Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Stomach Neoplasms

Metaplasia

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

narrow band imaging

white light endoscopy

Tiing Leong Ang, MBBS, MRCP

It is recognized that gastroscopy can miss intestinal metaplasia, dysplasia and early gastric cancer. This could conceivably be due to the fact that these lesions may only present as subtle mucosal changes on conventional white light endoscopy (WLE) and thus be easily missed. In narrow band imaging (NBI) a rotating interference narrow band filter is interposed after the xenon light source such that when the NBI mode is switched on, discrete blue and green wavelengths are used and this improves mucosal surface contrast and facilitates visualization of mucosal details. A new NBI system is available that allows brighter illumination. We hypothesize that bright -NBI is superior to WLE in detecting focal gastric lesions such as gastric intestinal metaplasia, dysplasia and early gastric cancer in subjects undergoing gastroscopy.

Background It is recognized that gastroscopy can miss intestinal metaplasia, dysplasia and early gastric cancer (EGC)\[1-3\]. This could conceivably be due to the fact that EGC, as well as premalignant changes, may only present as subtle mucosal changes on conventional white light endoscopy (WLE) and thus be easily missed.

Chromoendoscopy has been used routinely in some centers during upper gastrointestinal (UGI) endoscopy in an attempt to improve mucosal contrast and detect subtle mucosal lesions\[4\]. However, this is not the norm in most centers due to the inconvenience of dye spray. Narrow band imaging (NBI) facilitates the examination of the mucosal surface without a need for chromoendoscopy. It is based on the principle that the depth of penetration of light is wavelength dependent, with shorter wavelengths resulting in more superficial penetration i.e. blue light penetrates most superficially (mucosal imaging) while red light penetrates the deepest (submucosal imaging). In NBI a rotating interference narrow band filter is interposed after the xenon light source such that when the NBI mode is switched on, discrete blue and green wavelengths are used and this improves mucosal surface contrast and facilitates visualization of mucosal details\[5\]. Magnifying endoscopy (ME) is useful in assessing the gastric mucosal pit pattern and microvessel of gastric mucosal lesions, thus providing the possibility of predicting the histological nature of the mucosal lesion. Studies from Japan, a country with a high population risk for gastric cancer, which were based on preselected high risk patients or patients with known precancerous lesions or EGC, showed that NBI and NBI-ME could diagnose precancerous lesions such as intestinal metaplasia (IM)\[6\] as well as EGC\[7-11\].

However, there is a lack of published data on the clinical utility of NBI in the detection of gastric intestinal metaplasia, dysplasia and EGC in the unselected general population. A recent study from Singapore looked at the utility of NBI and NBI-ME in patients aged 35 to 70 years undergoing diagnostic UGI endoscopy and found that the detection rate of focal lesions was increased from 43.7% to 58.8% with NBI, compared to WLE. Among the additional lesions detected, NBI-ME identified 97.1% as IM, 1.4% as EGC and 1.4% as benign. The EGC was a synchronous cancer missed by WLE but detected by NBI\[12\].

The current NBI system is limited by the dark endoscopic view. This has the potential limitation of making the detection of subtle lesions more difficult and lesions could be missed. A new prototype NBI system has been designed that has a brighter appearance. This prototype bright NBI coupled with high definition resolution is likely to overcome this drawback of original NBI.

Hypothesis We hypothesize that bright -NBI is superior to WLE in detecting focal gastric lesions such as gastric intestinal metaplasia, dysplasia and EGC in subjects undergoing diagnostic upper GI endoscopy.

Materials and methods

1. Setting and trial design:

   A randomized controlled study.
2. Subjects:

   Inclusion criteria: 1) Subjects aged \> 50 years undergoing diagnostic or screening upper GI endoscopy; 2) ability to provide a written consent to trial participation. Exclusion criteria: 1) presence of active gastrointestinal bleeding; 2) presence of coagulopathy precluding biopsies; 3) absence of informed consent.
3. Informed Consent:

   The protocol will be approved by local Institutional Review Board. Trial subjects will sign informed consent prior to UGI endoscopy.
4. Interventions:

   Subjects are randomized to undergo UGI endoscopy in either WLE or bright light NBI modes, using a high definition gastroscope (Olympus 190 or 290 series). An endoscopy assistant will then open the next numbered sealed envelop at the instruction of the endoscopist. For subjects randomized to WLE, the entire examination will be performed using white light. For subjects randomized to NBI, the NBI mode will be switched on before insertion into the stomach. Once the gastroscope is inserted into the duodenum, the endoscopist can switch back to WLE to examine the duodenal mucosa. Before withdrawal from the duodenum back into the stomach, the NBI mode will be switched on and gastric mucosal examination carried out in the NBI mode. After the gastric examination findings using NBI have been recorded, the endoscopist is allowed to re-examine the gastric mucosa using white light, but any additional findings will not be recorded in the study data sheet. During withdrawal into the esophagus, the endoscopist can switch back to WLE to examine the esophageal mucosa.

   Recorded parameters include 1) presence or absence of focal lesions and the suspected diagnosis such as a) IM; b) cancer; c) early cancer; d) gastric ulcer or erosion; e) other focal lesions. Switching from WLE to NBI and vice versa is allowed at the discretion of endoscopist after detection of a lesion. Endoscopists may elect to remove these lesions using WLE. Magnification is allowed in either group. IM is diagnosed on white light endoscopy based on by whitish color change with plaques, patches, or homogeneous discoloration on the gastric mucosa\[13\].High definition white light endoscopy may possibly visualize the villous pattern. IM is diagnosed on NBI based on the criteria such as light blue crest and villous morphology\[14, 15\]. Early cancer may present on white light endoscopy with varied non-specific features such as a subtle polypoid protrusion, a superficial plaque, ulcer, depression, or even a mucosal discoloration. However distortions of the mucosal pit pattern and microvascular pattern on NBI have been found to be characteristic\[6\].

   Lesion size is measured by a comparison to known diameter of open forceps and grouped into size categories. The decision to perform hot/ cold biopsies or snaring is left to the endoscopist. Each lesion is retrieved separately for pathologic examination.

   Recognizing that the incidence rate of cancer may be low from the study populations\[16\], the decision was made to use as a surrogate intestinal metaplasia, a known premalignant lesion, as the main outcome variable.
5. Statistics:

   1. Methods of randomization:

      Randomization sequence will be generated using a computer program in blocks of 20 of equal assignment pertaining to individual endoscopists who participate in the trial.
   2. Primary outcome variables:

      Detection rate of IM
   3. Secondary outcome variables:

      1. Detection rate of gastric cancer
      2. Aggregate detection rate of focal gastric lesions The diagnostic performance of the imaging modality will form ancillary analyses. Histology will be the gold standard.
   4. Sample size calculation:

   In the UGI endoscopy study that compared NBI with WLE in the general population, it was found that most focal lesions were due to IM and that after age 50 years, the prevalence rate of IM was 36%\[12\]. In this study, WLE detected IM in 4.4% of cases, whereas NBI detected IM in 16.2% of cases. We arbitrarily assumed that HD WLE increase the detection rate of IM to 10%, while keeping the IM det4ection rate by NBI to 16.2%. We determine our sample size to detect a 6.2% difference with a power of 80% and a two sided type 1 error of 0.05. A total of 464 patients will be required.
6. Timetable of work:

The study will continue until the intended subject size of 464 subjects is reached. .

References

1. Hosokawa O, Tsuda S, Kidani E, et al. Diagnosis of gastric cancer up to three years after negative upper gastrointestinal endoscopy. Endoscopy 1998; 30:669-74.
2. Yalamarthi S, Witherspoon P, McCole D, Auld CD. Missed diagnoses in patients with upper gastrointestinal cancers. Endoscopy 2004; 36:874-9.
3. Raftopoulos SC, Segarajasingam DS, Burke V, et al. A cohort study of missed and new cancers after esophagogastroduodenoscopy. Am J Gastroenterol 2010; 105:1292-97.
4. Kiesslich R, Neurath MF. Magnifying chromoendoscopy for the detection of premalignant gastrointestinal lesions. Best Pract Res Clin Gastroenterol. 2006; 20: 59-78.
5. Kuznetsov K, Lambert R, Rey JF. Narrow band imaging: potential and limitations. Endoscopy 2006; 38:76-81.
6. Yao K, Anagnostopoulos GK, Ragunath K. Magnifying endoscopy for diagnosing and delineating early gastric cancer. Endoscopy 2009; 41:462-7.
7. Kato M, Kaise M, Yonezawa J, et al. Trimodal imaging endoscopy may improve diagnostic accuracy of early gastric neoplasia: a feasibility study. Gastrointest Endosc 2009; 70:899-906.
8. Kaise M, Kato M, Urashima M, et al. Magnifying endoscopy combined with narrow band imaging for differential diagnosis of superficial depressed gastric lesions. Endoscopy 2009; 41:310-5.
9. Yokoyama A, Inoue H, Minami H. Novel narrow band imaging magnifying endoscopic classification for early gastric cancer. Dig Liver Dis 2010; 42:704-8.
10. Nakamura M, Shibata T, Tahara T, et al. The usefulness of magnifying endoscopy with narrow band imaging to distinguish carcinoma in flat elevated lesions in the stomach diagnosed as adenoma by using biopsy samples. Gastrointest Endosc 2010; 71:1070-5.
11. Ezoe Y, Muto M, Horimatsu T, et al. Magnifying narrow band imaging versus magnifying white light imaging for the differential diagnosis of gastric small depressive lesions: a prospective study. Gastrointest Endosc 2010; 71:477-84.
12. Ang TL, Fock KM, Teo EK, Tan J, Poh CH, Ong J, Ang D. The diagnostic utility of narrow band imaging magnifying endoscopy in clinical practice in a population with intermediate gastric cancer risk. Eur J Gastroenterol Hepatol. 2012;24(4):362-7Lin BR, Shun CT, Wang TH, Lin JT. Endoscopic diagnosis of intestinal metaplasia of stomach: accuracy judged by histology. Hepatogastroenterology 1999;46:162-166.
13. Uedo N, Ishihara R, Iishi H, Yamamoto S, Yamamoto S, Yamada T, Imanaka K, Takeuchi Y, Higashino K, Ishiguro S, Tatsuta M. A new method of diagnosing gastric intestinal metaplasia: narrow-band imaging with magnifying endoscopy. Endoscopy. 2006 Aug;38(8):819-24.
14. Pimentel-Nunes P, Dinis-Ribeiro M, Soares JB, Marcos-Pinto R, Santos C, Rolanda C, Bastos RP, Areia M, Afonso L, Bergman J, Sharma P, Gotoda T, Henrique R, Moreira-Dias L. A multicenter validation of an endoscopic classification with narrow band imaging for gastric precancerous and cancerous lesions. Endoscopy 2012;44(3):236-46.
15. Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. J Gastroenterol Hepatol 2010;25:479-486.

RCT: WLE vs. NBI in Upper Gastrointestinal Endoscopy

A Randomized Comparison Between White Light Endoscopy (WLE) and Bright Narrow Band Imaging (B-NBI) in Subjects Undergoing Upper Gastrointestinal Endoscopy

Detection rate of intestinal metaplasia by white light endoscopy and by narrow band imaging

Changi General Hospital

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Herbal and Botanical

All Drugs and Chemicals

Cola

Use of White Light Endoscopy to detect colonic adenomas.

Using Bright Narrow Band Imaging to detect colonic adenomas.

Bright Narrow Band Imaging.

White Light Endoscopy

Removal of colorectal adenomas prevents the occurence of colorectal cancers. The use of chromo-endoscopy has been shown to improve the detection of flat adenomas. Narrow band imaging enables endoscopists to accurately describe the pit pattern of adenomas. By comparing White Light Endoscopy and Bright Narrow Band Imaging it will show if there is any comparable advantage to using one or the other for lesion detection and assessment.

Removal of colorectal adenomas prevents occurrence of cancers \[1\]. It is recognized that colonoscopy can miss colorectal adenomas and early cancers \[2\]. There is a need to further improve performance of colonoscopy. The use of chromoendoscopy has been shown to improve detection of flat adenomas \[3\]. Narrow band imaging was introduced in year 2006. It is similar to chromoendoscopy in that it provides more mucosal details. This enables endoscopists to accurately describe the pit pattern of adenomas. NBI has been used as a substitute to chromoendoscopy.

In pooled analysis, NBI is comparable to chromoendoscopy in their sensitivity and specificity in the diagnosis of malignant colorectal adenomas \[4\]. Unfortunately, the use of NBI has not been shown to conclusively improve rate of colorectal adenoma detection. Two of 3 randomized trials that compared WLE to NBI showed a higher adenoma detection rate with the use of NBI \[5, 6\]. In a study by Rex et al., the rate was however similar with either modality. In a pooled analysis, NBI was only marginally better than WLE \[7\].

The effective use of NBI depends on the quality of bowel preparation and the experience of endoscopist. In the presence of fecal matters, NBI tends to be dark and detection of small adenomas becomes difficult. The prototype bright NBI coupled with high definition resolution is likely to overcome this drawback of original NBI.

Comparison Between White Light Endoscopy and Bright Narrow Band Imaging in Diagnosis Colonic Adenomas.

A Randomised Comparison Between White Light Endoscopy (WLE) and Bright Narrow Band Imaging (B-NBI) in the Diagnosis of Colonic Adenomas in Asymptomatic Subjects Undergoing Screening Colonoscopy.

It is anticipated that colorectal adenomas will be more easily identifiable using Bright Narrow Band Imaging.

It is anticipated that the use of Bright Narrow Band Imaging will significantly improve the histological detection of colonic adenomas when detected as opposed to White Light Endoscopy.

Professor Michael Bourke

Director of Gastrointestinal Endoscopy

The patients enrolled in this group will undergo pan-colonic chromoendoscopy evaluation.

The patients enrolled in this group will undergo high definition white light endoscopy based evaluation

Participants randomised to Group A will undergo colonoscopic evaluation using dye-based chromoendoscopy

Chromoendoscopy

Participants randomised to Group B will undergo colonoscopic evaluation using high definition white light endoscopy

High definition white light colonoscopy

Colonoscopy is the technique of choice for evaluation of patients with positive fecal occult blood (FIT). Identification of polyps and their removal has been shown to decrease colorectal cancer incidence rates and mortality. Many endoscopic imaging technologies and devices have been developed to increase adenoma detection (ADR) during screening colonoscopies. They vary in the way they work, and some of the technologies are costly and not widely available. Studies has shown the simple to use pan-colonic chromoendoscopy can improve ADR compared to standard colonoscopy. However, there is little evidence on the utility of pan-colonic chromoendoscopy in asymptomatic individuals undergoing colonoscopy after a positive FIT test. In this randomized study, the investigators aim to compare the utility of chromoendoscopy and high-definition white-light endoscopy in asymptomatic individuals undergoing colonoscopy after a positive FIT test

Eligible subjects with positive screening FIT test referred to the Department of Gastroenterology, Singapore General Hospital will be approached and recruited. The included patients will be randomised to either a) Group A- Chromoendoscopy or b) Group B- high definition white light based evaluation.

Hypothesis:

The investigators hypothesize that application of non-absorbable dye during colonoscopy would enhance the mucosal contrast, delineate the border and surface patterns by accumulating in the innominate grooves and, thereby, enhance the detection of adenoma during colonoscopy

Procedure:

Pan-colonic chromoendoscopy and high-definition white light endoscopy will be performed by five experienced endoscopist, and hospital sedation guidelines will be followed. The colonoscopy will be performed using Olympus (CF-HQ190) or Fujifilm (EC-590) colonoscopies. Indigo carmine dye will be used for pan-colonic chromoendoscopy. Two ampules of Indigo carmine (0.8%, 5ml/ampule) will be dissolved in 250 ml of water and sprayed through the waterjet channel by using the auxiliary foot pump upon reaching the caecum.

The colonoscopy insertion will be performed using high-definition white light, and the scope will be advanced till the caecum. The quality of the bowel preparation will be rated according to the validated Boston bowel preparation score. Participants with inadequate bowel preparation score (Score \<6) will be excluded from the study. The fecal residue will be washed, suctioned and cleared during insertion to improve visibility. No special care will be taken to look for lesions during the insertion. Assessment for colonic lesions will only be performed during withdrawal of the endoscope. The minimum withdrawal time was set at 7 minutes. Randomization: Once the caecum is intubated and if the bowel preparation is adequate, the participants will be randomized to pan-colonic chromoendoscopy based withdrawal or high-definition while light based withdrawal. In the pan-colonic chromoendoscopy group, the indigo carmine was sprayed by pressing the auxiliary foot pump, and dye was delivered systematically to coat the entire colonic mucosa. In both, the groups, the lesion size, number, location, morphology will be documented during withdrawal. The investigators characterized the morphology of the lesion according to the established Paris classification. The investigators characterized the lesion as flat neoplasm if the lesion project \<2.5mm or polypoid lesion if lesion project \>2.5mm into the lumen. The investigators measured the size of the lesions using an open biopsy forceps when needed.

In both the groups, the identified polyps will be removed using the standard techniques, and the tissue will be placed in separate formalin bottles and sent for histology assessment. The histology of the polyps was assessed by dedicated pathologist trained in gastrointestinal pathology. Both the endoscopists and the pathologist will not be blinded to the study technique. The investigators defined advanced adenoma as any adenoma \>10 mm in size or with \>25% villous histology or high-grade dysplasia. The investigators classified hyperplastic polyps and sessile serrated polyps (SSA) as serrated lesions, The investigators excluded hyperplastic lesions in the rectum from the analysis as such lesions are frequently encountered in the rectum

The participants will be randomised to one of the two groups. The first group will undergo colonoscopy evaluation using pan-colonic chromoendoscopy during withdrawal of endoscope. In the second group, colonoscopy evaluation will be performed using high-definition white light endoscopy during withdrawal

Can Pan-Colonic Chromoendoscopy (PCC) Improve Adenoma Detection Rate in FIT-Positive-Patients: A Randomized Study

Singapore General Hospital

It is a High Definition system with narrow band imaging option in th endoscope.

Bright Narrow Band Imaging

White light Endoscopy

James YW LAU, MD

Early detection of colo-rectal adenoma using colonoscopy can prevent occurrence of colon cancers. While colonoscopy is a standard technique, it can miss early cancers. To improve the detection rate, Narrow Band Imaging (NBI) was introduced in 2006. It has been shown to compare favorably with chromo-endoscopy in the sensitivity and specificity in the diagnosis of malignant colo-rectal neoplasms. The major drawback of NBI is that images become dark in the presence of blood and fecal matters. The bright-NBI is a prototype imaging technology that enables endoscopists to obtain better images in suboptimal conditions. The study proposes to compare the performance of colonoscopy using either white light or bright NBI in subjects undergoing screening colonoscopy in search for colon adenomas.

Purpose

To determine that bright -NBI is superior to WLE in detecting colorectal adenomas in average risk subjects undergoing screening colonoscopy.

Removal of colorectal adenomas prevents occurrence of cancers \[1\]. It is recognized that colonoscopy can miss colorectal adenomas and early cancers \[2\]. There is a need to further improve performance of colonoscopy. The use of chromo-endoscopy has been shown to improve detection of flat adenomas \[3\]. Narrow band imaging was introduced in year 2006. It is similar to chromo-endoscopy in that it provides more mucosal details. This enables endoscopists to accurately describe the pit pattern of adenomas. NBI has been used as a substitute to chromo-endoscopy. In pooled analysis, NBI is comparable to chromo-endoscopy in their sensitivity and specificity in the diagnosis of malignant colorectal adenomas \[4\]. Unfortunately, the use of NBI has not been shown to conclusively improve rate of colorectal adenoma detection. Two of 3 randomized trials that compared WLE to NBI showed a higher adenoma detection rate with the use of NBI \[5, 6\]. In a study by Rex et al., the rate was however similar with either modality. In a pooled analysis, NBI was only marginally better than WLE \[4\].

The effective use of NBI depends on the quality of bowel preparation and the experience of endoscopist. In the presence of fecal matters, NBI tends to be dark and detection of small adenomas becomes difficult. The prototype bright NBI coupled with high definition resolution is likely to overcome this drawback of original NBI.

Diagnosis of Colonic Adenomas by Bright Narrow Band Imaging (B-NBI)

A Randomized Comparison Between White Light Endoscopy (WLE) and Bright Narrow Band Imaging (B-NBI) in the Diagnosis of Colonic Adenomas in Asymptomatic Subjects Undergoing Screening Colonoscopy

compare the rate in colorectal adenoma detection between B-NBI and conventional colonoscopy

compare the advanced neoplasm detection rate

compare the sensitivity and specificity between B-NBI and conventional colonoscopy

Chinese University of Hong Kong

Professor

In this arm1, an investigator observes a cancerous lesion using white light endoscopy. In addition, contrast dye for confocal laser endomicorscopy (fluorescein sodium 0.1mL/kg) is administered. Then, the cancerous lesion is observed using probe-based confocal laser endomicroscopy. The biopsy would be done 5 times at the most suspcious parts of the cancerous lesion.

Probe-based confocal laser endomicroscopy

In this arm2, an invesigator observes a cancerous lesion using white light endoscopy. The biopsy would be done 5 times at the most suspicious parts of the cancerous lesion.

White light endoscopy

The purpose of this study is to conduct a study on genetic pathology, obtaining of pure cancer tissues is mandatory. Although the endoscopy with biopsy has been a gold standard for diagnosing gastric cancer, percentage of cancer cells in biopsy samples is usually 30% or less. Recently, confocal laser endomicroscopy has been introduced for real-time histopathologic diagnosis in various cancers. The investigators aim to evaluate that biopsy using probe-based confocal laser endomicroscopy will increase the percentage of cancer cells in biopsy samples.

A Pilot Study on Usefulness of Probe-based Confocal Laser Endomicroscopy Targeted Gastric Biopsy

The percentages of cancer cells in biopsy samples according to the method of endoscopic method, probe-based confocal laser endomicroscopy versus white light endosocpy

Yonsei University

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Nervous System Diseases

Carcinoma

Carcinoma, Squamous Cell

Inflammation

Recurrence

Squamous Cell Carcinoma of Head and Neck

Carcinoma in Situ

Dysphonia

Hoarseness

Laryngeal Diseases

Laryngeal Neoplasms

Papilloma

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

Neoplasms, Squamous Cell

Voice Disorders

Respiration Disorders

Neurologic Manifestations

Signs and Symptoms, Respiratory

Chronic Graft Versus Host Disease

Recurrent Respiratory Papillomatosis

Laryngeal Cancer

150 patients with suspected lesion in larynx and hypopharynx on standard ENT white light endoscopy examination will undergo NBI endoscopy in order to compare the outcomes of these two examination methods

see in "detail description of the study" part of the protocol

NBI endoscopy

Pavel Kominek, MD,PhD,MBA

The aim of the project is to compare NBI endoscopy and standard endoscopic method using white light and evaluate accuracy both methods in early detection and diagnosis hypopharyngeal and laryngeal precancerous and cancerous lesions. A higher contrast between the mucosal epithelium and blood vessels is achieved in NBI endoscopy using filtered light comparing to white light observations. This allows detection of small mucosal changes, few millimetres in diameter, which are not observable using white light. The second aim in patients with squamous cell carcinoma of the upper aerodigestive tract is to compare extension of mucosal lesions by evaluation of NBI endoscopy and white light endoscopy, which is crucial for perform targeted biopsy and for determination of resection margins in cancer surgery. The investigators expect that dysplastic changes of mucosa or early laryngeal cancerous lesions are detected in white light endoscopy rarely. In case our hypothesis is confirmed, frequency of precancerous and early cancerous lesions of hypopharynx and larynx is more common in patients with non-specific symptoms of laryngeal and pharyngeal diseases.

Laryngeal squamous cell carcinoma (SCC) is one of the most common head and neck cancers. In many cases laryngeal SCC is diagnosed too late for curative treatment - the reasons are non-specific symptoms and very often poor social status of patients, on the other hand also limited diagnostics modalities. Its early detection and diagnosis is essential in order to maximise cure rates and to preserve vocal function. Radiological evaluation with computer tomography (CT) and magnetic resonance imaging (MRI) provides vital information on the extent of the primary tumor and the presence of cervical lymph node metastasis, but fails to identify superficial mucosal abnormalities. At present, white light laryngoscopy combined with biopsy is the standard diagnostic procedure in the assessment of laryngeal cancer and precancerous lesions. However, white light laryngoscopy provides poor quality images and has difficulty identifying epithelial changes and directly differentiating benign from malignant tumors in vivo.

The best case scenario for early detection of SCC of the upper aerodigestive tract (UADT) would be at the stage of squamous dysplasia or even carcinoma in situ. These early lesions are very difficult to detect even with multiple passes with the endoscope, if they are ≤ 1 cm in diameter. In gastroenterology are still more common used endoscopies with high magnification for detection pathological mucosal lesions, but in otorhinolaryngology is using these equipments still limited. However, in recent years are detected epithelial lesions more common by biological endoscopic methods. A well established technique, already in use for the oesophagus, is Lugol chromoendoscopy, where squamous dysplasia and carcinoma in situ appear as Lugol voiding lesions (Watanabe et al., 2003). These precancerous lesions can be easily resected via endoscopic mucosal resection, which is a minimally invasive procedure with short hospital stay. However, this technique cannot be applied in the head and neck region due to the severe mucosal irritation that may lead to severe dysphagia and even aspiration. Other biological endoscopic methods include autofluorescence, contact endoscopy or narrow band imaging.

Recently, a new high-resolution endoscopic technique, narrow band imaging, has begun to be widely used in the early diagnosis of gastrointestinal cancer. Narrow band imaging is based upon the fact that the depth of light penetration depends on the light wavelength: the longer the wavelength, the deeper the penetration. Narrow band imaging modifies the broadband white light from a xenon lamp into two narrow band illumination beams with central wavelengths of 415nm - blue light, which is designed to primarily penetrate the musoca and display superficial capillary networks, and 540 nm - green light designed to penetrate the submucosa and visualized subepithelial vessels. When these two wavelengths are used in combination, they provide and extremely high contrast image of the tissue surface. In literature (Ni et al., 2011) is described classification of intraepithelial papillary capillary loop features using narrow band imaging, which is used in diagnosis of epithelial lesions and ranging from benign to malignant. According to the literature sensitivity of NBI in detection malignant lesions (carcinoma in situ or invasive carcinoma) is 88.9%, significantly greater than that of white light visualization (68.9%), specificity of NBI is 93.2% (Ni et al., 2011).

It is possible to expect that using NBI endoscopy will be improved diagnostics early cancerous epithelial changes in hypopharynx and larynx in ENT patients with non-specific symptoms and in cases at the beginning of cancer growth, which is not detected by any other imaging methods. Also using peroperative NBI the investigators expect better detection of resection margin in cancer laser surgery and decrease of re-operations or adjuvant radiotherapy postoperatively.

Aims of project

* to evaluate the value of narrow band imaging in the early detection of laryngeal cancer and its precursor lesions and compare usefulness NBI endoscopy and assessment in standard white light endoscopy
* to carry out detection of epithelial lesions by NBI endoscopy and stroboscopic assessment in patients with changes on the vocal folds and to compare both methods
* to improve detection of precancerous and cancerous changes in hypopharynx and larynx
* to compare extension of mucosal lesions by evaluation of NBI endoscopy and white light endoscopy, and evaluate spreading of cancer in mucosa
* to evaluate influence of extraesophageal reflux (EER) to occurrence of dysplastic lesions

Working hypotheses

1. Precancerous lesions and early mucosal changes are detected in white light endoscopy rarely.
2. Frequency of precancerous lesions and early cancer in hypopharynx and larynx is more often in patients with non-specific symptoms of diseases of head and neck as the investigators thinking.

Methodology

The project is designed as a prospective study which is in compliance with the principles and policies of the Helsinki Declaration and has been approved by the Ethics Committee.

The patients will be enrolled into the study at the phoniatric out-patient part of the ENT department of the University Hospital in Ostrava and ENT department of the University Hospital Hradec Králové. A total of 120-150 patients will be enrolled into the study within 3 years (2012-2015).

Inclusion criteria

1. patients in age 30-80 years
2. patients with chronic inflammation of hypopharynx and larynx longer than 3 months (with pain in throat, globus pharyngeus,...) and/or
3. patients with hoarseness longer than 3 weeks and/or
4. patients with macroscopic laryngeal lesions (leukoplakia, erythroplakia, Reinke oedema, excluded polyps, cystic lesions and nodules)
5. patients with histological confirmation of dysplasia and/or
6. patients with carcinoma in situ/invasive carcinoma of hypopharynx or larynx and/or
7. patients with recurrent respiratory papillomatosis of all ages.

Entry examination Patient enrolled into the study will be asked to complete a questionnaire (age, sex, body weight, smoking habits, alcohol drinking, gastroesophageal/extraesophageal reflux disease in past), to complete Reflux symptom questionnaire (questionnaire used to determine the symptoms typical for EER) and Voice handicap questionnaire. They will undergo endoscopic evaluation of hypopharynx and larynx using flexible white light magnifying videolaryngoscopy with high definition television - lesions will be split according to type of macroscopic pathology (normal mucosa, chronic inflammation, leukoplakia/erythroplakia, papilloma, exophytic tumor, Reinke´s oedema, other), will be evaluated Reflux finding score, videostroboscopy. In narrow band imaging endoscopy will be evaluated epithelial capillary network and classified type of pathological microvasculature. In indicated cases will be performed targeted biopsy in local or general anesthesia.

Data collection, analysis of data and proposal of the statistical processing

The statistical processing will be carried out by Ing. Hana Tomášková, Ph.D. from the Institute of Epidemiology and Public Health, Medical Faculty of the Ostrava University. Suspicion at dysplasia/carcinoma will be compare based on:

1. evaluation of epithelial lesion in white light endoscopy and NBI endoscopy - how many times will be detected malignant lesion in NBI more often than in white light endoscopy
2. evaluation of laryngeal changes in white light endoscopy and videostroboscopy
3. evaluation of laryngeal epithelial changes in NBI endoscopy and videostroboscopy
4. histological evaluation and preoperative endoscopy (white light, NBI, videostroboscopy)
5. connection of EER and benign laryngeal lesion, dysplasia, early stages of carcinoma The methods of descriptive statistics will be used for statistical processing (arithmetic mean, standard deviation, frequency tables), X2 test, Fisher´s exact test, analysis of variance (ANOVA), OR calculation (odds ratio) with 95% confidence intervals and logistic regression. The statistics tests will be assessed on the significance level of 5%. The statistical analysis will be carried out with the Stata v.10 program. The investigators will use the MS Excel program for data collection.

Discussion

Endoscopic evaluation of hypopharyngeal and laryngeal mucosa is new, quite promising method in otorhinolaryngology, which has been established to the praxis 4 years ago. In this method have been examined maximally hundreds of patients. Now is necessary to validate correlation between symptoms of patients and clinical features in different groups of patients, which have non-specific manifestation of upper aero-digestive tract diseases and between patients in different ages. In literature are published reports Japanese gastroenterologists, especially, about impact of NBI endoscopy in diagnosis of epithelial changes. These studies were oriented on esophageal, gastric and intestinal pathologies, but suggest that NBI endoscopy can improve detections of early precancerous and cancerous lesions of hypopharynx and larynx. In case this declaration will be confirmed, in high number of patients with non-specific symptoms could have early diagnosis a strong importance for more successful oncologic treatment.

Benefit of this project in case the investigators confirm the hypothesis that frequency of precancerous lesions and early cancer in hypopharynx and larynx is more often in patients with non-specific symptoms of diseases of head and neck as the investigators thinking and precancerous lesions and early mucosal changes are detected in white light endoscopy rarely, it is possible to expect that the NBI method will be used more often for detection of early cancer in upper aero-digestive tract. This will improve the effect of oncologic treatment and quality of life of these patients.

Intervention

Standard white light magnifying endoscopy, Narrow Band Imaging endoscopy, videostroboscopy, pH monitoring

- see details in "detail description of the study" part of the protocol

Value of Narrow Band Imaging (NBI) Endoscopy in the Early Diagnosis of Laryngeal Cancer and Precancerous Lesions

The extension of mucosal lesions will be assessed by evaluation of NBI endoscopy and white light endoscopy, together with evaluation of spreading of cancer in mucosa. The total number of patients with larger extent of the laryngeal lesion on NBI examination will be determined, in comparison with the results obtained with standard white light endoscopy.

Findings on NBI endoscopy will be compared to findings obtained with white light endoscopy; the usefulness of both methods will be assessed. The number of patients with histologically proven laryngeal cancer will be determined.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
RCT: WLE vs. NBI in Upper Gastrointestinal Endoscopy	NCT01945177	Gastric Intesti... Gastric Cancer	narrow band ima... white light end...	50 Years -	Changi General Hospital
Comparison Between White Light Endoscopy and Bright Narrow Band Imaging in Diagnosis Colonic Adenomas.	NCT01737567	Colonic Adenoma...	Bright Narrow B... White Light End...	50 Years - 99 Years	Western Sydney Local Health District
Comparison Between White Light Endoscopy and Bright Narrow Band Imaging in Diagnosis Colonic Adenomas.	NCT01737567	Colonic Adenoma...	Bright Narrow B... White Light End...	50 Years - 99 Years	Western Sydney Local Health District
Can Pan-Colonic Chromoendoscopy (PCC) Improve Adenoma Detection Rate in FIT-Positive-Patients: A Randomized Study	NCT04512612	Colon Adenoma	Chromoendoscopy High definition...	50 Years -	Singapore General Hospital
Diagnosis of Colonic Adenomas by Bright Narrow Band Imaging (B-NBI)	NCT01422577	Colonic Adenoma...	Bright Narrow B... White light End...	40 Years -	Chinese University of Hong Kong
A Pilot Study on Usefulness of Probe-based Confocal Laser Endomicroscopy Targeted Gastric Biopsy	NCT02089373	Gastric Cancer	Probe-based con... White light end...	20 Years - 80 Years	Yonsei University
Value of Narrow Band Imaging (NBI) Endoscopy in the Early Diagnosis of Laryngeal Cancer and Precancerous Lesions	NCT02217358	Chronic Inflamm... Hoarseness Macroscopic Lar... Histological Co... Carcinoma in Si... Invasive Carcin... Invasive Carcin... Recurrent Respi...	NBI endoscopy	30 Years - 80 Years	University Hospital Ostrava
Value of Narrow Band Imaging (NBI) Endoscopy in the Early Diagnosis of Laryngeal Cancer and Precancerous Lesions	NCT02217358	Chronic Inflamm... Hoarseness Macroscopic Lar... Histological Co... Carcinoma in Si... Invasive Carcin... Invasive Carcin... Recurrent Respi...	NBI endoscopy	30 Years - 80 Years	University Hospital Ostrava

Spots Global Cancer Trial Database for white light endoscopy