Incidence and survival of neuroendocrine tumours in the Netherlands according to histological grade: experience of two decades of cancer registry.

Purpose: Epidemiological studies on neuroendocrine tumours (NETs) generally show a major increase in incidence. To investigate this increase, epidemiological data from the Netherlands were evaluated according to histological grade.

Methods: All 47,800 patients with NET (diagnosed 1990-2010) from the population-based Netherlands Cancer Registry were stratified according to the latest World Health Organization (WHO) classification for the digestive system: well-differentiated NET grade 1 and 2 (G1NET and G2NET), and poorly differentiated (grade 3) neuroendocrine carcinoma, subdivided into large cell (G3-LCNEC) and small cell (G3-SCNEC).

Choice of tumour markers in patients with neuroendocrine tumours is dependent on the histological grade. A marker study of Chromogranin A, Neuron specific enolase, Progastrin-releasing peptide and cytokeratin fragments.

Background: Chromogranin A (CgA) is the most important tumour marker for well-differentiated neuroendocrine tumours (NET) and neuron specific enolase (NSE) for poorly differentiated neuroendocrine carcinoma (NEC). This study investigated whether the markers progastrin-releasing peptide (proGRP) and cytokeratin fragments (CKfr) CK8, CK18 and CK19 (MonoTotal) can be of additional value to the histological classification and help predict survival in these patients.

Methods: CgA, NSE, proGRP and CKfr were measured in 242 patients with grade 1 NET (G1NET), 38 with grade 2 NET (G2NET), 42 with large cell NEC (LCNEC), 251 with small cell NEC (SCNEC) and in 282 healthy persons.

Somatostatin receptor scintigraphy and chromogranin A assay in staging and follow-up of patients with well-differentiated neuroendocrine tumors.

Introduction: Chromogranin A (CgA) assay and somatostatin receptor scintigraphy (SRS) are implemented in the standard workup of neuroendocrine tumors (NETs). The aim of this study was to assess the value of SRS and CgA in staging and follow-up patients with well-differentiated NETs.

Materials And Methods: A total of 88 consecutive patients with histologically confirmed well-differentiated NETs were included.

Increase of angiogenic growth factors after hepatic artery embolization in patients with neuroendocrine tumours.

In the event of diffuse hepatic metastases, hepatic artery embolization (HAE) can be a successful treatment option in patients with well-differentiated neuroendocrine tumours (NET). However, embolization causes hypoxia which stimulates angiogenesis and therefore tumour growth. This study investigates angiogenesis activity following HAE by measuring vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and C-terminal proendothelin-1 (proET-1) in blood.

Chromogranin-A and N-terminal pro-brain natriuretic peptide: an excellent pair of biomarkers for diagnostics in patients with neuroendocrine tumor.

Purpose: For the last decade chromogranin-A (CgA) has been a well-established marker for neuroendocrine tumor (NET), and N-terminal pro-brain natriuretic peptide (NT-proBNP) has been a useful marker for left ventricular dysfunction. This study examined the diagnostic value of CgA and NT-proBNP for carcinoid heart disease (CHD), and their prognostic value for overall survival in NET patients.

Patients And Methods: Serum samples were obtained and cardiac ultrasound studies performed in 102 NET patients.

Chromogranin A as an alternative to 5-hydroxyindoleacetic acid in the evaluation of symptoms during treatment of patients with neuroendocrine Tumors.

Background: Urinary 5-HIAA excretion is a well-known marker in neuroendocrine tumors (NETs), but it has a low sensitivity and the 24-hour collection is inconvenient for patients. Chromogranin A (CgA) is a promising marker, but a thorough evaluation during follow-up is still lacking.

Methods: 39 patients with metastatic gastrointestinal NETs were monitored during treatment with the long-acting octreotide SandostatinLAR.

Dynamic Bayesian networks as prognostic models for clinical patient management.

Prognostic models in medicine are usually been built using simple decision rules, proportional hazards models, or Markov models. Dynamic Bayesian networks (DBNs) offer an approach that allows for the incorporation of the causal and temporal nature of medical domain knowledge as elicited from domain experts, thereby allowing for detailed prognostic predictions. The aim of this paper is to describe the considerations that must be taken into account when constructing a DBN for complex medical domains and to demonstrate their usefulness in practice.

Selecting treatment strategies with dynamic limited-memory influence diagrams.

Objective: The development of dynamic limited-memory influence diagrams as a framework for representing factorized infinite-horizon partially observable Markov decision processes (POMDPs), the introduction of algorithms for their (approximate) solution, and the application to a dynamic decision problem in clinical oncology.

Materials And Methods: A dynamic limited-memory influence diagram for high-grade carcinoid tumor pathophysiology was developed in collaboration with an expert physician. Three algorithms, known as single policy updating, single rule updating, and simulated annealing have been examined for approximating the optimal treatment strategy from a space of 10(19) possible strategies.

Colorectal cancer in the family: psychosocial distress and social issues in the years following genetic counselling.

Background: This study examined: (1) levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC); (2) associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3) the impact of genetic counselling on family relationships, and (4) social consequences of genetic counselling.

Methods: In this cross-sectional study, individuals who had received genetic counselling for HNPCC during 1986-1998 completed a self-report questionnaire by mail.

Results: 116 individuals (81% response rate) completed the questionnaire, on average 4 years after the last counselling session.

Predicting carcinoid heart disease with the noisy-threshold classifier.

Objective: To predict the development of carcinoid heart disease (CHD), which is a life-threatening complication of certain neuroendocrine tumors. To this end, a novel type of Bayesian classifier, known as the noisy-threshold classifier, is applied.

Materials And Methods: Fifty-four cases of patients that suffered from a low-grade midgut carcinoid tumor, of which 22 patients developed CHD, were obtained from the Netherlands Cancer Institute (NKI).

Detection of small-bowel neuroendocrine tumors by video capsule endoscopy.

Objectives: Carcinoid tumors are the most common GI neuroendocrine tumors (NET). They often originate in the small intestine. The primary tumor is often difficult to locate, and resection in an early phase is recommended to prevent complications.

Local treatment in unresectable hepatic metastases of carcinoid tumors: Experiences with hepatic artery embolization and radiofrequency ablation.

Background: Hepatic metastases of carcinoid tumors cause incapacitating symptoms, but are usually diffuse and therefore unresectable. In this article we evaluate our experiences with local treatment techniques in the management of carcinoid patients with hepatic metastases and failing systemic treatment.

Methods: Fifteen consecutive carcinoid patients (11 men and 4 women; median age 60 years; range 45-71 years) were treated with either hepatic artery embolization (HAE) with Ivalon particles or radiofrequency ablation (RFA) (percutaneously or intra-operatively).

Metastatic carcinoid tumors: a clinical review.

Carcinoid tumors are neuroendocrine tumors derived from enterochromaffin cells, which are widely distributed in the body. They can originate from any location in the body, but they are traditionally described as originating from the foregut, midgut, and hindgut. Although the overall incidence of carcinoid tumors appears to have increased in the past decades, the prognosis for patients with metastatic carcinoid tumors has improved during the last decade.

Screening behavior of individuals at high risk for colorectal cancer.

Background And Aims: Periodic colonoscopy is an effective means of reducing the incidence and mortality of colorectal cancer in individuals with a family history of the disease. The aims of this study were to determine the degree of compliance and to identify the factors related significantly to noncompliance with periodic screening in this high-risk population.

Methods: A total of 178 individuals who had undergone genetic counseling for colorectal cancer between 1986 and 1998 and who had been advised to undergo periodic screening because of familial colorectal cancer (FCRC) or hereditary nonpolyposis colorectal cancer (HNPCC) were invited to complete a self-report questionnaire on psychosocial issues and screening experiences.

Daily cyclic changes in the urinary excretion of 5-hydroxyindoleacetic acid in patients with carcinoid tumors.

Background: Vasoactive peptides produced by neuroendocrine tumors can induce characteristic symptoms of the carcinoid syndrome (flushing, diarrhea, and wheezing). To what extent external factors provoke these symptoms and how excretion of 5-hydroxyindoleacetic acid (5-HIAA), the degradation product of serotonin, varies throughout the day remain unknown. In this study, we investigated whether symptoms and daily activity are related to 5-HIAA excretion and whether 24-h urine collection is needed.

On the use of vignettes for eliciting test-selection strategies.

Decision-support systems often include a strategy for selecting tests in their field of application. This strategy in essence captures procedural knowledge and serves to provide support for the reasoning processes involved. Generally, a test-selection strategy is offered in which tests are selected sequentially.

Carcinoid heart disease: the role of urinary 5-hydroxyindoleacetic acid excretion and plasma levels of atrial natriuretic peptide, transforming growth factor-beta and fibroblast growth factor.

Background: Serotonin excretion plays a role in the development of carcinoid heart disease (CHD), but the exact pathogenesis is not known. In the current study, the authors evaluated 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion, as well as plasma levels of transforming growth factor-beta (TGF-beta), fibroblast growth factor (FGF), and atrial natriuretic peptide (ANP) in patients with and without CHD determined by ultrasound examination.

Methods: Urine and plasma samples were obtained for 37 patients and cardiac ultrasound was performed during follow-up in 1999 and 2000.

Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families.

Purpose: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive surveillance program.

Classification of low-grade neuroendocrine tumors of midgut and unknown origin.

Metastasized neuroendocrine tumors of the gastrointestinal tract and of unknown origin show a highly variable clinical course. Within this group, low-grade and high-grade malignant tumors can be recognized based on the revised classification of neuroendocrine tumors of the lung, pancreas, and gut published by Capella et al in 1995. The present study investigated whether fine-tuning the prediction of prognosis was possible by dividing the group of low-grade malignant tumors of the midgut and of unknown origin into typical and atypical carcinoids by grading them according to the World Health Organization (WHO) classification criteria for neuroendocrine tumors of the lung.

T(11;18) is a marker for all stage gastric MALT lymphomas that will not respond to H. pylori eradication.

Background & Aims: Eradication of Helicobacter pylori leads to cure of gastric mucosa-associated lymphoid tissue (MALT) lymphoma in 75% of localized cases. However, prolonged follow-up is necessary to determine whether a lymphoma responds to therapy. In a small series of cases, we showed that t(11;18)(q21;q21)-positive MALT lymphomas failed to respond to H.