Prognostic Factors for Survival among Patients with Small Bowel Neuroendocrine Tumours Associated with Mesenteric Desmoplasia

Abstract

Background: Small intestinal neuroendocrine tumours (SI NETs) represent 30–50% of small bowel neoplasms and are often associated with diverse fibrotic complications. Mesenteric fibrosis is a hallmark of SI NETs which may cause substantial morbidity and is considered an adverse feature. However, survival analyses in this group of patients are lacking. Methods: The aim of this retrospective study was to determine the overall survival (OS) and factors affecting prognosis in a large cohort of 147 patients with SI NETs and radiological evidence of mesenteric desmoplasia from our centre. The severity of desmoplasia was graded radiologically and its effect on OS and long-term complications was assessed. The median follow-up period was 82 months. Results: The median OS was 8.7 years (95% CI 6.8–9.9) with an overall 5-year survival of 71%. The univariate analysis demonstrated that an age >65 years, a liver tumour burden >50% of the hepatic parenchyma, carcinoid heart disease, chromogranin A levels >10 times the upper limit of normal, and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels >5 times the upper limit of normal were poor prognosticators, while primary resection was associated with a longer OS. However, only an age >65 years and urinary 5-HIAA levels >10 times the upper limit of normal remained statistically significant after multivariate analysis. The severity of mesenteric desmoplasia did not seem to demonstrate a statistically significant relationship to OS or long-term outcomes. Conclusion: This study is the first comprehensive survival analysis of patients with SI NETs associated with mesenteric desmoplasia and has provided important and clinically relevant epidemiological data for this group of patients.

Evaluation of Clinical Prognostic Factors and Further Delineation of the Effect of Mesenteric Fibrosis on Survival in Advanced Midgut Neuroendocrine Tumours

“…However, a smaller study of 31 patients (17 with and 14 without intra-abdominal fibrosis) did not show a correlation between fibrosis and mean or peak urinary 5-HIAA levels, but the small study sample was certainly a limitation [18]. In a recent study of fibrotic SI NETs from our centre, we failed to detect significant differences in urinary 5-HIAA levels among different groups of MF severity (mild, moderate and severe), which were graded radiologically using a classification system based on the number and thickness of radiating fibrous strands, described originally by Pantongrag-Brown et al [6,28]. In this analysis of metastatic SI NETs, we found a statistically significant correlation of urinary 5-HIAA levels with the presence of MF (p = 0.02) which was less potent than the association with CHD (p < 0.001) (250 cases with available urinary 5-HIAA levels were assessed, as shown in Table 5).…”

“…These were detected by Ga68 PET imaging in approximately half of the cases, and therefore their true prevalence may be underestimated in our cohort. In other survival analyses of midgut NETs, bone metastases have not been assessed separately as a prognostic factor, although in some studies they have probably been included in a miscellaneous category of "distant metastases" along with other sites of extrahepatic disease [6]. A recent paper by Scharf et al [26] including 677 patients with NETs from the EN-ETS centre in Marburg, Germany, showed that bone metastases were present in 12.6% of cases (mainly small intestinal and pancreatic primaries) and were associated with a significantly shorter OS compared to other distant metastases (49 vs. 101 months, p = 0.01).…”

“…Although the precise pathogenesis of carcinoid-related fibrosis remains poorly understood [4,5], it is well known that circulating serotonin plays a central role in the development of CHD, while its involvement in mesenteric desmoplasia is less clear. In addition, even though MF is considered a hallmark of midgut NETs, which can lead to considerable morbidity and mortality [6][7][8], there is surprisingly very limited literature on the prevalence of MF in patients with SI NETs. This is partly because many of the previously published survival analyses of SI NETs were based on national registries or institutional databases that did not record this information.…”

Clinicopathological correlations of mesenteric fibrosis and evaluation of a novel biomarker for fibrosis detection in small bowel neuroendocrine neoplasms

“…The development of mesenteric fibrosis (MF) in small intestinal neuroendocrine tumours (SI NETs) is associated with significant morbidity [1,2] and may also adversely affect patient prognosis [3][4][5]. Despite its sinister and substantial clinical ramifications, MF remains an underresearched area of neuroendocrine neoplasia and its pathophysiology is poorly understood [1].…”

Update on Pathophysiology, Treatment, and Complications of Carcinoid Syndrome

“…In view of the risk of ischemia or small bowel obstruction, removal of the primary tumour and mesenteric mass is advised when possible [15,78,88,90]. Two recent studies [89,91] investigated the effect of mesenteric fibrosis diagnosed on CT scans and survival. Blažević et al [89] showed that mesenteric fibrosis was present in up to 41.4% of patients with biopsy-proven small bowel NEN visible on CT scan.…”