Carcinoid Syndrome

Question 1

What is the aetiology of carcinoid tumor?

Answer 1

Derived from enterocjromaffin cells also known as kulchitsky cells.
Arises from different embryonic divisions of the gut commonly the appendix

°

Question 2

What is carcinoid syndrome?

Answer 2

CARCINOID SYNDROME = clinical spectrum produced by release of amine and neuropeptide substances into systemic circulation by carcinoid cells

Question 3

Which amine and neuropeptide substances cause carcinoid syndrome

Answer 3

5-hydroxytryptamine-Serotonin-histamine-Tachykinins-Substance P-Calcitonin-gene related peptide

Question 4

How is carcinoid syndrome classified?

Question 5

What are the clinical manifestations of carcinoid syndrome?

Answer 5

Flushing 
Gi hyperactivity
Bronchospasm
Abdominal pain
Right heart failure 
Pellagra

Question 6

Clinical presentation

Answer 6

• slow growing-often asymptomatic

- often missed for many years

Question 7

Classic carcinoid syndrome

Answer 7

secondary to histamine, serotonin, vascoactives-episodic cutaneous flushing-vasovagal lability-hypovolaemia, hyponatreaemia, hypokalaemia, hypochloraemia-hyperglycaemia-gastrointestinal hypermotility-bronchoconstriction-carcinoid heart disease

Question 8

What is meant by Carcinoid crisis ?

Answer 8

• exaggerated form of carcinoid syndrome
• profound flushing, bronchospasm tachycardia, widely fluctuating BP
• precipitated by anaesthetic, radiological, surgical interventions

Question 9

Diagnosis

Answer 9

• urinary 5-HIAA (5-hydroxyindoleacetic acid - serotonin metabolite) and serum chromograffin A
• abdominal CT to detect metastatic disease or MRI or PET CT-somatostatin Ⓡ scintigraphy

Question 10

Treatment

Answer 10

1. Surgery
   - resection of primary localised tumour
   - en bloc resection of primary tumour and mesesnteric LN mets Somatostatin analogue - ocreotide is long acting, binds to somatostatin Ⓡ inhibiting release of vasoactive amines- symptom control, ↓ tumour markers, ↓ serotonin levels Liver therapies - complete hepatic resection of mets where possible- cryoreductive hepatic Ø (benefit in carefully selected patients)- embolisation

Question 11

Preoperative assessment

Answer 11

assess complications (obstruction, malnutrition, dehydration, anaemia, electrolyte abⓃ - assess uncontrolled ongoing excessive hormonal activity
① cardiovascular assessment
- Ⓡ or biventricular heart failure
- ↓ exercise tolerance, orthopnoea, PND, oedema- coronary artery spasm with flushing episodes

② unpredictable, uncontrolled hormone release

• hypo- or hypertensive crises
• HD collapse unresponsive to inotrope and pressor therapy

Question 12

Pharmacological mx

Answer 12

• ocreotide- corticosteroids- ketanserin (blocks 5HT)- methysergide- cyproheptadine (anti-5HT and antihistamine)- aprotinin (serine protease inhibitor, controls bradykinin release and flushing)

Question 13

Ocreotide

Answer 13

OCREOTIDE - somatostatin analogue- infusion 50 μg/hr for 12 hrs ore-op- more potent inhibitor than SS of GH, glucagon, inuslin- suppresses LH, GnRH- ↓ splanchnic blood flow- inhibits release of serotonin, gastrin, VIP, secretin, motilin, pancreatic polypeptide Effects - QT prolongation- bradycardia- conduction defects- abdominal cramps- nausea, vomiting

Question 14

Preoperative investigations

Answer 14

INVESTIGATIONS - baseline bloods (anaemia, electrolytes)- liver functions- clotting studies- cross match sample- CXR: carcinoid lesions or miliary pattern- ECH: RVH- echo: exclude Ⓡ sided carcinoid cardiac disease

Question 15

Intraoperative mx

Answer 15

• HD instability (vasoactive hormone release, blood loss++)- invasive arterial monitoring- CO monitor to guide fluid therapy and manage pre- and afterload changes- TOE useful- capography for bronchospasm- CVP - rapid infusion system, fluid warmer

Answer 16

REGIONAL - thoracic epidural ↓ stress response- may exacerbate intraop hypotension

Answer 17

GENERAL - stable, controlled conditions- TIVA or inhalational techniques acceptable- blunt intubation response- avoid hstamine releasing drugs (morphine, atracurium)- remifentanil infusion good because titrateable- monitor blood loss- clotting abⓃ if massive blood loss- hypertension can ise labetalol infusion- aqequate analgesia

Answer 18

Vasoconstrictors - response unpredictable- NE and adrenaline can trigger carcinoid crisis- PE, vasopressin helpful

Answer 19

POSTOPERATVE - high dependency care mandatory- may have carcinoid crises from lwftover mets- ongoing hormonal control of tumour (continue ocreotide)- continue invasive monitoring, analgesia and fluid managmenet for at leasr 48hrs