Comparison of Second Forward View Examination and Conventional Withdrawal Examination in the Right Colon on Polyp Detection in Screening and Surveillance Colonoscopies: A Randomized Controlled Study (SFVRC Study)
Phase: NA
Conditions: Colonic Polyp, Colorectal Cancer
Sponsor: Chinese University of Hong Kong

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SFVRC_Protocol_20180727 v.3 
 
Institute of Digestive Disease 
Department of Medicine and Therapeutics 
Faculty of Medicine 
The Chinese University of Hong Kong 
 
Study Protocol 
 
Study Title 
Comparison of second forward view examination and conventional withdrawal 
examination in the right colon on polyp detection in screening and surveillance 
colonoscopies: A randomized controlled study (SFVRC Study) 
 
Study registration: ClinicalTrials.gov (NCT03121495) 
 
Protocol date / version: SFVRC_Protocol_20180727 v.3 
 
 
 

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SFVRC_Protocol_20180727 v.3 
 
Principal Investigator 
Dr. Raymond S.Y. Tang, Department of Medicine and Therapeutics, CUHK 
 
Co-Investigators 
Dr. John C.T. Wong, Department of Medicine and Therapeutics, CUHK 
Dr. Moe Kyaw, Department of Medicine and Therapeutics, CUHK 
Dr. Angeline O.S. Lo, Department of Medicine and Therapeutics, PWH 
Dr. Wing Yan Mak, Department of Medicine and Therapeutics, PWH 
Prof. Martin C.S. Wong, School of Public Health and Primary Care, CUHK 
Prof. James Y.W. Lau, Department of Surgery, CUHK 
Prof. Joseph J.Y. Sung, Department of Medicine and Therapeutics, CUHK 
Ms. Jessica Y.L. Ching, Department of Medicine and Therapeutics, CUHK 
 
 
 

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SFVRC_Protocol_20180727 v.3 
 
BACKGROUND 
 
 It is estimated that there are about 1.4 million patients with colorectal cancer 
(CRC) worldwide, with a rising trend in CRC incidence in many Asian Pacific countries 
[1]. In Hong Kong, colorectal cancer ranks first in cancer incidence and second in cancer 
mortality based on data from 2013 [2].  
 
 
 CRC is one of the most preventable cancers because its development in general 
follows an adenoma-carcinoma sequence [3,4]. Adenomas are considered precursor 
lesions for CRC. Recent guidelines from USA, Europe and Asia Pacific region 
recommend CRC screening for average-risk asymptomatic individuals starting at age 50 
[5-7].  Modalities such as guaiac-based fecal occult blood tests (gFOBT), fecal 
immunochemical tests (FIT), flexible sigmoidoscopy (FS), and colonoscopy are among 
the acceptable options for CRC screening [5-7].  
 
 
While early detection and removal of colorectal adenoma by screening 
colonoscopy with polypectomy reduce CRC incidence and mortality, interval cancers 
(cancers that develop after a colonoscopy and before the next scheduled colonoscopy) 
may still occur and were reported to account for up to 10.5% of CRC [8-9]. The 
protective effect of colonoscopy against cancer in the right colon has not been 
consistently demonstrated [9-12]. Interval CRC has been associated with proximal colon 
location, small lesion, flat lesion, missed lesion, inadequate examination, incomplete 
resection of lesion, tumor biology, and low adenoma detection rate (ADR) [12-15].  
 
 
High ADR (eg, ≥ 20%) has been associated with a reduced risk of interval CRC 
[14,15] . Methods that can improve polyp detection in the right colon such as retroflexed 
examination of the right colon, second forward view examination of the right colon, use 
of colonic fold flattening device, colonoscope with an increased field of view may 
potentially reduce the risk of interval CRC, but data is still limited [16-20]. Performance 
of a second forward view (SFV) examination of the right colon may be the easiest and 
safest from a practical standpoint when compared to other options (eg, additional training 
is often needed for retroflexed examination of the right colon since there may be a 
potentially higher risk of perforation in endoscopists not familiar with the technique, 
additional equipment is needed when using a colonic fold flattening device, or a 
colonoscope with an increased field of view). In a recent randomized control study 
comparing retroflexed examination and SFV examination in the right colon in patients 
undergoing screening or surveillance colonoscopy, high ADRs were achieved by both 
methods (47% in retroflexed group vs 46% in SFV group, p = 0.75) [17]. A recent single 
arm prospective cohort study of 280 male veteran patients in USA showed that additional 
adenomas were detected in 15.4% of the patients after a SFV examination of the right 
colon [18]. The overall ADR increased by 3.2% and the ADR for the right colon 
increased by 6.7% after SFV examination of the right colon [18]. 3.6% of the patients had 
a change in their screening / surveillance interval with the addition of findings on the 
SFV examination of the right colon [18]. Of note, the overall ADR in this cohort of male 
veteran patients was very high and up to 71.8% on conventional withdrawal exam [18]. It 
is unclear whether a SFV examination of the right colon would still be beneficial in 
populations with both males and females and a lower overall ADR (eg, closer to the 

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SFVRC_Protocol_20180727 v.3 
 
recommended colonoscopy quality indicator of an ADR of 20% by the American Society 
of Gastrointestinal Endoscopy). To date, there has been no dedicated randomized 
controlled study comparing the yield of SFV examination in the right colon to that of 
conventional withdrawal examination of the right colon on adenoma /polyp detection in 
patients undergoing screening and surveillance colonoscopies. Our current study aims to 
determine whether a routine SFV examination in the right colon can lead to an increase in 
adenoma / polyp detection when compared to conventional withdrawal examination in 
the right colon in both male and female patients undergoing screening and surveillance 
colonoscopies.   
 
 
HYPOTHESIS 
 
Performance of a SFV examination in the right colon can increase adenoma / 
polyp detection when compared to conventional withdrawal examination of the right 
colon in patients undergoing screening and surveillance colonoscopies. 
 
 
 
 
AIM 
 
To investigate the impact of a SFV examination in the right colon on the right-
sided and overall adenoma / polyp detection in patients undergoing screening and 
surveillance colonoscopies in a randomized controlled study.   
  
 
METHODOLOGY 
 
Study Design 
 
It is an international multi-centre randomized controlled study  
 
Setting 
 
Endoscopy centers in Prince of Wales Hospital, combined endoscopy unit in 
Alice Ho Miu Ling Nethersole Hospital, and partner institutes of Asia-Pacific Working 
Group on Colorectal Cancer.  
 
Study Population 
The study protocol, risks and benefits of procedures, and informed consent would be 
discussed either in a pre-colonoscopy clinic visit or on the day of scheduled colonoscopy 
procedure at two endoscopy centres in Prince of Wales Hospital and combined 
endoscopy unit in Alice Ho Miu Ling Nethersole Hospital, and partner institutes of Asia-
Pacific Working Group on Colorectal Cancer based on the local institutional guidelines. 
After informed consent form is signed by the patient, patient will be enrolled into the 
study, with study randomization conducted on the day of procedure (see endoscopic 
procedure description below). 
 
Eligibility 

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Inclusion Criteria 
 Patients undergoing colonoscopy for CRC screening or polyp surveillance 
 Age 50 - 75 years 
 Written informed consent available 
 
Exclusion Criteria 
 Contraindications for endoscopy due to comorbidities 
 Unable to provide written informed consent 
 Personal history of prior resection of any portion of the colon, familial polyposis 
syndrome, inflammatory bowel disease 
 Patients with incomplete colonoscopy (i.e, inability to achieve cecal intubation), a 
Boston Bowel Preparation Scale (BBPS) score of 0 in either right colon, 
transverse colon, or left colon at the time of colonoscopy 
 Known history of coagulopathy and thrombocytopenia 
 Pregnant patients 
 
 
Study Flow 
 
Patients who fulfill inclusion criteria and sign informed consent form for the study 
will be assessed for the followings: 
 Demographics: age, gender, height, weight 
 Clinical Conditions: indication for colonoscopy, family history of CRC, personal 
history of colonic polyp, history of prior CRC screening, comorbidities (eg,  
diabetes, etc), smoking history, use of antiplatelets and antithrombotic 
medications 
 
Standard colonoscopy will be performed.  The only intervention in the study is the 
SFV in the right colon. The additional risk of SFV should be minimal and similar to 
standard colonoscopy since it does not involve a new endoscopic skill or new equipment. 
Patients’ vital signs will be monitored during colonoscopy.  Data such as cecal intubation 
time, total procedure withdrawal time, the size, morphology, and location of each polyp, 
bowel preparation quality assessment by BBPS, additional withdrawal time for the SFV 
in the right colon, presence of immediate complications such as perforation, bleeding, 
hypotension, etc and final histology of the removed polyps will be collected. 
 
After colonoscopy, patients will be monitored for any immediate complications. If 
no sign of immediate complication is detected, patient will be discharged according to 
standard discharge protocol for sedated procedure. Oral intake will be resumed with diet 
advancement as tolerated after discharge.  Patients will be given a designated telephone 
line for post-colonoscopy adverse events reporting and follow up during office hours 
within 30 days.  They will be instructed to attend the nearby Accident and Emergency 
Department for serious adverse events out of office hours.  All information about post-
colonoscopy serious adverse events will be retrieved from hospital record system on day 
30.  
 

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Patients will be followed up at their original clinic after colonoscopy.  The 
interval for next screening or surveillance colonoscopy will be determined based on 
findings of colonoscopy, number and histology of polyp removed during colonoscopy, 
patient’s clinical and family history accordingly to regional and international guidelines 
[5].  This follow up is not the study procedure but standard care. 
 
 
Endoscopic Procedures 
 
   Colonoscopy will be performed by investigators in their standard sessions. 
Olympus (Tokyo, Japan) high definition colonoscopes will be used in this study. Narrow 
band imaging (NBI), an image enhanced function on the endoscope, may be used for 
characterization of an identified polyp at the discretion of the endoscopist but not 
routinely for polyp detection during entire examination. In addition, chromoendoscopy 
can be used when sessile serrated adenoma is suspected. Conscious sedation with 
intravenous administration of midazolam and pethidine would be used during the 
procedure with regular monitoring of vital signs. A digital rectal (PR) examination will 
be performed before insertion of the endoscope. The colonoscope will be passed to 
cecum. A colonoscopy would be considered incomplete if cecal intubation cannot be 
achieved. Distal attachment (also known as a cap or hood) would not be used routinely 
during colonoscopy to enhance colonic fold flattening / exposure.  
 
Standard Colonoscopy Procedure (Conventional group) 
 
The colonoscope will then be withdrawn from the cecum with irrigation and 
aspiration of any residual colonic contents for careful examination of the colonic mucosa 
for polyps. During the initial colonoscope withdrawal from cecum to hepatic flexure (ie, 
the first forward view examination of the right colon), polyps detected in the right colon 
(ie, cecum and ascending colon) will be removed and sent for histopathological 
examination. Once the colonoscope is withdrawn to the level of hepatic flexure, patients 
will be randomized to either a SFV examination of the right colon, or continuation of the 
conventional colonoscope withdrawal for examination of colonic mucosa for polyps. In 
the conventional group, colonoscope withdrawal will be continued from hepatic flexure 
to rectum after randomization. Examination of colonic mucosa for polyps from hepatic 
flexure to rectum will be performed per standard of care. Polyps detected in these areas 
will be removed and sent for histopathological examination accordingly. Risks of 
colonoscopy such as perforation, bleeding, or infection were reported to be less than 1%.      
 
 
Second Forward View Colonoscopy Procedure (SFV group) 
 
During the initial colonoscope withdrawal from cecum to hepatic flexure (ie, the 
first forward view examination of the right colon), polyps detected in the right colon (ie, 
cecum and ascending colon) will be removed and sent for histopathological examination. 
Once the colonoscope is withdrawn to the level of hepatic flexure, patients will be 
randomized to either a SFV examination of the right colon, or continuation of the 
conventional colonoscope withdrawal for examination of colonic mucosa for polyps. For 
the SFV group, the colonoscope will be advanced to the cecum again when hepatic 
flexure was reached the first time, where a SFV examination of the right colon will be 

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SFVRC_Protocol_20180727 v.3 
 
performed. Additional polyps removed in the right colon during the SFV examination 
will be sent for histopathological examination in separate specimen containers to avoid 
being confused with the polyps removed during the first forward view examination of the 
right colon. Examination of colonic mucosa for polyps from hepatic flexure to rectum 
will follow standard practice.  
 
 
The risk of harm or discomfort of the second forward view examination of the 
right colon is similar to the risks of standard colonoscopy (less than 1% chance of 
perforation, bleeding, etc) because it does not involve a new endoscopic skill or new 
equipment. Based on local data at the Prince of Wales Hospital, the second forward view 
examination of right colon takes about an additional 2 minutes. No additional sedation 
medication was needed for the added time based on the local data.   
 
Randomization Method 
 
Block randomization generated by a computer program will be used at study site. 
Randomization will be in 1:1 ratio. 
 
 
 
OUTCOME MEASURES 
 
Primary Outcomes 
1) Per-patient ADR in the right colon in each group. For the SFV group, it is defined 
as the number of patients with at least 1 adenoma identified in the right colon on 
either the first or second examination of the right colon divided by the total 
number of patients in the SFV group. Thus, if a patient has at least 1 adenoma 
detected on both the first examination and the second examination of the right 
colon, then this patient will be counted once only. For the conventional group, it 
is defined as the number of patients with at least 1 adenoma identified in the right 
colon on the conventional withdrawal examination of the right colon divided by 
the total number of patients in the conventional withdrawal group. 
 
 
Secondary Outcomes 
1) Increase in per-patient ADR in the right colon in the SFV group.  
 It is defined as the difference between the new ADR in the right colon 
after the first examination and SFV (again, if a patient has at least 1 
adenoma detected on both the first examination and the second 
examination of the right colon, then this patient will be counted once only) 
and the ADR in the right colon after the first examination.   
2) Overall ADR for the entire colon in each group.  
 For the SFV group, it is defined as the number of patients with at least 1 
adenoma identified on either the second examination of the right colon or 
on the first examination of the right + examination from hepatic flexure to 
rectum, divided by the total number of patients in the SFV group. Thus, if 
a patient has at least 1 adenoma detected on both the first examination and 

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SFVRC_Protocol_20180727 v.3 
 
the second examination of the right colon, then this patient will be counted 
once only. For the conventional group, it is defined as the number of 
patients with at least 1 adenoma identified in the whole colon on the 
conventional withdrawal examination divided by the total number of 
patients in the conventional withdrawal group. 
3) The number of patients with at least 1 additional adenoma detected in right colon 
in the SFV group 
4) Adverse events during colonoscopy and up to 30 days post colonoscopy (eg, 
perforation, bleeding, etc)  
5) Total number of adenomas found on the first and second examinations of the right 
colon in the SFV group, and that on the examination of the right colon in the 
conventional group 
6) Total number of polyps (all pathological type) found on the first and second 
examinations of the right colon in the SFV group, and that on the examination of 
the right colon in the conventional group 
 
 
Bowel preparation quality assessment: 
 
Endoscopists will rate the quality of bowel preparation using the Boston bowel 
preparation scale (BBPS), a quantitative scale that assesses bowel preparation after all 
cleansing maneuvers are completed by the endoscopist [21]. A 4-point scoring system 
will be used to rate the following three main regions of the colon: right colon (ie, cecum, 
ascending colon), transverse colon (ie, hepatic flexure, transverse colon, splenic flexure), 
and left colon (ie, descending colon, sigmoid, rectum).  
Figure 1: A, Segment score 0, unprepared colon segment with mucosa not seen because 
of solid stool that cannot be cleared. B, Segment score 1, portion of mucosa of the colon 
segment seen, but other areas of the colon segment not well seen because of staining, 
residual stool, and/or opaque liquid. C, Segment score 2, minor amount of residual 
staining, small fragments of stool and/or opaque liquid, but mucosa of colon segment 
seen well. D, Segment score 3, entire mucosa of colon segment seen well with no residual 
staining, small fragments of stool and/or opaque liquid [21]. Therefore, the maximum 
BBPS score for a perfectly clean colon without any residual liquid is 9, and the minimum 
BBPS score for an unprepared colon is 0. 
 
 
 
Figure 1: (reference 21) 

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SFVRC_Protocol_20180727 v.3 
 
  
 
 
SAMPLE SIZE CALCULATION 
 
Based on an ADR in the right colon of 16.0% from a screening colonoscopy 
cohort in Hong Kong, and assuming a SFV examination of the right colon would give a 
6.7% increase in ADR in the right colon [18], we would need 502 patients per study 
group (ie, a total of 1004 patients for the study) in order to give a power of 80% at a type 
1 error of 5%.   
 
 
 
STATISTICAL ANALYSIS 
 
Categorical variables will be analyzed using chi-square test or Fisher’s exact test. 
Continuous variables will be analyzed using Student’s t-test or Mann-Whitney U test. P < 
0.05 is considered to be statistically significant. 
  
 
TIME TABLE OF WORK 
 
The ethics committee’s approval of the study will be sought. The study will 
commence in November / December 2016 upon ethics committee’s approval. The 
expected project duration is 24 months. 
 
 
DATA HANDLING AND DISSEMINATION OF INFORMATION 
 
All data obtained from the study will be kept confidential and be available only to 
personnel involved in the study and patient care. Case report forms and other documents 
will be kept in designated area of the Institute of Digestive Disease and retained for 7 
years after study completion. The results of this study will be presented in scientific 
meetings and medical journals. 
 

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DISCLOSURE 
 
The study would be conducted in compliance with the Declaration of Helsinki. 
 
 
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