Objectives: . Sinonasal squamous cell carcinoma (SqCC) often invades the orbit. The treatment approach for sinonasal cancer that has spread to the orbit varies across medical centers and depends on the extent of the invasion. The decision to preserve the orbit in the treatment strategy is made on a case-by-case basis and results in varying outcomes. Currently, a multimodal treatment regimen, which may include surgery, chemotherapy, radiotherapy (RT), or concurrent chemoradiotherapy (CCRT), is commonly adopted for managing sinonasal cancers. This study aims to assess the prognosis of sinonasal SqCC with orbital invasion from various perspectives. Methods: . We conducted a retrospective review of patients with primary sinonasal SqCC invading the orbit who were treated at Seoul National University Hospital and Seoul National University Bundang Hospital between 2009 and 2018. The extent of the tumor, orbital invasion, treatment strategies, recurrence rates, and survival rates were analyzed. Results: . Overall survival and disease-free survival (DFS) rates showed no significant differences based on the grade of orbital invasion. When tumor resection with orbit preservation was employed as the definitive treatment, DFS was significantly extended compared to cases where surgery was not the definitive treatment (RT or CCRT). Additionally, there was no significant difference in DFS between patients who underwent orbit exenteration and those who underwent tumor resection with orbit preservation as the definitive treatment. Conclusion . Tumor resection with orbit preservation as the definitive treatment appears to be the preferred approach, prolonging DFS and increasing the likelihood of longer-term survival in cases of SqCC with orbital invasion.

Objectives: . FDXR encodes mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. To date, only two studies have described FDXR-related hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiological mechanisms remain incompletely understood. Here we report a hearing-impaired individual with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiological mechanism of adult-onset ANSD involving mitochondrial dysfunction. Methods: . A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and a functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically evoked compound action potential (ECAP) responses were measured, and the mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. Results: . In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP levels, reduced mitochondrial membrane potential, and increased reactive oxygen species levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is post-synaptic. As a result of increasing the pulse width during mapping, the patient’s CI outcomes showed significant improvement over 1-year post-CI. Conclusion . A novel FDXR variant associated with mitochondrial dysfunction and post-synaptic ANSD was first identified in a Korean individual. Additionally, 1-year post-CI outcomes were reported for the first time in the literature. Excellent audiologic results were obtained, and our results reiterate the correlation between genotype and CI outcomes in ANSD.

Olfaction is one of the five basic human senses, and it is known to be one of the most primitive senses. The sense of olfaction may have been critical for human survival in prehistoric society, and although many believe its importance has diminished over time, it continues to have an impact on human interaction, bonding, and propagation of the species. Even if we are unaware of it, the sense of smell greatly affects our lives and is closely related to overall quality of life and health. Nonetheless, olfaction has been neglected from a scientific perspective compared to other senses. However, olfaction has recently received substantial attention since the loss of smell and taste has been noted as a key symptom of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Studies investigating olfaction loss in association with coronavirus disease 2019 (COVID-19) have revealed that olfactory dysfunction can be both conductive and sensorineural, possibly causing structural changes in the brain. Olfactory training is an effective treatment for olfactory dysfunction, suggesting the reorganization of neural associations. A reduced ability to smell may also alert suspicion for neurodegenerative or psychiatric disorders. Here, we summarize the basic knowledge that we, as otorhinolaryngologists, should have about the sense of smell and the peripheral and central olfactory pathways for managing and helping patients with olfactory dysfunction.

Objectives: Several criteria exist for classifying chronic rhinosinusitis with nasal polyps (CRSwNP) as eosinophilic or non-eosinophilic. This study attempted to evaluate several criteria for defining eosinophilic CRSwNP from clinical and immunological perspectives. Methods: A cohort of 84 patients (73 patients with CRSwNP and 11 control patients) was retrospectively analyzed. Patients were divided into eosinophilic and non-eosinophilic CRSwNP based on four different criteria: eosinophils (EOS) accounting for more than 20% of the total inflammatory cells; ≥70 EOS per high-power field (HPF); >55 EOS/HPF; and ≥10 EOS/HPF. Preoperative clinical characteristics, the immunological profiles of 14 cytokines from nasal tissue, and postoperative outcomes were compared between eosinophilic and non-eosinophilic CRSwNP based on each criterion. These criteria were immunologically validated by using 14 cytokines to predict the performance of tissue eosinophilia with a random forest model. Results: Patients with eosinophilic CRSwNP were significantly older when the criterion of ≥10 EOS/HPF or EOS >20% was used. The number of patients with aspirin intolerance was significantly higher in eosinophilic CRSwNP based on the criterion of EOS >20%. From an immunological perspective, non-type 2 inflammatory cytokines were significantly higher in non-eosinophilic CRSwNP with the criterion of EOS >20% of the total inflammatory cells. In addition, the criterion of EOS >20% of the total inflammatory cells resulted in the best prediction of eosinophilic CRSwNP, with an accuracy of 88.10% and area under the curve of 0.94. Conclusion Clinical and immunological characteristics were different between eosinophilic and non-eosinophilic CRSwNP depending on a variety of criteria, and the results of this study should be taken into account when choosing the criterion for defining eosinophilic CRSwNP and interpreting the data accordingly.

Background and Objectives: Sternberg’s canal is known to result from incomplete fusion of bony compartments constituting the sphenoid bone during the developmental process. This study aimed to evaluate the prevalence and clinical implications of Sternberg’s canal. Methods: A retrospective review of patients over the age of 18 years who had undergone endoscopic sinus surgery from 2014 to 2019 at a single institution was performed. Patients (n=98) were categorized into those with sphenoid fungal ball (SFB) (n=39), those with primary chronic rhinosinusitis (CRS) (n=39), and controls (n=20) and were evaluated radiologically. A small pit in the lateral wall, located medial to the maxillary division of the trigeminal nerve (V2), in front of the opticocarotid recess was regarded as Sternberg’s canal. Children under the age of 12 years (n=39) without any sinus disease were also evaluated to determine the prevalence of Sternberg’s canal in the pediatric population. Results: Patients with SFB showed the highest prevalence of Sternberg’s canal (56.4%), followed by those with CRS (20.5%) and controls (10.0%) (p<0.001). Logistic regression revealed that Sternberg’s canal was associated with osteitis of the sphenoid wall, and not with age, sex, or sphenoid sinus pathology. Children under the age of 12 years showed a significantly higher prevalence of the defect than adult controls (46.2%, p<0.001). Conclusion Sternberg’s canal was frequently identified in children under the age of 12 years. Sphenoid sinus pathology was often accompanied by osteitis. However, the presence of the canal alone did not predict skull base involvement in patients with SFB. A comprehensive evaluation should hence be performed if skull base involvement is suspected in such patients. Additionally, other clinical implications of Sternberg’s canal should be further evaluated.

Objectives: . Systemic inflammation plays a key role in the pathogenesis of obstructive sleep apnea (OSA); however, easy-to-use methods to evaluate the severity of systemic inflammation have yet to be developed. This study investigated the association between systemic inflammation markers that could be derived from the complete blood count (CBC) profile and sleep parameters in a large number of patients with OSA. Methods: . Patients who visited our hospital’s Otorhinolaryngology Sleep Clinic between January 2017 and April 2022 underwent polysomnography and routine laboratory tests, including a CBC. Associations between three systemic inflammatory markers—the systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR)—and polysomnographic and demographic factors including age, sex, body mass index, the apnea-hypopnea index (AHI), the hypopnea index (HI), lowest oxygen saturation (%), the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale, and percentages of non-rapid eye movement (REM) sleep stage 3, REM sleep, and snoring time were analyzed. The inflammation markers were compared among OSA subgroups, and associations were also analyzed in subgroups with different OSA severities. Results: . In total, 1,102 patients (968 men and 134 women) were included, and their mean AHI was 33.0±24.3. PSQI was significantly associated with SII (P=0.027). No independent significant factors were identified for the NLR or PLR. Within the simple snoring and mild OSA subgroups, no significant association was found between sleep parameters and the SII. In the severe OSA subgroup, the AHI (P=0.004) and PSQI (P=0.012) were independently associated with the SII. Conclusion . Our study analyzed systemic inflammatory markers based on the CBC, a simple, relatively cost-effective test, and showed that the AHI and SII were significantly correlated only in the severe OSA subgroup.

Reconstruction of subtotal maxillectomy defects with columella deficit is challenging. We report a unique case of facial reconstruction using a free radial forearm flap and a free preauricular flap for the maxillectomy and columella deficit. A 73-year-old woman was diagnosed with recurrent sebaceous carcinoma of the nose. We performed wide excision, including areas of the right cheek, nose, upper lip, maxilla, and columella. The resultant subtotal maxillectomy defect was reconstructed using a three-dimensional flap. First, a free radial forearm flap was transfered to resurface the nasal, oral, and external facial side. Second, a preauricular flap was positioned into the columella defect and anastomosed with the distal portion of the radial forearm flap pedicle. The two flaps survived, and the patient recovered uneventfully. We believe the radial forearm and preauricular double free flaps with the pedicle connection method were effective in reconstructing the present case of subtotal maxillectomy defect.

Objectives: . Inferior turbinate (IT) hypertrophy is the main cause of chronic nasal obstruction. We developed a high-intensity focused ultrasound (HIFU) ablation device to treat patients with IT hypertrophy. Methods: . First, computed tomography images of patients with no evidence of sinonasal disease were evaluated to measure and compare the IT, medial mucosal thickness (MT), and space between the nasal septum and IT according to clinical characteristics such as septal deviation. A HIFU prototype was developed based on the above human anatomical studies. The experimental study was performed in five pigs; the nasal volume and histological changes at 1 and 4 weeks postoperatively were evaluated to compare the efficacy of HIFU turbinoplasty with that of radiofrequency turbinoplasty and a control group. Results: . The mean medial MT of the anterior, middle, and posterior portions of the IT were 4.66±1.14, 4.23±0.97, and 6.17±1.29 mm, respectively. The mean medial space was 2.65±0.79 mm. The diameter and focal depth of the prototype were 4 mm and 3 mm, respectively. HIFU showed no postoperative complications, including bleeding or scar formation. After HIFU treatment, the nasal volume increased by 196.62 mm3 (7.8%) and 193.74 mm3 (8.3%) at 1 week and 4 weeks, compared with the increase of 87.20 mm3 (3.1%) and 213.81 mm3 (9.0%), respectively,after radiofrequency therapy. A qualitative histological analysis after radiofrequency turbinoplasty showed epithelial layer disruption at 1 week and increased fibrosis, along with decreased glandular structure, at 4 weeks. The HIFU group had an intact epithelial layer at 1 week postoperatively. However, significant differences were observed at 4 weeks, including increased fibrosis and decreased glandular structure. Conclusion . The efficacy and safety of HIFU turbinoplasty were demonstrated in an animal study. Our results warrant further human clinical trials.

Objectives: . This study was conducted to determine whether patients with allergic rhinitis might be more susceptible to human rhinovirus (HRV) infection and whether the effects of infection on the elicited immune responses are different in allergic and non-allergic patients with chronic rhinosinusitis (CRS). Methods: . Uncinate process tissues were obtained from 61 CRS patients (of whom 39 had allergies and 22 did not) and were infected with HRV-16 using an air-liquid interface organ culture system. The expression levels of programmed cell death-ligand (PD-L)1, PD-L2, intracellular adhesion molecule 1, interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, and IL-10 were evaluated in the infected nasal mucosa. Results: . The HRV infection rates were not significantly different between the allergy (74.4%) and non-allergy (72.7%) groups. In the allergy group, the expression of PD-L1 (P=0.013) and IL-10 (P=0.040) was significantly elevated in the HRV-infected tissues, and there was a strong correlation between PD-L1 and IL-10 (r=0.868, P<0.001). In contrast, infected tissues from the non-allergy group displayed increased levels of IL-4 (P=0.039), IL-5 (P=0.023), and IFN-γ (P=0.031), as well as an increased IL-4/IFN-γ ratio, after HRV infection (P=0.043). Conclusion . This study showed that HRV infection rates were similar in the nasal mucosa of patients with CRS regardless of the presence of allergic rhinitis. HRV infection enhanced the Th2 environment by modulating PD-L1 and PD-L2 expression levels in allergic mucosa and by increasing the IL-4/IFN-γ ratio in non-allergic mucosa.

Objectives: . This study was conducted to determine whether patients with allergic rhinitis might be more susceptible to human rhinovirus (HRV) infection and whether the effects of infection on the elicited immune responses are different in allergic and non-allergic patients with chronic rhinosinusitis (CRS). Methods: . Uncinate process tissues were obtained from 61 CRS patients (of whom 39 had allergies and 22 did not) and were infected with HRV-16 using an air-liquid interface organ culture system. The expression levels of programmed cell death-ligand (PD-L)1, PD-L2, intracellular adhesion molecule 1, interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, and IL-10 were evaluated in the infected nasal mucosa. Results: . The HRV infection rates were not significantly different between the allergy (74.4%) and non-allergy (72.7%) groups. In the allergy group, the expression of PD-L1 (P=0.013) and IL-10 (P=0.040) was significantly elevated in the HRV-infected tissues, and there was a strong correlation between PD-L1 and IL-10 (r=0.868, P<0.001). In contrast, infected tissues from the non-allergy group displayed increased levels of IL-4 (P=0.039), IL-5 (P=0.023), and IFN-γ (P=0.031), as well as an increased IL-4/IFN-γ ratio, after HRV infection (P=0.043). Conclusion . This study showed that HRV infection rates were similar in the nasal mucosa of patients with CRS regardless of the presence of allergic rhinitis. HRV infection enhanced the Th2 environment by modulating PD-L1 and PD-L2 expression levels in allergic mucosa and by increasing the IL-4/IFN-γ ratio in non-allergic mucosa.