Chromoendoscopy for Serrated Polyposis Syndrome
Condition: Colonic Polyp; Colonic Neoplasms; Colonic Cancer
MeSH terms: Colonic Neoplasms; Colonic Polyps
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): chromoendoscopy with indigo carmine
Intervention type(s): Device
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients are randomized into two groups with tandem explorations: in the group A or white light group (HR-WLE) where inspection is performed with white light in both colonoscopies, and in the group B or chromoendoscopy group (HR-CE) where a first inspection is performed with white light and the second with panchromoendoscopy with indigo carmine.
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: sessile serrated polyp; chromoendoscopy; indigo carmine