Recurrent Respiratory Papillomatosis Clinical Trial
Official title:
Value of Narrow Band Imaging (NBI) Endoscopy in the Early Diagnosis of Laryngeal Cancer and Precancerous Lesions
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
;
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
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