Neoplasms

Ear, Nose, and Throat Diseases

All Conditions

Ear Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Ear Diseases

Otorhinolaryngologic Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Pharmaceutical Solutions

Analgesics

Anesthetics

Propofol

Remifentanil

Analgesics, Opioid

Narcotics

The general anesthesia during the diagnostic panendoscopy of the upper airway will associate the target controlled infusion of propofol (pharmacologic model of Schnider et al.) and of remifentanil (pharmacologic model of Minto et al.) in the remifentanil group.

The arm will be randomized prior to the beginning of the surgical procedure and blinded to the investigator and to the practitioner in charge of the patient.

Two milligrams of remifentanil will be diluted in 40 cc of sodium chloride 0,9% in a 50 ml syringe.

The general anesthesia during the diagnostic panendoscopy of the upper airway will consist in the target controlled infusion of propofol alone (pharmacologic model of Schnider et al.) in the placebo group.

The placebo is a 40 ml sodium chloride 0,9% solution in a 50 ml syringe. No one can distinguish the syringe of placebo from the syringe of remifentanil.

Target-controlled infusion of remifentanil 50 µg/ml using the pharmacologic model of Minto et al. to achieve a theorical brain concentration of 1.5 ng/ml.

Sébastien Pili Floury, MD, PhD

Angéline Chopard-Guillemin, MD

Amélie Jurine, MD

Guillaume Besch, MD

Arnaud Causeret, MD

The most important considerations for the general anesthesia in diagnostic panendoscopy of the upper airway is the maintenance of a patient's airway for optimal surgical exposure, adequate ventilation and sufficient depth of anesthesia. Tubeless anesthestic techniques with preserved spontaneous ventilation and total intravenous administration of anesthetic drugs are widely use. Due to its pharmacological profile, propofol anesthesia is often considered as the gold standard for the anesthesia in the diagnostic panendoscopy. Previous studies suggested that adding remifentanil to propofol could improve the conditions for laryngoscopy and tracheal intubation.

The aim of this study is to assess the impact of propofol remifentanil general anesthesia compared to propofol general anesthesia on the conditions of the diagnostic panendoscopy of the upper airway.

Conditions of Diagnostic Panendoscopy of the Upper Airway Under Propofol Remifentanil General Anesthesia

Evaluation of the Impact of Adding Remifentanil to Propofol on the Conditions of the Diagnostic Panendoscopy of the Upper Airway Under General Anesthesia With Tubeless Spontaneous Ventilation.

The assessment of the conditions for the diagnotic panendoscopy of the upper airway will be based on: (1) the conditions for the laryngoscopy ("excellent"=easy; "good"=fair; "poor"=difficult), (2) the position of the vocal cords ("excellent"=abducted; "good"=intermediate; "poor"=closed), (3) the movements of the vocal cords ("excellent"=none; "good"=moving; "poor"=closing), (4) the movement of the limbs ("excellent"=none; "good"=sight; "poor"=vigorous), (5) the cough ("excellent"=none; "good"=diaphragm; "poor"=sustained (\>10 s)). The conditions for the diagnostic panendoscopy will be considered as "excellent" when all variables will be excellent, as "good" when all variables will be either good or excellent and as "poor" when one or more variables will be graded as poor. Clinically acceptable conditions are defined as either good or excellent conditions.

The DeltaHRmax characterises the amplitude of the maximal increase of the heart rate during the diagnostic panendoscopy of the upper airway. The DeltaHRmax is defined as following: deltaHRmax=((HRmax-HRt0)\*100)/HRt0). HRmax is the highest value of the heart rate observed during the panendoscopy and HRt0 is the basal value of the heart rate.

The DeltaHRmin characterises the amplitude of the maximal decrease of the heart rate during the diagnostic panendoscopy of the upper airway. The DeltaHRmin is defined as following: deltaHRmin=((HRt0-HRmin)\*100)/HRt0). HRmin is the lowest value of the heart rate observed during the panendoscopy and HRt0 is the basal value of the heart rate.

The DeltaMAPmin characterises the amplitude of the maximal decrease of the heart rate during the diagnostic panendoscopy of the upper airway. The DeltaHRmin is defined as following: deltaHRmin=((HRt0-HRmin)\*100)/HRt0). HRmin is the lowest value of the heart rate observed during the panendoscopy and HRt0 is the basal value of the heart rate.

The DeltaMAPmax characterises the amplitude of the maximal increase of the mean arterial pressure (MAP) during the diagnostic panendoscopy of the upper airway. The DeltaMAPmax is defined as following: deltaMAPmax=((MAPmax-MAPt0)\*100)/MAPt0). MAPmax is the highest value of the mean arterial pressure (MAP) observed during the panendoscopy and MAPt0 is the basal value of the mean arterial pressure (MAP).

Moderate hypoxemia is defined as a pulse oximetry value (SpO2) under 94% during the diagnostic panendoscopy of the upper airway.

Severe hypoxemia is defined as a pulse oximetry value (SpO2) under 90% during the diagnostic panendoscopy of the upper airway.

Invasive mechanical ventilation via an emergent surgical tracheotomy or an endotracheal intubation could be required in case of life-threatened hypoxemia during the diagnostic panendoscopy of the upper airway.

Surgical complications are defined as dental breakage, bleeding or mucosal injuries directly related to the diagnostic panendoscopy of the upper airway or to the biopsy.

Centre Hospitalier Universitaire de Besancon

Gland and Hormone Related Diseases

Adenoma

Thyroid Neoplasms

Thyroid Diseases

Thyroid Nodule

Endocrine System Diseases

Endocrine Gland Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Patients who will undergo thyroidectomy will be evaluated by an ENT physician by flexible fiberoptic laryngoscopy before the surgery

The same patients evaluated by flexible fiberoptic laryngoscopy will be evaluated by an anesthesiologist by direct laryngoscopy during surgery under general anesthesia

Patients who will undergo thyroidectomy will be evaluated by awake flexible fiberoptic laryngoscopy and during surgery by direct laryngoscopy under general anesthesia

Flexible fiberoptic laryngoscopy

Patients who will undergo thyroidectomy evaluated before by ENT physician, will be evaluated by anesthesiologist in means of MCL score by direct laryngoscopy during surgery under general anesthesia

Direct laryngoscopy

Cigdem Akyol Beyoglu, MD

Emine D Gozen, MD

Emine D Gozen

Guniz Koksal, Prof

Nowadays, 5-step modified Cormack-Lehane scoring (MCL) system is frequently used in the observation of laryngeal structures by direct laryngoscopy.

Upper airways with flexible fiberoptic laryngoscopy are routinely evaluated in patients who are predicted to be difficult intubation, who have undergone head or neck surgery previously and who require vocal cords to be evaluated preoperatively. During this examination patients are awake; so the upper airway and the muscles in the base of the mouth have normal tonus and airway reflexes are active. When general anesthesia is applied to the same patients during direct laryngoscopy, the laryngeal view may not be as clear as awake flexible fiberoptic laryngoscopy, since a tonus loss occurs in the muscles after general anesthesia.

The aim of the study is to investigate the relationship between preoperative awake flexible fiberoptic laryngoscopy performed by ear- nose- throat (ENT) physicians in patients undergoing total thyroidectomy, and the MCL score during direct laryngoscopy after general anesthesia in the same patients. Thus, investigators would like to determine the reliability of airway evaluation with preoperative awake flexible fiberoptic laryngoscopy in predicting intubation conditions during tracheal intubation under general anesthesia.

In daily practice, the upper airway evaluation is performed by the ENT physician with flexible fiberoptic laryngoscopy while the patients are awake one day before thyroidectomy. This evaluation will be done by the same ENT physician (EDG). Each patient will be kept in the neutral position and at the level of soft palate, the larynx will be observed by the flexible fiberoptic laryngoscopy and the laryngeal view and MCL score of these patients will be recorded.

The same patients will be taken to the preoperative care unit on the morning of operation and 20 G intravenous cannulation will be performed on the left hand. Patients' neck circumference and Mallampati score and presence of obstructive sleep apnea syndrome will be recorded. Patients will be taken to the operation theatre and standard monitoring will be performed consisting of electrocardiography (ECG), non-invasive blood pressure (BP) and peripheral O2 saturation. After induction of general anesthesia, the same anesthesiologist (CAB) will perform direct laryngoscopy by using Macintosh laryngoscope the MCL score will be recorded. The anesthesiologist will not know the MCL score that was previously evaluated by ENT physician during awake fiberoptic flexible laryngoscopy. Female and male patients will be intubated orotracheally with 7.5-8 internal diameter endotracheal tube, respectively. It will be recorded if the backward, upward, right, lateral pressure Maneuver (BURP) is applied during intubation. The maintenance of general anesthesia will be provided with 2% Sevoflurane in a 40% oxygen-air mixture.

After thyroidectomy is over patients will be extubated. The primary endpoint of the study was to evaluate the relationship between the MCL score, which was evaluated preoperatively, and the MCL score during direct laryngoscopy during intraoperative general anesthesia in awake patients.

Modified Cormack Lehane Scores Evaluated by Laryngoscopy During Awake Versus Under General Anesthesia

The Relationship of Modified Cormack Lehane Scores Between Preoperative Awake Flexible Fiberoptic Laryngoscopy and Intraoperative Direct Laryngoscopy in Thyroidectomies, a Prospective, Clinical Study

all collected individual participant data (IPD)

The primary outcome measure of the study is a 5 graded modified Cormack Lehane scores obtained from patients before and during thyroidectomy. The first measurement will be done one day before surgery, while patient is awake by flexible fiberoptic laryngoscopy. The second measurement will be done during surgery, after induction of general anesthesia by direct laryngoscopy

Istanbul University

Medical doctor

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Nervous System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Inflammation

Recurrence

Squamous Cell Carcinoma of Head and Neck

Carcinoma in Situ

Dysphonia

Hoarseness

Laryngeal Diseases

Laryngeal Neoplasms

Papilloma

Respiratory Tract Diseases

Respiratory Tract Neoplasms

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
Conditions of Diagnostic Panendoscopy of the Upper Airway Under Propofol Remifentanil General Anesthesia	NCT02093143	Tumor of Ear, N...	Remifentanil	18 Years - 80 Years	Centre Hospitalier Universitaire de Besancon
Modified Cormack Lehane Scores Evaluated by Laryngoscopy During Awake Versus Under General Anesthesia	NCT03826680	Thyroid Cancer Thyroid Nodule Thyroid Adenoma	Flexible fibero... Direct laryngos...	18 Years - 70 Years	Istanbul University
Conditions of Diagnostic Panendoscopy of the Upper Airway Under Propofol Remifentanil General Anesthesia	NCT02093143	Tumor of Ear, N...	Remifentanil	18 Years - 80 Years	Centre Hospitalier Universitaire de Besancon
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
Modified Cormack Lehane Scores Evaluated by Laryngoscopy During Awake Versus Under General Anesthesia	NCT03826680	Thyroid Cancer Thyroid Nodule Thyroid Adenoma	Flexible fibero... Direct laryngos...	18 Years - 70 Years	Istanbul University

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