Mistakes in colorectal cancer and how to avoid them

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Mistakes in colorectal cancer and how to avoid them

Antoni Castells, Francesc Balaguer

Summary

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This material addresses common mistakes in colorectal cancer diagnosis, prevention, and treatment and strategies to avoid them.

Colorectal cancer is a common and deadly disease, with advances in understanding having improved diagnosis, prevention, and treatment.
Genetic factors play a role in some cases, and identifying hereditary disorders has helped reduce morbidity and mortality.
Serrated polyps are precursors of colorectal cancer.
Colonoscopy is crucial for screening and prevention but is not perfect, as some lesions may be missed.

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References

Mistakes

References

Mistake 1 Mistake 2 Mistake 3 Mistake 4 Mistake 5 Mistake 6 Mistake 7 Mistake 8 Mistake 9 Mistake 10

Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71: 209-249. [Link]

Vasen HFA, Tomlinson I, Castells A. Clinical management of hereditary colorectal cancer syndromes. Nat Rev Gastroenterol Hepatol 2015; 12: 88-97. [Link]

IJspeert JEG, Vermeulen L, Meijer GA, et al. Serrated neoplasia-role in colorectal carcinogenesis and clinical implications. Nat Rev Gastroenterol Hepatol 2015; 12: 401-409. [Link]

Baile‐Maxía S, Mangas‐Sanjuan C, Sala‐Miquel N, et al. Incidence, characteristics, and predictive factors of post‐colonoscopy colorectal cancer. United Eur Gastroenterol J 2024; 12: 309-318. [Link]

Corley DA, Jensen CD, Marks AR, et al. Adenoma Detection Rate and Risk of Colorectal Cancer and Death. N Engl J Med 2014; 370: 1298-1306. [Link]

Win AK, Jenkins MA, Dowty JG, et al. Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 2017; 26: 404-412 [Link]

Dominguez-Valentin M, Sampson JR, Seppälä TT, et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet Med 2020; 22: 15-25. [Link]

Ten Broeke SW, Van Der Klift HM, Tops CMJ, et al. Cancer Risks for PMS2 -Associated Lynch Syndrome. J Clin Oncol 2018; 36: 2961-2968. [Link]

Moreira L, Balaguer F, Lindor N, et al. Identification of Lynch Syndrome Among Patients With Colorectal Cancer. JAMA 2012; 308: 1555. [Link]

10.

Parsons MT, Buchanan DD, Thompson B, et al. Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification. J Med Genet 2012; 49: 151-157. [Link]

11.

Leoz ML, Carballal S, Moreira L, et al. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. Appl Clin Genet 2015; 8: 95-107. [Link]

12.

Grover S, Kastrinos F, Steyerberg EW, et al. Prevalence and Phenotypes of APC and MUTYH Mutations in Patients With Multiple Colorectal Adenomas. JAMA; 308. Epub ahead of print 1 August 2012. [Link]

13.

The CORGI Consortium, The WGS500 Consortium, Palles C, et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet 2013; 45: 136-144. [Link]

14.

Lorca V, Rueda D, Martín-Morales L, et al. Contribution of New Adenomatous Polyposis Predisposition Genes in an Unexplained Attenuated Spanish Cohort by Multigene Panel Testing. Sci Rep 2019; 9: 9814. [Link]

15.

Muto T, Bussey HJR, Morson BC. The evolution of cancer of the colon and rectum. Cancer 1975; 36: 2251-2270. [Link]

16.

Carballal S, Balaguer F, IJspeert JEG. Serrated polyposis syndrome; epidemiology and management. Best Pract Res Clin Gastroenterol 2022; 58-59: 101791. [Link]

17.

Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology 2020; 76: 182-188. [Link]

18.

Crockett SD, Nagtegaal ID. Terminology, Molecular Features, Epidemiology, and Management of Serrated Colorectal Neoplasia. Gastroenterology 2019; 157: 949-966.e4. [Link]

19.

van Leerdam ME, Roos VH, van Hooft JE, et al. Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2019; 51: 877-895. [Link]

20.

Dekker E, Bleijenberg A, Balaguer F. Update on the World Health Organization Criteria for Diagnosis of Serrated Polyposis Syndrome. Gastroenterology 2020; 158: 1520-1523. [Link]

21.

Baile-Maxía S, Mangas-Sanjuan C, Medina-Prado L, et al. Diagnostic yield of early repeat colonoscopy after suboptimal bowel preparation in a fecal immunochemical test-based screening program. Endoscopy 2020; 52: 1093-1100. [Link]

22.

Kaminski M, Thomas-Gibson S, Bugajski M, et al. Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. Endoscopy 2017; 49: 378-397. [Link]

23.

Clark BT, Protiva P, Nagar A, et al. Quantification of Adequate Bowel Preparation for Screening or Surveillance Colonoscopy in Men. Gastroenterology 2016; 150: 396-405. [Link]

24.

Hassan C, East J, Radaelli F, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019. Endoscopy 2019; 51: 775-794. [Link]

25.

Atkin W, Wooldrage K, Brenner A, et al. Adenoma surveillance and colorectal cancer incidence: a retrospective, multicentre, cohort study. Lancet Oncol 2017; 18: 823-834. [Link]

26.

Cross AJ, Robbins EC, Pack K, et al. Colorectal cancer risk following polypectomy in a multicentre, retrospective, cohort study: an evaluation of the 2020 UK post-polypectomy surveillance guidelines. Gut 2021; 70:2307-2320. [Link]

27.

Hassan C, Antonelli G, Dumonceau J-M, et al. Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2020. Endoscopy 2020; 52: 687-700. [Link]

28.

Jover R, Bretthauer M, Dekker E, et al. Rationale and design of the European Polyp Surveillance (EPoS) trials. Endoscopy 2016; 48: 571-578. [Link]

29.

Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average‐risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin 2018; 68: 250-281. [Link]

30.

European guidelines for quality assurance in colorectal cancer screening and diagnosis: Overview and introduction to the full Supplement publication. Endoscopy 2012; 45: 51-59. [Link]

31.

Quintero E, Castells A, Bujanda L, et al. Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening. N Engl J Med 2012; 366: 697-706. [Link]

32.

Van Den Berg DMN, Nascimento De Lima P, Knudsen AB, et al. NordICC Trial Results in Line With Expected Colorectal Cancer Mortality Reduction After Colonoscopy: A Modeling Study. Gastroenterology 2023; 165: 1077-1079.e2. [Link]

33.

Atkin WS, Edwards R, Kralj-Hans I, et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. The Lancet 2010; 375: 1624-1633. [Link]

34.

Mandel JS, Bond JH, Church TR, et al. Reducing Mortality from Colorectal Cancer by Screening for Fecal Occult Blood. N Engl J Med 1993; 328: 1365-1371. [Link]

35.

Schoen RE, Pinsky PF, Weissfeld JL, et al. Colorectal-Cancer Incidence and Mortality with Screening Flexible Sigmoidoscopy. N Engl J Med 2012; 366: 2345-2357. [Link]

36.

Zauber AG, Winawer SJ, O'Brien MJ, et al. Colonoscopic Polypectomy and Long-Term Prevention of Colorectal-Cancer Deaths. N Engl J Med 2012; 366: 687-696. [Link]

37.

Van Rijn JC, Reitsma JB, Stoker J, et al. Polyp Miss Rate Determined by Tandem Colonoscopy: A Systematic Review. Am J Gastroenterol 2006; 101: 343-350. [Link]

38.

Kaminski MF, Wieszczy P, Rupinski M, et al. Increased Rate of Adenoma Detection Associates With Reduced Risk of Colorectal Cancer and Death. Gastroenterology 2017; 153: 98-105. [Link]

39.

Ji X. Poorly differentiated cluster grade-a vital predictor for lymph node metastasis and oncological outcomes in patients with T1 colorectal cancer: a retrospective study. [Link]

40.

Dang H, Dekkers N, Le Cessie S, et al. Risk and Time Pattern of Recurrences After Local Endoscopic Resection of T1 Colorectal Cancer: A Meta-analysis. Clin Gastroenterol Hepatol 2022; 20: e298-e314. [Link]

41.

Miyachi H, Kudo S, Ichimasa K, et al. Management of T1 colorectal cancers after endoscopic treatment based on the risk stratification of lymph node metastasis. J Gastroenterol Hepatol 2016; 31: 1126-1132. [Link]

42.

Beaton C, Twine CP, Williams GL, et al. Systematic review and meta‐analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer. Colorectal Dis 2013; 15: 788-797. [Link]

43.

Ozawa T, Kandimalla R, Gao F, et al. A MicroRNA Signature Associated With Metastasis of T1 Colorectal Cancers to Lymph Nodes. Gastroenterology 2018; 154: 844-848.e7. [Link]

44.

Zwager LW, Bastiaansen BAJ, Montazeri NSM, et al. Deep Submucosal Invasion Is Not an Independent Risk Factor for Lymph Node Metastasis in T1 Colorectal Cancer: A Meta-Analysis. Gastroenterology 2022; 163: 174-189. [Link]

45.

Brunori A, Daca-Alvarez M, Pellisé M. pT1 colorectal cancer: A treatment dilemma. Best Pract Res Clin Gastroenterol 2023; 66: 101854. [Link]

46.

Rutter MD, Beintaris I, Valori R, et al. World Endoscopy Organization Consensus Statements on Post-Colonoscopy and Post-Imaging Colorectal Cancer. Gastroenterology 2018; 155: 909-925.e3. [Link]

47.

Le Clercq CMC, Bouwens MWE, Rondagh EJA, et al. Postcolonoscopy colorectal cancers are preventable: a population-based study. Gut 2014; 63: 957-963. [Link]

48.

Singh H, Nugent Z, Demers AA, et al. Rate and Predictors of Early/Missed Colorectal Cancers After Colonoscopy in Manitoba: A Population-Based Study. Am J Gastroenterol 2010; 105: 2588-2596. [Link]

49.

Singh S, Singh PP, Murad MH, et al. Prevalence, Risk Factors, and Outcomes of Interval Colorectal Cancers: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2014; 109: 1375-1389. [Link]

50.

Adler J, Robertson DJ. Interval Colorectal Cancer After Colonoscopy: Exploring Explanations and Solutions. Am J Gastroenterol 2015; 110: 1657-1664. [Link]

51.

Robertson DJ, Lieberman DA, Winawer SJ, et al. Colorectal cancers soon after colonoscopy: a pooled multicohort analysis. Gut 2014; 63: 949-956. [Link]

52.

Leung LJ, Lee JK, Merchant SA, et al. Post-Colonoscopy Colorectal Cancer Etiologies in a Large Integrated US Health Care Setting. Gastroenterology 2023; 164: 470-472.e3. [Link]

53.

Sawhney MS, Farrar WD, Gudiseva S, et al. Microsatellite Instability in Interval Colon Cancers. Gastroenterology 2006; 131: 1700-1705. [Link]

54.

Imperiale TF, Glowinski EA, Lin-Cooper C, et al. Five-Year Risk of Colorectal Neoplasia after Negative Screening Colonoscopy. N Engl J Med 2008; 359: 1218-1224. [Link]

55.

Laiyemo AO, Murphy G, Sansbury LB, et al. Hyperplastic polyps and the risk of adenoma recurrence in the polyp prevention trial. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc 2009; 7: 192-197. [Link]

Abstract

Colorectal cancer (CRC) is a common and deadly disease. Advances in understanding the disease have improved diagnosis, prevention, and treatment. Genetic factors play a role in some cases of CRC, and identifying hereditary disorders has helped reduce morbidity and mortality. Serrated polyps are also precursors of CRC, and colonoscopy is crucial for screening and prevention. However, colonoscopy is not perfect, and some lesions may be missed. Here we discuss common mistakes in CRC diagnosis, prevention, and treatment, and how to avoid them.

Topics

Digestive Oncology

Citation

Balaguer F and Castells A. Mistakes in colorectal cancer and how to avoid them. UEG Education 2016: 16: 7–10.

Published

2025

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References

Mistakes

References

Mistake 1 Mistake 2 Mistake 3 Mistake 4 Mistake 5 Mistake 6 Mistake 7 Mistake 8 Mistake 9 Mistake 10

Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71: 209-249. [Link]

Vasen HFA, Tomlinson I, Castells A. Clinical management of hereditary colorectal cancer syndromes. Nat Rev Gastroenterol Hepatol 2015; 12: 88-97. [Link]

IJspeert JEG, Vermeulen L, Meijer GA, et al. Serrated neoplasia-role in colorectal carcinogenesis and clinical implications. Nat Rev Gastroenterol Hepatol 2015; 12: 401-409. [Link]

Corley DA, Jensen CD, Marks AR, et al. Adenoma Detection Rate and Risk of Colorectal Cancer and Death. N Engl J Med 2014; 370: 1298-1306. [Link]

Ten Broeke SW, Van Der Klift HM, Tops CMJ, et al. Cancer Risks for PMS2 -Associated Lynch Syndrome. J Clin Oncol 2018; 36: 2961-2968. [Link]

Moreira L, Balaguer F, Lindor N, et al. Identification of Lynch Syndrome Among Patients With Colorectal Cancer. JAMA 2012; 308: 1555. [Link]

10.

11.

Leoz ML, Carballal S, Moreira L, et al. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. Appl Clin Genet 2015; 8: 95-107. [Link]

12.

Grover S, Kastrinos F, Steyerberg EW, et al. Prevalence and Phenotypes of APC and MUTYH Mutations in Patients With Multiple Colorectal Adenomas. JAMA; 308. Epub ahead of print 1 August 2012. [Link]

13.

14.

15.

Muto T, Bussey HJR, Morson BC. The evolution of cancer of the colon and rectum. Cancer 1975; 36: 2251-2270. [Link]

16.

Carballal S, Balaguer F, IJspeert JEG. Serrated polyposis syndrome; epidemiology and management. Best Pract Res Clin Gastroenterol 2022; 58-59: 101791. [Link]

17.

Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology 2020; 76: 182-188. [Link]

18.

Crockett SD, Nagtegaal ID. Terminology, Molecular Features, Epidemiology, and Management of Serrated Colorectal Neoplasia. Gastroenterology 2019; 157: 949-966.e4. [Link]

19.

van Leerdam ME, Roos VH, van Hooft JE, et al. Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2019; 51: 877-895. [Link]

20.

Dekker E, Bleijenberg A, Balaguer F. Update on the World Health Organization Criteria for Diagnosis of Serrated Polyposis Syndrome. Gastroenterology 2020; 158: 1520-1523. [Link]

21.

22.

23.

Clark BT, Protiva P, Nagar A, et al. Quantification of Adequate Bowel Preparation for Screening or Surveillance Colonoscopy in Men. Gastroenterology 2016; 150: 396-405. [Link]

24.

Hassan C, East J, Radaelli F, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019. Endoscopy 2019; 51: 775-794. [Link]

25.

Atkin W, Wooldrage K, Brenner A, et al. Adenoma surveillance and colorectal cancer incidence: a retrospective, multicentre, cohort study. Lancet Oncol 2017; 18: 823-834. [Link]

26.

27.

28.

Jover R, Bretthauer M, Dekker E, et al. Rationale and design of the European Polyp Surveillance (EPoS) trials. Endoscopy 2016; 48: 571-578. [Link]

29.

Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average‐risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin 2018; 68: 250-281. [Link]

30.

European guidelines for quality assurance in colorectal cancer screening and diagnosis: Overview and introduction to the full Supplement publication. Endoscopy 2012; 45: 51-59. [Link]

31.

Quintero E, Castells A, Bujanda L, et al. Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening. N Engl J Med 2012; 366: 697-706. [Link]

32.

33.

34.

Mandel JS, Bond JH, Church TR, et al. Reducing Mortality from Colorectal Cancer by Screening for Fecal Occult Blood. N Engl J Med 1993; 328: 1365-1371. [Link]

35.

Schoen RE, Pinsky PF, Weissfeld JL, et al. Colorectal-Cancer Incidence and Mortality with Screening Flexible Sigmoidoscopy. N Engl J Med 2012; 366: 2345-2357. [Link]

36.

Zauber AG, Winawer SJ, O'Brien MJ, et al. Colonoscopic Polypectomy and Long-Term Prevention of Colorectal-Cancer Deaths. N Engl J Med 2012; 366: 687-696. [Link]

37.

Van Rijn JC, Reitsma JB, Stoker J, et al. Polyp Miss Rate Determined by Tandem Colonoscopy: A Systematic Review. Am J Gastroenterol 2006; 101: 343-350. [Link]

38.

Kaminski MF, Wieszczy P, Rupinski M, et al. Increased Rate of Adenoma Detection Associates With Reduced Risk of Colorectal Cancer and Death. Gastroenterology 2017; 153: 98-105. [Link]

39.

Ji X. Poorly differentiated cluster grade-a vital predictor for lymph node metastasis and oncological outcomes in patients with T1 colorectal cancer: a retrospective study. [Link]

40.

41.

42.

43.

Ozawa T, Kandimalla R, Gao F, et al. A MicroRNA Signature Associated With Metastasis of T1 Colorectal Cancers to Lymph Nodes. Gastroenterology 2018; 154: 844-848.e7. [Link]

44.

45.

Brunori A, Daca-Alvarez M, Pellisé M. pT1 colorectal cancer: A treatment dilemma. Best Pract Res Clin Gastroenterol 2023; 66: 101854. [Link]

46.

Rutter MD, Beintaris I, Valori R, et al. World Endoscopy Organization Consensus Statements on Post-Colonoscopy and Post-Imaging Colorectal Cancer. Gastroenterology 2018; 155: 909-925.e3. [Link]

47.

Le Clercq CMC, Bouwens MWE, Rondagh EJA, et al. Postcolonoscopy colorectal cancers are preventable: a population-based study. Gut 2014; 63: 957-963. [Link]

48.

Singh H, Nugent Z, Demers AA, et al. Rate and Predictors of Early/Missed Colorectal Cancers After Colonoscopy in Manitoba: A Population-Based Study. Am J Gastroenterol 2010; 105: 2588-2596. [Link]

49.

Singh S, Singh PP, Murad MH, et al. Prevalence, Risk Factors, and Outcomes of Interval Colorectal Cancers: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2014; 109: 1375-1389. [Link]

50.

Adler J, Robertson DJ. Interval Colorectal Cancer After Colonoscopy: Exploring Explanations and Solutions. Am J Gastroenterol 2015; 110: 1657-1664. [Link]

51.

Robertson DJ, Lieberman DA, Winawer SJ, et al. Colorectal cancers soon after colonoscopy: a pooled multicohort analysis. Gut 2014; 63: 949-956. [Link]

52.

Leung LJ, Lee JK, Merchant SA, et al. Post-Colonoscopy Colorectal Cancer Etiologies in a Large Integrated US Health Care Setting. Gastroenterology 2023; 164: 470-472.e3. [Link]

53.

Sawhney MS, Farrar WD, Gudiseva S, et al. Microsatellite Instability in Interval Colon Cancers. Gastroenterology 2006; 131: 1700-1705. [Link]

54.

Imperiale TF, Glowinski EA, Lin-Cooper C, et al. Five-Year Risk of Colorectal Neoplasia after Negative Screening Colonoscopy. N Engl J Med 2008; 359: 1218-1224. [Link]

55.

Abstract

Pancreatic exocrine insufficiency (PEI) is a common yet frequently under-recognised cause of maldigestion, malabsorption, and malnutrition. Although traditionally associated with primary pancreatic disorders such as chronic pancreatitis, cystic fibrosis, pancreatic cancer, or pancreatic surgery, it is now evident that PEI also occurs in a wide range of extra-pancreatic conditions and clinical settings. Advances in diagnostic testing and expanding clinical awareness have improved detection; however, significant misconceptions persist regarding when to suspect PEI; how to interpret diagnostic tests; and how to initiate, optimise, and monitor pancreatic enzyme replacement therapy (PERT). In everyday practice, these errors may lead to delayed diagnosis, inappropriate treatment, persistent symptoms, and preventable nutritional deficiencies. This “Mistakes in…” article highlights common pitfalls in the diagnosis and management of PEI, focusing on inappropriate reliance on faecal elastase testing, failure to recognise secondary causes, undertreatment with PERT, and inadequate nutritional assessment. By addressing these frequent mistakes, we aim to promote a more structured, patient-centred, and evidence-informed approach to PEI that improves clinical outcomes and quality of life.

Topics

Pancreas

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Ian Gralnek on UEG Week 2024

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Endoscopy

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