Carcinoid tumors are neuroendocrine tumors derived from enterochromaffin cells, which are widely distributed in the body. They can originate from any location in the body, but they are traditionally described as originating from the foregut, midgut, and hindgut. Although the overall incidence of carcinoid tumors appears to have increased in the past decades, the prognosis for patients with metastatic carcinoid tumors has improved during the last decade. Due to longer survival times, complications, such as carcinoid heart disease, and new metastatic patterns, like skin and bone metastases, may become more important features of carcinoid disease. Therapy focused on these complications should be part of the management. Combining new diagnostic and treatment modalities in metastatic carcinoid patients may result in better quality of life and longer survival times. The increasing number of therapeutic options and diagnostic procedures requires a multidisciplinary approach, with decisions made in multidisciplinary meetings focused on "tailor-made" therapy based on patients' specific conditions. Because carcinoid tumors are uncommon, effort should be made to treat these patients in specialized centers and for these centers to join together in multicenter studies. The Oncologist 2005;10:123-131The Oncologist 2005;10:123-131 www.TheOncologist.com
Carcinoid heart disease (CHD) occurs in 20 -70% of the patients with metastatic well-differentiated neuroendocrine tumours (NET). We evaluated whether natriuretic peptides (ANP or NT-proBNP) are useful in early detection of CHD. Blood samples from 32 patients with NET were compared with cardiac ultrasound follow-up. CHD was defined as thickening of the tricuspid valve in the presence of grade III -IV/IV tricuspid valve regurgitation. CHD was found in nine out of 32 patients (28%), all with symptoms of the carcinoid syndrome compared to 65% in the 23 patients without CHD (P ¼ 0.04). Median levels of NT-proBNP and 5-HIAA were significantly higher in patients with CHD (894 ng l À1 and 815 mmol 24 h À1 ) compared to those without (89 and 206 ng l À1 , Po0.001 and P ¼ 0.007). No significant differences were detected in ANP levels (P ¼ 0.11). Dilatation of the right atrium and ventricle as well as thickening of the tricuspid valve and degree of regurgitation were statistically significant correlated with NT-proBNP levels. The accuracy of NT-proBNP in the diagnosis of CHD was higher than that of ANP. A significantly better survival was observed in case of normal NT-proBNP values. In conclusion, NT-proBNP is helpful as a simple marker in the diagnosis of CHD. Survival is better in patients with normal levels of NT-proBNP.
BACKGROUNDSerotonin excretion plays a role in the development of carcinoid heart disease (CHD), but the exact pathogenesis is not known. In the current study, the authors evaluated 24‐hour urinary 5‐hydroxyindoleacetic acid (5‐HIAA) excretion, as well as plasma levels of transforming growth factor‐β (TGF‐β), fibroblast growth factor (FGF), and atrial natriuretic peptide (ANP) in patients with and without CHD determined by ultrasound examination.METHODSUrine and plasma samples were obtained for 37 patients and cardiac ultrasound was performed during follow‐up in 1999 and 2000. Median 5‐HIAA excretion was calculated for the period between diagnosis and ultrasound examination. CHD was defined as the thickening of the tricuspid valve with additional III–IV/IV tricuspid valve regurgitation.RESULTSCHD was found in 9 of 37 patients (24%). No significant differences were found for age, gender, presence, and duration of liver metastases. All CHD patients had symptoms of the carcinoid syndrome compared with 71% of the non‐CHD patients (P = 0.159). Median 5‐HIAA excretion was significantly higher in the CHD group compared with the non‐CHD group: 576 μmol/24 hours versus 233 μmol/24 hours (P = 0.02). No difference in TGF‐β and FGF plasma levels was observed between both groups (P = 0.139 and P = 0.985, respectively), nor was there a correlation with morphology of the tricuspid valve or degree of dilatation of the right atrium/ventricle. However, the CHD group had higher median ANP levels than the non‐CHD group: 48 ng/L and 25 ng/L, respectively (P = 0.026).CONCLUSIONSHigh levels of 5‐HIAA excretion and plasma ANP were found to be associated with CHD. No significant relation with TGF‐β or FGF was been found. Cancer 2003;97:1609–15. © 2003 American Cancer Society.DOI 10.1002/cncr.11226
Bone metastases are assumed to be rare in carcinoid disease and to be associated mainly with bronchial primaries. The aim of the present study was to evaluate the occurrence of bone metastases in patients with metastatic carcinoid tumours, and the role of various nuclear medicine modalities (bone scintigraphy, (111)In-pentetreotide and (131)I-MIBG) in its detection and clinical management. Nine (2 women, 7 men, median age 65 years) out of 86 consecutive carcinoid patients treated between 1987 and 1998 developed bone metastases (10%) with a median interval of 37 months between the diagnosis of metastatic carcinoid and bone metastases. Seven of them had non-bronchial primaries. (111)In-pentetreotide scintigraphy failed to detect the bone lesions in 50% of the cases, and (131)I-meta-iodobenzylguanidine(MIBG) scintigraphy in almost 80% of cases. Standard bone scintigraphy, however, was positive in all. Pain relief of bone metastases by means of radiation therapy was obtained in 5 of 6 patients. In another patient palliation of pain symptoms was obtained with Rhenium-186-hydroxyethylidene diphosphonate. Octreotide, Interferon of MIBG were ineffective for this purpose. It is concluded that bone metastases in carcinoid patients may be missed on (131)I-MIBG and (111)In-pentetreotide scintigraphy. Bone scintigraphy is a sensitive imaging technique. Diagnostic nuclear medicine modalities may be helpful in the clinical management of carcinoid disease.
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