Systematic review with meta-analysis: age-related malignancy detection rates at upper gastrointestinal endoscopy

Background: Age is an important and objective risk factor for upper gastrointestinal (GI) malignancy. The accuracy of various age limits to detect upper GI malignancy is unclear. Determination of this accuracy may aid in the decision to refer symptomatic patients for upper GI endoscopy. The aim of this analysis was to synthesize data on upper GI malignancy detection rates for various age limits worldwide through meta-analysis. Methods: We searched MEDLINE, EMBASE, and Web of Science in November 2018. Selection criteria included studies addressing malignant findings at upper GI endoscopy in a symptomatic population reporting age at time of diagnosis. Meta-analyses were conducted to derive continent-specific cancer detection rates. Results: A total of 33 studies including 346,641 patients across 21 countries fulfilled the inclusion criteria. To detect >80% of malignant cases all symptomatic patients over 40 years of age should be investigated in Africa, over 50 years of age in South America and Asia, and over 55 years of age in North America and Europe. Conclusion: This systematic review and meta-analysis provides data on intercontinental variation in age at time of upper GI malignancy diagnosis in symptomatic patients referred for upper GI endoscopy. Guideline recommendations for age-based selection should be tailored to local age-related detection rates.


Rationale
3 Describe the rationale for the review in the context of what is already known.
3 Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number. 4 Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

4-5
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

4
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.
Suppl. Table S2 Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

4
Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

Data items
11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

5
Risk of bias in individual studies 12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

6
Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means).

5-6
Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I 2 ) for each meta-analysis.

5-6
Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

RESULTS
Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

7
Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

7
Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).

7
Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot. 7 and suppl figure S1 Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency.

7-9
Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15).

8-9
DISCUSSION Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

9-10
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

11-12
Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

FUNDING
Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review. OR (95% CI) 0.6 (0.4-0.9); p < 0.001

Supplementary figure 2.
Funnel plot of included study to detect potential publication bias.