Carcinoid syndrome (CS) develops in patients with hormone-producing neuroendocrine neoplasms (NENs) when hormones reach a significant level in the systemic circulation. The classical symptoms of carcinoid syndrome are flushing, diarrhoea, abdominal pain, and wheezing. Neuroendocrine neoplasms can produce multiple hormones: 5-hydroxytryptamine (serotonin) is the most well-known one, but histamine, catecholamines, and brady/tachykinins are also released. Serotonin overproduction can lead to symptoms and also stimulates fibrosis formation which can result in development of carcinoid syndrome-associated complications such as carcinoid heart disease (CaHD) and mesenteric fibrosis. Transforming growth factor beta (TGF-β) is one of the main factors in developing fibrosis, but platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF2), and connective tissue growth factor (CTGF or CCN2) are also related to fibrosis development. Treatment of CS focuses on reducing serotonin levels with somatostatin analogues (SSA’s). Telotristat ethyl and peptide receptor radionuclide therapy (PRRT) have recently become available for patients with symptoms despite being established on SSA’s. Screening for CaHD is advised, and early intervention prolongs survival. Mesenteric fibrosis is often present and associated with poorer survival, but the role for prophylactic surgery of this is unclear. Depression, anxiety, and cognitive impairment are frequently present symptoms in patients with CS but not always part of their care plan. The role of antidepressants, mainly SSRIs, is debatable, but recent retrospective studies show evidence for safe use in patients with CS. Carcinoid crisis is a life-threatening complication of CS which can appear spontaneously but mostly described during surgery, anaesthesia, chemotherapy, PRRT, and radiological procedures and may be prevented by octreotide administration.

Neuroendocrine tumours are uncommon tumours; there is often a long period between the onset of symptoms and diagnosis. This study aims to address the symptoms prior to diagnosis of people with known neuroendocrine tumours and also the involvement of healthcare providers prior to the diagnosis. A web based survey was designed to cover two broad areas of patient symptoms and healthcare interactions prior to diagnosis. This was tested and adapted by patient and clinician input prior to distribution via Survey Monkey. The results demonstrated a median time from first symptom to diagnosis of 53.8 months. The most frequent initial symptoms were of pain, change in bowel habit and fatigue. 31% of respondents noted weight loss prior to diagnosis. 80% of respondents visited their GP regarding the symptoms a median of 11 times. 58% of respondents were referred to secondary care where they were seen a median 3 times. 30% presented acutely to A&E and this led to their diagnosis. In conclusion, there is a long time from onset of symptoms to diagnosis in all types of NETs. This is despite many respondents having alarm symptoms at diagnosis. Further education and awareness regarding malignancy may help with earlier diagnosis.

Purpose of Review: This review examines the variation in incidence of rectal neuroendocrine tumours across the globe. Rectal neuroendocrine tumours are a common type of gastrointestinal NET with an increasing incidence reported over the last 30 years. Recent Findings: There have been a number of publications examining the epidemiology of neuroendocrine tumours across the world. These have utilized a variety of different methodologies to examine both incidence of prevalence of NETs. We review the data published and describe any causative factors and findings regarding the epidemiology of rectal NETs. Summary: Rectal NETs account for 1–2% of all rectal cancers and are commonly diagnosed between 50–60 years of age. Most lesions are identified by chance at colonoscopy, commonly during colon cancer screening procedures, which is reflected in part in the age at diagnosis. Most lesions are small in size, < 10 mm and can be managed with endoscopic resection rather than requiring surgery. The highest incidence is reported in people of Asian ethnicity, with a tenfold increased incidence reported in some series compared with white population. There is also an increased incidence in Black and Hispanic population as identified through the Surveillance, Epidemiology and End Results (SEER) database. Endoscopic assessment of lesions is variable globally. Future work to better understand the cause of ethnic variation and development of comprehensive cancer registries would be helpful.

Neuroendocrine tumours (NETs) are often indolent malignancies that commonly present with metastatic disease in the liver. Surgical, locoregional, and systemic treatment modalities are reviewed. A multidisciplinary approach to patient care is suggested to ensure all therapeutic options explored.

Purpose: NETTER-R aimed to determine the efficacy, safety and tolerability of ¹⁷⁷Lu-DOTATATE in patients with progressive, advanced pancreatic neuroendocrine tumours (panNETs) using retrospective real-world data from multiple sites. Methods: This international study retrospectively included patients with panNETs treated with ¹⁷⁷Lu-DOTATATE. The primary endpoint was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included overall survival (OS), safety and tumour response. Results: In total, 110 patients with panNETs were studied; 65.5% received a cumulative dose of ¹⁷⁷Lu-DOTATATE 29.6 GBq ± 10% (median: 7.4 GBq). In 62 patients with available RECIST v1.1 tumour response, the median PFS was 24.8 months (95% confidence interval [CI]: 17.5–34.5), and the objective response rate was 40.3% (95% CI: 28.1–53.6); all responses were partial. With a median follow up of 24.5 months (range: 2.0–123.4 months) after the first cycle of ¹⁷⁷Lu-DOTATATE, the median OS in the full analysis set (n = 110) was 41.4 months (95% CI: 28.6–50.2). PFS (hazard ratio [HR]: 3.672; p = 0.0009) and OS (HR: 3.360; p < 0.0001) were longer in patients who received no chemotherapy prior to ¹⁷⁷Lu-DOTATATE than those who did. No treatment-emergent adverse events (TEAEs) led to treatment discontinuation. Grade 3 anaemia, lymphopenia and thrombocytopenia occurred in 0.9%, 5.4% and 0.9% of patients, respectively. No acute leukaemia or myelodysplastic syndrome was reported. Six patients (5.5%) had renal TEAEs. All renal grade ≥ 3 events were transient and did not lead to treatment modification. Conclusions: These results reinforce the role of ¹⁷⁷Lu-DOTATATE for the treatment of patients with advanced, somatostatin receptor-positive panNETs.