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Christos Toumpanakis, Nicola Fazio, Eva Tiensuu Janson, Dieter Hörsch, Andreas Pascher, Nicholas Reed, Dermot O'Toole, Els Nieveen van Dijkum, Stefano Partelli, Anja Rinke, Beata Kos-Kudla, Frederico Costa, Ulrich-Frank Pape, Simona Grozinsky-Glasberg, Jean-Yves Scoazec
Appendiceal neuroendocrine neoplasms (ANEN) are mostly discovered coincidentally during appendicectomy and usually have a benign clinical course, thus appendicectomy alone is considered as curative. However in some cases a malignant potential is suspected and therefore additional operations, such as completion right hemicolectomy, are considered. The existing European Neuroendocrine Tumour Society (ENETS) guidelines provide quite useful data about epidemiology and prognosis, as well as, practical recommendations with regards to the risk factors for a more aggressive disease course and the indications for a secondary operation...
September 20, 2018: Neuroendocrinology
John K Ramage, Juan Valle, Els J M Nieveen van Dijkum, Anders Sundin, Andreas Pascher, Anne Couvelard, Guenter Kloeppel
The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well-differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and poorly-differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according to the 2010 World Health Organisation (WHO) classification, has arguably not had as much attention or study as NENs occurring in other sites. Colorectal NETs and NECs are however easier to study than many others since they are usually not difficult to remove and are increasingly detected because of intensified colorectal cancer screening and surveillance programs...
September 16, 2018: Neuroendocrinology
Rose Crossin, Zane B Andrews, Natalie Sims, Terence Pang, Michael Mathai, Jonathan Gooi, Aneta Stefanidis, Brian J Oldfield, Andrew Lawrence, Jhodie Duncan
<br>Background/aims: Abuse of toluene products (e.g. glue-sniffing) primarily occurs during adolescence and has been associated with appetite suppression and weight impairments. However, the metabolic phenotype arising from adolescent inhalant abuse has never been fully characterised, and its persistence during abstinence and underlying mechanisms remain unknown. METHODS: Adolescent male Wistar rats (PND 27) were exposed to inhaled toluene (10,000ppm) (n=32) or air (n=48) for 1 hour/day, 3 days/week for 4 weeks, followed by 4 weeks abstinence...
September 12, 2018: Neuroendocrinology
Jaume Capdevila, Lisa Bodei, Philippa Davies, Vera Gorbounova, Robert T Jensen, Ulrich Knigge, Guenter J, Eric Krenning, Juan O''Connor, Marc Peeters, Guido Rindi, R Salazar, Marie Pierre Vullierme, Marianne Pavel
<br>Unmet medical needs are not infrequent in oncology and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade and currently a new WHO classification is being implemented and several treatment options are available in metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered and decisions in our daily clinical practice should be made with limited evidence...
August 28, 2018: Neuroendocrinology
Faidon-Marios Laskaratos, Martin Walker, Dominic Wilkins, Alexander Tuck, Krishnan Ramakrishnan, Edward Phillips, Julian Gertner, Maria Megapanou, Dimitrios Papantoniou, Ruchir Shah, Jamie Banks, Erasmia Vlachou, Jorge Garcia Hernandez, Lorna Woodbridge, Anthie Papadopoulou, Lee Grant, Eleni Theocharidou, Jennifer Watkins, Tu Vinh Luong, Dalvinder Mandair, Martyn Caplin, Christos Toumpanakis
Small intestinal neuroendocrine tumours (SI NETs) represent 30-50% of small bowel neoplasms and often present at an advanced stage. To date, there is relatively limited literature regarding prognostic factors affecting overall survival (OS) in stage IV disease. In addition, the prevalence of mesenteric fibrosis (MF) in SI NETs and its effect on OS have not been sufficiently explored in the literature. <br><br>Aim: The primary aim of this study was to perform a large scale survival analysis in an institutional cohort of 387 patients with metastatic (stage IV) SI NETs...
August 28, 2018: Neuroendocrinology
Halfdan Sorbye, Eric Baudin, Ivan Borbath, Martyn Caplin, Jie Chen, Jaroslaw Cwikla, Andrea Frilling, Ashley Grossman, Gregory Kaltsas, Aldo Scarpa, Staffan Welin, Rocio Garcia-Carbonero
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are classified based upon morphology and graded upon proliferation rate as either well-differentiated low-grade (G1-G2) neuroendocrine tumours (NET) or poorly differentiated high-grade (G3) neuroendocrine carcinoma (NEC). Recently, a new subgroup of well-differentiated high-grade pancreatic tumours (NET G3) has been defined. The GEP NEN G3 group consisting of both NEC and NET G3, has recently been shown to be a quite heterogeneous patient group concerning prognosis and treatment benefit, depending on factors such as primary tumour site, differentiation, proliferation rate and molecular alterations...
August 28, 2018: Neuroendocrinology
Ivan Kruljac, Ivan Vičić, Kristina Blaslov, Zorica Kolak, Martina Benkovic, Davor Kust, Blaženka Ladika Davidović, Gordan Tometic, Ivan Penavić, Nina Dabelić, Ljubica Vazdar, Tajana Pavic, Milan Vrkljan
Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA. <br><br>Methods: Our prospective study enrolled 45 patients from two different patient cohorts: 1) 29 patients with suspicion or presence of NEN (extensive work-up and subsequent biopsy confirmed 16 NENs); 2) 16 consecutive patients admitted via emergency department without NEN (nonNENs)...
August 16, 2018: Neuroendocrinology
Tobias Stemann Lau, Gitte Dam, Peter Jepsen, Henning Grønbæk, Klaus Krogh, Tine Gregersen
Second primary colorectal adenocarcinomas (SPCA) may occur with a higher frequency in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In a nationwide population based study, we investigated the risk of SPCA in GEP-NEN patients and compared it to the general population. <br><br>METHODS: Using the nationwide Danish registries, we identified 2,831 GEP-NEN patients (median age 63 years (IQR 50-73 years), 53 % women) diagnosed in 1995-2010. We used Cox regression to compare the incidence of SPCA in GEP-NEN patients relative to a gender- and age-matched general population sample of 56,044 persons...
August 9, 2018: Neuroendocrinology
Zhi Zhang, Frederico Machado, Li Zhao, Charlotte Heinen, Ewout Foppen, Mariëtte T Ackermans, Jiang-Ning Zhou, Peter Bisschop, Anita Boelen, Eric Fliers, Andries Kalsbeek
Cold exposure increases thyrotropin-releasing hormone (TRH) expression primarily in the hypothalamic paraventricular nucleus (PVN). The PVN is a well-known hypothalamic hub in the control of energy metabolism. TRH terminals and receptors are found on PVN neurons. We hypothesized that TRH release in the PVN plays an important role in the control of thermogenesis and energy mobilization during cold exposure. <br><br>Methods: Male Wistar rats were exposed to a cold environment (4oC) or TRH retrodialysis in the PVN for 2-hours...
August 9, 2018: Neuroendocrinology
Suvi Ruohonen, Laura Valve, Katja Tuomainen, Liisa Ailanen, Matias Röyttä, Georg Manz, Nadja Baur, Thomas Joos, Eriika Savontaus, Mika Scheinin
<br>The α2A-adrenoceptors (ARs) are Gi-coupled receptors, which prejunctionally inhibit the release of norepinephrine (NE) and epinephrine (Epi), and postjunctionally insulin secretion and lipolysis. We have earlier shown that α2A-/- mice display sympathetic hyperactivity, hyperinsulinemia and improved glucose tolerance. Here we employed α2A-/- mice and placed the mice on a high-fat diet (HFD) to test the hypothesis that lack of α2A-ARs protects from diet-induced obesity (DIO) and type 2 diabetes (T2D)...
July 24, 2018: Neuroendocrinology
Levent Dizdar, Jasmin Drusenheimer, Thomas Artur Werner, Birte Möhlendick, Sina Christin Schütte, Irene Esposito, Timm Filler, Wolfram Trudo Knoefel, Andreas Krieg
<br>Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are biologically aggressive tumors, associated with a very poor survival. Due to their rarity, our knowledge on GEP-NEC biology is very limited. The aim of this study was to establish a GEP-NEC cell line model that might contribute to a better understanding of this rare malignant disease to further develop novel therapeutic approaches in preclinical studies. METHODS: Small cell neuroendocrine cancer cell line NEC-DUE3 was derived from a lymph node metastasis of a neuroendocrine carcinoma (NEC) located at the anal canal...
July 19, 2018: Neuroendocrinology
Jerena Manoharan, Volker Fendrich, Pietro Di Fazio, Carmen Bollmann, Silvia Roth, Barbara Joos, Ioannis Mintziras, Max Albers, Annette Ramaswamy, Philippe Bertolino, Chang X Zhang, Emily P Slater, Detlef K Bartsch, Caroline Lopez-Lopez
<br>Pancreatic neuroendocrine neoplasias (pNEN) are the most common cause of death in adult patients with multiple endocrine neoplasia type 1 (MEN1). So far, only few chemopreventive strategies (e.g. with somatostatin analogues) have been evaluated for MEN1 associated pNENs. In this experimental study on 75 Men1(+ /T) knockout mice, the effect of aspirin (n=25) and an inhibitor of angiotensin-I converting enzyme (enalapril, n=25) compared to controls (n=25) were evaluated as single chemopreventive strategies for pNENs after 6,9,12,15 and 18 months...
July 19, 2018: Neuroendocrinology
Paula Jimenez-Fonseca, Sebastian Krug, Gianluca Tamagno, F Fierro Maya, A Monleon Getino, C I Rodriguez Casado, Frederico Costa, Wouter W de Herder, Henning Jann
<br>Pancreatic neuroendocrine tumours (pNETs) represent rare neoplasms of all NETs often presenting without functional activity. Many sporadic non-functioning pNET patients are already metastatic at the time of diagnosis, and the therapeutic approach to such patients is mostly palliative. In this international, multicenter, retrospective cohort study we assessed the prognostic value of a set of anthropometric, clinical, biochemical, radiological, and pathological parameters at baseline and the impact of the therapeutic strategies on the survival of patients with sporadic grade 1/2, stage IV, non-functioning pNETs...
July 19, 2018: Neuroendocrinology
Eric Raymond, Matthew Kulke, Shu-Kui Qin, Xianjun Yu, Michael Schenker, Antonio Cubillo, Wenhui Lou, Jiri Tomasek, Espen Thiis-Evensen, Jian-Ming Xu, Adina Croitoru, Mustafa Khasraw, Eva Sedlackova, Ivan Borbath, Paul Ruff, Paul Oberstein, Tetsuhide Ito, Liqun Jia, Pascal Hammel, Lin Shen, Shailesh V Shrikhande, Yali Shen, Jozef Sufliarsky, Gazala Khan, Chigusa Morizane, Salvatore Galdy, Reza Khosravan, Kathrine Fernandez, Brad Rosbrook, Nicola Fazio
<br>Background: In a phase III study, sunitinib led to a significant increase in progression- free survival (PFS) vs. placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. <br><br>Methods: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study...
July 10, 2018: Neuroendocrinology
Sophie Moog, Sébastien Houy, Elodie Chevalier, Stéphane Ory, Georges Weryha, Marion Rame, Marc Klein, Laurent Brunaud, Stéphane Gasman, Thomas Cuny
<br>Background: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging for the diagnosis of pheochromocytomas (PHEO). However, its utility as a predictive factor of the secretion of catecholamines remains poorly studied. METHODS: Thirty-nine histologically-confirmed PHEO were included in this retrospective monocentric study. Patients underwent 18F-FDOPA PET/CT before surgery with evaluation of several uptake parameters (SUVmax, SUVmean and the metabolic burden [MB] calculated as follows: MB = SUVmean x tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM) and chromogranin A (CGA)...
June 27, 2018: Neuroendocrinology
Michelle Bedenbaugh, Rick McCosh, Justin Lopez, John Connors, Robert L Goodman, Stan Hileman
<br> Background: Neuronal intermediates that communicate estrogen and progesterone feedback to gonadotropin-releasing hormone (GnRH) neurons are essential for modulating reproductive cyclicity. Individually, kisspeptin and nitric oxide (NO) influence GnRH secretion. However, it is possible these two neuronal intermediates interact with one another to affect reproductive cyclicity. METHODS: We investigated the neuroanatomical relationship of one isoform of the enzyme that synthesizes NO, neuronal nitric oxide synthase (nNOS), to kisspeptin and GnRH in adult female rhesus monkeys and sheep using dual-label immunofluorescence...
June 21, 2018: Neuroendocrinology
Lunpo Wu, Fei Chen, Shujie Chen, Liangjing Wang
<br>Background: The effectiveness of current Tumor, Lymph node, Metastases (TNM) staging system in small intestinal neuroendocrine tumors (SiNETs) is unsatisfactory. Current N classification only distinguishes between node-negative and node-positive status. We aim to refine the N classification for updated TNM stage. METHODS: Patients with non-metastatic SiNETs between 1988 and 2012 were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database. Using the X-tile program, we calculated an optimal cut-off value for lymph node ratio (LNR) and proposed a novel Nr category...
June 19, 2018: Neuroendocrinology
Sarah Robins, Maia Kokoeva
<br>There is increasing evidence that glia act not only as neuronal support cells, but that they can also influence physiological outcomes via effects on neural signalling. The role of NG2-glia in this regard is especially enigmatic, as they are known to interact with neural circuits but their precise functions other than as oligodendrocyte progenitor cells remain elusive. Here we summarise recent evidence suggesting that NG2-glia play a role in the maintenance of energy homeostasis, most notably via the support of leptin sensing neural circuits...
March 5, 2018: Neuroendocrinology
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2018: Neuroendocrinology
David H Abbott, Sarah H Vepraskas, Teresa H Horton, Ei Terasawa, Jon E Levine
BACKGROUND/AIMS: Ovarian theca cell hyperandrogenism in women with polycystic ovary syndrome (PCOS) is compounded by androgen receptor-mediated impairment of estradiol and progesterone negative feedback regulation of episodic luteinizing hormone (LH) release. The resultant LH hypersecretion, likely the product of accelerated episodic release of gonadotropin-releasing hormone (GnRH) from the median eminence of the hypothalamus, hyperstimulates ovarian theca cell steroidogenesis, enabling testosterone (T) and androstenedione excess...
2018: Neuroendocrinology
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