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Small bowel adenocarcinoma in Crohn’s disease: a systematic review and meta-analysis of the prevalence, manifestation, histopathology, and outcomes

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Abstract

Background and aims

Small bowel adenocarcinoma (SBA) is a rare neoplasm that is associated with Crohn’s disease (CD). This study aims to quantify the prevalence of CD-SBA, review the current evidence of histopathology and molecular analysis findings, and identify the clinical presentation and outcomes of CD-SBA.

Methods

Electronic databases Medline and Embase were searched for articles describing SBA in inflammatory bowel disease patients. The histopathology, molecular analysis findings, clinical presentation, prevalence, and outcomes of CD-SBA were extracted, and results were pooled with random effects.

Results

In total, 33 articles were included in the analysis. Prevalence of SBA was 1.15 (CI: 0.31–2.33) per 1000 CD patients. Only 11% (CI: 0.04–0.21) of CD-SBA patients had observable radiological features. CD-SBA was most commonly found in the ileum (84%), diagnosed at stage 2 (36%), with main presenting complaints including obstruction, weight loss, and abdominal pain. Significant histopathological findings included adjacent epithelial dysplasia, and an equal distribution of well-differentiated (49%) and poorly differentiated subtypes (46%). Most prevalent genetic mutation was KRAS mutation (18%), followed by mismatch repair deficiency (9.7%). The 5-year overall survival for CD-SBA patients was 29% (CI: 0.18–0.41), and 33% (CI: 0.26–0.41) for de novo SBA. No statistically significant increase in risk for CD-SBA was noted for treatment with thiopurines, steroids, and 5-ASA.

Conclusion

Our meta-analysis found the prevalence of CD-SBA to be 1.15 per 1000 CD patients. The 5-year overall survival for CD-SBA was poor. The presenting symptoms were non-specific, and therefore the diagnosis requires a high index of suspicion.

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Data availability

The articles included in this article are available on the search databases.

References

  1. (2020) SEER*Explorer: an interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute (NCI), United States

  2. Barsouk A, Rawla P, Barsouk A, Thandra KC (2019) Epidemiology of cancers of the small intestine: trends, risk factors, and prevention. Med Sci (Basel) 2019:7. https://doi.org/10.3390/medsci7030046

    Article  CAS  Google Scholar 

  3. Bilimoria KY, Bentrem DJ, Wayne JD, Ko CY, Bennett CL, Talamonti MS (2009) Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann Surg 249:63–71. https://doi.org/10.1097/SLA.0b013e31818e4641

    Article  PubMed  Google Scholar 

  4. Axelrad JE, Olen O, Sachs MC, Erichsen R, Pedersen L, Halfvarson J et al (2021) Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden. Gut 70:297–308. https://doi.org/10.1136/gutjnl-2020-320945

    Article  CAS  PubMed  Google Scholar 

  5. Jess T, Loftus EV Jr, Velayos FS, Harmsen WS, Zinsmeister AR, Smyrk TC et al (2006) Risk of intestinal cancer in inflammatory bowel disease: a population-based study from Olmsted County. Minnesota Gastroenterology 130:1039–1046. https://doi.org/10.1053/j.gastro.2005.12.037

    Article  PubMed  Google Scholar 

  6. Jess T, Winther KV, Munkholm P, Langholz E, Binder V (2004) Intestinal and extra-intestinal cancer in Crohn’s disease: follow-up of a population-based cohort in Copenhagen County. Denmark Aliment Pharmacol Ther 19:287–293. https://doi.org/10.1111/j.1365-2036.2004.01858.x

    Article  CAS  PubMed  Google Scholar 

  7. von Roon AC, Reese G, Teare J, Constantinides V, Darzi AW, Tekkis PP (2007) The risk of cancer in patients with Crohn’s disease. Dis Colon Rectum 50:839–855. https://doi.org/10.1007/s10350-006-0848-z

    Article  Google Scholar 

  8. Solem CA, Harmsen WS, Zinsmeister AR, Loftus EV Jr (2004) Small intestinal adenocarcinoma in Crohn’s disease: a case-control study. Inflamm Bowel Dis 10:32–35. https://doi.org/10.1097/00054725-200401000-00005

    Article  PubMed  Google Scholar 

  9. Ribeiro MB, Greenstein AJ, Heimann TM, Yamazaki Y, Aufses AH Jr (1991) Adenocarcinoma of the small intestine in Crohn’s disease. Surg Gynecol Obstet 173: 343–9

  10. Annese V (2020) Small bowel adenocarcinoma in Crohn’s disease: an underestimated risk? J Crohns Colitis 14:285–286. https://doi.org/10.1093/ecco-jcc/jjz168

    Article  PubMed  Google Scholar 

  11. Svrcek M, Piton G, Cosnes J, Beaugerie L, Vermeire S, Geboes K et al (2014) Small bowel adenocarcinomas complicating Crohn’s disease are associated with dysplasia: a pathological and molecular study. Inflamm Bowel Dis 20:1584–1592. https://doi.org/10.1097/MIB.0000000000000112

    Article  PubMed  Google Scholar 

  12. Aparicio T, Zaanan A, Svrcek M, Laurent-Puig P, Carrere N, Manfredi S et al (2014) Small bowel adenocarcinoma: epidemiology, risk factors, diagnosis and treatment. Dig Liver Dis 46:97–104. https://doi.org/10.1016/j.dld.2013.04.013

    Article  PubMed  Google Scholar 

  13. Diosdado B, Buffart TE, Watkins R, Carvalho B, Ylstra B, Tijssen M et al (2010) High-resolution array comparative genomic hybridization in sporadic and celiac disease-related small bowel adenocarcinomas. Clin Cancer Res 16:1391–1401. https://doi.org/10.1158/1078-0432.CCR-09-1773

    Article  CAS  PubMed  Google Scholar 

  14. Piton G, Cosnes J, Monnet E, Beaugerie L, Seksik P, Savoye G et al (2008) Risk factors associated with small bowel adenocarcinoma in Crohn’s disease: a case-control study. Am J Gastroenterol 103:1730–1736. https://doi.org/10.1111/j.1572-0241.2008.01847.x

    Article  PubMed  Google Scholar 

  15. Cahill C, Gordon PH, Petrucci A, Boutros M (2014) Small bowel adenocarcinoma and Crohn’s disease: any further ahead than 50 years ago? World J Gastroenterol 20:11486–11495. https://doi.org/10.3748/wjg.v20.i33.11486

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hoffman JP, Taft DA, Wheelis RF, Walker JH (1977) Adenocarcinoma in regional enteritis of the small intestine. Arch Surg 112:606–611. https://doi.org/10.1001/archsurg.1977.01370050066011

    Article  CAS  PubMed  Google Scholar 

  17. Dossett LA, White LM, Welch DC, Herline AJ, Muldoon RL, Schwartz DA et al (2007) Small bowel adenocarcinoma complicating Crohn’s disease: case series and review of the literature. Am Surg 73:1181–7

  18. Floch HF, Slattery LR, Hazzi CG (1978) Carcinoma of the small intestine in regional enteritis: presentation of a case and review of the literature. Am J Gastroenterol 70:520–7

  19. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med 6

  20. Schwarzer G, Chemaitelly H, Abu-Raddad LJ, Rucker G (2019) Seriously misleading results using inverse of Freeman-Tukey double arcsine transformation in meta-analysis of single proportions. Res Synth Methods 10:476–483. https://doi.org/10.1002/jrsm.1348

    Article  PubMed  PubMed Central  Google Scholar 

  21. Clopper CJ, Pearson ES (1934) The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 26:404–413. https://doi.org/10.2307/2331986

    Article  Google Scholar 

  22. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 2003(327):557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  Google Scholar 

  23. Hunter JP, Saratzis A, Sutton AJ, Boucher RH, Sayers RD, Bown MJ (2014) In meta-analyses of proportion studies, funnel plots were found to be an inaccurate method of assessing publication bias. J Clin Epidemiol 67:897–903. https://doi.org/10.1016/j.jclinepi.2014.03.003

    Article  PubMed  Google Scholar 

  24. Frolkis AD, Dykeman J, Negron ME, Debruyn J, Jette N, Fiest KM et al (2013) Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology 145:996–1006. https://doi.org/10.1053/j.gastro.2013.07.041

    Article  PubMed  Google Scholar 

  25. Katz D, Baptista J, Azen SP, Pike MC (1978) Obtaining confidence intervals for the risk ratio in cohort studies. Biometrics 34:469–474. https://doi.org/10.2307/2530610

    Article  Google Scholar 

  26. Hoy D, Brooks P, Woolf A, Blyth F, March L, Bain C et al (2012) Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. J Clin Epidemiol 65:934–939. https://doi.org/10.1016/j.jclinepi.2011.11.014

    Article  PubMed  Google Scholar 

  27. Liao X, Li G, McBride R, Houldsworth J, Harpaz N, Polydorides AD (2020) Clinicopathological and molecular characterisation of Crohn’s disease-associated small bowel adenocarcinomas. J Crohns Colitis 14:287–294. https://doi.org/10.1093/ecco-jcc/jjz135

    Article  PubMed  Google Scholar 

  28. Hussain T, Jeganathan NA, Karagkounis G, Stocchi L, Shawki S, Holubar SD et al (2020) Small bowel adenocarcinoma in Crohn’s disease: a rare but devastating complication. Tech Coloproctol 24:1055–1062. https://doi.org/10.1007/s10151-020-02269-8

    Article  CAS  PubMed  Google Scholar 

  29. Wieghard N, Mongoue-Tchokote S, Young JI, Sheppard BC, Tsikitis VL (2017) Prognosis of small bowel adenocarcinoma in Crohn’s disease compares favourably with de novo small bowel adenocarcinoma. Colorectal Dis 19:446–455. https://doi.org/10.1111/codi.13531

    Article  CAS  PubMed  Google Scholar 

  30. Weber NK, Fletcher JG, Fidler JL, Barlow JM, Pruthi S, Loftus EV Jr et al (2015) Clinical characteristics and imaging features of small bowel adenocarcinomas in Crohn’s disease. Abdom Imaging 40:1060–1067. https://doi.org/10.1007/s00261-014-0144-7

    Article  PubMed  Google Scholar 

  31. Lashner BA (1992) Risk factors for small bowel cancer in Crohn’s disease. Dig Dis Sci 37:1179–1184. https://doi.org/10.1007/BF01296557

    Article  CAS  PubMed  Google Scholar 

  32. Michelassi F, Testa G, Pomidor WJ, Lashner BA, Block GE (1993) Adenocarcinoma complicating Crohn’s disease. Dis Colon Rectum 36:654–661. https://doi.org/10.1007/BF02238592

    Article  CAS  PubMed  Google Scholar 

  33. Widmar M, Greenstein AJ, Sachar DB, Harpaz N, Bauer JJ, Greenstein AJ (2011) Small bowel adenocarcinoma in Crohn’s disease. J Gastrointest Surg 15:797–802. https://doi.org/10.1007/s11605-011-1441-x

    Article  PubMed  Google Scholar 

  34. Fields AC, Hu FY, Lu P, Irani J, Bleday R, Goldberg JE et al (2020) Small bowel adenocarcinoma: is there a difference in survival for Crohn’s versus sporadic cases? J Crohns Colitis 14:303–308. https://doi.org/10.1093/ecco-jcc/jjz157

    Article  PubMed  Google Scholar 

  35. Bojesen RD, Riis LB, Hogdall E, Nielsen OH, Jess T (2017) Inflammatory bowel disease and small bowel cancer risk, clinical characteristics, and histopathology: a population-based study. Clin Gastroenterol Hepatol 15(1900–7)

  36. Kaerlev L, Teglbjaerg PS, Sabroe S, Kolstad HA, Ahrens W, Eriksson M et al (2001) Medical risk factors for small-bowel adenocarcinoma with focus on Crohn disease: a European population-based case-control study. Scand J Gastroenterol 36:641–646. https://doi.org/10.1080/003655201750163150

    Article  CAS  PubMed  Google Scholar 

  37. Kvist N, Jacobsen O, Norgaard P, Ockelmann HH, Kvist HK, Schou G et al (1986) Malignancy in Crohn’s disease. Scand J Gastroenterol 21:82–86. https://doi.org/10.3109/00365528609034627

    Article  CAS  PubMed  Google Scholar 

  38. Simon M, Cosnes J, Gornet JM, Seksik P, Stefanescu C, Blain A et al (2017) Endoscopic detection of small bowel dysplasia and adenocarcinoma in Crohn’s disease: a prospective cohort-study in high-risk patients. J Crohns Colitis 11:47–52. https://doi.org/10.1093/ecco-jcc/jjw123

    Article  CAS  PubMed  Google Scholar 

  39. Grolleau C, Pote NM, Guedj NS, Zappa M, Theou-Anton N, Bouhnik Y et al (2017) Small bowel adenocarcinoma complicating Crohn’s disease: a single-centre experience emphasizing the importance of screening for dysplasia. Virchows Arch 471:611–617. https://doi.org/10.1007/s00428-017-2125-z

    Article  CAS  PubMed  Google Scholar 

  40. Elriz K, Carrat F, Carbonnel F, Marthey L, Bouvier AM, Beaugerie L et al (2013) Incidence, presentation, and prognosis of small bowel adenocarcinoma in patients with small bowel Crohn’s disease: a prospective observational study. Inflamm Bowel Dis 19:1823–1826. https://doi.org/10.1097/MIB.0b013e31828c84f2

    Article  PubMed  Google Scholar 

  41. Palascak-Juif V, Bouvier AM, Cosnes J, Flourie B, Bouche O, Cadiot G et al (2005) Small bowel adenocarcinoma in patients with Crohn’s disease compared with small bowel adenocarcinoma de novo. Inflamm Bowel Dis 11:828–832. https://doi.org/10.1097/01.mib.0000179211.03650.b6

    Article  PubMed  Google Scholar 

  42. Soyer P, Hristova L, Boudghene F, Hoeffel C, Dray X, Laurent V et al (2012) Small bowel adenocarcinoma in Crohn disease: CT-enterography features with pathological correlation. Abdom Imaging 37:338–349. https://doi.org/10.1007/s00261-011-9772-3

    Article  PubMed  Google Scholar 

  43. Yamamoto T, Allan RN, Keighley MR (2001) Long-term outcome of surgical management for diffuse jejunoileal Crohn’s disease. Surgery 129:96–102. https://doi.org/10.1067/msy.2001.109497

    Article  CAS  PubMed  Google Scholar 

  44. Connell WR, Sheffield JP, Kamm MA, Ritchie JK, Hawley PR, Lennard-Jones JE (1994) Lower gastrointestinal malignancy in Crohn’s disease. Gut 35:347–352. https://doi.org/10.1136/gut.35.3.347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lindgren A, Wallerstedt S, Olsson R (1996) Prevalence of Crohn’s disease and simultaneous occurrence of extraintestinal complications and cancer. An epidemiologic study in adults. Scand J Gastroenterol 31:74–8. https://doi.org/10.3109/00365529609031630

  46. Giuffrida P, Arpa G, Grillo F, Klersy C, Sampietro G, Ardizzone S et al (2020) PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability. Mod Pathol 33:1398–1409. https://doi.org/10.1038/s41379-020-0497-0

    Article  CAS  PubMed  Google Scholar 

  47. Biancone L, Armuzzi A, Scribano ML, Castiglione F, D’Inca R, Orlando A et al (2020) Cancer risk in inflammatory bowel disease: a 6-year prospective multicenter nested case-control IG-IBD study. Inflamm Bowel Dis 26:450–459. https://doi.org/10.1093/ibd/izz155

    Article  PubMed  Google Scholar 

  48. Katsanos KH, Christodoulou DK, Michael M, Ioachim E, Tsianos GV, Agnantis N et al (2005) Inflammatory bowel disease-related dysplasia and cancer: a referral center study in northwestern Greece. Eur J Intern Med 16:170–175. https://doi.org/10.1016/j.ejim.2004.09.016

    Article  CAS  PubMed  Google Scholar 

  49. Fireman Z, Grossman A, Lilos P, Hacohen D, Bar Meir S, Rozen P et al (1989) Intestinal cancer in patients with Crohn’s disease. A population study in central Israel. Scand J Gastroenterol 24:346–50. https://doi.org/10.3109/00365528909093058

  50. Bernstein CN, Blanchard JF, Kliewer E, A Wajda (2001) Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 91:854–862.

    Article  CAS  PubMed  Google Scholar 

  51. Algaba A, Guerra I, Marin-Jimenez I, Quintanilla E, Lopez-Serrano P, Garcia-Sanchez MC et al (2015) Incidence, management, and course of cancer in patients with inflammatory bowel disease. J Crohns Colitis 9:326–333. https://doi.org/10.1093/ecco-jcc/jjv032

    Article  PubMed  Google Scholar 

  52. Kamiya T, Ando T, Ishiguro K, Maeda O, Watanabe O, Hibi S et al (2012) Intestinal cancers occurring in patients with Crohn’s disease. J Gastroenterol Hepatol 27(Suppl 3):103–107. https://doi.org/10.1111/j.1440-1746.2012.07082.x

    Article  PubMed  Google Scholar 

  53. Jung YS, Han M, Park S, Kim WH, Cheon JH (2017) Cancer risk in the early stages of inflammatory bowel disease in Korean patients: a nationwide population-based study. J Crohns Colitis 11:954–962. https://doi.org/10.1093/ecco-jcc/jjx040

    Article  PubMed  Google Scholar 

  54. Chin YH, Ng CH, Lin SY, Jain SR, Kong G, Koh JWH et al (2021) Systematic review with meta-analysis: the prevalence, risk factors and outcomes of upper gastrointestinal tract. Crohn’s disease Dig Liver Dis. https://doi.org/10.1016/j.dld.2021.07.037

  55. Farmer RG, Whelan G, Fazio VW (1985) Long-term follow-up of patients with Crohn’s disease: relationship between the clinical pattern and prognosis. Gastroenterology 88:1818–1825. https://doi.org/10.1016/0016-5085(85)90006-X

    Article  CAS  PubMed  Google Scholar 

  56. Argollo M, Gilardi D, Peyrin-Biroulet C, Chabot J-F, Peyrin-Biroulet L, Danese S (2019) Comorbidities in inflammatory bowel disease: a call for action. The Lancet Gastroenterology & Hepatology 4:643–654. https://doi.org/10.1016/S2468-1253(19)30173-6

    Article  Google Scholar 

  57. Bhamre R, Sawrav S, Adarkar S, Sakaria R, J Bhatia S (2018) Psychiatric comorbidities in patients with inflammatory bowel disease. Indian J Gastroenterol 37:307–312. https://doi.org/10.1007/s12664-018-0870-9

    Article  PubMed  Google Scholar 

  58. Buckley JA, Siegelman SS, Jones B, Fishman EK (1997) The accuracy of CT staging of small bowel adenocarcinoma: CT/pathologic correlation. J Comput Assist Tomogr 21:986–991. https://doi.org/10.1097/00004728-199711000-00025

    Article  CAS  PubMed  Google Scholar 

  59. Martineau C, Lefèvre JH, Chafai N, O’Connell L, Svrcek M, Beaugerie L et al (2021) Intraoperative random biopsies of strictureplasty sites can detect early small-bowel adenocarcinoma in patients with Crohn’s disease. Dig Liver Dis 53:924–926. https://doi.org/10.1016/j.dld.2021.04.017

    Article  PubMed  Google Scholar 

  60. Bemelman WA, Warusavitarne J, Sampietro GM, Serclova Z, Zmora O, Luglio G et al (2018) ECCO-ESCP consensus on surgery for Crohn’s disease. Journal of Crohn’s and Colitis 12:1–16. https://doi.org/10.1093/ecco-jcc/jjx061

    Article  PubMed  Google Scholar 

  61. Partridge SK, Hodin RA (2004) Small bowel adenocarcinoma at a strictureplasty site in a patient with Crohn’s disease: report of a case. Dis Colon Rectum 47:778–781. https://doi.org/10.1007/s10350-003-0101-y

    Article  PubMed  Google Scholar 

  62. Axelrad JE, Lichtiger S, Yajnik V (2016) Inflammatory bowel disease and cancer: the role of inflammation, immunosuppression, and cancer treatment. World J Gastroenterol 22:4794–4801. https://doi.org/10.3748/wjg.v22.i20.4794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Vanoli A, Di Sabatino A, Martino M, Klersy C, Grillo F, Mescoli C et al (2017) Small bowel carcinomas in celiac or Crohn’s disease: distinctive histophenotypic, molecular and histogenetic patterns. Mod Pathol 30:1453–1466. https://doi.org/10.1038/modpathol.2017.40

    Article  CAS  PubMed  Google Scholar 

  64. Hong SH, Koh YH, Rho SY, Byun JH, Oh ST, Im KW et al (2009) Primary adenocarcinoma of the small intestine: presentation, prognostic factors and clinical outcome. Jpn J Clin Oncol 39:54–61. https://doi.org/10.1093/jjco/hyn122

    Article  PubMed  Google Scholar 

  65. Sakae H, Kanzaki H, Nasu J, Akimoto Y, Matsueda K, Yoshioka M et al (2017) The characteristics and outcomes of small bowel adenocarcinoma: a multicentre retrospective observational study. Br J Cancer 117:1607–1613. https://doi.org/10.1038/bjc.2017.338

    Article  PubMed  PubMed Central  Google Scholar 

  66. Wu TJ, Yeh CN, Chao TC, Jan YY, Chen MF (2006) Prognostic factors of primary small bowel adenocarcinoma: univariate and multivariate analysis. World J Surg 30:391–8; discussion 9. https://doi.org/10.1007/s00268-005-7898-6

  67. Strong S, Steele SR, Boutrous M, Bordineau L, Chun J, Stewart DB et al (2015) Clinical practice guideline for the surgical management of Crohn’s disease. Dis Colon Rectum 58:1021–1036. https://doi.org/10.1097/DCR.0000000000000450

    Article  PubMed  Google Scholar 

  68. Schrock AB, Devoe CE, McWilliams R, Sun J, Aparicio T, Stephens PJ et al (2017) Genomic profiling of small-bowel adenocarcinoma. JAMA Oncol 3:1546–1553. https://doi.org/10.1001/jamaoncol.2017.1051

    Article  PubMed  PubMed Central  Google Scholar 

  69. Jun SY, Lee EJ, Kim MJ, Chun SM, Bae YK, Hong SU et al (2017) Lynch syndrome-related small intestinal adenocarcinomas Oncotarget 2017(8):21483–21500. https://doi.org/10.18632/oncotarget.15277

    Article  Google Scholar 

  70. Yang J, Nie J, Ma X, Wei Y, Peng Y, Wei X (2019) Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer 18:26. https://doi.org/10.1186/s12943-019-0954-x

    Article  PubMed  PubMed Central  Google Scholar 

  71. Caputo F, Santini C, Bardasi C, Cerma K, Casadei-Gardini A, Spallanzani A et al (2019) BRAF-mutated colorectal cancer: clinical and molecular insights. Int J Mol Sci 2019:20. https://doi.org/10.3390/ijms20215369

    Article  CAS  Google Scholar 

  72. Wheeler JM, Warren BF, Mortensen NJ, Kim HC, Biddolph SC, Elia G et al (2002) An insight into the genetic pathway of adenocarcinoma of the small intestine. Gut 50:218–223. https://doi.org/10.1136/gut.50.2.218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Arai M, Shimizu S, Imai Y, Nakatsuru Y, Oda H, Oohara T et al (1997) Mutations of the Ki-ras, p53 and APC genes in adenocarcinomas of the human small intestine. Int J Cancer 70:390–395.

    Article  CAS  PubMed  Google Scholar 

  74. Breuhahn K, Singh S, Schirmacher P, Blaker H (2008) Large-scale N-terminal deletions but not point mutations stabilize beta-catenin in small bowel carcinomas, suggesting divergent molecular pathways of small and large intestinal carcinogenesis. J Pathol 215:300–307. https://doi.org/10.1002/path.2362

    Article  CAS  PubMed  Google Scholar 

  75. Mogire RM, Mutua A, Kimita W, Kamau A, Bejon P, Pettifor JM et al (2020) Prevalence of vitamin D deficiency in Africa: a systematic review and meta-analysis. Lancet Glob Health 8:e134–e142. https://doi.org/10.1016/S2214-109X(19)30457-7

    Article  PubMed  Google Scholar 

  76. Noubiap JJ, Nansseu JR, Nyaga UF, Nkeck JR, Endomba FT, Kaze AD et al (2019) Global prevalence of diabetes in active tuberculosis: a systematic review and meta-analysis of data from 2.3 million patients with tuberculosis. Lancet Glob Health 7:e448–e60. https://doi.org/10.1016/S2214-109X(18)30487-X

  77. Rucker G, Schwarzer G, Carpenter JR, Schumacher M (2008) Undue reliance on I2 in assessing heterogeneity may mislead. BMC Med Res Methodol 8:79. https://doi.org/10.1186/1471-2288-8-79

    Article  PubMed  PubMed Central  Google Scholar 

  78. Borges Migliavaca C, Stein C, Colpani V, Barker TH, Munn Z, Falavigna M et al (2020) How are systematic reviews of prevalence conducted? A methodological study. BMC Med Res Methodol 20:96. https://doi.org/10.1186/s12874-020-00975-3

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Yong Loo Lin School of Medicine, 10 Medical Dr, Singapore, 117597, Singapore

    Yip Han Chin, Sneha Rajiv Jain, Cheng Han Ng, Snow Yunni Lin, Aaron Shengting Mai, Mark Dhinesh Muthiah, Fung Joon Foo, Raghav Sundar & David Eng Hui Ong

  2. Faculty of Science, National University of Singapore, Singapore, Singapore

    Ming Hui Lee

  3. National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore

    Mark Dhinesh Muthiah & David Eng Hui Ong

  4. Department of General Surgery, Sengkang General Hospital, Singapore, Singapore

    Fung Joon Foo

  5. Department of Haematology-Oncology, National University Health System, Singapore, Singapore

    Raghav Sundar

  6. Division of Pathology, Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore

    Wei Qiang Leow

  7. Department of Anatomical Pathology, Duke-NUS Medical School, Singapore General Hospital, Singapore, Singapore

    Wei Qiang Leow

  8. The University of Sydney, Sydney, NSW, Australia

    Rupert Leong

  9. Concord Repatriation General Hospital, Sydney, NSW, Australia

    Rupert Leong

  10. Department of Gastroenterology, Singapore General Hospital, 16 College Road, Block 6 Level 6, Singapore, 169854, Singapore

    Webber Pak Wo Chan

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  13. Webber Pak Wo Chan
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Contributions

Yip Han Chin: conceptualization, data collection, methodology, data analysis, writing first draft of manuscript, critical revision of manuscript. Sneha Rajiv Jain: data collection, data analysis, methodology, writing first draft of manuscript, critical revision of manuscript. Ming Hui Lee: data collection, methodology, data analysis, critical revision of manuscript. Cheng Han Ng: conceptualization, data collection, methodology, data analysis, critical revision of manuscript. Snow Yunni Lin: data collection, methodology, critical revision of manuscript. Aaron Shengting Mai: data collection, methodology, critical revision of manuscript. Mark Dhinesh Muthiah: methodology, writing first draft of manuscript, critical revision of manuscript. Foo Fung Joon: methodology, writing first draft of manuscript, critical revision of manuscript. Raghav Sundar: data collection, writing first draft of manuscript, critical revision of manuscript. David Eng Hui Ong: writing first draft of manuscript, critical revision of manuscript. Raghav Sundar: data collection, writing first draft of manuscript, critical revision of manuscript. Rupert Leong: methodology, writing first draft of manuscript, critical revision of manuscript. Webber Pak Wo Chan: conceptualization, data collection, methodology, data analysis, writing first draft of manuscript, critical revision of manuscript. All authors approved the final version of the article, including the authorship list.

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Correspondence to Yip Han Chin or Webber Pak Wo Chan.

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Chin, Y.H., Jain, S.R., Lee, M.H. et al. Small bowel adenocarcinoma in Crohn’s disease: a systematic review and meta-analysis of the prevalence, manifestation, histopathology, and outcomes. Int J Colorectal Dis 37, 239–250 (2022). https://doi.org/10.1007/s00384-021-04050-1

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