GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOURS Flashcards
What are Gastroenteropancreatic neuroendocrine tumours (GEP-NETs)?
neuroendrocrine tumours originating from neuroendocrine cells in the gastrointestinal tract or the pancreas, all of which have malignant potential
What is the incidence of GEP-NETs?
2-3 per 100,000 persons per year
Where are most of the GEP-NETs in the GIT?
Most in small intestine
Rest in rectum or stomach
What are the risk factors of neuroendocrine tumours?
Majority sporadic but… may occur as part of complex familial endocrine cancer syndromes such as MEN1, MEN2, neurofibromatosis type 1 (NF1), Von Hippel Lindau (VHL), and Carney complex
Female gender
Family history of NETs
How are GEP-NETs classified?
Non-functioning tumours (majority)
Functioning tumours
How do GEP-NETs present?
Non-specific e.g. vague abdominal pain, nausea and vomiting, abdominal distension
Less commonly they may present with features of bowel obstruction requiring urgent intervention
What additional symptoms can functioning GEP-NETs present with?
Depends on the type of hormones they produce
Serotonin - flushing, diarrhoea, skin lesions, valvular heart disease
Gastrin - stomach ulcers, abdominal pain that spreads to back, diarrhoea, GERD
Insulin - hypoglycaemia sympotms, tachycardia
Glucagon - rash on face/stomach/legs, hyperglycaemia sympotms, unexplained weight loss, diarrhoea, thrombosis, sore younger/corners of mouth
VIP - watery diarrhoea, dehydration, hypokalaemia sympotms, abdominal pain, unexplained weight loss
Somatostatin - hyperglycaemia, diarrhoea, gallstones, steatorrhoea, jaundice, unexplained weight loss
20% of well-differentiated small bowel neuroendocrine tumours present with what?
Carcinoid syndrome
What is carcinoid syndrome?
Occurs following metastasis of a carcinoid tumour whereby the metastasised cells begin to oversecrete bioactive mediators, such as serotonin, prostaglandins, and gastrin, into the circulation. Patients present with symptoms of flushing, palpitations, intermittent abdominal pain, diarrhoea, and palpitations.
How do we investigate GEP-NETs?
Chromogranin A (CgA) - high concentrations in all NETs (if normal test for CgB)
If both are normal check for pancreatic polypeptide - this is secreted in high concentrations in. 50-80% of pancreatic NETs and >30% of all gut NETs
5-HIAA may be raised
CT imaging
Endoscopy for suspected gastric, duodenal and colorectal NETs
What is carcinoid syndrome?
Neuroendocrine tumours secretes hormones (serotonin, histamine, bradykinin) that leads to symptoms such as diarrhoea, SOB, itching and flushing
Where are neuroendocrine cells?
Throughout the body but particularly in the epithelial layer of gastrointestinal organs and the lungs
What hormones do neuroendocrine cells release?
Amines - serotonin and histamine
Polypeptides - bradykinin
Prostaglandins
Outline the pathophysiology of a carcinoid tumour secreting serotonin?
Serotonin enters liver through portal vein; some is converted to 5-HIAA and is excreted in the urine whilst the rest remains in circulation…
This causes increased motility and peristalsis in GIT, increases vasoconstriction and stimulates fibroblasts in the heart
What are common primary sites for neuroendocrine tumours?
Intestines
Stomach
Pancreas
Liver
Lungs
Ovaries
Thymus
Whats the most common site for metastases of neuroendocrine tumours?
Liver
Why is metastases of neuroendocrine tumours often necessary for carcinoid syndrome?
As they metastases to the liver which causes liver dysfunction
This leads to a decreased metabolism of hormones released from the tumour e.g. serotonin so they build up and cause symptoms
What causes flushing in carcinoid syndrome?
Increased histamine and bradykinin
What causes itching in carcinoid syndrome?
Increased histamine
What causes tricuspid regurgitation and pulomnary stenosis in carcinoid syndrome?
Increased serotonin -> fibrosis of heart
What causes asthma, SOB, wheeze in carcinoid syndrome?
Increased serotonin -> fibrosis of bronchioles
What causes urethral obstruction or impaired kidney function in carcinoid syndrome?
Increased serotonin = fibrosis of abdominal mesenteries and retroperitoneal area
What causes pellagra in carcinoid syndrome?
Increased serotonin causes decreased tryptophan which leads to decreased niacin (vitamin B3()
= inflamed skin and mental confusion
What can worsen carcinoid syndrome and why?
Alcohol and stress
As they further stimulate the neuroendocrine cells
How is carcinoid syndrome treated?
Somatostatin analogues (bind to somatostatin receptors and decreasing hormone release)
Decrease emtooonal stress and alcohol
Resection of primary tumour
What drugs are used for H.pylori eradication?
7 day course of PPI, amoxicillin and clarithromycin
Whats an example of a somatostatin analogue?
Octreotide
What typically causes a metabolic ketoacidosis with low or normal glucose?
Alcoholic ketoacidosis
What side efefcts can aminosalucylates cause?
Common - Arthralgia; cough; diarrhoea; dizziness; fever; gastrointestinal discomfort; headache; leucopenia; nausea; skin reactions; vomiting
Important - agranulocytosis, haemolytic anaemia and other haematological adviser effects (mist do FBC whilst on it)
What causes melanosis coli?
Chronic laxative use -> damages cells lining intestines -> apoptosis -> taken up by macrophages -> release of lipofuscin
