<p>Midgut carcinoid tumours are rare with an incidence of 0.5-2.1/100 000. The primary tumour is usually small and grows slowly but has almost always set metastases at diagnosis. When radically operated, most patients will eventually recur in their disease. </p><p>We evaluated different methods in detecting recurrent disease in 61 malignant midgut carcinoid tumours that had been radically operated. Thirty-eight patients have been diagnosed with a recurrence. In 32/38 of these patients P-Chromogranin A was the first method to indicate a recurrence. We therefore recommend using P-CgA in the work up in these patients.</p><p>We investigated characteristics, survival and independent factors that could be of bad prognostic value. We found that in our 284 malignant midgut carcinoid tumours, 208/284 (73%) had distant metastases and 30/284 (11%) had carcinoid heart disease. Median survival was 115.5 months and five-year survival was 77%. In a multivariate analysis liver metastases and carcinoid heart disease were poor prognostic factors.</p><p>We performed a phase II study with octreotide pamoate investigating the clinical effect in 12 malignant midgut carcinoid tumours in a progressive phase. We found that 9/12 (75%) were stabilised for a median duration of 12 months. We think that this is a good effect considering the advanced stage.</p><p>We investigated the frequency of four different tyrosine kinase receptors, platelet derived growth factor receptor (PDGR) α and β, epidermal growth factor receptor (EGFR) and c-kit, in 36 malignant midgut carcinoid tumours with immunohistochemistry. We found that 13/34 (38%) tumour samples expressed PDGFRα, 29/33 (88%) PDGFRβ, 24/33 (73%) EGFR, whereas none expressed c-kit. This implicates that midgut carcinoid tumours might be susceptible to treatment with tyrosine kinase receptor inhibitors. </p>

Midgut carcinoid tumours are rare with an incidence of 0.5-2.1/100 000. The primary tumour is usually small and grows slowly but has almost always set metastases at diagnosis. When radically operated, most patients will eventually recur in their disease. We evaluated different methods in detecting recurrent disease in 61 malignant midgut carcinoid tumours that had been radically operated. Thirty-eight patients have been diagnosed with a recurrence. In 32/38 of these patients P-Chromogranin A was the first method to indicate a recurrence. We therefore recommend using P-CgA in the work up in these patients. We investigated characteristics, survival and independent factors that could be of bad prognostic value. We found that in our 284 malignant midgut carcinoid tumours, 208/284 (73%) had distant metastases and 30/284 (11%) had carcinoid heart disease. Median survival was 115.5 months and five-year survival was 77%. In a multivariate analysis liver metastases and carcinoid heart disease were poor prognostic factors. We performed a phase II study with octreotide pamoate investigating the clinical effect in 12 malignant midgut carcinoid tumours in a progressive phase. We found that 9/12 (75%) were stabilised for a median duration of 12 months. We think that this is a good effect considering the advanced stage. We investigated the frequency of four different tyrosine kinase receptors, platelet derived growth factor receptor (PDGR) α and β, epidermal growth factor receptor (EGFR) and c-kit, in 36 malignant midgut carcinoid tumours with immunohistochemistry. We found that 13/34 (38%) tumour samples expressed PDGFRα, 29/33 (88%) PDGFRβ, 24/33 (73%) EGFR, whereas none expressed c-kit. This implicates that midgut carcinoid tumours might be susceptible to treatment with tyrosine kinase receptor inhibitors.

Un lien entre certaines dysfonctions du système sérotoninergique et la survenue de valvulopathies a été suggéré par les lésions valvulaires observées au cours de l’utilisation chronique de certains agonistes des récepteurs 5-HT2 (dérivés de l’ergot de seigle, fenfluramine) et les atteintes tumorales carcinoïdes (qui entrainent une augmentation des taux de 5-HT circulante). Les lésions dégénératives associent une fibrose, une sténose et/ou une régurgitation des valves pouvant conduire à de nombreuses complications cardiovasculaires. À l’heure actuelle, il n’existe aucune thérapeutique pouvant freiner ou faire régresser les lésions. Nos travaux démontrent à partir de modèles animaux et cellulaires, l’implication effective des récepteurs 5-HT2B et 5-HT2A dans l’initiation des lésions. L’analyse histologique des valves à partir de nos modèles animaux a révélé la contribution des cellules endothéliales au cours des stades précoces. Ces cellules sont des progéniteurs endothéliaux (CD34+) recrutés à partir de la moelle au sein de la valve sous la stimulation des récepteurs 5-HT2 et par un mécanisme intracellulaire impliquant la eNOS. Des travaux ultérieurs permettront de mieux caractériser les différents types cellulaires et les biomarqueurs d’initiation du processus afin de déterminer de nouvelles pistes thérapeutiques. / Several studies have reported a strong correlation between the development of cardiac valve injury and some dysfunctions of the serotonergic system. Valve lesions are observed during the chronic use of some 5-HT2 receptors agonists (ergot derivates or fenfluramine derivatives) or are secondary to metastatic carcinoid tumours (with increased circulating 5-HT amount). These lesions show fibrosis, with thickened leaflets, valves stenosis and/or regurgitation followed by several cardiovascular complications. There is no medical treatment to stop or alter the natural course of the lesions. Surgical replacement by prosthesis is the only effective therapy. Our study based on animal and cellular pharmacological models, demonstrates the serotonergic system contribution through 5-HT2B and 5-HT2A receptors in the pathogenesis of valve degeneration. Histological analysis of the lesions reveals the contribution of endothelial cells to the initiation process. These cells are probably endothelial progenitors (CD34+) recruited inside the valve implying a NO-dependent mechanism. Further studies will characterize the specific cells to find biomarkers of valve remodelling initiation and at term, will identify best therapeutic targets around the serotonergic system.