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Gastroduodenal Neuroendocrine Neoplasms, Including Gastrinoma — Management Guidelines (Recommended by the Polish Network of Neuroendocrine Tumours)

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Gastroduodenal Neuroendocrine Neoplasms, Including Gastrinoma — Management Guidelines (Recommended by the Polish Network of Neuroendocrine Tumours) SZKOLENIE PODYPLOMOWE/POSTGRADUATE EDUCATION Endokrynologia Polska DOI: 10.5603/EP.2017.0016 Tom/Volume 68; Numer/Number 2/2017 ISSN 0423–104X Gastroduodenal neuroendocrine neoplasms, including gastrinoma — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours) Michał Lipiński1*, Grażyna Rydzewska1*, Wanda Foltyn2, Elżbieta Andrysiak-Mamos3**, Agata Bałdys-Waligórska4**, Tomasz Bednarczuk5**, Jolanta Blicharz-Dorniak6**, Marek Bolanowski7**, Agnieszka Boratyn-Nowicka8**, Małgorzata Borowska6**, Andrzej Cichocki9**, Jarosław B. Ćwikła10**, Massimo Falconi11*, Daria Handkiewicz-Junak12**, Alicja Hubalewska-Dydejczyk4**, Barbara Jarząb12**, Roman Junik13**, Dariusz Kajdaniuk14**, Grzegorz Kamiński15**, Agnieszka Kolasińska-Ćwikła16**, Aldona Kowalska17**, Robert Król18**, Leszek Królicki19**, Jolanta Kunikowska19**, Katarzyna Kuśnierz20**, Paweł Lampe20**, Dariusz Lange21**, Anna Lewczuk-Myślicka22**, Andrzej Lewiński23**, Magdalena Londzin-Olesik6**, Bogdan Marek14**, Anna Nasierowska-Guttmejer24**, Ewa Nowakowska-Duława25**, Joanna Pilch-Kowalczyk26**, Karolina Poczkaj6**, Violetta Rosiek2**, Marek Ruchała27**, Lucyna Siemińska14**, Anna Sowa-Staszczak4**, Teresa Starzyńska28**, Katarzyna Steinhof-Radwańska26**, Janusz Strzelczyk2**, Krzysztof Sworczak22**, Anhelli Syrenicz3**, Andrzej Szawłowski29**, Marek Szczepkowski30**, Ewa Wachuła8**, Wojciech Zajęcki6**, Anna Zemczak6**, Wojciech Zgliczyński31**, Beata Kos-Kudła2*** 1Department of Gastroenterology, Central Clinical Hospital of the Ministry of Interior and Administration, Warsaw 2Department of Endocrinology and Neuroendocrine Tumours, Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice 3Department of Endocrinology, Metabolic and Internal Diseases, Pomeranian Medical University, Szczecin 4Chair and Department of Endocrinology, Jagiellonian University, Medical College, Krakow 5Department of Internal Medicine and Endocrinology, Medical University of Warsaw 6Department of Endocrinology and Neuroendocrine Tumours, Medical University of Silesia, Katowice 7Department of Endocrinology, Diabetes, and Isotope Therapy, Wroclaw Medical University 8Department of Oncology and Radiotherapy, Medical University of Silesia, Katowice 9Department of Oncological Surgery, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw 10Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn 11Pancreas Translational & Clinical Research Centre, Università Vita e Salute, Milano (Italy) 12Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch 13Chair and Department of Endocrinology and Diabetology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz 14Division of Pathophysiology, Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice 15Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine, Warsaw 16Department of Clinical Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw 17Endocrinology Clinic of Holycross Cancer Centre, Kielce 18Department of General Vascular and Transplant Surgery, Medical University of Silesia, Katowice 19Nuclear Medicine Department, Medical University of Warsaw 20Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice 21Department of Tumour Pathology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch 22Department of Endocrinology and Internal Diseases, Medical University of Gdansk 23Department of Endocrinology and Metabolic Diseases, Medical University of Lodz 24Department of Pathology, The Jan Kochanowski University, Kielce 25Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice 26Department of Radiology and Nuclear Medicine, Medical University of Silesia, Katowice 27Department and Clinic of Endocrinology, Metabolism, and Internal Diseases, University of Medical Sciences, Poznan 28Department of Gastroenterology, Pomeranian Medical University, Szczecin 29Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw 30Department of Colorectal, General, and Oncological Surgery, Centre of Postgraduate Medical Education, Warsaw 31Department of Endocrinology, Postgraduate Medical Education Centre, Warsaw *co-first authors **other authors in alphabetical order ***senior author Michał Lipiński M.D., Department of Gastroenterology, Central Clinical Hospital of the Ministry of Interior and Administration, Wołoska St. 137, 02–507 Warsaw, Poland, e-mail: [email protected] 138 Endokrynologia Polska 2017; 68 (2) Abstract This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neu- roendocrine 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 localisa- tion diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments. Finally, there are also recommendations on patient monitoring. (Endokrynol Pol 2017; 68 (2): 138–153) Key words: neuroendocrine neoplasms; stomach; duodenum; gastrinoma; diagnostics; therapy; guidelines 1. Epidemiology and pathogenesis following are also mentioned in the literature: protein inhibiting apoptosis BCL2, protein p53, fibroblast 1.1. Neuroendocrine neoplasms of the stomach growth factor (FGF), transforming growth factor-α Neuroendocrine neoplasms (NEN) constitute ap- (TGF-α), and incorrect function of the REGL protein proximately 1% of all neoplasms of the stomach [1]. (inhibiting proliferation of ECL cells) [7]. Between 5.6 and 8.7% of gastrointestinal NENs are gastric neuroendocrine neoplasms (g-NENs). However, Type 1 the rate of g-NENs in the overall group of NENs varies, Gastric neuroendocrine neoplasms of type 1 (70–80% of depending on the site where the studies are conducted. g-NENs) are found in patients with atrophic gastritis. Recently published data from Argentina indicate that They occur in less than 1% of patients, more often in g-NENs comprise 6.9% of all gastrointestinal NENs [2], women, and are diagnosed mostly between the ages of whereas the rate reported in an earlier Austrian study 40 and 60 years. The increased availability of endoscopic was 5.6% [1]. The percentage of g-NENs in relation to all examinations is expected to lower the age of patients NENs significantly differs between reports. An Austrian diagnosed with g-NETs of type 1 [8, 9]. study gave 23%, a Canadian study gave 5%, and Taiwan They rarely present clinical signs, and are diagnosed study gave 7.4%, whereas the SEER programme gave during an endoscopic examination performed due to 6% [3, 4]. The differences indicate the need for mul- dyspeptic symptoms or anaemia, more frequently due ticentre, prospective studies with long-term analysis to macrocytic than iron-deficiency anaemia [10]. in order to better describe the epidemiology of these They are usually small lesions (< 1–2 cm), 65% of neoplasms in Europe. The prevalence is estimated at them are multiple, and 78% are polyps [6]. 1-2 cases per 1,000,000 people per year, (1.2/1,000,000 70–85% of the tumours belong to the NET G1 group, males, 1.8/1,000,000 females). In the years 1981–2000, according to the World Health Organisation (WHO) an 8–9-fold increase in the diagnosis of g-NENs was 2017 classification [10, 11]. They are rarely invasive. observed, due to the continuously extending indica- 2–5% of cases are metastatic, and the ability to produce tions for endoscopic examinations [5,6]. metastases increases along with the tumour size [6]. In the stomach three clinical and pathogenetic types They are almost always slowly growing tumours with of g-NENs are found, with differences in their clinical good prognosis — mortality rates have not been described, and histopathological pictures, as well as in the diag- despite the disease advancement (up to 100% of patients nostics and therapeutic management (Table I). with 10-year survival rate). They are non-functional: less than 1% of patients with g-NETs of type 1 present the Pathogenesis symptoms of atypical carcinoid syndrome. Blood serum Type 1 and 2 tumours arise from the enterochromaffin- gastrin is significantly elevated, as well as gastric pH. like (ECL) cells of the gastric mucosa in response to chronic, excessive secretion of gastrin. Secondary Type 2 hypergastrinaemia, caused by achlorhydria accompa- This is the rarest (5–6%) form of g-NET. It occurs exclu- nying chronic atrophic gastritis (CAG), is responsible sively in the course of gastrinoma: in 23–29% of patients SZKOLENIE for the development of g-NENs of type 1. Primary with ZES/MEN-1, and in 1–3% of sporadic lesions PODYPLOMOWE hypergastrinaemia in Zollinger-Ellison Syndrome [5, 9, 12]. Zollinger-Ellison Syndrome is clinically pre- (ZES), sporadic or associated with multiple endocrine sent. Neoplasms are usually small (< 1–2 cm) and fre- neoplasia 1 (MEN-1), is responsible for g-NENs of type quently multiple, often in the form of polyps. They are 2. Gastrin and its derivatives stimulate the proliferation, mostly located in the fundus and body of the stomach, migration, and differentiation of ECL cells, which lead only occasionally in the gastric
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