Effectiveness of Cold Biopsy Forceps With Pre-lift for Complete Resection of Colonic Polyps ≤7mm in Size
Condition: Colorectal Polyps
MeSH terms: Polyps; Colonic Polyps
Study type: Observational

Summary: 
      There is no consensus method for removal of diminutive (5mm) to small(6-9mm) colorectal
      polyps at colonoscopy. Neither the European Society of Gastrointestinal Endoscopy or the
      American Society of Gastrointestinal Endoscopy have guidelines for the removal of these
      polyps, despite the fact that around 90% of lesions removed by polypectomy at colonoscopy are
      diminutive to small.

      Multiple techniques are used for polyp removal, especially diminutive lesions. These include
      either forceps, both hot and cold, as well as snare with electrocautery or cold snare.
      Forceps utilises shearing force to grasp tissue and remove it, with the hot method passing a
      current through the grasper to essentially burn tissue. Snare is the use of a small metal
      loop placed and tightened at the base of polyps to cut through the tissue either straight
      away in a cold method or with electrocautery where a small current is passed through the loop
      to assist cutting through tissue. Surveys of Colonoscopists and Gastroenterologists in
      Australia and the United States show that the choice of method used for diminutive to small
      polyps is highly variable with cold snaring marginally favoured.Studies into polypectomy
      techniques are limited and it is clear that additional data and the review of polypectomy
      methods needs to be undertaken in order determine the optimal method for the removal of
      diminutive and small colorectal polyps.

      A technique is used at the Gloucestershire National Health Service (NHS) trust involving a
      submucosal pre injection with a standard solution then the use of cold forceps for removal of
      polyps ≤7mm. This appears to be both very safe and highly effective method for the removal of
      these lesions compared to other techniques. No formal published studies have been completed
      to evaluate this method at national and international levels. We propose a study to evaluate
      the effectiveness, safety and costs of this method.
    

Detailed description: 
      Hypothesis A pre injection and cold forceps technique for removal of polyps ≤ 7mm is safe and
      results in retrieval rates >98% with complete histological resection >90% of the time.

      Objectives

        1. Determine the histological complete resection rate (CRR) using a pre injection lift and
           cold forceps for polypectomy of polyps ≤7mm.

        2. Determine the number of bites required for complete visual resection of these polyps and
           the time taken from the beginning of pre injection needle insertion till complete
           resection.

        3. To determine the polyp retrieval rate of this method.

        4. To record any complications from this technique.

        5. To compare the CRR, number of biopsies for visual eradication, time taken, polyp
           retrieval rate and complication rate of this method to cold forceps alone and cold snare
           from previous studies.

      Methods

      Participants:

      Sample size 150 polyps, anticipated to be captured in between 75 and 100 patients based on an
      average of 2 polyps per patient. There is no published data on this polypectomy technique and
      there is limited data on other diminutive to small polypectomy techniques. Other comparative
      published studies looking at polypectomy techniques for diminutive to small polyps have had
      polyp numbers between fifty four and one hundred and seventeen.The sample size of 150 polyps
      is an approximation based on the fact that it is an achievable figure within the scope of the
      project and local clinical service which should yield a relatively narrow confidence
      interval.

      Colonoscopists 3 experienced Gastroenterologists (JA, TB, PD) working within the
      Gloucestershire NHS Trust, each having performed over 3000 colonoscopies. All
      Gastroenterologists are certified British Bowel Cancer Screening Program Colonoscopists. As
      the technique being studied is already well practiced within the trust the extra time
      required for each polyp included in the study is negligible.

      Pathologist All Polypectomy specimens and EMR tissue will be examined by an expert
      Gastrointestinal Pathologist (NS) who will be blinded to the patient and colonoscopist
      details when examining specimens.

      The additional work for the pathology department is negligible. It can be routine practice to
      take additional material for analysis if incomplete removal of the polyp is suspect. In the
      study all polyps will have this review. NS will provide consistency and also time to support
      us in this project.

      Course of Action:

        1. Patients will be consented to participate in the study prior to their procedure.
           Information regarding the study will be posted to the patient at least a week prior to
           their colonoscopy.

        2. If patient agrees to participate details including age, sex and indication for scope
           will be recorded. This data will be recorded with a patient study number. The patients
           will be otherwise anonymised.

        3. Data from each colonoscopy and polypectomy will be recorded, including polyp size,
           location, time for resection, bites required for complete visual resection (another
           study showed the median number of bites to be at 2 with range 1-5 ), overall withdrawal
           time and quality of bowel preparation at the time of the procedure. Any adverse events
           at the time of colonoscopy, polypectomy and EMR or at subsequent patient follow up 7
           days post procedure will be recorded prospectively on form A (Appendix 1) and also
           reported to the Research and Development team within 7 days of the Investigators
           becoming aware of the adverse event.

      3. All colonoscopies will be performed using Olympus 240 and 260 colonoscopes with magnetic
      endoscopic imaging and Narrow band imaging (NBI) available to the Colonoscopist if required.

      5. The equipment used for each polypectomy and Endomucosal resection (EMR) of polypectomy
      site will include the following.

        1. Needle for pre injection

        2. Pre injection mix will include 19 ml gelofusine, 1ml 1:10000 adrenaline and 1ml indigo
           carmine.

        3. Cold forceps with span of 6.8mm and capacity of 7.22mm3

        4. Olympus snare master 10mm snare.

           6. Any complications relating to the polypectomy will be recorded. 7. Polyps ≤7mm will
           be included in the study if deemed appropriate by the colonoscopist. Polyps may be
           considered inappropriate if polyp location or appearance is not suitable for the
           technique being studied.

           8. These polyps will be resected with cold forceps after pre injection into the
           submucosa. Data related to this resection will be recorded as noted above.

           9. The polypectomy site will then be resected with EMR using conventional snare method
           to ascertain if there is any residual polyp tissue. This is the only additional step to
           the polypectomy process which would not otherwise take place. The risk from this step of
           an adverse event to the patient would be significantly less than the risk of
           complication from a therapeutic Colonoscopy which is between 0.05 and 0.07%. A maximum
           of 3 polyps per patient will be included for study analysis in order to ensure both
           patient and colonoscopist time at procedure does not differ significantly from what it
           would normally.

           10. Both EMR specimen and resected polyp tissue will be sent for histopathological
           evaluation by single expert Gastrointestinal Histopathologist who has kindly agreed to
           review the extra EMR tissue in his own time.

           11. Recruited patients will be called one-week post colonoscopy to ensure they do not
           wish to withdraw from the study and they have had no concerns post their procedure.

           Adverse Events As mentioned above the risk of adverse events related to the polypectomy
           technique being studied or the EMR of residual tissue is minimal.

           All adverse events (or medical occurrence) will be recorded in data collection
           spreadsheets. Any events classified as 'serious adverse events' (SAE) will be reported
           to the Research and Development Unit (RSDU).

           The following criteria will be used to assess the relationship (causality) of the
           adverse event to the polypectomy technique and EMR performed

             1. None: - The adverse event is definitely not associated with the investigational
                technique being used.

             2. Possible: - A causal relationship is possible when the adverse event follows a
                reasonable temporal sequence from the application of the intervention, but could
                have been produced by the patient's clinical state or other modes of treatment
                being administered to the patient.

             3. Probable: - The causal relationship is probable when the adverse event follows a
                reasonable temporal sequence from the application of the investigational technique.
                This is likely if the adverse event cannot be explained by the known
                characteristics of the patient's clinical state

           Adverse events will be assessed by one of the investigators who are qualified
           Gastroenterologists and managed accordingly.

           The severity of adverse events will be recorded using the following criteria:

             1. Mild: - Symptom(s) barely noticeable to the patient or does not make the patient
                uncomfortable. The AE does not influence performance or functioning.

                Prescription drugs are not ordinarily needed for relief of symptom(s).

             2. Moderate: - Symptom(s) of a sufficient severity to make the patient uncomfortable
                or require endoscopic intervention or other treatments.

             3. Severe: - Symptom(s) of a sufficient severity to cause the patient severe
                discomfort requiring subsequent treatment or require major endoscopic intervention,
                hospitalisation or surgery.

           A serious adverse event (SAE) includes adverse events that result in death, require
           either inpatient hospitalization or the prolongation of hospitalization, are life
           threatening, result in a persistent or significant disability/incapacity. Other
           important medical events, based upon appropriate medical judgement, may be considered
           Serious Adverse Events if a trial participant's health is at risk and intervention is
           required to prevent an adverse outcome.

           Dr Alex di Mambro FRCP (Gloucestershire NHS Trust Gastroenterologist) will evaluate,
           report and assist in patient management should there be a SAE. In no other way has she
           been involved in study development or will she be involved during the course of the
           study.

           All reports of serious adverse events (SAE) will be recorded on the SAE form for this
           trial and forwarded immediately to the Research & Development Unit (RSDU). A copy of
           this form can be seen in the appendix 1. In the event of a SAE persisting greater then
           24 hours another form will be submitted to the RSDU. Also, in the case of a persisting
           SAE the time of event resolution, patient death or discharge a subsequent form will be
           completed and submitted.

           Data recording and statistical analysis: All data will be recorded prospectively in a
           Microsoft excel spread sheet by the chief investigator (SO) and statistical analysis
           completed with SPSS version 16. Based on a target sample size of 150 polyps with 90%
           success rate the calculated 95% confidence interval will be 84.5-94.2%.

           Data storage: The collected data will be kept secure within the department of
           Gastroenterology and not shared with uninvolved persons. The data will be anonymised and
           the excel sheet the data is collected on will be password protected and not available to
           other individuals not involved with the study. All recorded data will be destroyed by
           the end of calendar year 2017 or once the anonymised results have been presented and
           published which is expected to be by the end of calendar year 2015.

           Results It is anticipated that results of this study will be completed for abstract
           submission for United European Gastroenterology Week by May 2015. This meeting will be
           held in Europe in October 2015. We will aim to publish this data in an international
           Endoscopic journal by late 2015. Results will be made available to our Bowel Cancer
           screening nurses who will be able to disseminate these results to various Bowel Cancer
           support groups.

           Funding

           Researchers and Time allocation The chief investigator has time (20hr/week) allocated
           into current Gloucestershire NHS Trust contract for education and development.
           Development of this study, data recording/entry and generation of an academic paper will
           all be undertaken in this time.

           Professor Neil Shepherd, Pathologist for this project has agreed to undertake the
           additional work of EMR tissue review in his own time.

           Additional time for colonoscopists will be for EMR of polypectomy site that is
           considered negligible in the course of a standard colonoscopy.

           Equipment As explained in the methods section minimal additional pieces of equipment are
           needed compared to the standard colonoscopy. Snares for EMR of polypectomy site will
           only be additional should a snare not have already been required for the removal of
           larger polyps during the course of the colonoscopy.

           Olympus will kindly provide the additional snares for the study. All other equipment
           such as pre injection solution, pre injection needle and cold forceps would normally be
           used in the course of colonoscopy and polypectomy.
    

Intervention name(s): Cold forceps polypectomy with pre lift
Intervention type(s): Procedure
Intervention description(s): Polyps ≤7mm will be included in the study if deemed appropriate by the colonoscopist..
These polyps will be resected with cold forceps after pre injection into the submucosa with a few millilitres of pre injection solution (19 ml gelofusine, 1ml 1:10000 adrenaline and 1ml indigo carmine). Polyps are grasped with the cold forceps and pulled away from the rest of the colonic mucosa. Attempt will be made to remove polyps with single attempt with the forceps however several grasps may be required for complete visual resection of the polyp.
The polypectomy site and a 5mm rim of normal appearing tissue will then be resected with endomucosal resection (EMR) using conventional snare method. This is to ascertain if there is any residual polyp tissue.
Other intervention name(s): polypectomy
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Residents from within Gloucestershire, United Kingdom whom have been referred for a
        Colonoscopy through either.

          1. Bowel cancer screening program or outpatient referral

          2. Outpatient clinics

          3. Inpatient referral