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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.

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. Najczęściej pierwszą manifestacją 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.

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.

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.

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, Żelechów, 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.

Opisujemy przypadek pacjentki z rozpoznaniem raka neuroendokrynnego trzustki z przerzutem do skory. Pierwotnie, w badaniu fizykalnym stwierdzono jedynie powiekszone wezly chlonne pachwinowe prawe. Pomimo wykonania wielu badan obrazowych i czynnościowych oraz przeprowadzenia licznych konsultacji specjalistycznych nie zlokalizowano ogniska pierwotnego. W wykonanych, w przebiegu choroby, kontrolnych badaniach obrazowych uwidoczniono ognisko pierwotne w trzustce. Pacjentke zakwalifikowano do zabiegu resekcyjnego. Jednak przed planowanym zabiegiem pacjentka zauwazyla szybkorosnącego guza przedramienia, ktory w badaniu histopatologicznym okazal sie przerzutem raka neuroendokrynnego do skory. Z powodu znacznej progresji guza trzustki odstąpiono od zabiegu operacyjnego. Pacjentke skierowano do paliatywnego leczenia onkologicznego, ktorego ze wzgledu na gwaltownie pogarszający sie stan ogolny nie otrzymala. Zmarla po 6 miesiącach.

Purpose. The peptide receptor radionuclide therapy (PRRT) is a treatment option for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours (NETs). The study aims to evaluate the safety, efficacy, and progression-free survival (PFS) of patients after retreatment (R-PRRT) and re-retreatment (RR-PRRT) with tandem isotopes [90Y]Y/[177Lu]Lu-DOTATATE. Material and Methods. Out of 99 treated patients with G1 and G2 NETs, 26 were included in the study and treated with the repeated PRRT (with 5 undergoing the re-repeated PRRT treatment) after an initial positive response to four PRRT cycles and later progression of the disease. [68Ga]Ga-DOTATATE PET/CT and CT/MRI procedures were performed before and after the treatment. Patients were treated with [90Y]Y/[177Lu]Lu-DOTATATE (1 : 1) with mixed amino acid infusion for kidney protection. Toxicity was evaluated using the CTCAE 3.0 criteria. Results. The median follow-up was 88 months (the range: 42–164). The median cumulative administered activity was 22.2 GBq (the range: 17.8–30.7 GBq). Myelodysplastic syndrome occurred in one patient (3.8%), and grade 4 renal toxicity was also detected in one patient (3.8%). No other cases of grade 3 or 4 bone marrow and renal toxicity were observed. The median PFS rate was 31 months after the PRRT and 23 months following the R-PRRT. The OS rate from the diagnosis (OS-d) was 109 months and from the start of the PRRT (OS-t)-92.4 months. During the restaging, 3–6 months after the PRRT, PR, SD, and PD were observed in 19.2%, 80.8%, and 0% of the patients, respectively. After the R-PRRT, PR, SD, and PD were observed in 50%, 42.3%, and 7.7% of the patients, respectively. Conclusions. The repeated therapy with [90Y]Y/[177Lu]Lu-DOTATATE is safe and effective for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours.

Introduction: Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). The aim of the study was the evaluation of the role of [ 18 F]FDG PET/CT in predicting response, progression-free survival (PFS) and overall survival (OS) after tandem therapy [ 90 Y]Y/[ 177 Lu]Lu-DOTATATE. Material and methods: Seventy-five patients with histopathologically proven NET G1 and G2 were included in the study. Before treatment [ 68 Ga]Ga-DOTATATE PET/CT and [ 18 F]FDG PET/CT was performed. Patients were treated with [ 90 Y]Y/[ 177 Lu]Lu-DOTATATE (1:1) with mixed amino-acid infusion for kidney protection. Results: Progression-free survival was 22.2 months for [ 18 F]FDG-positive patients and 59.3 months for [ 18 F]FDG-negative patients (p = 0.003). The OS from diagnosis (OS-D) and from the start of PRRT (OS-T) was not reached in [ 18 F]FDG-negative patients, and in [ 18 F]FDG-positive patients it was 71.8 months and 55.8 months, respectively. The observed overall one-year survival in [ 18 F]FDG-positive vs. [ 18 F]FDG-negative patients was 96.8% vs. 99.1%, two-year survival was 88.9% vs. 96%, and five-year survival was 58.8% vs. 88%, respectively. The one-year and two-year risk of progression was 15% vs. 58.9% in [ 18 F]FDG-positive patients and 11% vs. 32% in [18F]FDG-negative patients. The objective response rate (ORR) [ 18 F]FDG-positive vs. [ 18 F]FDG-negative patients was 41.7% vs. 17%. Conclusions: [ 18 F]FDG-positive patients have statistically significant shorter survival parameters than [ 18 F]FDG-negative patients. The risk of progression in [ 18 F]FDG-positive vs. [ 18 F]FDG-negative patients in one-year follow-up is comparable, whereas in two-year follow-up it is nearly two times higher for [ 18 F]FDG PET/CT-positive patients.

Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). The aim of the study was the evaluation of the role of [¹⁸F]FDG PET/CT in predicting response, progression-free survival (PFS) and overall survival (OS) after tandem therapy [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE.Seventy-five patients with histopathologically proven NET G1 and G2 were included in the study. Before treatment [⁶⁸Ga]Ga-DOTATATE PET/CT and [¹⁸F]FDG PET/CT was performed. Patients were treated with [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTATATE (1:1) with mixed amino-acid infusion for kidney protection.Progression-free survival was 22.2 months for [¹⁸F]FDG-positive patients and 59.3 months for [¹⁸F]FDG-negative patients (p = 0.003). The OS from diagnosis (OS-D) and from the start of PRRT (OS-T) was not reached in [¹⁸F]FDG-negative patients, and in [¹⁸F]FDG-positive patients it was 71.8 months and 55.8 months, respectively. The observed overall one-year survival in [¹⁸F]FDG-positive vs. [¹⁸F]FDG-negative patients was 96.8% vs. 99.1%, two-year survival was 88.9% vs. 96%, and five-year survival was 58.8% vs. 88%, respectively. The one-year and two-year risk of progression was 15%vs. 58.9% in [¹⁸F]FDG-positive patients and 11% vs. 32% in [18F]FDG-negative patients. The objective response rate (ORR) [¹⁸F]FDG-positive vs. [¹⁸F]FDG-negative patients was 41.7% vs. 17%.[¹⁸F]FDG-positive patients have statistically significant shorter survival parameters than [¹⁸F]FDG-negative patients. The risk of progression in [¹⁸F]FDG-positive vs. [¹⁸F]FDG-negative patients in one-year follow-up is comparable, whereas in two-year follow-up it is nearly two times higher for [¹⁸F]FDG PET/CT-positive patients.

A case of 25- years-old female with NET deriving from Meckel’s diverticulum is described. The patient had one year history of dermatological skin problems. Ultrasound examination of abdomen performed because of arterial hypertension, revealed multiple hepatic lesions, which was confirmed in contrast enhanced CT. The typical contrast enhanced metastatic lesions in CT and elevated levels of chromogranin A suggested NET of unknown origin. SRS with 99mTc-HYNICTOC was perform for primary tumor localization, and revealed liver and paraaortic lymph nodes metastases, but no sign of primary tumor location. As a next step for primary tumor localization 68Ga-DOTATATE PET/CT was done, which revealed focus of increased uptake in small intestine considered to be the primary tumor site. The imaging and clinical history of patient was discussed on ENETS Tumor Board. Due to location of primary tumor in the small intestine with no anatomical changes in CT, laparotomy guided with gamma probe after 68Ga-DOTATATE injection was performed. During surgery procedure, the primary tumor was hardly palpable in the tip of Meckel’s diverticulum, confirmed by gamma probe. After surgery, tandem peptide receptor radionuclide therapy (PRRT) was started. Patient received 4 doses of 90Y/177Lu-DOTATATE with total activity of 360 mCi (13.32 GBq). The three months follow up 68Ga-DOTATATE PET/CT had shown stable disease of patient. The presented case showed importance role of multidisciplinary team cooperation in patient management. Use of RGS is essential in cases like presented, when the tumor cannot be localized only by surgical palpation.

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.

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.

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.

There are no clear guidelines for the treatment of hepatic neuroendocrine tumours. Surgical resections - though rarely radical - seem to be the treatment of choice. Thermoablation, chemoembolisation, or cytoreductive surgery of hepatic focal lesions are often recommended. Pharmacological treatment is based on somatostatin analogues. Liver transplantation is available for a strictly selected group of patients with hepatic neuroendocrine tumours [5]. In the case described above, there were a number of factors that affected the decision about eligibility: first of all - very slow growth of the tumour, its size, and typical multifocality, which made it impossible to perform resection, lack of neoplastic focus outside the liver, and low Ki-67 proliferation index of ≤ 2%. The surgical risk was escalated due to the giant tumour mass and the laparotomy, which was performed twice.

A case of 25- years-old female with NET deriving from Meckel's diverticulum is described. The patient had one year history of dermatological skin problems. Ultrasound examination of abdomen performed because of arterial hypertension, revealed multiple hepatic lesions, which was confirmed in contrast enhanced CT. The typical contrast enhanced metastatic lesions in CT and elevated levels of chromogranin A suggested NET of unknown origin. SRS with 99mTc-HYNICTOC was perform for primary tumor localization, and revealed liver and paraaortic lymph nodes metastases, but no sign of primary tumor location. As a next step for primary tumor localization 68Ga-DOTATATE PET/CT was done, which revealed focus of increased uptake in small intestine considered to be the primary tumor site. The imaging and clinical history of patient was discussed on ENETS Tumor Board. Due to location of primary tumor in the small intestine with no anatomical changes in CT, laparotomy guided with gamma probe after 68Ga-DOTATATE injection was performed. During surgery procedure, the primary tumor was hardly palpable in the tip of Meckel's diverticulum, confirmed by gamma probe. After surgery, tandem peptide receptor radionuclide therapy (PRRT) was started. Patient received 4 doses of 90Y/177Lu-DOTATATE with total activity of 360 mCi (13.32 GBq). The three months follow up 68Ga-DOTATATE PET/CT had shown stable disease of patient. The presented case showed importance role of multidisciplinary team cooperation in patient management. Use of RGS is essential in cases like presented, when the tumor cannot be localized only by surgical palpation.

Introduction: The objective of this paper was to assess the safety and efficacy of sunitinib malate in patients with well-differentiated metastatic pancreatic neuroendocrine neoplasms (PNENs) who relapsed on standard therapy. Material and methods: Overall, eight patients with well-differentiated pancreatic neuroendocrine tumours/neoplasm (NET/NEN G1/G2, Ki-67 < 20%), who had relapsed on a standard therapy approach, were treated. All had non-resectable, progressive disease. All received therapy using a standard dose of sunitinib malate. Adverse events were evaluated using NCI-CTC AE v. 3.0. Results: Of the eight patients, seven had non-secretor and single secretor tumour (gastrinoma). Partial remission (PR) was noted in three patients (one after a single therapeutic line, two after two lines), five patients had stabilisation (SD) — including three individuals after three lines, one patient after two lines and another after a single line. Haematological adverse events: leukopenia (25%) — occurred in one patient after three lines and in one patient after two lines; anaemia (25%) — in one patient after three lines and in one patient after one therapeutic line. Mucocutaneous lesions were noted in 37.5% of patients after 2–3 lines of treatment. All of them experienced fatigue syndrome irrespective of the number of therapies. The majority of the patients simultaneously received somatostatin analogues, which did not exacerbate the toxicity profile. The median progression-free survival time (PFS) was 11 months. Conclusions: Sunitinib may be considered as a fairly well-tolerated and effective therapeutic option in progressive non-resectable PNEN patients in the second and subsequent lines of treatment, irrespective of the types of treatment previously applied. (Endokrynol Pol 2014; 65 (6): 472–478)

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/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.

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.

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 Żelechow 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.

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.

W niniejszej pracy przedstawiono uaktualnione zalecenia grupy ekspertow Polskiej Sieci Guzow Neuroendokrynnych dotyczące zasad postepowania w nowotworach neuroendokrynnych zolądka i dwunastnicy z uwzglednieniem gastrinoma . Omowiono epidemiologie, patogeneze i obraz kliniczny tych nowotworow. Przedstawiono zalecenia dotyczące zasad postepowania diagnostycznego, z uwzglednieniem diagnostyki biochemicznej, histopatologicznej oraz lokalizacyjnej. Uwzgledniono takze zasady postepowania terapeutycznego, w tym leczenie endoskopowe i chirurgiczne, oraz omowiono mozliwości leczenia farmakologicznego i radioizotopowego. Przedstawiono takze zalecenia odnośnie monitorowania chorych z NEN zolądka, dwunastnicy z uwzglednieniem gastrinoma .

Nowotwory neuroendokrynne (NENs) jelita grubego stanowią 20% wszystkich nowotworow neuroendokrynnych. Najczestszą ich lokalizacją jest odbytnica. Nowotwory neuroendokrynne jelita grubego są wykrywane coraz cześciej i liczba ta bedzie wzrastac z uwagi na powszechnośc wykonywania kolonoskopii, w tym badan przesiewowych oraz usuwanie wykrytych zmian. W pracy przedstawiono aktualne zalecenia dotyczące diagnostyki i terapii NEN jelita grubego, z uwzglednieniem diagnostyki biochemicznej, patomorfologicznej, nowych technik obrazowania oraz leczenia endoskopowego, chirurgicznego, farmakologicznego i radioizotopowego. Omowiono takze epidemiologie, charakterystyke kliniczną i monitorowanie leczenia.

The objective of this paper was to assess the safety and efficacy of sunitinib malate in patients with well-differentiated metastatic pancreatic neuroendocrine neoplasms (PNENs) who relapsed on standard therapy.Overall, eight patients with well-differentiated pancreatic neuroendocrine tumours/neoplasm (NET/NEN G1/G2, Ki-6720%), who had relapsed on a standard therapy approach, were treated. All had non-resectable, progressive disease. All received therapy using a standard dose of sunitinib malate. Adverse events were evaluated using NCI-CTC AE v. 3.0.Of the eight patients, seven had non-secretor and single secretor tumour (gastrinoma). Partial remission (PR) was noted in three patients (one after a single therapeutic line, two after two lines), five patients had stabilisation (SD) - including three individuals after three lines, one patient after two lines and another after a single line. Haematological adverse events: leukopenia (25%) - occurred in one patient after three lines and in one patient after two lines; anaemia (25%) - in one patient after three lines and in one patient after one therapeutic line. Mucocutaneous lesions were noted in 37.5% of patients after 2-3 lines of treatment. All of them experienced fatigue syndrome irrespective of the number of therapies. The majority of the patients simultaneously received somatostatin analogues, which did not exacerbate the toxicity profile. The median progression-free survival time (PFS) was 11 months.Sunitinib may be considered as a fairly well-tolerated and effective therapeutic option in progressive non-resectable PNEN patients in the second and subsequent lines of treatment, irrespective of the types of treatment previously applied.

Thyroid diseases, which may occur as focal or diffuse changes in thyroid parenchyma, are most often observed in women.Our aim was to assess the prevalence of incidental thyroid uptake of 68Ga-DOTATATE PET/CT in patients referred to the Nuclear Medicine Department for evaluation of neuroendocrine neoplasia (NEN).We retrospectively evaluated 1150 68Ga-DOTATATE PET/CT images. Clinical history, serum TSH and thyroid antibody (TAb) concentrations, ultrasonography, and cytological assessment of the material from fine-needle aspiration biopsy (FNA) of the thyroid lesion were investigated.We found incidental abnormalities in 46/1150 (4.1%) patients (12 men, 34 women). 34/46 patients (8 men, 26 women) showed diffuse 68Ga-DOTATATE thyroid uptake, with mean SUVmax 4.6 ± 1.6. Based on laboratory tests and ultrasound, we found: 38% of patients with an active autoimmune thyroiditis, 27% with benign goitre, and 6% with multinodular goitre with autoimmune thyroiditis. The remaining 29% of patients did not show any pathology. In 12/47 patients (4 men, 8 women) focal uptake in the thyroid with SUVmax 7.3 ± 3.3 was found. During one-year follow-up, category II and category III lesions (according to Bethesda classification) were revealed in 9/12 (75%) patients and in one patient, respectively. Histopathological examination after surgery revealed papillary thyroid carcinoma in one patient and benign multinodular goitre in another patient.Patients with focal 68Ga-DOTATATE uptake should undergo further examination (FNA) due to potential risk of malignancy. Diffuse 68Ga-DOTATATE uptake was predominantly associated with active autoimmune thyroiditis or benign goitre. The focal lesions and diffuse pathology diseases were frequently seen in women.

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.

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.

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.

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.

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.

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.

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.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 (RD Systems) in all the study subjects. The statistical calculations were performed using MedCalc.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.Patients with NENs secreted larger quantities of MMP2 and TIMP1. TIMP1 may be considered a marker of metastases in patients with GEP NENs.

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are a heterogenous group of tumours of various clinical presentations. Proliferative activity of tumour cells is an essential parameter determining the course of the disease and affecting the prognosis. The Ki-67 antigen is an important marker of cell proliferation, which shows activity in all the phases of the cell cycle, excluding the G0 phase.To assess the expression of Ki-67 in GEP NETs and to examine the association of Ki-67 with the stage of the tumour (tumour size, presence of metastases) and the hormonal function of the tumour.We included 61 patients with GEP NETs (25 males and 36 females aged between 20 and 82 years [mean age: 56 years]). The proliferative activity was examined in paraffin blocks containing surgically removed tumour samples and in core-needle biopsies of primary and metastatic tumours. The presence of the Ki-67 antigen was assessed by immunohistochemistry using MIB‑1 monoclonal antibodies. Based on the Ki-67 proliferative index we determined the tumour grade. In addition, we determined the tumour stage according to the TNM classification. In all the subjects we determined the levels of the non-specific NET marker (chromogranin A) and of specific NET markers (serotonin, insulin and gastrin in the blood and 5‑hydroxyindoleacetic acid [5‑HIAA] in 24-hour urine).The diagnoses of low-grade (Ki‑67 ≤ 2%), intermediate-grade (Ki-67 3-20%) and high-grade (Ki‑6720%) NET were established in 38, 12 and 11 patients, respectively. Metastatic disease was diagnosed in 36/61 patients. A significantly higher expression of K-67 was observed in patients with metastatic disease (p = 0.01). A positive correlation was demonstrated between Ki-67 and the stage of the disease (p = 0.01) and between the histologic grade of the tumour and the stage of the disease (p = 0.01). No association between Ki-67 and the levels of chromogranin A, serotonin, insulin, gastrin and 5-HIAA was shown. There was also no difference in Ki-67 expression relative to the location of the primary tumour and the tumour size.The Ki-67 proliferative index is an essential parameter predicting the course of GEP-NETs.

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.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.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).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.

The neuroendocrine tumors (NET) of the colon are rare with a rising incidence due to an increased number of diagnostic examination including screening colonoscopy. According to distinct prognosis and treatment these tumors are classified as colonic or rectal NET. This paper provides the consensus guidelines for management of patients with these neoplasms recommended by the Polish Neuroendocrine Tumor Network Group. Furthermore the epidemiology and clinical presentation are described.

Chromogranin A (CgA) is a non-specific marker of neuroendocrine tumors (NET) and is important in monitoring the disease course and NET treatment.Usefulness of suppression test of CgA secretion with octreotide in diagnosis and predicting the therapy outcome in NET patients.The study included 32 patients with NET of gastrointestinal tract, lung and of unknown origin. CgA level in blood plasma on fasting, before and 30, 60, 90 and 120 minutes after subcutaneous administration of 100 mug octreotide, was determined in all patients. The subjects were divided into two subgroups with relation to CgA level and to the results of somatostatin receptor scintigraphy (SRS).Statistically significant CgA decrease after octreotide administration in all study time points and positive results of SRS were found in the patients with the elevated CgA level. No statistically significant decrease of CgA level after octreotide was found in the group with normal CgA levels. In this group, 13 patients had a negative result of SRS, and somatostatin receptors expression was found in one patient. Tolerance of somatostatin analogs (SSA) therapy was very good.Octreotide suppression test with CgA level assessment in NET patients is a simple, straightforward examination, providing information on the predicted response to the applied SSA and the data on initial clinical tolerance of those agents. This examination can also be a screening test useful in planning the treatment with SSA in patients with NET.

Neuroendocrine tumors of digestive tract (GEP NET) occur rather rarely, causing many problems with both diagnosis and treatment. Thanks to the extreme devotion of specialists, a great leap has been made in the field development. Clinicians and scientists gathered in The European Neuroendocrine Tumour Society publish current proposals for diagnosis solutions, together with the most up-to-date methods of treatment, which we have attempted to present in this general overview. It describes general methods of treating patients with GEP NET, as well as discusses ways of dealing with cases of tumours type foregut, midgut and hindgut.

Neuroendocrine tumors are frequently associated with other primary malignancies. Plasmablastic lymphoma is a rare, aggressive neoplasm, derived from large B-cell, associated with human immunodeficiency virus infection. Plasmablastic lymphoma cells share many cytomorphologic and immunophenotypic features with plasmablastic cells, causing some diagnostic problems. We present a unique case of coexisting two very uncommon neoplasms: plasmablastic lymphoma and neuroendocrine carcinoma in 54-years-old men. This is the first report of caecum localization of plasmablastic lymphoma. Presented case images diagnostic problems in rare neoplasms.

It is well known that there is a higher prevalence of cardiovascular risk factors and metabolic syndrome (MS) in postmenopausal women. Recently it has become evident that adiponectin and leptin secreted by adipose tissue may be involved in the pathophysiology of MS.was to assess the effects of the menopause on the relationships between adiponectin and leptin and different cardiovascular and metabolic risk factors.A total of 56 postmenopausal women and 75 premenopausal subjects were enrolled in this study. We measured blood pressure, BMI, waist circumference and WHR, triglycerides (TG), high density lipoprotein cholesterol (cHDL) levels and fasting glucose and applied the oral glucose tolerance test (OGTT). Women were categorised as having 0, 1, 2, 3 or more risk factors. The presence of at least 3 abnormalities was defined as MS. Serum was assayed for adiponectin and leptin by the radioimmunoassay (RIA) method.A decline in adiponectin was related to an increased number of MS variables in postmenopausal and premenopausal women. Postmenopausal women with MS had significantly lower adiponectin concentrations than premenopausal women with MS. Serum adiponectin concentrations were inversely correlated to leptin in postmenopausal women. In premenopausal women no clear relationships were found between serum leptin and the number of metabolic disturbances. In contrast to young women, postmenopausal women showed an increase in leptin secretion with a growing number of MS elements. Compared to premenopausal women with MS, postmenopausal women with MS had higher levels of leptin. We found associations between leptin and different risk factors, mainly in the postmenopausal group. When the presence of MS was used as a dependent variable (yes/no) and adiponectin, leptin and menopause status as independent factors, adiponectin and leptin remained significant variables related to MS.The significant role of adiponectin in the pathophysiology of MS in premenopausal and postmenopausal women is confirmed in this study. Leptin is correlated with several MS components but this adipocytokine appears to play a role only in postmenopausal women.

Females with polycystic ovary syndrome (PCOS) are characterized by several metabolic abnormalities that favor the development of atherosclerosis. Atherosclerosis is possibly a chronic inflammatory process, and the markers of the inflammatory state, such as C-reactive protein (CRP) and fibrinogen may be useful to assess the global risk of developing cardiovascular diseases. These proteins might be helpful in finding females with subclinical atherosclerosis. The purpose of this study was to assess the serum CRP and fibrinogen concentrations in young females with PCOS and to clarify the possible correlations between their levels and selected anthropometric, metabolic and hormonal indices. Study assessed a group of 57 females with PCOS (mean age 28.2±6.4 years). That group was further divided into two subgroups: the first with body mass index (BMI)≤25 (21 females of mean age 27.4±7.0 years) and second with BMI>25 (36 females of mean age 28.6±6.0 years). In the control group there were 22 healthy females (mean age 31.6±8.5 years). That group was again divided into two subgroups: the first with BMI≤25 (10 females, mean age 30.2±8.4 years) and second with BMI>25 (12 females, mean age 31.7±8.7 years). Results demonstrated statistically significantly higher CRP concentration in females with PCOS compared to healthy individuals in both BMI subgroups. PCOS females showed also higher plasma insulin levels. There was, however, no statistically significant difference in fibrinogen concentrations. The hormonal profile of females with PCOS seems to influence the concentration of CRP and fibrinogen in different ways. This was evident in the positive correlation between plasma fibrinogen and androstenedione and in the lack of correlation between CRP and androgens and in the positive correlation between CRP and estradiol and the negative correlation between fibrinogen and estradiol. In conclusion, high CRP concentration in females with PCOS probably speaks for a higher risk for cardiovascular diseases.