Colorectal cancer (CRC) is the third most common cause of death due to cancer in Japan. The adenoma-carcinoma sequence is thought to be the primary route involved in the development of CRC (1), and neoplastic lesions found during colonoscopy are associated with a future risk of neoplasms. It has been demonstrated that colonoscopy with polypectomy reduces the risk of recurrent CRC and mortality (2,3); the colonoscopy surveillance interval is based on risk stratification according to the number of adenomas, the maximum size of polyps and the histopathological findings of all resected lesions (4,5). This is the primary screening method used in the US and several European countries (6,7). On the other hand, the most suitable colonoscopy interval was described briefly in the Japanese guidelines as follows: ‘<3 years surveillance colonoscopy is recommended after polypectomy’ (8). Additionally, Japanese guidelines indicate diminutive neoplastic lesions without carcinomatous findings can be left untreated and followed up (i.e., semi-clean colon). The vast majority of polyps removed during a colonoscopy are diminutive (≤5 mm in size), and approximately half of the diminutive polyps are adenomas (9–11). Furthermore, only a small percentage of diminutive adenomatous polyps (DAPs) contain advanced histological features (12). Indeed, some endoscopists in Japan leave DAPs unresected after a detailed observation and a close follow-up. This is because povlypectomy may be unnecessary because of the low prevalence of advanced features in these polyps, and it may be unnecessary to expose patients to added risks during colonoscopy (13).

In the PIT classification system described by Kudo et al (14) (Fig. 1), type I and type II lesions are defined as having non-neoplastic patterns; type IIIL, type IIIs and type IV are adenomatous; and type VI and type VN are cancerous. Concerning type IIIL, a previous study reported that lesions in this category exhibited no invasive characteristics (15). However, type III is a standard pit pattern observed in depressed-types of early cancer, and type IV lesions often contain characteristics of advanced neoplasia (e.g., high-grade adenomas or villous components).

Magnifying a chromoendoscopy with PIT assessment increases the diagnostic accuracy for both distinguishing adenomas from hyperplastic polyps (85–96%) as well as diagnosing massively invasive submucosal colorectal cancer which has the possibility of metastasising (76.4–89.3%) (16–18). Moreover, this classification system has a good-to-excellent inter-observer agreement (0.78–0.96) and could be used to accurately diagnose patients before treatment (19,20).

Recently, the number of patients taking antiplatelet or anticlotting medications to prevent cerebral vascular disease or myocardial infarction has increased. For patients who continue to take their antiplatelet or anticlotting medications, or those who have a large number of polyps with difficulty resecting at a time, we often recommend leaving type IIIL PIT DAPs untreated and conducting a follow-up without an immediate re-examination (semi-clean colon strategy). However, the risk and adequate surveillance intervals of the semi-clean colon are not clear.

Therefore, this retrospective case-control study was designed to investigate the feasibility of a semi-clean colon.

This study was a retrospective case-control study that analysed the concept of ‘semi-clean colon’ using Kudo's PIT classification assessed by magnifying the chromoendoscopy for the baseline colonoscopy. The results indicate that there was no significant difference in the cumulative incidence of ILs and invasive cancer among patients with type IIIL PIT DAPs that were left untreated and those in whom all neoplastic lesions were removed. Colonoscopy combined with the removal of all adenomatous polyps has been reported to reduce the risk of recurrent CRC and CRC-related mortality in the National Polyp Study, which has been conducted since 1980 (2,3). Although the Japanese guidelines indicate that some neoplastic lesions can be left untreated, diminutive polypoid lesions should be followed up (8). To our knowledge, this was the first study to analyse the semi-clean colon strategy and compare it to the clean colon strategy.

In addition, a previous study reported that advanced adenomas typically manifest with measurable interval growth, whereas non-advanced adenomas tend to demonstrate intermediate behaviour. Furthermore, the majority of other benign small polyps tend to remain stable or regress over time (25), and a follow-up of unresected colorectal polyps up to 9 mm is safe (14). However, some DAPs may have advanced histological features and may even develop into invasive cancer (26). PIT diagnosis by magnifying the chromoendoscopy enables the distinction of neoplasia from non-neoplasia in daily practice. While emerging virtual chromoendoscopy systems [e.g., narrow-band imaging or Fuji intelligent chromoendoscopy (17,18)] are very convenient tools, they do not replace PIT diagnosis in terms of diagnostic ability. Magnifying the chromo-observation is necessary to identify diminutive invasive cancer, even among DAPs. It is essential to perform magnifying chromo-observation to determine the feasibility of leaving diminutive adenomatous lesions in place.

In this study, 39 high grade dysplasia, 5 invasive cancer, 4 advanced cancer were detected in ‘semi-clean group’. However, Is it not possible to confirm definitely the relationship between untreated DAPs and these cancer lesions.

A previous study reported that the neoplastic lesions found during a colonoscopy are associated with the future risk of incident neoplasms (3), similar to the results of our study. In Japan, Matsuda, et al reported that patients with any adenomatous polyps >6 mm or intra-mucosal cancer at the time of the initial colonoscopy have a higher risk of advanced lesions than those with no initial neoplasia or small adenomas do (27). In this present study, the clean colon and the semi-clean colon group had a higher incidence of ILs than the internal control group did. This suggested that patients with high-risk polyps were at a future risk of incident neoplasms, regardless of whether their low-risk polyps were removed.

Another issue is that important lesions may be overlooked during the initial colonoscopy but detected during a follow-up colonoscopy. However, in the present study, all examinations were performed under the supervision of experts. It has been reported that one in 13 (7.9%) cases of CRC may be missed on the index colonoscopy (23). In our study, 12 invasive cancers, including eight advanced cancers, were diagnosed with interval cancers within 36 months. Many of these cases were likely because of the presence of lesions that were missed at the time of baseline colonoscopy. In our study, the ascending and sigmoid colon were the most common sites of interval cancer. Conversely, a previous report found that a history of prior colonoscopy with polypectomy is one of the strongest risk factors for interval cancer (i.e., early/missed cancer) (23). One reason for this may be that a polypectomy requires more time to perform, and it may be difficult to then set aside an adequate amount of time for observation. One strength of the semi-clean colon strategy is that it may save time.

The ‘resect and discard’ strategy, as proposed by Ignjatovic et al (28), has the potential to change the standard management of DAPs and reduce the cost of screening and surveillance colonoscopy. The primary benefit of this strategy is the cost savings that can be achieved by reducing the number of polyps that are sent out for histopathological examination, as low-risk lesions are not examined (29). Our strategy for DAPs using PIT classification also has the potential to lower costs by reducing both the number of lesions examined histopathologically, as well as the number of lesions that are treated. The resect and discard strategy for diminutive colorectal lesions was shown to be safe in earlier reports (28). However, the application of this strategy for all diminutive colorectal lesions is unsatisfactory since the evidence from earlier reports was primarily based on sessile lesions (30).

Recently, the number of patients who receive antiplatelet or anticoagulant drugs has increased. Discontinuation of these medications before the polypectomy increases the risk of certain adverse events (e.g., cerebral vascular disease, myocardial infarction, or even death) (31,32). Heparinization, as an alternative therapy, necessitates hospitalisation, increases cost, and is time-consuming for patients. The present study presents the semi-clean colon strategy for colorectal DAPs as a new treatment option.

Although the cumulative incidence of ILs between the semi-clean and clean colon groups was not significantly different in this study, the Kaplan-Meier curve of the semi-clean colon group exhibited a large increase over the last decade. Thus, we cannot exclude the future potential of DAP to be a malignancy.

However, a surveillance colonoscopy is recommended <3 years after endoscopic resection as per the Japanese guidelines (8). In addition to after endosopic resection, the semi-clean colon may be acceptable with a surveillance colonoscopy performed <3 years after the initial procedure.

There are several limitations to this study. First, we could not investigate the main indication for the initial colonoscopy. Patients were not limited strictly to asymptomatic cases. However, in this study, outcomes were evaluated based on the findings of the follow-up colonoscopy. Second, this study was a single-centre study. Both expert endoscopists and trainees were involved, but the trainees were always accompanied by experts when determining an on-site PIT diagnosis. Although the validity of the PIT classification was feasible among the expert endoscopists, the diagnostic ability of trainees and their learning curves should be evaluated for a more practical assessment of PIT. Third, this study was a retrospective study and thus might contain some methodological bias, thereby compromising the generalisation of the study results. To compensate for this defect in the study design, we accumulated a relatively large number of samples. However, further multi-centre randomised controlled studies are required to validate these results.

In conclusion, DAPs with type IIIL pit patterns may be left untreated and subsequently observed. The management of colorectal DAPs using pit pattern classification with magnifying chromoendoscopy has the potential to reduce cost, time and risk of polypectomy and repeated colonoscopy. To assess the clinical efficacy of the concept of ‘semi-clean colon’, further multi-centre prospective clinical trials involving a larger number patients and direct comparisons with a long-term clinical prognosis are required.