Clinical trial NCT04006197: Vocal Folds Irregular Mucosal Changes: A Clinical, Pathological and Genetic Study
Official title: Vocal Folds Irregular Mucosal Changes: A Clinical, Pathological and Genetic Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Vocal Cord Neoplasm
Keywords: vocal folds dysplasia
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: one hundred patient with localized or diffuse vocal folds irregularites wiii be examined for primary diagnosis at the phoniatric unit of ENT department in Assiut university hospital.main symptom of all patients is dysphonia of varying degree and dauration from afew days to several months .

Brief summary: simple combination of functional investigation, in form of laryngostroboscopy, together with conventional histopathological examination, provides a highly sensitive method in differential diagnosis of undiagnosed vocal folds irregularites

Detailed description: Vocal folds irregular mucosal changes often manifest as mucosal surface changes of leukoplakia, erythroplakia and keratosis associated with tissue irregularities. Lesions that go beyond the outermost layer of the vocal fold and invade the intermediate and deep layers. These gross mucosal changes may represent benign, premalignant, or malignant entities as they correspond to large spectrum of lesions ranging from simple totally benign keratosis with or without atypia up to invasive carcinoma, it is commonly encountered in phoniatrics clinic and presents diagnostic and therapeutic challenge as there is no unified surgical indication or guidelines.

Laryngostroboscopy is very important and primary tool for assessment of morphological features and vibratory functions of the vocal folds. Stroboscopic evaluation allows early detection of infiltrative processes of the vocal folds. However, the laryngoscope examination may not always be sufficient to assess premalignant lesions and their exact delineation.

Gugatschka et al., 2008 reported that videostroboscopic evaluation allows early detection of infiltrative processes of the vocal folds, as they achieved a sensitivity of more than 97 %, when used a combination of cytology and videostroboscopy, in contrast to 74 % as found by cytology alone.

Zhang et al., 2018 proposed to classify VF leukoplakia into three types according to the morphological appearance. The evaluated features included texture, color, and thickness. They proved that type III-bulge and rough-with irregular, nonhomogeneous leukoplakia higher than mucosa surface was more often associated with cancerization or severe dysplasia in 29.3% and 21.5% cases, respectively, comparing to the respective percentages of 4.0% and 3.7% for type I-flat and smooth leukoplakia. Anna Rzepakowska et al submitted a protocol for evaluation of the morphological characteristics of leukoplakia which involved the following features of the lesion: color, texture, size, thickness, symmetry and vibratory function. Each character was assigned with the score of zero or one (score zero was considered to be a clinical indicator of benign lesions, while, score one was a clinical indicator of malignancy).

Recent advances in basic research have improved understanding of underlying mechanisms of molecular processes in early stages of laryngeal cancer development. The SOX2 gene located at 3q26 is frequently amplified and overexpressed in multiple cancers, including head and neck squamous cell carcinomas (HNSCC). The tumor-promoting activity and involvement of SOX2 in tumor progression has been extensively demonstrated, thereby emerging as a promising therapeutic target. However, the role of SOX2 in early stages of tumorigenesis and its possible contribution to malignant transformation remain unexplored. Granda-Diaz etal., 2019 investigated for the first time SOX2 gene in precancerous lesion using real-time PCR and demonstrated that SOX2 protein expression and gene amplification are frequent events in early stages of laryngeal tumorigenesis

Eligibility criteria: inclusion criteria

1. Age 18-70 years old males
2. Unilateral or bilateral localized and diffuse vocal fold irregularities.
3. Patients with white (leukoplakia) patches on one or both vocal folds
4. No previous microphonosurgery.
5. No previous history of radiotherapy .6.No impairment of the vocal fold mobility.

exclusion criteria

1. Subject refusal.
2. Patients with large exophytic and/or ulcerated mass.
3. Vocal fold cysts or polyps, contact granulomas, or Reinke's edema
4. If there is a concern for rapid growth pattern, airway obstruction requiring urgent operative intervention
5. Vocal fold immobility
6. History of allergies and GERD.
7. Unfit for general anesthesia

Primary outcomes:
measure: measurment of incidance of vocal folds dysplasia from all cases of vocal folds irregular mucosal changes in phoniatric unit of assiut university hospital within the two years of study
timeFrame: baseline
Secondary outcomes:
measure: to correlate between laryngostroboscopic and histopathological finding
timeFrame: baseline
Other outcomes:
Locations:
Study officials:
References:
citation: Ferlito A, Devaney KO, Woolgar JA, Slootweg PJ, Paleri V, Takes RP, Strojan P, Bradley PJ, Rinaldo A. Squamous epithelial changes of the larynx: diagnosis and therapy. Head Neck. 2012 Dec;34(12):1810-6. doi: 10.1002/hed.21862. Epub 2011 Oct 3.
citation: Gugatschka M, Kiesler K, Beham A, Rechenmacher J, Friedrich G. Hyperplastic epithelial lesions of the vocal folds: combined use of exfoliative cytology and laryngostroboscopy in differential diagnosis. Eur Arch Otorhinolaryngol. 2008 Jul;265(7):797-801. doi: 10.1007/s00405-007-0549-9. Epub 2007 Dec 4.
citation: Sadri M, McMahon J, Parker A. Management of laryngeal dysplasia: a review. Eur Arch Otorhinolaryngol. 2006 Sep;263(9):843-52. doi: 10.1007/s00405-006-0078-y. Epub 2006 Jul 6.