Morbidity & mortality associated with desmoplasia in midgut (Carcinoid) neuroendocrine tumours

Abstract

INTRODUCTION Midgut neuroendocrine tumours (NETs) form part of a heterogenous group characterized by their ability to secrete hormones and other mediators which may cause carcinoid syndrome. They may also present with complex problems related to mesenteric fibrosis/desmoplasia. The cause of desmoplasia is unknown, however it may be associated with peptides secreted by NETs. It has been previously reported that 30% of patients with midgut NETs are found to have desmoplasia on CT at presentation and this increases as disease progresses. Desmoplasia may cause symptoms secondary to mesenteric artery/vein occlusion, as well as bowel obstruction. AIM To assess morbidity and mortality associated with desmoplasia in midgut NETs. METHODS A retrospective review of our NET database for patients with cofirmed midgut NET and desmoplasia was performed. Information available included: age, sex, diagnosis, previous treatments, current management and outcomes. 107 midgut NET patients with desmoplasia were identified. Full data was available for 99 patients (51 males and 48 females). Desmoplasia was identified at surgery or at CT imaging. Overall survival (OS) was calculated from time of diagnosis. RESULTS 61 (62%) patients were symptomatic at diagnosis or during the course of their disease, from either obstructive or ischaemic cause. The remaining 38 (38%) patients were asymptomatic and desmoplasia was diagnosed incidentally on CT. 68 (69%) patients had undergone surgical procedures, including resection of the primary, re-resection, stoma formation and bypass. Of the 48 patients who had undergone surgical resection of the primary tumour, 31 (65%) had presented with obstructive symptoms. 6 (6%) patients developed symptoms from superior mesenteric vein occlusion, needing long-term anticoagulation. 2 patients had short bowel syndrome and 5 (5%) patients required long-term total parenteral nutrition. 36 patients died. Total median OS was 96 months. The median OS survival in the symptomatic group was 81 months and not reached in the asymptomatic group (log-rank p=0.059). The median OS for those who underwent primary resection was 144 months, whilst the median OS for those not resected was 75 months (log-rank p=0.128). CONCLUSIONS The majority of patients with midgut NETs and desmoplasia are symptomatic requiring surgical intervention. Patients may present acutely with bowel obsturction due to tumour or the effects of desmoplasia. Desmoplasia may progress despite medical treatments. Patients with mesenteric artery/vein occlusion may be managed with anticoagulation. The median OS in symptomatic patients was less than the total median OS. These patients have complex symptomatology which can only be dealt with by experienced multidisciplinary approach. Further research is required into the pathogenesis of desmoplasia to enable better treatment.