Carcinoid heart disease--a hidden complication of neuroendocrine tumours.

Carcinoid heart disease (CHD) develops in serotonin-producing neuroendocrine tumours (NET) due to fibrotic endocardial plaques with associated valve dysfunction leading most often to right-sided heart failure. The classical carcinoid syndrome usually occurs when serotonin-producing NET metastasize to the liver. Up to 50% of those patients will exhibit carcinoid heart disease. The pathophysiological process is not yet completely understood: serotonin is considered to be a major initiator of the fibrotic process, but other tumour secreted factors may contribute to the pathogenesis. Histopathology reveals intact valvular cusps with superimposed fibrotic plaques, leading to thickening and retraction of the valves, causing valvular dysfunction. A high index of clinical suspicion to diagnose CHD is needed since symptoms can be rather non-specific. Transthoracic echocardiography is the gold standard for diagnosis and should probably be performed at the time of diagnosing serotonin-producing NET and then repeated annually. On the other hand, when diagnosing right-heart failure, the presence of CHD and underlying serotonin-producing NET should be taken into account. Therapeutic options include pharmacotherapy for heart failure, control of the systemic carcinoid disease and in selected individuals cardiac valve replacement. The elucidation of the pathologic process is necessary to develop targeted antifibrotic therapeutic agents since CHD seems to be irreversible and associated with poor prognosis.

The role of oral fluoropyrimidines in the treatment of advanced gastric cancer.

Although the incidence of gastric cancer is declining during the second half of the 20th century, it remains the second leading cause of cancer death worldwide. The majority of patients with gastric cancer will require palliative treatment at some point in the course of their disease. Approximately 50% of patients already have advanced incurable disease at the time of initial presentation, and even those who undergo potentially curative resection have high rates of distant as well as local recurrence. Chemotherapy in advanced gastric cancer demonstrated a significant survival benefit over best supportive care alone. Median overall survival increased from 3-5 to 8-12 months. Today, a platinum based regimen is considered as first-line treatment in advanced gastric cancer. Different regimens are investigated and used in routine practice. Similarly to fluorouracil, capecitabine is well tolerated in combination with a range of cytotoxic drugs. As a single agent, it has not undergone large scale randomised studies. S-1, another oral fluoropyrimidine, is a potential challenger to the role of capecitabine, but is lacking phase III data in Western population.