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Miguel Sampedro-Núñez, Ana Serrano-Somavilla, Magdalena Adrados, José M Cameselle-Teijeiro, Concepción Blanco-Carrera, José Manuel Cabezas-Agricola, Rebeca Martínez-Hernández, Elena Martín-Pérez, José Luis Muñoz de Nova, José Ángel Díaz, Rogelio García-Centeno, Javier Caneiro-Gómez, Ihab Abdulkader, Roberto González-Amaro, Mónica Marazuela
The immune checkpoint based therapy targeting the programmed death-1 (PD-1) receptor and its PD-L1 ligand has recently been approved for the therapy of different malignant conditions, but not yet for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In this context, we evaluated the expression of PD-1 and PD-L1 in GEP-NETs and its potential correlations with clinical outcomes. Expression of PD-1/PD-L1 was analyzed by immunohistochemistry in 116 GEP-NETs and 48 samples of peritumoral tissue. In addition, the expression of these molecules was assessed by flow cytometry in peripheral blood mononuclear cells (PBMC) from patients with GEP-NETs (n = 32) and healthy controls (n = 32) and in intratumoral mononuclear cells (TMCs) (n = 3)...
December 13, 2018: Scientific Reports
Junho Kang, Changhoon Yoo, Hee-Sang Hwang, Seung-Mo Hong, Kyu-Pyo Kim, Sun Young Kim, Yong-Sang Hong, Tae Won Kim, Baek-Yeol Ryoo
Lanreotide autogel is a long-acting somatostatin analogue with proven efficacy and safety in patients with well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) in a prior randomized phase III trial (CLARINET). However, the CLARINET study only enrolled patients with Ki-67 index <10%, and few patients of Asian ethnicity were included. We retrospectively analyzed the efficacy and safety of lanreotide in Korean patients with GEP-NETs in the daily practice setting. Between January 2015 and May 2018, 64 patients with metastatic WD GEP-NETs received lanreotide at Asan Medical Center, Seoul, Korea...
December 10, 2018: Investigational New Drugs
Luigi Barrea, Barbara Altieri, Giovanna Muscogiuri, Daniela Laudisio, Giuseppe Annunziata, Annamaria Colao, Antongiulio Faggiano, Silvia Savastano
Neuroendocrine tumors (NETs) are rare neoplasms mostly originating from the gastroenteropancreatic tract (GEP-NETs). Data regarding nutritional status in GEP-NET patients are limited. The aim of the study was to investigate the nutritional status and adherence to the Mediterranean Diet (MD) in GEP-NET patients and to correlate them with tumor aggressiveness. A cross-sectional case-control observational study was conducted enrolling 83 patients with well-differentiated G1/G2 GEP-NETs after resection, as well as 83 healthy subjects, age, sex and body mass index-matched...
December 1, 2018: Nutrients
Yi Wang, Kun Huang, Jie Chen, Yanji Luo, Yu Zhang, Yingmei Jia, Ling Xu, Minhu Chen, Bingsheng Huang, Dong Ni, Zi-Ping Li, Shi-Ting Feng
Objective: We propose a computer-aided method to assess response to drug treatment, using CT imaging-based volumetric and density measures in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and diffuse liver metastases. Methods: Twenty-five patients with GEP-NETs with diffuse liver metastases were enrolled. Pre- and posttreatment CT examinations were retrospectively analyzed. Total tumor volume (volume) and mean volumetric tumor density (density) were calculated based on tumor segmentation on CT images...
2018: Contrast Media & Molecular Imaging
Eva Lesén, Åse Björstad, Ingela Björholt, Tom Marlow, Entela Bollano, Marion Feuilly, Florence Marteau, Staffan Welin, Anna-Karin Elf, Viktor Johanson
OBJECTIVES: To quantify healthcare resource use (HRU) and costs in relation to carcinoid syndrome (CS) and carcinoid heart disease (CHD) in a real-world setting, and to provide perspective on treatment patterns. MATERIALS AND METHODS: Patient data and HRU were collected retrospectively from three Swedish healthcare registers. Adult patients diagnosed with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) grade 1 or 2 and CS who purchased somatostatin analogs (SSAs), and experienced controlled (defined by SSAs use) and uncontrolled (defined by SSAs dose escalation) CS for ≥8 months during the study period were included...
November 19, 2018: Scandinavian Journal of Gastroenterology
Rohit Dhingra, Julie Y Tse, Muhammad Wasif Saif
Background: Gastroenteropancreatic neuroendocrine tumors are neoplasms commonly found within the gastrointestinal tract that originate from endocrine cells. These are slow progressive tumors and often metastasize to other elements of the gastrointestinal tract including the liver. Consequently, these tumors release hormones including serotonin and/or histamine that are responsible for the symptoms including intermittent flushing and diarrhea. Metastasis of gastroenteropancreatic neuroendocrine tumors, although rare, is possible and may extend to local lymph nodes and viscera...
September 2018: JOP: Journal of the Pancreas
Fatih Mert Dogukan, Banu Yilmaz Ozguven, Rabia Dogukan, Fevziye Kabukcuoglu
Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are classified according to tumor grade. Ki-67 and mitotic count are the two determinants of this classification. Therefore, Ki-67 scoring becomes very important in classifying the patients accurately. Eye-balling, counting of cells through the microscope, automated image analysis systems, and manual counting of printed image are the four major scoring methods in use. The aim of this study is to show the agreement between monitor-image method (MIM) and printout-image method (PIM) of Ki-67 scoring...
October 26, 2018: Endocrine Pathology
Xavier M Keutgen, Erik Schadde, Rodney F Pommier, Thorvardur R Halfdanarson, James R Howe, Electron Kebebew
Over 50% of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have stage IV disease at presentation and the most likely organ to be affected by metastases is the liver. Hepatic involvement and hepatic tumor burden is a key prognostic factor affecting survival of these patients and 80% eventually die of liver failure due to tumor dissemination within the liver. This commentary explores the efficacy and limitations of systemic treatments in patients with GEP-NETs and liver metastases. Landmark randomized trials using systemic therapies including sandostatin (PROMID), lanreotide (CLARINET), everolimus (RADIANT 3 and 4), sunitinib and Peptide Receptor Radionuclide Therapy (NETTER-1) have not shown efficacy in reducing liver tumor burden in patients with stage IV GEP-NETs with liver metastases as outlined in this review...
October 11, 2018: Seminars in Oncology
Ashwini Kalshetty, Anant Ramaswamy, Vikas Ostwal, Sandip Basu
BACKGROUND AND AIMS: Functioning and symptomatic disease resistant to conventional therapies constitutes a subset amongst neuroendocrine tumors (NETs) that are commonly considered for peptide receptor radionuclide therapy (PRRT). The aim of this study was to evaluate the efficacy of Lu-DOTATATE PRRT in this group with objective assessment criteria. MATERIALS AND METHODS: A total of 46 patients with refractory or progressive symptomatic GEP-NETs (previously treated at various stages with long-acting octreotide, chemotherapy, multikinase inhibitors, etc...
December 2018: Nuclear Medicine Communications
Thomas Cuny, Wouter de Herder, Anne Barlier, Leo J Hofland
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a group of heterogeneous tumors whose incidence increased over the past few years. Around half of patients already present with metastatic disease at the initial diagnosis. Despite extensive efforts, cytotoxic and targeted therapies have provided only limited efficacy for patients with metastatic GEP-NETs, mainly due to the development of a certain state of resistance. One factor contributing to both the failure of systemic therapies and the emergence of an aggressive tumor phenotype may be the tumor microenvironment (TME), comprising dynamic and adaptative assortment of extracellular matrix components and non-neoplastic cells, which surround the tumor niche...
November 1, 2018: Endocrine-related Cancer
Aura D Herrera-Martínez, Manuel D Gahete, Rafael Sánchez-Sánchez, Emilia Alors-Perez, Sergio Pedraza-Arevalo, Raquel Serrano-Blanch, Antonio J Martínez-Fuentes, Maria A Gálvez-Moreno, Justo P Castaño, Raúl M Luque
OBJECTIVES: The association between the presence and alterations of the components of the ghrelin system and the development and progression of neuroendocrine tumors (NETs) is still controversial and remains unclear. METHODS: Here, we systematically evaluated the expression levels (by quantitative-PCR) of key ghrelin system components of in gastroenteropancreatic (GEP)-NETs, as compared to non-tumor adjacent (NTA; n = 42) and normal tissues (NT; n = 14)...
October 8, 2018: Clinical and Translational Gastroenterology
Mauro Cives, Jonathan R Strosberg
Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in the last 3 decades. Fundamental biologic and genomic differences underlie the clinical heterogeneity of NETs, and distinct molecular features characterize NETs of different grades and different primary sites. Although surgery remains the cornerstone of treatment for localized tumors, systemic treatment options for patients with metastatic NETs have expanded considerably...
October 8, 2018: CA: a Cancer Journal for Clinicians
Nelli Roininen, Sari Takala, Kirsi-Maria Haapasaari, Arja Jukkola-Vuorinen, Johanna Mattson, Päivi Heikkilä, Peeter Karihtala
OBJECTIVES: Due to the rarity of breast carcinomas with neuroendocrine features (NEBC), the knowledge on their biology is very limited but the identification of their biology and prognostic factors is essential to evaluate both pathogenesis and possible targeted treatment options. We assessed the expression of the well-characterized prognostic factors of gastroenteropancreatic neuroendocrine tumors (GEP-NET) in NEBC. METHODS: We assessed the immunohistochemical expression of neuron-specific enolase (NSE), thymidylate synthase (TS), p27, CD56, menin, and somatostatin receptor type 2A (SSTR-2A) in a series of 36 NEBC and 45 invasive ductal carcinomas (IDC)...
October 3, 2018: Oncology
W A van der Zwan, T Brabander, B L R Kam, J J M Teunissen, R A Feelders, J Hofland, E P Krenning, W W de Herder
PURPOSE: Therapy with [177 Lu-DOTA,Tyr3 ]octreotate is effective in patients with grade I/II metastasized and/or inoperable bronchial neuroendocrine tumour (NET) or gastroenteropancreatic NET (GEP-NET). In this study, we investigated the efficacy and safety of salvage treatment with [177 Lu-DOTA,Tyr3 ]octreotate. METHODS: Patients with progressive bronchial NET or GEP-NET were selected for re-(re)treatment if they had benefited from initial peptide receptor radionuclide therapy (I-PRRT) with a minimal progression-free survival (PFS) of 18 months...
September 28, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Aura D Herrera-Martínez, Sergio Pedraza-Arevalo, Fernando L-López, Manuel D Gahete, María A Gálvez-Moreno, Justo P Castaño, Raúl M Luque
Background: Biguanides and statins have been reported to exert beneficial effects on various cancer types. However, their precise effects and underlying molecular mechanisms are still poorly understood. Materials and Methods: We analyzed the relation between metabolic-syndrome, i.e., presence of type-2 diabetes (T2DM), hyperlipidemia and their treatment, with histological, epidemiological, and prognosis variables in two patient cohorts with neuroendocrine-tumors [NETs: lung-carcinoids (LCs; n=81) and gastro-entero-pancreatic (GEP-NET; n=100)]...
September 27, 2018: Journal of Clinical Endocrinology and Metabolism
Jean E Boucher, Robin Sommers
Neuroendocrine tumors (NETs), including gastroenteropancreatic NETs, or GEP-NETs, are heterogenous tumors that arise from diffuse neuroendocrine cells and other organs, such as the lung, ovary, and thyroid. Lutetium Lu 177 dotatate (Lutathera®) is a newly approved targeted therapy for patients with advanced GEP-NETs. Patients treated with octreotide long-acting release may be candidates for this second-line therapy. This article discusses lutetium Lu 177 dotatate therapy administration and patient care considerations...
October 1, 2018: Clinical Journal of Oncology Nursing
Ana P Santos, Ana C Santos, Clara Castro, Luís Raposo, Sofia S Pereira, Isabel Torres, Rui Henrique, Helena Cardoso, Mariana P Monteiro
The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether well-differentiated GEP-NETs were associated with obesity and MetS. Patients with well-differentiated GEP-NETs ( n = 96) were cross-matched for age, gender, and district of residence with a control group ( n = 96) derived from the general population in a case-control study...
August 27, 2018: Cancers
Changyin Feng, Qiaoling Zheng, Yinghong Yang, Meifang Xu, Yuane Lian, Jianping Huang, Yiting Jiang
PURPOSE: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is known as a source of mutations in multiple cancers. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a group of heterogeneous tumors. However, the expression and significance of APOBEC3B in GEP-NENs remains unclear. MATERIALS AND METHODS: A total of 158 cases of GEP-NENs, including 78 cases of biopsy or endoscopic submucosal dissection resection specimens and 83 cases of surgical resection specimens were collected in this study...
August 8, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Andrea Palermo, Ettore Capoluongo, Rossella Del Toro, Silvia Manfrini, Paolo Pozzilli, Daria Maggi, Giuseppe Defeudis, Francesco Pantano, Roberto Coppola, Francesco Maria Di Matteo, Marco Raffaelli, Paola Concolino, Alberto Falchetti
CONTEXT: Clinical phenotype variability in MEN1 syndrome exists and evidence for an established genotype-phenotype is lacking. However, a higher aggressiveness of MEN1-associated gastro-entero-pancreatic (GEP) (neuro)endocrine tumours (NETs) tumours has been reported when MEN1 gene truncating mutations are detected. We found a novel germline truncating mutation of MEN1 gene at exon 10 in a subject with an aggressive clinical behavior of GEP-NETs. Successively, other two mutant-affected familial members have been identified...
September 2018: Hormones: International Journal of Endocrinology and Metabolism
Sally C Lau, Omar Abdel-Rahman, Winson Y Cheung
Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) represent a heterogeneous group of tumors that is associated with an indolent course. Octreotide has a positive effect on disease stabilization in well-differentiated midgut NETs, but a meaningful survival analysis was not possible due to insufficient events. Higher doses of octreotide long-acting release (LAR) are often used in clinical practice for control of carcinoid symptoms and our objective was to determine if dose of octreotide correlates with survival...
August 4, 2018: Medical Oncology
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