{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:23:52Z","timestamp":1793298232657,"version":"4.5.0"},"reference-count":136,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Lung carcinoids are neuroendocrine tumors, categorized as typical or atypical carcinoids based on their histological appearance. While most of these tumors are slow-growing neoplasms, they still possess malignant potential. Many patients are diagnosed incidentally on chest X-rays or CT scans. Presenting symptoms include cough, hemoptysis, wheezing, dyspnea, and recurrent pneumonia. Endocrine symptoms, such as carcinoid syndrome or ectopic Cushing\u2019s syndrome, are rare. Surgery is the primary treatment and should be considered in all patients with localized disease, even when thoracic lymph node metastases are present. Patients with distant metastases may be treated with somatostatin analogues, chemotherapy, preferably temozolomide-based, mTOR inhibitors, or peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. Most patients have an excellent prognosis. Poor prognostic factors include atypical histology and lymph node metastases at diagnosis. Long-term follow-up is mandatory since metastases may occur late.<\/jats:p>","DOI":"10.3390\/cancers15225440","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T08:19:43Z","timestamp":1700122783000},"page":"5440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Lung Carcinoids: A Comprehensive Review for Clinicians"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4854-6075","authenticated-orcid":false,"given":"Dan","family":"Granberg","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden"},{"name":"Department of Breast, Endocrine Tumors and Sarcomas, Karolinska University Hospital Solna, 17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5945-9081","authenticated-orcid":false,"given":"Carl Christofer","family":"Juhlin","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, 17164 Stockholm, Sweden"},{"name":"Department of Pathology and Cancer Diagnostics, Karolinska University Hospital Solna, 17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-6987","authenticated-orcid":false,"given":"Henrik","family":"Falhammar","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden"},{"name":"Department of Endocrinology, Karolinska University Hospital Solna, 17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1352-4332","authenticated-orcid":false,"given":"Elham","family":"Hedayati","sequence":"additional","affiliation":[{"name":"Department of Breast, Endocrine Tumors and Sarcomas, Karolinska University Hospital Solna, 17176 Stockholm, Sweden"},{"name":"Department of Oncology-Pathology, Karolinska Institutet, 17164 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"ref_1","first-page":"517","article-title":"Die \u201cHelle Zelle\u201d der Bronchialschleimhaut und ihre Beziehungen zum Problem der Chemoreceptoren","volume":"60","year":"1949","journal-title":"Frankf. Z. Pathol."},{"key":"ref_2","first-page":"73","article-title":"\u00dcber die Argyrophilie des Helle-Zelle-Systems in Bronchialbaum des Menschen","volume":"61","author":"Feyrter","year":"1954","journal-title":"Z. Mikrosk. Anat. Forsch."},{"key":"ref_3","first-page":"519","article-title":"Neuroendocrine Components of the Bronchopulmonary Tract: Hyperplasias, Dysplasias, and Neoplasms","volume":"49","author":"Gould","year":"1983","journal-title":"Lab. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/ar.1091720301","article-title":"Neuro-epithelial Bodies (Neuroreceptor or Secretory Organs?) in Human Infant Bronchial and Bronchiolar Epithelium","volume":"172","author":"Lauweryns","year":"1972","journal-title":"Anat. Rec."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1002\/1097-0142(196811)22:6<1163::AID-CNCR2820220612>3.0.CO;2-L","article-title":"Oat-Cell Carcinoma of the Lung. Its Origin and Relationship to Bronchial Carcinoid","volume":"22","author":"Bensch","year":"1968","journal-title":"Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/1097-0142(196505)18:5<592::AID-CNCR2820180508>3.0.CO;2-6","article-title":"Electron Microscopic and Biochemical Studies on the Bronchial Carcinoid Tumor","volume":"18","author":"Bensch","year":"1965","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/S0046-8177(82)80240-2","article-title":"Pulmonary neuroepithelial bodies, neuroendocrine cells, and pulmonary tumors","volume":"13","author":"Gould","year":"1982","journal-title":"Hum. Pathol."},{"key":"ref_8","first-page":"202","article-title":"Observations on Small Granule Cells in Adult Human Bronchial Epithelium and in Carcinoid and Oat Cell Tumors","volume":"34","author":"McDowell","year":"1976","journal-title":"Lab. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0022-5223(19)39836-8","article-title":"Atypical carcinoid tumors of the lung","volume":"64","author":"Arrigoni","year":"1972","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1002\/cncr.11105","article-title":"A 5-decade analysis of 13,715 carcinoid tumors","volume":"97","author":"Modlin","year":"2003","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/cncr.29099","article-title":"Exploring the rising incidence of neuroendocrine tumors: A population-based analysis of epidemiology, metastatic presentation, and outcomes","volume":"121","author":"Hallet","year":"2015","journal-title":"Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1001\/jamaoncol.2017.0589","article-title":"Trends in the Incidence, Prevalence, and Survival Outcomes in Patients with Neuroendocrine Tumors in the United States","volume":"3","author":"Dasari","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1378\/chest.119.6.1647","article-title":"Pulmonary carcinoid: Presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from the literature","volume":"119","author":"Fink","year":"2001","journal-title":"Chest"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.rmed.2008.05.003","article-title":"Clinico-pathologic study of pulmonary carcinoid tumours\u2014A retrospective analysis and review of literature","volume":"102","author":"Thomas","year":"2008","journal-title":"Respir. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20406223211035288","DOI":"10.1177\/20406223211035288","article-title":"Multiple endocrine neoplasia 1: A broad overview","volume":"12","author":"Thompson","year":"2021","journal-title":"Ther. Adv. Chronic. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.anndiagpath.2006.04.006","article-title":"Changing trends in the distribution of the histologic types of lung cancer: A review of 4439 cases","volume":"11","author":"Wahbah","year":"2007","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_17","first-page":"105","article-title":"Bronchial Carcinoid Tumors\u2014A Clinicopathologic Study of 82 Cases","volume":"19","author":"Bertelsen","year":"1985","journal-title":"Scand. J. Thor. Cardiovasc. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/0003-4975(92)91139-Z","article-title":"Bronchial Carcinoid Tumors: A Retrospective Analysis of 126 Patients","volume":"54","author":"Harpole","year":"1992","journal-title":"Ann. Thorac. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0022-5223(19)38842-7","article-title":"Bronchial carcinoids\u2014Review of 124 cases","volume":"89","author":"McCaughan","year":"1985","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/BF01658116","article-title":"Bronchial Carcinoids: An Analysis of 91 Cases","volume":"11","author":"Hambraeus","year":"1987","journal-title":"World J. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S0025-6196(12)60641-7","article-title":"Bronchial Carcinoid Tumors","volume":"68","author":"Davila","year":"1993","journal-title":"Mayo Clin. Proc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s002689900029","article-title":"Pulmonary and Thymic Carcinoid Tumors","volume":"20","author":"Dusmet","year":"1996","journal-title":"World J. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0002-9610(73)80020-0","article-title":"Carcinoid Syndrome in Bronchial Adenoma","volume":"126","author":"Ricci","year":"1973","journal-title":"Am. J. Surg."},{"key":"ref_24","first-page":"211","article-title":"Bronchopulmonary Carcinoids: An Analysis of 1,875 Reported Cases with Special Reference to a Comparison between Typical Carcinoids and Atypical Varieties","volume":"5","author":"Soga","year":"1999","journal-title":"Ann. Thorac. Cardiovasc. Surg."},{"key":"ref_25","first-page":"555","article-title":"Somatotroph Hyperplasia without Pituitary Adenoma Associated with a Long Standing Growth Hormone-Releasing Hormone-Producing Bronchial Carcinoid","volume":"78","author":"Ezzat","year":"1994","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1002\/1097-0142(19910515)67:10<2538::AID-CNCR2820671025>3.0.CO;2-A","article-title":"Growth-Hormone Releasing Hormone in a Bronchial Carcinoid","volume":"67","author":"Huber","year":"1991","journal-title":"Cancer"},{"key":"ref_27","unstructured":"Colby, T.V. (1994). Carcinoid and Other Neuroendocrine Tumors, Tumors of the Lower Respiratory Tract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/S0003-4975(10)64915-6","article-title":"Carcinoid Tumors of the Lung","volume":"22","author":"Okike","year":"1976","journal-title":"Ann. Thorac. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.36740\/WLek202010139","article-title":"Lung Nodule 25 Years after Lobectomy\u2014Recurrence of Bronchial Carcinoid","volume":"73","author":"Rosiek","year":"2020","journal-title":"Wiad. Lek."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Hay, I.D., and Wass, J.A.H. (2008). Clinical Endocrine Oncology, Blackwell Publishing Ltd.. [2nd ed.].","DOI":"10.1002\/9781444300222"},{"key":"ref_31","unstructured":"Mortensen, R. (1993). Current Protocols in Molecular Biology, Wiley."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Travis, W.D., Colby, T.V., Corrin, B., Shimosato, Y., and Brambilla, E. (1999). World Health Organization. Histological Typing of Lung and Pleural Tumours, Springer. [3rd ed.].","DOI":"10.1007\/978-3-642-60049-4"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1097\/00000478-199808000-00003","article-title":"Survival Analysis of 200 Pulmonary Neuroendocrine Tumors with Clarification of Criteria for Atypical Carcinoid and Its Separation From Typical Carcinoid","volume":"22","author":"Travis","year":"1998","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_34","unstructured":"Travis, W.D., Brambilla, E., M\u00fcller-Hermelink, H.K., and Harris, C.C. (2004). World Health Organization Classification of Tumours. Pathology & Genetics. Tumours of the Lung, Pleura, Thymus and Heart, IARCPress."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1097\/JTO.0000000000000630","article-title":"The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification","volume":"10","author":"Travis","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3109\/01913128409016661","article-title":"Immunohistochemical and Ultrastructural Analysis of Bronchopulmonary Neuroendocrine Neoplasms. I. Carcinoids","volume":"6","author":"Warren","year":"1984","journal-title":"Ultrastruct. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/S0344-0338(11)80538-8","article-title":"Bronchial Carcinoids with S-100 Positive Sustentacular Cells. A Comparative Study with Gastrointestinal Carcinoids, Pheochromocytomas and Paragangliomas","volume":"186","author":"Barbareschi","year":"1990","journal-title":"Path. Res. Pr."},{"key":"ref_38","first-page":"229","article-title":"Bronchial Carcinoids and Pheochromocytomas\u2014A Comparative Study with Special Emphasis on S-100 Protein, Serotonin and Neuron-Specific Enolase (NSE) Immunoreactivity","volume":"94","author":"Lundqvist","year":"1986","journal-title":"Acta Path. Microbiol. Immunol. Scand. Sect. A"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1002\/(SICI)1097-0215(19991022)84:5<484::AID-IJC6>3.0.CO;2-V","article-title":"Decreased Survival in Patients with CD44-negative Typical Bronchial Carcinoid Tumors","volume":"84","author":"Granberg","year":"1999","journal-title":"Int. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/path.1711660405","article-title":"Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms","volume":"166","author":"Barbareschi","year":"1992","journal-title":"J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1165\/ajrcmb.18.2.3008","article-title":"Mechanism of Retinoblastoma Gene Inactivation in the Spectrum of Neuroendocrine Lung Tumors","volume":"18","author":"Gouyer","year":"1998","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_42","first-page":"484","article-title":"Bcl-2, p53, CD44, and CD44v6 isoform expression in neuroendocrine tumors of the lung","volume":"9","author":"Coppola","year":"1996","journal-title":"Mod. Pathol."},{"key":"ref_43","first-page":"907","article-title":"Mutational Spectrum of the p53 Gene in Human Small-Cell Lung Cancer and Relationship to Clinicopathological Data","volume":"142","author":"Lohmann","year":"1993","journal-title":"Am. J. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/his.13096","article-title":"Limited additive value of the Ki-67 proliferative index on patient survival in World Health Organization-classified pulmonary carcinoids","volume":"70","author":"Swarts","year":"2017","journal-title":"Histopathology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1053\/hupa.2001.28245","article-title":"Cytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors","volume":"32","author":"Cai","year":"2001","journal-title":"Hum. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.humpath.2004.02.016","article-title":"TTF-1 expression is specific for lung primary in typical and atypical carcinoids: TTF-1-positive carcinoids are predominantly in peripheral location","volume":"35","author":"Du","year":"2004","journal-title":"Hum. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0196-9781(85)90359-6","article-title":"Bombesin in Human Neuroendocrine (NE) Neoplasms","volume":"6","author":"Chejfec","year":"1985","journal-title":"Peptides"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/S0002-9440(10)65653-2","article-title":"Typical and Atypical Carcinoid Tumors of the Lung Are Characterized by 11q Deletions as Detected by Comparative Genomic Hybridization","volume":"153","author":"Walch","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1093\/hmg\/6.13.2285","article-title":"Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung","volume":"6","author":"Debelenko","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1093\/ajcp\/95.6.828","article-title":"Typical and Atypical Bronchopulmonary Carcinoids\u2014A Clinicopathologic and Flow Cytometric Study","volume":"95","author":"Ballance","year":"1991","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1136\/thx.43.3.195","article-title":"DNA ploidy in bronchopulmonary carcinoid tumours","volume":"43","author":"Jones","year":"1988","journal-title":"Thorax"},{"key":"ref_52","first-page":"119","article-title":"Bronchopulmonary Carcinoids and Regional Lymph Node Metastases\u2014A Quantitative Pathologic Investigation","volume":"132","author":"Thunnissen","year":"1988","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1097\/00000478-199106000-00003","article-title":"Neuroendocrine Tumors of the Lung with Proposed Criteria for Large-Cell Neuroendocrine Carcinoma. An Ultrastructural, Immunohistochemical, and Flow Cytometric Study of 35 Cases","volume":"15","author":"Travis","year":"1991","journal-title":"Am. J. Surg. Patol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00428-020-03015-z","article-title":"Morphologic and molecular classification of lung neuroendocrine neoplasms","volume":"478","author":"Metovic","year":"2021","journal-title":"Virchows Arch."},{"key":"ref_55","first-page":"607","article-title":"Carcinoid tumors of the lung. An analysis of 65 operated cases","volume":"40","author":"Stefani","year":"1999","journal-title":"J. Cardiovasc. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1148\/radiographics.22.2.g02mr01351","article-title":"Bronchial carcinoid tumors of the thorax: Spectrum of radiologic findings","volume":"22","author":"Jeung","year":"2002","journal-title":"Radiographics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.2214\/AJR.10.5954","article-title":"CT features of peripheral pulmonary carcinoid tumors","volume":"197","author":"Meisinger","year":"2011","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.lungcan.2003.08.017","article-title":"Clinical-radiological presentation and outcome of surgically treated pulmonary carcinoid tumours: A long-term single institution experience","volume":"43","author":"Schrevens","year":"2004","journal-title":"Lung Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1046\/j.1365-2265.2003.01931.x","article-title":"Octreoscan in patients with bronchial carcinoid tumours","volume":"59","author":"Granberg","year":"2003","journal-title":"Clin. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"508","DOI":"10.2967\/jnumed.106.035667","article-title":"68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: Comparison with somatostatin receptor scintigraphy and CT","volume":"48","author":"Gabriel","year":"2007","journal-title":"J. Nucl. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1093\/annonc\/mdv041","article-title":"Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids","volume":"26","author":"Caplin","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1136\/pgmj.73.865.737","article-title":"Adrenocorticotropin-secreting carcinoid tumour identified and treated 12 years after presentation with Cushing\u2019s syndrome","volume":"73","author":"Vaidya","year":"1997","journal-title":"Postgrad. Med. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.2214\/AJR.06.0503","article-title":"Integrated PET\/CT of pulmonary neuroendocrine tumors: Diagnostic and prognostic implications","volume":"188","author":"Chong","year":"2007","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.2214\/ajr.170.5.9574618","article-title":"Evaluation of Primary Pulmonary Carcinoid Tumors Using FDG PET","volume":"170","author":"Erasmus","year":"1998","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1378\/chest.06-0711","article-title":"The utility of fluorodeoxyglucose positron emission tomography in the evaluation of carcinoid tumors presenting as pulmonary nodules","volume":"131","author":"Daniels","year":"2007","journal-title":"Chest"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1136\/thx.39.8.617","article-title":"Carcinoid tumours of the bronchus: A 33 year experience","volume":"39","author":"Hurt","year":"1984","journal-title":"Thorax"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1309\/QYV05VGEGKUL2RTT","article-title":"Ki-67 immunoreactivity in the differential diagnosis of pulmonary neuroendocrine neoplasms in specimens with extensive crush artifact","volume":"123","author":"Aslan","year":"2005","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/01.pas.0000149690.75462.29","article-title":"Typical and atypical pulmonary carcinoid tumor overdiagnosed as small-cell carcinoma on biopsy specimens: A major pitfall in the management of lung cancer patients","volume":"29","author":"Pelosi","year":"2005","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.chest.2016.10.010","article-title":"The Eighth Edition Lung Cancer Stage Classification","volume":"151","author":"Detterbeck","year":"2017","journal-title":"Chest"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ejca.2016.11.034","article-title":"Antitumour activity of somatostatin analogues in sporadic, progressive, metastatic pulmonary carcinoids","volume":"75","author":"Sullivan","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"669484","DOI":"10.3389\/fendo.2021.669484","article-title":"Outcome of Patients with Metastatic Lung Neuroendocrine Tumors Submitted to First Line Monotherapy with Somatostatin Analogs","volume":"12","author":"Lenotti","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000354760","article-title":"Effect of Temozolomide in Patients with Metastatic Bronchial Carcinoids","volume":"98","author":"Crona","year":"2013","journal-title":"Neuroendocrinology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1016\/S1470-2045(17)30681-2","article-title":"Efficacy and safety of long-acting pasireotide or everolimus alone or in combination in patients with advanced carcinoids of the lung and thymus (LUNA): An open-label, multicentre, randomised, phase 2 trial","volume":"18","author":"Ferolla","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1159\/000502864","article-title":"Capecitabine and Temozolomide in Patients with Advanced Pulmonary Carcinoid Tumours","volume":"110","author":"Papaxoinis","year":"2020","journal-title":"Neuroendocrinology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1007\/s00259-006-0355-4","article-title":"Peptide receptor radionuclide therapy with (177)Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin","volume":"34","author":"Krenning","year":"2007","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1200\/JCO.2010.33.7873","article-title":"Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers","volume":"29","author":"Imhof","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1007\/s00259-015-3262-8","article-title":"Peptide receptor radionuclide therapy with (177)Lu-DOTATATE in advanced bronchial carcinoids: Prognostic role of thyroid transcription factor 1 and (18)F-FDG PET","volume":"43","author":"Ianniello","year":"2016","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_78","first-page":"74","article-title":"Efficacy of peptide receptor radionuclide therapy with (177)Lu-octreotate in metastatic pulmonary neuroendocrine tumors: A dual-centre analysis","volume":"7","author":"Sabet","year":"2017","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00259-015-3190-7","article-title":"Long-term results of PRRT in advanced bronchopulmonary carcinoid","volume":"43","author":"Mariniello","year":"2016","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1378\/chest.12-1108","article-title":"Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: Analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study","volume":"143","author":"Fazio","year":"2013","journal-title":"Chest"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/cas.13427","article-title":"Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis","volume":"109","author":"Fazio","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1530\/ERC-20-0382","article-title":"Spartalizumab in metastatic, well\/poorly-differentiated neuroendocrine neoplasms","volume":"28","author":"Yao","year":"2021","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1002\/cncr.32883","article-title":"Pembrolizumab for the treatment of programmed death-ligand 1-positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE-028 study","volume":"126","author":"Mehnert","year":"2020","journal-title":"Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.athoracsur.2020.08.035","article-title":"Total Lung-sparing Surgery for Tracheobronchial Low-grade Malignancies","volume":"112","author":"Chen","year":"2021","journal-title":"Ann. Thorac. Surg."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S1010-7940(02)00089-1","article-title":"Surgery in bronchial carcinoids: Experience with 83 patients","volume":"21","author":"Kurul","year":"2002","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.lungcan.2019.04.016","article-title":"Endobronchial and surgical treatment of pulmonary carcinoid tumors: A systematic literature review","volume":"134","author":"Reuling","year":"2019","journal-title":"Lung Cancer"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.amjsurg.2012.05.008","article-title":"Surgical management of pulmonary carcinoid tumors: Sublobar resection versus lobectomy","volume":"205","author":"Fox","year":"2013","journal-title":"Am. J. Surg."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.lungcan.2021.04.010","article-title":"Long-term survival and recurrence after resection of bronchopulmonary carcinoids: A single-center cohort study of 236 patients","volume":"156","author":"Soldath","year":"2021","journal-title":"Lung Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/resp.13920","article-title":"Video-assisted thoracoscopic surgery as the gold standard for lung cancer surgery","volume":"25","author":"Sihoe","year":"2020","journal-title":"Respirology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1007\/s00464-015-4492-3","article-title":"Causes, predictors and consequences of conversion from VATS to open lung lobectomy","volume":"30","author":"Augustin","year":"2016","journal-title":"Surg. Endosc."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.jtcvs.2006.12.013","article-title":"Initial bronchoscopic treatment for patients with intraluminal bronchial carcinoids","volume":"133","author":"Brokx","year":"2007","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1097\/LBR.0b013e3182446b52","article-title":"Endoscopic treatment of bronchial carcinoids in comparison to surgical resection: A retrospective study","volume":"19","author":"Neyman","year":"2012","journal-title":"J. Bronchol. Interv. Pulmonol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.athoracsur.2017.05.011","article-title":"Adjuvant Chemotherapy Does Not Confer Superior Survival in Patients with Atypical Carcinoid Tumors","volume":"104","author":"Anderson","year":"2017","journal-title":"Ann. Thorac. Surg."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.athoracsur.2014.08.030","article-title":"Defining the role of adjuvant chemotherapy after lobectomy for typical bronchopulmonary carcinoid tumors","volume":"99","author":"Nussbaum","year":"2015","journal-title":"Ann. Thorac. Surg."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4656","DOI":"10.1200\/JCO.2009.22.8510","article-title":"Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group","volume":"27","author":"Rinke","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1056\/NEJMoa1316158","article-title":"Lanreotide in metastatic enteropancreatic neuroendocrine tumors","volume":"371","author":"Caplin","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"S906","DOI":"10.1016\/j.annonc.2021.08.178","article-title":"Lanreotide autogel\/depot (LAN) in patients with advanced bronchopulmonary (BP) neuroendocrine tumors (NETs): Results from the phase III SPINET study","volume":"32","author":"Baudin","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1159\/000127382","article-title":"Pulmonary carcinoid tumours: Indolent but not benign","volume":"73","author":"Bajetta","year":"2007","journal-title":"Oncology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1023\/A:1012569909313","article-title":"Experience in treatment of metastatic pulmonary carcinoid tumors","volume":"12","author":"Granberg","year":"2001","journal-title":"Ann. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1038\/sj.bjc.6605618","article-title":"Chemotherapy with 5-fluorouracil, cisplatin and streptozocin for neuroendocrine tumours","volume":"102","author":"Turner","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.lungcan.2003.11.016","article-title":"Outcome of patients with pulmonary carcinoid tumors receiving chemotherapy or chemoradiotherapy","volume":"44","author":"Wirth","year":"2004","journal-title":"Lung Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.lungcan.2014.08.012","article-title":"Chemotherapy for locally advanced and metastatic pulmonary carcinoid tumors","volume":"86","author":"Chong","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3892\/mco.2016.1097","article-title":"Systemic chemotherapy with FOLFOX in metastatic grade 1\/2 neuroendocrine cancer","volume":"6","author":"Faure","year":"2017","journal-title":"Mol. Clin. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1159\/000444087","article-title":"Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors","volume":"103","author":"Spada","year":"2016","journal-title":"Neuroendocrinology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1056\/NEJMoa1009290","article-title":"Everolimus for advanced pancreatic neuroendocrine tumors","volume":"364","author":"Yao","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1056\/NEJMoa1003825","article-title":"Sunitinib malate for the treatment of pancreatic neuroendocrine tumors","volume":"364","author":"Raymond","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/j.jtho.2020.06.021","article-title":"Commonwealth Neuroendocrine Tumour Research Collaboration and the North American Neuroendocrine Tumor Society Guidelines for the Diagnosis and Management of Patients with Lung Neuroendocrine Tumors: An International Collaborative Endorsement and Update of the 2015 European Neuroendocrine Tumor Society Expert Consensus Guidelines","volume":"15","author":"Singh","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1159\/000092718","article-title":"Expression of tyrosine kinase receptors in lung carcinoids","volume":"27","author":"Granberg","year":"2006","journal-title":"Tumor Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1093\/annonc\/mdv252","article-title":"Pazopanib in pretreated advanced neuroendocrine tumors: A phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE)","volume":"26","author":"Grande","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1200\/JCO.2007.15.9020","article-title":"Activity of sunitinib in patients with advanced neuroendocrine tumors","volume":"26","author":"Kulke","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.lungcan.2017.03.006","article-title":"PD-L1 expression in neuroendocrine tumors of the lung","volume":"108","author":"Tsuruoka","year":"2017","journal-title":"Lung Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0140-6736(16)32517-X","article-title":"Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial","volume":"389","author":"Rittmeyer","year":"2017","journal-title":"Lancet"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1002\/bjs.9262","article-title":"Outcome after resection and radiofrequency ablation of liver metastases from small intestinal neuroendocrine tumours","volume":"100","author":"Norlen","year":"2013","journal-title":"Br. J. Surg."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Sobash, P.T., Ullah, A., and Karim, N.A. (2022). Survival Benefit of Adjuvant Chemotherapy in Pulmonary Carcinoid Tumors. Cancers, 14.","DOI":"10.3390\/cancers14194730"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1093\/ejcts\/ezt470","article-title":"Prognostic factors in a multicentre study of 247 atypical pulmonary carcinoids","volume":"45","author":"Daddi","year":"2014","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.annonc.2021.01.003","article-title":"Lung and thymic carcinoids: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"32","author":"Baudin","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1080\/14656566.2016.1254191","article-title":"Telotristat ethyl: A new option for the management of carcinoid syndrome","volume":"17","author":"Lamarca","year":"2016","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s40265-018-0935-1","article-title":"Telotristat Ethyl: A Review in Carcinoid Syndrome Diarrhoea","volume":"78","year":"2018","journal-title":"Drugs"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1530\/EJE-19-0877","article-title":"Management of endocrine disease: Cushing\u2019s syndrome due to ectopic ACTH secretion: An expert operational opinion","volume":"182","author":"Young","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_120","first-page":"92","article-title":"Cyclic ectopic Cushing\u2019s syndrome and somatostatin analogue treatment","volume":"122","author":"Falhammar","year":"2009","journal-title":"N. Z. Med. J."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.chest.2020.01.031","article-title":"Somatostatin Analogs Improve Respiratory Symptoms in Patients with Diffuse Idiopathic Neuroendocrine Cell Hyperplasia","volume":"158","author":"Strosberg","year":"2020","journal-title":"Chest"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/cncr.26200","article-title":"Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and the associated lung neuroendocrine tumors: Clinical experience with a rare entity","volume":"118","author":"Gorshtein","year":"2012","journal-title":"Cancer"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1164\/rccm.201010-1685PP","article-title":"Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: A systematic overview","volume":"184","author":"Nassar","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S0039-6060(97)90090-8","article-title":"Bronchial carcinoid\u2014Twenty years\u2019 experience defines a selective surgical approach","volume":"122","author":"Chughtai","year":"1997","journal-title":"Surgery"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1378\/chest.119.4.1143","article-title":"Typical and atypical pulmonary carcinoids: Outcome in patients presenting with regional lymph node involvement","volume":"119","author":"Thomas","year":"2001","journal-title":"Chest"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S0046-8177(98)90047-8","article-title":"Reproducibility of Neuroendocrine Lung Tumor Classification","volume":"29","author":"Travis","year":"1998","journal-title":"Hum. Pathol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1159\/000493944","article-title":"Lung Carcinoids: Long-Term Surgical Results and the Lack of Prognostic Value of Somatostatin Receptors and Other Novel Immunohistochemical Markers","volume":"107","author":"Daskalakis","year":"2018","journal-title":"Neuroendocrinology"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1097\/JTO.0b013e31829f097a","article-title":"Outcome and Prognostic Factors in Bronchial Carcinoids: A Single-Center Experience","volume":"8","author":"Filosso","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1055\/s-0035-1544211","article-title":"Predictors of Disease-free Survival and Recurrence in Patients with Resected Bronchial Carcinoid Tumors","volume":"64","author":"Osakwe","year":"2016","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ejcts.2006.11.031","article-title":"Typical and atypical carcinoid tumours: Analysis of the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung","volume":"31","author":"Matilla","year":"2007","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1055\/s-0035-1555125","article-title":"Bronchopulmonary Carcinoids causing Cushing Syndrome: Results from a Multicentric Study Suggesting a More Aggressive Behavior","volume":"64","author":"Margaritora","year":"2016","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"ref_132","first-page":"3425","article-title":"Prognostic Markers in Patients with Typical Bronchial Carcinoid Tumors","volume":"85","author":"Granberg","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1136\/thoraxjnl-2013-204102","article-title":"Atypical carcinoid tumours of the lung: Prognostic factors and patterns of recurrence","volume":"69","author":"Canizares","year":"2014","journal-title":"Thorax"},{"key":"ref_134","first-page":"884","article-title":"Late recurrent pulmonary typical carcinoid tumor: Case report and review of the literature","volume":"73","author":"Ciment","year":"2006","journal-title":"Mt. Sinai J. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.athoracsur.2013.05.047","article-title":"Recurrence of pulmonary carcinoid tumors after resection: Implications for postoperative surveillance","volume":"96","author":"Lou","year":"2013","journal-title":"Ann. Thorac. Surg."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1159\/000480015","article-title":"Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study","volume":"106","author":"Marciello","year":"2018","journal-title":"Neuroendocrinology"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/22\/5440\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:23:56Z","timestamp":1760131436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/22\/5440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,16]]},"references-count":136,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["cancers15225440"],"URL":"https:\/\/doi.org\/10.3390\/cancers15225440","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,16]]}}}