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

Abstract

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.

Prognostic impact of a large mesenteric mass >2 cm in ileal neuroendocrine tumors

“…i‐NETs secrete serotonin and other factors, and thereby interact with the tumor microenvironment, including cancer‐associated fibroblasts, causing a mesenteric desmoplastic reaction and LMM . Therefore, the presence of mesenteric desmoplasia/mass may represent aggressive biology; though the prognostic impact is not clear . Bösch et al reported that the presence of a desmoplastic reaction on imaging was associated with disease progression (not limited to the liver), but was not associated with OS.…”

“…Bösch et al reported that the presence of a desmoplastic reaction on imaging was associated with disease progression (not limited to the liver), but was not associated with OS. Laskaratos et al showed that mesenteric lymphadenopathy was associated with short OS, but the definition of lymphadenopathy was unclear. The latest AJCC TNM staging (8th edition) newly defined LMM >2 cm as N2 .…”

“…The cutoff point of the size was in accordance with the definition of N2 in the latest AJCC TNM staging . Extent of liver involvement was evaluated on preoperative imaging as absent, <25%, 25% to 50%, and ≥50%, as previously described . Complete or incomplete mesenteric mass resection was judged based on the operative findings, perioperative imaging, and pathology, where a residual mesenteric mass ≥1 cm was regarded as an incomplete resection.…”

“…Because i‐NETs are asymptomatic at an early stage, they are frequently diagnosed at an advanced stage with metastases involving regional lymph node (34%‐88%) and the liver (56%‐78%) . Regional lymphadenopathy is associated with desmoplasia of the mesentery forming a mesenteric mass . Mesenteric desmoplasia/mass causes abdominal pain and small bowel obstruction due to the kinking of the small bowel and mesenteric ischemia, which severely impairs the quality of life .…”

“…The latest American Joint Committee on Cancer (AJCC) TNM staging for NETs of the jejunum and ileum (8th edition) defined a new category of N2 as a large mesenteric mass (LMM) >2 cm, 12 or more positive nodes, or involving the main superior mesenteric vessels . While liver metastasis is a well‐established prognostic factor, the prognostic significance of LMM is ill‐defined . Therefore, in this study, we evaluated whether the LMM is prognostic for patients with i‐NETs.…”