Endocrine Abstracts

Introduction: Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response.Aim of the study: To profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers.Material and methods: Two independent miRNA profiling experiments were performed (n=90), including pr...

Background: New nuclear medicine imaging techniques have improved diagnosis, staging and treatment planning for BC. 68Ga-DOTA PET is preferable to standard somatostatin receptor scintigraphy where available (ENETS guidelines); however, its role in the management of BC remains unclear.Methods: All consecutive patients diagnosed with BC from two ENETS Centres of Excellence were identified retrospectively; patients with high grade tumours or lack...

Background: In patients with advanced GEPNETs, psychological symptoms may result due to potential disturbances in biogenic amines, particularly serotonin. This study compared HRQoL, anxiety, depression, and impulsivity in patients with and without carcinoid syndrome (CS) and correlated with serum 5-HIAA.Methods: Consecutive patients with advanced GEPNETs (with liver metastases) receiving treatment, with and without CS completed (single time-point) HRQoL ...

Introduction: In neuroendocrine tumours (NETs), the urinary concentration of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) is used to monitor disease progression or treatment response. The sensitivity and specificity in the presence of the carcinoid syndrome are approximately 70 and 90%, respectively. Collecting a 24 hour urine specimen is difficult and inconvenient for patients and increases analytical variability. In addition, serotonin-containing foods may i...

Background: Colorectal cancer is the third most common cancer in the UK this had led to development of the bowel cancer screening programmes (BCSPs). It is known that ileo-colonic NETs are increasing in incidence in part thought to be related to increased endoscopy. There are few epidemiological data on rectal or ileal NETs diagnosed in BCSPs. This study aims to identify the number of NETs diagnosed through the UK BCSP.Methods: UK bowel cancer colonoscop...

Limited survival of patients with adrenocortical carcinoma (ACC) makes it imperative to understand the genetic basis of disease and support development of new therapies.Between 2010–2015, tissues from nine adrenalectomy patients (5M:4F, age 30–68 years) were snap frozen in liquid nitrogen and DNA extracted. Adjacent normal adrenal tissue (n=3) excised at adrenalectomy was collected as matched ‘normal’ controls. Whole-exome se...

Background: NET-related symptoms such as flushing and diarrhoeas as well as disease related worries reduce quality of life in patients with neuroendocrine tumours (NETs). Peptide receptor radionuclide therapy (PRRT) is an established treatment in NETs and has been shown to prolong survival. However quality of life data post PRRT is lacking.Aim: To evaluate the symptoms prevalence, intensity and their relation to quality of life in patients receiving PRRT...

Background: Surgery is the only curative treatment for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but the prediction of residual disease/recurrence is limited in the absence of optimal biomarkers. We examined whether a blood-based multianalyte neuroendocrine gene transcript assay (NETest) would define tumor cytoreduction and therapeutic efficacy.Methods: The NETest is a polymerase chain reaction–based analysis of 51 genes. Disease acti...

Background: Despite encouraging advances in the systemic therapy options for patients with pNETs (sunitinib and everolimus), no predictive biomarkers have been established for these drugs. We aimed to identify distinctive genomic alterations associated with benefit from treatment in patients with pNETs, by comparing exceptional-responders (ER) to poor-responders (PO).Methods: Patients who achieved an objective radiological response (complete or partial) ...

Introduction: Carcinoid heart disease (CHD) develops in patients with small bowel NETs with carcinoid syndrome. Currently NT-proBNP (NTP) is suggested as the best current biomarker to screen for CHD and monitor heart failure. A number of other markers have been investigated for heart failure, however, none of these have been explored in NET patients with CHD or carcinoid syndrome. Galectin-3 (GAL3) promotes fibroblast proliferation and correlates with worse outcomes in heart f...

Background: Telotristat etiprate (TE), an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome (CS) by reducing serotonin production. TE was evaluated in TELESTAR, a phase 3 study; the primary endpoint showed significant reductions in bowel movement (BM) frequency for 2 TE dosages + standard of care (SOC) vs. SOC. TELESTAR patients had CS inadequately controlled on somatostatin analog therapy with ≥4 BMs per day. They were interviewed about base...

Background: The identification and characterization of CTCs as part of a minimally invasive “liquid biopsy” has potential as a real-time biomarker in cancer patients. Using blood samples from NET patients, we evaluate the epitope-independent Parsortix, which enriches CTCs based on size and rigidity, and compare to the EpCAM-dependent CellSearch platform.Methods: About 10 patients with histologically confirmed metastatic NET had synchronous 7.5 ...

Introduction: The role of surgery to resect the primary lesion in incurable metastatic small intestinal (SI-NET) and pancreatic neuroendocrine tumours (P-NET) remains controversial. Recent evidence suggests that palliative surgery may increase survival even in asymptomatic patients with non-functioning tumours. The present study investigated the value of palliative resection of the primary tumour in SI-NET and P-NET by systematic literature review and meta-analysis.<p clas...

Introduction: Carcinoid crisis, as an entity is poorly defined, but can be seen in patients with small bowel NET tumours after open bowel surgery or tumour unrelated procedures as cardiovascular instability (CI). Recent evidence suggests that cardiovascular instability (CI) during NET surgery is more common than previously considered.Aims and methods: We audited the incidence of CI during procedures and determined the relationship to perioperative octreo...

Background: Assessment of psychological burden of disease forms one criterion for accreditation of a cancer specialist center. Patient Health Questionnaire-4 (PHQ-4), a validated self-report ultra-short questionnaire was used to assess anxiety and depression level in patients with GEP NETs, attending the clinics at an ENETS Centre of Excellence.Methods: PHQ-4 was completed during routine outpatient visits over a three month period by 48 patients, who wer...

Although initially considered rare, the incidence of pancreatic neuroendocrine tumours (P-NETs) has progressively increased. A population-based study conducted in England and Wales (1986–1999) found that 5-year survival was 29% for non-functioning and 41% for functioning tumours when considering well-differentiated P-NETs. Traditional treatments show very limited effectiveness; novel targeted therapies are, therefore, required and identification of key molecules driving n...

Background: Everolimus, a mammalian target of rapamycin inhibitor, is licensed for use in adult pts with advanced well-differentiated pNETs in the UK. Limited Health-Related Quality-of-Life (HrQOL) data are available for everolimus therapy in these pts.Methods: This prospective study assessed changes in HrQoL (by monthly patient-reported EORTC QLQ-C30, -G.I.NET21 and EQ-5D questionnaires), in pts with pNETs during the first 6 months (mo) of treatment wit...

Background: High-grade neuroendocrine tumours (HGNETs) of the oesophagus are extremely rare and few cases have been reported worldwide. Here we aim to understand clinical profile, treatment strategy and outcomes for oesophageal HGNETs.Methods: We report a single-centre retrospective review of 21 patients with oesophageal HGNETs treated between 2011–2016. Data on incidence, tumour location, stage at presentation, histopathology, treatment protocol an...

Introduction: Carcinoid Heart Disease (CHD) can occur in up to 50% of patients with long standing carcinoid syndrome as a result of metastatic neuroendocrine tumour (NET). It is associated with poor prognosis due to the development of right side heart failure. High circulating levels of serotonin cause cardiac fibrosis leading to tricuspid and pulmonary valve regurgitation and poor ventricular function. Cardiac surgery with valve replacement in combination with cytoreductive s...

Introduction: Standard endoscopic resection of rectal neuroendocrine tumours (NETs) is often associated with histological incomplete excision due to the submucosal position of the tumour within the bowel. This can lead to multiple attempts to achieve a complete excision or uncertainty leading to ongoing endoscopic surveillance. Endoscopic full thickness resection may allow early definitive management. We report a simple definitive technique for the full thickness excision of r...

Background: Pulmonary carcinoids (PC) are rare neuroendocrine tumors (NETs). The course of PCs is considered to be indolent, but patients with advanced disease have low survival rates and their treatment options are limited. As PCs are under-represented in trials, therapeutic decisions are based on evidence extrapolated from other types of NETS. Capecitabine-Temozolamide (CAPTEM) has demonstrated significant efficacy in pancreatic NETs. However, its role in PCs is still unexpl...

Introduction: We previously reported the first documented case of a novel approach in a patient with extensive mesenteric metastases from a small bowel (SB) NET: this combined multivisceral transplantation (MVT) and a vascularised sentinel forearm flap (VSFF) from the same donor.Aim(s): We re-present this case after 38-month follow-up post-MVT/VSFF.Materials and methods: A 44-year old male patient was diagnosed with a well-differen...

Monitoring patients with NETs reveals a significant prevalence of gastrointestinal symptoms, often unrelated directly to the tumour1. Exocrine pancreatic insufficiency exemplifies a common treatable cause of gastrointestinal symptoms in NET patients undergoing therapy with somatostatin analogues. There is a paucity of data regarding this important issue which affects quality of life in NETs. We explored the value of faecal elastase (FE) as a marker of exocrine pancr...

Introduction: There remains controversy about which patients benefit from removal of their primary small bowel tumour and whether this should be performed in a specialist tertiary referral hospital as an elective procedure. Part of the decision making and consenting process in patients with metastases will be a shared decision about surgery with the patient in light of symptoms, morbidity from surgery and survival. The aim of this study was to elucidate important institution s...

Background: Appendiceal neuroendocrine tumours (aNETs) are usually diagnosed incidentally at appendicectomy, are indolent and rarely recur. Current ENETS guidelines inform aNETs management and highlight areas of uncertainty. We aimed to identify risk factors that predict lymph node metastasis, residual disease at completion surgery, or disease recurrence and also assessed survival according to ENETS stage.Methods: We retrospectively analysed a prospectiv...

Insulin autoimmune syndrome (Hirata syndrome) is a rare cause of hypoglycaemia. It was described by Hirata in 1970 and characterised as spontaneous hypoglycaemia, with elevated insulin levels, and associated high titres of insulin autoantibodies. It is most commonly reported in Japan and is associated with autoimmune disease or exposure to sulfhydryl-containing drugs.Continuous glucose monitoring (CGM) devices measure interstitial glucose and were initia...

Background: Pancreatic neuroendocrine tumours (pNETs) are commonly reported in patients with MEN1. The estimated incidence is reported as 40–80% of adults with MEN1 and pNETs are frequently multifocal. Guidelines recommend that CT, MRI and endoscopic ultrasound (EUS) can be used for detection and surveillance of pNETs in MEN1. MRI has been the most commonly used modality, but EUS may be more sensitive in detecting pNETs.Objective: To compare the sen...

Background: Peptide receptor radionuclide therapy (PRRT) can be an option for advanced pancreatic neuroendocrine neoplasms (PNENs) to allow patients undergo resection. Whether or not neoadjuvant PRRT increases postoperative morbidity remains unclear.Methods: Patients with initially metastatic and/or locally advanced PNEN who underwent neoadjuvant PRRT (neoadjuvant group) were compared with a group of patients who underwent upfront surgery (control group)...

Case Report: A 42 year-old male, with a family history of phaeochromocytomas and paragangliomas, was diagnosed as a carrier of the succinate dehydrogenase subunit-B (SDHB) mutation. He was also diagnosed with macroprolactinoma and treated with cabergoline (currently 250 mcg weekly). A contrast CT chest scan, performed as part of the surveillance program for SDHB-associated tumours, revealed a small right lung lesion, which was found to be OctreoScanTM positive. The ...

The Beatson West of Scotland Cancer Centre (BWoSCC) is a Regional Service for the West of Scotland and beyond. It is considered to be a Centre of Excellence in the delivery of 21st century cancer care.Whilst the role of site specific specialist nurses has been integral to many cancer teams for in excess of 20 years, this has not been the case for neuroendocrine tumours in Scotland until May 2016.An international study ca...

Introduction: Appendiceal NENs are usually diagnosed incidentally on histology following an appendicectomy. They include carcinoid tumours (appendiceal neuroendocrine tumours, NETs) and GCC. GCC neoplasms are able to transform to an adenocarcinoma phenotype. There are several important criteria to review when deciding on the treatment and follow up for appendiceal NENs, in particular when to offer further surgery to patients.Aim: To assess whether the ma...

Introduction: Orbital metastases from Neuroendocrine tumours (NET) are reported to be very rare, and can be the primary presentation or become evident up to 20 years after diagnosis. We report a series presented in the NET MDT, where ocular metastasis occurred.Case series: A 69-yr-old woman presented with blurred vision, pain and perception of a lump around the left eye. MRI showed a lacrimal gland mass within the orbit. Excision biopsy revealed a TTF1-p...

Severe tricuspid regurgitation (TR) leads to a reduction in cardiac output and an increase in the central venous pressure, resulting in secondary organ dysfunction. Surgery for severe TR is a high-risk procedure, particularly in the presence of uncontrolled carcinoid syndrome (CS) symptoms. Replacement of leaking tricuspid valves can lead to reduction in tumour markers and improvement in carcinoid symptoms. Transcatheter valve implantation into the vena cava may be an alternat...

Introduction: Psychological symptoms such as aggression, confusion, irritation, anxiety and depression have been observed clinically in patients with carcinoid syndrome. It has been suggested that vasoactive-hormone secretion are involved in provoking psychological symptoms. The objective of this qualitative study is to explore the presence and experience of specific psychological symptoms in vasoactive hormone-secreting NET (carcinoid syndrome).Methods:...

Background: Intracardiac metastasis of carcinoid tumours are rare (incidence 2–4%). Their presence without carcinoid valvulopathy or carcinoid syndrome is unusual.Case Discussions: A 70 year old male presented with abdominal pain. CT imaging revealed a small intestinal tumor with liver and mesenteric metastasis. Biopsy showed a neuroendocrine tumour (NET). Clinical and biochemical evidence of functionality was absent. He underwent definitive small b...