Non functioning tumours cause symptoms of intermittent intestinal entrapment secondary to mesenteric fibrosis. Functional tumours secrete notably serotonin, leading to the manifestations of carcinoid syndrome, characterized by diarrhea, bronchoconstriction and palpitations. Excess serotonin contributes to carcinoid heart disease (endomyocardial fibrosis, tricuspid insufficiency and pulmonary valvular disease). Liver metastasis and a large tumour burden contribute to the severity of the carcinoid syndrome.

5-hydroxy-indole-acetic acid (5-HIAA) is the metabolite of serotonin metabolism. A 24-hour urine sample of 5-HIAA has a sensitivity of 73% and a specificity of 100% for diagnosing carcinoid. It also reflects the response to treatment with somatostatin analogues. It should be measured at baseline and every 4-6 months thereafter.

Chromogranin A (CgA) is found in the walls of synaptic vesicles that store serotonin. CgA levels correlate with tumour bulk. Both non-functioning and functioning tumours have elevated levels. The specificity of CgA is 98.4% and its sensitivity is 63%. Although CgA measurements are helpful especially if the 5-HIAA is negative, inflammatory conditions and renal insufficiency should be excluded because these conditions may cause an increase in CgA levels. CgA should be measured every 3 months in the first year. Elevated CgA in the absence of other altered parameters warrants further investigation.

Ki67 antigen is a nuclear protein expressed by proliferating cells. Antibodies to Ki67 in tissue specimens are a reliable marker of cell proliferation. Its assessment can be useful if chemotherapy is considered. Low values (<2%) are unlikely to benefit from chemotherapy.

Diagnostic imaging includes 111Indium-Pentetreotide Scintigraphy (Octreotide scan) is highly sensitive and specific for both functioning and non-functioning carcinoid tumours which express somatostatin receptors. It can show early evidence of lesions not revealed by other procedures. It should be done at baseline, after curative surgery and annually thereafter.

Meta-iodobenzylguanidine (MIBG) scan may also be done especially in tumours that do not take up octreotide- seen in 10-20% of cases. MIBG testing is useful in identifying patients who can benefit from MIBG therapy.

CT scan, MRI and ultrasound may also be helpful in evaluating the extent of disease.

The main goals of carcinoid tumour management include: symptom, biochemical and objective tumor control, and quality of life improvement.

Debulking (cytoreductive surgery) is the mainstay of therapy. The aim is for curative resection. In metastatic disease, it can facilitate medical treatment. Laser treatment of metastasis, radiofrequency ablation and embolization of liver metastasis are possible options. Octreotide administration should be given before surgery. A loading dose of 500 ug-1000 ug IV bolus is given 1-2 hours pre-op followed by an IV infusion at 50-200ug/hr to prevent carcinoid crisis. Prophylactic cholecystectomy is advised to offset the biliary toxicity of somatostatin analogue therapy.

Somatostatin analogues relieve symptoms and reduce hormone levels. Patients with 5-HIAA levels > 50 mg/24 hours should be considered for octreotide therapy. Since octreotide has an anti-proliferative action, it can also be given for asymptomatic patients with progressive disease. Immediate release octreotide is given in doses from 100-500 mcg s.c. 2-4x/day for 7 days. Thereafter, the LAR formula may be given 10-20 mg once monthly. Good response to therapy is defined as a reduction in hypersecretion-related symptoms, reduction in tumor bulk-related symptoms and improvement in quality of life and a decrease by >50% in tumour markers.

Interferon alfa can be given for low-proliferating tumours or as a second-line therapy, either alone or in combination with somatostatin analogues.

Cytotoxic treatment is employed for tumours with high proliferative capacity or high tumour burden (Ki67 antibody > 5%). Agents used are streptozocin and 5fluoro-uracil.

External radiation therapy is recommended for bone and brain metastasis. Tumour targeted treatment with radioactive octreotide derivatives are associated with tumour shrinkage in up to 25% and biochemical response in up to 50%. However, the exact role of this treatment is not yet defined, but it is an accepted alternative in the therapy of these neoplasms.

Sources:
1. Maroun, J et.al. Guidelines for the diagnosis and management of carcinoid tumours. Part 1: The gastrointestinal tract. A statement from a Canadian National Carcinoid Expert Group. Current Oncology – Vol.13, No. 2 2006

2. Eriksson, B et. al. Consensus guidelines for the management of patients with digestive neuro-endocrine tumours – well-differentiated jejuna-ileal tumor/carcinoma. Neuroendocrinology 2008; 87:8-19

3. Oberg, K et.al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Annals of Oncology 15:966-973, 2004

4. Ramage, J et.al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut 2005;54