Water Exchange Colonoscopy Decreased Adenoma Miss Rates in the Right and Proximal Colon: An Observational Study Using A Tandem Colonoscopy Approach
Conditions: Colonic Adenoma, Water Exchange Colonoscopy
Sponsor: Evergreen General Hospital, Taiwan

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Title: Water Exchange Colonoscopy Decreased Adenoma Miss Rates in the Right and 
Proximal Colon: An Observational Study Using A Tandem Colonoscopy Approach 
NCT Number: NCT03832322 
Unique Protocol ID: EGH-2018 
Date: Jan 3, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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STUDY PROTOCOL 
BACKGROUND 
Colonoscopy is currently regarded as the gold standard to detect and prevent 
colorectal cancer (CRC). It is widely practiced and generally safe and accurate, but not 
perfect. A substantial number of neoplastic lesions were missed according to 
back-to-back (tandem) air insufflation colonoscopy studies. In a systematic review of 
tandem colonoscopy studies, a 22% pooled miss-rate for adenomas were reported. 
Of all post-colonoscopy CRCs (PCCRCs), 58% were attributed to lesions missed during 
examination. Colonoscopy maneuvers helping to reduce AMR, particularly in the 
proximal and right colon, have the potential to decrease the incidence of PCCRCs. 
Water exchange (WE) colonoscopy is characterized by the gasless insertion to the 
cecum in clear water and maximizing cleanliness during insertion. WE colonoscopy 
has been shown to improve the overall adenoma detection rate (ADR), compared to 
air insufflation colonoscopy. The impact of optimal WE with near-complete removal 
of infused water on proximal and right colon AMR has not been reported.  
The primary outcomes of this study were the right and proximal colon AMRs 
determined by tandem colonoscopy using WE or CO2 insufflation for screening and 
surveillance indications. The secondary outcomes were the combined right and 
proximal colon AMR and hyperplastic polyp miss rate (HPMR), overall ADR and other 
adenoma detection related metrics between the two colonoscopy methods. 
METHODS 
This was an observational study comparing consecutive group of WE and CO2 
insufflation in terms of right and proximal colon AMR by tandem colonoscopy. 
Consecutive patients were enrolled from July 2018 to November 2018 at Evergreen 
General Hospital, Taoyuan, Taiwan.  
Participants 
Consecutive patients aged 20 years or older undergoing colonoscopy for screening 
and surveillance indications were considered for enrollment. Exclusion criteria 
included familial adenomatous polyposis and hereditary non-polyposis CRC 
syndrome, personal history of inflammatory bowel disease, previous colonic 
resection, inability to achieve cecal intubation, obstructive lesions of the colon, poor 
colon preparation, inability to completely remove a polyp, gastrointestinal bleeding, 
allergy to fentanyl or midazolam, American Society of Anesthesiology classification of 

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physical status grade 3 or higher, mental retardation, pregnancy, and refusal to 
provide a written informed consent.  
Bowel Preparation and Sedation 
Patients were instructed to eat low-residual foods for two days before colonoscopy. 
All patients received a split dose of 3-L polyethylene glycol (Klean-Prep) for bowel 
preparation. Colonoscopy were performed with moderate sedation (intravenous 
fentanyl plus midazolam) administered by the colonoscopist. 
First-pass Colonoscopy Procedure 
Colonoscopies are performed by two board-certified colonoscopists (Chi-Liang 
Cheng, Yen-Lin Kuo) using a standard colonoscopy (CF-Q260AL/I; Olympus Medical 
Systems Corp., Tokyo, Japan). Felix W. Leung was involved in the study design, data 
analyses, and report preparation, but not in patient enrollment. Colonoscopy began 
with the patients in the left lateral position. In the WE group, the air pump was 
turned off before starting the procedure. During the insertion phase, air and residual 
water or feces in the rectum were aspirated, and then the colon was irrigated with 
water using flushing pumps (Olympus AFU-100; Olympus Corp.). There was no 
restriction placed on the overall volume of water infused to achieve adequate 
cleansing. WE entailed the infusion of water to open the lumen and sequential 
suction of water. Air pockets, when encountered, was aspirated. When the cecum 
was reached and after most of the water was suctioned to collapse the cecal lumen, 
CO2 was opened. In the CO2 group, colonoscopy was performed in the usual fashion, 
with minimal insufflation required to aid insertion. Cleaning in the CO2 group was 
predominantly performed during withdrawal. Polyp resection was done during 
insertion and withdrawal in both groups.  
Second-pass Colonoscopy Procedure 
After the first complete withdrawal of the colonoscope, a second colonoscopic 
examination aided by CO2 insufflation during insertion and withdrawal was 
performed by the same endoscopist. In both groups, the colonoscope was reinserted 
into the cecum as quickly as possible, and the entire colon was re-examined. Polyp 
resection was carried out during insertion and withdrawal in both groups during the 
second-pass examination. All polyps identified in the second-pass examination were 
defined as missed polyps with the exception of the diminutive polyps in the 
rectosigmoid colon that remain after the first-pass colonoscopy.  

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Definition 
Complete colonoscopy was defined as successful cecal intubation. Insertion time 
was defined as the time between the scope insertion and cecal intubation. 
Withdrawal time was defined as the time from cecal intubation to the time when the 
colonoscope was withdrawn from the anus, including the time taken for mucosal 
cleaning and polypectomy. Total procedure time was the sum of insertion time and 
withdrawal time. A Poor colon preparation was defined as a total BBPS score of 5 or 
less. 
All colonic polyps removed during procedures were sent for histological 
examination with clear labeling of location and sequences of colonoscopy. The 
location of colonic polyps was defined according to the anatomical distribution. Right 
colon was defined as cecum, ascending colon, and hepatic flexure. Proximal colon 
was defined as right and transverse colon. Diminutive polyps were defined as polyps 
with size ≤5 mm. Small polyps were defined as polyps with size 6-9 mm. Large polyps 
were defined as polyps with size ≥10 mm. Adenomas included all adenomas and 
sessile serrated adenoma. Advanced adenomas were defined as those lesions with 
one of the following criteria: 1) lesions larger than 10 mm in diameter; 2) lesions with 
a villous component; 3) lesions with high-grade dysplasia; and 4) lesions with invasive 
features.  
Lesions detected on the first-pass examination were used for the calculation of 
adenoma detection. ADR was defined as the proportion of colonoscopies where at 
least one adenoma was found. Proximal hyperplastic polyp detection rate (PHP-DR) 
was defined as the proportion of patients undergoing colonoscopy in whom at least 
one hyperplastic polyp was identified in the proximal colon.  
Lesions detected on the second-pass examination were used for the calculation of 
adenoma or polyp miss. AMR and HPMR were calculated as the number of 
adenomas and hyperplastic polyps missed in the first colonoscopy divided by the 
total number of adenoma and hyperplastic polyps detected during both the first and 
second colonoscopies.  
STATISTICAL ANALYSIS PLAN 
Sample size estimation 

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 The sample size estimation was based on the assumption that WE colonoscopy 
reduced proximal colon AMR compared to conventional CO2 insufflation colonoscopy. 
We estimated the proximal colon AMR in the CO2 group to be 30% and the average 
detected number of proximal colon adenoma to be 0.9 per subject after first colon 
examination. To show a clinically important improvement of proximal colon AMR 
reduction by the WE colonoscopy, we assumed that WE colonoscopy should reduce 
the AMR by 18%. With a statistical power of 80% and a two-side significance level of 
0.05, 82 patients were needed in each study arm.  
Statistical analysis 
 Summary statistics were presented as frequencies and percentages in the case of 
categorical variables and as the means with standard deviations (SD) in the case of 
continuous variables. Student’s t-test for continuous factors, Wilcoxon rank sum test 
for ordinal variables (such as polyp size), and Chi-square test for categorical variables 
were used to assess differences in demographic and clinical characteristics of patients 
in each group. All statistical analyses were performed by using SAS version 9.3 or 
later (SAS Institute Inc., Cary, NC, USA). The criterion for statistical significance will be 
P value <0.05.