Impacts of Inspection During Instrument Insertion on Colonoscopy Quality: a Prospective Randomized Controlled Trial
Phase: NA
Conditions: Colon Polyp, Colon Adenoma
Sponsor: Evergreen General Hospital, Taiwan

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Title: Impacts of inspection during instrument insertion on colonoscopy 
quality: A prospective randomized controlled trial  
 
INTRODUCTION  
 
  Colonoscopy is considered the preferred modality for colorectal cancer (CRC) 
screening since it has both diagnostic and therapeutic capabilities. However, 
colonoscopy is not a perfect test. It misses a substantial number of neoplastic lesions 
[1,2]. In a systematic review of tandem (same-day back-to-back) colonoscopy, the 
pooled miss rate for polyps of any size was 22%, and the adenoma miss rate by size 
was 2.1% for ≥10 mm, 13% for 6-9 mm, and 26% for ≤5 mm, respectively [3]. 
Researches continue to explore methods to improve the polyp and adenoma 
detection during colonoscopy and many of them focus on the withdrawal phase of 
the examination [4-5]. Thus, colonoscopy is typically performed with rapid passage of 
the instrument through the loops and bends of the colon to the cecum and then 
performing a slow deliberate withdrawal. As a consequence, all removal of polyps is 
done when the instrument is pulled back. 
  Many experienced endoscopists recognized that small polyps seen incidentally but 
not removed during insertion are sometimes quite difficult to find during withdrawal. 
This may be due to different anatomical conformations of the colon during 
instrument insertion and withdrawal. The insertion and withdrawal phases may 
expose somewhat different sections of the mucosal surface to the colonoscope, and 
inspection on insertion and withdrawal are possibly complementary. Most 
endoscopists agree that advanced (≥10 mm) polyps should be removed only during 
withdrawal [6]. Whether smaller polyps (<10 mm) should be removed during 
insertion phase is controversial. Some studies showed that inspection and 
polypectomy during insertion phase reduced colorectal polyp/adenoma miss rate 
[7-9]. But other studies found that inspection and polypectomy during insertion 
phase offered no additional benefit on adenoma detection [10-12].  
  The adenoma detection rate (ADR) has become a validated quality indicator for 
colonoscopy; the higher the ADR of colonoscopists, the lower the risk of interval CRC 
and the lower the risk of dying from CRC [13-14]. However, the ADR may not provide 
a comprehensive assessment of the adequacy and thoroughness of colonoscopic 

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examination. Recent study has shown that the standard ADR cannot distinguish high 
versus low endoscopist performance [15]. Other secondary quality measures have 
been suggested to supplement the ADR and include the polypectomy rate (PR), the 
mean adenoma per procedure (MAP), the mean adenoma per positive procedure 
(MAP+), the mean additional adenomas detected beyond the first adenoma per 
positive procedure (ADR-Plus), and the proximal serrated polyp detection rate 
(PSP-DR) [15-21]. The impact of the inspection and polypectomy during insertion 
phase of colonoscopy upon these secondary quality indicators is not known.  
  The primary aim of this study is to compare the impact upon the colonoscopy 
quality (including ADR, PR, MAP, MAP+, ADR-Plus, and PSP-DR) of additional 
inspection and polypectomy during insertion as opposed to the traditional practice of 
careful inspection and polypectomy performed entirely during withdrawal in patients 
undergoing routine colonoscopy with moderate sedation for screening or 
surveillance indications. The secondary aim of this study is to compare the impact of 
such endoscopic strategy on procedure times, distraction during withdrawal, 
procedure difficulty, sedative doses, and intra-procedure abdominal pain. 
 
METHODS 
This is an investigator-initiated prospective randomized controlled study. The study 
will be conducted at Evergreen General Hospital, Taoyuan, Taiwan. We plan to enroll 
patients since October of 2017 and the study is expected to be completed within 18 
months after patient enrollment. A written informed consent will be obtained from 
all patients. 
 
Participants 
  Patients aged 45 years or older who are able to give informed consent and are 
scheduled for elective colonoscopy at Evergreen General Hospital are eligible for 
enrollment. Exclusion criteria are previous surgical resection of the colon or rectum, 
inflammatory bowel disease, polyposis syndrome, previously incomplete colonoscopy, 
obstructive lesions of the colon, inadequate bowel preparation (defined as Boston 
Bowel Preparation Scale [BBPS] score of 0 or 1 in any colon segment) [22,23], 
gastrointestinal bleeding, allergy to fentanyl or midazolam, American Society of 
Anesthesiology (ASA) classification of physical status grade 3 or higher, mental 

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retardation, pregnancy, and refusal to provide a written informed consent. Patients 
will be enrolled by the primary investigator or co-primary investigators.  
 
Intervention and randomization 
  Patients will be randomly assigned by a research assistant, by using a 
computer-generated randomization sequence to undergo colonoscopy with either 
inspection and polypectomy during both insertion and withdrawal of colonoscope 
(study group) or inspection and polypecotmy entirely during withdrawal of 
colonoscope (control group). Randomization will be done via concealed allocation 
with a sealed envelope that designate study group or control group. The 
colonoscopist is not blinded to group assessment. 
 
Procedure 
Colonoscopies will be performed by two experienced colonoscopists by using a 
standard colonoscopy (CF-Q260AI or CF-Q260AL; Olympus Medical Systems Corp., 
Tokyo, Japan). All procedures are performed under moderate conscious sedation with 
fentanyl (United Biomedical, Taipei, Taiwan) and midazolam (Dormicum; Roche 
Pharmaceuticals, Basel, Switzerland) according to the current guidelines [24]. Carbon 
dioxide insufflation is used for all endoscopic procedures. All patients receive 3-L 
polyethylene glycol (PEG; Klean-Prep, Helsinn Birex Pharmaceuticals Ltd., Dublin, 
Ireland) for bowel preparation. A split-dose of the PEG preparation is provided for 
morning colonoscopy (2 L consumed in the evening before the colonoscopy and 1 L 
consumed in the early morning of the colonoscopy) and a same-day preparation is 
provided for the afternoon colonoscopy. The level of colon cleansing is prospectively 
evaluated with the BBPS score after all cleansing maneuvers are completed.  
For patients in the study group, the colonic lumen is washed with saline and the 
fluid and debris are suctioned as the instrument is slowly inserted from rectum to 
cecum. Deliberate and systematic inspection of the colonic mucosa is performed 
with adequate luminal insufflations during both the insertion and withdrawal phases. 
Polyp size is determined by comparison with open colonoscopic biopsy forceps 
pushed against the polyp or, in some cases of pedunculated polyp by direct 
measurement after retrieval. Polyps with size <10mm are removed as they are 
identified on insertion and withdrawal. Polyps with size ≥10mm are removed only 

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during withdrawal.  
For patients in the control group, deliberate mucosal inspection and polyp removal 
are performed exclusively on instrument withdrawal. During insertion, minimal 
mucosal inspection and insufflation are applied to efficiently advance the instrument 
into cecum. If a polyp is found during insertion, endoscopists are instructed to make 
a mental note of it and find it during withdrawal for polypectoymy.  
 
Definition 
Complete colonoscopy is defined as reaching and taking pictures of the cecum and 
ileocecal valve. Insertion time is defined as the time between the scope insertion and 
cecal intubation, including the time taken for mucosal clearing and polypectomy. 
Withdrawal time is defined as the duration between the time at which the cecum is 
reached and the time at which the scope is withdrawn from the anus, including the 
time taken for mucosal clearing and polypectomy. Total procedure time is the sum of 
insertion time and withdrawal time. The quality of bowel preparation is classified as 
excellent (BBPS score of 8 or higher), good (BBPS score of 7), or fair (BBPS score of 6). 
The location of colorectal polyps is defined according to the anatomical 
distribution. The portion of the colon above the level of the splenic flexure is defined 
as the proximal colon. Diminutive polyp is defined for polyp with size ≤5mm. Small 
polyp is defined for polyp with size 6-9mm. Large polyp is defined for polyp with size  
≥10mm. Adenomas include all adenomas and sessile serrated adenoma. Advanced 
adenoma is 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. ADR is defined as the 
proportion of colonoscopies where at least one adenoma is found. Advanced ADR is 
defined as the proportion of colonoscopies where at least one advanced adenoma is 
found. PR is defined as the proportion of patients undergoing colonoscopy in whom 
at least one polyp is removed. MAP is defined as the total number of adenomas 
detected divided by the number of colonoscopies. MAP+ is defined as the total 
number of adenoma detected divided by the number of colonoscopies in which at 
least one adenoma is found. ADR-Plus is defined as the mean number of adenomas 
detected after the first adenoma in procedures in which at least one adenoma is 
found. PSP-DR is defined as the proportion of patients undergoing colonoscopy in 

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whom at least one serrated polyp (hyperplastic polyp, sessile serrated 
adenoma/polyp, traditional serrated adenoma) is identified proximal to the splenic 
flexure. The mean neoplastic polyp detection rate (MNP-DR) is defined as the total 
number of adenomas plus proximal serrated polyps (hyperplastic polyp, sessile 
serrated polyp) divided by the number of colonoscopies. 
The grade of the colonoscopy difficulty is rated by the endoscopist using a 10-point 
Likert scale: 1, being extremely easy; and 10, being extremely difficult. Distraction 
during withdrawal phase is determined by the time of mucosal clearing and suction 
divided by the total withdrawal time and the total water volume required for 
mucosal claering. Patient’s subjective assessment of discomfort during the procedure 
is graded by patients with a 10-cm visual scale: 0, being no pain; and 10: being 
extremely severe pain. 
 
Statistical analysis 
The primary aim of the study is to evaluate whether there is a difference in the 
ADR between the two study groups. We calculate the required sample size by using 
the assumption of a 40% ADR in the control group [25]. For the study to have 85% 
power to detect a 15% increase in ADR with a 5% significance level, the study needs 
211 participants per group to achieve significance (two sided). To account for 
dropouts, incomplete procedures, and inadequate preparation, an additional 10% 
will be enrolled. Therefore a total of 464 patients (232 in each group will be enrolled. 
Summary statistics are presented as frequencies and percentages in the case of 
categorical variables and as the means with standard deviations in the case of 
continuous variables. Student’s t tests for continuous factors, Wilcoxon rank sum 
tests for ordinal variables (such as polyp size), and Chi-square tests for categorical 
variable are uses to assess differences in demographic and clinical characteristics of 
patients in each group. All calculations are conducted using SAS version 9.3 or later 
(SAS Institute Inc., Cary, NC, USA). The criterion for statistical significance is P <0.05. 
 
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