Midgut carcinoid tumours - biochemical and therapeutic aspects

Abstract

The biology of human midgut carcinoid tumour was studied experimentally in primary cell culture and clinically in patients with the midgut carcinoid syndrome. In cell cultures, tumour cells had a secretory pattern of 5-HTP, 5-HT and 5-HIAA specific for each tumour indicating individual regulation of synthesis/degradation. Intracellular stores of 5-HT were dose-dependently depleted by reserpine. Monoamine oxidase (MAO) activity was shown by morphological and pharmacological means, which indicates intrinsic 5-HT degradation by tumour cells. The spontaneous secretion of 5-HT was markedly reduced after incubation with the somatostatin analogue octreotide with no intracellular accumulation of 5-HT. Dexamethasone reduced 5-HT secretion via a different mechanism indicating synergistic effects by the combination of the two drugs. Octreotide also reduced the spontaneous secretion of chromogranin A and B from primary tumour cell cultures. In the clinical situation, this may limit the validity of chromogranins and 5-HIAA in the evaluation of tumour mass during octreotide treatment.Sixty-four consecutive patients with the midgut carcinoid syndrome were treated according to a program including surgery, hepatic arterial embolization and octreotide. A favourable 5-year survival was seen together with good symptom relief from hormonal symptoms. Surgery may be curative in individual patients (22% in this series), but should be performed in all patients to reduce tumour burden and local intraabdominal complications. In patients with bilobar hepatic metastases, selective arterial embolization substantially reduced tumour burden at low risk. Carcinoid heart disease was investigated. Tricuspid valvular abnormalities were found in 65% of the patients, while the pulmonary valves were affected in 19%. Severe tricuspid abnormalities demonstrated by echocardiography were associated with high urinary 5-HIAA levels and poor 5-year survival. Age and tricuspid regurgitation were shown to be independent risk factors for death. Despite the prevalence of carcinoid heart disease in this series only one patient died from right heart failure. These findings support the value of active tumour reduction and close surveillance of cardiac function in patients with the midgut carcinoid syndrome.