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 role of endoscopic and demographic features in the diagnosis of gastric precancerous conditions.

INTRODUCTION: The diagnosis of atrophic gastritis (AG) and intestinal metaplasia (IM) is a crucial screening and surveillance strategy for gastric adenocarcinoma. OBJECTIVES: The main objective was to assess the performance of endoscopic diagnosis of gastric precancerous conditions in a real­life scenario. PATIENTS AND METHODS: A total of 2099 gastroscopies with biopsy to evaluate gastritis performed in 3 endoscopic centers from March 2018 to October 2019 were retrospectively analyzed. Endoscopic data regarding gastritis, atrophy, and intestinal metaplasia were compared with histopathological reports. RESULTS: The endoscopic diagnosis sensitivity was 69.5% for AG and 19.4% for IM. The specificity of endoscopic detection of AG was 69.5% and of IM, 97.9%. The endoscopic detection of gastritis was a risk factor for AG and IM diagnosis (odds ratio [OR], 5.1; 95% CI, 1.9-14.1 and OR, 14.5; 95% CI, 5.9-35.8, respectively) and the patient's age was a risk factor for AG, IM, dysplasia, and advanced stage of AG (ASAG) diagnosis (OR, 1.05; 95% CI, 1.04-1.06; OR, 1.035; 95% CI, 1.03-1.04; OR, 1.04; 95% CI, 1.02-1.06; and OR, 1.05; 95% CI, 1.02-1.09, respectively). The age threshold of 45 or 40 years with endoscopically diagnosed gastritis for obtaining biopsy would result in 96.3% and 95% ASAG or dysplasia diagnosis sensitivity, and in the reduction of the number of biopsies by 20.2% and 20.5%, respectively. CONCLUSIONS: The application of the age threshold with or without an endoscopic diagnosis of gastritis could reduce the number of mapping biopsies to detect advanced stages of atrophic gastritis or dysplasia with high sensitivity.

Ultrasound predictors of left adrenal metastasis in patients with lung cancer: a comparison of computed tomography, positron emission tomography-computed tomography, and endoscopic ultrasound using ultrasound bronchoscope.

INTRODUCTION: Patients with resectable lung cancer require invasive evaluation of the enlarged left adrenal gland (LAG). Few studies showed the utility of endoscopic ultrasound using ultrasound bronchoscope (EUS­B) in LAG assessment. Moreover, little is known on the combination of computed tomography (CT), positron emission tomography-computed tomography (PET­CT), and EUS­B for predicting left adrenal metastasis. PATIENTS AND METHODS: In this retrospective cohort study performed from 2012 to 2019, patients with left adrenal enlargement were evaluated by CT, PET­CT, and EUS­B, followed by complete endoscopic mediastinal staging. The adrenal glands were sampled by EUS­B-guided fine­needle aspiration. Patients were followed for 6 months. RESULTS: During the staging of lung cancer in 2176 patients, 113 enlarged LAGs (5.19%) were biopsied. Malignancy was reported in 51 LAGs (45.13%). Endoscopic ultrasound upstaged 7 patients (6.2%) and downstaged 11 patients (9.37%) after false CT or PET­CT findings. There were no biopsy­related complications. Radiologic predictors of left adrenal metastases had the highest yield at the following cutoff points: Hounsfield units >23, standardized uptake value >4.2, and LAG size >25 mm. Hypoechogenic LAGs with loss of sea­gull shape on EUS­B were associated with a 28.67­fold higher likelihood of metastases. The sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for all ultrasound predictors were 86.21%, 85.45%, 85.84%, 85.45%, and 86.21%, respectively. When combined with radiologic features, the respective values were 93.10%, 94.55%, 93.81%, 92.86%, and 94.74%. CONCLUSIONS: Hypoechogenicity and loss of sea­gull shape on EUS­B are the most reliable predictors of left adrenal metastasis. The combination of CT, PET­CT, and EUS­B improves the noninvasive diagnosis of left adrenal metastases in lung cancer patients.

Composite detection rate as an upper gastrointestinal endoscopy quality measure correlating with detection of neoplasia.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is commonly used diagnostic method with no widely accepted quality measure. We assessed quality indicator-composite detection rate (CDR)-consisting of detection of at least one of the following: cervical inlet patch, gastric polyp and post-ulcer duodenal bulb deformation. The aim of the study was to validate CDR according to detection rate of upper gastrointestinal neoplasms (UGN). METHODS: It was a multicenter, prospective, observational study conducted from January 2019 to October 2019. The endoscopic reports from 2896 symptomatic patients who underwent diagnostic EGD were analyzed. The EGDs were performed in three endoscopy units located in tertiary university hospital, private outpatient clinic and local hospital. RESULTS: 64 UGNs were detected. The mean CDR was 21.9%. The CDR correlated with UGN detection rate (R = 0.49, p = 0.045). Based on CDR quartiles, operators were divided into group 1 with CDR < 10%, group 2 with CDR 10-17%, group 3 with CDR 17.1-26%, and group 4 with CDR > 26%. Detection rate of UGN was significantly higher in the group 4 in comparison to group 1 (OR 4.4; 95% CI 2.2 - 9.0). In the multivariate regression model, patient age, male gender and operator's CDR > 26% were independent risk factors of UGN detection (OR 1.03; 95% CI 1.01 - 1.05, OR 2; 95% CI 1.2 - 3.5, and OR 5.7 95% CI 1.5 - 22.3, respectively). CONCLUSIONS: The CDR is associated with the detection of upper gastrointestinal neoplasms. This parameter may be a useful quality measure of EGD to be applied in general setting.

Prospective Evaluation of the NETest as a Liquid Biopsy for Gastroenteropancreatic and Bronchopulmonary Neuroendocrine Tumors: An ENETS Center of Excellence Experience.

BACKGROUND: There is a substantial unmet clinical need for an accurate and effective blood biomarker for neuroendocrine neoplasms (NEN). We therefore evaluated, under real-world conditions in an ENETS Center of Excellence (CoE), the clinical utility of the NETest as a liquid biopsy and compared its utility with chromogranin A (CgA) measurement. METHODS: The cohorts were: gastroenteropancreatic NEN (GEP-NEN; n = 253), bronchopulmonary NEN (BPNEN; n = 64), thymic NEN (n = 1), colon cancer (n = 37), non-small-cell lung cancer (NSCLC; n = 63), benign lung disease (n = 59), and controls (n = 86). In the GEPNEN group, 164 (65%) had image-positive disease (IPD, n = 135) or were image-negative but resection-margin/biopsy-positive (n = 29), and were graded as G1 (n = 106), G2 (n = 49), G3 (n = 7), or no data (n = 2). The remainder (n = 71) had no evidence of disease (NED). In the BPNEN group, 43/64 (67%) had IPD. Histology revealed typical carcinoids (TC, n = 14), atypical carcinoids (AC, n = 14), small-cell lung cancer (SCLC, n = 11), and large-cell neuroendocrine carcinoma (LCNEC, n = 4). Disease status (stable or progressive) was evaluated according to RECIST v1.1. Blood sampling involved NETest (n = 563) and NETest/CgA analysis matched samples (n = 178). NETest was performed by PCR (on a scale of 0-100), with a score ≥20 reflecting a disease-positive status and >40 reflecting progressive disease. CgA positivity was determined by ELISA. Samples were deidentified and measurements blinded. The Kruskal-Wallis, Mann-Whitney U, and McNemar tests, and the area under the curve (AUC) of the receiver-operating characteristics (ROC) were used in the statistical analysis. RESULTS: In the GEPNEN group, NETest was significantly higher (34.4 ± 1.8, p < 0.0001) in disease-positive patients than in patients with NED (10.5 ± 1, p < 0.0001), colon cancer patients (18 ± 4, p < 0.0004), and controls (7 ± 0.5, p < 0.0001). Sensitivity for detecting disease compared to controls was 89% and specificity was 94%. NETest levels were increased in G2 vs. G1 (39 ± 3 vs. 32 ± 2, p = 0.02) and correlated with stage (localized: 26 ± 2 vs. regional/distant: 40 ± 3, p = 0.0002) and progression (55 ± 5 vs. 34 ± 2 in stable disease, p = 0.0005). In the BPNEN group, diagnostic sensitivity was 100% and levels were significantly higher in patients with bronchopulmonary carcinoids (BPC; 30 ± 1.3) who had IPD than in controls (7 ± 0.5, p < 0.0001), patients with NED (24.1 ± 1.3, p < 0.005), and NSCLC patients (17 ± 3, p = 0.0001). NETest levels were higher in patients with poorly differentiated BPNEN (LCNEC + SCLC; 59 ± 7) than in those with BPC (30 ± 1.3, p = 0.0005) or progressive disease (57.8 ± 7), compared to those with stable disease (29.4 ± 1, p < 0.0001). The AUC for differentiating disease from controls was 0.87 in the GEPNEN group and 0.99 in BPC patients (p < 0.0001). Matched CgA analysis was performed in 178 patients. In the GEPNEN group (n = 135), NETest was significantly more accurate for detecting disease (99%) than CgA positivity (53%; McNemar test χ2 = 87, p < 0.0001). In the BPNEN group (n = 43), NETest was significantly more accurate for disease detection (100%) than CgA positivity (26%; McNemar's test χ2 = 30, p < 0.0001). CONCLUSIONS: The NETest is an accurate diagnostic for GEPNEN and BPNEN. It exhibits tumor biology correlation with grading, staging, and progression. CgA as a biomarker is significantly less accurate than NETest. The NETest has substantial clinical utility that can facilitate patient management.

Usefulness of combined endobronchial and endoscopic ultrasound-guided needle aspiration in the diagnosis of sarcoidosis: a prospective multicenter trial.

INTRODUCTION: Needle biopsy of enlarged lymph nodes is an accepted method for the diagnostic workup of sarcoidosis, but the optimal endosonography­guided approach is yet to be determined. OBJECTIVES: The aim of our study was to assess the relative diagnostic yield of combined ultrasound­guided needle aspiration (CUS­b­NA), which includes endobronchial ultrasound­guided transbronchial needle aspiration (EBUS­TBNA) with endoscopic ultrasound fine­needle aspiration (EUS­b­FNA), as well as the role of the cell block (CB) technique and lymph node localization in the diagnostic workup of sarcoidosis. PATIENTS AND METHODS: This was a prospective multicenter study including consecutive patients with clinical suspicion of stage I or II sarcoidosis. CUS­b­NA with smears and CB technique were performed in the whole study group. If a biopsy result was not conclusive, an invasive diagnostic workup and a 6-month follow­up were scheduled. RESULTS: Out of 77 screened patients, 54 signed written consent and 50 were enrolled for the final analysis. The overall sensitivity of EBUS­TBNA, EUS­b­FNA, and CUS­b­NA was 76.6%, 70.2%, and 91.7%, respectively. There were no differences between EBUS­TBNA and EUS­b­FNA (P = 0.52) but CUS­b­NA had a higher diagnostic yield (P = 0.005 and P = 0.001, respectively). Adding the CB method to smear technique (P = 0.008) and biopsy of the subcarinal lymph nodes increased the diagnostic yield (P = 0.001).  Conclusions: The diagnostic yield of CUS­b­NA is higher than that of endosonographic techniques alone in the diagnostic workup of stage I and II sarcoidosis. The preparation of cytological material including CB and the choice of the subcarinal lymph node station for the biopsy increase the diagnostic efficacy.

NETest liquid biopsy is diagnostic of small intestine and pancreatic neuroendocrine tumors and correlates with imaging.

INTRODUCTION: Current monoanalyte biomarkers are ineffective in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). NETest, a novel multianalyte signature, provides molecular information relevant to disease biology. AIM(S): Independently validate NETest to diagnose GEP-NETs and identify progression in a tertiary referral center. MATERIALS AND METHODS: Cohorts: 67 pancreatic NET (PNETs), 44 small intestine NETs (SINETs), 63 controls. Well-differentiated (WD): PNETs, n=62, SINETs, all (n=44). Disease extent assessment at blood draw: anatomical (n=110)- CT(n=106), MRI(n=7) and/or functional- 68Ga-SSA-PET/CT(n=69) or 18F-FDG-PET/CT (n=8). Image positive disease (IPD) was defined as either CT/MRI or 68Ga-SSA-PET/CT/18F-FDG-PET/CT-positive. Both CT/MRI and 68Ga-SSA-PET/CT-negative in WD-NETs was considered image negative disease (IND). NETest (normal: 20): PCR (spotted plates). DATA: mean±SD. RESULTS: Diagnosis: NETest was significantly increased in NETs (n=111; 26±21) vs. controls (8±4, p<0.0001). 75 (42 PNET, 33 SINET) were image-positive. Eleven (8 PNET, 3 SINET; all WD) were IND. In IPD, NETest was significantly higher (36±22) vs. IND (8±7, p<0.0001). NETest accuracy, sensitivity, specificity: 97%, 99%, 95%. Concordance with imaging: NETest was 92% (101/110) concordant with anatomical imaging, 94% (65/69) with 68Ga-SSA-PET/CT, 96% (65/68) dual modality (CT/MRI and 68Ga-SSA-PET/CT). In 70 CT/MRI-positive, NETest was elevated in all (37±22). In 40 CT/MRI-negative, NETest was normal (11±10) in 31. In 56 68Ga-SSA-PET/CT-positive, NETest was elevated (36±22) in 55. In 13 68Ga-SSA-PET/CT-negative, NETest was normal (9±8) in 10. Disease status: NETest was significantly higher in progressive (61±26; n=11) vs. stable disease (29±14; n=64; p<0.0001) (RECIST 1.1). CONCLUSION: NETest is an effective diagnostic for PNETs and SINETs. Elevated NETest is as effective as imaging in diagnosis and accurately identifies progression.

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.

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

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.

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

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.

Hepatic chemerin and chemokine-like receptor 1 expression in patients with chronic hepatitis C.

INTRODUCTION: Chemerin seems to be involved in pathogenesis of chronic hepatitis C (CHC). Hepatic expressions of chemerin and its receptor, chemokine receptor-like 1 (CMKLR1), in CHC have not been studied so far. AIM: To evaluate chemerin and CMKLR1 hepatic expression together with serum chemerin concentration in CHC patients and to assess their relationship with metabolic and histopathological abnormalities. METHODS: The study included 63 nonobese CHC patients. Transcription of chemerin and CMKLR1 was assessed by quantitative real-time PCR, while serum chemerin was assessed by enzyme-linked immunosorbent assay. RESULTS: Expression of chemerin and CMKLR1 was present in the liver of all CHC patients regardless of sex or age. This expression was not associated with necroinflammatory activity and steatosis grade, fibrosis stage, and metabolic abnormalities. There was a negative association between serum chemerin and chemerin hepatic expression (r = (-0.41), P = 0.006). CONCLUSION: The study for the first time confirmed a marked expression of chemerin and CMKLR1 in the liver of CHC patients. The study was performed using the homogenates of human liver tissue, so it is not possible to define whether hepatocytes or other cell types which are abundantly represented in the liver constitute the main source of chemerin and CMKLR1 mRNA.

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

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

The value of the Ki-67 proliferation marker as a prognostic factor in gastroenteropancreatic neuroendocrine tumours.

INTRODUCTION: 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. AIM OF THE STUDY: 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. MATERIAL AND METHODS: 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 MIB­1 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 5­hydroxyindoleacetic acid [5­HIAA] in 24-hour urine). RESULTS: The diagnoses of low-grade (Ki­67 ≤ 2%), intermediate-grade (Ki-67 3-20%) and high-grade (Ki­67 > 20%) 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. CONCLUSIONS: The Ki-67 proliferative index is an essential parameter predicting the course of GEP-NETs.