Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2019; 25(35): 5376-5387
Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5376
Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis
Apostolos V Tsolakis, Athanasia Ragkousi, Miroslav Vujasinovic, Gregory Kaltsas, Kosmas Daskalakis
Apostolos V Tsolakis, Department of Oncology and Pathology, Karolinska Institute, Stockholm 17177, Sweden
Apostolos V Tsolakis, Cancer Centre Karolinska, CCK, Karolinska University Hospital, Stockholm 17176, Sweden
Athanasia Ragkousi, Gregory Kaltsas, Kosmas Daskalakis, 1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
Miroslav Vujasinovic, Department of Digestive Diseases, Karolinska University Hospital, Stockholm 14186, Sweden
Kosmas Daskalakis, Department of Surgical Sciences, Uppsala University, Uppsala 75185, Sweden
Author contributions: Tsolakis AV contributed to conception and design of the study, selection and assessment of the quality of the eligible studies, analysis and interpretation of data, drafting of the manuscript and final approval of the manuscript; Ragkousi A contributed to statistical consultation, analysis and interpretation of data and final approval of the manuscript; Vujasinovic M contributed to drafting of the manuscript, final approval of the manuscript; Kaltsas G contributed to analysis and interpretation of the data, drafting of the manuscript, final approval of the manuscript; Daskalakis K contributed to conception and design of the study, acquisition of studies, selection and assessment of the quality of the eligible studies, analysis and interpretation of data, writing and drafting the manuscript, study supervision and final approval of manuscript.
Supported by Swedish Society of Medicine Post Doctoral Scholarship, No. SLS-785911; the Lennander Scholarship.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Apostolos V Tsolakis, MD, PhD, Doctor, Department of Oncology and Pathology, Karolinska Institute, Solna R8:04, Stockholm 17177, Sweden. apobtsol@hotmail.com
Telephone: +46-8-58580000
Received: April 30, 2019
Peer-review started: April 30, 2019
First decision: June 6, 2019
Revised: June 12, 2019
Accepted: July 19, 2019
Article in press: June 6, 2019
Published online: September 21, 2019
Abstract
BACKGROUND

To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated.

AIM

To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters.

METHODS

The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis.

RESULTS

We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3% (25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8; heterogeneity: P = 0.126; I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2; 95%CI: 1.8-161.1; heterogeneity: P = 0.165; I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2; 95%CI: 0.3-11.6; heterogeneity: P = 0.304; I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3; 95%CI: 0.1-1.1; heterogeneity: P = 0.173; I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively.

CONCLUSION

This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5-year disease-specific survival rates reported; hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Keywords: Gastric neuroendocrine neoplasms type 1, Meta-analysis, Lymph node metastasis, Tumor size, Invasion, Endoscopy, Surgery

Core tip: Hitherto, risk parameters predicting metastatic disease and the appropriateness of endoscopic vs surgical management of patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been thoroughly investigated. The present systematic review and meta-analysis prove that locoregional lymph node (LN) metastases in GNENs1 are relatively rare (3.3%). Furthermore, tumour size ≥ 10 mm and the presence of the muscularis propria invasion are associated with an increased risk for LN metastasis. The latter finding suggests that endoscopic ultrasound investigation is very valuable in the work up of these lesions. Finally, surgical resection is linked to a lower risk for recurrence.