Water exchange colonoscopy decreased adenoma miss rates compared with literature data and local data with CO₂ insufflation: an observational study

Colonoscopy is widely practiced, generally safe, accurate for detecting and prevention of colorectal cancer (CRC) [1], but is not perfect. A substantial number of neoplastic lesions are missed, according to tandem air insufflation colonoscopy studies [2‐6]. The adenoma miss rates (AMRs) in the right and proximal colon ranged from 22.5 to 27% and 23.4 to 33.3%, respectively [2‐6]. It has been reported that 58% of postcolonoscopy CRCs (PCCRCs) were attributed to missed lesions [7]. PCCRCs were 2.4 times more likely to arise in the proximal than in the distal colon [8]. Inadequate bowel preparation, lesions located behind folds or having a nonpolypoid shape, incomplete colonoscopy, a short withdrawal time, and suboptimal inspection techniques contributed to missed neoplasias [9, 10]. Small sessile polyps with advanced histology are more common in the proximal colon and are easily missed [11, 12]. For performance improvement, approaches that increase adenoma detection rate (ADR) conceivably could reduce AMR.

Water exchange (WE) colonoscopy is characterized by gasless insertion into the cecum in clear water and has been shown to significantly reduce insertion pain, facilitate the completion of colonoscopy and significantly increase bowel cleanliness, even in the right colon [13, 14]. WE with near-complete removal of infused water during insertion improved the overall ADR [13‐17], right and proximal colon ADRs [14‐18] compared with those of air insufflation. The impact of WE on AMR, however, had not been reported.

The lead author attended a research seminar in 2017 on WE colonoscopy. After mastering the basic skills of WE, the first performance improvement study (study 1) pertained to collection of data on WE AMRs in the right and proximal colon compared with those reported in the literature. When WE showed considerably lower AMRs, the second observational study (study 2) evaluated the corresponding AMRs with CO₂ insufflation. The two studies demonstrated how WE could fit into the goal of performance improvement in our practice setting. The data in these two consecutive studies were compared to determine if our local data could show significant AMR differences to warrant implementation of a randomized controlled trial (RCT).

This was a retrospective observational study. Consecutive patients of tandem colonoscopy were enrolled in these two performance improvement studies from July to November 2018 at Evergreen General Hospital, Taoyuan, Taiwan. Written informed consent was obtained from all participating patients for tandem colonoscopy. The Joint Institutional Review Board of Taiwan approved report of the prospectively collected AMR data (for 172 patients).

The study flow charts are shown in Figs. 1 and 2. In study 1 (the WE group), WE directed at near-complete removal netted 89% of infused water upon arrival to the cecum. WE showed considerably lower AMRs in the right (17.5%) and proximal (15.5%) colon than those in the literature (22.5–27% in the right and 23.4–33.3% in the proximal colon) [2, 3]. In study 2 (the CO₂ group), the AMRs in the CO₂ group were 33.8% (right colon) and 30.4% (proximal colon).

The demographic variables were comparable except that a significantly higher proportion of patients (61.6%) underwent colonoscopy for surveillance in the WE group, while a significantly higher proportion of patients (55.8%) underwent colonoscopy for screening in the CO₂ group (Table 1).

Table 2 details the procedural outcomes. For the first-pass examination, the insertion time and infused water volume during insertion in the WE group were significantly longer and greater, respectively, than those in the CO₂ group. The withdrawal time and infused water volume during withdrawal in the CO₂ group were significantly longer and higher, respectively, than those in the WE group. The total procedure time of the first-pass examination was comparable between the two studies. However, the withdrawal time and total procedure time of the second-pass examination were significantly longer in the CO₂ group. The cleansing scores were significantly higher in the WE group. Compared with the CO₂ group, a significantly lower portion of participants in the WE group required abdominal compression to reach the cecum. There was no significant difference between the two studies with respect to the doses of sedative agents in patients undergoing colonoscopy alone. There were no adverse events in either study.

The detection of adenoma and proximal hyperplastic polyps is reported in Table 3. There was no significant difference in the overall ADR or for adenomas in any location between the two studies. Similarly, the overall MAP, right colon MAP, and proximal colon MAP did not differ statistically between the two studies. The overall and proximal colon advanced ADRs were also comparable. There was no significant difference in the PHP-DR between the two studies.

The per-participant miss rates for adenoma and proximal hyperplastic polyps are reported in Table 4. There were no significant differences in the miss rates between the WE and CO₂ groups for any adenoma, right colon adenoma, distal colon adenoma, or right and proximal colon hyperplastic polyps. Compared with the WE group, the CO₂ group showed significantly higher per-participant miss rates for proximal colon adenoma, as well as for right and proximal colon combined adenoma and hyperplastic polyps.

The per-adenoma/polyp AMR and HPMR details are presented in Table 5. Compared with the CO₂ group, the WE group showed significantly lower AMR (17.5% vs. 33.8% [right colon], P = 0.034; 15.5% vs. 30.4% [proximal colon], P = 0.018) and combined AMR and HPMR (13.6% vs. 32.4% [right colon], P = 0.002; 15.2% vs. 30.5% [proximal colon], P = 0.003). There was no significant difference in the AMR of the distal colon (26.3% [WE group] vs. 23.5% [CO₂ group], P = 0.81). According to the United States Multi-Society Task Force on Colorectal Cancer guidelines for colonoscopy surveillance after screening and polypectomy, a significant change in the postpolypectomy surveillance schedule was indicated by the second examination in 15 patients (8 patients in the WE group vs. 7 patients in the CO₂ group, P = 1.00) [20].

Study 1 showed WE considerably lowered AMRs in the right and proximal colon compared with data in the literature. Study 2 found that compared with CO₂ insufflation, WE significantly reduced the right and proximal colon AMRs in our hands (16 and 15%), respectively. Furthermore, WE significantly decreased the combined AMR and HPMR in the right and proximal colon (19 and 15%), respectively.

In a meta-analysis of 17 RCTs with 10,350 patients, WE achieved a significantly higher overall ADR than air (OR, 1.40; 95% credible interval [CrI], 1.22 to 1.62), or CO₂ (OR, 1.48; 95% CrI, 1.15 to 1.86) insufflation [18]. WE achieved the highest ADR in the right colon and in screening cases. Improved bowel cleanliness and reduced withdrawal cleaning-related multitasking distractions were plausible mechanisms by which WE improved ADR [18, 21]. These advantages of WE may translate into reduced AMRs. The impact of WE with near-complete removal of infused water during insertion on AMR, however, had not been reported.

In a meta-analysis of 43 tandem colonoscopy studies, the pooled per-adenoma AMR was 26% (95% CI, 23–30%), and the AMR by size was 6% (95% CI: 2–11%) for large adenomas, 17% (95% CI, 11–24%) for small adenomas, and 28% (95% CI: 23–34%) for diminutive adenomas [6]. Additionally, a right colon AMR of 22.5 to 27% and a proximal colon AMR of 23.4 to 33.3% have been reported [2‐6]. The lower AMR (15.5%, proximal colon) of WE compared with that in previous reports prompted us to evaluate the AMR of CO₂ insufflation. In study 2, the overall AMR and the AMRs in the right and proximal colon in the CO₂ group were similar to those in previous reports. In our studies, the AMRs in the right colon (17.5% [WE] vs. 33.8% [CO₂]) and proximal colon (15.5% [WE] vs. 30.4% [CO₂]) were significantly lower (both P < 0.05) in the WE group, suggesting that WE increased effectiveness by lowering the AMRs compared with those of CO₂ insufflation. The hypotheses supporting our observation that WE decreased right and proximal colon AMRs compared with CO₂ insufflation comprised of facilitation of cecal intubation, improvement of right colon cleanliness, increased ADR in the right and proximal colon, and reduction of cleaning-related multitasking distractions during withdrawal, all by WE.

The results in the current report were in contrast with a recent study of total underwater colonoscopy versus CO₂ insufflation [22]. In that study, the authors hypothesized that water was a superior medium to gas for visualizing the mucosa, and they filled the lumen with water during withdrawal in addition to water infusion during insertion. The results showed that total underwater colonoscopy had a significantly higher overall AMR than colonoscopy performed with CO₂ insufflation (36% vs. 23%, P = 0.025). The discrepancy could be explained by the proportion of infused water removed during insertion, i.e., 66% (moderate) in the total underwater colonoscopy study and 89% (near-complete) in the current study. In previous RCTs showing that WE significantly increased the ADR, 91 to 102% of infused water was suctioned upon arrival to the cecum [14‐17]. With limited water and debris removal, optimal salvage cleaning could not be achieved during insertion and the endoscopists using total underwater colonoscopy had impaired visualization under water during withdrawal, possibly accounting for the higher miss rates.

Our study has some limitations. First, this investigation consisted of two consecutive observational studies with unblinded examiners, not a RCT with blinded colonoscopists. Second, the significant difference in the indications for colonoscopy between the WE and CO₂ groups could have introduced confounding issues. Third, there was a significant difference in the withdrawal times of the first- and second-pass examinations. In the WE group, the possibility that the examiner exerted less effort reflected by the shorter withdrawal time to detect fewer lesions could not be excluded. In the CO₂ group, the increased withdrawal time of the first-pass and second-pass examinations was likely attributed to the additional time for mucosal cleaning, and more polyps removed, respectively. Our study has some strength. The high ADR in both groups (> twice the recommended standard) attested to the high quality of the examinations. The results in this report are important observations that will provide data for sample size calculation in a RCT.

In conclusion, in contrast to total underwater colonoscopy (with insertion suction of only 66% of infused water), which increased the AMR, WE with near-complete (89%) removal of infused water during insertion significantly decreased the AMRs and combined AMR and HPMR in the right and proximal colon compared with those of CO₂ insufflation. The provocative data warrant confirmation in a RCT.