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.

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.

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. (6) w mniej niż 10% przypadków. W diagnostyce laboratoryjnej najbardziej przydatne jest oznaczenie stężenia chromograniny A, badanie stężenia kwasu 5-hydroksyindolooctowego jest pomocne w monitorowaniu zespołu rakowiaka. W obrazowaniu stosuje się ultrasonografię, tomografię komputerową, rezonans magnetyczny, kolonoskopię, wideoendoskopię kapsułkową, enteroskopię dwubalonową, scyntygrafię receptorów somatostatynowych. Szczegółowe badanie histologiczne jest kluczowym dla właściwego rozpoznania i leczenia chorych z NEN jelita cienkiego i wyrostka robaczkowego. Leczeniem z wyboru jest postępowanie chirurgiczne, radykalne lub paliatywne. W leczeniu farmakologicznym czynnych i nieczynnych hormonalnie NEN jelita cienkiego i wyrostka robaczkowego podstawowe znaczenie mają analogi somatostatyny. Terapia radioizotopowa u chorych z dobrą ekspresją receptorów somatostatynowych stanowi kolejną opcję terapeutyczną. Chemioterapia jest na ogół nieskuteczna. U pacjentów z rozsianym NEN jelita cienkiego i progresją choroby oraz nieskutecznością innych metod terapii można zastosować ewerolimus. Przedstawiono także zalecenia odnośnie monitorowania chorych z NEN jelita cienkiego i wyrostka robaczkowego. (Endokrynol Pol 2013; 64 (6): 444-493)

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially  388 Guidelines Beata Kos-Kudła et al. Guidelinespersons/year, with the primary lesion most frequently found in the small intestine (37.4%). Since 2000, rectal NENs have been diagnosed more frequently than small intestine NENs [2, 6-8]. The incidence of GEP-NETs in the USA, based on SEER data, was 3.56/100,000 persons/year. In Europe, the incidence of GEP-NETs is also increasing -from 1.33 to 2.33/100,000 persons/year; however, these data come from different registries and are mainly retrospective. Higher incidence is observed among men (5.35/100,000 persons/year) compared to women (4.76/100,000 persons/year) [1, 5-7]. The vast majority of NENs are sporadic, well-differentiated tumours. However, GEP-NETs originating from the pancreas, duodenum, stomach, and much less frequently, from the thymus and lungs sometimes constitute an element of multiple endocrine neoplasia type 1 (MEN-1) syndrome. Pancreatic neuroendocrine tumours (PanNETs) may also be associated with von Hippel-Lindau (VHL) syndrome, tuberous sclerosis complex (TSC), and neurofibromatosis (NF). In these congenital diseases, NETs can be multifocal and occur 10-20 years earlier than in sporadic cases. The frequency of the hereditary causes (MEN-1, VHL) is estimated at about 5%. Genome studies revealed the presence of germline mutations in, e.g., MUTYH, CHEK2, and BRCA2 and a propensity to PanNETs in approximately 17% of the studied population [1]. Diagnostics Biochemical diagnosticsBiochemical diagnostics of NENs involves the following: A. Non-specific markersThe most frequently used diagnostic method is determination of the chromogranin A (CgA) concentration in the serum (less frequently in the plasma) [1,8,9]. CgA is a relatively stable protein in blood. However, there are two different methods for determining the concentration of CgA: radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) in Neuroendocrine neoplasms (NENs) arise from the disseminated system of neuroendocrine cells and can occur in various parts of the body. However, they are most often found in the gastrointestinal tract and lungs. The term NENs includes both well-differentiated neuroendocrine tumours and neuroendocrine carcinomas (NECs), which account for 10-20% of all NENs. The following characteristics of NENs should be considered in the diagnostic and therapeutic process: proliferative activity, presence of somatostatin receptors (SSTRs), tumour growth rate, and extent of the neoplastic disease [1].

 224Neuroendocrine neoplasms of the small intestine and appendix -management guidelines Bednarczuk Tomasz et al. SZKOLENIE PODYPLOMOWE AbstractThis 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 histological 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 radioisotope therapy, while targeted therapies, such as everolimus, should be considered afterwards. When the above therapies are exhausted, in certain cases chemotherapy may be considered.(Endokrynol Pol 2017; 68 (2): 223-236)