The Cap-Assisted Resection Margin Assessment (CARMA) Technique After Polyp Resection: a Prospective Feasibility Study of a "Novel" Approach to Reduce Polyp Recurrence
Phase: NA
Conditions: Colonic Polyp, Colonic Sessile Serrated Lesion
Sponsor: Princess Alexandra Hospital, Brisbane, Australia

 
 
 
 
 
 
 
STUDY PROTOCOL 
 
 
 
The Cap-Assisted Resection Margin Assessment (CARMA) technique after polyp resection: a 
prospective feasibility study of a “novel” approach to reduce polyp recurrence 
 
 
 
Document date: 14 October 2021 
NCT number: not yet assigned 
 
 
 
 
 
 

 
 
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PROJECT TEAM ROLES AND RESPONSIBILITIES 
Principle Investigator:  
Dr Alexander Huelsen Katz, Gastroenterologist, Department of Gastroenterology and Hepatology, 
Princess Alexandra Hospital 
Additional Investigators:  
Dr Zaki Hamarneh, Gastroenterologist, Department of Gastroenterology and Hepatology, Princess 
Alexandra Hospital 
Dr Prabha Selvanathan, Gastroenterology Principal House Officer, Department of Gastroenterology 
and Hepatology, Princess Alexandra Hospital 
Other Collaborators:  
Dr Jennifer Borowsky, Anatomical Pathologist, Department of Anatomical Pathology, Pathology 
Queensland, Princess Alexandra Hospital  
Dr Caroline Cooper, Anatomical Pathologist, Department of Anatomical Pathology, Pathology 
Queensland, Princess Alexandra Hospital 
Research Site: Princess Alexandra Hospital 
 
RESOURCES 
No additional resources or funding are required for this observational study.  
 
BACKGROUND 
Colorectal cancer forms 11 per cent of new cancer diagnoses in Australia each year and contributes 
to 11 per cent of cancer-related deaths annually (1). Colonoscopic removal of polyps is an important 
and well-established tool in the prevention of colorectal cancers (2-5). However, high polyp 
recurrence rates after endoscopic resection, with resultant development of interval cancers, 
remains a problem (6-16). In fact, some studies report polyp recurrence rates as high as 48 per cent, 
and post-colonoscopy interval cancers may account for up to 27 per cent of all colorectal cancers 
(6-16). This most commonly stems from unrecognised incomplete polyp resection, especially at the 
margin of the resection site, with recent studies finding residual adenoma in up to 13 per cent of 
rim biopsies after removal of small polyps (12-13). This risk is seen across all types of polyps and all 
methods of polyp resection, though factors such as larger polyp size and sessile serrated lesions 
have been associated with a higher risk of recurrence (13). Studies to date have also found 
significant variability in rates of achieving clear margins between different endoscopists (12,17) 

 
 
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Thus, a standardised endoscopic technique is needed that will allow endoscopists to consistently 
achieve a clear margin of resection, independent of the method of polyp resection used. This should 
reduce the recurrence rate of polyps in general, as well as reducing the heterogeneity of polyp 
recurrence rates between endoscopists, leading to an overall reduced risk of interval cancers.  
We believe the Cap Assisted Resection Margin Assessment (CARMA) technique will address this 
problem. This novel technique focuses on a standardised assessment of the resection margin after 
endoscopic polypectomy utilising available standard high-definition video endoscopes with imaging 
features including narrow band imaging (NBI) and magnification endoscopy. We hypothesise that 
normal colonic mucosa can be identified at the resection margin and differentiated from residual 
polyp tissue with this technique, thus allowing confirmation of a complete polyp resection.  
This prospective study aims to evaluate the CARMA technique, primarily looking at the rate of 
achieving a clear resection margin. Secondary outcomes that will be examined include sensitivity 
and specificity of the CARMA technique for residual polyp detection, frequency of residual polyp 
prior to use of the CARMA technique, time required for CARMA technique assessment, incomplete 
resection rate with the CARMA technique, the effect of hot and cold snare use on rates of achieving 
clear resection margins in polyps larger than 10mm, the effect of hot and cold snare use on rates of 
polyp recurrence, and the effect of polyp size on recurrence rates.  
We expect that the CARMA technique will be effective in confirming a clear resection margin 
(without residual polyp tissue).  
 
PROJECT DESIGN 
Research project setting 
This study will be conducted at a single centre, Princess Alexandra Hospital. Procedures will be 
performed by up to three endoscopists at this study centre.  
Methodological approach 
This study aims to evaluate the use of the CARMA technique for the endoscopic resection of 60-100 
polyps. In order to assess the applicability of this technique to polyps of various types and sizes, this 
will include polyps < 10mm (conventional adenomas or sessile serrated adenomas), sessile serrated 
adenomas > 10mm and conventional adenomas > 10mm.  
All colonoscopies will be performed using high-definition video colonoscopes with distal cap 
attachment. The distal cap attachment is made from clear silicone and extends 2-4mm beyond the 
distal endoscope tip which includes the camera chip. It serves as a space holder between the camera 
chip and the mucosa allowing a consistent in focus assessment of the area of interest.    
1) Initial assessment 

 
 
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Polyps will first be resected using standard resection techniques; this forms the control group of the 
study. Polyps < 10mm will be resected with cold snare without lifting. Sessile serrated adenomas > 
10mm will undergo piecemeal resection with cold snare after lifting. Conventional adenomas > 
10mm will be resected either with hot or cold snare, using lifting and single (“en bloc”) resection or 
piecemeal resection technique, at the endoscopist’s discretion. Mucosal lifting will be performed 
with a standard endoscopic needle injector and a standard solution of gelofusine, methylene blue 
and adrenaline 1:100 000 which is injected into the submucosal space underneath the lesion to 
reduce thermal or mechanical injury to the deeper tissue layers during resection.  
Once standard polyp resection and assessment of the polypectomy site without magnification is 
completed, the CARMA technique will be applied; this forms the intervention group of the study. 
This will involve an assessment of the entire polypectomy margin using cap assisted magnification 
endoscopy with the ability to also use NBI (at the endoscopist’s discretion) and documentation of 
any residual polyp noted. If residual polyp is noted, the scope channel will be flushed and cleared, 
and the abnormal margin will be resected with a cold snare, with the sample collected in a separate 
specimen pot labelled “residual margin”. Once this is complete, the scope channel will again be 
flushed and cleared. A 2-3mm safety margin of the entire polypectomy rim will be resected, with 
this sample collected in a separate specimen pot labelled “normal margin”. A single tattoo may be 
placed to mark the polypectomy site, to allow for accurate identification of the site when evaluating 
for recurrence at the time of re-assessment.  
2) Follow-up assessment 
Patients will undergo repeat colonoscopy as per national colonoscopic polyp surveillance guidelines 
at which time we will also re-assess for polyp recurrence. At the time of repeat colonoscopy, a 
picture and, if needed, a biopsy at the polypectomy site will be used to confirm clearance. Any 
residual polyp will be resected as per standard colonoscopy practice.   
Participants 
This study aims to evaluate the resection of 60-100 polyps, with a maximum of two polyps evaluated 
from each individual patient. Thus, it is expected that 50-60 participants will be enrolled in this trial. 
The study aims to assess 20 polyps < 10mm with resection not well-visualised (conventional 
adenomas or sessile serrated adenomas), 20-40 polyps that are > 10mm and endoscopically in 
keeping with sessile serrated adenomas, and 20-40 polyps that are > 10mm and endoscopically in 
keeping with conventional adenomas.  
Given that this is a pilot feasibility study, power calculations have not been used to determine the 
sample size. In discussion with our biostatistical support service, it was felt that observation of 60-
100 polypectomies would be adequate to demonstrate the ability of the CARMA technique to 
identify normal colonic mucosa without any residual polyp tissue at the resection margin.  
Inclusion criteria:  
- 
any polypectomy (though only a maximum of two polyps from one individual participant) 

 
 
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Exclusion criteria:  
- 
polyps less than 10mm which were resected under endoscopic view with a definite > 1mm 
clear margin 
- 
scar site recurrence polyps 
- 
polyps with endoscopic evidence of invasion 
- 
pedunculated polyps 
- 
pseudopolyps 
- 
participants who will not be available for follow up endoscopy 
Participant recruitment  
Participants for this study will be recruited from patients booked for routine diagnostic and 
surveillance colonoscopies at the study centre over a maximum 18-month period. The study 
endoscopists will review their booked procedure lists 1-2 weeks in advance and identify any patients 
booked for colonoscopies. Patients will be contacted by a member of the study team by phone at 
this stage to offer involvement in this study and address any initial queries they may have regarding 
the study. If the patient is agreeable to participating in the study, a copy of the Patient Information 
and Consent form (described below) will be posted to the patient to allow them time to peruse the 
information and discuss the study with their family or health care providers if required. On the day 
of the patient’s procedure, they will be reviewed by the member of the study team performing the 
procedure to confirm their willingness to participate in the study, address any queries or concerns, 
and complete the consent process if they choose to proceed.   
Provision of information to participants and consent  
Patients will have already received standard information materials regarding colonoscopy and 
preparation for their colonoscopy at the time that their procedure was booked, as is routine practice 
for all patients undergoing colonoscopy at the study centre. A Patient Information and Consent form 
has been created specifically for this study and will be provided to patients enrolling in this study, 
in addition to the study institution’s standard information materials and consent form for 
colonoscopy. In the study-specific Patient Information and Consent form, the CARMA technique and 
rationale for this study are outlined in simple language. The form explains that the initial polyp 
resection occurs using standard polypectomy techniques, and the CARMA technique is then applied 
to  meticulously examine the polypectomy margin to identify residual polyp tissue which can then 
be resected. The form outlines that the use of a cap, endoscopic magnification and tattoo placement 
are all accepted and established techniques for polypectomy, and all devices and materials to be 
used (snares, needles, tattoo, lift) are standard TGA-approved equipment already used at the study 
centre. The form also explains that the resection of any residual polyp found is a required and 
standard practice, and will not add additional risk to the procedure. Similarly, the form explains that 
the resection of a safety margin is in keeping with standard best practice to avoid polyp recurrence, 
and does not increase risk of bleeding, perforation, or other complications, nor does it significantly 
increase procedure time (with time required for the CARMA assessment and technique anticipated 

 
 
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to be less than one to two minutes). The form also explains that the requirement for repeat 
colonoscopy for assessment for polyp recurrence is standard practice and will be arranged as per 
national colonoscopy polyp surveillance guidelines. Participation in this study will be strictly 
voluntary, with patients having the option to withdraw from the study at any point. 
Research Activities 
The expected project duration is 18 months for the initial assessments and 5 years for the follow up 
assessments. Participant commitment to this study will only involve their initial colonoscopy and 
repeat colonoscopy for assessment for recurrence, the latter which will be scheduled as per national 
colonoscopy polyp surveillance guidelines.  
Outcome measures 
Primary outcome: 
- 
Rate of achieving a clear resection margin using the CARMA technique 
Secondary outcomes: 
- 
Sensitivity and specificity of the CARMA technique for residual polyp detection  
- 
Frequency of residual polyp without CARMA assessment (control group) 
- 
Incomplete resection rate with use of CARMA technique 
- 
Incomplete resection rate with use of the CARMA technique in polyps > 10mm with hot snare 
- 
Incomplete resection rate with use of the CARMA technique in polyps > 10mm with cold 
snare 
- 
Residual polyp rate after CARMA technique with hot snare 
- 
Residual polyp rate after CARMA technique with cold snare 
- 
Time required for application of the CARMA technique with < 10mm  
- 
Time required for application of the CARMA technique with > 10mm polyps 
- 
Polyp recurrence rate for < 10mm polyps 
- 
Polyp recurrence rate for > 10mm polyps 
Data Collection 
Patient information collected from their electronic medical record will include age, gender and 
indication for colonoscopy. Information collected at each participant’s initial colonoscopy, from the 
procedure report and histology results, will include number of polyps resected, polyp size, Paris and 
NICE classifications of polyps, polyp resection technique used (use of hot or cold snare, and use of 
lifting, en bloc resection or piecemeal resection), time taken for application of the CARMA 
assessment/technique, and histological diagnosis. Information collected at each participant’s repeat 
colonoscopy, from the procedure report and histology results, will include endoscopic impression 
of recurrence and histological confirmation of recurrence from scar biopsy.  
Data Management 

 
 
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A unique patient identification number will be assigned to each patient and will serve as the 
patient’s identifier for the study, with all patient data stored and collected under this number. De-
identified patient information and study data will be stored in a password-protected electronic data 
collection form (in a Microsoft Excel spreadsheet), which will be saved in the study centre’s 
computer system. Any hard copies of source notes containing identifiable medical information will 
be stored in a locked office area in the study centre. Identifying information will not be shared with 
any other institutions. Data protection and privacy regulations will be observed in capturing, 
forwarding, processing, and storing of patient data. Investigators and research staff will assure that 
patient anonymity is strictly maintained and that patient identifiers are protected from 
unauthorised parties. Study data will be stored for a maximum of 15 years, after which any 
electronic records will be deleted from the study centre’s computer system and any paper records 
will be destroyed through a confidential waste disposal service.  
Data Analysis 
The primary outcome of rate of achieving clear resection margins, as well as the secondary 
outcomes of frequency of residual polyp and incomplete resection rate, will be calculated using 
simple frequencies and percentages. Standard calculations will be used to determine the sensitivity 
and specificity of the CARMA technique for residual polyp detection. The effect of polyp size and 
resection technique on polyp recurrence rates, incomplete resection rates and time required for 
application of the CARMA technique will be analysed using an unpaired student’s t test.  
Data Linkage 
Nil applicable 
 
RESULTS, OUTCOMES AND FUTURE PLANS 
For patients enrolled in this study, as per usual practice at the study centre, a copy of their individual 
procedure report will be sent to the patient’s general practitioner and referring physician, and the 
patient can obtain the results of their colonoscopy through them. The patient can also request the 
discuss their procedure findings with the treating endoscopist immediately following their 
procedure if they wish, as is standard practice in the study centre’s endoscopy unit.  
With regards to the study findings, given the outcomes of the study will be analysed as grouped 
data, it is unlikely that the study findings will be meaningful or relevant to the individual patient’s 
clinical management; thus, there are no plans to return the research results to patients enrolled in 
the study. We aim to present the results of this study at national and international scientific 
meetings, and publish the analysed data in a peer-reviewed medical journal.  
There are no plans for further use of the data from this project once this study is complete.  
 

 
 
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