Neoplasms

All Conditions

Symptoms and General Pathology

Adenoma

Colonic Polyps

Hyperplasia

Polyps

Pathological Conditions, Anatomical

Intestinal Polyps

Herbal and Botanical

All Drugs and Chemicals

Cola

Patients undergoing colonoscopy where one or more polyps up to 10mm in size are found.

examination of the surface patterns of polyps using FICE and indigo carmine dye spray

Observation of surface patterns of polyps

Pradeep Bhandari, MBBS,MD,MRCP

It is current practice to remove any polyps found during colonoscopy. This is because adenomatous polyps have the potential to turn into cancer. However, a proportion of polyps \<10mm in size are hyperplastic, which cannot turn into cancer. Current practice requires these to be removed, as it is traditionally felt that they cannot be separated clinically from adenomas. This increases the risk of perforation and results in a significant cost in processing the samples. However, it has been suggested that it is possible to differentiate neoplastic from non neoplastic lesions using skills in polyp surface pattern recognition. If this is the case the investigators may be able to reduce the need for polypectomy The investigators believe that it is possible to tell the difference between polyps with cancerous potential and those that are harmless by assessment of surface patterns. This may enable us to improve the investigators clinical decisions when assessing polyps during colonoscopy, and reduce the number of unnecessary polypectomys being performed.

Polyps are a common finding during colonoscopy. It is current practice to remove these lesions, as some have the potential to turn into cancer. However, not all polyps are the same. Polyps can be of three different types:

1. Hyperplastic, which have negligible potential to turn into cancer and if left would cause no harm. These account for around one third of all small polyps encountered
2. Adenomas, which can turn into cancer and should be removed
3. Polyp cancers, which should be either biopsied or removed completely

The management pathway for polyps \>10mm is very simple as they are either likely to be adenomas which need removal or cancers which need a biopsy and tattoo. There is a rare possibility of these big polyps being hyperplastic / serrated adenomas and given the risk of malignant transformation, they need removal as well.

It has been traditionally felt that hyperplastic polyps cannot be separated clinically from adenomas or polyp cancers by the endoscopist. It is for this reason that all polyps are removed. However, polypectomy increases the risk of perforation and results in a significant cost in processing the samples. Recently it has been suggested that it is possible to differentiate neoplastic from non neoplastic lesions in the colon using skills in polyp surface pattern recognition.

Kudo's pit pattern is an effective way of in-vivo prediction of histology and differentiating neoplastic from non neoplasic polyps. However, it was originally described using vial staining which is cumbersome, time consuming and is not possible to perform outside Japan due to lack of availability and fears of toxicity related to gentian violet. It does however produce excellent results when used for pit pattern recognition. (Hurlstone DP C. S., 2004) It works by irreversibly binding microbial DNA and directly inhibiting cell replication. (Wakelin LPG, 1981).

Gentian violet is not the only way to examine the surface patterns of polyps. Many of the features can be seen with white light endoscopy. (Fu KI, 2004). Furthermore, there is extensive experience with other dies which are commonly used in Western Europe. Indigo carmine dye spray has been performed in studies in Japan, and has proven to be very effective in the assesment of polyp characteristics. It has been used for over 14 years in colonoscopy (Axelrad, 1996). Overall diagnostic accuracy by conventional view, chromoendoscopy and chromoendoscopy with magnification ranged from 68% to 83%, 82% to 92%, and 80% to 96%, respectively. (Axelrad AM, 1996) (Tung SY, 2001) (Eisen GM, 2002) (Su MY, 2004) (Apel D, 2006). It has the advantage over gentian violet that it does not bind to tissues and is therefore very safe. It has been questioned whether widespread applications of the techniques could influence the indications for biopsy sampling during colonoscopy and the indication for mucosectomy (Yasushi Sano, 2005).

When compared to standard colonoscopy, indigo carmine chromoendoscopy, with magnification, has been shown to increase the accuracy for polyp differentiation from 84% to 96% (Fu KI, 2004). High-resolution indigo carmine chromoendoscopy demonstrated a small increase in accuracy over chromoendoscopy without magnification from 81% to 83% . (Hurlstone DP K. M., 2005).

Because of its numerous benefits in lesion detection and assessment of polyps indigo carmine has become a standard part of colonoscopy and is recognised by the British Society of Gastroenterology as an important skill for the practicing endoscopist. It has become standard practice within Portsmouth Hospitals NHS trust when performing colonoscopy. This is a position which is reflected nationally in most large units which participate in the bowel cancer screening programme.

White light endoscopy and chromoendoscopy are not the only methods of examining colonic polyps. Computed virtual colonoscopy, where a video computer processor within the endoscopy equipment enhances the endoscopic picture have become commonly available. There are systems available from all of the main endoscope manufacturers, including narrow band imaging from Olympus and i-scan from Pentax. Fujinon has developed a very effective post processor technology called FICE which helps define the surface pattern of polyps in great detail. This is now a standard feature on all of the endoscopes produced by the company. It has been shown in a limited number of studies to offer a potentially useful alternative to dye spray in predicting in-vivo histology. (J. Pohl, 2008). A prospective randomised multicentre study looked at 764 patients with FICE compared to white light with targeted indigocarmine spray. It found that FICE and indigocarmine were both able to differentiate adenomas from neoplasia. There was a sensitivity in differentiating adenomas from non-neoplastic polyps of 92.7%,with FICE, comparable but not superior to that of indigocarmine (90.4%), with no statistically significant difference between the two techniques observed. (p=0.44.) FICE did not shorten the procedure time. A prospective series looking at FICE in the evaluation of colononic polyps up to 2cm in size by the same team suggested a sensitivity of 89% could be achieved. Unfortunately these studies looked at larger lesions and therefore it is difficult to say whether this could be achieved with polyps \<1cm, where accurate assessment is clearly more difficult. However, it is in the smaller lesions where the greatest gain in terms of a change in management exists. (Pohl J N.-T. M., 2008).

It is generally accepted that further research is needed in this field. If it is possible for endoscopists to differentiate neoplastic from non neoplastic polyps the potential benefits both in terms of safety and histopathology costs would be significant. The current policy of polypectomy or biopsy of all polyps detected during colonoscopy is a very expensive option (£ 80-120) and carries a significant risk of perforation.

Within Portsmouth Hospitals NHS trust it has become standard practice to assess all polyps with FICE and dye spray with indigo carmine prior to removal. This is consistent with current guidelines from the British society of Gastroenterologists and is important both in the detection and assessment of polyps. These techniques are established and their importance in colonoscopy is not under investigation. What is unclear is whether endoscopists are able to differentiate neoplastic from non-neoplastic lesions on a basis of surface pattern recognition accurately enough to be able to change clinical practice.

We aim to assess the impact of surface pattern assessment on the potential management of patients, and whether it has the potential to safely replace the policy of biopsy / polypectomy for pateints with polyps \<10mm in size.

All polyps are sent for histological analysis as per standard protocol. This is not additional for the study and part of routine NHS practice. They will be kept and stored as per standard NHS protocols.

The Value of Polyp Surface Pattern Recognition in the Identification of Neoplasia: a Prospective Study

Polyp Surface Pattern Recognition in the Identification of Neoplastic Polyps

Portsmouth Hospitals NHS Trust

Digestive System Diseases

Colitis

Colitis, Ulcerative

Ulcer

Gastroenteritis

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Inflammatory Bowel Diseases

Methylene Blue

Group A: HDTV Olympus colonoscopes and Chromo-endoscopy, methylene blue 0.1%

Group B: Virtual chromoendoscopy: HDTV Olympus colonoscopes and Narrow band Imaging (NBI)

Group C: CCD Fujinon colonoscopes and Chromo-endoscopy, methylene blue 0.1%

Group D: Virtual chromoendoscopy: CCD Fujinon colonoscopes and Fujinon Intelligent Color Enhancement n° 4

Group E: HD-Pentax colonoscopes and Chromo-endoscopy, methylene blue 0.1%

Group F: Virtual chromoendoscopy: HD Pentax colonoscopes and I-scan 2 settings

Virtual chromoendoscopy

Panchromocolonoscopy with methyleen blue 0.1%

Chromoendoscopy

Vera Ballet

Hilde Willekens

Raf Bisschops, MD PhD

Marc Ferrante, MD PhD

Raf Bisschops, PD PhD

Gert Van Assche, MD PhD

Ingrid Demedts, Md PhD

Paul Rutgeerts, MD PhD

Filip Baert, MD

Filip Baert, MD PhD

Talat Bessissow, MD PhD

John Gasdal Karstensen, MD

Jakob Hendel, MD PhD

Rogier De Ridder, MD

Marie Pierik, MC PhD

The risk for colon cancer in patients with longstanding ulcerative colitis exceeding the rectum is increased and therefore patients should be enrolled in a surveillance program eight years after the diagnosis. Until today, official international guidelines for endoscopic screening in patients with ulcerative colitis advise to take 4 biopsies every 10 centimeters (with a minimum of 32) and of each suspected visible lesion. These guidelines are merely based on consensus during expert opinion meetings rather than evidence based. Recent studies have shown that chromo-endoscopy guided biopsies significantly reduced the number of biopsies for each procedure and detected more neoplastic lesions. Chromo-endoscopy is therefore considered the gold standard in this study in which we want to compare it to the performance and efficiency of new endoscopic imaging techniques.

Narrow-Band Imaging (NBI) selectively uses certain wavelengths of the visible light leading to a shift in the excitation spectrum towards blue light. The first studies with NBI showed that the additional value of NBI in the detection of neoplastic lesions is comparable to chromo-endoscopy, but time saving and easier to perform. The Fujinon Intelligent Chromo-Endoscopy (FICE) system uses a similar theoretical principal as NBI but this is achieved via the use of post hoc computer algorithms, applying different filters to the stored endoscopic images and enabling a theoretically endless number of combinations of filters that can be used. The Pentax I-scan system also allows post hoc modification of the images. On the one hand, surface enhancement enables to better highlight mucosal changes. Spectral modification allows to apply different modes in analogy with to FICE system.

These new imaging techniques have a theoretical advantage which is extendedly used for sales purposes but has however so far not been proven in ulcerative colitis patients. We want to test their clinical use in the screening for neoplastic lesions in patients with long standing ulcerative colitis.

The risk for colon cancer in patients with longstanding ulcerative colitis exceeding the rectum is increased and therefore patients should be enrolled in a surveillance program eight years after the diagnosis. Surveillance endoscopies are advised 8 to 10 years after the diagnosis of ulcerative colitis. The first decade every 3 years, the second decade every 2 years and thereafter every year Until today, most official international guidelines for endoscopic screening in patients with ulcerative colitis advise to take 4 random biopsies every 10 centimeters (with a minimum of 32) and of each suspected visible lesion using standard white light endoscopy.

These guidelines are merely based on consensus during expert opinion meetings rather than evidence based.

However, some studies have shown that the sensitivity for the detection of dysplasia during colonoscopy in patients with ulcerative colitis can significantly be enhanced by using chromo-endoscopy. These studies used methylene blue or indigo carmine as a contrast agent with or without high magnification endoscopy. Chromo-endoscopy guided targeted biopsies significantly reduced the number of biopsies for each procedure and detected more neoplastic lesions. It was therefore concluded that colonoscopy with chromo-endoscopy guided biopsies is more efficient and cost saving. Chromo-endoscopy with targeted biopsies is an alternative to white light endoscopy with random biopsies every 10cm. The European Crohn and Colitis association now suggests that the use of methylene blue or indigo carmine chromoendoscopy is an alternative to random biopsies for appropriately trained endoscopists and is superior to random biopsies in the detection rate of neoplastic lesions In this study we want to compare chromoendoscopy with targeted biopsies as the gold standard with new new endoscopic image techniques called virtual chromoendoscopy.

From 2005 new endoscopic imaging modalities have been commercialized and are now generally available to gastroenterologists. They all claim a theoretical advantage in comparison to standard white light high resolution video endoscopy. These new techniques are called virtual chromoendoscopy (VC). There are three different systems developed by the three major competitors of endoscopic equipment: Olympus, Pentax and Fujinon.

Narrow-Band Imaging (NBI) is developed by Olympus inc. and selectively uses certain wavelengths of the visible light leading to a shift in the excitation spectrum towards blue light. The intensity of the blue bandwidth is also enhanced. This leads to a more superficial penetration of the emitted light into the mucosa of the intestine and enhancement of more superficial structures (e.g. irregularities, small flat lesions or polyps) and small superficial mucosal vessels (indicative of neoplasia).

The first studies using NBI in Barrett's esophagus demonstrated that the additional value of NBI in the detection of neoplastic lesions is comparable to chromo-endoscopy (Kara et al., 2005). However NBI is time saving and easier to perform than chromo-endoscopy because there is no need to additionally spray dye onto the mucosa.

In a standard population screening study, NBI has shown to aid in the detection and characterization of polyps in the colon. In particular the presence of a brownish meshed capillary network has a high diagnostic value in the prediction of the neoplastic nature of a lesion.

In a very recent tandem study in which white light endoscopy was compared with NBI in 48 patients with longstanding UC there was no additional benefit of NBI. In the 25 patients who were first endoscoped with white light 8 dysplastic lesions were found. After NBI imaging another 7 lesions were found. In the 23 patients which were first imaged with NBI 7 lesions were found and an additional 8 after white light endoscopy (Van den Broek FJ et al 2011.

The Fujinon Intelligent Chromo-Endoscopy (FICE) system uses a similar theoretical principal as NBI but this is achieved via the use of post hoc computer algorithms, applying different filters to the stored endoscopic images and enabling a theoretically endless number of combinations of filters that can be used. Currently 10 different spectrum filters can be used. There are predefined settings for visualization of the colonic mucosa. There are no previous data comparing white light endoscopy and FICE in the detection of dysplasia in longstanding ulcerative colitis.

Finally, Pentax released a new high definition endoscopy system in 2007, the I-scan system, which also allows post hoc modification of the images. On the one hand, surface enhancement enables to better highlight mucosal changes. Spectral modification allows to apply different modes in analogy with to FICE system. For instance the p-mode for pattern recognition helps to accentuate epithelial features. The TE-mode helps to assess the vasculature of the gastrointestinal mucosa. Recently new filters were developed such as the colon mode, specifically designed for the colon. In one study VC with I-scan TE-mode was compared to CE and standard white light endoscopy in 69 patients. In both the VC and CE mode 11 dysplastic lesions were found (Hoffman et al 2010). Data about the improvement of detection of dysplasia are lacking until now.

Adjustment of the light spectrum is usually combined with a better and higher image resolution of the new generation endoscopes. Fujinon and Pentax use a so called super-CCD to increase the pixel resolution of the scope to 1.300.000 and 1.400.000 respectively and combined it with a DVI output signal. Olympus opted for an improved video resolution by incorporating high definition television (HDTV) in the latest processors.

These new imaging techniques have a theoretical advantage which is extendedly used for sales purposes but has however so far not been proven in ulcerative colitis patients. We want to test their clinical use in the screening for neoplastic lesions in patients with long standing ulcerative colitis. The scientific and clinical relevance of this study is clear. If NBI and/or FICE and/or I-scan have a better detection rate than chromo-endoscopy, the latter can be replaced by virtual chromo-endoscopy. Even if the detection by NBI and/or FICE and/or I-scan is not statistically different from standard chromo-endoscopy, they still can replace the latter because it is technically easier to use. If however these techniques have a lower adenoma detection rate than classical chromo-endoscopy we will be able to show that there is no place for these techniques in the detection of UC related neoplasia, despite the theoretical advantage.

Because the multicenter character of the study, and the availability of only one system in most hospitals, we will test the differences between all three modalities and classical chromoendodoscopy.

The endoscopic procedure as such is not much different from a standard endoscopic procedure that patient should be advised to undergo according to good clinical practice. The bowel preparation is similar as in a normal colonoscopy, and can be performed either at home or in the endoscopy department. The endoscopes used in the study include the H180Q series of Olympus, the 5000 series of Fujinon and the HD series of Pentax. They are not different in terms of design or size compared to standard colonoscopies and are all commercially available.

Patients will be randomized between one of the following techniques:

1. Chromo-endoscopy with methylene blue 0,1% (groups A-C-E) An Olympus spray catheter is used through the biopsy channel of the endoscope to apply the dye, a saline solution with methylene blue in a concentration of 0.1%. This technique was already validated in previous studies. Besides the extra time needed for dying the entire colon mucosa, no other manipulations are needed for this technique. Moreover, the time needed to dye can be recovered because only chromo-endoscopy guided biopsies will be taken instead of random biopsies throughout the colon, which normally also requires a considerable amount of time. Previous studies using chromo-endoscopy versus conventional screening colonoscopy did not show a significant difference in total procedure time. The endoscopes used do not differ from the ones used in the other randomization arms and include either an Olympus H180Q colonoscope, Fujinon EC 590 ZW/M colonoscope or a Pentax 3890i colonoscope. All three endoscopes are CE approved and are commercially available.
2. Narrow band imaging with HDTV (Group B) This technique involves an Olympus H180Q colonoscope that is CE approved and commercially available. The procedure involves a normal white light endoscopy during progression of the scope. Once the caecum is reached the entire procedure will be performed in NBI modus. This has no influence or side effects for the patients because NBI modus is switched on by pushing a button on the scope.
3. Fujinon Intelligent Color Enhancement (FICE) with super CCD chip (Group D) This technique involves a Fujinon EC 590ZW/M colonoscope that is CE approved and commercially available. The procedure involves a normal white light endoscopy during progression of the scope. Once the caecum is reached the entire procedure will be performed in FICE modus n° 4. This has no influence or side effects for the patients because FICE modus is switched on by pushing a button on the scope.
4. I-scan with High Definition colonoscope (group F) This technique involves a PENTAX EC3890Fi colonoscope that is CE approved and commercially available. The procedure involves a normal white light endoscopy during progression of the scope. Once the caecum is reached the entire procedure will be performed in the TE- modus (Tissue enhancement mode) with surface enhancement on medium (range low-medium-high). This has no influence or side effects for the patients because the c- modus is switched on by pushing a button on the scope.

Only targeted biopsies of visible mucosal abnormalities during chromo-endoscopy, NBI, FICE or I-scan endoscopy will be taken. This is in concordance with the standard approach during chromo-endoscopy directed screening colonoscopy for ulcerative colitis. The disposable biopsy forceps are commercially available (Boston Scientific) and do not differ from the ones used during normal endoscopic procedures.

Power calculation

A power analysis was performed to detect a statistical significance between group A and B, group C and D and between group E and F. In a previous study dysplasia was found three times more often using CE compared to white light endoscopy: 32/84 versus 10/81 patients. This wil give an increase from approximate 10 to 30 percent. It is expected that in both study groups the percentage of dysplasia equals.

Inclusion of 67 patients in each group will allow to detect a 20% increase of dysplasia from 10 to 30% compared to white light endoscopy with a power of 80% (beta error 0.2; alpha error 0.05). We expect to include a total of (67 x 6 =) 402 patients in the study.

5.5 Co-variables

Multiple factors will be used as co-variables

* Age
* Duration of disease
* Existence of PSC
* Use of medication

  * Mesalazine/Sulfazalazine
  * Thiopurines
  * Biologicals

Comparison Between Chromoendoscopy and Virtual Chromoendoscopy (NBI, I-scan, FICE) for Detection of Neoplasia in Long Standing Ulcerative Colitis

Endoscopic Screening for Dysplasia in Patients With Longstanding Ulcerative Colitis: Classical Chromo-endoscopy Versus NBI , FICE and EPK-i.

The endpoint will be assessed in three subgroups comparing :

1 )Group A: HDTV Olympus colonoscopes and Chromo-endoscopy, methylene blue 0.1% to Group B: HDTV Olympus colonoscopes and Narrow band Imaging (NBI) 2) Group C: CCD Fujinon colonoscopes and Chromo-endoscopy, methylene blue 0.1% to Group D: CCD Fujinon colonoscopes and Fujinon Intelligent Color Enhancement 3) Group E: HD-Pentax colonoscopes and Chromo-endoscopy, methylene blue 0.1% to Group F: HD Pentax colonoscopes and I-scan As such this is not a comparison between different endoscopy systems, but a comparison of chromoendoscopy and virtual chromoendoscopy within each different system.

The primary endpoint will be assessed in three subgroups comparing :

1 )Group A: HDTV Olympus colonoscopes and Chromo-endoscopy, methylene blue 0.1% to Group B: HDTV Olympus colonoscopes and Narrow band Imaging (NBI)

2) Group C: CCD Fujinon colonoscopes and Chromo-endoscopy, methylene blue 0.1% to Group D: CCD Fujinon colonoscopes and Fujinon Intelligent Color Enhancement

3) Group E: HD-Pentax colonoscopes and Chromo-endoscopy, methylene blue 0.1% to Group F: HD Pentax colonoscopes and I-scan

As such this is not a comparison between different endoscopy systems, but a comparison of chromoendoscopy and virtual chromoendoscopy within each different system.

The total endoscopy time is recorded from the start until the end of the entire procedure. After the caecum is reached, time is recorded. Total retraction time is the time between reaching the caecum and the end of the procedure and includes time for rinsing, dye spraying, biopsy or poliepectomy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Value of Polyp Surface Pattern Recognition in the Identification of Neoplasia: a Prospective Study	NCT01182623	Colonic Polyps	Observation of ...	18 Years -	Portsmouth Hospitals NHS Trust
The Value of Polyp Surface Pattern Recognition in the Identification of Neoplasia: a Prospective Study	NCT01182623	Colonic Polyps	Observation of ...	18 Years -	Portsmouth Hospitals NHS Trust
Comparison Between Chromoendoscopy and Virtual Chromoendoscopy (NBI, I-scan, FICE) for Detection of Neoplasia in Long Standing Ulcerative Colitis	NCT01882205	Ulcerative Coli...	Virtual chromoe... Chromoendoscopy	18 Years -	Universitaire Ziekenhuizen KU Leuven

Spots Global Cancer Trial Database for fice

Every month we try and update this database with for fice cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for fice

Every month we try and update this database with for fice cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for fice cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.