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Johannes Hofland, Aura D Herrera-Martínez, Wouter T Zandee and Wouter W de Herder

Carcinoid syndrome (CS) is a debilitating disease caused by functional neuroendocrine tumors. Several treatment options are available to alleviate the hormonal symptoms, but their relative efficacy is unknown. Online databases were searched for publications on the treatment of CS symptoms. Independent reviewers assessed relevant publications for study quality and outcome. Meta-analysis of the outcomes of the intervention on CS-related symptoms was stratified by the type of treatment. We found 3682 therapeutic interventions on CS-specific outcomes were collected from 93 studies. Overall, the study qualities were poor with only six randomized controlled clinical trials. The somatostatin analogs octreotide and lanreotide induced symptomatic improvement in 65–72% and biochemical response in 45–46% of patients. An increase in dose or frequency or interclass switch led to a reduction of flushes and/or diarrhea in 72–84% of cases. Retrospective, institutional series showed that liver-directed therapy can improve symptoms in 82% of CS patients with a liver-dominant disease. The serotonin synthesis inhibitor telotristat ethyl reduced bowel movements in 40% of patients with diarrhea refractory to somatostatin analogs. Interferon-alpha controlled CS symptoms in 45–63% of cases. Favorable response has been noted after radionuclide therapy in subgroup analyses of studies not specifically involving CS patients. Chemotherapy and everolimus did not induce a significant response in the CS. We conclude that several treatment lines can be offered to patients suffering from the carcinoid syndrome. Initiation of randomized controlled trials with a primary outcome on carcinoid syndrome symptoms is strongly recommended.

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J M Zuetenhorst, R A Valdes Olmos, M Muller, C A Hoefnagel and B G Taal

Interferon (IFN) and meta-iodobenzylguanidin (MIBG) are active in metastatic carcinoids. In a phase II study, we evaluated the effect upon diagnostic 131I-MIBG uptake and the clinical response of the combination.

131I-MIBG scintigraphy was performed prior to treatment, after 8 weeks of IFN and after unlabelled MIBG. The tumour over non-tumour (T/NT) ratios were quantitatively determined by comparing counts in the centre of the tumour (liver metastases) with those in an adjacent area of normal liver uptake (T/NT1) and with abdominal background area (T/NT2).

The T/NT1 ratio showed an increase of > 10% in only four out of 21 patients (19%) after IFN (p = 0.178) and significantly more often in nine out of 18 patients (50%) after unlabelled MIBG (p = 0.016). The absolute uptake in tumour deposits was also increased if compared with the abdominal background (T/NT2:23% increase after IFN and 83% increase after unlabelled MIBG). The combination produced 91% of patients with stable disease (using World Health Organisation criteria) at computed tomography scan and a biochemical response (a reduction of at least 50% in urinary 5-hydroxyindolacetic acid excretion) in 39%.

IFN-α did not significantly improve tumour retention of 131I-MIBG. In contrast, unlabelled MIBG significantly improved biodistribution and tumour uptake in 83%. A synergistic effect was not seen.

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L D de Hosson, J Stelwagen, G Bouma, B Sijtema, S Huitema, H J R van Faassen, G H de Bock, D J A de Groot, M J E Campmans-Kuijpers, I P Kema, E G E de Vries and A M E Walenkamp

assessed in PRP samples ( Kema et al . 2001 ). 24-h Urine was used for analysis of 5-hydroxyindolacetic acid and N 1 -methylnicotinamide (N 1 -MN), the main metabolite of vitamin B 3 , ( Bouma et al . 2016 ). Mean and standard deviation ( s.d. ) for

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Kjell Oberg

glycoprotein hormones X X  HCGβ X X  Gastrin X  Glucagon X  Insulin X  Proinsulin X  Somatostatin X  Ghrelin X  Substance P X X  Neuropeptide K (NPK) X  Vasoactive intestinal polypeptide (VIP) X  Calcitonin X Urinary markers  5-hydroxyindolacetic acid (5-HIAA

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Cosimo Durante, Houda Boukheris, Clarisse Dromain, Pierre Duvillard, Sophie Leboulleux, Dominique Elias, Thierry de Baere, David Malka, Jean Lumbroso, Joël Guigay, Martin Schlumberger, Michel Ducreux and Eric Baudin

No 72 45 44 Yes 46 21 70 0.4 0.2–0.7 0.002 0.9 0.2–3.9 0.8 Abbreviations: CGA, Chromogranin A; 5HIAA, 5 hydroxyindolacetic acid; HR, Hazard risk; USR, Upper superior range; Synchr, Synchronous; Metachr, Metachronous. a P value univariate. b Adjusted

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Gregory A Kaltsas, Janet L Cunningham, Sture E Falkmer, Lars Grimelius and Apostolos V Tsolakis

, male; F, female; CTGF, connective tissue growth factor; IGF1, insulin-like growth factor 1; IR, immunoreactive; U-5-HIAA, urinary 5-hydroxyindolacetic acid (reference range: <60 μmol/24 h); diameter, diameter of primary tumour in millimetres (if

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Aura D Herrera-Martínez, Rosanna van den Dungen, Fadime Dogan-Oruc, Peter M van Koetsveld, Michael D Culler, Wouter W de Herder, Raúl M Luque, Richard A Feelders and Leo J Hofland

compound on serotonin secretion in NETs. Interestingly, while octreotide is widely used for reducing 5-hydroxyindolacetic acid in patients with NETs ( O’Toole et al. 2000 ), in our PNET model, octreotide did not significantly decrease serotonin release in

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Francesca Marini, Francesca Giusti, Francesco Tonelli and Maria Luisa Brandi

predictive value in the Japanese experience, but similar accuracy was not reproduced in other studies ( Tonelli et al . 2012 ). i Biochemical dosages of urinary 5-hydroxyindolacetic acid and of serum chromogranin A are not helpful for carcinoid