Differential diagnosis of thyroid orbitopathy - diseases mimicking the presentation or activity of thyroid orbitopathy.

Thyroid orbitopathy (TO) is the most common cause of orbital tissue inflammation, accounting for about 60% of all orbital inflammations. The inflammatory activity and severity of TO should be diagnosed based on personal experience and according to standard diagnostic criteria. Magnetic resonance imaging (MRI) of the orbit is used not only to identify swelling and to differentiate inflammatory active from non-active TO, but also to exclude other pathologies, such as orbital tumours or vascular lesions. However, a group of diseases can mimic the clinical manifestations of TO, leading to serious diagnostic difficulties, especially when the patient has previously been diagnosed with a thyroid disorder. Diagnostic problems can be presented by cases of unilateral TO, unilateral or bilateral TO in patients with no previous or concomitant symptoms of thyroid disorders, lack of symptoms of eyelid retraction, divergent strabismus, diplopia as the only symptom of the disease, and history of increasing diplopia at the end of the day. The lack of visible efficacy of ongoing immunosuppressive treatment should also raise caution and lead to a differential diagnosis of TO. Differential diagnosis of TO and evaluation of its activity includes conditions leading to redness and/or swelling of the conjunctiva and/or eyelids, and other causes of ocular motility disorders and eye-setting disorders. In this paper, the authors review the most common diseases that can mimic TO or falsify the assessment of inflammatory activity of TO.

Transforming growth factors ß and their signaling pathway in renal cell carcinoma and peritumoral space-transcriptome analysis.

PURPOSE: The aim of the study was to verify hypotheses: Are transforming growth factors TGFß1-3, their receptors TGFßI-III, and intracellular messenger proteins Smad1-7 involved in the pathogenesis of kidney cancer? What is the expression of genes of the TGFß/Smads pathway in renal cell carcinoma (RCC) tissues, peritumoral tissues (TME; tumor microenvironment), and in normal kidney (NK) tissue?. METHODS: Twenty patients with RCC who underwent total nephrectomy were included into the molecular analysis. The mRNA expression of the genes was quantified by RT-qPCR. RESULTS: The study showed that the expression of the genes of TGFß/Smads pathway is dysregulated in both RCC and the TME: TGFß1, TGFß3 expression is increased in the TME in comparison to the NK tissues; TGFß2, TGFß3, TGFßRI, TGFßRIII, Smad1, Smad2, Smad3, and Smad6 are underexpressed in RCC comparing to the TME tissues; TGFßRI, TGFßRIII, and Smad2 are underexpressed in RCC in comparison to the NK tissues. CONCLUSION: On the one hand, the underexpression of the TGFß signaling pathway genes within the malignant tumor may result in the loss of the antiproliferative and pro-apoptotic activity of this cytokine. On the other hand, the overexpression of the TGFß/Smads pathway genes in the TME than in tumor or NK tissues most probably results in an immunosuppressive effect in the space surrounding the tumor and may have an antiproliferative and pro-apoptotic effect on non-neoplastic cells present in the TME. The functional and morphological consistency of this area may determine the aggressiveness of the tumor and the time in which the neoplastic process will spread.

[Multiple bone fractures caused by severe hypophosphatemia in the course of the mandible tumour].

Not required for Clinical Vignette.

[Optimization of the treatment of moderate to severe and active thyroid orbitopathy considering the recommendations of the European Group on Graves' Orbitopathy (EUGOGO) [Optymalizacja leczenia umiarkowanej do ciezkiej i aktywnej orbitopatii tarczycowej z uwzglednieniem zalecen European Group on Graves' Orbitopathy (EUGOGO)]].

Graves' disease (GB), also known as Basedow's disease, is the most common cause of hyperthyroidism, and thyroid orbitopathy (TO) is its most common non-thyroid manifestation with an incidence of 42.2/million people/year. Based on the guidelines of the European Graves' Orbitopathy Group (EUGOGO), certain management standards presented in our publication should be used to optimize and improve the efficacy of TO treatment. Deciding on the optimal treatment for both hyperthyroidism and TO requires a cooperative team of specialists: endocrinologist, ophthalmologist, radiation therapist, and surgeon, as well as consideration of the risk of relapse and possible complications of the treatment method. The inflammatory activity and severity of TO should be diagnosed based on the investigator's own experience and according to standard diagnostic criteria. Assessment of the inflammatory activity of TO can be performed using the clinical activity score (CAS) and using imaging methods - mainly MRI. The severity of TO is assessed using a seven-grade NOSPECS classification and a three-grade EUGOGO scale. In moderate to severe and active TO, i.v. methylprednisolone pulses are the treatment of choice. It is important to maintain the standard and regimen of treatment. The recommended standard as first-line treatment in most patients with moderate to severe and active TO is the combined use of methylprednisolone i.v. (cumulative dose of 4.5 g over 12 weeks) with concurrent administration of mycophenolate sodium 0.72 g per day for 24 weeks. In more severe forms of moderate to severe and active TO, a higher cumulative dose of methylprednisolone i.v. is recommended as an alternative first-line treatment (7.5 g) as monotherapy starting with a dose of 0.75 g once a week for 6 weeks and 0.5 g for a further 6 weeks. EUGOGO guidelines recommend that in cases of no clinical response after 6 weeks of first-line treatment with i.v. methylprednisolone and mycophenolate, after 3-4 weeks, a second course of i.v. methylprednisolone monotherapy should be started with a higher cumulative dose of 7.5 g. Other second-line treatment options are orbital radiotherapy with or without oral or i.v. systemic glucocorticosteroid therapy, cyclosporine, or azathioprine in combination with p.o. glucocorticosteroid, methotrexate monotherapy, and a group of biologic drugs rituximab, tocilizumab, teprotumumab). Keeping in mind that TO is a sight-threatening disease, we expect, through the treatment applied, to maintain full visual acuity, pain relief, single vision in the useful part of the visual field, and a positive cosmetic effect.

Update of the diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours) [Aktualizacja zalecen ogólnych dotyczacych postepowania diagnostyczno-terapeutycznego w nowotworach neuroendokrynnych ukladu pokarmowego (rekomendowane przez Polska Siec Guzów Neuroendokrynnych)].

Continuous progress in the diagnostics and treatment of neuroendocrine neoplasms (NENs), the emerging results of new clinical trials, and the new guidelines issued by medical societies have prompted experts from the Polish Network of Neuroendocrine Tumours to update the 2017 recommendations regarding the management of neuroendocrine neoplasms. This article presents the general recommendations for the management of NENs, resulting from the findings of the experts participating in the Fourth Round Table Conference, entitled "Polish Guidelines for the Diagnostics and Treatment of Neuroendocrine Neoplasms of the gastrointestinal tract, Zelechów, June 2021". Drawing from the extensive experience of centres treating these cancers, we hope that we have managed to formulate the optimal method of treating patients with NENs, applying the latest reports and achievements in the field of medicine, which can be effectively implemented in our country. The respective parts of this work present the approach to the management of: NENs of the stomach and duodenum (including gastrinoma), pancreas, small intestine, and appendix, as well as large intestine.

Pancreatic neuroendocrine neoplasms - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne trzustki - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polska Siec Guzów Neuroendokrynych)].

In this paper, we present the current guidelines for the diagnostics and management of pancreatic neuroendocrine neoplasms (PanNENs) developed by Polish experts providing care for these patients in everyday clinical practice. In oncological diagnostics, in addition to biochemical tests, molecular identification with the use of NETest liquid biopsy and circulating microRNAs is gaining importance. Both anatomical and functional examinations (including new radiopharmaceuticals) are used in imaging diagnostics. Histopathological diagnosis along with immunohistochemical examination still constitute the basis for therapeutic decisions. Whenever possible, surgical procedure is the treatment of choice. Pharmacological management including biotherapy, radioisotope therapy, targeted molecular therapy and chemotherapy are important methods of systemic therapy. Treatment of PanNENs requires a multidisciplinary team of specialists in the field of neuroendocrine neoplasms.

Gastroduodenal neuroendocrine neoplasms including gastrinoma - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne zoladka i dwunastnicy z uwzglednieniem gastrinoma - uaktualnione zasady postepowania (rekomendowane przez Polska Siec Guzów Neuroendokrynnych)].

After another meeting of experts of the Polish Network of Neuroendocrine Tumours, updated recommendations for the management of patients with gastric and duodenal neuroendocrine neoplasms, including gastrinoma, have been issued. As before, the epidemiology, pathogenesis and clinical symptoms of these neoplasms have been discussed, as well as the principles of diagnostic procedures, including biochemical and histopathological diagnostics and tumour localisation, highlighting the changes introduced in the recommendations. Updated principles of therapeutic management have also been presented, including endoscopic and surgical treatment, and the options of pharmacological and radioisotope treatment. The importance of monitoring patients with gastric and duodenal NENs, including gastrinoma, has also been emphasised.

Colorectal neuroendocrine neoplasms - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne jelita grubego - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polska Siec Guzów Neuroendokrynych)].

Colorectal neuroendocrine neoplasm (CRNEN), especially rectal tumours, are diagnosed with increased frequency due to the widespread use of colonoscopy, including screening examinations. It is important to constantly update and promote the principles of optimal diagnostics and treatment of these neoplasms. Based on the latest literature and arrangements made at the working meeting of the Polish Network of Neuroendocrine Tumours (June 2021), this paper includes updated and supplemented data and guidelines for the management of CRNEN originally published in Endokrynologia Polska 2017; 68: 250-260.

Neuroendocrine neoplasms of the small intestine and the appendix - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne jelita cienkiego i wyrostka robaczkowego - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polska Siec Guzów Neuroendokrynnych)].

Updated Polish recommendations for the management of patients with neuroendocrine neoplasms (NENs) of the small intestine (SINENs) and of the appendix (ANENs) are presented here. The small intestine, and especially the ileum, is one of the most common locations for these neoplasms. Most of them are well-differentiated and slow-growing tumours; uncommonly - neuroendocrine carcinomas. Their symptoms may be untypical and their diagnosis may be delayed or accidental. Najczesciej pierwsza manifestacja ANEN jest jego ostre zapalenie. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of SINENs patients with distant metastases. In laboratory diagnostics the assessment of 5-hydroxyindoleacetic acid concentration is helpful in the diagnosis of carcinoid syndrome. The most commonly used imaging methods are ultrasound examination, computed tomography, magnetic resonance imaging, colonoscopy and somatostatin receptor imaging. Histopathological examination is crucial for the proper diagnosis and treatment of patients with SINENs and ANENs. The treatment of choice is a surgical procedure, either radical or palliative. Long-acting somatostatin analogues (SSAs) are essential in the medical treatment of functional and non-functional SINENs. In patients with SINENs, at the stage dissemination with progression during SSAs treatment, with high expression of somatostatin receptors, radioisotope therapy should be considered first followed by targeted therapies - everolimus. After the exhaustion of the above available therapies, chemotherapy may be considered in selected cases. Recommendations for patient monitoring are also presented.

The impact of levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with autoimmune hypothyroidism and early-onset androgenetic alopecia.

INTRODUCTION: Administration of testosterone or dehydroepiandrosterone to subjects with low levels of these hormones was found to reduce thyroid antibody titres. Male-pattern baldness is accompanied by mildly increased androgen levels. The present study was aimed at investigating whether early-onset androgenetic alopecia determines the impact of exogenous levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in young men with autoimmune hypothyroidism. MATERIAL AND METHODS: The study included 2 thyroid-antibody-matched groups of men with autoimmune hypothyroidism: subjects with early-onset androgenetic alopecia (group 1; n = 24) and subjects with no evidence of hair loss (group 2; n = 24). All patients were treated with exogenous levothyroxine. Circulating titres of thyroid peroxidase and thyroglobulin antibodies, as well as levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin, total testosterone, calculated bioavailable testosterone, dehydroepiandrosterone-sulphate, and oestradiol were measured before levothyroxine treatment and 6 months later. RESULTS: In both study groups, levothyroxine decreased thyroid antibody titres, reduced thyrotropin levels and increased free thyroid hormone levels. However, these effects were less pronounced in the men with early-onset male-pattern baldness than in the control men. The degree of reduction in antibody titres and thyrotropin levels correlated with baseline levels of total and calculated bioavailable testosterone, as well with baseline insulin sensitivity and treatment-induced improvement in insulin sensitivity. Concentrations of the remaining variables remained unchanged throughout the study period. CONCLUSIONS: The results of the current study suggest that the benefits of levothyroxine therapy in men with autoimmune hypothyroidism are less pronounced in individuals with early-onset androgenetic alopecia.

Therapeutic effect of presurgical treatment with longacting octreotide (Sandostatin® LAR®) in patients with acromegaly.

INTRODUCTION: The aim of this study was to assess the therapeutic effect and the safety of pre-surgical treatment with long-acting octreotide in patients with acromegaly. MATERIAL AND METHODS: This project was conducted in 25 centres across Poland as a non-interventional, multicentre, observational study in patients with acromegaly, in which long-acting octreotide Sandostatin® LAR®) was administered before surgery. They were 148 patients included into the study: 88 females and 60 males aged 18-86 years (51.3 ± 13.4). RESULTS: Eighty patients completed the study (underwent tumour surgery). The CRF included: baseline visit, four follow-up visits every three months before surgery, and two follow-up visits every three months after surgery. Sandostatin® LAR® was administered every four weeks. The efficacy measures were as follows: change of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, number of patients fulfilling criteria of cure, and change of adenoma (micro- and macroadenomas) size during the treatment. Normalisation of GH and IGF-1 concentrations were obtained in 42.4 and 49.1% of patients at the end of medical therapy, respectively. Normalisation of GH and IGF-1 concentrations were obtained in 77.9 and 83.8% of patients after surgery, respectively. Reduction of microadenoma size was documented in 58.8% of patients, and in 70% of patients with macroadenomas at the end of medical therapy. In 74.0% of patients no pituitary tumour was shown on MRI after surgery. CONCLUSION: We have shown good surgical outcome in patients with acromegaly after pre-treatment with somatostatin analogue, and good tolerance and safety of the therapy, supporting the national recommendation for pre-surgical treatment with long-acting somatostatin analogues in acromegaly patients.

Antibodies involved in the development of pernicious anemia and other autoimmune diseases.

INTRODUCTION: Pernicious anemia (PA) is an autoimmune hematopoietic disease. OBJECTIVES: The aim of the study was to determine autoantibodies involved in the pathogenesis of PA and the development of other autoimmune disorders such as connective tissue diseases and celiac disease. We also aimed to assess the potential usefulness of the specific diagnostic and screening tests in patients with PA. PATIENTS AND METHODS: The study group comprised 124 women and men with newly diagnosed PA and 41 healthy controls. Intrinsic factor (IF) antibodies, gastric parietal cell (GPC) antibodies, endomysium antibodies (EmAs), and antinuclear antibodies (ANAs) were determined in blood samples. RESULTS: IF or GPC antibodies were present in 61.3% of patients, GPC antibodies, in 46%, IF antibodies, in 30.6%, IF and GPC antibodies, in 15.3%. There was no difference in the occurrence of ANAs and EmAs between the PA and control groups. However, ANAs were found in 16.1% of patients with PA and in 4.9% of controls. The occurrence of EmAs in both groups was similar (3.2% vs 2.4%); however, it has been shown that patients with IF or GPC antibodies are more prone to be EmA positive (P = 0.009). CONCLUSIONS: Simultaneous determination of IF and GPC antibodies increases the chances of confirming the diagnosis of PA. Also, screening for connective tissue diseases and celiac disease may be considered in patients with PA, due to the presence of ANAs and EmAs in that population.

Selected adipose tissue hormones in the blood of patients with ischaemic cerebral stroke.

INTRODUCTION: Despite considerable progress in knowledge, ischaemic stroke is still a disease that causes serious clinical problems. A role in its pathogenesis can be attributed to i.a. adipose tissue hormones. The aim of this paper is to assess the blood levels of selected adipocytokines in patients during the acute phase of ischaemic stroke as compared to healthy persons, and an attempt to indicate a correlation between their blood concentrations and the level of stroke severity and its outcomes. MATERIAL AND METHODS: The study included 46 patients with fresh ischaemic stroke (27 females, 19 males, average age 67.6 years). All patients had a CT scan of the head, their neurological condition was assessed using a stroke severity scale, and their blood levels of resistin, chemerin, and visfatin were tested. The control group consisted of 32 patients (16 females, 16 males, average age 64.1 years) who had never suffered cerebrovascular diseases. RESULTS: Elevated levels of both resistin and chemerin were found in the group of patients with ischaemic stroke (9.17 ± 2.95 ng/mL vs. 6.55 ± 2.01 ng/mL for resistin and 265.0 ± 59.3 ng/mL vs. 191.0 ± 43.6 ng/mL for chemerin). It was also found that the blood concentration of chemerin was higher in females than in males with stroke. However, no difference was found in visfatin blood concentration between the group with ischaemic stroke and the control group (1.65 ± 1.09 ng/mL vs. 1.5 ± 1.39 ng/mL). CONCLUSIONS: Higher resistin and chemerin blood concentrations significantly increase the risk of ischaemic stroke. The level of stroke severity at the moment of its occurrence and during its course do not depend on the concentrations of adipocytokines under analysis.

Assessment of selected adipocytokines in obese women with postmenopausal osteoporosis.

INTRODUCTION: Osteoporosis and obesity are considered civilisation diseases. Menopause is a time of increased bone resorption and increased mass of adipose tissue. Adipocytokines secreted by the adipose tissue are believed to be a potential factor in the pathogenesis of osteoporosis. MATERIAL AND METHODS: The aim of this research was to assess leptin, adiponectin, and resistin secretion in obese postmenopausal women with osteoporosis and determine whether obesity might be a factor mitigating the risk of osteoporosis. The study involved 80 postmenopausal women with osteoporosis divided into groups: I with BMI of 30.0 34.9, obese; and II with BMI of 18-24.9, normoweight. Leptin, adiponectin and resistin concentrations were assessed, and bone mineral density (BMD) was measured in the L1-L4 section of the spine using the DXA densitometric method. RESULTS: The results of the comparison of the two groups indicate a statistically significant dependence in groups regarding leptin secretion; the group of obese women demonstrated significantly higher concentrations. No differences between the groups were demonstrated for adiponectin or resistin secretion. CONCLUSIONS: Higher leptin concentration and a positive correlation with BMI was confirmed in obese postmenopausal women with osteoporosis. It was also demonstrated that BMD increases with growing BMI. No effect of obesity on the secretion of adiponectin or resistin in women with postmenopausal osteoporosis was found. From among the investigated adipocytokines, only leptin can be considered a bone tissue protective factor in postmenopausal women.

Sexual function and depressive symptoms in men with overt hyperthyroidism.

INTRODUCTION: Although hyperthyroidism is characterised by female predominance, its presence may lead to the development of numerous complications in both sexes. This study was aimed at investigating sexual function and depressive symptoms in men with overt hyperthyroidism of autoimmune and non-autoimmune origin. MATERIAL AND METHODS: The study population consisted of three age-matched groups: men with overt hyperthyroidism and Graves' disease (group A; n = 20), men with overt hyperthyroidism and toxic multinodular goitre or toxic adenoma (group B; n = 21), and men with normal thyroid function (group C; n = 23). As well as measuring serum hormone levels and antibody titres, and determining calculated parameters of thyroid homeostasis, all included patients filled in questionnaires evaluating sexual function (International Index of Erectile Function-15: IIEF-15) and assessing the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition - BDI-II). RESULTS: Compared with control subjects, men with overt hyperthyroidism obtained lower scores for erectile function, intercourse satisfaction, orgasmic function and overall satisfaction. Scores for erectile function, orgasmic function, and sexual desire differed between both groups of men with thyroid hyperfunction and inversely correlated with thyrotropin receptor antibody titres. The BDI-II score was higher in patients with Graves' disease than in men with normal thyroid function. CONCLUSIONS: The obtained results indicate that overt hyperthyroidism in men causes multidimensional impairment of sexual function, which is particularly pronounced if excessive hormone production results from Graves' disease.

Serum concentrations of adipokines in men with prostate cancer and benign prostate hyperplasia.

INTRODUCTION: Obesity and prostate cancer are related, but the causal relationship remains unknown. The aim of the study was to compare concentrations of leptin, adiponectin and chemerin in patients with prostate cancer and benign prostate hyperplasia and to examine associations of the adipokines with the grade of prostate cancer, interleukin-6 (IL-6), insulin resistance and anthropometric and metabolic variables. MATERIAL AND METHODS: The study group consisted of 140 men divided into two groups: I- prostate cancer (n=74) and II- with benign hyperplasia (n=66). Serum leptin, adiponectin, chemerin, IL-6 and metabolic profile were measured. Considering histological differentiation prostate cancer patients were divided into 3 subgroups: well differentiated (Gleason score ≤ 6), moderately differentiated subgroup (Gleason 7), and poorly differentiated (Gleason ≥8). RESULTS: There were no differences between groups in BMI, waist circumference, HOMA-I, serum levels of total cholesterol, glucose, triglycerides, adiponectin, leptin and chemerin. However, the concentrations of PSA, leptin-to-adiponectin ratio and IL-6 were significantly higher in cancer group compared with benign hyperplasia group. In the poorly differentiated cancer subgroup, subjects had higher PSA, leptin, chemerin, IL-6 and triglycerides concentrations. Overweight and obese men with prostate cancer were more likely to have moderately or poorly differentiated cancer than those with normal BMI. In the all men serum adiponectin was significantly correlated with HOMA-I, BMI, glucose, triglycerides, cHDL. There were significant correlations between leptin and BMI, HOMA-I, waist, glucose, triglycerides and cHDL. Among all the participants we observed associations between chemerin and waist as well as triglycerides. In prostate cancer patients chemerin correlated with IL-6 and leptin. We measured significant positive correlations between Gleason score and chemerin and leptin concentrations. There was a positive correlation between adiponectin and PSA levels in all men, as well as in cancer group. CONCLUSION: Leptin-to-adiponectin ratio and IL-6 were elevated in men with prostate cancer. Leptin, chemerin and IL-6 were associated with Gleason score. The relationships between leptin, chemerin and IL-6 were dependent on each other. Overweight and obese men had a higher Gleason score.

Metformin - a new old drug.

For many years metformin has been the gold standard in the treatment of type 2 diabetes. According to recommendations of the most important diabetes associations, this is the first-choice drug for use as monotherapy in patients with newly diagnosed type 2 diabetes. Metformin is also recommended in combined treatment when monotherapy is no longer effective. It is then combined with a sulfony-lurea, an incretin, flozin, or insulin, irrespective of the number of insulin injections per day. Besides its properties used in the treatment of diabetes, metformin has been treated for some time as a drug of a so-called pleiotropic activity, as each year brings new reports about its favourable effect in different conditions. At present, the scope of reimbursed indications of this drug has been expanded to include prediabetes, insulin resistance syndromes, and polycystic ovary syndrome. Metformin does not stimulate insulin secretion by the beta cells of the pancreas, and thus it is a drug that does not cause hypoglycaemia. The blood glucose-lowering effect of the drug is a consequence of hepatic glucose production inhibition, and of peripheral tissue (muscle tissue, fatty tissue) sensitisation to the effect of insulin of both endogenous and exogenous origin. The exact mechanism of metformin action at the cellular level remained unknown for a long time. Studies performed in recent years have provided a great deal of information that enables better understanding of the mechanism of action of the drug as well as the clinical effects resulting from its use. Metformin, besides improvement of glycaemia, is neutral to body weight, is cardioprotective, improves lipid profile, and has a probable anti-cancer effect. Metformin accumulation in the intestinal mucosa may interfere with FDG (18F-deoxyglucose) PET-CT image assessment. The aim of this article is a detailed discussion of metformin properties, its mechanisms of action, and clinical effects.

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.