Water Immersion and Polyp Detection: A Randomized Controlled Trial
Phase: NA
Conditions: Adenoma, Colonic Neoplasms
Sponsor: White River Junction Veterans Affairs Medical Center

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Water Immersion and Polyp Detection: A Randomized Controlled Trial 
 
Edited April 23rd 2019 
 
NCT03231917 
 

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Introduction 
Although water can be used to facilitate colonoscope insertion1-13, the use of two 
techniques employing water have been evaluated for their effects on adenoma detection 
as compared to standard insertion methods which employ air or CO214, 15. These 
techniques are called water exchange (WE) and water immersion (WI). In WI, water is 
used to distend the colon during insertion and is removed largely during withdrawal. WI 
utilizes enough water during insertion to identify the luminal direction but dirty water is 
removed primarily during withdrawal. WE is a slower insertion technique in which the air 
valve is turned off and clean water is infused and dirty water is suctioned during 
insertion and the instrument is not advanced until the lumen is clean. WE also involves 
aspiration of retained gas pockets during insertion. Both WE and WI use air or CO2 
rather than water to distend the lumen during withdrawal, and therefore it is not known 
whether visualization of the mucosa using water as a medium, as opposed to air or 
CO2, increases adenoma detection16. In contrast to the other methods, TUC involves 
water exchange (WE) during insertion followed by continuous water infusion (rather 
than gas) on withdrawal in order to distend the lumen for total underwater mucosal 
visualization. 
The use of water during colonoscopy may improve adenoma detection through 
several possible mechanisms17. It may help to further clear the bowel of any residual 
stool. In addition, since water may allow for mucosal inspection without fully distending 
the lumen like air does, water techniques might increase the yield for flat lesions. Very 
flat lesions may be less visible with full distention of the lumen. Finally, water has a 
magnifying effect, which may also increase detection. Thus, TUC, in which the entire 
procedure including withdrawal is performed underwater, could potentially improve 
polyp detection compared to gas insufflation.  
The goal of our study was to use TUC in tandem with standard CO2 insufflation to 
determine if water is a better medium than CO2 for visualizing and detecting polyps and 
adenomas. Our goal was to randomize patients to tandem colonoscopy performed first 
with either TUC or CO2 followed by the other medium in order to compare miss rates for 

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polyps and adenomas. Our hypothesis was that TUC was associated with a lower 
adenoma and polyp miss rate for tandem performance of colonoscopy than CO2. 
 
 
Methods  
We conducted a randomized trial of tandem colonoscopies comparing TUC to CO2 
insufflation. Our study was approved by the Institutional Review Boards at the White 
River Junction Veterans Affairs Medical Center and Indiana University. All patients were 
consented with written consent prior to the colonoscopies.  In one group, TUC was 
employed as the first method for mucosal inspection while in a second group, CO2 
insufflation was used first. 
Study Population 
Eligible subjects were adults 50-80 years who presented for colonoscopy at White 
River Junction VAMC, Indianapolis VAMC, and Indiana University. Exclusion criteria 
included a co-morbid status of American Society of Anesthesiologists physical status 
classification system ASA of III (severe systemic disease) or higher, Inflammatory 
Bowel Disease (IBD), surgical resection of the large bowel, as well as the use of non-
aspirin anticoagulants. Finally, potential subjects who did not report a clear effluent in 
the most recent bowel movement at time of colonoscopy were excluded from the study. 
Randomization 
The participants were randomized using a random number generator, stratified by 
endoscopist/site. The results of the randomization were opened prior to the initial 
insertion of the colonoscope, informing the endoscopist which method was first, CO2 or 
TUC. 
Colonoscopy 
Consenting adults were randomized to undergo colonoscopy with either TUC or 
CO2 insufflation for the first colonoscopy followed by an examination using the other 
technique. All examinations were performed by one of three experienced endoscopists 
(JCA, CJK, DKR). Participants were sedated using propofol or moderate sedation with 
midazolam/fentanyl and diphenhydramine. All colonoscopies were performed with high 
definition colonoscopes. (Olympus CF-HQ190L; Olympus (Tokyo, Japan)) 

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The randomization envelope was opened prior to the initial insertion. An assistant 
measured the inspection time with a stopwatch from insertion of scope into the rectum 
until the cecum was reached, stopping the watch during insertion for polyp resection in 
both techniques or for time spent washing or suctioning (in CO2 arm only). For the arm 
where CO2 insufflation was used first, the lumen was distended with the gas during 
insertion. When the TUC technique was used first, the air valve was shut off and water 
was infused and any residual stool or air was suctioned out during insertion. After the 
cecum was intubated, the endoscopist attempted to intubate the terminal ileum. The 
mucosal inspection was then initiated during withdrawal when the distention with water 
or CO2 was adequate for visualization. Measurement of withdrawal and inspection 
times was initiated at this point. Inspection time was the withdrawal time minus the time 
for biopsy or polypectomy or for time spent washing or suctioning (in CO2 arm only). 
The assistant with a stopwatch announced the withdrawal time periodically with the goal 
to equalize inspection times. 
When the withdrawal of the colonoscope reached the rectum and after the retro-
flexion was performed, the endoscopist re-inserted the colonoscope using the other 
technique. For the exams with TUC as the first method, water was suctioned out of the 
lumen as CO2 was introduced into the lumen during the second insertion. Upon 
withdrawal, the remaining water was aspirated and CO2 was used to distend the lumen 
to allow for adequate inspection of the mucosa. In the group in which CO2 is used first, 
CO2 was suctioned out during the second colonoscopy as the scope was inserted with 
water infusion. As the scope was withdrawn, water was infused with the air valve turned 
off. Inspection was not started until after cecal intubation and the lumen was filled with 
water allowing for adequate visualization of the mucosa through the infused water. 
Inspection time was measured as outlined above. 
Outcomes 
The primary outcome measure and study endpoint was the miss rate for polyps and 
adenomas in the two study groups 18. Miss rates were also calculated for participant 
level for each technique. Adenoma-level miss rates were calculated as the number of 
additional adenomas detected during the second examination (for both insertion and 
withdrawal) divided by the total number of adenomas detected during insertion and 

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withdrawal for both examinations. These miss rates were reported for the technique 
used for the first examination. Participant-level miss rates were calculated as the 
number of participants with one or more adenomas detected during the second 
examination, divided by the total number of participants with at least one adenoma in 
either examination. We also examined proximal (cecum, ascending colon, transverse 
colon and splenic flexure) adenoma miss rates as a secondary outcome, which were 
calculated as above. Finally, we also calculated serrated polyp (hyperplastic, sessile 
serrated polyp and traditional serrated adenoma) 
For each polyp, we estimated size by open forceps, and noted location, method of 
removal, whether polyps were detected by insertion or withdrawal and whether CO2 or 
TUC was used for mucosal inspection. 
We used the Boston Bowel preparation score to assess the quality of the preparation. 
We also used a scale of good (3), fair (2) and poor (1) to assess the clarity or turbidity of 
the water during TUC for 3 segments, right, transverse and left colons. 
Co-variates 
Data collected included participant age and sex, exam indication, personal history of 
colorectal neoplasia, family history of CRC, time (total procedure, insertion and 
inspection), volume of water infused during insertion and withdrawal, quality of bowel 
preparation as measured by the Boston Bowel Preparation Score and medications 
provided during the procedure. 
Statistical considerations  
In calculating a sample size required to detect a clinically important difference in 
miss rates between TUC and CO2 we used  the following assumptions: a 30% 
adenoma miss rate for regular colonoscopy19, 20; a 10% adenoma miss rate with TUC; 
50% of participants would have at least one adenoma, and participants with adenomas 
would have an average of two adenomas. We based this in part on a tandem study 
using cap since the cap had similar reported increase in adenoma detection to water 
exchange18. For the study to have 80% power to detect a 3-fold reduction in adenoma 
miss rates, by using a chi-square test with a 5% significance level, the study needed 60 
adenomas per group. We assumed that each participant would have on average two 
polyps and planned to enroll at least 120 participants (60 at each site).  

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Participants who underwent initial colonoscopy with TUC were compared with 
participants who underwent colonoscopy with CO2 first for differences in age and 
propofol dose by using 2-sample t-tests, for differences in sex and indication by using 
chi square tests, and for a difference in quality of bowel preparation by using a Mantel-
Haenszel test for ordered categories. Logistic regression was used to compare the miss 
rates between participants who underwent TUC first and participants who underwent 
CO2 first. The model was adjusted for participant age, sex, family history of CRC, exam 
indication, time for inspection, insertion time and volume of water infused/aspirated. A 
generalized estimating equation was used to control for the effect of the endoscopist.  
 
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