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      Tumor size and perineural invasion predict outcome of gastric high-grade neuroendocrine neoplasms

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          Abstract

          A new subcategory, grade 3 neuroendocrine tumors, is incorporated into the grading system of pancreatic neuroendocrine neoplasms in the 2017 WHO classification in order to differentiate grade 3 neuroendocrine tumors from neuroendocrine carcinomas. The 2019 WHO classification extends the concept of grade 3 neuroendocrine tumors to gastrointestinal high-grade neuroendocrine neoplasms. However, there is still limited study focusing on the gastric grade 3 neuroendocrine tumors and gastric neuroendocrine carcinomas. We retrospectively enrolled 151 gastric high-grade neuroendocrine neoplasms patients, who underwent radical resection from January 2007 to December 2015. Clinicopathologic and prognostic features were studied. The Surveillance, Epidemiology, and End Results (SEER) database was used to verify the prognostic determinants found in the Zhongshan cohort. Neuroendocrine carcinomas showed a higher Ki67 index and higher mitotic count than grade 3 neuroendocrine tumors. We identified 109 (72.2%) patients with neuroendocrine carcinomas, 12 (7.9%) patients with grade 3 neuroendocrine tumors, and 30 (19.9%) patients with mixed neuroendocrine-non-neuroendocrine neoplasms. Although neuroendocrine carcinomas demonstrated higher Ki67 index ( P = 0.004) and mitoses ( P = 0.001) than grade 3 neuroendocrine tumors, their prognosis after radical resection did not demonstrate significant differences ( P = 0.709). Tumor size, perineural invasion, and TNM stage were independent prognostic factors of gastric high-grade neuroendocrine neoplasms.

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          A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal

          The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested is based on a consensus conference held at the International Agency for Research on Cancer (IARC) in November 2017 and subsequent discussion with additional experts. The key feature of the new classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated NECs, as they both share common expression of neuroendocrine markers. This dichotomous morphological subdivision into NETs and NECs is supported by genetic evidence at specific anatomic sites as well as clinical, epidemiologic, histologic, and prognostic differences. In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis; NECs are considered high grade by definition. We believe this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically.
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            Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study.

            As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67<55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67<55% had a lower response rate (15% versus 42%, P<0.001), but better survival than patients with Ki-67≥55% (14 versus 10 months, P<0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.
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              Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                21 July 2021
                01 August 2021
                : 10
                : 8
                : 947-954
                Affiliations
                [1 ]Department of General Surgery , Zhongshan Hospital, Fudan University, Shanghai, China
                [2 ]Department of Pathology , Zhongshan Hospital, Fudan University, Shanghai, China
                Author notes
                Correspondence should be addressed to Y Ji or Y Sun: ji.yuan@ 123456zs-hospital.sh.cn or sun.yihong@ 123456zs-hospital.sh.cn

                *(Q Zhang and H Wang contributed equally to this work)

                Author information
                http://orcid.org/0000-0002-2574-7499
                http://orcid.org/0000-0001-7371-4133
                Article
                EC-21-0017
                10.1530/EC-21-0017
                8428078
                34289448
                36afdde8-9fef-47e1-8129-e84dfa2cc056
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 22 June 2021
                : 21 July 2021
                Categories
                Research

                gastric high-grade neuroendocrine neoplasms,grade 3 neuroendocrine tumors,surgical resected,prognosis

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