Patient delay and its clinical significance among head and neck cancer patients in Hungary.

Introduction: Head and neck cancers represent a major health problem in Hungary. With their high incidence and mortality rates, Hungary is one of the world leaders in these indicators. The length of patient delay, defined as time from onset of symptoms to first medical consultation, is unknown in Hungarian patients with head and neck cancer. We aimed to use a representative sample of the Hungarian head and neck cancer patient population to determine patient delay according to disease localization and stage and to identify correlations with other clinical parameters. Methods: In our retrospective study, we reviewed patient documentation. For the inclusion, the patients had to be diagnosed with malignant tumors of the oral cavity, oropharynx, hypopharynx or larynx at the Department Head and Neck Surgery of Semmelweis University between 2012 and 2017. Results: We identified 236 patients who met the inclusion criteria. The median delay was 9.5 weeks (range 0-209 weeks) and the mean delay of patients was 17.57 weeks (SD 23.67). There was a significant difference in patient delay data by location. Among glottic cancers, the most common diagnosis was an early stage (67%), compared with other localizations, including most commonly the oropharynx (81%) and hypopharynx (80%), where a locoregionally advanced stage was more frequent. Discussion: Compared to data from different countries, the delay of Hungarian patients with head and neck cancer is significantly longer, which may contribute to the high mortality in Hungary. Screening and patient education in high-risk groups could contribute to earlier diagnosis and thus improve prognosis.

Primary ossiculoplasties provide better hearing results than revisions: a retrospective cohort study.

PURPOSE: To evaluate the efficacy of ossicular chain reconstruction (OCR) in primary and revision surgeries, and to investigate the impact of the number of previous surgeries on hearing outcomes. METHODS: Retrospective analysis of cases with OCR due to chronic otitis in a tertiary center between January 2018 and September 2021. RESULTS: Altogether, 147 cases of ossicle involvement were assessed. In 91.83% (n = 135) OCR was performed, 96.26% of them with titanium TORP/PORP (n = 130), two cases with autologous prosthesis and three with piston. Mean follow-up was 8.8 months. The ABG significantly improved in the total group (TORP/PORP) from a mean (SD) of 30.94 (15.55) to 19.76 (13.36) dB (p < 0.0001) with 60.86% success. The best results were achieved in primary OCR with PORP implantation without cholesteatoma (89.47%). Primary cases have a significantly higher success rate in contrary to revision surgeries (72.27%, vs. 52.00%, p = 0.032). The only relevant predictive factor proved to be the fact of revision (p = 0.029). A statistically significant correlation between the number of previous surgeries and hearing results could not be proved. There was no difference in hearing outcomes between patients with only one or more than one previous surgeries in the revision groups. Neither the presence of cholesteatoma, nor the type of OCR (TOPR/PORP) and the indication of revision had an impact on postoperative ABG. CONCLUSIONS: Titanium prostheses are effective in OCR both in primary and revision cases. It is not the number of previous surgeries, but the fact of revision that influences postoperative hearing results.

Revision Stapedotomies: The Role of Periprosthetic Scar Tissue Formation in the Development of Unsatisfactory Hearing Results after Stapedotomy

Abstract Introduction Revision stapes surgeries are difficult to perform, and their audiological results are inferior to primary surgeries. Objective Our goal was to identify the most common and most influential postoperative reasons that cause persistent air-bone gap (ABG) after the primary surgery. Our focus was concentrated on the mechanical dysfunctions in the middle ear, with special regard to postoperative adhesion formation. Methods We performed a retrospective case series study with 23 cases that underwent revision stapedotomies. Results A significant improvement was seen in ABG and air conduction levels after surgery. The periprosthetic adhesion formation was seen in 65% of the cases, and it was the primary cause behind the unsatisfactory hearing result in 30% of cases. There was no significant difference in the level of persistent ABGs after the primary surgery, in case of the intratympanic adhesion presence, compared with the presence of other surgical failures. Concerning hearing and ABG gain after revision surgery, the non-inferiority of the negative effect associated with adhesion was shown compared with the other reasons. Conclusion The revision stapedotomy is an efficient treatment option in case of persistent ABG. Periprosthetic adhesions are the most common intratympanic reasons for compromised audiological outcomes after stapedotomy.

Revision Stapedotomies: The Role of Periprosthetic Scar Tissue Formation in the Development of Unsatisfactory Hearing Results after Stapedotomy.

Introduction Revision stapes surgeries are difficult to perform, and their audiological results are inferior to primary surgeries. Objective Our goal was to identify the most common and most influential postoperative reasons that cause persistent air-bone gap (ABG) after the primary surgery. Our focus was concentrated on the mechanical dysfunctions in the middle ear, with special regard to postoperative adhesion formation. Methods We performed a retrospective case series study with 23 cases that underwent revision stapedotomies. Results A significant improvement was seen in ABG and air conduction levels after surgery. The periprosthetic adhesion formation was seen in 65% of the cases, and it was the primary cause behind the unsatisfactory hearing result in 30% of cases. There was no significant difference in the level of persistent ABGs after the primary surgery, in case of the intratympanic adhesion presence, compared with the presence of other surgical failures. Concerning hearing and ABG gain after revision surgery, the non-inferiority of the negative effect associated with adhesion was shown compared with the other reasons. Conclusion The revision stapedotomy is an efficient treatment option in case of persistent ABG. Periprosthetic adhesions are the most common intratympanic reasons for compromised audiological outcomes after stapedotomy. Adhesion formations have the same negative effect on ABG development as any other surgical failure, and the revision could be more challenging in these cases. These findings highlight the use of the most atraumatic surgical technique and preservation of intact intratympanic mucosa during middle ear surgery.

Early postoperative gustatory dysfunction after middle ear surgery / Korai posztoperatív ízérzészavar középfülsebészeti beavatkozásokat követoen

Introduction: Preserving maximal quality of life is an important factor in middle ear surgery according to current standards. Taste disturbance is a common postoperative complication, which can be explained with the risk of injury due to the localisation of chorda tympani. The knowledge about this complication is mandatory for optimal surgical decision-making and for patient education as well. Objective: Investigation of early postoperative taste disturbances, to clarify the differences between the impact of different surgical interventions, and the impact of nerve manipulation. Methods: 15 stapes surgeries and 28 tympanoplasties were investigated. Patients answered subjective questionnaires before surgery and on the first postoperative day. Visual analogue scale (VAS) was used to measure the degree of disturbances (0-10). Degree of nerve manipulation was classified into 5 groups. Results: No significant differences between the impact of stapes surgeries and tympanoplasties could be found (9, 9.1; p = 0.861). In groups '0', '1' and '2', the VAS scores were 10, 9.26, and 8.5. Between the groups no manipulation (0) and significant manipulation without macroscopic injury (2), the difference was significant (10, 8.5; p = 0.039). In the stapes surgery group, no severe taste disturbance (VAS<5) was found. Discussion: In the case of adequate microscopic surgical technique, the rate of postoperative taste disturbances is relatively low. Conclusions: The rate of postoperative taste disturbance could be kept at a low level while the continuity of the chorda tympani could be preserved in the majority of cases. The postoperative morbidity rate is primarily influenced by the degree of nerve manipulation and not by the type of surgery.

Chronic Oral Selegiline Treatment Mitigates Age-Related Hearing Loss in BALB/c Mice.

Age-related hearing loss (ARHL), a sensorineural hearing loss of multifactorial origin, increases its prevalence in aging societies. Besides hearing aids and cochlear implants, there is no FDA approved efficient pharmacotherapy to either cure or prevent ARHL. We hypothesized that selegiline, an antiparkinsonian drug, could be a promising candidate for the treatment due to its complex neuroprotective, antioxidant, antiapoptotic, and dopaminergic neurotransmission enhancing effects. We monitored by repeated Auditory Brainstem Response (ABR) measurements the effect of chronic per os selegiline administration on the hearing function in BALB/c and DBA/2J mice, which strains exhibit moderate and rapid progressive high frequency hearing loss, respectively. The treatments were started at 1 month of age and lasted until almost a year and 5 months of age, respectively. In BALB/c mice, 4 mg/kg selegiline significantly mitigated the progression of ARHL at higher frequencies. Used in a wide dose range (0.15-45 mg/kg), selegiline had no effect in DBA/2J mice. Our results suggest that selegiline can partially preserve the hearing in certain forms of ARHL by alleviating its development. It might also be otoprotective in other mammals or humans.

Accuracy of the preoperative diagnostic workup in patients with head and neck cancers undergoing neck dissection in terms of nodal metastases.

PURPOSE: The presence of cervical lymph node metastases is one of the most influential prognostic factors in head and neck squamous cell carcinomas. The management of clinically N0 neck in patients with head and neck cancer remains controversial: elective neck dissection has relatively high morbidity, adversely affecting the quality of life, however, abandoning elective neck dissection is known to compromise overall survival in numerous primaries. The purpose of this study was to evaluate the accuracy of the conventional imaging modalities (CT, MRI, US) and fine-needle aspiration cytology (FNAC) in the detection of lymph node metastases in the neck. METHODS: Sixty two patients were included in the study, who underwent primary tumor resection and neck dissection. Preoperative nodal status was compared with postoperative histopathology nodal status. In our retrospective study, we reviewed the patient documentation. Statistical analysis of the data-with descriptive statistics and correlation analysis-was performed with Chi-square test. RESULTS: The sensitivity of conventional imaging modalities and FNAC were 82.8% and 81.8%, respectively, while specificity were 73.9% and 100%, respectively. Positive predictive value calculated for imaging modalities and FNAC were 82.8%, 100%, respectively, while negative predictive values were 73.9% and 66.6%, respectively. CONCLUSION: Neither the sensitivity of imaging modalities (CT, MRI, US) nor FNAC reached 100%, none of these methods can definitively exclude the presence of regional tumor metastasis. According to these data, no permissive alteration should be allowed from the current guidelines (e.g. NCCN) based on imaging/FNAC examinations regarding the need for elective neck dissection.

External Auditory Canal Cholesteatoma Causing Simultaneous Bezold Abscess and Sinus Thrombosis.

Extra- and intracranial complications of cholesteatoma are rare in the new era of antibiotics. The rarity of the severe complications and the atypical symptoms cause difficulties to set up proper diagnosis and treatment. We report about a 76-year old patient with external auditory canal cholesteatoma causing Bezold abscess and sigmoid sinus thrombosis. The patient underwent canal wall up mastoidectomy and mastoid obliteration with abdominal fat and Bezold abscess drainage. Systemic antibiotic and anticoagulant therapy were applied. The treatment resulted in fast improvement in the general condition of the patient, and the control magnetic resonance imaging (MRI) showed no recurrence of the disease. Laryngoscope, 131:E1282-E1285, 2021.

Limitations of non-echo planar diffusion weighted magnetic resonance imaging (non-EPI MRI) in cholesteatoma surveillance after ossicular chain reconstruction. A prospective study.

OBJECTIVE: Non-echo planar diffusion weighted magnetic resonance imaging is a reliable surveillance tool of residual cholesteatoma nowadays. It is not known whether the material of the ossicular chain prosthesis modifies the sensitivity and specificity of MRI in these cases. The aim of the study was to compare the sensitivity, specificity and a localization-specific accuracy of non-EPI DW MRI sequences for residual cholesteatoma in the following 3 subgroups: patients with titanium ossicular prosthesis (group T), with autologous cortical bone columella (group A) or without any reconstruction (group WR) of hearing bones. METHODS: This prospective study covered 28 cases with cholesteatoma of the middle ear undergone second-look surgery, who had preoperative PROPELLER DW-MRI. Surgical findings were compared to the results of the DWI-MRI. RESULTS: The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were: 0.76-0.8-0.76-0.8. Group T, group A and group WR sensitivity was 0.83-0.6-1, specificity: 0.75-0.75-0.85, PPV: 0.83-0.75-0.66, NPV: 0.75-0.6-1. Overall accuracy was 0.78. Size of missed cholesteatoma was 2-4 mm (mean: 2.66±1.15). CONCLUSIONS: Various materials are suitable for ossicular chain reconstruction. The poor detectability of residual or recurrent cholesteatoma in the middle ears reconstructed with autologous bony prosthesis may still claim second-look surgery instead of the usage of non- EPI DWI sequences independently in these patients.

Anti-PD-1 Therapy Does Not Influence Hearing Ability in the Most Sensitive Frequency Range, but Mitigates Outer Hair Cell Loss in the Basal Cochlear Region.

The administration of immune checkpoint inhibitors (ICIs) often leads to immune-related adverse events. However, their effect on auditory function is largely unexplored. Thorough preclinical studies have not been published yet, only sporadic cases and pharmacovigilance reports suggest their significance. Here we investigated the effect of anti-PD-1 antibody treatment (4 weeks, intraperitoneally, 200 µg/mouse, 3 times/week) on hearing function and cochlear morphology in C57BL/6J mice. ICI treatment did not influence the hearing thresholds in click or tone burst stimuli at 4-32 kHz frequencies measured by auditory brainstem response. The number and morphology of spiral ganglion neurons were unaltered in all cochlear turns. The apical-middle turns (<32 kHz) showed preservation of the inner and outer hair cells (OHCs), whilst ICI treatment mitigated the age-related loss of OHCs in the basal turn (>32 kHz). The number of Iba1-positive macrophages has also increased moderately in this high frequency region. We conclude that a 4-week long ICI treatment does not affect functional and morphological integrity of the inner ear in the most relevant hearing range (4-32 kHz; apical-middle turns), but a noticeable preservation of OHCs and an increase in macrophage activity appeared in the >32 kHz basal part of the cochlea.

[Effect of the stapedius and tensor tympani muscles tenotomy on the quality of life of patients suffering from Ménière's disease]. / A musculus tensor tympani és a musculus stapedius ín átvágásának hatása a Ménière-betegségben szenvedok életminoségére.

Introduction: Tenotomy of the tendon of the stapedius and tensor tympani (TT) muscles is a minimal-invasive surgical therapeutic procedure in Ménière's disease (MD). It has been assumed that the TT medializes the stapes into the oval window, resulting in changes in perilymphatic pressures of the inner ear. By cutting the tendons of both middle ear muscles, they affect the pressure dynamics by not augmenting this pressure even further. Aim: The immediate and long-term investigation of the effect of middle ear muscle tenotomy on the quality of life of patients suffering from Ménière's disease, measured by the Dizziness Handicap Inventory (DHI) and the Tinnitus Handicap Inventory (THI). Method: A follow-up study of 22 patients with definite, unilateral Ménière's disease had undergone tenotomy under general or local anesthesia through an endaural approach. Pre- and postoperative DHI values were compared for all patients. Statistical analysis: The statistical analysis was completed by using the IBM SPSS V24 software. Since the parameters did not show normal distribution, non-parametric test (Mann-Whitney U test) was used. The significance level was specified as p<0.05. Results: A statistically significant reduction of DHI scores was noted in all patients. The tinnitus significantly reduced and all of the patients mentioned improved symptoms of MD. Conclusion: Although the follow-up period is short, and the pathomechanism (decrease of stapes medialization in the oval window) is not exactly clear, tenotomy seems to be a successful promising surgical treatment method with a high reduction of dizziness handicap score in conservative therapy-resistant Ménière's disease. Orv Hetil. 2020; 161(5): 177-182.

[The role of the microbiome in otorhinolaryngology]. / A mikrobiom szerepe a fül-orr-gégészetben.

Our health is highly determined by the diverse microbial community living within our body and upon our skin. Balance among the members of the commensal microbiota is essential for the preservation of health. New generation sequencing is a rapid, sensitive method for determining the whole microbiome without prior hypothesis and also gives information on the resistance and virulence status. Application of this method can help to identify the pathogens contributing to different diseases, and also the protective bacteria inhibiting their growth. Detecting the changes of the microbiome helps to identify new therapeutic targets and establish targeted antibiotic therapy. Broad-spectrum antibiotics also act against the beneficial members of the microbial flora, which may lead to the development of recurrent or chronic disease. Ear, nose and throat infections are the most common infective diseases in humans and the leading cause for antibiotic prescription worldwide. In recent years, many studies using molecular biology methods were performed examining the microbiome of healthy humans and in otorhinolaryngologic diseases. In the present work, the authors review the changes of the microbiological communities in the healthy state and in various pathologic states in the anatomic regions of the ear, nose and throat. Orv Hetil. 2019; 160(39): 1533-1541.

Expression of PD-L1 on Immune Cells Shows Better Prognosis in Laryngeal, Oropharygeal, and Hypopharyngeal Cancer.

Despite great enthusiasm towards immunotherapy, reliable biomarkers are still lacking. The importance of subsets based on human papillomavirus (HPV) status is supported by a growing body of evidence. However, role of other possible subgroups such as anatomic localization of primary tumor remains controversial. Our objective was to investigate immune cell infiltrate and checkpoint inhibitor proteins in above-mentioned head and neck cancer subsets. Archival tumor samples of 106 laryngeal, oropharyngeal, and hypopharyngeal cancer patients were stained with PD-L1, PD-L2, PD-1, and CTLA-4 antibodies. Proportion of tumor-infiltrating lymphocytes was assessed as well. In HPV-negative tumors, PD-L1 immune cell positivity was associated with better disease-specific survival. PD-L1 expression on immune cells correlated with improved disease-specific survival in laryngeal tumors. Furthermore, PD-L1 immune cell positivity correlated with CTLA-4 expression on immune cells and it was accompanied by high tumor-infiltrating lymphocyte rate. PD-L1 expression on tumor cells and PD-1 status showed strong correlation in all patients and in oropharyngeal and laryngeal localization, but not in hypopharynx. HPV-negative oropharyngeal cancers showed negative PD-L1 status on tumor cells. CTLA-4 positivity was observed in 49.5% and 20.6% on immune cells and on tumor cells, respectively. We concluded that PD-L1 expression on immune cells indicates better prognosis in laryngeal squamous cell carcinoma and in HPV-negative head and neck squamous cell carcinoma. We have not found any essential differences between anatomic subgroups. A possibly distinct role of hypopharyngeal localization regarding immune activity requires further clarification.

p16INK4 expression is of prognostic and predictive value in oropharyngeal cancers independent of human papillomavirus status: a Hungarian study.

Head and neck cancer treatment protocols still lack well-established biomarkers of prognostic and predictive value. It is well known that human papillomavirus (HPV)-related and non-HPV-related oropharyngeal cancers are distinct entities concerning tumor biology and clinical outcome. However, there is an ongoing debate whether tumor suppressor p16INK4 status alone or both p16INK4 and HPV detection should be used in clinical settings. The aim of this study was to investigate p16INK4-immunolabelled and HPV-induced rates and determine their clinical significance in 110 primary head and neck squamous cell carcinomas. The expression of p16INK4 protein was assessed with immunohistochemistry, while high-risk HPV detection was performed using DNA PCR method. P16INK4 immunolabelling was detected in 17.3% of all tumor samples, and in 38.1% of oropharyngeal malignancies. Oropharyngeal, p16INK4-immunolabelled tumors showed an improved disease-specific survival compared to the non-p16INK4-immunolabelled group (median survival: 30.3 vs. 8.8 months, p < 0.001 with the log-rank test). Furthermore, 56% of p16INK4-immunolabelled cases were tested positive for HPV-DNA. The HPV-induced group presented better disease-specific survival compared to the non-HPV-induced cases (median survival: 25.9 vs. 9.5 months, p = 0.024 with the log-rank test). Improved response rates to neoadjuvant chemotherapy were observed both in p16INK4-immunolabelled and p16INK4- immunolabelled/HPV DNA- containing groups (Fisher's exact test: p = 0.025 and p = 0.009). In conclusion, p16INK4 immunohistochemistry proved to be a reliable and affordable tool for prognostic and predictive testing of head and neck squamous cell cancers. The p16INK4 immunopositivity status alone was confirmed to be an equally precise indicator of clinical outcome as p16INK4/HPV DNA PCR double testing.

Impact of 3T multiparametric MRI and FDG-PET-CT in the evaluation of occult primary cancer with cervical node metastasis.

BACKGROUND: This study aimed to determine the ability of multimodal evaluation with multiparametric 3T-MRI (MPMRI) and positron emission tomography - computed tomography (PET/CT) to detect cancer of unknown primary origin (CUP) with neck lymph node (LN) metastasis. METHODS: The study group comprised 38 retrospectively analysed consecutive patients with LN metastasis in the head and neck (HN) region without known primary tumours (PTs). Statistical values of 3T-MRI and of FDG-PET/CT scans were evaluated. RESULTS: Of the 38 CUPs, conventional native T1-, T2-weighted and STIR sequences detected 6 PTs. Native sequences plus diffusion-weighted imaging (DWI) found 14-, and with fat suppression contrast-enhanced T1-weighted measurement as well as with the complex MPMRI found 15 primaries and with PET/CT 17 CUPs could be evaluated, respectively. The detection rates were 15.8, 36.8, 39.5, 39.5 and 44.7 % for conventional native MRI, native plus DWI, native with contrast-enhanced MRI (CE-MRI), for MPMRI, and for PET/CT, respectively. The overall detection rate proved by histology was 47.4 %. PET/CT provided the highest sensitivity (Sv: 94.4 %) but a lower specificity (Sp: 65.0 %), using MPMRI (Sv: 88.2 %) the specificity increased to 71.4 %. DWIincreased specificity of the native sequences (Sp: 76.2 %). Conventional native sequences plus DWI as well as 3T-MPMRI and PET/CT were same accurate (Acc: 79.0 %) and had similar likelihood ratio (LR: 3.42, 3.03 and 2.62) in detecting unknown PT sites. CONCLUSIONS: The accuracy of FDG-PET/CT and MPMRI in case of CUP in finding the primary cancer in the neck regions is identical. While using PET/CT whole body information can be obtained in one examination. MPMRI shows the local soft tissue status more accurately. In cases of CUP PET/CT should be the first method of choice if it is available. MPMRI can clarify the exact primary tumor stage, and it can be advantageous in clarifying the prognostic factors, which is necessary in case of advanced tumor stage and when surgery is under consideration. In case low N stage is likely after the clinical examination and wait and see policy can be considered, MPMRI is recommended, and in this case the significance the of radiation free MPMRI is increasing.

Dynamic Contrast-Enhanced MRI Parameters as Biomarkers in Assessing Head and Neck Lesions After Chemoradiotherapy Using a Wide-Bore 3 Tesla Scanner.

Pilot studies have shown promising results in characterizing head and neck tumors (HNT) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), differentiating between malignant and benign lesions and evaluating changes in response to chemoradiotherapy (CRT). Our aim was to find DCE-MRI parameters, biomarkers in evaluating the post-CRT status. Two hundred and five patients with head and neck lesions were examined with DCE-MRI sequences. The time intensity curves (TIC) were extracted and processed to acquire time-to-peak (TTP), relative maximum enhancement (RME), relative wash-out (RWO), and two new parameters attack and decay. These parameters were analyzed using univariate tests in SPSS (Statistical Package for the Social Sciences, version 17, SPSS Inc. Chicago, USA) to identify parameters that could be used to infer tumor malignancy and post-CRT changes. Multiple parameters of curve characteristics were significantly different between malignant tumors after CRT (MACRT) and changes caused by CRT. The best-performing biomarkers were the attack and the decay. We also found multiple significant (p < 0.05) parameters for both the benign and malignant status as well as pre- and post-CRT status. Our large cohort of data supports the increasing role of DCE-MRI in HNT differentiation, particularly for the assessment of post-CRT status along with accurate morphological imaging.

Chemical neuroprotection in the cochlea: the modulation of dopamine release from lateral olivocochlear efferents.

The prevalence of sensorineural hearing loss is increasing worldwide, mainly due to ageing, increased noise exposure and cardiovascular risk factors. Several papers dealt with the mechanisms underlying the primary causes of impaired hearing and eventual deafness, including the damage and loss of auditory hair cells; however, very little is known about the protective mechanisms that exist for hearing. Several recent investigations have implicated dopamine (DA) in a neuroprotective circuit for the cochlea. The lateral olivocochlear (LOC) efferents provide axonal innervation of the inner hair cell afferent synapses and release DA and other substances in response to different stimuli. Under ischemic conditions or during noise exposure, DA has been proven to play a neuroprotective role against glutamate excitotoxicity. This review summarises what is currently known about the modulation of DA release in the cochlea, using primarily in vitro experimental data. Based on recent knowledge, there could be two functional subgroups within the LOC fibres, i.e., the DA- and GABA-containing projections. In this review, we attempt to show the neurochemical interactions between these two subsystems. Other aspects of cochlear neurotransmission are also discussed to provide a complete picture of cochlear dopaminergic function in physiological and pathophysiological cases with particular reference to excitotoxicity.