Accepted Manuscript En bloc resection for 10-20 mm polyps to reduce post-colonoscopy cancer and surveillance C. Hassan, M. Rutter, A. Repici PII: S1542-3565(19)30412-4 DOI: https://doi.org/10.1016/j.cgh.2019.04.022 Reference: YJCGH 56447 To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 9 April 2019 Please cite this article as: Hassan C, Rutter M, Repici A, En bloc resection for 10-20 mm polyps to reduce post-colonoscopy cancer and surveillance, Clinical Gastroenterology and Hepatology (2019), doi: https://doi.org/10.1016/j.cgh.2019.04.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
En bloc resection for 10-20 mm polyps to reduce post-colonoscopy cancer and surveillance. Hassan C 1, Rutter M, 2,3 Repici A 4 1 Endoscopy Unit, Nuovo Regina Margherita Hospital, Rome, Italy 2 Northern Institute for Cancer Research, Newcastle University, Newcastle, UK. 3 Department of Gastroenterology, University Hospital of North Tees, Stockton-on-Tees, Cleveland, UK. 3 Endoscopy Unit, Humanitas University, Rozzano, Milano, Italy No conflict of interest for all authors Corresponding author: Cesare Hassan, MD Nuovo Regina Margherita Via Morosini 30, 00153, Tel: +39065844-6608, Fax: - 6533 Roma, Italia cesareh@hotmail.com
The dominant paradigm underpinning colonoscopy quality is that an optimized colorectal inspection technique will reduce the risk of missed lesions to insignificant levels, resulting in a negligible risk of post-colonoscopy Colorectal Cancer (CRC). 1 This assumption led to more efficient strategies for CRC screening and surveillance where a prolonged 10-year interval is considered appropriate before repeating a screening colonoscopy in patients with a negative initial examination. Similarly, a (5-)10-year surveillance interval is now recommended after removal of low-risk adenomas. 2 In the European programs a non-endoscopic strategy, based on immunochemical faecal test (FIT), is considered a more convenient policy following a negative colonoscopy 3 or following removal of low-risk adenomas.. 3, 4 Undoubtedly, the shift of endoscopic resources from an (intensive) surveillance to more of a screening setting has been a major consequence of the quality assurance (QA) process in diagnostic colonoscopy. However, this shift is based on the assumption that the initial examination was indeed a high-quality examination. Can we reduce the burden of post-polypectomy surveillance also for high-risk adenomas? There is no apparent reason for high-quality colonoscopy being less effective in finding all lesions in those with high-risk adenomas as compared with low-risk or no adenomas. Encouragingly, a large sub-group of patients with high-risk adenomas namely those with <20 mm distal lesions without high-grade dysplasia has been shown to be at very low risk of subsequent cancer, questioning the value of intensive or indeed any surveillance. 5 This has been well substantiated in the ongoing European Polyp Surveillance trials where a 5-year rather than 3-year surveillance interval for high-risk adenomas is being assessed. 6 Longer surveillance intervals rely on the assumption of a negligible risk of post-colonoscopy CRC due to missed or de novo lesions. An alternative consideration is the risk of an incomplete polypectomy at baseline colonoscopy. Incomplete polypectomy accounts for up to one third of postcolonoscopy CRC, 7, 8 often occurring early after the baseline colonoscopy. This may explain, at least in part, the higher risk of post-colonoscopy CRC in patients with high-risk adenomas without endoscopic surveillance, 5, 9 as well as in those with >20 mm or proximal lesions. 5 There is a widelyheld belief amongst endoscopists that the risk is mainly confined to large i.e. >20 mm lesions because piecemeal rather than en bloc resection is used in these cases. 10 This conviction translated in the clinical recommendation of a short-term i.e. 3 to 6 months site-check after piecemeal removal of these lesions, before entering patients into a surveillance regimen. 2, 4 Implementation of new techniques i.e., Endoscopic Submucosal Dissection (ESD) for an en bloc resection of these large lesions is expected to minimize the risk of endoscopic recurrence and adverse oncological outcomes. However, most high-risk adenomas are 10-20 mm in size: can we confidently exclude the risk of incomplete polypectomy for these? As endoscopists, we often have little if any doubt of our ability to completely remove these relatively small lesions, regardless of the morphology or technique.
In addition, submucosal injection i.e., Endoscopic Mucosal Resection (EMR) facilitates en bloc resection for most of the non-pedunculated lesions, and facilitates careful endoscopic and histological assessment of the resection margins. Isn t it quite rare in our practice to find a recurrence of a previously resected <20 mm lesion? This conviction was recently challenged by the publication of the Complete Adenoma Resection (CARE) study, 11 unexpectedly showing a high rate of incomplete polypectomy i.e., 17% for 10-20 mm lesions. However, such evidence was based on an artificial setting i.e., biopsies of the post-polypectomy resection margin and the cross-sectional design meant it could not assess the clinical implications of the findings. 11 Does this unexpected rate of incomplete resection for 10-20 mm lesions affect the long-term risk of colorectal neoplasia? Previous epidemiological studies on post-colonoscopy CRC risk mainly based on whether a polypectomy was previously performed in the same segment where CRC developed failed to address such an issue due to lack of endoscopic data. For this reason, Adler J et al. applied the same segmental methodology to an endoscopic setting by comparing the risk of metachronous neoplasia during surveillance colonoscopy in segments based on whether 10-20 mm lesions had or had not been removed. 12 First, the over 2-fold increase in metachronous lesions in segments where a 10-20 mm lesion had been removed depressingly confirmed the high rate of incomplete resection previously shown in the CARE study. 11 Second, by acting as a proxy for the risk of post-colonoscopy CRC, the 13% rate of metachronous neoplasia attributed to incomplete resection of 10-20 mm lesions suddenly elevated incomplete polypectomy within this size range as the putative factor for an adverse oncological outcome. The advantage of an endoscopic 11 rather than epidemiological 7, 8 design was illustrated by the ability to explore possible predictors for incomplete polypectomy, which revealed an over 5-fold increase in metachronous neoplasia following piecemeal resection of a 10-20 mm (non-pedunculated) lesion, accounting for around half of all the metachronous neoplasia detected at surveillance. 12 These data clearly show how the completeness of endoscopic resection remains a critical prerequisite before planning endoscopic surveillance, especially now that prolongation of surveillance intervals is under scrutiny. Regrettably, more intensive surveillance may not be an effective solution to the problem of incomplete resection, as malignant progression may occur before or irrespective of the surveillance. The 28% incomplete resection rate estimated by Adler J et al. for piecemeal resection of a 10-20 mm lesion is simply unacceptable, 12 especially considering similar or lower rates have been shown for >20 mm lesions. 10 If early work-up of any >10 mm lesion with piecemeal or incomplete resection is to be considered, a standardization of the snare-based technique to assure en bloc resection of these lesions would be needed to avoid unnecessary additional procedures. Unfortunately, few studies have addressed the technical efficacy of removing 10-20 mm lesions, 13 generating uncertainty on the optimal technique. In addition, there is significant inter-endoscopist
variability in the performance of polypectomy or EMR, further questioning its generalizability in community-based endoscopy. 11 Assurance of high levels of completeness of polypectomy is necessary to minimize the risk of metachronous neoplasia and ultimately of post-colonoscopy CRC at surveillance. However, it is challenging in clinical practice as it requires both adequate endoscopic and histological information. In this regard, the segmental methodology by Adler J et al. simplifies this assessment. By performing a Copernican revolution, the Authors exploited the first post-polypectomy surveillance examination to infer the completeness of resection rate at the baseline colonoscopy. This methodology offers unique advantages. First, no major deviation from clinical practice or additional resources are required. Of note, the focus should not be restricted to 10-20 mm lesions in clinical practice, further simplifying its assessment. Secondly, the retrospective assessment prevents operator-related bias at the time of the baseline polypectomy, as well as the intra-patient inter-segmental comparison prevents bias due to disease prevalence distribution. Third, possible improvements in resection technique may be identified by periodic auditing of this indicator. Potential drawbacks include misclassification of the segment at the time of polypectomy or surveillance, misdiagnosis of de novo or missed lesions as residual polyp, and suboptimal compliance of patients with surveillance. However, these are likely to represent systematic bias with no effect on the relative distribution of individual endoscopists according to their technical expertise. In addition, these preliminary data need confirmation in future studies; they also underscore the potential need to retrain pathologists to report on the R0 resection also for <20 mm lesions. In conclusion, the dramatic improvement in our diagnostic accuracy has been effective in minimizing the need for endoscopic surveillance in those with no or low-risk lesions. However, effort is now required in polypectomy competency to ensure a high rate of en bloc resection for 10-20 mm lesions. Such step seems critical to reduce the risk of post-colonoscopy CRC in these patients, and the associated burden of surveillance.
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