Chromoendoscopy for Serrated Polyposis Syndrome (SERRADA)

March 25, 2018 updated by: Jorge Lopez Vicente, Hospital Universitario de Móstoles

Panchromoendoscopy for the Surveillance of Serrated Polyposis Syndrome, a Multicenter, Prospective and Randomized Trial.

Serrated polyposis syndrome (SPS) is the most common colorectal polyposis syndrome and is characterized by the combination of large and/or numerous serrated lesions (SLs) throughout the colorectum. SLs are classified into sessile serrated polyps (SSP) with or without dysplasia, hyperplastic polyps (HP) and traditional serrated adenomas (TSA). In 2010 the World Health Organization (WHO) defined this syndrome by any one of the following conditions: criterion I, at least 5 SLs proximal to the sigmoid colon with 2 or more of these being >10mm in size; criterion II, any SLs proximal to the sigmoid colon in a first-degree relative with SPS; criterion III, more than 20 SLs of any size distributed throughout the colon. It has been demonstrated that 11.8-28.5% of patients with SPS present with colorectal cancer (CRC) at diagnosis. Tandem colonoscopy studies have demonstrated that a significant number of lesions are missed during conventional colonoscopy. This finding is even more evident when focusing SLs where a 31% miss rate has been reported. SLs are often overlooked due to their typical appearance: flat morphology, similar colour to the surrounding mucosa, subtle and indistinctive borders. Chromoendoscopy (dye spraying onto the surface of the colon) enhances the detection of subtle and flat polyps in the colon. Until the date no studies have assessed the use of dye-based chromoendoscopy in SPS patients.

The aim of this trial was to evaluate the usefulness of panchromoendoscopy with indigo carmine for the detection of polyps in the colon in patients with SPS. Secondary aims were to estimate the SLs and adenoma miss rates in these patients.

Patients were randomized in a 1:1 distribution to one of the two arms of the study by a list of random numbers distributed by the coordinator center. After randomization, patients were submitted to tandem colonoscopies by the same endoscopist:

  • In group A (HR-WLE) the first inspection was on high-resolution white-light endoscopy from the cecum/ileo-colonic anastomosis to the rectum, followed by a second inspection also on HR-WLE.
  • In group B (HR-CE) the first inspection was on HR-WLE from the cecum/ileo-colonic anastomosis to the rectum, followed by a second inspection with panchromoendoscopy. For this, the lumen was sprayed in a segmental fashion using 0.4% indigo carmine delivered via a specially designed dye spray catheter (Olympus PW-5V1) or via the accessory channel with a 50cc syringe filled with indigo carmine and air. After allowing a few seconds for the dye to settle onto the mucosal surface, excess pools of indigo carmine were suctioned and the mucosa was then scrutinised.

Time to withdrawal from the cecum was measured using a stopwatch excluding time needed for polypectomy and biopsies.

Lesions detected during each inspection were described and then removed. Size (measured in comparison with an open biopsy forceps), morphology (using the Paris classification), location and polypectomy technique were recorded before removal. Histology was used as gold standard.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Serrated polyposis syndrome (SPS) is the most common colorectal polyposis syndrome and is characterized by the combination of large and/or numerous serrated lesions (SLs) throughout the colorectum. SLs are classified into sessile serrated polyps (SSP) with or without dysplasia, hyperplastic polyps (HP) and traditional serrated adenomas (TSA). In 2010 the World Health Organization (WHO) defined this syndrome by any one of the following conditions: criterion I, at least 5 SLs proximal to the sigmoid colon with 2 or more of these being >10mm in size; criterion II, any SLs proximal to the sigmoid colon in a first-degree relative with SPS; criterion III, more than 20 SLs of any size distributed throughout the colon. It has been demonstrated that 11.8-28.5% of patients with SPS present with colorectal cancer (CRC) at diagnosis. Tandem colonoscopy studies have demonstrated that a significant number of lesions are missed during conventional colonoscopy. This finding is even more evident when focusing SLs where a 31% miss rate has been reported. SLs are often overlooked due to their typical appearance: flat morphology, similar colour to the surrounding mucosa, subtle and indistinctive borders. Chromoendoscopy (dye spraying onto the surface of the colon) enhances the detection of subtle and flat polyps in the colon. Until the date no studies have assessed the use of dye-based chromoendoscopy in SPS patients.

The aim of this trial was to evaluate the usefulness of panchromoendoscopy with indigo carmine for the detection of polyps in the colon in patients with SPS. Secondary aims were to estimate the SLs and adenoma miss rates in these patients.

Patients were randomized in a 1:1 distribution to one of the two arms of the study by a list of random numbers distributed by the coordinator center. After randomization, patients were submitted to tandem colonoscopies by the same endoscopist:

  • In group A (HR-WLE) the first inspection was on high-resolution white-light endoscopy from the cecum/ileo-colonic anastomosis to the rectum, followed by a second inspection also on HR-WLE.
  • In group B (HR-CE) the first inspection was on HR-WLE from the cecum/ileo-colonic anastomosis to the rectum, followed by a second inspection with panchromoendoscopy. For this, the lumen was sprayed in a segmental fashion using 0.4% indigo carmine delivered via a specially designed dye spray catheter (Olympus PW-5V1) or via the accessory channel with a 50cc syringe filled with indigo carmine and air. After allowing a few seconds for the dye to settle onto the mucosal surface, excess pools of indigo carmine were suctioned and the mucosa was then scrutinised.

Time to withdrawal from the cecum was measured using a stopwatch excluding time needed for polypectomy and biopsies.

Lesions detected during each inspection were described and then removed. Size (measured in comparison with an open biopsy forceps), morphology (using the Paris classification), location and polypectomy technique were recorded before removal. Histology was used as gold standard. Biopsies were processed and stained using standard methods, and were subsequently evaluated by experienced gastrointestinal pathologists in each center according to Vienna criteria of gastrointestinal epithelial neoplasia. Serrated lesions were classified according to the WHO 2010 classification into hyperplastic polyps, sessile serrated polyps, and traditional serrated adenomas. Cytological dysplasia among serrated polyps was analyzed both as presence/absence of dysplasia, as well as the presence of low-grade and high-grade dysplasia. Neoplastic extension vertically into the submucosal layer or beyond was classified as invasive cancer.All the procedures were done under superficial sedation (midazolam and/or fentanyl or pethidine) or under deep sedation with propofol at the discretion of the endoscopist. Procedures were performed with high definition systems [i.e: 180/190 series in combination with EVIS EXERA II-III processors (Olympus, Tokyo, Japan), EC 390 LI scope in combination with Pentax processor (Pentax, Tokyo, Japan) or 590 WL and 580 ZW endoscopes in combination with Fujinon 4400/4450 processors (Fujifilm medical systems, USA)].

Quality of bowel cleansing was graded by each endoscopist following the Boston Bowel Preparation Scale. Adequate preparation was defined as a total score ≥6 with no segments <2. Procedures in which the quality of preparation was inadequate were excluded.

Sample size calculation: a polyp miss rate of 29% with HR-WLE was described previously in a Dutch multicenter study with SPS patients. Estimating a power of 80% and a significance level of 0.05, the investigators calculated 516 lesions would be required to measure a difference of 15% on HR-CE. In a previous study a median of 6 polyps was found on annual surveillance4. The investigators calculated a simple size of 86 patients for the study, 43 on each group.

Statistical analysis was performed with SPSS version 15.0 for windows. Numeric variables are presented as mean and standard deviation in case of a normal distribution and compared with a Student´s t test. Categorical variables are presented as frequencies and compared with the Chi Square test. Polyp miss rates were compared with chi square test. Logistic regression analysis was used to compare polyp characteristics and miss rates and was expressed as Odds ratio with the confidence intervals (95% CIs) to quantify the magnitude of the associations.

Study Type

Interventional

Enrollment (Actual)

86

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with Serrated Polyposis Syndrome aged 18 years or older, fulfilling WHO criteria I or III.
  • Clearing of all polyps previously achieved. Polyp "clearing" considered when all polyps >3 mm were removed during previous colonoscopies and/or partial colonic surgery when needed.
  • Surveillance colonoscopy.

Exclusion Criteria:

  • Inflammatory bowel disease.
  • Hereditary CRC syndromes (i.e, APC, MUTYH - biallelic - and MMR genes germline mutations).
  • Total colectomy.
  • Decline for participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: group A (HR-WLE)
Two tandem colonoscopies: first inspection was on high-resolution white-light endoscopy from the cecum/ileo-colonic anastomosis to the rectum, followed by a second inspection also on HR-WLE.
Experimental: group B (HR_CE)
two tandem colonoscopies: first inspection was on HR-WLE from the cecum/ileo-colonic anastomosis to the rectum, followed by a second inspection with panchromoendoscopy on indigo carmine.
Device: chromoendoscopy with indigo carmine
the lumen of the colon is sprayed in a segmental fashion using 0.4% indigo carmine delivered via a specially designed dye spray catheter (Olympus PW-5V1) or via the accessory channel with a 50cc syringe filled with indigo carmine and air.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
polyp miss rate
Time Frame: through study completion, an average of 2 years
number of polyps detected during the second inspection divided by the total number of polyps detected during the first and the second examination
through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
serrated lesions miss rate
Time Frame: through study completion, an average of 2 year
number of serrated lesions detected during the second inspection divided by the total number of serrated lesions detected during the first and the second examination
through study completion, an average of 2 year
adenoma miss rate
Time Frame: through study completion, an average of 2 year
number of adenomas detected during the second inspection divided by the total number of adenomas detected during the first and the second examination
through study completion, an average of 2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitario de Móstoles

Investigators

  • Principal Investigator: Jorge Lopez Vicente, Hospital Universitario de Móstoles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2015

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

March 18, 2018

First Submitted That Met QC Criteria

March 22, 2018

First Posted (Actual)

March 26, 2018

Study Record Updates

Last Update Posted (Actual)

March 27, 2018

Last Update Submitted That Met QC Criteria

March 25, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUMostoles 29115

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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