Neuroendocrine Tumour Markers

The neuroendocrine cells of the gastroenteropancreatic (GEP) axis belong to the APUD-system, because they are capable of amine precursor uptake and decarboxylation, leading to the production of amines and small peptides. Currently, over 50 peptides have been identified, secreted by more than IS different types of neuroendocrine cells scattered throughout the gut. Tumours of these cells are generally characterized by an excessive production of one or several of these peptides. The presence of peptides in tumour tissue can usually be easily identified with immunohistochemical methods, or by demonstrating their mRNA with in situ hybridization techniques . The peptides are also frequently released into the circulation, where they can exert their endocrine effects on various targets, often inducing a typical clinical syndrome of hormonal overproduction. These tumours can be called clinically jilllctioning neuroendocrine tumours. The circulating peptides can usually be measured with radioimmunologic methods, allowing them to be used as tumour markers. One tumour generally releases several amilles or peptides in the circulation. Therefore the choice of possible tumour markers is much wider than in the case of non-endocrine tumours. The situation is much more difficult in so-called clinically nonjilllctioning neuroendocrine tumours, not inducing symptoms or signs relating to hormonal hypersecretion. Sometimes, these tumours remain hormonally active, producing peptides without clinical effect, which still can be used as tumour markers. When the tumour has lost all abilities to produce hormonally active substances one has to resort to the use of non-endocrine secretion markers, such as certain enzymes or other contents of secretory granules. In the choice of an adequate tumour marker, the following criteria should be taken into account: the marker must be useful (l) to screen populations for the presence of a tumour, (2) to differentiate between the different types of neuroendocrine tumours, (3) to distinguish between benign, intermediate or malignant tumour types, (4) to provide an estimate of the tumour load, (5) to follow the course of a particular tumour over time, in order to be able to evaluate the response to therapeutic interventions, and to rapidly detect an eventual relapse, and (6) to assess the prognosis. Unfortunately none of the current tumour markers can fulfill all these goals. Therefore, the search for better markers still goes on, and is at present one of the main activities of neuroendocrine research. In addition to the use of the circulating peptides themselves, the receptors for some peptides have recently been shown to be velY valuable markers. Their presence on tumour tissue can be demonstrated in vivo by radioisotopic techniques, using radionuclide labeled peptide, which specifically binds to a specific receptor

Delivering diabetes education through nurseled telecoaching : cost-effectiveness analysis

Background : People with diabetes have a high risk of developing micro-and macrovascular complications associated with diminished life expectancy and elevated treatment costs. Patient education programs can improve diabetes control in the short term, but their cost-effectiveness is uncertain. Our study aimed to analyze the lifelong cost-effectiveness of a nurse-led tele-coaching program compared to usual care in people with type 2 diabetes from the perspective of the Belgian healthcare system. Methods : The UKPDS Outcomes Model was populated with patient-level data from an 18-month randomized clinical trial in the Belgian primary care sector involving 574 participants; trial data were extrapolated to 40 years; Quality Adjusted Life Years (QALYs), treatment costs and Incremental Cost-Effectiveness Ratio (ICER) were calculated for the entire cohort and the subgroup with poor glycemic control at baseline ("elevated HbA1c subgroup") and the associated uncertainty was explored. Results : The cumulative mean QALY (95% CI) gain was 0.21 (0.13; 0.28) overall and 0.56 (0.43; 0.68) in elevated HbA1c subgroup; the respective incremental costs were (sic)1,147 (188; 2,107) and (sic)2,565 (654; 4,474) and the respective ICERs (sic)5,569 ((sic)677; (sic)15,679) and (sic)4,615 (1,207; 9,969) per QALY. In the scenario analysis, repeating the intervention for lifetime had the greatest impact on the cost-effectiveness and resulted in the mean ICERs of (sic) 13,034 in the entire cohort and (sic)7,858 in the elevated HbA1c subgroup. Conclusion : Taking into account reimbursement thresholds applied in West-European countries, nurseled telecoaching of people with type 2 diabetes may be considered highly cost-effective within the Belgian healthcare system

Patient and provider acceptance of telecoaching in type 2 diabetes : a mixed-method study embedded in a randomised clinical trial

Background: Despite advances in diagnosis and treatment of type 2 diabetes, suboptimal metabolic control persists. Patient education in diabetes has been proved to enhance self-efficacy and guideline-driven treatment, however many people with type 2 diabetes do not have access to or do not participate in self-management support programmes. Tele-education and telecoaching have the potential to improve accessibility and efficiency of care, but there is a slow uptake in Europe. Patient and provider acceptance in a local context is an important precondition for implementation. The aim of the study was to explore the perceptions of patients, nurses and general practitioners (GPs) regarding telecoaching in type 2 diabetes. Methods: Mixed-method study embedded in a clinical trial, in which a nurse-led target-driven telecoaching programme consisting of 5 monthly telephone sessions of +/- 30 min was offered to 287 people with type 2 diabetes in Belgian primary care. Intervention attendance and satisfaction about the programme were analysed along with qualitative data obtained during post-trial semi-structured interviews with a purposive sample of patients, general practitioners (GPs) and nurses. The perceptions of patients and care providers about the intervention were coded and the themes interpreted as barriers or facilitators for adoption. Results: Of 252 patients available for a follow-up analysis, 97.5 % reported being satisfied. Interviews were held with 16 patients, 17 general practitioners (GPs) and all nurses involved (n = 6). Themes associated with adoption facilitation were: 1) improved diabetes control; 2) need for more tailored patient education programmes offered from the moment of diagnosis; 3) comfort and flexibility; 4) evidence-based nature of the programme; 5) established cooperation between GPs and diabetes educators; and 6) efficiency gains. Most potential barriers were derived from the provider views: 1) poor patient motivation and suboptimal compliance with "faceless" advice; 2) GPs' reluctance in the area of patient referral and information sharing; 3) lack of legal, organisational and financial framework for telecare. Conclusions: Nurse-led telecoaching of people with type 2 diabetes was well-accepted by patients and providers, with providers being in general more critical in their reflections. With increasing patient demand for mobile and remote services in healthcare,the findings of this study should support professionals involved in healthcare policy and innovation

Nurse-led telecoaching of people with type 2 diabetes in primary care: rationale, design and baseline data of a randomized controlled trial

Background: Despite the efforts of the healthcare community to improve the quality of diabetes care, about 50% of people with type 2 diabetes do not reach their treatment targets, increasing the risk of future micro-and macro-vascular complications. Diabetes self-management education has been shown to contribute to better disease control. However, it is not known which strategies involving educational programs are cost-effective. Telehealth applications might support chronic disease management. Transferability of successful distant patient self-management support programs to the Belgian setting needs to be confirmed by studies of a high methodological quality. "The COACH Program" was developed in Australia as target driven educational telephone delivered intervention to support people with different chronic conditions. It proved to be effective in patients with coronary heart disease after hospitalization. Clinical and cost-effectiveness of The COACH Program in people with type 2 diabetes in Belgium needs to be assessed. Methods/Design: Randomized controlled trial in patients with type 2 diabetes. Patients were selected based on their medication consumption data and were recruited by their sickness fund. They were randomized to receive either usual care plus "The COACH Program" or usual care alone. The study will assess the difference in outcomes between groups. The primary outcome measure is the level of HbA1c. The secondary outcomes are: Total Cholesterol, LDL-Cholesterol, HDL-Cholesterol, Triglycerides, Blood Pressure, body mass index, smoking status; proportion of people at target for HbA1c, LDL-Cholesterol and Blood Pressure; self-perceived health status, diabetes-specific emotional distress and satisfaction with diabetes care. The follow-up period is 18 months. Within-trial and modeled cost-utility analyses, to project effects over life-time horizon beyond the trial duration, will be undertaken from the perspective of the health care system if the intervention is effective. Discussion: The study will enhance our understanding of the potential of telehealth in diabetes management in Belgium. Research on the clinical effectiveness and the cost-effectiveness is essential to support policy makers in future reimbursement and implementation decisions

Long-term treatment with the dopamine agonist quinagolide of patients with clinically non-functioning pituitary adenoma

OBJECTIVE: This study was performed to evaluate the effect of prolonged treatment with the dopamine agonist quinagolide on serum gonadotropin and alpha-subunit concentrations and tumor volume in patients with clinically non-functioning pituitary adenomas (CNPA). DESIGN: Ten patients with CNPA were treated with quinagolide (0.3 mg daily). The median duration of treatment was 57 months (range 36-93 months). Blood samples for measurement of serum gonadotropin and alpha-subunit concentrations were drawn before treatment, after 5 days, and at each outpatient visit. Computerized tomography or magnetic resonance imaging of the pituitary region and Goldmann perimetry were done before and at regular intervals during treatment. RESULTS: A significant decrease of serum FSH, LH or alpha-subunit concentrations was found in nine patients. The levels remained low during the entire treatment period. In two out of three patients with pre-existing visual field defects a slight improvement was shown during the first months of treatment, but eventually deterioration occurred in all three patients. A fourth patient developed unilateral ophthalmoplegia dur

Classification of forefoot plantar pressure distribution in persons with diabetes : a novel perspective for the mechanical management of diabetic foot?

Background: The aim of this study was to identify groups of subjects with similar patterns of forefoot loading and verify if specific groups of patients with diabetes could be isolated from non-diabetics. Methodology/Principal Findings: Ninety-seven patients with diabetes and 33 control participants between 45 and 70 years were prospectively recruited in two Belgian Diabetic Foot Clinics. Barefoot plantar pressure measurements were recorded and subsequently analysed using a semi-automatic total mapping technique. Kmeans cluster analysis was applied on relative regional impulses of six forefoot segments in order to pursue a classification for the control group separately, the diabetic group separately and both groups together. Cluster analysis led to identification of three distinct groups when considering only the control group. For the diabetic group, and the computation considering both groups together, four distinct groups were isolated. Compared to the cluster analysis of the control group an additional forefoot loading pattern was identified. This group comprised diabetic feet only. The relevance of the reported clusters was supported by ANOVA statistics indicating significant differences between different regions of interest and different clusters. Conclusion/s Significance: There seems to emerge a new era in diabetic foot medicine which embraces the classification of diabetic patients according to their biomechanical profile. Classification of the plantar pressure distribution has the potential to provide a means to determine mechanical interventions for the prevention and/or treatment of the diabetic foot

Engaging GPs in insulin therapy initiation : a qualitative study evaluating a support program in the Belgian context

Background: A program supporting the initiation of insulin therapy in primary care was introduced in Belgium, as part of a larger quality improvement project on diabetes care. This paper reports on a study exploring factors influencing the engagement of general practitioners (GPs) in insulin therapy initiation (research question 1) and exploring factors relevant for future program development (research question 2). Methods: We have used semi-structured interviews to answer the first research question: two focus group interviews with GPs who had at least one patient in the insulin initiation program and 20 one-to-one interviews with GPs who were not regular users of the overall support program in the region. To explore factors relevant for future program development, the data from the GPs were triangulated with data obtained from individual interviews with patients (n=10), the diabetes nurse educator (DNE) and the specialist involved in the program, and data extracted from meeting reports evaluating the insulin initiation support program. Results: We found differences between GPs engaged and those not engaged in insulin initiation in attitude, subjective norm and perceived behavioural control regarding insulin initiation. In general the support program was evaluated in a positive way by users of the program. Some aspects need further consideration: job boundaries between the DNE and GPs, job boundaries between GPs and specialists, protocol adherence and limited case load. Conclusion: The study shows that the transition of insulin initiation from secondary care to the primary care setting is a challenge. Although a support program addressing known barriers to insulin initiation was provided, a substantial number of GPs were reluctant to engage in this aspect of care. Important issues for future program development are: an interdisciplinary approach to job clarification, a dynamic approach to the integration of expertise in primary care and feedback on protocol adherence. Trial registration: ClinicalTrials.gov Identifier:NCT0082449

Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones

Chromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgA was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSE was most frequently elevated in patients with small cell lung carcinoma (74%), and alpha-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had elevated CgA concentrations. A significant positive relationship was demonstrated between the tumor load and serum CgA levels (P < 0.01, by chi 2 test). Elevated concentrations of CgA, NSE, and alpha-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300 micrograms/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSE and alpha-SU. Elevated levels are strongly correlated with tumor volume; therefore, small tumors may go undetected. Although its specificity cannot compete with that of the specific hormonal secretion products of most neuroendocrine tumors, it can have useful clinical applications in subjects with neuroendocrine tumors for whom either no marker is available or the marker is inconvenient for routine clinical use