{"title":"The role of NMDA receptors in fish stress response: Assessments based on physiology of the caudal neurosecretory system and defensive behavior.","authors":"Yeyang Qin, Mengmeng Shi, Yanyan Wei, Weiqun Lu","doi":"10.1111/jne.13448","DOIUrl":"10.1111/jne.13448","url":null,"abstract":"<p><p>Stress strongly influences the physiology and behavior of animals, and leads into a pathological condition and disease. NMDA receptors (NMDARs) play a crucial role in the modulation of neural activity. To understand the role of NMDARs in fish stress response, we used NMDARs agonist aspartate to test the functional role of its input on the Dahlgren cell population in the caudal neurosecretory system (CNSS) of the olive flounder. In addition, the effect of the NMDARs antagonist D-AP5 on the expression of genes of the main secretory products of the CNSS after stress was investigated by using qPCR technology and the effect of the NMDARs antagonist D-AP5 on post-stress behavior was explored by behavioral methods. Ex vivo electrophysiological experiments showed that the NMDARs agonist aspartate enhanced the firing frequency of Dahlgren cells. Additionally, aspartate treatment increased the incidence of cells exhibiting bursting firing pattern, this result is corroborated by the observed upregulation in the expression of ion channels and major hormone genes in the CNSS. Furthermore, the excitatory influence of aspartate was effectively counteracted by NMDARs antagonist D-AP5. Interestingly, NMDARs antagonist D-AP5 treatment also significantly decreased the plasma cortisol levels and the expression of CRH, UI, and UII in CNSS after acute stress. Treatment with D-AP5 effectively attenuated the stress response, as evidenced by alterations in respiratory metabolism, sand-burying behavior, swimming distance, simulated capture, and escape response. In conclusion, modulation of Dahlgren cell excitability in the CNSS by NMDARs contributes to the regulation of the stress response, NMDARs antagonist D-AP5 can effectively suppress stress response in flounder by regulating the stress hormone expression and secretion. CLINICAL TRIAL REGISTRATION: Project code SHOU-DW-2022-032.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13448"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthieu J Maroteaux, Claire T Noccioli, Jill M Daniel, Laura A Schrader
{"title":"Rapid and local neuroestrogen synthesis supports long-term potentiation of hippocampal Schaffer collaterals-cornu ammonis 1 synapse in ovariectomized mice.","authors":"Matthieu J Maroteaux, Claire T Noccioli, Jill M Daniel, Laura A Schrader","doi":"10.1111/jne.13450","DOIUrl":"10.1111/jne.13450","url":null,"abstract":"<p><p>In aging women, cognitive decline and increased risk of dementia have been associated with the cessation of ovarian hormones production at menopause. In the brain, presence of the key enzyme aromatase required for the synthesis of 17-β-estradiol (E2) allows for local production of E2 in absence of functional ovaries. Understanding how aromatase activity is regulated could help alleviate the cognitive symptoms. In female rodents, genetic or pharmacological reduction of aromatase activity over extended periods of time impair memory formation, decreases spine density, and hinders long-term potentiation (LTP) in the hippocampus. Conversely, increased excitatory neurotransmission resulting in rapid N-methyl-d-aspartic acid (NMDA) receptor activation rapidly promotes neuroestrogen synthesis. This rapid modulation of aromatase activity led us to address the hypothesis that acute neuroestrogens synthesis is necessary for LTP at the Schaffer collateral-cornu ammonis 1 (CA1) synapse in absence of circulating ovarian estrogens. To test this hypothesis, we did electrophysiological recordings of field excitatory postsynaptic potential (fEPSPs) in hippocampal slices obtained from ovariectomized mice. To assess the impact of neuroestrogens synthesis on LTP, we applied the specific aromatase inhibitor, letrozole, before the induction of LTP with a theta burst stimulation protocol. We found that blocking aromatase activity prevented LTP. Interestingly, exogenous E2 application, while blocking aromatase activity, was not sufficient to recover LTP in our model. Our results indicate the critical importance of rapid, activity-dependent local neuroestrogens synthesis, independent of circulating hormones for hippocampal synaptic plasticity in female rodents.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13450"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Photoperiodism, testosterone and adult neurogenesis in canaries (Serinus canaria)","authors":"Jacques Balthazart","doi":"10.1111/jne.13449","DOIUrl":"https://doi.org/10.1111/jne.13449","url":null,"abstract":"Domestic strains of canaries (<jats:italic>Serinus canaria</jats:italic>) variably respond to photoperiod changes and apparently stay in breeding state for extended periods. Fife Fancy canaries are supposed to be similar to the native species living at 27–39° north where photoperiod significantly changes across the year. Our birds showed reproductive cycles when exposed to light regimes mimicking the annual cycle of photoperiod. However after 6 months in short days (SD: 8L:16D), males developed large testes, as observed by X‐ray tomography, and intense singing. Switching to long days (LD: 16L:8D) did not further increase song rate nor testes size but increased song duration, number of syllables per song, and trill occurrence frequency. No sign of regression was observed after 12 weeks in LD but return to SD produced a rapid decrease in testes size and singing activity below values in birds maintained throughout in SD. Fife Fancy thus does not seem to develop absolute but only relative refractoriness. The relatively high singing activity expressed by SD‐photosensitive males does not seem to depend on high testosterone (T) concentrations. Singing did not correlate with plasma testosterone (T). Treatment with ATD + Flutamide only marginally decreased song rate and did not affect song quality nor song control nuclei volume. These birds are either supersensitive to low T levels or their reproductive physiology is activated by other mechanisms. Neurogenesis is increased by T and by LD but the function of new neurons incorporated in HVC is poorly understood. We developed a procedure based on X‐ray focal irradiation to deplete neural progenitors adjacent to HVC and study the functional consequences. The decrease in neurogenesis increased the variability of T‐induced songs in females and decreased their bandwidth. Neurogenesis in HVC thus plays a role in song production and X‐ray focal irradiation represents an excellent tool to analyze adult neurogenesis.","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"119 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel W. Hart, E. Roberts, M. J. O'Riain, R. P. Millar, N. C. Bennett
{"title":"The curious case of the hypothalamic–pituitary–gonadal axis dysfunction in subordinate female naked mole-rats (Heterocephalus glaber): No apparent role of opioids and glucocorticoids","authors":"Daniel W. Hart, E. Roberts, M. J. O'Riain, R. P. Millar, N. C. Bennett","doi":"10.1111/jne.13444","DOIUrl":"10.1111/jne.13444","url":null,"abstract":"<p>The naked mole-rat (<i>Heterocephalus glaber</i>) is a unique model mammal in which to study socially induced inhibition of the hypothalamic–pituitary–gonadal (HPG) axis. Naked mole-rat groups exhibit a high degree of reproductive bias in which breeding is restricted to one female (the queen) and one male, with subordinate non-breeding colony members rarely, if ever, having the opportunity to reproduce due to a dysfunctional HPG axis. It is posited that aggression directed at subordinates by the queen suppresses reproduction in these subordinates, yet the underlying physiological mechanisms causing this dysfunction are unknown. This study aimed to investigate the possible factors contributing to the dysfunction of the HPG axis in subordinate female naked mole-rats with a specific focus on the role of ovarian feedback and stress-related factors such as circulating glucocorticoid and endogenous opioid peptides. The results showed that stress-related factors appear to not mediate the suppression of reproductive function in subordinate female naked mole rats. Indeed, in some cases, the activation of the stress axis may lead to reproductive activation instead of deactivation. At the same time, the role of ovarian sex steroid feedback in reproductive suppression is likely limited and not clearly delineated. This study highlights the need for detailed studies to elucidate the mechanism of reproductive suppression in this unique model mammalian species which may shed light on, and reveal novel mechanisms, in the social regulation of reproduction.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shiwei Guo, Heshui Wu, Suizhi Gao, Weiyu Hu, Hui Jiang, Yun Bian, Yijie Zhang, Bo Li, Gang Li, Xuefeng Xu, Min Wang, Chenglin Zhu, Linlin Qu, Qiang Huang, Renyi Qin, Wenhui Lou, Gang Jin
{"title":"Real‐world effectiveness of adjuvant octreotide therapy in patients with pancreatic neuroendocrine tumors at high recurrence risk: A multicenter retrospective cohort study","authors":"Shiwei Guo, Heshui Wu, Suizhi Gao, Weiyu Hu, Hui Jiang, Yun Bian, Yijie Zhang, Bo Li, Gang Li, Xuefeng Xu, Min Wang, Chenglin Zhu, Linlin Qu, Qiang Huang, Renyi Qin, Wenhui Lou, Gang Jin","doi":"10.1111/jne.13442","DOIUrl":"https://doi.org/10.1111/jne.13442","url":null,"abstract":"Adjuvant therapy for pancreatic neuroendocrine tumors (PanNETs) after radical resection lacks evidence‐based data and remains controversial. This study aimed to validate whether long‐acting octreotide is a potential candidate for adjuvant therapy in patients with G2 PanNETs at high recurrence risk by clustering real‐world data. A retrospective review of patients with nonmetastatic grade 2 PanNETs who underwent radical resection at six research centers between 2008 and 2020 was conducted. Propensity score matching and inverse probability of treatment weight analysis were used to control confounding factors. Overall, 357 patients (octreotide group, <jats:italic>n</jats:italic> = 82; control group, <jats:italic>n</jats:italic> = 275) were analyzed. Kaplan–Meier survival analyses showed that the octreotide group had longer disease‐free survival (DFS) compared with the control group (36 months: 93.3% vs. 79.0%, <jats:italic>p</jats:italic> = .0124; 60 months: 71% vs. 67.6%, <jats:italic>p</jats:italic> = .0596, respectively), as well as overall survival (OS) (60 months: 98% vs. 83.8%, <jats:italic>p</jats:italic> = .0117, respectively). Multivariate analyses indicated that octreotide long‐acting repeatable (LAR) adjuvant therapy was associated with higher OS (<jats:italic>p</jats:italic> = .0270) at 60 months. Propensity score matching analysis showed that octreotide adjuvant therapy was associated with higher DFS (<jats:italic>p</jats:italic> = .0455) and OS (<jats:italic>p</jats:italic> = .0190) at 60 months. Similar results were obtained via inverse probability of treatment weight analysis. Subgroup analysis indicated that octreotide LAR was associated with a high DFS in patients with lymph node metastasis or Ki‐67 <10% PanNETs. Adjuvant therapy with long‐acting octreotide following radical resection of nonmetastatic G2 PanNETs may be associated with improved DFS and OS in a real‐world setting.","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"1 1","pages":"e13442"},"PeriodicalIF":3.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lacey Plummer, Ravikumar Balasubramanian, Maria Stamou, Mark Campbell, Pranav Dewan, Nora Bryant, Kathryn Salnikov, Margaret Lippincott, Stephanie Seminara
{"title":"Lack of a genetic risk continuum between pubertal timing in the general population and idiopathic hypogonadotropic hypogonadism","authors":"Lacey Plummer, Ravikumar Balasubramanian, Maria Stamou, Mark Campbell, Pranav Dewan, Nora Bryant, Kathryn Salnikov, Margaret Lippincott, Stephanie Seminara","doi":"10.1111/jne.13445","DOIUrl":"10.1111/jne.13445","url":null,"abstract":"<p>Pubertal timing is a highly heritable trait in the general population. Recently, a large-scale exome-wide association study has implicated rare variants in six genes (<i>KDM4C</i>, <i>MC3R</i>, <i>MKRN3</i>, <i>PDE10A</i>, <i>TACR3</i>, and <i>ZNF483</i>) as genetic determinants of pubertal timing within the general population. Two of the genes (<i>TACR3</i>, <i>MKRN3</i>) are already implicated in extreme disorders of pubertal timing. This observation suggests that there may be a pervasive “genetic risk continuum” wherein genes that govern pubertal timing in the general population, by extension, may also be causal for rare Mendelian disorders of pubertal timing. Hence, we hypothesized that the four novel genes linked to pubertal timing in the population will also contribute to idiopathic hypogonadotropic hypogonadism (IHH), a genetic disorder characterized by absent puberty. Exome sequencing data from 1322 unrelated IHH probands were reviewed for rare sequence variants (RSVs) (minor allele frequency bins: <1%; <0.1%; <0.01%) in the six genes linked to puberty in the general population. A gene-based rare variant association testing (RVAT) was performed between the IHH cohort and a reference public genomic sequences repository—the Genome Aggregation Database (gnomAD). As expected, RVAT analysis showed that RSVs in <i>TACR3</i>, a known IHH gene, were significantly enriched in the IHH cohort compared to gnomAD cohort across all three MAF bins. However, RVAT analysis of the remaining five genes failed to show any RSV enrichment in the IHH cohort across all MAF bins. Our findings argue strongly against a pervasive genetic risk continuum between pubertal timing in the general population and extreme pubertal phenotypes. The biologic basis of such distinct genetic architectures' merits further evaluation.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"36 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jannis Ulke, Simran Chopra, Otsuware Linda‐Josephine Kadiri, Peter Geserick, Vanessa Stein, Sahar Cheshmeh, André Kleinridders, Kai Kappert
{"title":"PTPRJ is a negative regulator of insulin signaling in neuronal cells, impacting protein biosynthesis, and neurite outgrowth","authors":"Jannis Ulke, Simran Chopra, Otsuware Linda‐Josephine Kadiri, Peter Geserick, Vanessa Stein, Sahar Cheshmeh, André Kleinridders, Kai Kappert","doi":"10.1111/jne.13446","DOIUrl":"https://doi.org/10.1111/jne.13446","url":null,"abstract":"Central insulin resistance has been linked to the development of neurodegenerative diseases and mood disorders. Various proteins belonging to the enzyme family of protein tyrosine phosphatases (PTPs) act as inhibitors of insulin signaling. Protein tyrosine phosphatase receptor type J (PTPRJ) has been identified as a negative regulator in insulin signaling in the periphery. However, the impact of PTPRJ on insulin signaling and its functional role in neuronal cells is largely unknown. Therefore, we generated a <jats:italic>Ptprj</jats:italic> knockout (KO) cell model in the murine neuroblast cell line Neuro2a by CRISPR‐Cas9 gene editing. <jats:italic>Ptprj</jats:italic> KO cells displayed enhanced insulin signaling, as shown by increased phosphorylation of the insulin receptor (INSR), IRS‐1, AKT, and ERK1/2. Further, proximity ligation assays (PLA) revealed both direct interaction of PTPRJ with the INSR and recruitment of this phosphatase to the receptor upon insulin stimulation. By RNA sequencing gene expression analysis, we identified multiple gene clusters responsible for glucose uptake and metabolism, and genes involved in the synthesis of various lipids being mainly upregulated under PTPRJ deficiency. Furthermore, multiple Ca<jats:sup>2+</jats:sup> transporters were differentially expressed along with decreased protein biosynthesis. This was accompanied by an increase in endoplasmic reticulum (ER) stress markers. On a functional level, PTPRJ deficiency compromised cell differentiation and neurite outgrowth, suggesting a role in nervous system development. Taken together, PTPRJ emerges as a negative regulator of central insulin signaling, impacting neuronal metabolism and neurite outgrowth.","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"31 1","pages":"e13446"},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicolas Gutierrez‐Castellanos, Inês C. Dias, Basma F. A. Husain, Susana Lima
{"title":"Functional diversity along the anteroposterior axis of the ventromedial hypothalamus","authors":"Nicolas Gutierrez‐Castellanos, Inês C. Dias, Basma F. A. Husain, Susana Lima","doi":"10.1111/jne.13447","DOIUrl":"https://doi.org/10.1111/jne.13447","url":null,"abstract":"Innate behaviors ensure animal survival and reproductive success. Defending their territory, escaping from predators or mating with a sexual partner, are fundamental behaviors determining the ecological fitness of individuals. Remarkably, all these behaviors share a common neural substrate, as they are under the control of the ventromedial hypothalamus (VMH). Decades of research have contributed to understanding the exquisite diversity of functional ensembles underlying the wide array of functions that the VMH carries out. These functional ensembles are usually distributed throughout the dorsoventral and mediolateral axes of this nucleus. However, increasing evidence is bringing to attention the functional diversity of the VMH across its anteroposterior axis. In this review, we will overview our current understanding of how different ensembles within the VMH control a wide array of animal behaviors, emphasizing the newly discovered roles for its anterior subdivision in the context of conspecific self‐defense.","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"254 1","pages":"e13447"},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Halfdan Sorbye, Grace Kong, Simona Grozinsky-Glasberg, Jonathan Strosberg
{"title":"PRRT in high-grade digestive neuroendocrine neoplasms (NET G3 and NEC).","authors":"Halfdan Sorbye, Grace Kong, Simona Grozinsky-Glasberg, Jonathan Strosberg","doi":"10.1111/jne.13443","DOIUrl":"https://doi.org/10.1111/jne.13443","url":null,"abstract":"<p><p>Peptide receptor radionuclide therapy (PRRT) has been primarily studied in low and intermediate-grade digestive neuroendocrine tumors (NET G1-G2). The documentation of a similar benefit for high-grade digestive neuroendocrine neoplasms (NEN) has been limited. This review evaluates the use of PRRT for high-grade digestive NEN (well-differentiated NET G3 and poorly differentiated neuroendocrine carcinomas [NEC]). We identified one phase III trial and seven retrospective studies reporting specifically on PRRT outcome of >10 digestive high-grade NEN patients. The retrospective single-arm studies indicate a benefit for PRRT in NET G3. The randomized phase III NETTER-2 trial demonstrates major PFS superiority of PRRT versus somatostatin analog therapy as the first-line treatment for the NET G3 subgroup. PRRT can now be considered a potential first-line treatment for somatostatin receptor-positive NET G3 patients, but whether it should be the first-line standard of care for all NET G3 patients is still not clarified. For NEC, scarce data are available, and pathologic distinction between NEC and NET G3 can be difficult when Ki-67 is below 55%. PRRT could be considered as a treatment for refractory NEC in very selected cases when there is a high uptake on somatostatin receptor imaging, Ki-67 is below 55%, and there is no rapid tumor progression.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13443"},"PeriodicalIF":3.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Davide Ravizza, Mariangela Giunta, Isabella Sala, Vincenzo Bagnardi, Darina Tamayo, Giuseppe de Roberto, Cristina Trovato, Ivana Bravi, Pietro Soru, Margherita Maregatti, Eleonora Pisa, Emilio Bertani, Guido Bonomo, Francesca Spada, Fazio Nicola
{"title":"Gastric neuroendocrine tumors: 20-Year experience in a reference center.","authors":"Davide Ravizza, Mariangela Giunta, Isabella Sala, Vincenzo Bagnardi, Darina Tamayo, Giuseppe de Roberto, Cristina Trovato, Ivana Bravi, Pietro Soru, Margherita Maregatti, Eleonora Pisa, Emilio Bertani, Guido Bonomo, Francesca Spada, Fazio Nicola","doi":"10.1111/jne.13440","DOIUrl":"https://doi.org/10.1111/jne.13440","url":null,"abstract":"<p><p>Few studies have been published on the long-term outcomes of patients with gastric neuroendocrine tumors (gNETs). We analyzed their management over a two-decade period, focusing on endoscopic and clinical outcomes. Clinical, laboratory, endoscopic, surgical, and histopathological data from Types 1 and 3 gNETs histologically diagnosed between March 2000 and December 2021 at the European Institute of Oncology (IEO, Milan) were retrospectively collected. Sixty-nine patients were included (60 Type 1, 9 Type 3): 53 (77%) were treated endoscopically, 6 (9%) surgically, and 10 (14%) did not receive any treatment. Overall, 293 lesions were removed endoscopically: 74% by forceps, 20% by endoscopic mucosal resection (EMR), and 5% by endoscopic submucosal dissection (ESD). No differences were observed between EMR and ESD in terms of complete resection rate (p value = .50) and complications rate (p value = .084). The median follow-up period was 5.8 years (range: 0.3-20.5), during which no gNET-related deaths were observed. Metachronous gNETs developed in 60% of patients with Type 1 gNET. Six patients with lymph node metastases (LNM) were younger (p value = .006) and had larger lesions (p value <.001) than patients without LNM. Most Type 1 gNETs were successfully excised using forceps, with EMR and ESD being equally effective. The presence of incomplete resection was not associated with a worse prognosis, which remains excellent in this highly recurrent disease. Younger age and a size ≥10 mm were associated with an increased risk of LNM. CLINICAL TRIAL REGISTRATION: Project code UID 2854.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13440"},"PeriodicalIF":3.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}