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

BACKGROUND: Small intestinal neuroendocrine tumours (SI NETs) represent 30-50% of small bowel neoplasms and often present at an advanced stage. To date, there is relatively limited literature regarding prognostic factors affecting overall survival (OS) in stage IV disease. In addition, the prevalence of mesenteric fibrosis (MF) in SI NETs and its effect on OS have not been sufficiently explored in the literature. AIM: The primary aim of this study was to perform a large-scale survival analysis in an institutional cohort of 387 patients with metastatic (stage IV) SI NETs. The secondary aim was to provide epidemiological information regarding the prevalence of MF and to evaluate its effect on OS. RESULTS: The median OS was 101 months (95% CI 84, 118). Age > 65 years, mesenteric metastases with and without desmoplasia, liver metastases, carcinoid heart disease (CHD) and bone metastases were associated with a significantly shorter OS, while primary tumour resection was predictive of a longer OS. The benefit of surgical resection was limited to symptomatic patients. MF was present in approximately 50% of patients with mesenteric lymphadenopathy. Elevated urinary 5-HIAA levels correlated strongly with the presence of CHD (p < 0.001) and to a lesser extent (p = 0.02) with MF. MF and CHD did not usually co-exist, suggesting that different mechanisms are likely to be involved in the development of these fibrotic complications. CONCLUSIONS: This study has identified specific prognostic factors in a large cohort of 387 patients with advanced SI NETs and has provided useful epidemiological data regarding carcinoid-related fibrotic complications.

The Clinical Utility of the NETest in Patients with Small Intestinal Neuroendocrine Neoplasms (Si-NENs): A "Real-Life" Study.

Current biomarkers do not adequately predict the behaviour of neuroendocrine neoplasms (NENs). This study assessed the NETest, a multianalyte blood biomarker, in patients with small intestinal NENs (Si-NENs). We studied two patient groups: Group 1: metastatic Si-NENs (n = 102) and Group 2: post-operatively disease-free according to 68Ga-DOTATATE PET (n = 16). NETest scores were ≤20% (normal), 21-40% (low), 41-79% (intermediate), or ≥80% (high). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In Group 1, the median NETest score was 40% (IQR: 33.3-46.7%). The NETest value (HR: 1.032, 95% CI: 1.003-1.062, p = 0.033) and high-risk NETest category (HR: 10.5, 95% CI: 1.35-81.7, p = 0.025) were independent predictors of PFS, along with presence of lung metastases, CgA levels > 10 × ULN, and tumour growth rate (TGR). Independent predictors of OS were the NETest value (HR: 1.035, 95% CI: 1.005-1.066, p = 0.024) and high-risk NETest category (HR: 15.2, 95% CI: 1.52-151, p = 0.02), along with presence of lung metastases and CgA levels > 10 × ULN. In Group 2, ROC analysis identified an AUC of 0.909 (95% CI: 0.75-0.100) for prediction of local or metastatic recurrence. Blood NETest scores were associated with PFS and OS in patients with metastatic Si-NENs, along with TGR, CgA > 10 × ULN, and presence of lung metastases.

Diagnostic and Management Challenges in Vasoactive Intestinal Peptide Secreting Tumors: A Series of 15 Patients.

OBJECTIVES: Vasoactive intestinal peptide-secreting tumors (VIPomas) are rare functioning neuroendocrine tumors often characterized by a difficult-to-control secretory syndrome and high potential to develop metastases. We hereby present the characteristics of 15 cases of VIPomas and provide a recent literature review. METHODS: This was a retrospective data analysis of 15 patients with VIPoma from 3 different centers and literature research through PubMed database during the last 10 years. RESULTS: Fifteen patients with VIPomas (9 with hepatic metastases at diagnosis) with watery diarrhea and raised VIP levels were studied. Ten patients (67%) had grade 2 tumors, 6 of 15 had localized disease and underwent potentially curative surgery, whereas the remaining 9 received multiple systemic therapies; 3 patients died during follow-up. The median overall survival was 71 months (range, 41-154 months). Patients who were treated with curative surgery (n = 7) had longer median overall survival compared with patients who were treated with other therapeutic modalities (44 vs 33 months). CONCLUSIONS: The management of VIPomas is challenging requiring the application of multiple treatment modalities. Patients who underwent surgical treatment with curative intent appear to have higher survival rate. Central registration and larger prospective studies are required to evaluate the effect of currently employed therapies in these patients.