Study eligibility criteria

The present systematic review included all studies which involved (I) FIT-positive patients who underwent a colonoscopy (II) and went for UGI screening concurrently or post-colonoscopy, (III) were peer-reviewed with full texts in English, and (IV) were published between 2008–2022. Inclusion criteria IV was used to ensure that the current review would only examine studies published after the search period captured by Allard et al.’s prior systematic review [7]. Articles were excluded if they were (i) not peer-reviewed and (ii) articles that did not include primary data (e.g. reviews, meta-analyses, commentaries, editorials).

Search strategy

Keywords, titles, and abstracts in three electronic databases (PubMed, CINAHL and Scopus) were searched using appropriate text words and related terms pertaining to colonoscopy, gastroscopy and gastrointestinal neoplasms. MeSH terms were utilised where possible. The search was conducted on articles published on these respective databases from 01 January 2008 through 09 June 2022. To improve the thoroughness of our search strategy, hand-searching of reference lists and a forward citation search from the included articles was also performed. The full search strategies for the respective databases can be found in S1 Appendix.

Selection of studies

Following extraction of records from the search yields of each electronic database, EndNote X9 was utilised to remove duplicates. Titles and abstracts of each record were reviewed independently by two authors (LC and LT-SY) using the aforementioned inclusion and exclusion criteria. Thereafter, full-texts of all records that met the criteria were screened and discussed between the same two authors. A third author (JL) resolved any cases of disagreements. The reference lists from the included articles were hand-searched by LC and LT-SY to check for additional studies of relevance. After confirming the studies to be included, LC and LT-SY performed a quality appraisal on each of the studies included in the final sample using the appropriate Joanna Briggs Institute (JBI) critical appraisal tool, depending on the study design [9].

Article evaluation

A total of 2409 records were extracted from the three electronic databases. Forty-four duplicates were detected by EndNote, with an additional 136 manually detected and removed by the authors. The initial screening of titles and abstracts resulted in 14 articles that seemed to meet the criteria and subsequently underwent full-text review. Of these, only three articles (from PubMed and Scopus) fulfilled the selection criteria and were retained [10–12]. Unfortunately, CINAHL did not yield any papers of relevance. The fourth and final article included was from the forward citation search [13]. The detailed breakdown of the 2409 records can be seen in the flow diagram, Fig 1.

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Fig 1. PRISMA flow diagram of study selection process.

https://doi.org/10.1371/journal.pone.0281557.g001

The JBI critical appraisal tools cohort study checklist was used for all four articles included [10–13]. Overall, all four studies had high quality, fulfilling more than 85% of the critical appraisal criteria–in which higher scores suggest more robustly designed studies with a lower likelihood of bias influencing the findings. Key characteristics from each included article (see Table 1) were then recorded by two authors (LC and LT-SY) using a standardised data collection form.

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Table 1. Key characteristics, main findings, conclusions and limitations of the included studies.

https://doi.org/10.1371/journal.pone.0281557.t001

Study characteristics

All four studies reviewed patient’s medical records retrospectively to examine if OGD should be conducted in patients with positive FIT results [10–13]. Patients in all four studies had positive FIT results and underwent OGD concurrently with or after colonoscopy. Three of the four studies stratified their respective samples to include various patient sub-groups such as (i) FIT-positive/colonoscopy-negative patients, (ii) FIT-positive/colonoscopy-positive, (iii) FIT-positive/colonoscopy-negative/OGD-positive or (iv) FIT-positive/colonoscopy-negative/OGD-negative results [10, 11, 13]. Krustri et al., Choi et al. and Planade et al. managed to specifically study the OGD results of patients who had positive FIT and negative colonoscopy results [10, 11, 13]. Ng et al., however, were less specific and included all FIT positive patients who underwent concurrent OGD [12].

A full description of study characteristics such as the study design, country of study, aims and objectives, methodology, data collection period, key findings, and JBI scoring can be seen in Table 1.

Outcomes of interest

Limitations across the included studies

Despite the 14 years that have elapsed between Allard et al.’s review and the present research, our review found that the existing body of relevant evidence examining whether OGD should be considered for FIT-positive/colonoscopy patients remains scant and derived from retrospective study designs [10–13]. Three of the four studies had relatively small study samples which may demonstrate skewed baseline characteristics and outcomes due to chance bias, leading to potential limitations in generalisability of the study findings [10, 12, 13]. Furthermore, small samples tend to produce smaller effect sizes, which could be a reason for the extremely low incidence of gastric cancer found in the included studies. The retrospective nature of the included studies means that the possibility of selection biases also cannot be discounted, as treating physicians may have offered OGD to certain groups of patients with higher inherent risk of gastric pathologies, rather than all patients with a positive FIT. Additionally, three studies were conducted in Asian populations where the incidence of gastric cancer and H. pylori infection is higher than that in the West [28]. These findings should therefore be generalised to Western populations only with some caution. The absence of cost-effectiveness data also makes it more difficult to conclude whether OGD should generally be considered by clinicians for patients with positive FIT results, as relatively low procedure costs and risk of complications to the individual can still add up to a substantial financial burden on the healthcare system at large.

Lastly, our review found dissimilarities in how specific the respective studies were in evaluating patient characteristics. For example, Ng et al. did not stratify FIT-positive patients by their colonoscopy result, and both Ng et al. and Choi et al. did not report their OGD findings based on whether patients were symptomatic or asymptomatic [11, 12]. Future studies should attempt to understand if OGD outcomes are significantly different across these patient sub-groups as these may further inform risk stratification protocols.

Taking these limitations into consideration, future research should prospectively establish clinical outcomes and cost-effectiveness of performing OGD on FIT-positive individuals using larger, more representative patient cohorts. Confounding factors, such as anaemia, related medical prescriptions, and baseline clinical and sociodemographic characteristics should also be taken into consideration, as these may influence the likelihood of bleeding lesions, leading to a higher incidence of false-positive FIT. While randomised or cluster randomised controlled trial designs would be ideal in establishing the clinical efficacy of OGD on such patients, the lack thereof is perhaps understandable given the financial, logistical and ethical challenges associated with the present research question.

Limitations of the current review

Our review utilised a multi-database search strategy, with the inclusion of MeSH terms where possible to broaden the likelihood of capturing all articles of relevance. However, it is possible that we may have missed some studies as we were only able to include full-texts that were available in English, especially from studies with findings that may be more locally relevant and whose authors may have published in local or regional journals. Nonetheless, as our search strategy exhaustively examined the body of literature in three of the largest academic databases relevant to the research question, the findings of this review are still representative of the limited evidence internationally available to clinicians and healthcare researchers on recommending OGD in this patient population.