{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:15:08Z","timestamp":1789578908882,"version":"build-2803163510"},"reference-count":30,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>One of the major prognostic indices in neuroendocrine tumors (NETs) is Ki67 proliferation index.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To identify optimal grading Ki67 cutoffs to delineate differences in prognosis of patients with small intestinal NETs (SI-NETs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Multicenter retrospective cohort analysis of 551 SI-NET patients diagnosed from 1993 through 2021 at 5 European referral centers with a mean (\u00b1SD) follow-up time of 51.5 (\u00b152.9) months, measuring rates of overall survival (OS) and event-free survival (EFS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Median age at baseline was 62.3 (range, 17-90) years; 252 (45.7%) patients were female. All SI-NETs were well-differentiated, with 326 being grade 1 (G1; 59.2%), 169 G2 (30.7%), and 8 G3 (1.5), while 48 tumors were unspecified grade (8.7%). The median Ki67 was 2% (range, 1%-70%). At baseline, 247 (44.8%) patients had distant metastases (stage IV), 217 locoregional disease (41.1%; stage III), while 29 (7.1%) and 25 (4.5%) presented at stages II and I, respectively. Median OS was 214.7 (95% CI, 152.7-276.6) months and median EFS was 79.8 (68.2-91.5) months. In multivariable Cox-regression OS analysis, the proposed modified histopathological Ki67 grading system (Ki67 5%-10% group: HR = 2.2 [95% CI, 1.15-4.31], P = .018 and Ki67 \u2265 10% group: HR = 5.11 [2.87-9.09], P &amp;lt; .001), age (HR = 1.07 [1.04-1.09], P &amp;lt; .001), Charlson Comorbidity Index (HR = 1.08 [1-1.16], P = .028), and TNM stage (HR = 1.79 [1.05-3.06], P = .034) were independent predictors for death. Pertinent EFS analysis confirmed the proposed modified histopathological Ki67 grading system (Ki67 \u2265 10% group: HR = 4.01 [2.6-6.37], P &amp;lt; .001) and age (HR = 1.04 [1.02-1.05], P &amp;lt; .001) as independent predictors for recurrence, progression, and\/or death.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Ki67 proliferation index was a strong and independent predictor of OS and EFS. A modified histopathological grading system applying Ki67 cutoffs of 5% and 10% could be superior to predict differences in SI-NET patient survival outcomes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae111","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T12:44:25Z","timestamp":1709124265000},"page":"e2222-e2230","source":"Crossref","is-referenced-by-count":6,"title":["Modified Histopathological Grading Optimizes Prediction of Survival Outcomes in Small Intestinal Neuroendocrine Tumors"],"prefix":"10.1210","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4224-8912","authenticated-orcid":false,"given":"Kosmas","family":"Daskalakis","sequence":"first","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Health, \u00d6rebro University , 703 62 \u00d6rebro ,","place":["Sweden"]},{"name":"Second Department of Surgery, \u201cKorgialenio-Benakio,\u201d Red Cross General Hospital , 11526 Athens 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