Carcinoid tumour and carcinoid syndrome

• What is Carcinoid Tumour and Carcinoid Syndrome?
• Statistics
• Risk Factors
• Progression
• Symptoms
• Clinical Examination
• How is it Diagnosed
• Prognosis
• Treatment
• References

What is Carcinoid Tumour and Carcinoid Syndrome?

Carcinoid tumour is a type of neuroendocrine tumour. Neuroendocrine tumours are tumours of the neuroendocrine cells that secrete regulatory hormones and are present in the nervous and endocrine/hormonal system.
Most primary carcinoid tumours arise from enterochromaffin cells of the gastrointestinal/digestive tract, with the most common sites being the appendix, small bowel and rectum. They can also be seen in the liver, pancreas, bronchus (branch of the windpipe into the lung), and ovaries.
Carcinoid tumours can be classified based on the primitive gut that gives rise to the tumour (i.e. foregut, midgut, hindgut). Examples of foregut carcinoid tumours are carcinoids of the bronchus, stomach, beginning portion of the small bowel (proximal part of duodenum) and pancreas. Midgut tumours are derived from the rest of the small bowel (second portion of duodenum, jejunum, ileum), and part of the large bowel (right colon). These are the most common type of carcinoid tumours in adults. Hindgut carcinoid tumors include those of the large bowel (transverse colon, descending colon, and rectum).
Carcinoid tumours produce, store, and release a variety of hormones and other substances (polypeptides, biogenic amines, and prostaglandins). Amines produced include serotonin, 5-hydroxytryptophan, norepinephrine, histamine and dopamine. Examples of polypeptides produced are kallikrein, bradykynin, somatostatin, neuropeptide K, neurokinin A, ACTH, growth hormone, glucagon, etc.
Carcinoid syndrome is the term applied to a group of symptoms mediated by various substances produced by some carcinoid tumours. Symptoms commonly experienced in carcinoid syndrome are flushing, diarrhoea and cramping. Heart failure due to valve problems may also occur. The main biologically active peptides secreted in carcinoid syndrome are serotonin and possibly tachykinins, motilin, prostaglandins.
In intestinal carcinoid tumours, the occurrence of carcinoid syndrome usually implies liver involvement.

Statistics

Carcinoid tumours are rare. In the United States, there were about 13,000 cases identified from 1950 to 1999. The estimated occurrence rate is 2.0/100,000 for men and 2.4/100,000 for women. The tumour is most common among African males. The age range at which the tumour occurs is between the second and the ninth decade. About 67% of cases occur in the digestive tract while another 25% occur in the airway and lungs.
Carcinoid syndrome is relatively rare. The number of new cases per year is 0.5–2.0 per 1,000,000 population. It occurs in approximately 10% of patients with small bowel carcinoid tumour. Less than 1% of carcinoid tumours in the appendix are associated with carcinoid syndrome. Among patients with carcinoid syndrome, a large proportion (75-80%) has small bowel carcinoids.

Risk Factors

The cause if virtually unknown. Factors that are associated with an increased occurrence of carcinoid tumour are:

• A family history of carcinoid in a first-degree relative (3.6 times the risk);
• A well-educated social background (2.8 times the risk);
• Birth in a large city (1.39 times the risk).

Genetic influences are suspected. Reported genetic abnormalities include changes in the chromosome.

Progression

When carcinoid tumours happen alone (without carcinoid syndrome), diagnosis is often delayed due to the vagueness of symptoms. Carcinoids in the duodenum (first part of small bowel), stomach and rectum are most frequently found by chance at endoscopy (a procedure involving passing a tube with a camera through the mouth or the bottom end to look at the digestive tract). Those in the appendix are almost always found incidentally during surgery.
Carcinoid tumours are slow-growing. About one in nine patients with carcinoid have distant spread to other organs (metastasis) when carcinoid tumour is diagnosed. Metastasis at diagnosis is most common in small bowel and large bowel carcinoids, whereas carcinoids in the rectum, airway and stomach are less likely to spread.
In the majority (about 90%) of cases, carcinoid syndrome occurs after distant spread to the liver. There are, however, exceptions, for example carcinoids in the airway or ovaries, where carcinoid syndrome can rarely happen without liver involvement.

How is it Diagnosed

The usual basic tests will be done, including those to look at the blood and other blood components. Other general tests will determine the function of the liver and kidney.

Prognosis

The survival rate at 5 years following diagnosis (5-year survival rate) for all carcinoid tumours, regardless of the site of tumour, is 67%. The potential for distant spread to other organs and the probability of the disease reoccurring correlate with the size and site of the tumour. A tumour less than 2 cm in diameter carries a better disease outcome. Carcinoid tumours that occur in the rectum have the best 5-year survival rate of more than 80%. Tumours in the airway, lungs and appendix also have 5-year survival of more than 70%. The presence of the carcinoid syndrome confers a poorer survival rate, ranging from less than one year to 38 months.

Treatment

Treatment aims to:

• Locate the tumour;
• Remove the tumour if metastasis (spread to other organs) has not occurred;
• Control carcinoid symptoms if present.

Surgery

• Surgery is the treatment of choice for carcinoid tumours which remain at the site of origin (localised). The extent of the surgical resection depends on the site and size of the tumour;
• Limited role in carcinoid syndrome because almost all have spread to other regions;
• Surgery in carcinoid syndrome has the risk of provoking carcinoid crisis during induction of anaesthesia. This can be prevented by giving octreotide before the surgery.

Symptom control

• Avoidance of factors that provoke flushing episodes (e.g. alcohol, physical exertion);
• For mild diarrhoea, codeine phosphate can be used;
• In patients with severe symptoms of the carcinoid syndrome, octreotide (a drug resembling the hormone somatostatin) is likely to be effective. The drug is usually well tolerated, with some side effects (e.g. nausea, bloating, loose stools) which often subside. Some patients may develop gallstones;
• Patients with diarrhoea who cannot tolerate octreotide can be treated with another drug called cyproheptadine.

Metastatic disease

• In patients whose disease has spread/metastasised, surgery is most often considered if the liver is involved. Other treatment approaches include radiofrequency ablation and cryoablation;
• Octreotide decreases symptoms of metastatic disease and slows tumour growth;
• Chemotherapy has been used but with only minor efficacy;
• Another treatment modality is embolisation of the hepatic artery (blocking the blood vessel supplying the liver to cut off blood supply to the tumour).

Carcinoid crisis

• In the carcinoid crisis, the blood pressure should be supported by blood transfusion and octreotide should be given.

References

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