ABSTRACT
No required for Clinical Vignette.
Subject(s)
Neuroendocrine Tumors , Ovarian Neoplasms , Humans , Female , Somatostatin , Intestine, SmallABSTRACT
Data on the possible connection between circulating adipokines and PanNENs are limited. This novel study aimed to assess the serum levels of leptin and adiponectin and their ratio in patients with PanNENs and to evaluate the possible relationship between them and PanNEN's grade or stage, including the presence of metastases. The study group consisted of PanNENs (n = 83), and healthy controls (n = 39). Leptin and adiponectin measurement by an ELISA assay was undertaken in the entire cohort. The serum concentration of adiponectin was significantly higher in the control group compared to the study group (p < 0.001). The concentration of leptin and adiponectin was significantly higher in females than in males (p < 0.01). Anincreased leptin-adiponectin ratio was observed in well-differentiated PanNENs (G1) vs. moderatelydifferentiated PanNENs (G2) (p < 0.05). An increased leptin-adiponectin ratio was found in PanNENs with Ki-67 < 3% vs. Ki-67 ≥ 3% (p < 0.05). PanNENs with distal disease presented lower leptin levels (p < 0.001) and a decreased leptin-adiponectin ratio (p < 0.01) compared with the localized disease group. Leptin, adiponectin, and the leptin-adiponectin ratio may serve as potential diagnostic, prognostic, and predictive biomarkers for PanNENs. Leptin levels and the leptin-adiponectin ratio may play an important role as predictors of malignancy and metastasis in PanNENs.
ABSTRACT
We investigated the diagnostic capacity of selected circulating biomarkers (CBMs) for the early detection of bone metastasis (BMets) in patients with pancreatic neuroendocrine neoplasms (PanNENs). A total of 115 patients with PanNENs and 40 controls were enrolled. We measured the serum levels of ferritin, cytokeratin 18 (CY18), CA19-9, CA125, AFP, CEA, and beta-2 microglobulin (B2M). A total of eight PanNEN patients developed BMets, and one hundred seven remained BMets-free. We observed a significantly higher level of CA125 and CY18 in BMets patients vs. non-BMets patients (p = 0.01 and p = 0.04, respectively). CA125, CY18, and B2M area under receiver operator characteristic (AUROC) analyses differentiated both patients groups; CA125 area under the curve (AUC) 0.77, p < 0.01; CY18 AUC data were 0.72, p = 0.03, and B2M AUC 0.67, p = 0.02. On the basis of CBM metrics in both subgroups, we reached a sensitivity/specificity for CA125 of 75/76%; for CY18 of 75/69%, for B2M of 100/50%, for CA125, and the CY18 combination of 93/90%, respectively. According to current results, CA125 and CY18 seem to have the potential capacity as fair biomarkers for BMets detection, despite the small number of cases. Further studies are warranted in the larger PanNEN patient group.
ABSTRACT
There is a lack of effective biomarkers for diagnosing lung neuroendocrine neoplasms (LNENs). A known small cell lung cancer (SCLC) biomarker is a pro-gastrin-releasing peptide (ProGRP), but not for all LNENs, especially for bronchopulmonary carcinoids. This study aimed to evaluate the diagnostic value of ProGRP and chromogranin A (CgA) in diagnosing LNENs. The ProGRP and CgA levels in 290 cases of LNENs and 54 healthy controls (HCs) were measured. The median ProGRP concentration in the group of LNEN patients was 136.4 pg/mL, higher than that of HCs at 6.5 pg/mL. Most of the LNEN cohort was well-differentiated tumors (typical and atypical carcinoids, n = 262, 91.7% of all LNENs). The sensitivity, specificity, and area under the curve (AUC) of ProGRP when distinguishing LNENs vs. HCs were 94.8%, 100%, and 0.995. CgA (AUC = 0.375) could not determine LNENs vs. HCs. Therefore, based on these results, ProGRP may be considered as an effective marker for diagnosing LNENs.
ABSTRACT
Metabolic abnormalities are well-known risk factors for many cancers, even though no clearly established link with pancreatic neuroendocrine neoplasms (PanNENs) has yet been investigated. This research aimed to assess the serum levels of leptin, chromogranin A (CgA), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) in patients with PanNENs and to search for associations between PanNENs, these selected serum biomarkers, and metabolic abnormalities in the form of metabolic syndrome (MS). Second, we aimed to investigate whether MS increases the risk of PanNENs. The serum concentrations of biomarkers, metabolic parameters (glucose, cholesterol, triglycerides), and anthropometric measurements (weight, height, BMI) were assessed in 106 patients with PanNENs and 40 healthy volunteers. Patients with PanNENs showed higher serum concentrations of CA19-9, CEA, and CgA in comparison to controls (p < 0.001, p = 0.042, and p = 0.025, respectively). Statistically significant differences in CEA levels were found in PanNENs patients with MS (p = 0.043). PanNENs patients with a BMI ≥ 25 kg/m2 and who were female exhibited significantly higher leptin levels (p < 0.001 and p = 0.013, respectively). Additionally, this study reflects the importance of determining markers. Future research should focus on understanding the impact of metabolic disturbances on PanNENs and accounting for the relationship between PanNENs and MS, such as other malignancies.
ABSTRACT
Angiogenic factors (AF) promote vascular formation and may thus support neuroendocrine tumour (NET) development. This study aimed to assess AF serum level changes in NET patients treated with prolonged-acting somatostatin analogues (SSAs). The study enrolled 49 healthy volunteers (Group A) and 56 NET patients: treatment naïve (Group B) and after-SSA treatment in various periods (months): under 12 (Group C), 13-24 (Group D), 25-36 (Group E), 37-60 (Group F), and over 60 months (Group G). The serum vascular endothelial growth factor receptors 2, 3 (VEGF-R2, VEGF-R3), and vascular cell adhesion molecule-1 (VCAM-1) concentrations were tested using the ELISA. We noted significant differences in the concentrations of VEGF-R2, VEGF-R3, and VCAM-1 depending on the SSA treatment duration (p < 0.001). In the studied AFs, the highest decreasing levels of VEGF-R2 were observed after two years of therapy. However, monitoring VEGF-R2, VEGF-R3, and VCAM-1 during SSA treatment did not allow for the identification of good responders for this kind of therapy. Therefore, these biomarker measurements were not helpful in assessing SSA treatment effectiveness in NET patients.
ABSTRACT
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.
Subject(s)
Endocrinology , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Medical Oncology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/therapy , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , Poland , StomachABSTRACT
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.
Subject(s)
Endocrinology , Neuroendocrine Tumors , Humans , Medical Oncology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/therapy , PolandABSTRACT
INTRODUCTION: Vascular endothelial growth factor (VEGF) is a known promoter of angiogenesis that can support neuroendocrine neoplasm (NEN) development. The aim of the study was to evaluate the serum VEGF and vascular endothelial growth factor receptor 1 (VEGF R1) concentration changes in patients with NEN treated with first-generation long-acting somatostatin analogues (SSA). MATERIAL AND METHODS: The study comprised 55 controls and 56 NEN patients before and after SSA treatment in various periods of time (months): 1-12 (n = 54), 13-24 (n = 46), 25-36 (n = 35), 37-60 (n = 26), and over 60 months (n = 22). An analysis of medical records and serum VEGF and VEGF R1 concentration measurements of NEN patients, by enzyme-linked immunosorbent assay (ELISA) were made. RESULTS: During SSA treatment time, a decrease of the VEGF and an increase of VEGF R1 concentrations was observed. We confirmed significant VEGF differences between 2 pairs of SSA-treated NEN patient subgroups: Group 1-12 vs. Group 37-60 (p = 0.039) and Group 1-12 vs. Group > 60 (p = 0.026). We did not note significant differences of VEGF R1 levels between SSA-treated NEN patient subgroups. Among the studied biomarkers, VEGF R1 exhibited the best performance in distinguishing between NEN patients with controls; area under the curve (AUC) = 1 (p < 0.001). CONCLUSIONS: The examined angiogenesis factors (VEGF and VEGF R1) seem to have limited usage in the assessment of SSA treatment effectiveness in NEN. However, the assessment of serum levels of these factors may help in the differentiation of NEN patients and healthy controls; in particular, VEGF R1 seems to be a good diagnostic biomarker for NEN patients.
Subject(s)
Neuroendocrine Tumors , Vascular Endothelial Growth Factor A , Humans , Neovascularization, Pathologic , Neuroendocrine Tumors/drug therapy , Somatostatin/therapeutic use , Vascular Endothelial Growth FactorsABSTRACT
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.
Subject(s)
Duodenal Neoplasms , Endocrinology , Gastrinoma , Neuroendocrine Tumors , Pancreatic Neoplasms , Duodenal Neoplasms/diagnosis , Duodenal Neoplasms/therapy , Gastrinoma/diagnosis , Gastrinoma/therapy , Humans , Medical Oncology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/therapy , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , PolandABSTRACT
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.
Subject(s)
Colorectal Neoplasms , Endocrinology , Neuroendocrine Tumors , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/therapy , Humans , Medical Oncology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/therapy , PolandABSTRACT
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.
Subject(s)
Appendix , Carcinoid Tumor , Endocrinology , Neuroendocrine Tumors , Humans , Intestine, Small/diagnostic imaging , Medical Oncology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/drug therapy , PolandABSTRACT
Not required for Clinical Vignette.
Subject(s)
Gastrinoma , Pancreatic Neoplasms , Gastrinoma/surgery , Humans , Pancreatic Neoplasms/therapy , Somatostatin/therapeutic useABSTRACT
BACKGROUND: Bone metastases (BM) are related to worse outcome in patients with neuroendocrine neoplasms (NENpts). AIM: Assess utility of serum tumor markers (STM) for detection of BM in lung NENpts. MATERIAL AND METHODS: Diagnostic metrics of STM, such as ferritin, carbohydrate antigens 19-9 (CA19-9), cancer antigen 125 (CA125), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and beta-2 microglobulin (BMG) were assessed in 62 Lung NEN patients (LNENpts), both with BM (BM-LNENpts) and without BM (non-BM-LNENpts) and 40 controls. RESULTS: Except AFP, the mean circulating STM levels in LNENpts were significantly increased vs controls (p<0.04), but the most significant difference was in CA19-9 and CEA. BM-LNENpts exhibited an elevated level only for ferritin (n=6; 180.75±53.73 ng/ml; [182.68] compared to non-BM-LNENpts (n=56; 94.33±98.80 ng/ml; [70.35], p<0.001). Three from all used STM (ferritin, BMG and CA125) could differentiate BM-LNENpts from nonBM-LNENpts (area under the curve (AUC)=0.884 for ferritin, 0.74 for BMG and 0.658 for CA 125, p<0.05). These all three STM showed significant sensitivity (100%) by lower specificity in the detection of BM. CONCLUSIONS: Some of the STM seem to have clinical utility for detection of BM-LNEN. The single good marker was ferritin (the high AUC, sensitivity and specificity) and fair biomarker was BMG. BM-LNENpts could be diagnosed by using CEA. The follow-up with combinations of STM (ferritin, BMG) could increase the diagnostic efficacy of BM-LNENpts. This requires further studies with larger patient groups.
Subject(s)
Bone Neoplasms , Carcinoma, Neuroendocrine , Lung Neoplasms , Biomarkers, Tumor , Bone Neoplasms/diagnosis , CA-125 Antigen , CA-19-9 Antigen , Carcinoembryonic Antigen , Ferritins , Humans , Lung , Lung Neoplasms/diagnosis , alpha-Fetoproteins/metabolismABSTRACT
OBJECTIVE: Introduction: Bronchopulmonary (BP) carcinoids are low and intermediate grade tumors, seen in adults between fourth to sixth decade, where no clear association with tobacco smoking is established. Most often they are sporadic lesions (95%). Half of patients have no symptoms and the tumor is incidentally found on a chest x- ray. BP carcinoids have a good prognostic, however there is a risk of distant metastasis and the recurrences are frequent. Therefore a crucial role of vigilant follow- up, extending far beyond 5 years. PATIENTS AND METHODS: Case presentation: We report a case of 73 years old women, with history of recurrent pulmonary infections, and positive family history for lung cancer. Patient underwent left inferior lobectomy for BP carcinoid 25 years before and completed a 5 years long follow- up. On a thoracic computed tomography scan a nodule in the right lung was detected. Patient benefited from surgery and the pathological result was typical carcinoid with Ki67<1%. Follow- up CT scans showed stable images, with no signs of spread or recurrence. CONCLUSION: Conclusions: Although there is a low risk of distant spread in such tumors, the recurrences are frequent. Moreover, patients may exhibit a higher risk of development of second tumors and there is a risk of metachronous tumors. The post-operative follow-up should be prolonged.
Subject(s)
Carcinoid Tumor , Lung Neoplasms , Adult , Aged , Female , Humans , Lung , Neoplasm Recurrence, Local , Tomography, X-Ray ComputedABSTRACT
INTRODUCTION: The aim of this study was to assess the therapeutic effect and the safety of pre-surgical treatment with long-acting octreotide in patients with acromegaly. MATERIAL AND METHODS: This project was conducted in 25 centres across Poland as a non-interventional, multicentre, observational study in patients with acromegaly, in which long-acting octreotide Sandostatin® LAR®) was administered before surgery. They were 148 patients included into the study: 88 females and 60 males aged 18-86 years (51.3 ± 13.4). RESULTS: Eighty patients completed the study (underwent tumour surgery). The CRF included: baseline visit, four follow-up visits every three months before surgery, and two follow-up visits every three months after surgery. Sandostatin® LAR® was administered every four weeks. The efficacy measures were as follows: change of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, number of patients fulfilling criteria of cure, and change of adenoma (micro- and macroadenomas) size during the treatment. Normalisation of GH and IGF-1 concentrations were obtained in 42.4 and 49.1% of patients at the end of medical therapy, respectively. Normalisation of GH and IGF-1 concentrations were obtained in 77.9 and 83.8% of patients after surgery, respectively. Reduction of microadenoma size was documented in 58.8% of patients, and in 70% of patients with macroadenomas at the end of medical therapy. In 74.0% of patients no pituitary tumour was shown on MRI after surgery. CONCLUSION: We have shown good surgical outcome in patients with acromegaly after pre-treatment with somatostatin analogue, and good tolerance and safety of the therapy, supporting the national recommendation for pre-surgical treatment with long-acting somatostatin analogues in acromegaly patients.
Subject(s)
Acromegaly/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Octreotide/therapeutic use , Premedication/methods , Acromegaly/surgery , Adult , Aged , Aged, 80 and over , Delayed-Action Preparations , Female , Growth Hormone/blood , Humans , Injections, Subcutaneous , Male , Middle Aged , Poland , Treatment Outcome , Young AdultABSTRACT
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.
Subject(s)
Disease Management , Gastrointestinal Neoplasms/diagnosis , Neuroendocrine Tumors/diagnosis , Pancreatic Neoplasms/diagnosis , Societies, Medical , Endocrinology , Female , Gastrointestinal Neoplasms/therapy , Humans , Male , Medical Oncology , Neuroendocrine Tumors/therapy , Pancreatic Neoplasms/therapy , PolandABSTRACT
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.
Subject(s)
Disease Management , Duodenal Neoplasms/diagnosis , Gastrinoma/diagnosis , Neuroendocrine Tumors/diagnosis , Societies, Medical , Stomach Neoplasms/diagnosis , Duodenal Neoplasms/etiology , Duodenal Neoplasms/pathology , Duodenal Neoplasms/therapy , Endocrinology , Female , Gastrinoma/therapy , Humans , Male , Medical Oncology , Neuroendocrine Tumors/etiology , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/therapy , Poland , Stomach Neoplasms/etiology , Stomach Neoplasms/pathology , Stomach Neoplasms/therapyABSTRACT
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.
Subject(s)
Disease Management , Neuroendocrine Tumors/diagnosis , Pancreatic Neoplasms/diagnosis , Societies, Medical , Endocrinology , Female , Humans , Male , Medical Oncology , Neuroendocrine Tumors/therapy , Pancreatic Neoplasms/therapy , PolandABSTRACT
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.