Carcinoid

Neuroendocrine tumour that:

Epidemiology and Risk Factors

Pathophysiology

Derived from neuroendocrine cells:

  • Enterochromaffin cells

  • Kulchitsky cells

  • Frequency of occurrence related to neuroendocrine cell density

Aetiology

Clinical Features

  • Many are asymptomatic and found incidentally due to long lead time to diagnosis
  • Average time from diagnosis to symptoms is 8 years

Presentation may be from mass effect or carcinoid syndrome, and varies depending on location:

  • Pulmonary
    • Pneumonia
    • Cough
    • Haemoptysis
    • Chest pain
  • Gastric
    • Zollinger-Ellison syndrome
      Peptic ulcers occurring due to excessive acid production, in turn occurring due to a gastrin-producing tumour.
    • Atrophic gastritis
  • Bowel
    • Mass effect
      • Obstruction
      • Abdominal pain

Carcinoid Syndrome

Syndrome associated with secretion of vasoactive mediators from the tumour. Carcinoid syndrome is:

  • Rare
    ~10% of patients with carcinoid tumours.
  • Unpredictable clinical effects
    Variable:
    • Secretion of (usually) histamine and serotonin
    • First-pass hepatic metabolism
      Depending on location.
  • Usually intermittent symptoms
    Associated with:
    • Exercise
    • Tyramine ingestion
      Cheese, chocolate.
  • Common symptoms:
    • Flushing (80%)
    • Diarrhoea (70%)
  • Less common symptoms:
    • Lacrimation
    • Rhinorrhoea
    • Bronchospasm
    • Carcinoid heart disease

Carcinoid Heart Disease

Characteristic cardiac lesions:

  • Associated with high circulating 5-HT
    Rarely seen if 5-HIAA levels are ≤50mg/24 hours.
  • Classically right-sided endocardial thickening:
    • Leads to retraction and fixation of valve leaflets
    • TR near-universal
    • TS, PR, and PS may occur
  • Left sided disease may occur in the presence of an intracardiac shunt (e.g. PFO) that leads to serotonin entering left-sided chambers

Carcinoid Crises

Exaggerated form of carcinoid syndrome that is:

  • Potentially fatal
  • Associated with medical intervention
  • Characterised by:
    • Profound flushing
    • Bronchospasm
    • Tachycardia
    • Widely fluctuating BP
  • Requires octreotide to control haemodynamics
    0.5-1mg IV followed by infusion of 50-200μg/hr.

Diagnostic Approach and DDx

Investigations

Tumour activity:

  • Blood
    • Plasma CgA
    • LFTs
    • Coags
    • UECs
    • S. Protein
  • Urine
    • 24 hour 5-HIAA levels
      Serotonin metabolite.

Tumour localisation:

  • Octreotide scan
  • Gallium PET/CT
  • Echocardiography

Management

Medical

Premedication:

  • Octreotide therapy
    • 100-500μg/day in divided doses
    • 30-60mg long-acting octreotide given IM every 4 weeks

Surgical

Anaesthetic Considerations

Surgery should proceed when: * Symptom control achieved * 2 weeks after last long-acting octreotide dose

Premedication:

  • Octreotide
    • Give usual dose of subcutaneous octreotide or 500μg (if untreated, or emergency) 2 hours pre-surgery
    • Commence infusion at 1μg/kg/hr in holding bay, prior to insertion of invasive monitoring
  • Ranitidine 50mg IV/150mg PO 2 hours prior
  • Promethazine 12.5mg IV/10-20mg PO 2 hours prior
  • Ondansetron 4-8mg IV 2 hours prior
  • Dexamethasone 2-4mg IV
    For gastric neuroendocrine tumours.

General:

  • Disposition:
    • HDU post-operatively
      • Haemodynamic monitoring
      • Continuation of octreotide infusion
    • Endocrinology involvement
  • B
    • Perioperative bronchospasm
      • Octreotide 10-200μg boluses
      • Antihistamine
      • Ipratropium nebuliser
      • Steroid
  • C
    • ECG
    • TTE
    • Arterial line
    • CVC
    • Cardiac disease
      • Carcinoid cardiac disease
      • Coronary spasm
      • Erratic BP
        Hypo- or hypertensive crises may:
        • Occur due to variation in hormone secretion
        • Unresponsive to conventional vasoactives
    • Haemodynamic goals
      • Deep, stable anaesthesia prior to resection
      • Avoid:
        • Morphine
        • Atracurium
        • Suxamethonium
      • Low CVP during resection
      • Avoid inotropes and vasopressors
        Unpredictable and potentially paradoxical response.
        • Noradrenaline may release kallikrein from tumour, leading to vasodilation
        • Exaggerated hypertension also described
        • Vasopressin is appropriate to use as a vasopressor, if required.
        • Short-acting α-blockade ideal for managing persistent hypertension
    • Perioperative hypotension
      • Inform surgeon
      • Cease tumour handling
      • Octreotide bolus, 10-100μg
      • Phenylephrine 50-100μg bolus
      • Avoid indirect acting adrenergics
        • Cautious use acceptable for inotropy if on octreotide
      • Consider steroids, calcium, and vasopressin for unresponsive hypotension
    • Perioperative hypertension
      • ↑ depth of anaesthesia
      • Octreotide 10-200μg bolus
      • Labetalol, GTN, and esmolol if unresponsive
  • D
    • Consider epidural if major abdominal surgery
      Avoid loading until after tumour resection to avoid hypotension.
  • E
    • Octreotide infusion
      Used to limit vasoactive crises. Octreotide has many effects, however its key:
      • Mechanism of action is via:
        • Reducing splanchnic blood flow
        • Reducing secretion of vasoactive peptides
      • Adverse effects include:
        • Conduction defects
          • QT prolongation
          • Bradycardia
        • Abdominal cramps

Marginal and Ineffective Therapies

Complications

Prognosis

Death:

  • 70% 5 year survival

Key Studies

References

  1. Powell B, Al Mukhtar A, Mills GH. Carcinoid: the disease and its implications for anaesthesia. Continuing Education in Anaesthesia Critical Care & Pain. 2011;11(1):9-13.