{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:35:43Z","timestamp":1789079743066,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Updates in classification of gastro\u2010entero\u2010pancreatic neuroendocrine neoplasms better reflect the biological characteristics of these tumours. In the present study, we analysed the characteristics of neuroendocrine tumours that could aid in a more precise stratification of risk groups. In addition, we have highlighted the importance of grade (re)assessment based on investigation of secondary tumour lesions. Two hundred and sixty\u2010four cases of neuroendocrine tumours of gastro\u2010entero\u2010pancreatic origin from three centres were included in the study. Tumour morphology, mitotic count and Ki67 labelling index were evaluated in specimens of primary tumours, lymph node metastases and distant metastases. These variables were correlated with overall survival (OS) and relapse\u2010free survival (RFS). Tumour stage, number of affected lymph nodes, presence of tumour deposits and synchronous\/metachronous metastases were tested as possible prognostic features. Mitotic count, Ki\u201067 labelling index, primary tumour site, tumour stage, presence of tumour deposits and two or more affected lymph nodes were significant predictors of OS and RFS. At the same time, mitotic count and Ki\u201067 labelling index can be addressed as continuous variables determining prognosis. We observed a very high correlation between the measures of proliferative activity in primary and secondary tumour foci. The presence of isolated tumour deposits was identified as an important determinant of both RFS and OS for pancreatic (hazard ratio [HR]\u00a0=\u00a07.61, 95% confidence interval [CI]\u00a0=\u00a03.96\u201014.6,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.0001 for RFS; HR\u00a0=\u00a03.28, 95% CI\u00a0=\u00a01.56\u20106.87,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.0017 for OS) and ileal\/jejunal neuroendocrine tumours (HR\u00a0=\u00a01.98, 95% CI\u00a0=\u00a01.25\u20103.13,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.0036 for RFS and HR 2.59, 95% CI\u00a0=\u00a01.27\u20105.26,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.009 for OS). The present study identifies the presence of mesenterial tumour deposits as an important prognostic factor for gastro\u2010entero\u2010pancreatic neuroendocrine tumours, provides evidence that proliferative parameters need to be treated as continuous variables and further supports the importance of grade determination in all available tumour foci.\n                  <\/jats:p>","DOI":"10.1111\/jne.13000","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:33:36Z","timestamp":1623976416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Prognostic features of gastro\u2010entero\u2010pancreatic neuroendocrine neoplasms in primary and metastatic sites: Grade, mesenteric tumour deposits and emerging novelties"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6944-971X","authenticated-orcid":false,"given":"Ketevani","family":"Kankava","sequence":"first","affiliation":[{"name":"Teaching, Scientific and Diagnostic Pathology Laboratory Tbilisi State Medical University Tbilisi Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Maisonneuve","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Biostatistics IEO European Institute of Oncology IRCCS Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7910-1274","authenticated-orcid":false,"given":"Alessandro","family":"Mangogna","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health IRCCS Burlo Garofalo Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Centonze","sequence":"additional","affiliation":[{"name":"1st Pathology Division Department of Pathology and Laboratory Medicine Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"1st Pathology Division Department of Pathology and Laboratory Medicine Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Prinzi","sequence":"additional","affiliation":[{"name":"Medical Oncology Department Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Pusceddu","sequence":"additional","affiliation":[{"name":"Medical Oncology Department Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Fazio","sequence":"additional","affiliation":[{"name":"Gastrointestinal and Neuroendocrine Oncology Unit European Institute of Oncology (IEO) Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Pisa","sequence":"additional","affiliation":[{"name":"Division of Pathology IEO European Institute of Oncology Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Di Domenico","sequence":"additional","affiliation":[{"name":"Department of General Surgery IRCCS Policlinico San Martino University Hospital Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Bertani","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Surgery European Institute of Oncology Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Mazzaferro","sequence":"additional","affiliation":[{"name":"Gastrointestinal Surgery and Liver Transplantation Department Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Albertelli","sequence":"additional","affiliation":[{"name":"Endocrinology Department (DiMi) Policlinico San Martino University Hospital IRCCS Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Grillo","sequence":"additional","affiliation":[{"name":"Unit of Pathology Department of Surgical Sciences and Integrated Diagnostics (DISC) IRCCS University of Genova and Policlinico San Martino University Hospital Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Milione","sequence":"additional","affiliation":[{"name":"1st Pathology Division Department of Pathology and Laboratory Medicine Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"WHO Classification Of Tumours Of Endocrine Organs","author":"Lloyd R","year":"2017"},{"key":"e_1_2_9_3_1","volume-title":"WHO Classification Of Tumours Of Digestive System","author":"Klimstra DS","year":"2019"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2017-0364"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-019-1606-8"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002123"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.10.036"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-40618-3"},{"issue":"1","key":"e_1_2_9_9_1","first-page":"1","article-title":"Peritoneal carcinomatosis in well\u2010differentiated small\u2010intestinal neuroendocrine tumors with mesenteric tumor deposits","volume":"4","author":"Das S","year":"2019","journal-title":"J Med Surg Pathol"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0075-x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000751"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13771"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000089"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-018-0274-y"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPQ55SKOCYFZHN"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31821a0696"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2019.12.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-018-6518-2"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000503722"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.03.304"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443167"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2258-0"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000369275"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2011.06.011"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000439434"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-017-5899-y"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9871319"}],"container-title":["Journal of Neuroendocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jne.13000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jne.13000","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jne.13000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T16:44:19Z","timestamp":1693327459000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jne.13000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,16]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1111\/jne.13000"],"URL":"https:\/\/doi.org\/10.1111\/jne.13000","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JNE.13000\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13000\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13000\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13000\/v2\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13000\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13000\/v1\/review4","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13000\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13000\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13000\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNE.13000\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0953-8194","1365-2826"],"issn-type":[{"value":"0953-8194","type":"print"},{"value":"1365-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,16]]},"assertion":[{"value":"2020-12-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13000"}}