Clinical and Experimental Otorhinolaryngology最新文献

Objectives: Particulate matter (PM) is well established as an environmental hazard linked to an increased risk of disease. Although numerous studies have explored PM-induced cellular responses, a comprehensive understanding of PM toxicity requires integrating advanced imaging techniques with quantitative biochemical assays.

Methods: Herein, we address this gap by combining these techniques with quantitative and functional assays to investigate the cellular effects of PM. PM collected from South Korea was used to assess toxicity in macrophages exposed to PM-containing medium. Three-dimensional (3D) holotomography revealed PM distribution and microstructural changes in cells following exposure.

Results: Cell viability and inflammation analyses across PM concentrations highlighted its harmful effects. Lipid metabolism and mitochondrial dysfunction assays helped elucidate the underlying mechanisms, whereas a comparative study of oxidative potential between PM and gold nanoparticles (AuNPs) further demonstrates PM-induced hazards. Oxidative stress drove PM-induced physicochemical changes in macrophages. The oxidative potential of PM is a measurable factor that determines its oxidative stress properties. In addition, PM contains several components including transition metals and organic chemicals. Metallic components in PM particularly exhibited redox activity associated with oxidative stress and inflammation.

Conclusion: Overall, our findings advance the mechanistic understanding of PM-cell interactions and introduce a novel methodological paradigm for studying the toxicological effects of environmental pollutants.

Objectives: Temporal bone squamous cell carcinoma (TBSCC) is the most common subtype of the temporal bone malignancies. Due to its low incidence, high rates of misdiagnosis, and challenges in conducting large-scale studies and clinical trials, its mechanisms of occurrence and progression remain unclear, and both diagnostic and therapeutic biomarkers are lacking. These challenges largely depend on our understanding of the tumor heterogeneity and microenvironment of TBSCC. Our study is aiming at revealing the tumor heterogeneity and microenvironment characteristics of TBSCC.

Methods: Since single-cell RNA sequencing (scRNA-seq) is an effective tool for studying tumor heterogeneity, we here first reported the scRNA-seq data of TBSCC in this study. We collected and sequenced a total of 113,344 cells from 9 samples (i.e., 5 cancer and 4 histologically verified adjacent normal temporal-bone tissues) of 6 TBSCC patients.

Results: We found the proportion of S-phase cancer cells was higher in samples with tumor invasion, and the pseudo-time trajectory of cancer cells closely corresponded with TBSCC differentiation level. We also detected higher communication intensity between some immune cell pairs in cancer tissues than in histologically verified adjacent normal temporal-bone tissues. Additionally, some cancer-related genes are identified as potential diagnostic markers of TBSCC.

Conclusion: This study is the first to unveil the complex heterogeneity and tumor microenvironment characteristics of TBSCC using scRNA-seq technology, offering new avenues for diagnosing, classifying, and treating this rare carcinoma.

Objectives: Obturator and free flap reconstruction differ in their postoperative visibility, potentially affecting cancer surveillance. This study compared clinicopathologic and survival outcomes after maxillectomy in patients with maxillary sinus malignancies and evaluated overall survival (OS) and disease-free survival (DFS) in both the overall cohort and a squamous cell carcinoma (SCC) subgroup.

Methods: A retrospective review of 61 patients (41 obturator, 20 free flap) who underwent maxillectomy between 2002 and 2021 was performed. Clinicopathologic features, resection margin status (clear, close, positive), recurrence patterns, and survival outcomes were analyzed. OS and DFS were estimated using Kaplan-Meier methods, and multivariable Cox models included reconstruction method, overall stage, resection margin status, and postoperative adjuvant therapy in the entire cohort and the SCC subgroup.

Results: Patients in the obturator group were older (63.7 vs. 54.1 years, P=0.046) and more often underwent total maxillectomy (80.5% vs. 50.0%, P=0.039). SCC was the most frequent histology (80.5% vs. 65%). OS and DFS did not differ significantly between groups: 2- and 5-year DFS were 56.1% and 44.1% (obturator) vs. 44.1% and 33.1% (free flap; P=0.931); 2- and 5-year OS were 68.0% and 50.0% vs. 77.1% and 44.1%, respectively (P=0.990). Among 46 patients with SCC (33 obturator, 13 free flap), survival outcomes were comparable. In multivariable analyses, close and positive margins and absence of postoperative adjuvant therapy were independently associated with poorer OS and DFS, whereas reconstruction method was not. Local recurrence was the most common failure pattern in both groups.

Conclusion: Obturator and free flap reconstruction showed comparable survival after maxillectomy for maxillary sinus malignancies. Resection margin status and postoperative adjuvant therapy were the major prognostic factors, underscoring individualized reconstruction and the importance of adequate margins, appropriate adjuvant treatment, and consistent follow-up.

Objectives: A markedly decreased speech intelligibility is reported to be a major feature of vestibular schwannoma (VS); however, details such as the relationship between speech intelligibility and hearing levels have not yet been adequately clarified.

Methods: Among 473 patients with sporadic unilateral vestibular schwannoma, scatter plots of pure tone audiometry (PTA) thresholds and speech discrimination scores were created. Simple regression analysis was conducted, and the Pearson correlation coefficient was calculated. The results were compared with those of 173 patients with asymmetric cochlear hearing loss, including the percentage of patients with unserviceable speech intelligibility.

Results: In patients with vestibular schwannoma, a strong correlation was found between the speech discrimination score and PTA threshold on the affected side, regardless of Koos grade or audiogram shape. In most patients, there was no significant difference in distribution compared with patients with asymmetric cochlear hearing loss. Although the proportion of patients with unserviceable speech discrimination was higher for vestibular schwannoma than asymmetric cochlear hearing loss across all hearing levels, the condition was limited to a small number of cases; a significant difference was only observed in cases with severe hearing loss.

Conclusion: Considering its relationship with hearing level, a markedly decreased speech discrimination score is no longer a major feature of vestibular schwannoma.

Objectives: Spatial mapping of sound frequencies along the auditory pathway is refined by sound-evoked activity during early development. However, the extent to which neonatal auditory deprivation alters this organization remains unclear. This study uniquely examined frequency-specific spatial representations in the inferior colliculus (IC) using targeted low-frequency (apical) and high-frequency (basal) cochlear stimulation, enabling the direct evaluation of low-frequency pathway integrity after neonatal deafness.

Methods: Sixteen Sprague-Dawley rats (8 normal-hearing [NH] and 8 neonatally deafened [ND] rats) were studied. Neonatal deafness was induced by daily kanamycin injections from postnatal days 4 to 17. At 8-10 weeks of age, the animals underwent unilateral cochlear implantation with bipolar electrode pairs positioned in the apical and basal cochlear regions to activate low- and high-frequency pathways. Multiunit responses were recorded from the contralateral IC using a multichannel linear electrode array. Spatial tuning curves (STCs) based on cumulative discriminability were used to assess the thresholds, spread of excitation, and tonotopic precision. Spiral ganglion neuron (SGN) density was histologically assessed.

Results: Despite 48-67 % SGN loss across cochlear turns, electrically evoked auditory brainstem response and IC thresholds were comparable between groups, indicating preserved peripheral excitability. However, ND rats showed significantly broader STCs (p = 0.002) and reduced dorsoventral separation of apical and basal best sites (1.18 ± 0.24 mm vs 1.80 ± 0.30 mm, p = 0.039), reflecting degraded central tonotopic precision. These effects were most pronounced for apical (low-frequency) stimulation, consistent with the selective vulnerability of lowfrequency pathways to early auditory deprivation.

Conclusion: These findings provide direct physiological evidence that early auditory experience is critical for refining the frequency-organized connectivity in the auditory midbrain. The preferential degradation of apical (low-frequency) spatial tuning offers translational insights for optimizing stimulation strategies in early-onset deafness.

Objective: In this study, we aimed to investigate the effects of preoperative auditory rehabilitation using hearing aids in patients with prolonged hearing deprivation.

Design: We retrospectively enrolled 204 patients who underwent cochlear implantation (CI) surgery at age >60 years using a single university hospital database. A total of 135 patients with a duration of deafness (DOD) > 10 years were divided into 3 groups according to perioperative hearing aids: unaided (n=22, 16.3%), aided (n=92, 68.1%, comprising 22 ipsilateral hearing aid and 70 bilateral hearing aids patients), and aided on the contralateral side groups (n=21, 15.5%). We analyzed the highest score on the postoperative sentence recognition test (Max_S) for each group.

Results: Max_S was significantly higher in the DoD < 10 years group (72.38 ± 25.74 vs. 64.09 ± 32.29, p = 0.048). Among the patients whose DoD was ≥ 10 years, the aided group showed significantly better Max_S than the unaided group, (69.84 ± 28.72 vs. 47.86 ± 37.14, p = 0.015). After one-to-two propensity score matching, Max_S was significantly better in the aided group than in the unaided group (73.64±29.10 vs 47.86±37.14, p=0.007).

Conclusion: Our study demonstrated the necessity of hearing rehabilitation, including for the surgical side ear regardless of whether it was beneficial to the hearing level, during the hearing deprivation period.

Objectives: This study aimed to evaluate the prognostic value of the margin-to-depth of invasion ratio (MDR) in patients with locally advanced oral squamous cell carcinoma (LAOSCC) who underwent curative surgery followed by adjuvant concurrent chemoradiotherapy (CCRT).

Methods: We analyzed 422 consecutive LAOSCC patients treated at a single institute between 2007 and 2017. The MDR was defined as the ratio of the closest surgical margin (mm) to tumor depth of invasion (DOI, mm). Survival outcomes, including overall survival (OS), cancer-specific survival (CSS) and relapse-free survival (RFS) were assessed. The optimal MDR cutoff was determined by X-tile analysis and validated using repeated k-fold cross-validation.

Results: The optimal MDR cutoff for predicting survival was 0.35. Patients with MDR ≥ 0.35 (high MDR, n = 205) demonstrated significantly better 5-year OS (66.1% vs. 47.6%, p < 0.001), CSS (77.5% vs. 57.4%, p < 0.001), and RFS (71.5% vs. 53.8%, p = 0.001) compared with those with MDR < 0.35 (low MDR, n = 217). In multivariate analysis, low MDR remained an independent adverse prognostic factor for OS (HR = 1.61, p = 0.005), CSS (HR = 2.05, p = 0.001) and RFS (HR = 1.50, p = 0.033). Among patients with adequate margins (≥5 mm), MDR retained significant prognostic value (OS, p = 0.008; CSS, p = 0.001; RFS, p = 0.015). Cross-validation confirmed the robustness of the MDR threshold value of 0.35 across all survival endpoints.

Conclusion: MDR is an independent prognostic marker in LAOSCC treated with surgery and adjuvant CCRT. A cutoff of 0.35 effectively stratifies survival risk, even among patients with adequate surgical margins. Incorporating MDR into postoperative assessment could refine risk stratification and guide individualized follow-up and adjuvant treatment planning.

Objective: This study aimed to explore the role of the Pcdh15 gene in hearing maintenance, observe the effects of its deficiency on cochlear structure, function, and hearing loss in mice.

Methods: We used CRISPR/Cas9 to generate Pcdh15 knockout (KO) mice. Auditory function was assessed via hearing tests, while histological were used to observe morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA-seq analyzed cochlear tissue from P18 wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). DEGs underwent functional annotation and pathway analysis, focusing on oxidative phosphorylation. Reactive oxygen species (ROS) levels were measured using flow cytometry and DCFH-DA assays.

Results: Pcdh15 KO mice showed progressive sensorineural hearing loss, worsening to profound deafness by P18. Notably, cochlear hair cells and SGNs exhibited significant loss and morphological abnormalities, particularly in the basal high-frequency region. RNA-seq identified 1,359 DEGs (1,024 downregulated, 335 upregulated). Analysis revealed that Pcdh15 deficiency was associated with inhibition of the oxidative phosphorylation pathway, which may disrupt mitochondrial respiratory chain complexes I, III, IV, and V, thereby potentially impairing energy production and ATP metabolism. Moreover, early-stage cochleae in KO mice showed elevated ROS activity and oxidative stress, suggesting redox imbalance may contribute to hearing damage.

Conclusion.: Pcdh15 is crucial for hearing maintenance. Its deficiency is associated with severe hearing loss and cochlear abnormalities, linked to the inhibition of oxidative phosphorylation, disruption of energy metabolism, and exacerbation of oxidative stress. These findings provide new insights into hearing loss mechanisms and potential therapeutic targets.

Objective.: Differentiated thyroid cancer (DTC) has a favorable prognosis. As indeterminate nodes are common, distinguishing recurrent and persistent DTC remains challenging. Previous studies have not specifically focused on prognosis between recurrent and persistent DTC. Thus, we aimed to compare prognosis and oncologic characteristics of two groups.

Methods.: This retrospective cohort study was conducted at a single tertiary care institution, enrolling 265 patients (recurrent: 109, persistent: 156) who underwent re-operation from November 1, 1999 to August 31, 2018 due to structural diseases. Those with distant metastasis at the time of initial diagnosis were excluded. Clinical and oncologic characteristics, patterns of lymph node (LN) metastasis, disease-free survival (DFS), and overall survival (OS) were compared between two groups. The time zero used for DFS is the time of the second operation.

Results.: Recurrent DTC exhibited higher incidence of central LN metastasis (p-value = 0.003), infield recurrence (p-value < 0.001), and distant metastasis (p-value < 0.001). In contrast, persistent DTC showed more lateral LN metastasis (p-value = 0.003) and outfield recurrence (p-value < 0.001). The most common site of neck LN metastasis was ipsilateral level VI/VII (51.4%) for recurrent DTC and ipsilateral level IV (43.0%) for persistent DTC. Ten-year DFS was significantly lower for recurrent DTC (41.0%) than for persistent DTC (67.9%) (p-value < 0.001). Recurrent DTC, older age, higher total metastatic LN at the second operation (first re-operation), and R1/R2 resection at the second operation were associated with decreased DFS. OS isn't significantly different between recurrent and persistent DTC (p-value = 0.160).

Conclusion.: : Recurrent DTC has poorer DFS than persistent DTC, although OS isn't significantly different.

Objectives.: To evaluate the therapeutic efficacy of intranasal insulin for treating persistent and refractory olfactory dysfunction following viral infections.

Methods.: A comprehensive literature search was performed across PubMed, SCOPUS, Embase, Web of Science, Google Scholar, and the Cochrane Database, covering all indexed articles up to July 2025. Studies were included if they evaluated changes in olfactory scores in patients receiving intranasal insulin, either compared with a control group (placebo or no treatment) or between pre- and post-treatment measurements. Secondary outcomes, including serum glucose and insulin levels and the proportion of patients achieving significant olfactory recovery, were also assessed.

Results.: Eight studies including 457 participants were reviewed. Intranasal insulin was generally associated with improvements in olfactory scores. Delivery via absorbable materials may enhance both threshold and discrimination outcomes, whereas self-administration showed minimal benefit. Some studies also reported higher rates of substantial olfactory recovery with absorbable material-based delivery. Combination therapy with intranasal insulin and budesonide was suggested to further improve threshold scores. Overall, treatment was well tolerated, with no major changes in serum glucose levels, though one study reported a mild hypoglycemic event.

Conclusion.: Current evidence suggests that intranasal insulin, particularly via absorbable material-based delivery, may offer therapeutic benefit for persistent post-viral olfactory dysfunction, with possible additional gains from corticosteroid coadministration. These findings remain preliminary and require confirmation in larger, well-controlled studies.