GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOURS

Question 1

What are Gastroenteropancreatic neuroendocrine tumours (GEP-NETs)?

Answer 1

neuroendrocrine tumours originating from neuroendocrine cells in the gastrointestinal tract or the pancreas, all of which have malignant potential

Question 2

What is the incidence of GEP-NETs?

Answer 2

2-3 per 100,000 persons per year

Question 3

Where are most of the GEP-NETs in the GIT?

Answer 3

Most in small intestine
Rest in rectum or stomach

Question 4

What are the risk factors of neuroendocrine tumours?

Answer 4

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

Question 5

How are GEP-NETs classified?

Answer 5

Non-functioning tumours (majority)
Functioning tumours

Question 6

How do GEP-NETs present?

Answer 6

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

Question 7

What additional symptoms can functioning GEP-NETs present with?

Answer 7

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

Question 8

20% of well-differentiated small bowel neuroendocrine tumours present with what?

Answer 8

Carcinoid syndrome

Question 9

What is carcinoid syndrome?

Answer 9

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.

Question 10

How do we investigate GEP-NETs?

Answer 10

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

Question 11

What is carcinoid syndrome?

Answer 11

Neuroendocrine tumours secretes hormones (serotonin, histamine, bradykinin) that leads to symptoms such as diarrhoea, SOB, itching and flushing

Question 12

Where are neuroendocrine cells?

Answer 12

Throughout the body but particularly in the epithelial layer of gastrointestinal organs and the lungs

Question 13

What hormones do neuroendocrine cells release?

Answer 13

Amines - serotonin and histamine
Polypeptides - bradykinin
Prostaglandins

Question 14

Outline the pathophysiology of a carcinoid tumour secreting serotonin?

Answer 14

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

Question 15

What are common primary sites for neuroendocrine tumours?

Answer 15

Intestines
Stomach
Pancreas
Liver
Lungs
Ovaries
Thymus

Question 16

Whats the most common site for metastases of neuroendocrine tumours?

Answer 16

Liver

Question 17

Why is metastases of neuroendocrine tumours often necessary for carcinoid syndrome?

Answer 17

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

Question 18

What causes flushing in carcinoid syndrome?

Answer 18

Increased histamine and bradykinin

Question 19

What causes itching in carcinoid syndrome?

Answer 19

Increased histamine

Question 20

What causes tricuspid regurgitation and pulomnary stenosis in carcinoid syndrome?

Answer 20

Increased serotonin -> fibrosis of heart

Question 21

What causes asthma, SOB, wheeze in carcinoid syndrome?

Answer 21

Increased serotonin -> fibrosis of bronchioles

Question 22

What causes urethral obstruction or impaired kidney function in carcinoid syndrome?

Answer 22

Increased serotonin = fibrosis of abdominal mesenteries and retroperitoneal area

Question 23

What causes pellagra in carcinoid syndrome?

Answer 23

Increased serotonin causes decreased tryptophan which leads to decreased niacin (vitamin B3()
= inflamed skin and mental confusion

Question 24

What can worsen carcinoid syndrome and why?

Answer 24

Alcohol and stress
As they further stimulate the neuroendocrine cells

Question 25

How is carcinoid syndrome treated?

Answer 25

Somatostatin analogues (bind to somatostatin receptors and decreasing hormone release)
Decrease emtooonal stress and alcohol
Resection of primary tumour

Question 26

What drugs are used for H.pylori eradication?

Answer 26

7 day course of PPI, amoxicillin and clarithromycin

Question 27

Whats an example of a somatostatin analogue?

Answer 27

Octreotide

Question 28

What typically causes a metabolic ketoacidosis with low or normal glucose?

Answer 28

Alcoholic ketoacidosis

Question 29

What side efefcts can aminosalucylates cause?

Answer 29

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)

Question 30

What causes melanosis coli?

Answer 30

Chronic laxative use -> damages cells lining intestines -> apoptosis -> taken up by macrophages -> release of lipofuscin