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Prevalence of gastrointestinal malignancy in iron deficiency without anaemia: A systematic review and meta-analysis

Published:January 13, 2020DOI:https://doi.org/10.1016/j.ejim.2019.12.015

      Highlights

      • The overall risk of gastrointestinal cancer in IDWA is low.
      • However, older and non-screened populations with IDWA are at a higher risk.
      • Whilst asymptomatic younger patients with IDWA are at a lower risk.
      • Those at a higher risk should have endoscopic investigations.
      • Whereas those at a lower risk may not require endoscopic investigations.

      Abstract

      Background

      Iron deficiency anaemia is associated with gastrointestinal (GI) malignancy and is an indication for GI investigations. However, the relevance of iron deficiency without anaemia (IDWA) and the underlying risks of GI malignancy are uncertain. Therefore, the aim of this study was to estimate the prevalence of GI malignancy in patients with IDWA overall and in clinically relevant subgroups.

      Methods

      We searched MEDLINE and EMBASE for studies that reported on the prevalence or risk of GI malignancy in patients with confirmed IDWA. We performed a random effects meta-analysis of proportions and assessed statistical heterogeneity using the I2 statistic.

      Results

      A total of 1923 citations were screened and 5 studies (4 retrospective cohorts, 1 prospective cohort) comprising 3329 participants with IDWA were included in the meta-analysis. Overall pooled random-effects estimates for prevalence of GI malignancy in those with IDWA were low (0.38%, 95% CI 0.00%–1.84%, I2 = 87.7%). Older patients (2.58%, 95% CI 0.00%–8.77%); non-screening populations (2.45%, 95% CI 0.16%–6.39%) and men and post-menopausal women (0.90%, 95% CI 0.11%–3.23%) with IDWA were at increased risk of GI malignancy compared to younger patients (0.00%, 95% CI 0.00%–0.21%); screened populations (0.24%, 95% CI 0.00%–1.10%) and pre-menopausal women (0.00%, 95% CI 0.00%–1.05%).

      Conclusion

      Overall, IDWA is associated with a low risk of GI malignancy. Older patients and non-screening populations are at elevated risk and require GI investigations. Those not in these subgroups have a lower risk of GI malignancy and may wish to be monitored following discussion of the risk and potential benefits of GI investigations.

      Keywords

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      References

        • Stewart B.W.
        • Wild C.P.
        World cancer report.
        International Agency for Research on Cancer, Lyon, France2014: 623
        • Kepczyk T.
        • Kadakia S.C.
        Prospective evaluation of gastrointestinal tract in patients with iron-deficiency anemia.
        Dig Dis Sci. 1995; 40: 1283-1289
        • McIntyre A.S.
        • Long R.G.
        Prospective survey of investigations in outpatients referred with iron deficiency anaemia.
        Gut. 1993; 34: 1102-1107
        • Rockey D.C.
        • Cello J.P.
        Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia.
        N Engl J Med. 1993; 329: 1691-1695
        • Sinclair M
        Clinical update: iron deficiency.
        Gastroenterol Soc Aust. 2015; (Updated)
        • Goddard A.F.
        • James M.W.
        • McIntyre A.S.
        • Scott B.B.
        Guidelines for the management of iron deficiency anaemia.
        Gut. 2011; 60: 1309-1316
        • Ioannou G.N.
        • Spector J.
        • Scott K.
        • Rockey D.C
        Prospective evaluation of a clinical guideline for the diagnosis and management of iron deficiency anemia.
        Am J Med. 2002; 113: 281-287
        • Paterson W.G.
        • Depew W.T.
        • Pare P.
        • Petrunia D.
        • Switzer C.
        • Veldhuyzen van Zanten S.J.
        • et al.
        Canadian consensus on medically acceptable wait times for digestive health care.
        Can J Gastroenterol. 2006; 20: 411-423
        • Ioannou G.N.
        • Rockey D.C.
        • Bryson C.L.
        • Weiss N.S
        Iron deficiency and gastrointestinal malignancy: a population-based cohort study.
        Am J Med. 2002; 113: 276-280
        • Park J.S.
        • Park D.I.
        • Park S.K.
        • Choi J.S.
        • Kim Y.H.
        • Chang D.K.
        • et al.
        Endoscopic evaluation of significant gastrointestinal lesions in patients with iron deficiency with and without anaemia: a Korean Association for the Study of Intestinal Disease study.
        Intern Med J. 2009; 39: 441-446
        • Shamseer L.
        • Moher D.
        • Clarke M.
        • Ghersi D.
        • Liberati A.
        • Petticrew M.
        • et al.
        Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation.
        BMJ. 2015; 350: g7647
        • Peyrin-Biroulet L.
        • Williet N.
        • Cacoub P
        Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review.
        Am J Clin Nutr. 2015; 102: 1585-1594
        • Herzog R.
        • Alvarez-Pasquin M.J.
        • Diaz C.
        • Del Barrio J.L.
        • Estrada J.M.
        • Gil A
        Are healthcare workers' intentions to vaccinate related to their knowledge, beliefs and attitudes? A systematic review.
        BMC Public Health. 2013; 13: 154
        • Nyaga V.N.
        • Arbyn M.
        • Aerts M
        Metaprop: a stata command to perform meta-analysis of binomial data.
        Arch Public Health. 2014; 72: 39
        • Clopper C.J.
        • Pearson E.S.
        The use of confidence or fiducial limits illustrated in the case of the binomial.
        Biometrika. 1934; 26: 404-413
        • Freeman M.F.
        • Tukey J.W.
        Transformations related to the angular and the square root.
        Ann Math Stat. 1950; 21: 607-611
        • DerSimonian R.
        • Laird N.
        Meta-analysis in clinical trials.
        Control Clin Trials. 1986; 7: 177-188
        • van Rossum L.G.
        • van Rijn A.F.
        • Laheij R.J.
        • van Oijen M.G.
        • Fockens P.
        • Jansen J.B.
        • et al.
        Cutoff value determines the performance of a semi-quantitative immunochemical faecal occult blood test in a colorectal cancer screening programme.
        Br J Cancer. 2009; 101: 1274-1281
        • Carter D.
        • Bardan E.
        • Derazne E.
        • Tzur D.
        • Avidan B
        The incidence of gastrointestinal pathology and subsequent anemia in young men presenting with iron deficiency without anemia.
        Eur J Gastroenterol Hepatol. 2016; 28: 1126-1129
        • Garcia Garcia de Paredes A.
        • Teruel Sanchez-Vegazo C.
        • Hernanz Ruiz N.
        • Ferre Aracil C.
        • Rodriguez de Santiago E.
        • Aguilera Castro L.
        • et al.
        Do patients with iron deficiency without anemia benefit from an endoscopic examination?.
        J Dig Dis. 2017; 18: 416-424
        • Joosten E.
        • Meeuwissen J.
        • Vandewinckele H.
        • Hiele M
        Iron status and colorectal cancer in symptomatic elderly patients.
        Am J Med. 2008; 121: 1072-1077
        • Bergamaschi G.
        • Di Sabatino A.
        • Albertini R.
        • Ardizzone S.
        • Biancheri P.
        • Bonetti E.
        • et al.
        Prevalence and pathogenesis of anemia in inflammatory bowel disease. Influence of anti-tumor necrosis factor-alpha treatment.
        Haematologica. 2010; 95: 199-205
        • Culliford A.
        • Daly J.
        • Diamond B.
        • Rubin M.
        • Green P.H
        The value of wireless capsule endoscopy in patients with complicated celiac disease.
        Gastrointest Endosc. 2005; 62: 55-61
        • Hunt G.C.
        • Faigel D.O.
        Endoscopic evaluation of patients with partial gastrectomy and iron deficiency.
        Dig Dis Sci. 2002; 47: 641-644
        • Ludwig H.
        • Muldur E.
        • Endler G.
        • Hubl W
        Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia.
        Ann Oncol. 2013; 24: 1886-1892
        • Masson S.
        • Chinn D.J.
        • Tabaqchali M.A.
        • Waddup G.
        • Dwarakanath A.D
        Is anaemia relevant in the referral and diagnosis of colorectal cancer?.
        Colorectal Dis. 2007; 9: 736-739
        • Rai S.
        • Hemingway D.
        Iron deficiency anaemia–useful diagnostic tool for right sided colon cancers?.
        Colorectal Dis. 2005; 7: 588-590
        • Baicus C.
        • Caraiola S.
        • Rimbas M.
        • Patrascu R.
        • Baicus A
        Ferritin above 100 mcg/L could rule out colon cancer, but not gastric or rectal cancer in patients with involuntary weight loss.
        BMC Gastroenterol. 2012; 12: 86
        • Clere-Jehl R.
        • Schaeffer M.
        • Vogel T.
        • Kiesmann M.
        • Pasquali J.L.
        • Andres E.
        • et al.
        Upper and lower gastrointestinal endoscopies in patients over 85 years of age: risk-benefit evaluation of a longitudinal cohort.
        Medicine. 2017; 96: e8439
        • Edwards A.
        • Penney M.
        • Allison M
        Using iron deficiency tests for colorectal cancer screening: a feasibility study in one UK general practice.
        J Eval Clin Pract. 2004; 10: 475-479
        • Hamilton W.
        • Lancashire R.
        • Sharp D.
        • Peters T.J.
        • Cheng K.
        • Marshall T
        The risk of colorectal cancer with symptoms at different ages and between the sexes: a case-control study.
        BMC Med. 2009; 7: 17
        • James M.W.
        • Chen C.M.
        • Goddard W.P.
        • Scott B.B.
        • Goddard A.F
        Risk factors for gastrointestinal malignancy in patients with iron-deficiency anaemia.
        Eur J Gastroenterol Hepatol. 2005; 17: 1197-1203
        • Kidney E.
        • Berkman L.
        • Macherianakis A.
        • Morton D.
        • Dowswell G.
        • Hamilton W.
        • et al.
        Preliminary results of a feasibility study of the use of information technology for identification of suspected colorectal cancer in primary care: the Credible study.
        Br J Cancer. 2015; 112: S70-S76
        • Kim N.H.
        • Lee M.Y.
        • Park J.H.
        • Park D.I.
        • Sohn C.I.
        • Choi K.
        • et al.
        A combination of fecal immunochemical test results and iron deficiency anemia for detection of advanced colorectal neoplasia in asymptomatic men.
        Yonsei Med J. 2017; 58: 910-917
        • Kinar Y.
        • Akiva P.
        • Choman E.
        • Kariv R.
        • Shalev V.
        • Levin B.
        • et al.
        Performance analysis of a machine learning flagging system used to identify a group of individuals at a high risk for colorectal cancer.
        PLoS One. 2017; 12e0171759
        • Kinar Y.
        • Kalkstein N.
        • Akiva P.
        • Levin B.
        • Half E.E.
        • Goldshtein I.
        • et al.
        Development and validation of a predictive model for detection of colorectal cancer in primary care by analysis of complete blood counts: a binational retrospective study.
        J Am Med Inform Assoc. 2016; 23: 879-890
        • Mankodi S.
        • Hayee B.H.
        • O'Donohue J.
        • Reffitt D
        Anaemia investigation in practice: inappropriate, cost inefficient with a risk of missing gastrointestinal cancer. Can we improve?.
        Clin Med. 2010; 10: 115-118
        • Niv E.
        • Elis A.
        • Zissin R.
        • Naftali T.
        • Novis B.
        • Lishner M
        Iron deficiency anemia in patients without gastrointestinal symptoms – a prospective study.
        Fam Pract. 2005; 22: 58-61
        • Park D.I.
        • Ryu S.H.
        • Oh S.J.
        • Yoo T.W.
        • Kim H.J.
        • Cho Y.K.
        • et al.
        Significance of endoscopy in asymptomatic premenopausal women with iron deficiency anemia.
        Dig Dis Sci. 2006; 51: 2372-2376
        • Saks K.
        • Enestvedt B.K.
        • Holub J.L.
        • Lieberman D
        Colonoscopy identifies increased prevalence of large polyps or tumors in patients 40–49 years old with hematochezia vs other gastrointestinal indications.
        Clin Gastroenterol Hepatol. 2016; 14: 843-849
        • Sawhney M.S.
        • Lipato T.
        • Nelson D.B.
        • Lederle F.A.
        • Rector T.S.
        • Bond J.H
        Should patients with anemia and low normal or normal serum ferritin undergo colonoscopy?.
        Am J Gastroenterol. 2007; 102: 82-88
        • Shaw A.G.
        • Simpson J.
        • Tierney G.
        • Goddard A.F.
        • Reynolds J.R.
        • Lund J.N
        Referral of patients with iron deficiency anaemia under the lower gastrointestinal two-week wait rule.
        Colorectal Dis. 2008; 10: 294-297
        • Spell D.W.
        • Jones Jr., D.V.
        • Harper W.F.
        • David Bessman J
        The value of a complete blood count in predicting cancer of the colon.
        Cancer Detect Prev. 2004; 28: 37-42
        • Thompson M.R.
        • O'Leary D.P.
        • Flashman K.
        • Asiimwe A.
        • Ellis B.G.
        • Senapati A
        Clinical assessment to determine the risk of bowel cancer using Symptoms, Age, Mass and Iron deficiency anaemia (SAMI).
        Br J Surg. 2017; 104: 1393-1404
        • Beg S.
        • Ragunath K.
        • Wyman A.
        • Banks M.
        • Trudgill N.
        • Pritchard D.M.
        • et al.
        Quality standards in upper gastrointestinal endoscopy: a position statement of the British Society of Gastroenterology (BSG) and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS).
        Gut. 2017; 66: 1886-1899
        • Coates A.
        • Mountjoy M.
        • Burr J
        Incidence of iron deficiency and iron deficient anemia in elite runners and triathletes.
        Clin J Sport Med. 2017; 27: 493-498
        • Epstein D.
        • Borohovitz A.
        • Merdler I.
        • Furman M.
        • Atalli E.
        • Sorkin A.
        • et al.
        Prevalence of iron deficiency and iron deficiency anemia in strenuously training male army recruits.
        Acta Haematol. 2018; 139: 141-147
        • Ayling R.M.
        • Lewis S.J.
        • Cotter F
        Potential roles of artificial intelligence learning and faecal immunochemical testing for prioritisation of colonoscopy in anaemia.
        Br J Haematol. 2019; 185: 311-316
        • Cilona A.
        • Zullo A.
        • Hassan C.
        • Ridola L.
        • Annese M
        Is faecal-immunochemical test useful in patients with iron deficiency anaemia and without overt bleeding?.
        Dig Liver Dis. 2011; 43: 1022-1024
        • Selby K.
        • Levine E.H.
        • Doan C.
        • Gies A.
        • Brenner H.
        • Quesenberry C.
        • et al.
        Effect of sex, age, and positivity threshold on fecal immunochemical test accuracy: a systematic review and meta-analysis.
        Gastroenterology. 2019; 157: 1494-1505