Wanda Foltyn

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

We present revised Polish guidelines regarding the management of patients harbouring neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common origin of these neoplasms. Most of them are well differentiated with slow growth. Rarely, they are less differentiated, growing fast with a poor prognosis. Since symptoms can be atypical, the diagnosis is often accidental. Typical symptoms of carcinoid syndrome occur in less than 10% of patients. The most useful laboratory marker is chromogranin A; 5-hydroxyindoleacetic acid is helpful in the monitoring of carcinoid syndrome. Ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, balloon enteroscopy and somatostatin receptors scintigraphy are used in the visualisation. A histological report is crucial for the proper diagnostics and therapy of NENs, and it has been extensively described. The treatment of choice is surgery, either radical or palliative. Somatostatin analogues are crucial in the pharmacological treatment of the hormonally active and non-active small intestine NENs and NENs of the appendix. Radioisotope therapy is possible in patients with a good expression of somatostatin receptors. Chemotherapy is not effective in general. Everolimus therapy can be applied in patients with generalised NENs of the small intestine in progression and where there has been a failure or an inability to use other treatment options. Finally, we make recommendations regarding the monitoring of patients with NENs of the small intestine and appendix.

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 Kamień Śląski 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.

Associations between metabolic syndrome, serum thyrotropin, and thyroid antibodies status in postmenopausal women, and the role of interleukin-6

INTRODUCTION The prevalence of metabolic syndrome increases after menopause; however, the role of concomitant subclinical hypothyroidism has not been completely elucidated. The aim of the study was to identify associations between thyrotropin, immune status, inflammation, and metabolic syndrome in postmenopausal women. The specific goals were: to assess thyrotropin (TSH) and interleukin-6 (IL-6) concentrations in the serum of subclinical hypothyroid postmenopausal women with and without metabolic syndrome and compare them with euthyroid controls; to test whether immune status is related to metabolic syndrome in postmenopausal women and determine the role of IL-6; to examine the relationships between TSH and different features of metabolic syndrome: insulin resistance, waist circumferences, waist-to-hip ratio (WHR), BMI, metabolic parameters (triglycerides, total cholesterol and high-density lipoprotein cholesterol), and inflammatory cytokines (IL-6). MATERIAL AND METHODS Three hundred and seventy-two postmenopausal women were included in the study: 114 women had subclinical hypothyroidism (10.0 uIU/mL > TSH ≥ 4.5 uIU/mL, normal fT4), and 258 women were in euthyreosis (TSH 0.35-4.5 uIU/mL, normal fT4); both groups were matched by age. Anthropometric measurements were conducted (BMI, waist circumference, WHR) and blood pressure was measured. In all subjects the following were assessed in serum: lipid profile, glucose, insulin, TSH, fT4, thyroid antibodies (T-Abs) - TPO-Abs, TG-Abs, and IL-6 concentrations. RESULTS The prevalence of metabolic syndrome was 49.12% in subclinical hypothyroid women and 46.89% in euthyroid women. However, the proportion of subjects with one or two abnormalities was significantly higher in the subclinical hypothyroid group (45.61%) than in the euthyroid group (32.17%). When we compared subclinical hypothyroid women with and without metabolic syndrome, subjects with metabolic syndrome had higher BMI, abdominal circumferences, WHR, and HOMA-I. They presented higher systolic and diastolic blood pressure. Serum concentrations of cholesterol, triglycerides, fasting glucose, IL-6, TSH, T-Abs were also higher and serum cHDL was lower. There were no significant differences in fT4 concentrations. A similar comparison was made for euthyroid women with and without metabolic syndrome. Higher BMI, waist circumference, WHR, HOMA-I, and systolic blood pressure were observed in subjects with metabolic syndrome. Serum concentrations of TSH, triglycerides, glucose, and IL-6 were also higher, but the concentration of cHDL was significantly lower. There were no significant differences in fT4, T-Abs, cholesterol levels, and diastolic pressure. When we compared euthyroid women T-Abs (+) and T-Abs (-), the prevalence of metabolic syndrome was similar (48.68% vs. 46.15%). There were no differences in BMI, waist circumference, WHR, lipid profile, glucose, and HOMA-I, fT4. However, thyroid autoimmunity was associated with elevated TSH and IL-6 levels. When we analysed subclinical hypothyroid women with and without thyroid autoimmunity, there were no significant differences in glucose and lipid profile. However, Hashimoto`s subjects were more obese, had higher waist circumference, WHR, HOMA-I, and higher prevalence of metabolic syndrome. Serum concentrations of TSH and IL-6 were also higher and fT4 was lower. Among all of the women, serum TSH concentration was significantly correlated with BMI, waist circumference, WHR, systolic blood pressure, cholesterol, triglycerides, and TPO-Abs. When the variables of subjects with upper quartile of TSH were compared with lower quartile of TSH, we found significantly higher BMI, waist circumference, WHR, increased concentration of IL-6, cholesterol, triglycerides, and T-Abs, and concentrations of cHDL and fT4 were lower. OR for metabolic syndrome in subjects with upper quartile TSH vs. lower quartile was 1.35 (95% confidence interval [CI] 1.10-1.60). CONCLUSIONS Our study confirms that metabolic syndrome in both euthyroid and subclinical hypothyroid women is connected with obesity, visceral fat accumulation, and higher TSH and IL-6 concentrations. Immune thyroiditis is associated with higher TSH and IL-6 levels. Obese subclinical hypothyroid women with Hashimoto`s thyroditis have a higher prevalence of metabolic syndrome when compared with subclinical hypothyroid women without thyroid autoimmunity. It is possible that in the crosstalking between subclinical hypothyroidism and metabolic syndrome, enhanced proinflammatory cytokine release in the course of immunological thyroiditis plays a role.

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

We present revised diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine neoplasms (PNENs) proposed by the Polish Network of Neuroendocrine Tumours.These guidelines refer to biochemical (determination of specific and nonspecific neuroendocrine markers) and imaging diagnostics (EUS, CT, MR, and radioisotope examination with a 68Ga or 99Tc labelled somatostatin analogue).A histopathological diagnostic, which determines the further management of patients with PNENs, must be necessarily confirmed by immunohistochemical tests. PNENs therapy requires collaboration between a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment. Medical therapy requires a multidirectional procedure, and therefore the rules of biotherapy, peptide receptor radionuclide therapy, chemotherapy and molecular targeted therapy are discussed.

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 diagnosis. The principles of treatment are discussed, including endoscopic, surgical, pharmacological and radionuclide treatment. Finally, recommendations on patient monitoring are given.

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

Neuroendocrine neoplasms of the large intestine account for 20% of all neuroendocrine neoplasms (NENs) and are most commonly found in the rectum. The rate of detection of colorectal NENs is increasing, and this tendency will continue due to the widespread use of colonoscopy as a screening tool and the removal of all diagnosed lesions. This paper provides updated guidelines for the management of patients with colorectal NENs. Recent data on epidemiology, clinical characteristics, biochemical, and pathomorphological diagnosis as well as useful imaging techniques are presented. We look in detail at novel methods of treatment including endoscopic and surgical management, pharmacological and radioisotope therapy. We summarise monitoring of the treatment.

Zalecenia ogólne dotyczące postępowania diagnostyczno-terapeutycznego w nowotworach neuroendokrynnych układu pokarmowego (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)

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 Żelechów 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.

Assessment of real-world usage of lanreotide AUTOGEL 120 in Polish acromegalic patients – results from the prospective 12-month phase of Lanro-Study

Aim of the study To assess resource utilization and costs of treatment with lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. Material and methods A multicentre, non-interventional, observational study on resource utilization in Polish acromegalic patients treated with ATG120 at 4 weeks or extended (> 4 weeks) dosing interval. The study recruited adult acromegalic patients treated medically for ≥ 1 year including at least 3 injections of ATG120. Data on dosing interval, aspects of administration, and resource utilization were collected prospectively during 12 months. Costs were calculated in PLN from the public health-care payer perspective for the year 2013. Results 139 patients were included in the analysis. Changes in dosing regimen were reported in 14 (9.4%) patients. Combined treatment was used in 11 (8%) patients. Seventy patients (50%) received ATG120 at an extended dosing interval; the mean number of days between injections was 35.56 (SD 8.4). ATG120 was predominantly administered in an out-patient setting (77%), by health-care professionals (94%). Mean time needed for preparation and administration was 4.33 and 1.58 min, respectively, mean product wastage – 0.13 mg. Patients were predominantly treated in an out-patient setting with 7.06 physician visits/patient/year. The most common control examinations were magnetic resonance imaging of brain and brain stem (1.36/patient/year), ultrasound of the neck (1.35/patient/year), GH (1.69/patient/year), glycaemia (1.12/patient/year), IGF-1 (0.84/patient/year), pituitary-thyroid axis hormone levels assessment (TSH-0.58/patient/year, T4-0.78/patient/year). There were 0.43 hospitalizations/patient/year. For direct medical costs estimated at PLN 50 692/patient/year the main item was the costs of ATG120 (PLN 4103.87/patient/month; 97%). The mean medical cost, excluding pharmacotherapy, was PLN 1445/patient/year (out-patient care – 49%, hospitalization – 23%, diagnostics/laboratory tests – 28%). Conclusions These results represent the current use of ATG120 in the population of Polish acromegalic patients in a realistic clinical setting. Findings that 50% of patients could be treated with dose intervals of longer than 28 days support the potential of ATG120 to reduce the treatment burden.