[15,41,42] Vanoli et al reported in 1 patient with type A-CAG and type I gastric NET treated by antrectomy a decrease in gastrin levels to undetectable levels, and a regression of ECL cell hyperplasia postoperatively, without NET recurrence. patients were diagnosed with FGPs, 1.8% with hyperplastic polyps, 0.1% with gastric adenomas and 0.06% with type I neuroendocrine tumours (NETs). Cells were positive for synaptophysin present in aggregates measuring up to 0.9 mm (Figure 2). Search for Similar Articles Machado JC, Carneiro F, Blin N, Sobrinho-Simes M. Eur J Cancer Prev. The excess gastrin binds to enterochromaffin-like cells causing hyperplasia, which may progress to dysplasia and rarely to gastric neuroendocrine tumors. 1993;7 Suppl 1:25-8, discussion 29-31. 2019 Sep 6;7(17):2413-2419. doi: 10.12998/wjcc.v7.i17.2413. There are no specific recommendations for the study of the hormone secretion profile, however, There is very limited data about molecular alterations in colorectal neuroendocrine tumors; most molecular analyses have been performed in pancreatic and small intestine tumors (, Well differentiated neuroendocrine tumor, WHO grade 2 (G2), 7 mm (see comment), Comment: There are 2 mitotic figures in 2 mm, High grade tumors with poorly differentiated morphology, Atypical small or large cells organized in diffuse sheets with little nesting, Apoptotic bodies and necrosis are usually observed, They are high grade by definition (mitoses > 20 per 10 high power fields or, Remember that there are some G3 neuroendocrine tumors; poorly differentiated morphology is the main feature to distinguish neuroendocrine carcinomas from G3 neuroendocrine tumors, CD56 immunostaining is more specific than synaptophysin for its diagnosis, CDX2 expression may indicate the site of origin of this type of tumor, Presence / absence of necrosis is the main feature in defining the tumor grade, Proliferative activity is not relevant in these tumors. [46]. Wolters Kluwer Health 2005 May-Jun;52(63):731-41. 1 Introduction. Post author: Post published: March 31, 2022 Post category: how to recover my mahzooz account Post comments: cu restaurant lisburn road cu restaurant lisburn road Modlin IM, Lye KD, Kidd M. Carcinoid tumors of the stomach. Am J Surg Pathol. It is unclear whether the two pathologies occurred simultaneously or independently. Gastroenterol Res Pract 2014;2014: 253860. Consequently, these lesions tend to remain widely underdiagnosed until they progress to easily recognizable neuroendocrine tumors. noma, neuroendocrine carcinomas, and small cell Barrett's esophagus and adenocarcinoma remain carcinoma, also occur . Careers. Endoscopy 2010;42:66471. Department of Pathology Stanford University School of Medicine Stanford CA 94305-5342 . The cells were positive for chromogranin A, synaptophysin, gastrin and cluster of differentiation 56 (Fig. and transmitted securely. Thus, for patients with atrophic gastritis and associated G-cell hyperplasia, consideration should be given to evaluate with interval surveillance endoscopy with gastric mapping biopsies to assess for gastric intestinal metaplasia and stomach cancer. 2. ACG Case Reports Journal8(8):e00649, August 2021. EUS was grossly normal without findings of a primary tumor or mucosal abnormalities. These NENs precursor endocrine cells may vary from 1 site to the other, depending on the functional necessities of each site. The authors thank Ms. Stephanie Stebens, MLIS, AHIP, and Dr. Karla D. Passalacqua, PhD, at Henry Ford Hospital for editorial assistance and manuscript formatting. [15]. The neuroendocrine . [1]. Virchows Arch 1995;425:54760. Front Med (Lausanne). Although few previous cases have reported autoimmune gastritis and its association with G-cell hyperplasia and hypergastrinemia,79 this is the first known report of endoscopic findings of AMAG associated with G-cell hyperplasia showing the full developmental spectrum of ECL cell proliferation from hyperplasia to dysplasia to neuroendocrine tumor. Atrophic body gastritis patients with enterochromaffin-like cell dysplasia are at increased risk for the development of type I gastric carcinoid. 6. 2020;59(6):799803. Pathol Oncol Res 2011;17:75963. Sato Y. Endoscopic diagnosis and management of type I neuroendocrine tumors. Alsaad KO, Serra S, Schmitt A, Perren A, Chetty R. Cytokeratins 7 and 20immunoexpression profile in goblet cell and classical carcinoids of appendix. Given the potential to develop type 1 GNET and metastatic disease, these patients may benefit from routine endoscopy for dysplasia surveillance. Neuroendocrinology 2004;80: (Suppl 1): 125. Tumors were limited to the superficial part of the submucosa, without lymph node involvement. Patients with small intestinal neuroendrocrine tumors frequently show clinical symptoms and develop distant metastases more often than those with neuroendocrine tumors of other organs. World J Clin Cases. Occurrence of gastric cancer and carcinoids in atrophic gastritis during prospective long-term follow up. 11. The unique aspect of this case consists of the presence of a previously treated prostatic malignancy, with an apparently good outcome in the absence of lymph nodes and bone metastasis, and the subsequent detection of an advanced metastatic disease. Immunohistochemical profile showed positive staining with chromogranin A (Fig. ScientificWorldJournal. The largest gastric tumor represented a G2 NET, infiltrating the gastric submucosa. Hypergastrinemia represents the stimulus for hyperplastic proliferation of ECL cells and the development of NETs. G1 NETs are tumors presenting <2 mitoses/10 HPF, with a Ki-67 index <2%. Careers. Unable to load your collection due to an error, Unable to load your delegates due to an error. . (B) Biopsies of the gastric body revealed hallmark features of autoimmune gastritis including antralization with loss of oxyntic glands and showed (C) the full spectrum of disordered enterochromaffin-like cell proliferation from hyperplasia to dysplasia to microneuroendocrine tumor (1 mm, MIB1 < 3%). The smaller gastric nodules were G1 NETs, with Ki-67 index <2%, and 1 mitosis/10 HPF. FOIA Yao JC, Hassan M, Phan A, et al. Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment and is raised in both functioning and non-functioning neuroendocrine tumors. [49] In the presence of metastases, cytoreduction surgery is recommended to control symptoms and hormonal hypersecretion. In these circumstances, we concluded that the tumor represented a type 3 gastric NET, detected in an advanced, metastatic stage. Disclaimer, National Library of Medicine In all cases, the neuroendocrine component was present within and between the hyperplastic foveolar glands of the polyps and overall formed the minor part of the polyps. Thymus and lung. Manneh R, Castellano D, Caso O, et al. An official website of the United States government. As a result, the marked hypergastrinemia was considered to have been caused by G-cell hyperplasia related to a block in the negative feedback mechanism of somatostatin against achlorhydria with autoimmune gastritis. WebPathology is a free educational resource with 11,859 high quality pathology images of benign and malignant neoplasms and related entities. -, Taal BG, Visser O. [53]. Endocr Pathol 2021;32:51723. Nassereddine H, Chicaud M, Rebah K, et al. The histopathological evaluation of the polypectomy specimen revealed a nodular tumor of 10 mm diameter, with typical neuroendocrine features invading the mucosa, and with minimal extension in the submucosa. Surgery for GEP-NETs. Published by Wolters Kluwer Health, Inc. Tsai HJ, Wu CC, Tsai CR, et al. Autoimmune atrophic gastritis with hypergastrinemia. WHO Classification of Tumours of the Digestive System. MeSH Autoimmune metaplastic atrophic gastritis (AMAG) is a chronic inflammatory disease characterized by immune-mediated replacement of gastric parietal cells with atrophic and metaplastic mucosa.1 Patients with AMAG often present with dyspepsia or symptomatic anemia; however, many remain asymptomatic in the early stages of the disease. 2015;50(7):85665. One review article suggests that surveillance every 612 months with endoscopic mucosal resection is sufficient for tumors less than 2 cm vs surgical antrectomy for larger or progressive tumors; however, data are limited on the optimal management of microneuroendocrine tumors.2 Some options to consider include EGD with EUS as was performed for our patient or potentially using virtual chromoendoscopy, an imaging technique that evolving research has shown to be beneficial in identifying and classifying neuroendocrine tumors.12,13. Serum parathormon, calcium and prolactin levels were normal. Disclaimer, National Library of Medicine Haruma K, Sumii K, Yoshihara M, Watanabe C, Kajiyama G. J Clin Gastroenterol. Endocrine cells in the GI tract consist of less than 1% of the mucosa; are normally distributed at the surface or base of glandular epithelial cells, such as in the gastric pits of the stomach and the crypts of the small intestine and colorectum; and contain secretory . Most of them are G1 NETs, rarely G2 NETs. PGAs most frequently present in the stomach, 12, . She underwent esophagogastroduodenoscopy (EGD) with random gastric biopsies showing grossly normal mucosa, was consistent with chronic inflammation and focal foveolar hyperplasia, and negative for Helicobacter pylori (Figure 1). Autoimmune metaplastic atrophic gastritis and association with neuroendocrine tumors of the stomach. Stanford University School of Medicine Autoimmune metaplastic atrophic gastritis is caused by immune-mediated destruction of gastric parietal cells. Metastases may occur in 10% to 30% of patients. Department of Pathology Stanford University School of Medicine Stanford CA 94305-5342 . [17]. The histological diagnosis and tumor grading according to standard terminology is important in estimating tumor behavior and in adopting the best therapeutic decision. [33]. Veyre F, Lambin T, Fine C, et al. Neuroendocrine nuttiness in the digestive system - Dr. Raul S. Gonzalez, GI neuroendocrine tumors classification - Dr. Vikram Deshpande. Exarchou K, Nathan Howes N, Pritchard DM. The https:// ensures that you are connecting to the bPathology Department, University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania. We wish to highlight the unusual occurrence of gastric neuroendocrine cell hyperplasia and type I neuroendocrine tumours within three hyperplastic polyps. The https:// ensures that you are connecting to the This leads to the absence of gastric acid production causing compensatory hyperplasia of gastric antral G-cells with hypergastrinemia.10 Furthermore, there is potentially decreased inhibition from gastric D-cells, contributing to increased gastrin production. [36], Type 3 NETs represent 15% to 20% of all g-NETs. government site. Carolina Martinez Ciarpaglini, M.D., Ph.D. Best Pract Res Clin Gastroenterol 2012;26:775, J Laparoendosc Adv Surg Tech A 2006;16:435, WHO Classification of Tumours Editorial Board: Digestive System Tumours, 5th Edition, 2019, Well differentiated tumors demonstrating morphological and immunohistochemical neuroendocrine differentiation, May be indolent and incidental or present with widespread metastases and have aggressive clinical course, The term neuroendocrine tumor (NET) comprises WHO G1, G2 and rare G3 lesions (depending on the proliferative activity), According to the 2017 WHO classification, the term MiNEN (mixed neuroendocrine neoplasm) comprises mixed neuroendocrine and nonneuroendocrine proliferations (, The nonneuroendocrine component may be adenocarcinoma, squamous cell carcinoma, among others, Each component must be 30% to fall into the category of MiNEN, Incidence of colorectal neuroendocrine tumors has been continuously increasing over the past few decades (incidence: 1.04 per 100,000 persons) (, Colorectal neuroendocrine tumors comprise roughly 30% of neuroendocrine tumors in the digestive system (, According to the WHO classification (5th edition), there is a slight male predominance and the median age of presentation is 56 years for rectal tumors and 65 years for colonic tumors, In the large intestine (excluding the appendix), the most frequent location is the rectum (34% of all gastrointestinal neuroendocrine tumors) (, In the colon, neuroendocrine tumors are more frequent in the cecum (69.6%), followed by sigmoid (13.0%), ascending colon (13.0%) and transverse colon (4.3%) (, Colon proper is the least common site for intestinal well differentiated neuroendocrine tumors; around 7.5% of all neuroendocrine tumors are of colonic origin (, Colonic NETs arise from Kulchitsky cells or enterochromaffin cells located within the crypts of Lieburkuhn of the colon (, Patients with colonic neuroendocrine tumors may present with pain, bleeding, altered bowel habits, weight loss, anorexia or even bowel obstruction (, Carcinoid syndrome occurs in patients with liver metastasis, Prognosis largely depends on the grade and stage of the tumor; median overall survival ranges from 22 months in G1 - G2 tumors to 12 months in G3 tumors according to the WHO classification (5th edition), Increased risk of lymph node metastasis according to size: around 1% in tumors < 10 mm, 23% in tumors from 10 - 20 mm and 50% in tumors > 20 mm (, G3 colorectal neuroendocrine tumors show an intermediate behavior between G2 neuroendocrine tumors and neuroendocrine carcinomas (, > 50% are discovered during routine colonoscopy for colorectal cancer screening (, Rectal tumors may present with symptoms such as bleeding or change in bowel habits (, Since few colorectal neuroendocrine tumors produce serotonin, routine analysis of plasma or urinary 5-hydroxyindoleacetic acid (5-HIAA) is not useful (, Serum chromogranin A (CgA) is the most common biomarker used to assess the bulk of disease and monitor treatment; it is elevated in both functioning and nonfunctioning neuroendocrine tumors (, Rectal neuroendocrine tumors are commonly small and generally low to intermediate grade (G1 or G2), whereas colonic tumors are often aggressive, poorly differentiated and higher grade (G3) (, Colorectal tumors < 10 mm have a low rate (1.95%) of lymph node metastasis (, Lymphatic invasion and WHO grade are independent predictive factors of lymph node metastasis (, Number of positive locoregional lymph nodes is an independent prognostic factor of survival (, HES77 expression is also linked to worse prognosis (, 47 year old man with a polypoid mass in the right colic flexure (, 57 year old man with perforatedcolonictumor with liver metastasis(, 64 year old man presented with carcinoidsyndrome (, 85 year old woman presented with mixed neuroendocrine and nonneuroendocrine neoplasms (, For lesions < 10 mm with no involvement of muscularis propria, transanal endoscopic microsurgery is usually sufficient (, Larger or high risk tumors may require surgery (, Positive margins may not increase risk of recurrence (, Most colorectal neuroendocrine tumors appear as yellow or pale, polypoid or flat, doughnut shaped lesions or submucosal nodules (. N Engl J Med 2000;343:5514. The features are consistent with autoimmune gastritis in the appropriate clinical context. . [35]. [7]. We performed an upper gastrointestinal endoscopy with narrow-band imaging. During Caduet drug therapy, a variety of unwanted effects may arise, among which the most common is peripheral edema. [24] There are solitary and large tumors (>2 cm) arising in any part of the stomach, most frequently in males over 50 years old, unrelated to gastrin levels. 2022 Oct 26;10(30):10906-10920. doi: 10.12998/wjcc.v10.i30.10906. In our case series we presented different clinical scenarios that may be encountered in practice regarding gastric NENs. The Author(s) 2020. MeSH Proposed grading scale based on proliferation. Critical evaluation of a histological classification. Department of Pathology [6]. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocr Pathol. Tumors occur in normal (nonatrophic) mucosa, without ECL cells proliferations. Contributed by Carolina Martinez Ciarpaglini, M.D., Ph.D. HE = hematoxylineosin stain. WHO Classification of Tumours of the Digestive System. Unusually aggressive type 1 gastric carcinoid: a case report with a review of the literature. In conclusion, AMAG is a rare but important condition to consider on the differential diagnosis in patients with dyspepsia, especially in the setting of other autoimmune comorbidities. Islet Cell Hyperplasia / Aggregation Pancreatic Neuroendocrine Microadenoma; Irregular, non-circumscribed : . stomach, Neuroendocrine cell - Hyperplasia in a female F344/N rat from a chronic study (Sevier-Munger stain). The surrounding mucosa was hypertrophic, with different type of ECL cell proliferation, including linear, nodular and dysplastic lesions in the antrum as well as in the corpus, without metaplastic changes or glandular atrophy. Please enable scripts and reload this page. Li TT, Qiu F, Qian ZR, et al. [27]. In the second clinical case a 61-year-old man was admitted with heartburn, abdominal pain, diarrhea and mild iron deficiency anemia. 1995;19 Suppl 1:S1-7. WHO International Histological Classification of Tumours 2nd edBerlin: Springer; 2000. She was subsequently diagnosed with a type 1 microneuroendocrine tumor with reconfirmation of AMAG and G-cell hyperplasia, and she is currently undergoing surveillance endoscopy for cancer progression. In countries with a socialized healthcare sys- can outline an individualized goal-directed . Copyright PathologyOutlines.com, Inc. Click, 30100 Telegraph Road, Suite 408, Bingham Farms, Michigan 48025 (USA). g-NENs are rare tumors with distinct clinical and histological features. Tumor has non-ECL origin and is not associated with autoimmune gastritis or gastrinoma, being gastrin-independent. They may display different proliferation degrees (G1, G2, or G3). [58] Although up to 5 neuroendocrine cell types have been described in human gastric mucosa, most g-NENs are composed of nonfunctioning ECL (enterochromaffin-like) cells. WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010. 10. [24]. Clin Med Res 2010;8:1821. However, we cannot answer medical or research questions or give advice. Epithelial dysplasia of the stomach with gastric immunophenotype shows features of biological aggressiveness. Highlight selected keywords in the article text. A possible explanation for this behavior could be the persistence of ectopic gastrin cells in atrophic corporeal mucosa and hypergastrinemia which promotes tumor growth. [15] Peritumoral mucosa in both type 1 and type 2 g-NETs shows hyperplastic and/or dysplastic proliferations of ECL cells, which are regarded as precursor lesions for these NETs. https://www.cancer.net/cancer-types/neuroendocrine-tumor-gastrointestina NCI CPTC Antibody Characterization Program, Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. http://surgpathcriteria.stanford.edu/, Robert V Rouse MD AMAG is characterized by immune-mediated destruction of gastric parietal cells. [10]. This website uses cookies. Autoimmune gastritis: Pathologist's viewpoint. South Med J. Praxis (Bern 1994). The gastrointestinal tract has different types of endocrine cells that vary from 1 site to another, depending of the functional needs of each region. 1976;69(12):15513. Hum Pathol 2013;44:182737. Neuroendocrine Tumor of the Gastrointestinal Tract: Introduction. Federal government websites often end in .gov or .mil. Nehme F, Rowe K, Palko W, et al. Biopsies were performed from the antral lesion, from the surrounding antral mucosa and from the corporeal mucosa. Caduet Side Effects. [36]. [55,56] Another particularity of this case is the detection of a well-differentiated G2 tumor with liver metastases. The antrum contains gastrin secreting cells or G-cells. Rindi G, Klimstra DS, Abedi-Ardekani B, et al. The immunohistochemical examination with chromogranin A and synaptophysin highlighted also a linear and nodular hyperplasia of endocrine cell only in the corpus. 2001 Dec;13(12):1449-56. Neuroendocrinology 2004;80: (Suppl 1): 169. Examining rectal carcinoids in the era of screening colonoscopy: a surveillance, epidemiology, and end results analysis. By continuing to use this website you are giving consent to cookies being used. The stomach of MEN-1 patients with ZES shows diffuse hyperplasia of enterochromaffin-like (ECL) cells in the corpus-fundus mucosa. Case Report: Two Is Not (Always) Better Than One: Pyloric Gland Adenoma of the Gastric Cardia and Concurrent Neuroendocrine Cell Dysplasia Arising From Autoimmune Gastritis. The classifications of neuroendocrine proliferations that lead from enterochromaffin-like cell hyperplasia to neuroendocrine tumors in the stomach are complicated and relatively inaccessible to nonspecialists. Department of Pathology, University of Szeged and Albert Szent-Gyrgyi Health Center, Szeged, Hungary. The changing face of chronic autoimmune atrophic gastritis: An updated comprehensive perspective. Endoscopic characterization of rectal neuroendocrine tumors with virtual chromoendoscopy: Differences between benign and malignant lesions. The pathologist who follows our simple steps will be better aware of this neglected area of gastric pathology and will learn to suspect, recognize, and accurately diagnose the most common abnormalities of the neuroendocrine system in the stomach. Endoscopic images of the (A) gastric fundus, (B) body, and (C) antrum. Download Citation | On Jan 15, 2023, Yi-Lin Zhong and others published Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer: A critical review | Find . Aliment Pharmacol Ther. Correlation with clinical and laboratory findings is recommended. Endoscopy 2003;35:2036. [57]. [25]. Endocrinol Diabetes Metab Case Rep 2018;2018: 18-0048. Some error has occurred while processing your request. Prostate carcinoma metastatic to the stomach: report of two cases and review of the literature. In such cases, immunostaining positive for prostate-specific antigen and cytokeratin, and negative for chromogranin suggests the diagnosis. Patients with colonic neuroendocrine tumors may present with pain, bleeding, altered bowel habits, weight loss, anorexia or even bowel obstruction ( Best Pract Res Clin Gastroenterol 2012;26:775 ) Carcinoid syndrome occurs in patients with liver metastasis. [56]. Oesophageal neuroendocrine tumours-case series of a rare malignancy. [19]. [25,26] The histological evaluation shows well-differentiated cells, growing in trabecular patterns, usually confined to mucosa or submucosa, immunoreactive for chromogranin A and synaptophysin, vesicular monoamine transporter 2, and somatostatin receptor 2A. Gastric neuroendocrine neoplasms (g-NENs) represent a distinctive group of gastric tumors, stratified into different prognostic categories according to different histological characteristics, put forth in the 2018 World Health Organization classification system. G-cells are located at the base of mucous neck cells and in the superficial mucous gland cells. doi: 10.1093/jscr/rjac582. Roberto GA, Rodrigues CMB, DAlpino Peixoto R, Younes RN. Random biopsies were obtained of the gastric antrum and body with immunohistochemistry demonstrating G cells by (A) gastrin immunostaining, (B) positive synaptophysin present in aggregates measuring up to 0.9 mm, and (C) Ki-67 proliferation index of less than 3% within these aggregates with MIB1 staining. 2012;2012:869769. Adv Anat Pathol. Nikou GC, Lygidakis NJ, Toubanakis C, Pavlatos S, Tseleni-Balafouta S, Giannatou E, Mallas E, Safioleas M. Hepatogastroenterology. Liver metastases in prostate carcinoma: clinical characteristics and outcome. Clipboard, Search History, and several other advanced features are temporarily unavailable. Tumors characterized by more than 20 mitoses/10 HPF, and a Ki-67 proliferative index >20% represent NECs. Risk factors and clinical correlates of neoplastic transformation in gastric hyperplastic polyps in Chinese patients. Their morphology, histogenesis, and natural history. Miyazaki Y, Shinomura Y, Murayama Y, et al. Chromogranin immunostaining revealing a nodular proliferation of positive cells in the mucosa in the setting of extensive intestinal metaplasia and glandular atrophy (2). After a literature search, we found that liver metastases secondary to prostatic adenocarcinoma are very uncommon, and usually occur in patients presenting a systemic aggressive disease with bone and/or lymph node metastases. In type 2 g-NET associated with pancreatic gastrinoma, pancreaticoduodenectomy with total gastrectomy were performed. 2021;53(6):E2156. The cells were positive for chromogranin A and synaptophysin (Fig. Next, EGD with endoscopic ultrasound (EUS) of the gastrinoma triangle was performed. Most of the lesions are represented by tumors.[14]. . Bordi C, Azzoni C, D'Adda T, Caruana P, Carlinfante G. Pathologe. Laboratory showed elevated fasting serum gastrin levels (969 pg/mL). Gastric neuroendocrine neoplasms. [58]. 2021 Nov 15;11(11):2113. doi: 10.3390/diagnostics11112113. Clipboard, Search History, and several other advanced features are temporarily unavailable. Systematic review: management of localised low-grade upper gastrointestinal neuroendocrine tumours. At the level of duodenum, multiple ulcers were found (Fig. Histologic changes in type A chronic atrophic gastritis indicating increased risk of neuroendocrine tumor development: the predictive role of dysplastic and severely hyperplastic enterochromaffin-like cell lesions. An official website of the United States government. Endocrine tumours of the gastrointestinal tract-selected topics. Rev Med Liege. to maintaining your privacy and will not share your personal information without [8]. Scand J Gastroenterol. The classifications of neuroendocrine proliferations that lead from enterochromaffin-like cell hyperplasia to neuroendocrine tumors in the stomach are complicated and relatively inaccessible to nonspecialists. Am J Surg Pathol. Vanoli A, La Rosa S, Luinetti O, et al. PMC
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