Comparison of Right Colon Flat Polyp Detection Rate by Water Exchange Versus Water Immersion-pooled Results of Data File of 3 Published Reports.

GOALS: We tested the hypothesis that water exchange (WE) achieved a significantly higher right colon flat polyp detection rate (rFPDR) than water immersion (WI). BACKGROUND: Current endoscopy methods provide real-time morphology but not histopathology. Flat serrated polyps are difficult to find during colonoscopy. In 2022 2 studies reported that the serrated polyp detection rate (SPDR) significantly inversely predicted the development of interval cancers. In 2021 1 systemic review with meta-analysis showed that WE, but not WI increased SPDR. The relative contributions of WE and WI on rFPDR are unknown. STUDY: Individual patient data from 3 reports comparing air insufflation, WI, and WE were pooled. Multiple logistic regression analysis was used to assess the factors associated with a higher rFPDR. RESULTS: The pooled data showed that the rFPDR of air insufflation, WI, and WE were 15.4%, 14.1%, and 19.4% ( P =0.009), respectively. After adjusting for age and withdrawal time, multiple logistic regression analysis revealed that WE, when compared with WI, was significantly associated with a higher rFPDR (adjusted odds ratio[aOR]=1.53, P =0.002). Analysis of data on pathology and size were omitted to avoid duplicating our earlier publications. CONCLUSIONS: Significantly higher rFPDR was achieved by WE. Water exchange rather than WI merits consideration for use to maximize rFPDR. Removal of flat polyps, and by inference serrated polyps, ensures their optimal management to minimize the occurrence of interval cancers. The potential benefit of WE in maximizing SPDR and minimizing interval cancers deserves evaluation in long-term randomized controlled studies focused on flat polyps detection.

Polyp detection and false-positive rates by computer-aided analysis of withdrawal-phase videos of colonoscopy of the right-sided colon segment in a randomized controlled trial comparing water exchange and air insufflation.

BACKGROUND AND AIMS: Water exchange (WE) improves lesion detection but misses polyps because of human limitations. Computer-aided detection (CADe) identifies additional polyps overlooked by the colonoscopist. Additional polyp detection rate (APDR) is the proportion of patients with at least 1 additional polyp detected by CADe. The number of false positives (because of feces and air bubble) per colonoscopy (FPPC) is a major CADe limitation, which might be reduced by salvage cleaning with WE. We compared the APDR and FPPC by CADe between videos of WE and air insufflation in the right-sided colon. METHODS: CADe used a convolutional neural network with transfer learning. We edited and coded withdrawal-phase videos in a randomized controlled trial that compared right-sided colon findings between air insufflation and WE. Two experienced blinded endoscopists analyzed the CADe-overlaid videos and identified additional polyps by consensus. An artifact triggered by CADe but not considered a polyp by the reviewers was defined as a false positive. The primary outcome was APDR. RESULTS: Two hundred forty-five coded videos of colonoscopies inserted with WE (n = 123) and air insufflation (n = 122) methods were analyzed. The APDR in the WE group was significantly higher (37 [30.1%] vs 15 [12.3%], P = .001). The mean [standard deviation] FPPC related to feces (1.78 [1.67] vs 2.09 [2.09], P = .007) and bubbles (.53 [.89] vs 1.25 [2.45], P = .001) in the WE group were significantly lower. CONCLUSIONS: CADe showed significantly higher APDR and lower number of FPPC related to feces and bubbles in the WE group. The results support the hypothesis that the strengths of CADe and WE complement the weaknesses of each other in optimizing polyp detection.

Factors associated with prolonged cecal insertion time in patients undergoing water exchange colonoscopy.

BACKGROUND AND AIM: Water exchange is superior to air insufflation in reducing discomfort and increasing adenoma detection during colonoscopy. However, prolonged cecal insertion time is a drawback. This study aims to investigate the factors affecting cecal insertion during water exchange colonoscopy. METHODS: We pooled data from five randomized clinical trials that included patients undergoing water exchange colonoscopy. Logistic analysis was performed to determine the independent factors associated with prolonged cecal insertion time (> 15 min). RESULTS: The cohort included 912 patients (493 men and 419 women) with a median age of 57 years (interquartile range, 49-64 years). The median cecal insertion time was 13.5 min (interquartile range, 10.9-17.0 min). Multivariate logistic regression analysis indicated that female sex, body mass index < 25 kg/m2 , a history of constipation, no sedation, less experienced endoscopist, Boston Bowel Preparation Scale score ≤ 6, infused water volume during insertion ≥ 1000 mL, and scope length at the cecum ≥ 85 cm were associated with prolonged cecal insertion time. With increasing volume of infused water (1000-2000 mL), the median cecal insertion time increased gradually from 11.4 to 23.0 min (P < 0.001). CONCLUSIONS: The current study identified independent factors associated with prolonged cecal insertion time during water exchange colonoscopy. Several factors are modifiable to achieve a shorter insertion time, including better bowel preparation, the use of sedation, more experienced endoscopist, infusing less water during insertion, and maintaining a shorter scope length.

A survey of colonoscopists with and without in-depth knowledge of water-aided colonoscopy.

BACKGROUND AND AIM: Endoscopy featured water-aided colonoscopy (WAC) as novel in the Innovation Forum in 2011. Gastrointestinal Endoscopy published a modified Delphi consensus review (MDCR) that supports WAC for clinical practice in 2021. We tested the hypothesis that experience was an important predictor of WAC use, either as water immersion (WI), water exchange (WE), or a combination of WI and WE. METHODS: A questionnaire was sent by email to the MDCR authors with an in-depth knowledge of WAC. They responded and also invited colleagues and trainees without in-depth knowledge to respond. Logistic regression analysis was used with the reasons for WAC use treated as the primary outcome. Reports related to WAC post MDCR were identified. RESULTS: Of 100 respondents, > 80% indicated willingness to adopt and modify practice to accommodate WAC. Higher adenoma detection rate (ADR) incentivized WE use. Procedure time slots ≤ 30 and > 30 min significantly predicted WI and WE use, respectively. Co-authors of the MDCR were significantly more likely to perform WAC (odds ratio [OR] = 7.5, P = 0.037). Unfamiliarity with (OR = 0.11, P = 0.02) and absence of good experience (OR = 0.019, P = 0.002) were associated with colonoscopists less likely to perform WAC. Reports related to WAC post MDCR revealed overall and right colon WE outcomes continued to improve. Network meta-analyses showed that WE was superior to Cap and Endocuff. On-demand sedation with WE shortened nursing recovery time. CONCLUSIONS: An important predictor of WAC use was experience. Superior outcomes continued to be reported with WE.

Water-assisted colonoscopy: an international modified Delphi review on definitions and practice recommendations.

BACKGROUND AND AIMS: Since 2008, a plethora of research studies has compared the efficacy of water-assisted (aided) colonoscopy (WAC) and underwater resection (UWR) of colorectal lesions with standard colonoscopy. We reviewed and graded the research evidence with potential clinical application. We conducted a modified Delphi consensus among experienced colonoscopists on definitions and practice of water immersion (WI), water exchange (WE), and UWR. METHODS: Major databases were searched to obtain research reports that could potentially shape clinical practice related to WAC and UWR. Pertinent references were graded (Grading of Recommendations, Assessment, Development and Evaluation). Extracted data supporting evidence-based statements were tabulated and provided to respondents. We received responses from 55 (85% surveyed) experienced colonoscopists (37 experts and 18 nonexperts in WAC) from 16 countries in 3 rounds. Voting was conducted anonymously in the second and third round, with ≥80% agreement defined as consensus. We aimed to obtain consensus in all statements. RESULTS: In the first and the second modified Delphi rounds, 20 proposed statements were decreased to 14 and then 11 statements. After the third round, the combined responses from all respondents depicted the consensus in 11 statements (S): definitions of WI (S1) and WE (S2), procedural features (S3-S5), impact on bowel cleanliness (S6), adenoma detection (S7), pain score (S8), and UWR (S9-S11). CONCLUSIONS: The most important consensus statements are that WI and WE are not the same in implementation and outcomes. Because studies that could potentially shape clinical practice of WAC and UWR were chosen for review, this modified Delphi consensus supports recommendations for the use of WAC in clinical practice.

Comparison of Right Colon Adenoma Miss Rates Between Water Exchange and Carbon Dioxide Insufflation: A Prospective Randomized Controlled Trial.

GOALS: To test the hypothesis that water exchange (WE), when compared with carbon dioxide (CO2) insufflation, significantly reduces the right colon adenoma miss rate (rAMR) in a blinded randomized controlled trial with cap-assisted colonoscopy. BACKGROUND: The unblinded consecutive group observational data showed that WE significantly decreased rAMR. The unblinded data are limited by potential bias. STUDY: Consecutive patients aged 45 years or more were randomized to undergo insertion with WE or CO2. Withdrawal and polypectomy were performed with CO2 in both groups to the hepatic flexure. The colonoscope was reinserted to the cecum. A second colonoscopist re-examined the right colon. The second colonoscopist was unaware, but made a guess, of the initial insertion method. The number of additional adenomas divided by the total number detected in both examinations equaled rAMR. RESULTS: Among 262 patients (131/group), demographic variables were similar. The body mass index was significantly higher in the WE group. Compared with CO2, WE significantly decreased rAMR [18.0% (33/183) vs. 34.6% (62/179), P=0.0025] and right colon serrated polyp miss rate [17.4% (27/155) vs. 39.3% (33/84), P=0.002]. Multivariate logistic regression analysis showed that WE was an independent predictor of rAMR (odds ratio, 0.42; 95% confidence interval, 0.21-0.86), and so was ≥2 adenomas in the right colon (odds ratio, 2.35; 95% confidence interval, 1.17-4.76). Whether the second colonoscopist guessed the insertion method correctly or not, and demographic and procedure variables were not associated with rAMR. CONCLUSIONS: The randomized controlled trial validated unblinded observational data showing that WE significantly decreased rAMR and right colon serrated polyp miss rate (clinical trial registration number: NCT03845933).

Heat sink effect of underwater polypectomy in a porcine colon model.

BACKGROUND: Underwater polypectomy without the need for submucosal injection has been reported. A heat-sink effect by immersing the polyp in water was proposed but no such experiment has been performed to support the claim. We compared the temperature rise on the serosal side during polypectomy between air- and water-filled colon. METHOD: Freshly harvested porcine colons were placed in a metal tray with cautery electrode pad attached to its bottom. An upper endoscope was used with a cap and a rubber band mounted to the distal end. A mucosal site was randomly selected and identified on its serosal surface with a marker while suction was applied. Suction was applied again and a ligation band was applied to create a polyp. A cautery snare grasped the artificial polyp just below the band. An assistant placed the tip of a thermometer at the marked site on the serosal surface to record the baseline temperature before cautery and the highest temperature during polypectomy. Seven polypectomies in air and underwater were performed. RESULTS: Mean (standard deviation) baseline temperature were 23.3 (0.6) °C and 23.4 (0.6) °C in the air and water groups, respectively. The maximum rise in temperature during polypectomy was 6.1 (4.5) °C and 1.4 (1.0) °C in the air and water groups, respectively (P = 0.004). CONCLUSIONS: The maximum temperature rise during polypectomy was significantly less when polypectomy was performed underwater, supporting the hypothesis that a heat-sink effect does exist during underwater polypectomy.

Water Exchange (WE) and Quality Improvement-Enhanced Advanced Adenoma Detection: A Pooled Data Analysis of 6 Randomized Controlled Trials.

INTRODUCTION: Advanced adenomas (≥10 mm in diameter, >25% villous, or high-grade dysplasia), a marker of colorectal cancer risk, are used to stratify patients for closer surveillance. Modern accessories, endoscopes, and age-adjusted evaluation have variable impacts on the advanced adenoma detection rate (AADR). In 1 randomized controlled trial (RCT) comparing air insufflation (AI) with water exchange (WE), the right colon AADR was significantly increased by WE. Four network meta-analyses reported that WE significantly increased overall adenoma detection rate (ADR), but the impact on AADR was not addressed. AIM: The aim of this study was to test the hypothesis that WE significantly increased AADR compared with AI. METHOD: Six Clinicaltrial.gov-registered RCTs were reported by a group of WE investigators. Data including AADR (primary outcome) and overall ADR (secondary outcome) were pooled. RESULTS: A total of 5407 patients were randomized to AI (2699) and WE (2708). Compared with AI, WE significantly increased AADR (5.7% vs. 8.3%, P=0.001) and overall ADR (20.9% vs. 27.4%, P=0.001). CONCLUSIONS: In contrast to published reports, which showed variable impacts on AADR, WE was consistent in increasing AADR in 6 reported RCTs. The pooled data confirm that the impact of WE in increasing AADR was significant. The significantly enhanced overall ADR indicated that WE provided a higher quality outcome than AI. The significant improvement in AADR confirmed WE to be clinically relevant and has finally arrived as a timely addition to colorectal cancer prevention programs.

Feasibility of sedation on demand in Taiwan using water exchange and air insufflation: A randomized controlled trial.

BACKGROUND AND AIM: Completion of colonoscopy without sedation eliminates sedation cost and complications. Reported in the United States and Europe, on-demand sedation is not routine practice in Taiwan. Water exchange (WE), characterized by infusion and nearly complete removal of infused water during insertion, reduces insertion pain compared to air insufflation (AI) during colonoscopy. We evaluated the feasibility of on-demand sedation in Taiwan. In a randomized controlled trial of WE vs AI colonoscopy, we also aimed to determine if WE augmented the implementation by reducing insertion pain and decreasing sedation requirement. METHODS: This prospective patient-blinded study randomized patients to AI or WE (75 patients/group) to aid insertion. The primary outcome was the proportion of patients completing without sedation. RESULTS: In the AI and WE groups, 76.0% and 93.3% (P = 0.006) completed without need for sedation, respectively. The WE group had lower insertion pain score (mean [SD]) (4.0 [2.9] vs 2.1 [2.6], P < 0.001), lower doses of propofol (25.7 [52.7] mg vs 9.1 [35.6] mg, P = 0.012), and less time in the recovery room (3.4 [7.4] vs 1.5 [5.5], P = 0.027) than the AI group. Patient satisfaction scores and willingness to repeat if needed in the future were similar. CONCLUSION: On-demand sedation was feasible in Taiwan. The completion rate without sedation was high in patients (76.0% with standard AI) open to the option (no prior intent to receive the standard of full or minimal sedation). WE augmented the implementation by reducing insertion pain and decreasing sedation requirement without adversely affecting patient satisfaction or willingness to repeat.

Cecal intubation time between the use of one-channel and two-channel water exchange colonoscopy: A randomized controlled trial.

BACKGROUND AND AIM: Water exchange (WE) colonoscopy is the least painful insertion technique with high adenoma detection rate but requires a longer intubation time. In the published literature, some investigators used the instrument channel for both infusing and suctioning of water (one channel), while others use colonoscopes with an integrated water-jet channel specifically designed for infusing water (two channel). The aim of this study was to compare cecal intubation time between one-channel and two-channel WE. METHODS: A total 120 patients undergoing colonoscopy from May 2017 to April 2019 at a regional hospital in southern Taiwan were randomized to either a two-channel group (n = 60) or a one-channel group (n = 60). The primary outcome was cecal intubation time. RESULTS: The mean cecal intubation time was significantly shorter in the two-channel group compared with the one-channel group (14.0 ± 4.0 vs 17.4 ± 6.7 min, P < 0.001). The two-channel group required less water infused during insertion (564.8 ± 232.4 vs 1213.3 ± 467.5 mL, P < 0.001) but achieved a significantly higher Boston Bowel Preparation Scale score (8.4 ± 0.8 vs 7.5 ± 1.1, P < 0.001) than did the one-channel group. The adenoma detection rate was comparable in the two groups (50.0% vs 48.3%, P = 0.855). CONCLUSIONS: In comparison with the one-channel WE, two-channel WE showed a shorter cecal intubation time, required less amount of water during insertion, and provided a better salvage cleansing effect. (NCT03279705).

Factors Associated With Adenoma Detection in Propofol-sedated Patients.

GOALS: To assess the factors associated with adenoma detection in propofol-sedated patients. BACKGROUNDS: Low adenoma detection rate (ADR) are linked to increased risk of interval cancer and related deaths. Compared with air insufflation (AI) colonoscopy, the method of water exchange (WE) significantly decreased insertion pain and increased ADR in unsedated patients. Deep sedation with propofol has been increasingly used in colonoscopy. One report suggested that WE significantly increased ADR in propofol-sedated patients, but the factors associated with adenoma detection were not analyzed. STUDY: Post hoc multiple logistic regression analyses were performed based on pooled data from 2 randomized controlled trials to assess the factors associated with adenoma detection in propofol-sedated patients. RESULTS: Propofol-sedated patients (n=510) were randomized to AI and WE. The baseline characteristics were comparable. Multiple logistic regression analyses show that age, withdrawal time, indications (screening vs. diagnostic), and WE were significantly and independently associated with higher ADR. WE had fewer patients with inadequate Boston Bowel Preparation Scale score of <6. Despite a significantly shorter inspection time, WE had significantly higher overall ADR than AI, especially in those with adequate Boston Bowel Preparation Scale of ≥6. Right colon ADR (17.5% vs. 10.5%), flat ADR (32.3% vs. 19.4%), combined advanced and sessile serrated ADR (13.1% vs. 7.4%) of WE were significantly higher than those of AI. CONCLUSIONS: WE enhanced quality of colonoscopy in propofol-sedated patients by significantly improving colon cleanliness and overall ADR. Colonoscopists with patients under propofol sedation might consider evaluating WE method for performance improvement.

Water Exchange Produces Significantly Higher Adenoma Detection Rate Than Water Immersion: Pooled Data From 2 Multisite Randomized Controlled Trials.

GOALS: To test the hypothesis that water exchange (WE) significantly increases adenoma detection rates (ADR) compared with water immersion (WI). BACKGROUND: Low ADR was linked to increased risk for interval colorectal cancers and related deaths. Two recent randomized controlled trials of head-to-head comparison of WE, WI, and traditional air insufflation (AI) each showed that WE achieved significantly higher ADR than AI, but not WI. The data were pooled from these 2 studies to test the above hypothesis. STUDY: Two trials (5 sites, 14 colonoscopists) that randomized 1875 patients 1:1:1 to AI, WI, or WE were pooled and analyzed with ADR as the primary outcome. RESULTS: The ADR of AI (39.5%) and WI (42.4%) were comparable, significantly lower than that of WE (49.6%) (vs. AI P=0.001; vs. WI P=0.033). WE insertion time was 3 minutes longer than that of AI (P<0.001). WE showed significantly higher detection rate (vs. AI) of the >10 mm advanced adenomas. Right colon combined advanced and sessile serrated ADR of AI (3.4%) and WI (5%) were comparable and were significantly lower than that of WE (8.5%) (vs. AI P<0.001; vs. WI P=0.039). CONCLUSIONS: Compared with AI and WI, the superior ADR of WE offsets the drawback of a significantly longer insertion time. For quality improvement focused on increasing adenoma detection, WE is preferred over WI. The hypothesis that WE could lower the risk of interval colorectal cancers and related deaths should be tested.

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

BACKGROUND: Reports showed adenoma miss rates (AMRs) of 22.5-27% in the right colon and 23.4-33.3% in the proximal colon. Missed lesions could contribute to postcolonoscopy cancers. Water exchange (WE) with near-complete removal of infused water during insertion increased adenoma detection rate but the impact on AMR had not been reported. We hypothesized that WE could reduce AMRs. Study 1 compared the AMRs of WE with literature data. Study 2 developed local AMR data with CO2 insufflation. METHODS: The lead author attended a research seminar in 2017 on WE colonoscopy. For performance improvement, study 1 was undertaken. When data in study 1 confirmed WE produced a considerably lower AMRs in the right and proximal colon, study 2 with CO2 insufflation was performed. RESULTS: Eighty-six patients completed each study. In study 1, WE removed 89% of infused water upon arrival to the cecum. The AMRs of right colon (17.5%) and proximal colon (15.5%) were considerably lower than those in the literature. Upon completion of study 2, compared with local data of CO2 insufflation, WE showed a significantly lower AMR in the right (17.5% vs. 33.8%, P = 0.034) and proximal (15.5% vs. 30.4%, P = 0.018) colon, respectively. The major limitation was that the investigation consisted of two consecutive observational studies, not a randomized controlled trial (RCT). CONCLUSIONS: WE with near-complete (89%) removal of infused water during insertion significantly decreased AMRs in the right and proximal colon compared with literature data and those of CO2 insufflation in our hands. The provocative data warrant confirmation in a RCT. TRIAL REGISTRATION: NCT03832322 (Retrospectively registered on February 2, 2019).

Prospective multicenter randomized controlled trial comparing adenoma detection rate in colonoscopy using water exchange, water immersion, and air insufflation.

BACKGROUND AND AIMS: Adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma of any size, is a quality indicator. We tested the hypothesis that water exchange (WE) improves ADR but water immersion (WI) has no adverse effect on ADR compared with air insufflation (AI). METHODS: A prospective study was conducted at the Dalin Tzu Chi Hospital in southern Taiwan and the Hualien Tzu Chi Hospital in eastern Taiwan on patients randomly assigned to WE, WI, or AI with stratification by the 3 study colonoscopists. The primary outcome was ADR. RESULTS: From July 2013 to December 2015, 651 patients were recruited and randomized into 3 groups with a 1:1:1 ratio (217 patients per group). Overall, ADR met quality standards: WE 49.8% (95% CI, 43.2%-56.4%), AI 37.8% (95% CI, 31.6%-44.4%), and WI 40.6% (95% CI, 34.2%-47.2%). Compared with AI, WE significantly increased ADR (P = .016). There was no difference between WI and WE. ADRs of WI and AI were comparable. Compared with AI, WE confirmed a longer insertion time, higher cleanliness score, but similar adenoma per positive colonoscopy (APPC) and withdrawal time with polypectomy. Subgroup analysis found WE significantly increased ADR in propofol-sedated patients. Multivariate generalized linear mixed model analysis revealed that age ≥50 years, WE (vs AI), colonoscopy indication, no previous history of colonoscopy, and withdrawal time >8 minutes were significant predictors of increased ADR. CONCLUSIONS: Confirmation of prior reports showing WE, but not WI, increased ADR further strengthened the validity of our observations. WE significantly increased ADR in propofol-sedated patients. The outcome differences justify assessment of the role of WE in colorectal cancer prevention. Similar APPC and withdrawal times suggest that adequate inspection was performed on colonoscope withdrawal in each of the study arms. (Clinical trial registration number: NCT01894191.).

Mortality Following Catheter Drainage Versus Thoracentesis in Cirrhotic Patients with Pleural Effusion.

BACKGROUND: Pleural effusion is an abnormal collection of body fluids that may cause related morbidity or mortality in cirrhotic patients. There are insufficient data to determine the optimal method of drainage, for symptomatic relief in cirrhotic patients with pleural effusion. AIMS: In this study, we compare the mortality outcomes of catheter drainage versus thoracentesis in cirrhotic patients. METHODS: The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify cirrhotic patients with pleural effusion requiring drainage between January 1, 2007, and December 31, 2010. In all, 2556 cirrhotic patients with pleural effusion were selected for the study and divided into the two groups (n = 1278/group) after propensity score matching. RESULTS: The mean age was 61.0 ± 14.3 years, and 68.9% (1761/2556) were men. The overall 30-day mortality was 21.0% (538/2556) and was higher in patients treated with catheter drainage than those treated with thoracentesis (23.5 vs. 18.6%, respectively, P < 0.001 by log-rank test). After Cox proportional hazard regression analysis adjusted by patient sex, age, and comorbid disorders, the risk of 30-day mortality was significantly higher in cirrhotic patients who accepted catheter drainage compared to thoracentesis (hazard ratio 1.30, 95% confidence interval 1.10-1.54, P = 0.003). Old age, hepatic encephalopathy, bleeding esophageal varices, hepatocellular carcinoma, ascites, and pneumonia were associated with higher risks for 30-day mortality. CONCLUSION: In cirrhotic patients with pleural effusion requiring drainage, catheter drainage is associated with higher mortality compared to thoracentesis.

A patient-blinded randomized, controlled trial comparing air insufflation, water immersion, and water exchange during minimally sedated colonoscopy.

OBJECTIVES: Minimal sedation obviates patient recovery burdens, but intolerable pain limits success of cecal intubation. Painless or minimally uncomfortable insertion ensures success of cecal intubation, current patient satisfaction, and willingness to repeat future colonoscopy with minimal sedation. Water immersion (WI) and water exchange (WE), when separately compared with air insufflation (AI), significantly reduced insertion pain. To assess comparative effectiveness, we conducted a randomized controlled trial with head-to-head comparison of these three methods. We hypothesized that WE could produce the highest proportion of patients reporting painless insertion. METHODS: This prospective patient-blinded trial (NCT01535326) enrolled minimally sedated (25 mg intramuscular meperidine) patients randomized to AI, WI, or WE (90 patients/group) to aid insertion. The previously validated primary outcome was the proportion of patients reporting painless insertion. RESULTS: Painless insertion was reported by 30.0% (AI), 43.3% (WI), and 61.1% (WE) of patients (P<0.001). Multivariate logistic regression analysis revealed that, after adjusting for gender, body mass index, abdominal compression, position change, insertion time to cecum, and length of scope at cecum, only WE was significantly associated with painless insertion compared with AI (odds ratio (OR)=0.08, 95% confidence interval (CI)=0.03-0.24, P<0.001) or WI (OR=0.14, 95% CI=0.05-0.40, P<0.001). Adenoma detection rate (ADR) in the right (cecum and ascending) colon was 11.1% (AI), 14.4% (WI), and 26.7% (WE) (P=0.015). The limitations included single site study with unblinded colonoscopist and assistant. CONCLUSIONS: This head-to-head comparison of AI vs. WI vs. WE confirmed that WE was superior to WI and AI, with a significantly greater proportion of patients reporting painless insertion. The significantly higher ADR in the right colon in the WE group warrants further investigations.