Introduction

Recent advances in treatment approaches for lesions around 20 mm in size including wide-field endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), or endoscopic full-thickness resection (EFTR), increase the importance of the accuracy in tumor size measurement due to higher risks of perforation in en bloc EMR for lesions ≥25 mm⁽¹⁾, unexpectedly prolonged operation time in ESD, or incomplete resection in EFTR for lesions ≥20 mm⁽²⁾. However, available data on the accuracy of tumor size measurement for lesions ≥20 mm is scarce.

Aims & Methods

We aimed to assess the accuracy and the presence of biases in tumor size measurement for lesions ≥20 mm, and factors related to underestimated lesion size as 20 mm using large-scale, prospectively-collected data from en bloc resected specimens. In this post-hoc analysis of an ESD cohort study, pathologically-proven colorectal epithelial neoplasms resected in en bloc fashion were included from the data of the CREATE-J study^{(3, 4)}. Exclusion criteria were neuroendocrine tumor, residual or recurrent lesions after previous treatments, colitis-associated dysplasia, or insufficient data. The reference standard was pathologically-measured lesion size. Study measurements were endoscopic measurement accuracy defined within a 5 mm margin of error, the proportion of lesions with a size discrepancy ≥10 mm or ≥20 mm, and terminal digits preferences in endoscopically assessed lesion size. In addition, we examined characteristics and predictors of endoscopically 20 mm lesions with pathologically ≥ 25 mm size.

Results

Of 1889 en bloc resected lesions in 1809 patients, a total of 61 lesions (14 neuroendocrine tumors, 34 residual lesions, 4 colitis-related lesions, and 9 lesions with insufficient data) in 60 patients were excluded. Finally, 1828 lesions in 1749 patients were analyzed. The accuracy of endoscopic measurement in total, 20-29 mm, 30-39 mm, and 40- mm size categories was 53.4%, 63.7%, 47.5%, and 40.3%, respectively. Discrepancies of ≥10 mm or ≥20 mm occurred in 19.1% and 4.5% of lesions, respectively. Size measurement inaccuracies tended to be more frequent with increasing endoscopic lesion size (Table). In terminal digits of an endoscopic size measurement, endoscopists strongly preferred to select 0 (65.2%, 1192/1828) or 5 (30.0%, 548/1828). Of 366 endoscopically 20 mm lesions, 26.7% were found to be pathological ≥ 25 mm lesions. Multivariate analysis revealed that endoscopic 20-mm sized lesions with pathological ≥ 25-mm were significantly associated with polypoid lesions [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.1-6.8] and laterally spreading tumors granular type (OR 2.0, 95% CI: 1.1-3.5).

Table. Lesions with the difference between endoscopic and pathologic lesion sizes ≥ 10 mm and ≥ 20 mm

Conclusion

Colonoscopists may be inaccurate and biased in the measurement of lesion size in large colorectal lesions. These findings suggest potential risks associated with size-based therapeutic decisions for large colorectal lesions ≥20 mm.

References

1. Burgess NG, Bassan MS, McLeod D, Williams SJ, Byth K, Bourke MJ. Deep mural injury and perforation after colonic endoscopic mucosal resection: a new classification and analysis of risk factors. Gut. 2017;66(10):1779-89.
2. Didden P, van Eijck van Heslinga RAH, Schwartz MP, Arensman LR, Vleggaar FP, de Graaf W, et al. Relevance of polyp size for primary endoscopic full-thickness resection of suspected T1 colorectal cancers. Endoscopy. 2022;54(11):1062-70.
3. Kobayashi N, Takeuchi Y, Ohata K, Igarashi M, Yamada M, Kodashima S, et al. Outcomes of endoscopic submucosal dissection for colorectal neoplasms: Prospective, multicenter, cohort trial. Dig Endosc. 2022;34(5):1042-51.
4. Ohata K, Kobayashi N, Sakai E, Takeuchi Y, Chino A, Takamaru H, et al. Long-term Outcomes After Endoscopic Submucosal Dissection for Large Colorectal Epithelial Neoplasms: A Prospective, Multicenter, Cohort Trial From Japan. Gastroenterology. 2022;163(5):1423-34.e2.

Introduction

Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk of CRC. However, new associations between FAP and the risk of other cancers have subsequently emerged. In this study, we aimed to assess the risk of specific primary and secondary cancers among FAP patients in comparison with matched controls.

Aims & Methods

All known FAP patients up until April 2021 were identified in the nationwide Danish Polyposis Register and paired with four unique controls matched by birth year, sex, and zip code. Risk of overall cancers, specific cancer types, and risk of a second primary cancer were assessed and compared with controls.

Results

The analysis included 565 FAP patients and 1,890 controls. The overall risk of cancer was significantly higher for FAP patients than controls (hazard ratio (HR): 4.12, CI 95%, 3.28-5.17, p<0.001). The increased risk was mainly due to CRC (HR: 4.61, CI 95% 2.58-8.22, p<0.001), pancreatic cancer (HR: 6.45, CI 95% 2.02-20.64, p=0.002), and duodenal/small bowel cancer (HR: 14.49, CI 95% 1.76-119.47, p=0.013), while no significant difference was observed for gastric cancer (HR: 3.29, CI 95% 0.53-20.23, p=0.20). Furthermore, the risk of a second primary cancer was significantly higher for FAP patients (HR: 1.89, CI 95% 1.02-3.50, p=0.042). After 15 years, the point estimates for FAP patients and controls were 83.6 % vs. 94.8% being alive without cancer, 7.2% vs. 1.9% developing cancer, and 15.1% vs. 3.4% were deceased, respectively. When extending the period to 30 years, 60.7% vs. 81.1% were alive without cancer, 11.4% vs. 5.6% developed cancer, and 27.9% vs. 13.4% were deceased for FAP patients and controls, respectively. Between 1980 and 2020, the risk of cancer among FAP patients decreased by approximately 50%.

Conclusion

Analyzing national data for Danish polyposis patients and matched controls, we found that although the risk of developing cancer among FAP patients has been reduced by 50% over the last forty years, that risk is still significantly higher than for matched controls. Colorectal, pancreatic, and duodenal/small bowel cancer, as well as development of second primary cancers, are the main contributors to this increased risk. The risk of gastric cancer did not differ between FAP patients and controls. These findings should be included in future surveillance protocols and treatment guidelines for FAP patients.

References

Karstensen JG, Burisch J, Pommergaard HC, et al. Colorectal Cancer in Individuals With Familial Adenomatous Polyposis, Based on Analysis of the Danish Polyposis Registry. Clin Gastroenterol Hepatol 2019;17(11):2294-300 e1.
Monahan KJ, Bradshaw N, Dolwani S, et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut 2020;69(3):411-44.
Karstensen JG, Bulow S, Burisch J, et al. Validation of the Endoscopic Part of the Spigelman Classification for Evaluating Duodenal Adenomatosis in Familial Adenomatous Polyposis: A Prospective Study of Interrater and Intrarater Reliability. Am J Gastroenterol 2022;117(2):343-45.
Monahan KJ, Bradshaw N, Dolwani S, et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut 2020;69(3):411-44.

Disclosure

JGK is a consultant for SNIPR BIOME.