Systematic Reviews
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 16, 2022; 10(23): 8212-8223
Published online Aug 16, 2022. doi: 10.12998/wjcc.v10.i23.8212
Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review
Xing-Chen Cai, Sheng-Dong Wu
Xing-Chen Cai, Sheng-Dong Wu, Department of Hepato-Pancreato-Billiary Surgery, The affiliated Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, China
Author contributions: Wu SD contributed to the article framework guidance and revision; and Cai XC contributed to the data acquisition, statistical analysis and article writing.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
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 that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sheng-Dong Wu, Doctor, Department of Hepato-Pancreato-Billiary Surgery, The affiliated Lihuili Hospital, Ningbo University, No. 818 Fenghua Road, Ningbo 315300, Zhejiang Province, China. b407167953@163.com
Received: January 18, 2022
Peer-review started: January 18, 2022
First decision: April 11, 2022
Revised: April 21, 2022
Accepted: July 11, 2022
Article in press: July 11, 2022
Published online: August 16, 2022
Processing time: 195 Days and 5.6 Hours
ARTICLE HIGHLIGHTS
Research background

Neuroendocrine neoplasms (NENs) have been reported in nearly every tissue. According to the International Agency for Research on Cancer – World Health Organization, neuroendocrine tumors (NETs) are composed of cells with distinctive phenotype characterized by the expression of general and specific neuroendocrine biomarkers. NETs account for about 0.5% of all newly diagnosed malignancies. Gallbladder neuroendocrine carcinoma (GB-NEC) is extremely rare; thus, many clinical questions related to it are yet to be fully explored.

Research motivation

To investigate GB-NEC, we reviewed recent research and analyzed corresponding data in the Surveillance Epidemiology and End Results (SEER) database.

Research objectives

We found the following problems. (1) The epidemiological characteristics, clinical features, treatment and prognosis of GB-NEC are still unclear; (2) Most studies compared the prognosis of GB-NEC to that of adenocarcinoma; however, the results reported are still contradictory. In most of the studies, the sample sizes were small and as such, the results may not be objective; and (3) Most studies only focused on the clinical manifestations and prognosis of GB-NEC. Few articles explored the pathogenesis and mechanism of GB-NEC. So in this study, we attempted to address the three problems stated above.

Research methods

Data of GB-NEC (n = 287) and gallbladder adenocarcinoma (GB-ADC) (n = 19 484) patients from 1975 to 2016 were extracted from the SEER database. Survival analysis was performed using Kaplan–Meier and Cox proportional hazards regression. P < 0.05 was considered statistically significant. We also reviewed 108 studies retrieved from PubMed and Reference Citation Analysis (https://www.referencecitationanalysis.com/). The keywords used for the search were: "(carcinoma, neuroendocrine) AND (gallbladder neoplasms)".

Research results

The GB-NEC incidence rate was 1.6% (of all gallbladder carcinomas), male to female ratio was 1:2 and the median survival time was 7 mo. The 1-, 2-, 3- and 5-year overall survival (OS) was 36.6%, 17.8%, 13.2% and 7.3%, respectively. Serum chromogranin A levels maybe a specific tumor marker for the diagnosis of GB-NEC. Elevated carcinoembryonic antigen, carbohydrate antigen (CA)-19-9 and CA-125 levels were associated with poor prognosis. Age and liver metastasis were independent prognostic risk factors for OS. Patients with advanced GB-NEC treated with surgical resection combined with radiotherapy and/or chemotherapy may have a better prognosis than those treated with surgical resection alone. There was no significant difference in OS between GB-NEC and GB-ADC.

Research conclusions

GB-NEC has a low incidence rate, high degree of malignancy and poor prognosis. The incidence is significantly higher in older women. GB-NEC is difficult to diagnose and most patients have advanced disease at the time of diagnosis. Therefore, the focus should be on investigating the pathogenesis and treatment rather than the atypical clinical manifestations of GB-NEC.

Research perspectives

Many researchers pay too much attention to the differences between GB-ADC and GB-NEC. In our study, except for blood biomarkers, there were no significant differences between the above two diseases. Therefore, focus should be on investigating the pathogenesis and treatment rather than the atypical clinical manifestations of GB-NEC.