A Pilot Randomized Trial of Polypectomy Techniques for 4-6 mm Colonic Polyps
Condition: Colon Polyps
MeSH terms: Polyps; Colonic Polyps
Study type: Interventional

Summary: 
      Complete polypectomy is one of the major factors for effectiveness of colonoscopy to prevent
      colon cancer. Given the prevalence of the 4-6 mm polyp, and the concern about interval
      cancers at polypectomy sites, there is a clear and significant need to determine which
      technique(s) are most appropriate for clinical practice. This study was to compare the three
      commonly used polypectomy techniques in terms of efficacy and efficiency.
    

Detailed description: 
      Colonoscopic polypectomy is one of the most commonly performed procedures in the United
      States. Despite the frequency with which polypectomy is performed, there is a remarkable
      absence of data regarding which polypectomy techniques most effectively remove polyps and
      minimize complications. As a result, polypectomy practice is based on the observational
      experience of experts and is how it is taught by attending physicians in fellowship training
      programs. It is not surprising therefore, that polypectomy practice is not consistent across
      the U.S., particularly for polyps in the 4-6 mm range, with 19% of endoscopists using cold
      forceps, 21% using hot forceps, 31% using a hot snare, 15% using a cold snare, and the
      remainder using a combination of these techniques.

      The effectiveness of colonoscopy in the prevention of colorectal cancer (CRC) depends on
      polypectomy; most polyps removed during colonoscopy are < 1 cm in size. Because of their
      greater prevalence relative to larger polyps, polyps < 1 cm are responsible for most cases of
      post-polypectomy bleeding (even though the absolute risk is higher with larger polyps).
      Perhaps more concerning, several studies of surveillance colonoscopy have reported finding
      CRC within a few years of a complete colonoscopy. Nearly 30% of these cancers have occurred
      in colonic segments where prior polypectomy was performed, suggesting that incomplete removal
      may be responsible for the recurrence of neoplasia; in more than half of these cases, the
      initial polyp removed was 1 cm or less in size. Unfortunately, these studies are limited
      because the precise location of the polypectomy site relative to the subsequent cancer is
      uncertain.

      Given the prevalence of the 4-6 mm polyp, the variation in polypectomy technique among
      endoscopists, and the concern about interval cancers at polypectomy sites, there is a clear
      and significant need to determine which technique(s) are most appropriate for clinical
      practice in terms of having the lowest risk for recurrent neoplasia and for major adverse
      effects (major bleeding, perforation).

      The goal of this trial is to determine the superior method for polypectomy [cold biopsy
      forceps (CF), cold snare (CS), or hot snare (HS)] in the removal of adenomatous colonic
      polyps that are 4-6 mm in maximal diameter for the subsequent risk of recurrent neoplasia at
      the polypectomy site. A randomized trial comparing these three polypectomy techniques for the
      outcome of recurrent neoplasia at the polypectomy site requires at least 700 persons per
      group (at least 2100 persons total). (A trial powered to compare complication rates would
      require a sample size that is an order of magnitude greater than this and is beyond the
      feasibility and scope of both pilot and definitive trials.) Further, patients would need to
      undergo 3- or 5-year surveillance colonoscopy, which requires a research infrastructure to
      ensure complete and accurate data collection. Before embarking on this large-scale trial to
      examine effectiveness of polypectomy techniques, we must first demonstrate feasibility of
      conducting such a trial and determine the time frame, sampling frame, and resources required.

      The specific aim of this proposal is to conduct a pilot randomized trial to establish:

        1. the feasibility of conducting a definitive, single-institution, multi-site clinical
           trial comparing the three modalities for removing adenomatous colonic polyps 4-6 mm. The
           processes that will be assessed are patient enrollment, recruitment, exclusion, and
           determination of final eligibility for the trial.

        2. the numbers of patients at each site (IU Hospital, Wishard Memorial Hospital/Eskenazi
           Health Hospital) who would be candidates for the larger, definitive study (This
           information will help estimate the time line and resources required for the definitive
           study).

        3. the proportions of recruited patients that fall into the 3- and 5-year surveillance
           groups (or other surveillance interval, along with the reason(s) for the interval).

      Hypotheses:

        1. A single-institution, three-site clinical trial is feasible: patients can be recruited
           and enrolled as potential subjects; final eligibility based on endoscopic and
           histological findings can be established within a week of enrollment.

        2. Investigators can identify the number of patients at each site who would be eligible for
           participation in a larger, more definitive study, from all patients undergoing
           colonoscopy. Investigators can establish refusal and exclusion rates. (Knowing both
           rates is necessary for planning the larger study.)

        3. The proportion of recruited patients in the 5-year surveillance group is approximately
           80% of all persons with neoplasia; the remaining 20% comprise the 3-year surveillance
           group.

      MATERIALS AND METHODS:

      The investigators conducted an randomized controlled trial (RCT) comparing polypectomy using
      CF, CS and HS. This trial was approved by the Institutional Review Board at Indiana
      University on March 6, 2008. It was conducted at three endoscopy units staffed by Indiana
      University Medical Center Gastroenterology faculty: Indiana University Hospital, Springmill
      endoscopy center and Eskenazi Health Hospital. Patients were recruited between September 2009
      and May 2013 and were followed with surveillance colonoscopy until October 2019. Sample size
      for the study was estimated based on the primary outcome of recurrent neoplasia at the
      polypectomy site at surveillance.

      Outpatients between ages 18- and 70 years undergoing outpatient screening, surveillance, or
      diagnostic colonoscopy and able to provide informed consent were eligible. Eligible patients
      presenting for colonoscopy, at 1 of 3 endoscopy units, from July 2009 to May 2013 were
      invited to participate in the study by research coordinators (RC).

      Colonoscopy was performed in standard fashion with Olympus 180 series colonoscopes. If the
      subject was found to have ≥1 adenomatous colon polyps (as predicted by endoscopist) 4-6 mm in
      size with Paris morphology of types I or Paris morphology IIa in the colon, randomization to
      one of three polypectomy methods was done in a 1:1:1 ratio.

      The following parameters for each study polyp (SP) were recorded: a) location, b) size, c)
      morphology (flat, sessile, or pedunculated), d) method of removal and e) pathology. For CF
      polypectomy, standard-sized radial jaw 4 biopsy forceps with a 2.8 mm needle were used and
      the number of bites for complete polypectomy was recorded. Polypectomy time was measured from
      time of appearance of forceps through the endoscope channel to polyp retrieval. For CS and HS
      polypectomy, 11 mm snares were used and the number of times the snare was used to complete
      the polypectomy was recorded. The size of the polyps was assessed using the span of the open
      radial jaw 4 forceps (7 mm) and the diameter of the snare catheter (2.5 mm) or the open snare
      diameter (11 mm). For any single patient, up to 5 SPs were removed under research protocol.
      HS polypectomy was performed using monopolar forced coagulation current, wattage range 18-20.
      There was no limit to the non-study polyps (NSP) resected.

      The time to perform CS polypectomy was recorded from the time of appearance of snare through
      endoscope channel to polyp retrieval or the determination that the polyp was not retrievable.
      For HS, time was recorded from initiation of cautery set up to polyp retrieval or the
      determination that the polyp was not retrievable. For any single patient all SPs were removed
      using the same technique. Patients with non-neoplastic polyps were excluded post hoc from the
      analytical sample. Patients were also excluded post randomization if the assigned polypectomy
      method could not be used or if additional methods were required.

      Following polyp resection and retrieval, 2-5 ml of tattoo ink (SPOTⓇ Ex stain) was injected
      1-2 cm to the left and proximal to the polypectomy site. The surveillance interval was
      determined according to guidelines as follows: a) For 1-2 tubular adenomas (TA), 5-10 years;
      b) For 3 or more TAs, 3 years; c) For a TA >= 1 cm, a polyp with villous histology, or one
      with high-grade dysplasia, 3 years; d) For a large sessile polyp removed piecemeal, 3-6
      months.

      During surveillance colonoscopy, the previous polypectomy site was examined. Adequacy of
      polypectomy was determined by absence of recurrent adenoma tissue. Biopsy of the previous
      polypectomy site was not required unless neoplasia recurrence was suspected based on visual
      inspection.

      Data were collected using standardized data collection forms, and the information was
      transferred to an Excel spreadsheet (Version 16) for analysis.
    

Intervention name(s): Cold forceps; Cold snare; Hot snare
Intervention type(s): Procedure; Procedure; Procedure
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: There were 3 arms: cold forceps, cold snare, hot snare. Randomization was computer generated. Subjects were assigned to one of the 3 arms. Up to 5 study polyps were removed under research protocol from each subject using the same technique
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: polypectomy; cold snare; hot snare; cold forceps