Significance of MYB and NTRK Expression in Head and Neck Adenoid Cystic Carcinoma.

BACKGROUND/AIM: Adenoid cystic carcinoma (ACC) is an aggressive neoplasm even though it has low-grade histological appearance and slow growth. The aim of this study was to identify the immunohistochemical and molecular characteristics of ACC, as well as their correlation with the clinical course of patients. PATIENTS AND METHODS: This is a retrospective multicenter analysis. We included 50 patients diagnosed with ACC in the head and neck between 2000 and 2021. The expression of MYB proto-oncogene transcription factor (MYB), neurotrophic tyrosine kinase receptor (NTRK), human epidermal receptor-2 (HER-2), and Ki-67 was examined through immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). We also performed a clinical follow-up of the patients. RESULTS: The median age of the patients was 58.5 years; moreover, 54% of the patients were male. Compared with female patients, male patients were at a higher risk of both recurrence and death. No HER-2-positive cases were revealed. MYB expression was positive in 28 (56%) cases. However, MYB expression did not significantly affect survival. NTRK expression was positive in eight (16%) cases. NTRK-positive patients had worse overall survival (OS) than NTRK-negative patients (p=0.0246). Additionally, the percentage of NTRK-stained cells was negatively correlated with disease-free survival (p=0.0016) and OS (p=0.0027). CONCLUSION: There was no correlation between MYB positivity and survival. Contrarily, NTRK-positive patients had worse survival, indicating that NTRK is a negative prognostic factor. Tropomyosin receptor kinase inhibitors can be used to treat these patients. Furthermore, MYB-targeted inhibitors are promising therapeutic agents.

Pediatric Laryngopharyngeal Reflux in the Last Decade: What Is New and Where to Next?

BACKGROUND: Laryngopharyngeal reflux may affect people of any age; still, most of the accumulated knowledge concerns adults, and evidence regarding pediatric populations remains relatively restricted. This study aims to review the most recent and emerging aspects of pediatric laryngopharyngeal reflux from the last ten years. It also attempts to identify gaps in knowledge and highlight discrepancies that future research should urgently address. METHODS: An electronic search of the MEDLINE database was conducted, limited to January 2012 through December 2021. Non-English language articles, case reports, and studies that concerned a purely or predominantly adult population were excluded. The information from the articles with the most relevant contribution was initially categorized by theme and subsequently synthesized into a narrative form. RESULTS: 86 articles were included, of which 27 were review articles, eight were surveys, and 51 were original articles. Our review systematically maps the research done in the last decade and provides an updated overview and the current state-of-the-art in this subject. CONCLUSIONS: Despite discrepancies and heterogeneity in accumulating research, evidence gathered so far endorses a need for refining an escalating multiparameter diagnostic approach. A step-wise therapeutic plan appears to be the most reasonable management approach, starting with behavioral changes for mild to moderate, uncomplicated cases and escalating to personalized pharmacotherapy options for severe or nonresponsive cases. Surgical options could be considered in the most severe cases when potentially life-threatening symptoms persist despite maximal medical therapy. Over the past decade, the amount of available evidence has been gradually increasing; however, its strength remains low. Several aspects remain markedly under-addressed, and further adequately powered, multicenter, controlled studies with uniformity in diagnostic procedures and criteria are urgently needed.

Fourteen cases of acute invasive fungal rhinosinusitis: is there a place for less aggressive surgical treatment?

PURPOSE: Acute invasive fungal rhinosinusitis (AIFRS) is a rare, fulminant, angio-invasive infection with high mortality rate. Treatment of AIFRS includes aggressive surgical debridement combined with antifungal agents and treatment of the underlying disease. The aim of this study is to report our experience with this often fatal disease and estimate the long-term survival of AIFRS patients with more conservative surgery. METHODS: A retrospective study was performed on immunocompromised adults with AIFRS from January 2011 to December 2020. The diagnosis was histologically confirmed by tissue fungus invasion. We analyze epidemiological and microbiological findings, the underlying disease and discuss our patients' treatment plan and long-term survival. RESULTS: Fourteen patients were included in the study. Mean age was 53.8 ± 18.9 years. The underlying disease was hematologic malignancy in nine patients, diabetes mellitus in three, aplastic anemia in one, and renal/liver failure in one. Leukopenia was not significantly correlated with outcome or survival. Histological and culture findings revealed that Mucor/Rhizopus were the causative organisms in nine cases. All patients received systemic antifungal therapy. Surgery was performed in nine patients (endoscopic for all patients, combined in three with an external approach). Overall survival was 35.7% as five patients survived, two who underwent surgery, and three who were treated non-surgically. Nine patients died, two from AIFRS after central nervous system involvement and seven from their primary disease, free of fungi. Older individuals and patients with hematologic malignancies had a worse outcome. CONCLUSION: Early surgical debridement, antifungal agents, and treatment of the underlying disease remain the cornerstones of AIFRS management. Prognosis is overall defined by the underlying disease and in some selected cases, medical treatment alone could be a reasonable option.

The long-term need for calcium supplementation after incidental parathyroidectomy.

Objectives: Hypocalcaemia and hypoparathyroidism are the most frequent complications of total thyroidectomy that may result in the need for lifelong calcium supplementation. This study aims to investigate the impact of incidental parathyroidectomy on short- and long-term hypocalcaemia. Methods: This retrospective study was conducted on patients who underwent total thyroidectomy with or without central neck dissection between March 2016 to May 2018. All procedures were performed by three surgeons with similar experience levels. Histopathology reports were reviewed, the number of resected parathyroid glands and the underlying pathology reports were recorded, and the patients were divided into two groups; groups A and B comprised those with and without parathyroid glands respectively. The incidence rates of short- and long-term hypocalcaemia were recorded. The former was obtained through blood tests during hospitalisation and the latter via phone calls to patients 3, 6, and 12 months postoperatively. Results: A total of 116 patients participated, 18 (15.5%) in group A and 98 (84.5%) in group B. No statistical significance was detected between the two groups regarding early postoperative (p = 0.109) or long-term hypocalcaemia (p = 0.48). These results were similar in patients with cancer (n = 40) (p = 0.855, p = 0.08). Conclusion: Incidental parathyroidectomy of one parathyroid gland was not correlated with a higher incidence of hypocalcaemia, even in cases with thyroid cancer.

Is Auditory Steady-State Response Testing the Key for Diagnosing Non-Organic Hearing Disorders? Implications for Current Audiological Practice.

BACKGROUND AND OBJECTIVES: To describe all possible facets of non-organic hearing disorders (NOHD) and emphasize the superiority of auditory steady-state response (ASSR) over previously employed hearing assessment tools. SUBJECTS AND METHODS: A series of seven patients consisting of three males and four females with NOHD were assessed at Attikon University Hospital (age range: 17-59 years). Three patients had Munchausen syndrome, three intentionally feigned hearing loss, and one intentionally feigned normal hearing. The audiological evaluation consisted of tympanometry, pure-tone audiometry, and ASSR testing. RESULTS: The hearing of all patients was accurately determined using ASSR. The results were confirmed by auditory brainstem responses (ABR) and otoacoustic emissions. CONCLUSIONS: NOHD is a multi-faceted condition encompassing various etiologies. ASSR testing represents an objective and reliable method of hearing assessment, which can serve as a gold standard method for distinguishing NOHD from actual hearing loss. It can reliably indicate the hearing levels at the four main frequencies (500, 1,000, 2,000, and 4,000 Hz) by obtaining a valid estimated audiogram through statistical measures. Compared to ABR testing, ASSR thresholds are closer to the actual audiometric thresholds in the presence of hearing impairment and are superior when the corresponding pure-tone audiogram is widely ranging between the adjacent frequencies or when the obtained ABR curves are not easily distinguished. A non-confrontational approach should be adopted by ENT doctors towards cases of suspected NOHD as the use of ASSR could reliably assess hearing even when medical or medico-legal implications are involved.

Management of paranasal sinus osteomas: A comprehensive narrative review of the literature and an up-to-date grading system.

BACKGROUND: Surgical excision represents the unequivocal treatment modality for symptomatic paranasal sinus osteomas. However, the optimal surgical approach and the extent of the surgery, as well as the management stance in the case of an asymptomatic tumor, remain controversial. METHODS: The MeSH terms 'Osteoma', 'Nasal Cavity', and 'Paranasal Sinuses' were used to retrieve articles concerning the management of paranasal sinus osteomas that were published in the last 30 years, the vast majority of which comprised case reports of one or two cases. Original articles or large series of more than six cases were prioritized. RESULTS: Our review summarizes previous findings and opinions relevant to the management of symptomatic and asymptomatic paranasal sinus osteomas. The recent shifts in trends of their management are thoroughly discussed. Currently, an extension of the lesion through the anterior frontal sinus wall; an erosion of the posterior wall of the frontal sinus; a far-anterior intraorbital extension; an attachment to the orbital roof beyond the midorbital point; and some patient-specific adverse anatomic variations that may restrict access, are considered strong contraindications to a purely endoscopic approach. On the grounds of this thorough review, a new grading system for frontal and frontoethmoidal osteomas is proposed to allow better conformity to recent advancements and current clinical, research, and educational needs. CONCLUSION: Over the past 30 years, endoscopic techniques have emerged as the new standard of care for favorably located paranasal sinus osteomas. Nonetheless, open approaches remain indispensable for the management of the more perplexing cases of frontal sinus osteomas.

Gigantic paranasal sinuses osteomas: clinical features, management considerations, and long-term outcomes.

PURPOSE: Paranasal sinus osteomas are slow-growing, benign bony tumours that when larger than 30 mm, they are termed 'gigantic'. Special considerations apply for tumours of this calibre, and their rarity renders their management fairly controversial. This study seeks to contribute to an increased understanding concerning their management by presenting a 12-year experience from a single institution. METHODS: Retrospective review of files of patients treated for a gigantic paranasal sinus osteoma from January 2008 to December 2019. Additionally, all patients were prospectively reexamined in early 2020 for late complications or clinical recurrence. RESULTS: Ten patients were included, with a mean age of 53.8 years (range: 23-77 years). The leading presenting findings were proptosis (80%) and diplopia (70%). Transient visual impairment was remarkably frequent (30%). Five patients were managed with an open approach, two with an endoscopic, and three with a combined technique. The most common adverse characteristics that dictated the use of an open approach, alone or in combination with an endoscopic approach, were the involvement of the anterior wall of the frontal sinus (40%), erosion of its posterior wall (30%), and a far-anterior intraorbital extension (30%). No major postoperative complications were observed, and also no recurrences. CONCLUSION: Our study illustrates that these tumours may require a different management attitude. Despite substantial advances in the endoscopic management of benign sinonasal tumours, managing these massive tumours solely endoscopically could, in many cases, be inefficacious or impossible. Open approaches remain valuable, representing a safe and straightforward method for adequate exposure.

Short-Term Follow-Up of Self-Isolated COVID-19 Patients with Smell and Taste Dysfunction in Greece: Two Phenotypes of Recovery.

INTRODUCTION: The course of anosmia and ageusia in COVID-19 patients is not yet clearly known. We present short-term follow-up data concerning mild to moderate disease in home-quarantined COVID-19 patients in Greece. METHODS: We provided a symptom questionnaire and instructions for a self-administered home smell-and-taste test to 79 positive COVID-19 patients from 2 tertiary hospitals in Greece. The patients recorded their subjective symptoms before and during infection as well as 4 weeks after the diagnosis. The patients also underwent the home test during infection and 4 weeks later. RESULTS: Twenty-nine patients (36.7%) reported a loss of smell, and 21 (27.8%) reported a loss of taste, with equal prevalences between genders. We observed 2 types of recovery, i.e., a rapid, almost complete recovery, and a second slower and partial recovery. The type of recovery was not age related. A rapid recovery was observed in two thirds of the patients, with their olfactory ratings presenting a trend towards significance in correlation with nasal obstruction. A slow recovery in olfaction was correlated with low intensity ratings in odors with a trigeminal compound. The loss of taste was more pronounced in sweet and salty intensity ratings. CONCLUSION: Chemosensory deficits associated with COVID-19 infection were quite frequent among the Greek patients with mild or moderate disease who, in most cases, returned to normal within 4 weeks. However, 1 in 3 patients presented with persistent olfactory and gustatory dysfunction in the short term.

Paraglottic and Pre-epiglottic Space Abscess in Adults: Report of Two Cases.

INTRODUCTION: Acute epiglottitis or supraglottitis is a rapidly progressing upper respiratory tract infection that can often threaten the airway patency. Epiglottic abscess that expands to the paraglottic (PGS) or preepiglottic (PES) space and acute airway obstruction constitute rare complications, exclusively presented in adults. CASE REPORT: We report two cases. In the first case flexible fiberoptic Rhino-Pharyngo-Laryngoscopy showed epiglottitis that was obstructing the airway and abscesses on the lingual surface of the epiglottis. Abscesses were opened using laser CO2. In the following days flexible fiberoptic endoscopy revealed persisting protrusion of the left hemilarynx. A CT scan was performed showing an abscess in the paraglottic space. Under direct laryngoscopy the abscess was drained. In the second case endoscopic examination revealed epiglottitis that did not cause airway obstruction. The patient was admitted for follow-up and treated with intravenous antibiotics. On the 5th day showed an exacerbation of her symptoms. A CT scan was performed that showed the existence of an abscess in the preepiglottic space. She was taken to surgery and the abscesses were drained through a cervical- U shaped- incission. CONCLUSION: Existance of an abscess means, by default, an adequate surgical treatment to ensure the airway, and immediate drainage under direct laryngoscopy or through an external approach. Diagnosis is based exclusively on medical history and clinical examination. CT scan is necessary to reveal "secret" abscesses and "silent" extension of the infection inside pre-epiglottic and paraglottic space even if epiglottitis is mild. Postoperative management includes proper care of the surgical wound and antibiotics.

Timing of Tracheotomy in Intubated Patients With COVID-19.

Timing of elective tracheotomy in the intensive care unit for intubated patients with COVID-19 is still unclear. Recent recommendations and guidelines describe the surgical steps to achieve maximum protection of the involved medical staff and propose a delay of the procedure, so the viral load is decreased. Most authors of these recommendations agree that tracheotomy should be performed after at least 14 days from intubation, but data on this subject are still lacking. We discuss the issue of timing for such a procedure in regard to viral load and propose that the decision should be predominately based on its calculation.

Prognostic impact of indoleamine 2,3-dioxygenase 1 (IDO1) mRNA expression on circulating tumour cells of patients with head and neck squamous cell carcinoma.

BACKGROUND: We sought to determine the prognostic role of indoleamine 2,3-dioxygenase 1 (IDO1) by evaluating IDO1 expression in circulating tumour cells (CTCs) at baseline and after completion of chemoradiotherapy in patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) treated with curative intent. METHODS: In a prospective cohort of 113 patients with LA HNSCC, we evaluated expression of IDO1 in the EpCAM+ CTC fraction at baseline and after cisplatin chemoradiation. The prognostic value of combined programmed cell death ligand-1 (PDL-1) and IDO1 expression was assessed. RESULTS: IDO1 was significantly overexpressed at baseline compared with the post-treatment counterparts (p=0.007). IDO1 messenger RNA (mRNA) expression at baseline was associated with better survival in terms of progression-free survival (PFS) (HR=0.19, p=0.017). Post-treatment IDO1 mRNA levels were correlated with unfavourable prognosis in terms of overall survival (OS) (HR=3.27, p=0.008). Patients with combined decreased expression levels of PDL-1 and IDO1 after treatment exhibited superior PFS (p=0.043) and OS (p=0.021). CONCLUSIONS: Our results strongly suggest that IDO1 mRNA expression is an independent prognostic factor for clinical outcome. Our study provides useful information for future trials combining chemoradiation with immune checkpoint inhibitors and IDO1 inhibitors.

Surrogates of immunologic cell death (ICD) and chemoradiotherapy outcomes in head and neck squamous cell carcinoma (HNSCC).

OBJECTIVES: Chemoradiation can induce immunogenic (ICD) or tolerogenic cell death. ICD relies on the generation of damage-associated molecular patterns which can stimulate toll-like receptors (TLRs). We sought to determine whether we can predict responses to chemoradiation by measuring surrogate biomarkers of ICD in a cohort of patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: In a cohort of 113 LA HNSCC pts we evaluated expression of TLR4, TLR7 and TLR9 in the EpCAM + circulating tumor cell (CTC) fraction at baseline and after cisplatin chemoradiation. We also quantified changes in chemokines CXCL10, CXCL16 and IL-2R in the serum. RESULTS: Seventy three patients had evaluable specimens. Among cases with biomarker assessment at baseline and post treatment, 36.8% had an increase in CXCL10 levels (p = 0.022), 73.7% had an increase in CXCL16 levels (p = 0.002) and 63.8% had an increase in IL2Ra levels (p = 0.032) with treatment. 52.0% of evaluable cases at baseline and post-treatment had an increase in TLR4 levels (p = 0.996), 42.9% had an increase in TLR7 levels (p = 0.042) and 27.7% had increase in TLR9 levels (p = 0.011) with treatment. CXCL10 levels at baseline were significantly associated with PFS and OS (p = 0.010 and p = 0.032, respectively). CONCLUSIONS: Our results suggest that chemoradiation leads to quantifiable effects in surrogate markers of ICD. These effects may inform trials combining chemoradiation with immune checkpoint inhibitors. In addition, CXCL10 has prognostic effect in pts treated with chemoradiation.

HPV16 E6/E7 expression in circulating tumor cells in oropharyngeal squamous cell cancers: A pilot study.

OBJECTIVES: Human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) is increasing in incidence. Although HPV+ OPSCC has favorable prognosis, 10 to 25% of HPV+ OPSCCs eventually recur. We sought to evaluate the feasibility of detection of HPV16 E6/E7 expression in Circulating Tumor Cells (CTCs) and its utility as a prognostic tool in HPV16-associated OPSCC. MATERIALS AND METHODS: We developed a highly sensitive RT-qPCR assay for HPV mRNA expression in EpCAM(+) CTCs. In 22 patients with early stage and locally advanced OPSCC we evaluated HPV16 E6/E7 expression in the EpCAM(+) CTC fraction at baseline and at the end of concurrent chemoradiotherapy. HPV status in pre-therapy formalin-fixed paraffin-embedded (FFPE) tumor biopsies was assessed by p16 immunohistochemistry and polymerase chain reaction (PCR) and double positives were subjected to Real-time qPCR assay for detection of HPV16, 18 and 31 types. RESULTS: Fourteen of 22 OPSCC (63.6%) were HPV DNA+/p16+. Among HPV+/p16+ patients, 10 patients (71.4%) were HPV16 DNA+. HPV16 E6/E7(+) CTCs were detected in 3 of 10 patients (30%) at baseline and 4 of 9 patients (44.4%) at the end-of-treatment, all of which were p16+/HPV16 DNA+. Survival analysis showed a significantly higher risk for disease relapse (p = 0.001) and death (p = 0.005) in patients with HPV16 E6/E7(+) baseline CTCs. CONCLUSION: Detection of HPV E6/E7(+) CTCs might be a useful noninvasive test in liquid biopsy samples for determination of a clinically relevant HPV infection in HPV+ OPSCC. Combined interpretation of HPV E6/E7(+) CTCs with UICC staging data may lead to alteration of risk definition of patient subsets, with improved risk discrimination in early-stage disease.

Partial Recurrent Laryngeal Nerve Paralysis or Paresis? In Search for the Accurate Diagnosis.

"Partial paralysis" of the larynx is a term often used to describe a hypomobile vocal fold as is the term "paresis." We present a case of a dysphonic patient with a mobility disorder of the vocal fold, for whom idiopathic "partial paralysis" was the diagnosis made after laryngeal electromyography, and discuss a proposition for a different implementation of the term.

Dysphagia Caused by Chronic Laryngeal Edema.

A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office.

Prevalence of human papillomavirus infection in Greek patients with squamous cell carcinoma of the larynx.

BACKGROUND/AIM: The causal relation between human papillomavirus (HPV) infection and squamous cell carcinoma (SCC) of the larynx has not been yet clarified. The aim of the present study was to investigate HPV infection in 54 SCC of the larynx and correlate it with patients' epidemiological and clinicopathological data. MATERIALS AND METHODS: Fifty-four biopsies were collected from patients with laryngeal SCC and tested for HPV DNA. Local recurrence analysis was performed at the 2- year follow-up. RESULTS: HPV DNA was detected in 18.5% (10/54) of laryngeal SCC; infection from high risk (hr) HPV and low risk (lr) HPV types was found in 16.7% (9/54) and 1.8% (1/54) of the samples, respectively. HPV 16 was the commonest type detected in 7.5% (4/54). The presence of HPV DNA was significantly associated with the absence of tobacco use (p=0.001) and poorly differentiated tumors (p=0.003). CONCLUSION: This study confirms the prevalence of HPV infection among patients with SCC of the larynx.