Gaps in the Care of Familial Hypercholesterolaemia in Australia: First Report From the National Registry.

Background: Familial hypercholesterolaemia (FH) is under-diagnosed and under-treated worldwide, including Australia. National registries play a key role in identifying patients with FH, understanding gaps in care and advancing the science of FH to improve care for these patients.

Methods: The FH Australasia Network has established a national web-based registry to raise awareness of the condition, facilitate service planning and inform best practice and care services in Australia.

Neurokinin A monitoring of response to interferon alpha in a patient with an advanced small bowel neuroendocrine tumour uncontrolled by somatostatin analogue therapy.

A 52-year-old lady presented with a history of occasional, severe abdominal cramps, postprandial diarrhoea and weight loss. After routine gastrointestinal investigations, she was diagnosed with irritable bowel syndrome. Over six months, she developed occasional facial flushing prompting assessment of neuroendocrine tumour markers.

Biochemical markers of placental dysfunction in assisted conception.

A possible mechanism for poor perinatal outcomes in singleton pregnancies conceived following assisted reproductive technologies (ART) and those conceived naturally following a period of infertility (>12 months) is thought to be placental dysfunction. This was investigated by measuring plasma concentrations of biochemical markers: (i) soluble fms-like tyrosine kinase1 (sFlt1); (ii) placental growth factor (PlGF); (iii) leptin; and (iv) plasminogen activator inhibitor 2 (PAI-2), serially at four antenatal time points. Baseline concentrations of each marker after delivery were also measured.

Raised circulating Neurokinin A predicts prognosis in metastatic small bowel neuroendocrine tumours. Lowering Neurokinin A indicates improved prognosis.

Background: Assessing prognosis is important in patients with neuroendocrine tumours of the small bowel as disease progression and survival is variable. We previously identified raised Neurokinin A as an independent indicator of poor prognosis and have shown that prognosis worsens when circulating Neurokinin A rises ≥50 ng/L. In the present study we have examined survival in relation to Neurokinin A concentrations.

Neuroendocrine tumours of the small bowel: interpretation of raised circulating chromogranin A, urinary 5 hydroxy indole acetic acid and circulating neurokinin A.

Background: Neuroendocrine tumours (NETs) of the small bowel are difficult to diagnose as symptoms are non-specific and more often found in common gastrointestinal diseases. Chromogranin A (CGA), urinary 5 hydroxy indole acetic acid (U-5HIAA) and Neurokinin A (NKA) are used as laboratory diagnostic tests but results may be misleading or confusing.

Aim: To clarify the relevance of NET biomarkers for diagnosis of small bowel NETs.

The association of a panel of biomarkers with the presence and severity of carcinoid heart disease: a cross-sectional study.

Purpose: Metastatic neuroendocrine tumors secrete serotonin and other vasoactive substances that are responsible for carcinoid syndrome and carcinoid heart disease. We sought to evaluate the discriminatory utility of diagnostic biomarkers in determining the presence and severity of carcinoid heart disease in patients with metastatic neuroendocrine tumors.

Patients And Methods: A cross-sectional study of patients with neuroendocrine tumors with documented liver metastases and/or carcinoid syndrome between April 2009-October 2012 in 5 tertiary referral centers.

Validation of the EORTC QLQ-GINET21 questionnaire for assessing quality of life of patients with gastrointestinal neuroendocrine tumours.

Background: Quality of life is an important end point in clinical trials, yet there are few quality of life questionnaires for neuroendocrine tumours.

Methods: This international multicentre validation study assesses the QLQ-GINET21 Quality of Life Questionnaire in 253 patients with gastrointestinal neuroendocrine tumours. All patients were requested to complete two quality of life questionnaires - the EORTC Core Quality of Life questionnaire (QLQ-C30) and the QLQ-GINET21 - at baseline, and at 3 and 6 months post-baseline; the psychometric properties of the questionnaire were then analysed.

Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs).

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009.

Validation of neurokinin a assays in the United States and Europe.

Objectives: International cooperative group trials require specific, sensitive biomarker assays that are validated between continents. Neurokinin A (NKA) has been shown to be a powerful independent predictor of a poor prognosis in well-differentiated midgut neuroendocrine tumors. We hypothesized that NKA concentrations of clinical specimens evaluated in NKA assays in the United States and the United Kingdom would be equivalent, even though assay techniques were significantly different.

Circulating biomarkers in neuroendocrine tumors of the enteropancreatic tract: application to diagnosis, monitoring disease, and as prognostic indicators.

Neuroendocrine tumors (NETs) are difficult to diagnose. Their symptoms may be vague or intermittent, and are frequently associated with much more common diseases; many of the tumors may be asymptomatic. Therefore, diagnosis can be delayed for some years.

Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study.

We intended to identify the prognostic factors and the results of interventions on patients with liver metastatic midgut carcinoids. Five institutions that are part of United Kingdom and Ireland neuroendocrine tumour (NET) group took part in this study. Patients were included if they had histology proven NET of midgut origin and liver metastases at the time of the study.

Circulating markers for endocrine tumours of the gastroenteropancreatic tract.

The diffuse endocrine system (DES) includes a wide range of secretory cells that may be the source of tumours. Gastroenteropancreatic endocrine (GEP) tumours arising within the DES secrete a variety of peptides and amines that are found in the circulation and are responsible for the syndromes associated with these tumours. In this review, the most common tumours of the GEP tract are outlined and the circulating products of these tumours identified.

Vasoactive intestinal polypeptide secreting pancreatic tumour with hepatic metastases: long term survival after orthotopic liver transplantation.

Background: VIPomas are rare neuroendocrine tumours, with metastases often confined to the liver. Orthotopic liver transplantation may be considered in patients with metastases confined to the liver, however the long term benefits have yet to be shown.

Aims: To discuss the role of orthotopic liver transplantation for neuroendocrine tumours including VIPomas.

A rapid rise in circulating pancreastatin in response to somatostatin analogue therapy is associated with poor survival in patients with neuroendocrine tumours.

Aim: To assess the value of pancreastatin as a predictive factor for identifying patients with neuroendocrine tumours (NETs) who respond poorly to somatostatin analogues.

Methods: A retrospective study of patients with NETs. Patient records from the Northern Ireland Neuroendocrine Tumour Register were interrogated.

Cyclooxygenase-2 expression correlates with phaeochromocytoma malignancy: evidence for a Bcl-2-dependent mechanism.

Aims: Phaeochromocytomas are rare but potentially life-threatening neuroendocrine tumours of the adrenal medulla or sympathetic nervous system ganglia. There are no histological features which reliably differentiate benign from malignant phaeochromocytomas. The aim of the study was to evaluate cyclooxygenase (COX)-2 and Bcl-2 as tissue-based biomarkers of phaeochromocytoma prognosis.

An evaluation of cyclooxygenase-2 as a prognostic biomarker in mid-gut carcinoid tumours.

Background/aims: Mid-gut carcinoids (MGC) are the most common of the gastrointestinal carcinoid tumours. There is a lack of reliable prognostic indicators for MGC. Cox-2 and Bcl-2 were evaluated as prognostic biomarkers in a cohort of well-characterised non-appendiceal MGC.

Cox-2 promotes chromogranin A expression and bioactivity: evidence for a prostaglandin E2-dependent mechanism and the involvement of a proximal cyclic adenosine 5'-monophosphate-responsive element.

The prostanoid biosynthetic enzyme cyclooxygenase-2 (Cox-2) is up-regulated in several neuroendocrine tumors. The aim of the current study was to employ a neuroendocrine cell (PC12) model of Cox-2 overexpression to identify gene products that might be implicated in the oncogenic and/or inflammatory actions of this enzyme in the setting of neuroendocrine neoplasia. Expression array and real-time PCR analysis demonstrated that levels of the neuroendocrine marker chromogranin A (CGA) were 2- and 3.

Increased tachykinin levels in induced sputum from asthmatic and cough patients with acid reflux.

Background: Acid reflux may aggravate airway disease including asthma and chronic cough. One postulated mechanism concerns a vagally-mediated oesophageal-tracheobronchial reflex with airway sensory nerve activation and tachykinin release.

Aim: To test the hypothesis that patients with airways disease and reflux have higher airway tachykinin levels than those without reflux.

Calcitonin gene-related peptide relates to cough sensitivity in children with chronic cough.

Airway neuropeptides, in particular calcitonin gene-related peptide (CGRP), are likely to be important in the pathogenesis of chronic cough. The present authors evaluated the following: 1) the relationship between cough sensitivity and bronchoalveolar lavage (BAL) neuropeptides; and 2) the effect of reflux oesophagitis (RO) on cough, cough sensitivity and BAL neuropeptides in children not selected for cough. It was hypothesised that CGRP would be increased in children with chronic cough and would relate to cough sensitivity.

Vasoactive intestinal polypeptide (VIP) and VPAC1 receptor in adult human dental pulp in relation to caries.

Objective: To quantitatively measure VIP levels and to qualitatively study the distribution of VIP fibres and demonstrate the presence of the VPAC1 receptor in human dental pulp from carious and non-carious adult human teeth.

Design: Dental pulp samples were collected from non-carious, moderately carious and grossly carious adult human teeth. VIP levels were determined using radioimmunoassay.

Circulating markers of prognosis and response to treatment in patients with midgut carcinoid tumours.

Background And Aims: Midgut carcinoid tumours are uncommon tumours with an unpredictable clinical behaviour and few useful prognostic markers. Somatostatin analogues are widely used in treatment but a survival advantage has not been proven. We analysed features associated with poor prognosis and assessed the clinical implications of the biochemical response to therapy.

Development of a disease-specific Quality of Life questionnaire module for patients with gastrointestinal neuroendocrine tumours.

Quality of life (QoL) measurements are increasingly being used as an end point in cancer clinical trials. Standard generic QoL questionnaires may not assess symptoms produced by neuroendocrine tumours. Here we report the development of a disease-specific quality of life score questionnaire for patients with neuroendocrine tumours of the gut to supplement the EORTC core cancer questionnaire, the QLQ-C30.

Plasma concentrations of glucagon-like peptide-2 in adult patients with treated and untreated coeliac disease.

Background: Coeliac disease is a common chronic inflammatory enteropathy characterized by villous atrophy and crypt hyperplasia in the small intestine. The mechanism of the intestinal damage in coeliac disease remains unclear. Glucagon-like peptide (GLP)-2 is an enterotrophic peptide that causes crypt hyperplasia and intestinal cell proliferation.

Endobronchial adenosine monophosphate challenge causes tachykinin release in the human airway.

Background: Adenosine 5 monophosphate (AMP) has been shown to cause bronchoconstriction and a sensation of chest tightness when inhaled by asthmatic subjects. This response is attenuated after repeated inhalation of bradykinin, suggesting that AMP may act in part by the release of neuropeptides.

Objective: This study examined neuropeptide release in the human airway after endobronchial AMP challenge.