Adenoma Detection Rate With a New Pediatric Colonoscope With a Short Turn Radius (Pentax Retroview) Compared With a Standard Pentax Pediatric Colonoscope
Phase: NA
Conditions: Colonoscopy
Sponsor: Massachusetts General Hospital

 
 
 
 
 
 
 
 
 
 
 
 
Adenoma Detection Rate With a New Pediatric Colonoscope With a Short Turn Radius 
(Pentax Retroview) Compared With a Standard Pentax Pediatric Colonoscope 
 
 
Date of Document: 6/13/2014 

Page 1 of 6 
6/13/2014 
 
Adenoma detection rate with a new pediatric colonoscope with a short turn radius 
(Pentax Retroview) compared with a standard Pentax pediatric colonoscope. 
 
Norman S. Nishioka, MD 
Principal Investigator 
 
I. 
BACKGROUND AND SIGNIFICANCE 
 
Colonoscopy is widely thought to be the best screening test for detection of colorectal 
polyps and cancers. However, colonoscopy is not a perfect test and 6-11% of large polyps 
and higher numbers of smaller polyps may be missed during routine colonoscopy. The 
colon is a tube like organ but has many folds, and some polyps may be located proximal 
to (behind) these folds. One of the reasons polyps may be missed at colonoscopy is that a 
standard colonoscope cannot easily look behind colonic folds. The purpose of the study is 
to evaluate whether a new colonoscope that can easily bend to look behind these folds 
can detect more polyps than a standard colonoscope. As colorectal cancer is the second 
most common cause of cancer related mortality in the United States with over 50,000 
deaths reported annually, the impact of such new knowledge would be highly significant. 
One of the reasons for the development of these interval colon cancers is polyps missed 
at colonoscopy. Polyps that are located on the proximal side of haustral folds or flexures 
can be difficult to detect using a conventional forward-viewing colonoscope and may 
contribute to adenoma miss rates. It is plausible to hypothesize that the inability to 
efficiently look behind colonic folds may therefore contribute to the development of 
interval colon cancers. An improved colonoscope that finds more precancerous and 
cancerous lesions could potentially protect more patients from colon cancer and decrease 
interval cancer rates. 
 
Colorectal Cancer in the United States 
Of cancers that affect both men and women, colorectal cancer is the second leading cause 
of cancer death in the United States. In 2006, 139,000 patients were newly diagnosed 
with colorectal cancer, and 53,000 patients died from it. Colorectal cancer is thought to 
develop from precancerous polyps. 
 
Colorectal Cancer Screening, Adenoma Miss Rates and Interval Cancers 
The current standard of care to prevent colorectal cancer includes colonoscopy with 
removal of adenomatous polyps of the colon and rectum. There is evidence that screening 
with colonoscopy and removal of polyps decreases the incidence of colorectal cancer 
compared to reference populations that are not screened. Though colonoscopy is an 
important method to detect precancerous polyps, it is not perfect. Tandem colonoscopy 
studies (where patients undergo two colonoscopies, the second performed immediately 
following the first) indicate a >20% miss rate for adenomatous polyps at the first 
colonoscopy, even when the procedure is performed by skilled endoscopists. It is known 
that in patients who have a normal colonoscopy, a small number will develop 'interval' 
colorectal cancer prior to the next planned surveillance colonoscopy. In one study of 
patients with colorectal cancer, 5% had a reportedly normal colonoscopy in the three 
years prior to diagnosis. 
One of the reasons for the development of these interval colon cancers is polyps missed 
at colonoscopy. Polyps that are located on the proximal side of haustral folds or flexures 

Page 2 of 6 
6/13/2014 
 
can be difficult to detect using a conventional forward-viewing colonoscope and may 
contribute to adenoma miss rates. It is plausible to hypothesize that the inability to 
efficiently look behind colonic folds may therefore contribute to the development of 
interval colon cancers. 
 
Colonoscopes that Offer a Retrograde View: 
Recently, devices that allow visualization behind haustral folds with a retrograde view 
have been developed with the objective to discover lesions missed by conventional 
endoscopy. One such device is the Third Eye Retroscope, a retrograde viewing device 
that is advanced through the accessory channel of the endoscope. This device provides a 
simultaneous anterograde and retrograde view of the colon as the colonoscope is 
withdrawn. In a multi-center study utilizing this device 448 patients underwent two 
colonoscopies, once with the colonoscope plus the Third Eye and once by standard 
colonoscopy. The order was randomized. The second look by Third Eye colonoscope 
found more additional adenomas (46% more) than a second look by standard 
colonoscope (20% more). This suggests that the benefit of the Third Eye Retroscope 
exceeds the benefit of a second look endoscopy by a standard colonoscope. 
 
Performance and Retroflexion Properties of Colonoscopes 
In contrast to a retrograde viewing device that is passed through the colonoscope's 
accessory device, another option for allowing a retrograde view is a colonoscope whose 
tip is able to bend with a shorter turning radius than a traditional colonoscope. Current 
colonoscopes have a longer bending radius at the tip of the instrument which makes 
bending the tip backwards (retroflexion)to visualize the proximal aspect of colonic folds 
difficult.  
 
Kessler et al. showed that a prototype pediatric colonoscope with a short bending section 
at the tip was able to successfully retroflex at the cecum more often compared to one with 
a standard bending section, without compromising the ability to reach the cecum or need 
to change patient position. 
 
We plan to study a new pediatric colonoscope (Pentax Retroview) which has a short 
turning radius and can easily retroflex within the colon to provide both an anterograde 
and retrograde view, though not simultaneously. Pediatric colonoscopes are widely used 
for adult colonoscopy, and are more flexible than adult colonoscopes. We have studied 
the new colonoscope in anatomic bench models, and it led to higher detection rates of 
simulated polyps, especially those found behind folds. This study will compare the 
detection of precancerous and cancerous lesions utilizing the new colonoscope to that of 
a standard pediatric colonoscope with a standard bending section. We will measure the 
number of precancerous and cancerous lesions found at the colonoscopy. 
 
References 
Colorectal (Colon) Cancer. Centers for Disease Control and Prevention. 6 Jul 2010. 
Winawer SJ, Zauber AG, Ho MN, O'Brien MJ, Gottlieb LS, Sternberg SS, Waye JD, 
Schapiro M, Bond JH, Panish JF, et al. Prevention of colorectal cancer by colonoscopy 
polypectomy. The National Polyp Study Workgroup. N Engl J Med. 1993 Dec 30; 
329(27):1977-81. 
 

Page 3 of 6 
6/13/2014 
 
Rex DK, Cutler CS, Lemmel GT, Rahmani EY, Clark DW, Helper DJ, Lehman GA, 
Mark DG. Colonoscopic miss rates of adenomas determined by back-to-back 
colonoscopies. Gastroenterology. 1997 Jan; 112(1):24-28. 
 
Rex DK, Rahmani EY, Haseman JH, et al. Relative sensitivity of colonoscopy and 
barium enema for detection of colorectal cancer in clinical practice. Gastroenterology 
1997; 112: 17-23. 
 
Baxter N, Goldwasser M, Paszat L, Saskin R, Urbach D, Rabeneck L. Association of 
Colonoscopy and Death Rates from Colorectal Cancer. Annals of Internal Medicine. 
2009 Jan; 1250(1): 1-8. 
 
Demarco DC, Odstreil E, et al. Impact of experience with a retrograde-viewing device on 
adenoma detection rates and withdrawal times during colonoscopy : the Third Eye 
Retroscope study group. Gastrointestinal Endoscopy. 2010 Mar; 71(3): 542-5 
 
Kessler WR, Rex DK. Impact of bending section length on insertion and retroflexion 
properties of pediatric and adult colonoscopes. Am J Gastroenterology. 2005 Jun; 100 
(6):1290-5. 
 
Waye JD, Heigh, JH et al. A retrograde viewing device improves detection of adenoma in 
the colon: a prospective efficacy evaluation (with videos). Gastrointestinal Endoscopy. 
2010 Mar; 71(3):551-6. 
 
II. 
SPECIFIC AIMS 
 
Objective: We would like to learn whether the new colonoscope that provides both a 
traditional and a retrograde view (bending 180 degrees to look behind itself) of the colon 
can detect more polyps than a standard colonoscope that only provides a forward-facing 
view. We wish to effectively demonstrate the utility of the new colonoscope (Pentax 
Retroview Colonoscope) as the objective of this study is to determine polyp (adenoma) 
detection rates in human subjects undergoing colonoscopy for polyp surveillance. 
 
III. 
SUBJECT SELECTION 
 
Subjects will be recruited from patients already referred to the physician investigators for 
surveillance due to personal history of colon polyps found during colonoscopy done 3 or 
more years previously. This will allow for evaluation of the colonoscope in a population 
that requires surveillance colonoscopy. The physician investigators have a sufficiently 
large referral base for surveillance colonoscopy that will allow recruitment for this 
number of participants. The participants will be undergoing a colonoscopy by attending 
endoscopists, regardless of whether they enroll in the study or not. 
 
This is a multi-site study. 
 
IV. 
SUBJECT ENROLLMENT 
 

Page 4 of 6 
6/13/2014 
 
For those randomized to the new colonoscope, the colonoscope will provide a forward-
facing view of the colon during advancement to the cecum (standard of care). The scope 
will then be withdrawn all the way to the rectum and the colon will be inspected using the 
forward-facing view (standard of care). The colonoscope will then be re advanced to the 
cecum and be withdrawn using the retrograde view. 
 
For those randomized to the control arm, colonoscopy will be performed with a 
conventional colonoscope. During withdrawal in the control group, the colon will be 
inspected using the forward-facing view (standard of care). The colonoscope will then be 
re-advanced to the cecum and again withdrawn using the forward-facing view. 
 
Patients will be randomized equally to either the new colonoscope (Pentax Retroview) or 
the control arm with a standard pediatric colonoscope. A total of 300 subjects will be 
enrolled. 
 
V. 
STUDY PROCEDURES 
 
1. Patients with prior history of colon polyps (adenomas) are referred for surveillance 
colonoscopy (standard of care) due to personal history of colon polyps found during 
colonoscopy done 3 or more years previously 
2. The patients will undergo standard bowel preparation for colonoscopy (standard of 
care) 
3. Patients will be asked during routine pre-procedure examination for colonoscopy if 
they are interested in participating in the study 
3. Following consent, patients will be randomized to colonoscopy with either the new 
colonoscope or conventional colonoscope. 
4. Patients will undergo colonoscopy (standard of care). All colonoscopies will be 
performed by a GI attending.  
 
For those randomized to the new colonoscope, the colonoscope will provide a forward-
facing view of the colon during advancement to the cecum (standard of care). The scope 
will then be withdrawn all the way to the rectum and the colon will be inspected using the 
forward-facing view (standard of care). The colonoscope will then be re advanced to the 
cecum and be withdrawn using the retrograde view. In subjects that are randomized to the 
Retroview scope, the scope is advanced to cecum and then withdrawn to rectum in 
forward position. The subject is reintubated. At the cecum, scope is retroflexed and 
withdrawn till before hepatic flexure. Then straightened out, pulled through flexure and 
retroflexed again. The scope is withdrawn through transverse in retroflexed view until the 
rectum. There has been a 50 subject trial in which the withdrawal time was recorded and 
an additional 9.8 minutes were added to the total withdrawal time. It is unknown if there 
is additional risk in the retroflexed view. 
For those randomized to the control arm, colonoscopy will be performed with a 
conventional colonoscope. During withdrawal in the control group, the colon will be 
inspected using the forward-facing view (standard 
of care). The colonoscope will then be re-advanced to the cecum and again withdrawn 
using the forward-facing view. 

Page 5 of 6 
6/13/2014 
 
 
During colonoscopy, any polyps that are found will be removed and any cancers noted 
will be biopsied (standard of care). 300 patients will be recruited at each site (Stanford 
and MGH), and the number of precancerous lesions (polyps) and cancers found at 
colonoscopy utilizing the two different colonoscopes will be evaluated. The adenoma 
detection rate (ADR), the adenoma per colonoscopy (APC) rate and the adenoma miss 
rate (AMR) at first pass for the two colonoscopes will be calculated. 
 
The major endpoints are number of precancerous or cancerous lesions found during 
colonoscopy. We do not plan to terminate the study before enrollment has been met. The 
study will be terminated at the enrollment of 300 participants at each of the two sites. 
 
6. Data sources will include procedure report, patient's electronic medical record, 
pathology reports and demographic information. These will be recorded in a confidential 
manner with PHI de-identified. 
 
Inclusion Criteria:  
1. Ability to provide informed consent 
2. Adult men and women age 40 years old or older 
3. Colonoscopy patients with a history of adenomatous colorectal polyps and are 
returning for a follow up colonoscopy 3 yrs or more after their previous procedure 
Exclusion Criteria: 
1. Poor or fair bowel preparation 
2. Difficult first insertion of colonoscope 
3. Conserved status 
4. Familial polyposis 
5. Inflammatory bowel disease 
6. Pregnancy 
7. Active GI bleeding 
8. Prior colonic or rectal resection (colon not intact) 
9. Screening colonoscopy 
10. Colonoscopy done to evaluate symptoms like abdominal pain, diarrhea, constipation, 
change in bowel habit. 
 
 
 
 
VI. 
BIOSTATISTICAL ANALYSIS 
 
The primary endpoint is the adenoma detection rate (ADR) for the control and Retroview 
group. The ADR is the percentage of patients with at least one adenoma. The numbers 
will be compared using standard statistical analysis of proportions (e.g., 
http://www.ltcconline.net/greenl/courses/201/estimation/ciprop.htm). Both groups will be 
assumed to be normally distributed. Secondary endpoints will be the ADR for each pass 
of the colonoscope (i.e., the incremental adenoma pick-up rate), the overall polyp 
detection rate (adenomas and non-adenomas) and the mean number of adenomas 
identified per patient with polyps. We hypothesize that the Retroview colonoscope will 
detect additional adenomas at a rate of 30% compared to the a rate of 20% when using a 

Page 6 of 6 
6/13/2014 
 
conventional colonoscope.  Assuming a significance level of 5% and a power level of 
80%, 294 patients in each arm (total of 588 patients) would be required to demonstrate 
this improved performance.  
 
VII. 
RISKS AND DISCOMFORTS 
 
The risk of perforation of the colon during screening/surveillance colonoscopy with 
polypectomy is 1:1000. There is risk of bleeding following polypectomy, but bleeding is 
readily fixable. These risks would apply to the patients regardless of whether they choose 
to participate in the study or not. It is not anticipated that participation in this study will 
directly pose any psychological risks to the patient. 
 
VIII. 
POTENTIAL BENEFITS 
 
The potential benefits to study subjects will be an improved colonoscopy with fewer 
missed precancerous (polyps) and cancerous lesions. In addition, both arms of the study 
will benefit by a more thorough examination of the colon (second look colonoscopy), as 
data from numerous studies confirms that a second look increases the number of 
precancerous polyps that are detected at colonoscopy. Identification of an improved 
colonoscope may aid future patients who undergo screening and surveillance 
colonoscopy in order to prevent colorectal cancer. 
 
IX. 
MONITORING AND QUALITY ASSURANCE 
 
This study will be closely monitored by Dr. James Richter, Director of Quality Assurance 
for the MGH GI Unit and Dr. Nishioka, the Principal Investigator of this study. Dr. 
Richter oversees Quality Assurance for all gastrointestinal endoscopic procedures and Dr. 
Nishioka as the Principal Investigator of this trial, will be responsible for ensuring that 
the study is conducted according to the IRB-approved protocol and regulations, and for 
protecting the rights, safety and welfare of the subjects. Dr. Nishioka or another physician 
investigator will be responsible for obtaining informed consent from study participants. 
Dr. Nishioka will be responsible for reporting any adverse events to the IRB. In 
accordance with Partners Human Research Committee (PHRC) guidelines, adverse 
events will be reported to the PHRC along with appropriate forms within the required 
time frame.  Dr Nishioka is the principal investigator of this study and is directly 
responsible for the conduct of the study. 
 
This is a two site study. When 100 subjects have been enrolled at a site, de-identified 
study data will be jointly reviewed by the lead investigators at the two sites. Any serious 
adverse event will be reviewed by the two lead investigators within 48 hours. The two 
lead investigators will be responsible for determining whether the research should be 
altered or stopped. 
 
X. 
REFERENCES 
 
Embedded within the body of this document.