanreotide are octapeptide somatostatin analogues that have been shown to inhibit the release of many gut hormones. They alleviate the flushing and diarrhoea and can control a carcinoid crisis. Octreotide is given subcutaneously in doses up to 200 μg three times daily initially; a depot preparation 30 mg every 4 weeks can then be used. Lanreotide 30 mg is given every 7-10 days, or as a gel 60 mg every 28 days.

Long-acting octreotide also sometimes inhibits tumour growth and, since its introduction, other therapy is usually unnecessary. Interferon and other chemotherapeutic regimens occasionally reduce tumour growth, but have not been shown to increase survival. Most patients survive for 5-10 years after diagnosis. Pancreatic NET: 1- Gastinoma: gastrin producing tumour Rare, few than 1% of patients presenting with PUD Frequently associated with MEN1 50% of gastinomas occur in the duodenal wall, and the second common place is the pancreas. result in hypersecretion of acid which result in severe PUD, maily multiple duodenal ulcers. 50% have diarrhea due to the effect of acid in small bowel. If a patient present with duodenal ulcer which is not due to H pylori infection or NSAIDs, or present with the ucer and diarrhea, the concurrent presence of gastrinoma should be considered. Surgical resection is the treatment of choice for patients with resectable disease. If resection is not possible, medical treatment consist of PPI and octreotide. 2-insulinoma: insulin secreting ilet tumour that cause hypoglycaemia. 3-VIPoma: pancreatic tuomour that secrete vasoactive intetinal polypeptide. the syndrome is characterized by;  severe watery diarrhea, hypokalaemia, and achlorohydria (Vernaer-Morison syndrome)