P53 Functional Assay (FASAY) in Head and Neck Squamous Cell Carcinoma : preanalytical issues and value as indicator of field cancerization?

Head and Neck Squamous Cell Carcinoma (HNSCC) is a complex disease arising in various localisations of the upper aerodigestive tract, caused by tobacco and alcohol consumption or by high-risk types of human papillomavirus. These tumors often develop within pre-neoplastic fields of genetically altered cells that often extend out of the clinically and macroscopically involved area where the focus of treatment is. This phenomenon is a major cause of locoregional recurrences or second primary tumors and subsequently of poor survival improvement in HNSCC patients. Among the numerous genetic alterations found in HNSCC carcinogenesis, mutations of TP53 tumor suppressor gene were found to be one of the earliest and the most significant events of invasive cancer development. TP53 gene encodes the p53 protein that plays a crucial role in apoptosis and cell cycle control, making it a plausible predictive biomarker for HNSCC survival. The purpose of the study was to investigate the field cancerization through the analysis of p53 functionality on both tumoral and histologically normal tissue distant from the tumor. As expected, alteration of p53 functionality was encountered in 88% of tumoral samples. More interestingly, the loss of p53 transcriptional activity was detected in 18% of distant histologically normal samples and was significantly associated with loco-regional recurrences. We demonstrated that FASAY positivity indicates field cancerization in a subgroup of patients with HNSCC. These findings prompted us to pursue the study on p53 functional status of normal mucosa in patients with HNSCC in a homogeneous cohort of patients with oropharyngeal squamous cell carcinoma, stratified for HPV status, obtained by multicentric study. In order to avoid underestimation of the FASAY positive rate in histologically normal surrounding mucosa, we developed a non-invasive collection method allowing the study of a wider mucosal surface. While this sample collection method deals with scarce tissue material and in order to circumvent the material loss due to manual homogenization of samples, we studied an automated extraction process. This technique appeared to be a versatile, quick, safe, and reliable homogenization method, especially useful for small ≤10 mg oral squamous cell carcinoma samples. With the improved rate of RNA extraction obtained when using an automated method, FASAY on scant target cells obtained by scraping the oral mucosa appeared feasible and reproducible. Our experience with the FASAY technique showed that both tissue quantity and quality are mandatory. Keeping in mind the perspective of a multicentric trial, we set up a method to store and transport easily and safely our tissue samples in optimal conditions for further RNA extraction and FASAY processing. This work demonstrated that FASAY positivity is the hallmark of HNSCC and a reliable and sensitive tool to demonstrate the presence of field cancerization in a subgroup of patients. A prospective multicentric study on the p53 functional status of normal mucosa in patients with HNSCC or even who are still cancer-free but heavily exposed to HNSCC risk factors is needed.(MED 3) -- UCL, 201

Un kyste cervical chez l’adulte : prudence !

Toute lésion kystique cervicale apparue après 40 ans doit faire l’objet d’investigations approfondies de la sphère ORL et en particulier de l’amygdale palatine et de la base de langue homolatérales.[Cervical cysts in adults: caution!] Any cervical cystic lesion detected after the age of 40 should lead to thorough investigations in the ear-nose-throat (ENT) sphere and in particular in the homolateral palatine tonsil and tongue base

Successful management of hereditary angioedema during tonsillectomy: a case report

Hereditary angioedema (HAE) is a rare genetic disorder causing a deficiency in C1 esterase inhibitor (C1-INH) that is manifested through unpredictable oedema. We describe a case of a patient with HAE who had previously been refused surgery for tonsillitis due to the potential for oedema, in whom regular monitoring of C1-INH levels combined with intensified therapy with danazol, tranexamic acid and C1-INH concentrate enabled an uncomplicated procedure with no oedema crisis. However, clinicians should be alerted that higher overall dosages of C1-INH concentrate for perioperative prophylaxis may be required than those typically used to treat acute HAE attacks

Transoral robotic surgery (TORS) for head and neck cancer

Transoral robotic surgery (TORS) in Head and Neck oncology is a recent technical option with continued refinements. The management of head and neck cancer is currently based on organ preservation strategy. Surgery when required can be a first-line or as part of a salvage surgery. It is performed by open neck approach or transorally. In the case of a transoral surgery, the contribution of the robot is outlined. In this article, we have reviewed the existing published data and based on our expertise provided to the reader the evidence about the role of TORS for head and neck cancer, current indications for this procedure, advantages, disadvantages future developments as well as the user’s expectations

Severe dysphagia caused by vagus nerve herpetic neuropathy: a case report

In this study, we report a rare case of herpetic infection of the larynx with vagus nerve palsy. Herpes simplex virus (HSV) and varicella zoster virus (VZV) are among the most common viral causes of vagus nerve (VN) dysfunction. The clinical presentation of herpetic laryngitis is variable. The diagnosis is clinical and can be confirmed by serological test or better yet by a PCR. When HSV or VZV infection is suspected, it is mandatory to start the antiviral treatment rapidly, within 72 hours. The use of corticosteroids remains a controversial subject. The consequences of vagus nerve damage are not negligible in terms of quality of life and may cause multiple symptoms due to the anatomical distribution of the nerve. Once the diagnosis is confirmed, intensive voice and swallowing rehabilitation must be undertaken to limit the functional impact and quality of life degradation

Transoral Robotic Surgery and Geriatric Population: Which Benefit?

1.1. Purpose: As a result of increased life expectancy, the proportion of elderly patients with head and neck cancer is constantly rising. Transoral robotic surgery has been developed over the last ten years as a minimal invasive surgical procedure. The purpose of this study is to evaluate the place of this technique for elderly patients. 1.2. Methods & material: Study data related to elderly (age over 75 years) patients who underwent TORS between March 2008 and March 2018 were analyzed. 28 elderly patients were included; the different locations were 18 laryngeal (10 glottic and 8 supraglottic), 3 hypopharyngeal, 2 oral cavities and 5 oropharyngeal carcinoma respectively. 1.3. Results: 28 patients, 23 men and 5 women, with an average of 79 years old were successfully operated without external conversion. The 3-year Disease-Specific Survival (DSS) rate is 87.3% and the 3-year overall survival (OS) rate is 65,6%. Surgery was completed in a mean of 131 minutes (including exposure). All patients were extubated the same day (56%) or the day after the surgery (44%). Except for total laryngectomies, three patients (10.7%) received transient tracheostomies. Oral feeding was started after an average of 11 days after surgery. The hospitalization stay was 27 days on average. 1.4. Conclusions: Trans-oral Robotic surgery is a valuable technical option to address selected head and neck carcinoma in the elderly population. Early postoperative rehabilitation limits swallowing disorders and pulmonary complications. The surgical time is reduced compared to conventional open surgery which is a great advantage for this fragile population

Use of cidofovir in HPV patients with recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis is a viral-induced disease, associated with exophytic epithelial lesions affecting the upper airways. Problem of treatment is the high recurrence of papilloma growth after surgical removal; therefore, adjuvant therapy schemes have been established. We used cidofovir, 7.5 mg/ml, in adjuvant therapy in the past years. Out of 31 adult patients treated with the drug, 26 (83.9 %) are at the moment in complete response. 19 (73 % of pts with CR) of those 26 patients were cured with a number of injections between 1 and 4 (mean 2.5). We did not see any clinical manifestation of renal toxicity or neutropenia (superinfection) necessitating a blood test. Six patients presented dysplasia during the treatment with the drug, while six patients had dysplasia prior to cidofovir injection. Due to recurrent nature of the disease and the high number of mechanical and laser surgeries required we treated one tracheal stenosis, two scarred larynx, and two glottic synechiaes. There is still an ongoing discussion within the European Laryngological Society about the effectiveness and possible side effects of this drug. Results show promising long-term effects of adjuvant use of cidofovir, without any relevant side effects

Transoral robotic surgery hypopharyngectomy (TORSH): feasibility and outcomes.

With the development of minimal invasive procedure, trans-oral robotic surgery (TORS) is expanding in the field of ENT. Most reviews focus on oropharyngeal and laryngeal (supra-glottic) localization. We report here the feasibility and outcomes of TORS hypopharyngectomy (TORSH) for selected patients with hypopharyngeal tumor. Between September 2009 and July 2017, 22 patients, retrospectively included, underwent TORSH with curative intent. From 22 successful hypopharyngectomy, no conversion to open procedure was needed. Three patients (13%) presented a post-operative bleeding and were managed by surgical revision. No fistula was encountered. The 3-year overall survival and disease-specific survival rates were 54 and 92%, respectively. Patients started oral feeding after an average of 7 days. Naso-gastric feeding tubes were removed after a median period of 16 days. Two patients (9%) needed a transient gastrostomy (< 1 year). Three patients (13%) received a transient tracheostomy (< 2 months). Median hospitalization stay was 13 days. TORSH is a safe technique. Patients' outcomes are favorable and the post-operative morbidity is reduced compared to open neck approach. Hospitalization length and safe swallowing time are reduced