Spatio-temporal image correlation (STIC) in evaluation of advanced neuroendocrine tumours.

INTRODUCTION: 4D Ultrasound technology merging the Power Doppler option called High-Definition Flow (HDF) with Spatio-Temporal Image Correlation (STIC) is used in gynaecology and obstetrics. It seems to be a promising tool in assessing tissue vascularisation. The aim of the paper was to assess whether HDF STIC technique could be a useful tool for the evaluation of gastro-entero-pancreatic neuroendocrine neoplasm (GEP-NEN) advancement. MATERIAL AND METHODS: Forty-eight patients [mean age 57.7 ± 10.3 years; male 40.9% (n = 18)] diagnosed with metastatic GEP-NENs were included in the analysis. All subjects were enrolled in the Department of Endocrinology and Neuroendocrine Tumours, Medical University of Silesia, Katowice. We analysed liver metastases. Patients with G3 grading or faintly vascularised lesions were excluded. HDF STIC volumes were acquired during USG examination. 4D indices [volumetric pulsatility index (vPI) and volumetric systolic/diastolic index (vS/D)] were calculated using dedicated software. RESULTS: There were no correlations between vS/D and Ki-67 [p = 0.67; r = -0.19; (-0.28-0.19)], CgA [p = 0.47; r = -0.11; (-0.38-0,19)], 5-HIAA [p = 0.52; r = -0.09 (-0.37-0.2)], serotonin [p = 0.83; r = -0.03 (-0.32-0.26)], and VCAM-1 (p = 0.62; r = 0.09 (-03-0.47)]. The were no correlations between vPI and Ki-67 [p = 0.29; r = -0.16 (-0.45-0.14)], CgA (p = 0.46; r = -0.11 (-0.39-0.19)], 5-HIAA [p = 0.52; r = -0.09 (-0.37-0.2)], serotonin [p = 0.82; r = -0.03 (-0.32-0.26)], and VCAM-1 (p = 0.62; r = -0.09 (-03-0.47)]. There was no significant difference between carcinoid versus non-carcinoid patients if compared by vS/D and vPI (p = 0.62, p = 0.61, respectively). CONCLUSIONS: HDF STIC seems not to be an efficient marker to assess advancement of NENs, due to lack of correlation with widely used and approved markers of progression.

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Zelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.

Gastroduodenal neuroendocrine neoplasms, including gastrinoma - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis, and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological, and localisation diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments. Finally, there are also recommendations on patient monitoring.

Pancreatic neuroendocrine neoplasms - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

This article presents updated diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine tumours (PNEN), proposed by the Polish Network of Neuroendocrine Tumours. The guidelines contain new data received in the years 2013-2016, which confirm previous recommendations, and have led to modification of previous guidelines or have resulted in the formulation of new guidelines. Biochemical and imaging (anatomical and functional) tests are of great importance in diagnostics, as well as histopathological diagnosis to determine the management of PNEN patients, but they must be confirmed by an immunohistochemical examination. PNEN therapy requires collaboration among the members a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment in many cases. Further therapy requires a multidirectional procedure; therefore, the rules of biotherapy, peptide receptor radionuclide therapy, molecular targeted therapy, and chemotherapy are discussed.

Neuroendocrine neoplasms of the small intestine and appendix - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

This study presents the revised Polish guidelines regarding the management of patients suffering from neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common location for these neoplasms. Most are well differentiated and slow growing. Their symptoms may be atypical, which can result in delayed or accidental diagnosis. Appendicitis is usually the first manifestation of NEN in this location. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of patients suffering from small intestinal NENs with distant metastases. The main cause of death in patients with carcinoid syndrome is carcinoid heart disease. The most useful laboratory test is the determination of chromogranin A, while concentration of 5-hydroxyindoleacetic acid is helpful in the diagnostics of carcinoid syndrome. For visualisation, ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, double-balloon enteroscopy, and somatostatin receptor scintigraphy may be used. A detailed his-tological report is crucial for the proper diagnostics and therapy of NENs of the small intestine and appendix. The treatment of choice is surgical management, either radical or palliative. The pharmacological treatment of the hormonally active and non-active small intestinal NENs as well as NENs of the appendix is based on long-acting somatostatin analogues. In patients with generalised NENs of the small intestine in progress during the SSA treatment, with good expression of somatostatin receptors, the first-line treatment should be radio-isotope therapy, while targeted therapies, such as everolimus, should be considered afterwards. When the above therapies are exhausted, in certain cases chemotherapy may be considered.

Colorectal neuroendocrine neoplasms - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

Neuroendocrine neoplasms/tumours (NENs/NETs) of the large intestine are detected increasingly often, especially rectal tumours, which is probably associated with the widespread use of screening colonoscopy. There is a growing body of evidence supporting the thesis that the NENs of the rectum and the NENs of the colon are two different diseases. Rectal NENs are usually small lesions, of low to moderate histological malignancy, associated with good prognosis, and most may be treated endoscopically. NENs of the colon, however, are often aggressive, poorly differentiated, associated with a poor or uncer-tain prognosis, and require surgical treatment. The management guidelines regarding these groups of patients are constantly changing. On the basis of the recent literature data and conclusions reached by the working meeting of the Polish Network of Neuroendocrine Tumours (December 2016), this study completes and updates the data and management guidelines regarding colorectal NENs published in Endokrynologia Polska 2013; 64: 358-368.

An atypical course of pancreatic neuroendocrine tumour manifesting as cardiac metastasis - a clinical case.

This paper presents a ten-year course of the disease in a patient with pancreatic neuroendocrine tumour NEN G1, and with confirmed single, asymptomatic metastasis to the left cardiac ventricle. Initially, the cardiac metastasis was visible only on a positron emission tomography (PET) scan using gallium-68-labelled somatostatin analogue; the sensitivity of an echocardiography scan was lower. Despite the advanced stage of the disease, surgical excision of the cardiac metastasis was performed. The patient underwent a total of eight operations, and received chemotherapy, radiotherapy and somatostatin analogues. Currently, he is on a targeted therapy with everolimus. As a result of the treatment, the patient remains in a good general condition. This is the second described case of cardiac metastasis of PNEN. Using different methods of treatment in the case of generalised pancreatic neuroendocrine tumour with low proliferative potential, patients are offered the chance to prolong their survival and maintain a good quality of life.

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

An increased interest in gastro-entero-pancreatic neuroendocrine neoplasms (GEP NENs) has recently been observed. These are rare neoplasms and their detection in recent years has improved. Over 50% of GEP NENs are carcinoids, and they are usually found incidentally during surgery in the small intestine and appendix and at diagnosis in distant metastases, mainly to the liver. There is a need for co-operation between specialists in various disciplines of medicine in order to work out the diagnostic and therapeutic guidelines. In this publication, we present general recommendations of the Polish Network of Neuroendocrine Tumours for the management of patients with GEP NENs, developed at the Consensus Conference which took place in Kamien Slaski in April 2013. Members of the guidelines working groups were assigned sections of the 2008 guidance to update. In the subsequent parts of this publication, we present the rules of diagnostic and therapeutic management of: - neuroendocrine neoplasms of the stomach and duodenum (including gastrinoma); - pancreatic neuroendocrine neoplasms; - neuroendocrine neoplasms of the small intestine and the appendix; - colorectal neuroendocrine neoplasms. The proposed recommendations by Polish and foreign experts representing different fields of medicine (endocrinology, gastroenterology, surgery, oncology, nuclear medicine and pathology) will be helpful in the diagnosis and treatment of GEP NENs patients.

Is determination of matrix metalloproteinases and their tissue inhibitors serum concentrations useful in patients with gastroenteropancreatic and bronchopulmonary neuroendocrine neoplasms?

INTRODUCTION: Gastroenteropancreatic (GEP) and bronchopulmonary (BP) neurendocrine neoplasms (NENs) are rare and slowly growing tumours. Matrix metalloproteinases (MMPs) degrade extracellular matrix and are responsible for invasion and metastasis. Tissue inhibitors of matrix metalloproteinases (TIMPs) affect the invasiveness of tumour cells and the formation of distant metastases. The aim of this study was to evaluate selected MMPs (MMP2 and MMP9) and their tissue inhibitors (TIMP1 and TIMP2) depending on the pTNM classification, grading, and the occurrence of metastases. MATERIAL AND METHODS: The study group consisted of 86 patients with GEP NENs. The control group consisted of 31 healthy volunteers. Serum levels of TIMP1, TIMP2, MMP2 and MMP9 were determined by ELISA (R&D Systems) in all the study subjects. The statistical calculations were performed using MedCalc. RESULTS: We observed significant differences in MMP2 and TIMP1 levels between the study group with NENs and the control group. TIMP1 levels were significantly higher in patients with high-grade NEN (NEC, neuroendocrine carcinoma) compared to patients with low-grade tumour (NET G1, neuroendocrine tumours G1) (p 〈 0.017). We also observed a significant correlation between TIMP1 levels and the presence of metastases in the group of patients with GEP NENs, and also higher TIMP1 levels than those in the patients without metastases (p 〈 0.05). We also found a higher likelihood of metastases in patients with GEP NENs with TIMP1 levels exceeding 206.4 ng/mL. CONCLUSIONS: Patients with NENs secreted larger quantities of MMP2 and TIMP1. TIMP1 may be considered a marker of metastases in patients with GEP NENs.

Selected neuroendocrine tumour markers, growth factors and their receptors in typical and atypical bronchopulmonary carcinoids.

INTRODUCTION: Bronchopulmonary neuroendocrine tumours (BP NET) cause many diagnostic and therapeutic problems. There is an ongoing search for biochemical markers of activity of these tumours. The use of polypeptide growth factors seems potentially feasible in establishing the diagnosis, prognosis and treatment of these tumours. MATERIAL AND METHODS: We included 41 patients aged 25 to 78 years with histopathologically confirmed typical and atypical bronchopulmonary carcinoid tumours and 20 healthy volunteers. We assessed the levels of specific and non-specific markers of these tumours and of selected growth factors relative to TNM classification. RESULTS: The levels of specific markers (serotonin and its metabolite, 5-hydroxyindoleacetic acid [5HIAA]) and non-specific markers (chromogranin A [CgA]) were significantly higher in patients with atypical carcinoid tumours. The serum levels of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and VEGF receptor-1 (VEGFR-1) were significantly higher in patients with carcinoid tumours versus the control group. The levels of VEGFR-1 closely correlated with TNM classification. No such correlation could, however, be confirmed for the levels of HGF, VEGF or VEGFR-2. CONCLUSIONS: Determination of CgA, serotonin and 5HIAA may be useful in the diagnosis of BP NET, particularly in atypical carcinoid tumours, and their levels depend on the presence of distant metastases. Determination of growth factors (VEGF and its receptor, VEGFR­1, and HGF) may prove useful in the clinical diagnosis of these tumours, while the assessment of VEGFR­1 expression may be helpful in tumour staging.

Selected markers of endothelial dysfunction in women with polycystic ovary syndrome.

BACKGROUND: The increased incidence of cardiovascular disease in women with polycystic ovary syndrome (PCOS) has prompted researchers to look for indicators of early atherosclerotic changes in these patients. One of the earliest stages of atherogenesis is endothelial cell dysfunction. The aim of this study was to assess the levels of selected plasma markers of endothelial injury [E-selectin, endothelin-1 (ET-1) and von Willebrand Factor antigen (vWF:Ag)] in PCOS women before and after six months of treatment. MATERIAL AND METHODS: 32 patients with PCOS aged 18-36 years (mean age 25.16 ± 5.80) were included in the study. The control group consisted of 20 healthy women matched for age and body mass. The levels of ET-1, vWF:Ag, E-selectin, fasting glucose, insulin, total cholesterol, HDL and LDL-cholesterol and triglycerides were assessed. In the PCOS group, all these tests were repeated after six months of treatment. RESULTS: The study showed higher levels of vWF:Ag (p = 0.043), E selectin (p = 0.028), insulin (p = 0.044), glucose (p = 0.036) and LDL (p = 0.006) in PCOS patients versus healthy women. A positive correlation was demonstrated between E selectin and glucose (p = 0.0001), triglycerides (p = 0.014) and uric acid (p = 0.008). vWF:Ag levels showed a positive correlation with glucose (p = 0.04) and triglycerides (p = 0.036). A positive correlation was also found between ET-1 and total cholesterol levels (p = 0.012) in PCOS women. After treatment, there was a significant reduction in E-selectin levels from baseline (p = 0.002) and an increase in the levels of HDL (p = 0.0002) and triglycerides (p = 0.033). CONCLUSIONS: Elevated levels of vWF:Ag and E selectin in PCOS women suggest endothelial dysfunction in this group of patients. Glucose and triglyceride are significant factors affecting endothelial function in PCOS.

Polypeptide growth factors in gastroenteropancreatic neuroendocrine tumours.

Polypeptide growth factors form a potent class of extracellular signal molecules in the regulation of cellular differentiation and proliferation. Disturbances in the expression of growth factors influence the normal pathway of differentiation and lead to cellular transformation and tumour progression. Contemporary medical studies report that various growth factors such as those for platelet-derived growth factor, vascular endothelial growth factor, epidermal growth factor, hepatocyte growth factor and insulin-like growth factor are expressed in gastroenteropancreatic neuroendocrine tumours (GEP/NET). Polypeptide growth factors have great significance in the growth, progression and development of metastases by various tumours. We describe the role of growth factors in GEP/NET on the basis of the available reports of medical research.