Colorectal Neuroendocrine Neoplasms: Areas of Unmet Need

Abstract

The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well-differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and poorly differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according to the 2010 World Health Organisation (WHO) classification, has arguably not had as much attention or study as NENs occurring in other sites. Colorectal NETs and NECs are however easier to study than many others since they are usually not difficult to remove and are increasingly detected because of intensified colorectal cancer screening and surveillance programmes. Colorectal NETs and NECs show site-specific heterogeneity with variable behaviour and different therapeutic options; these various aspects provide unique challenges. Because of bowel cancer screening programmes, colorectal NENs, like conventional adenocarcinomas, may be diagnosed at a stage that is associated with improved survival. In this article we intend to describe and define areas of unmet needs relating to the epidemiology, classification, pathology, diagnosis and therapy of colorectal NETs (including NETs G3), colorectal NECs, and finally, mixed adeno-neuroendocrine carcinomas (MANECs) by reviewing and discussing the relevant literature.

Rectal neuroendocrine tumors: is it all on first sight?

“…Prediction of advanced disease [3] 1 Proposed algorithm for the management of a rectal neuroendocrine tumor suspected during initial colonoscopy. This personal view from the authors relies on the current recommendations [5][6] and integrates the score proposed by Chen et al [3] in the present issue of Endoscopy. CT, computed tomography; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; EUS, endoscopic ultrasonography; LNM, lymph node metastases; MRI, magnetic resonance imaging; PET, positron emission tomography; TEM, transanal endoscopic microsurgery.…”

“…As local excision of these small rectal NETs is often also the definitive treatment, endoscopic resection should best be performed radically. It is now well recognized that polypectomy or endoscopic mucosal resection (EMR) do not provide sufficient resection margins [1,5]. Instead, advanced EMR (with cap aspiration or ligation assistance) or endoscopic submucosal dissection (ESD) appear more appropriate for rectal NETs < 10 mm, and ESD or transanal endoscopic microsurgery (TEM) for those ≥ 10 mm (▶ Fig.…”

“…Instead, advanced EMR (with cap aspiration or ligation assistance) or endoscopic submucosal dissection (ESD) appear more appropriate for rectal NETs < 10 mm, and ESD or transanal endoscopic microsurgery (TEM) for those ≥ 10 mm (▶ Fig. 1) [1,5,6]. Should these advanced resection techniques not be available on site, it is preferable to refer the patient to an expert endoscopy center rather than attempt standard polypectomy/EMR.…”

“…However, while training in the recognition of other adenomatous polyps (Paris and Kudo classifications) is well advanced, training in the recognition of rectal NETs currently remains in its early stages. In response to this area of unmet need, the European Neuroendocrine Tumor Society have proposed that endoscopic training programs should include a rectal NET recognition module and such a development has started [5].…”

Combined Detection of Free Fatty Acid (FFA) and High-Density Lipoprotein Cholesterol (HDL-C) is a Promising Pretreatment Biomarker for Predicting the Overall Prognosis (OS) of Neuroendocrine Tumours (NETs) in the Colorectum: A Case-Control Study.

“…Therefore, patient with high FFA and low HDL-C had a worse prognosis than patients with only high FFA, only low HDL-C and patients with low FFA or high HDL-C. Some researchers have suggested that FFA and HDL-C may promote cancer progression by different signalling pathways (Ganjali et al 2021; Kawaguchi et al 2016; Pascual et al 2021; Zhang et al 2020), so the combined detection of FFAs and HDL-C may have a complementary effect, consistent with our ndings.Mixed adenoneuroendocrine carcinoma of the colon and rectumare rare cancers; they are characterized by the presence of a combination of epithelial and neuroendocrine elements, where each component represents at least 30% of the tumour(Qiu et al 2018), and are anunmet area where NETs need to be described and de ned(Ramage et al 2019). In our study, there were more colorectal NET patents with positive LNM than with negative LNM, which may be due to not excluding mixed adenoneuroendocrine carcinoma among the patient groups, which is composed of poorly differentiated neuroendocrine carcinoma and easily metastasizes(Milione et al 2018;Qiu et al 2018).…”