Carcinoid tumours are rare and slow-growing neuroendocrine tumours. They generally arise from tissues associated with the embryonic gut. They have some specific aspects that make them challenging to manage from an anaesthetic perspective.
They are the most common neuroendocrine tumour. They have an incidence of around 3 in 100,000. However, it is reported that incidental tumours may be found in up to 10% of autopsies.
The majority of tumours (approx 70%) arise in the GI tract. The majority of the remainder (around 25%) are found in the lungs. Of those in the GI tract:
40% small intestine
The liver is the most common site for metastasis.
Carcinoid tumours arise from the enterochromaffin or Kulchitsky cells of the embryonic gut, but can be of a wide range of neuroendocrine cell types. They contain numerous neurosecretory granules, potentially containing a number of important, physiologically active substances:
Carcinoid syndrome (see below) describes the effects that occur as a result of these substances, but only occurs in around 10% of patients with carcinoid tumours. This is because a lot of the active substances secreted by gut tumours pass through the portal circulation and are metabolised by the liver. The incidence of features is higher in those with metastatic disease. The syndrome is related to release of vasoactive substances from the tumour into the circulation.
Carcinoid heart disease refers to the endocardial fibrosis that occurs in response to exposure to the vasoactive substances. It primarily affect the right side of the heart, resulting in retraction of the valve leaflets and tricuspid regurgitation (most commonly) or tricuspid stenosis and pulmonary valve disease. Left sided heart disease is less common.
There may also be other fibrosis arising from carcinoid disease:
Retroperitoneal - may cause urinary obstruction
The majority of tumours are clinically silent. They may be discovered:
Due to mass effect e.g. bowel obstruction, respiratory
Due to carcinoid syndrome.
The GI symptoms of bowel tumours are often mild, with vague abdominal discomfort that has often been present for years before diagnosis. They may present in an emergency with bowel obstruction.
Pulmonary carcinoid tumours only account for around 2% of lung cancers and present in a similar way: cough, haemoptysis, recurrent infection. Rarely they may present with chest pain, or have associated cushingoid or acromegaly effects.
This is the typically intermittent symptoms caused by release of vasoactive substances from the tumour. It may be triggered by alcohol, coffee, exercise, tyramine rich foods (blue cheese, chocolate). The symptoms include:
Carcinoid crisis is an exaggerated form of this, often iatrogenically precipitated (anaesthesia, surgery) which can be fatal. It can include:
Hypotension (and cardiovascular collapse)
There are a couple of useful serological investigations.
5-HIAA (5 Hydroxyindoleacetic acid) is a metabolite of serotonin. It is detected via a 24 hour urine collection. A positive result has a specificity of nearly 100% but a sensitivity of 73%. Some false positives may be generated by foods (pineapple, banana) or drugs (paracetamol, warfarin).
Chromagraffin A is a glycoprotein secreted by neuroendocrine tumors. It is detected from a serum sample. It has a higher sensitivity than 5-HIAA so may be more useful for screening.
Imaging tests may also aid diagnosis
Bronchoscopy may identify the disease in patients with lung disease.
Where possible, surgical resection is the management option of choice. This also includes some metastatic disease where it may prolong survival. The 5 year survival for multi-lobar liver metastases resection may be up to 87%.
Other management options include:
Somatostatin analogues e.g. octreotide
Patients my present for resection of primary disease +/- resection of a liver lesion. They may also require cardiac surgery to treat carcinoid heart disease before tumour resection. Some of the key principle of the anaesthetic approach include:
Identify possible complications of the disease
Minimising the risk of carcinoid crisis
The preoperative assessment will include a full anaesthetic assessment, covering routine aspects, as well as specific enquiry about adverse features that may be associated with the condition. In the history this will include:
Features of carcinoid syndrome
Features of heart failure
History of diarrhoea and dehydration
Any features of obstruction
A cardiovascular examination is important to assess for any signs of right heart failure or specific valvular disease.
Investigations should include:
U&E - may be deranged if intake has been disturbed
LFTs - rarely liver failure caused by metastatic disease
ECG - looking for evidence of right heart disease
CXR - may show evidence of lung lesion
An important part of the preoperative preparation involves minimising the potential cardiovascular instability that can occur from release of the vasoactive substances found within the tumour. Even if the patient has no features of carcinoid syndrome, the anaesthetic and surgical stress can precipitate a carcinoid crisis. This may result in significant cardiovascular dysfunction, from hypertension to hypotension to complete cardiovascular collapse, resistant to usual vasoactive agents. Prophylaxis against this involves the use of somatostatin analogues, usually in the form of octreotide. It is commenced as a an infusion of 50 mcg/h for at least 12 hours prior to surgery. Side effects include GI upset (pain, diarrhoea), QT prolongation, bradycardia, and cardiac conduction abnormalities.
Invasive cardiovascular monitoring is essential due to the significant potential for cardiovascular instability. This may be invasive BP measurements or specific methods of cardiac output monitoring may be preferred e.g. oesophageal doppler.
Thoracic epidural analgesia is often employed to provide adequate analgesia postoperatively, with the benefits essentially the same as for other major abdominal surgery. The hypotension associated with their use is a slight drawback, due to the unpredictable, possibly exaggerated response associated with vasopressors in carcinoid disease. Low dose anaesthetic should be the target.
General anaesthesia should aim to provide as stable physiology as possible to reduce the risk of triggering a carcinoid crisis. Airway manipulation should be performed only with adequate anaesthesia and relaxation on board. The actual anaesthetic technique does not matter much beyond this, but remifentanil has some favourable characteristics in this regard. Histamine releasing agents (atracurium, morphine) should aim to be avoided.
The unpredictable response to vasopressors is a particularly concerning features of anaesthesia for carcinoid syndrome. Any pharmacological stimulation of the autonomic nervous system can result in release of vasoactive substances, worsening the cardiovascular state further. Cautious use of phenylephrine appears to be the best of the usual vasopressors to use. However, if there is concern about the release of vasoactive substances intraoperatively, the best management strategy is titrated doses of octreotide (25-50 mcg).
There can be significant bleeding during resection surgery, particularly with liver resection, and so fluid balance is also an important consideration. This is particularly important so as not to ascribe all cardiovascular changes to vasoactive substance release.
Postoperative care will need to be provided in a highly monitored environment, usually a critical care environment. Monitoring should continue in the immediate postoperative period. Similarly, it is important to continue octreotide, as the risks of stimulation continue.
The presence of metastases has a significant impact on reducing long term outcome. Patients with fully resected local disease have an excellent long term outcome. The site of the tumour also has some impact. Lung carcinoid has the best 5 year outcomes.