The role of SLC26A4 in bony labyrinth development and otoconial mineralization in mouse models.

Inner ear malformations are predominantly attributed to developmental arrest during the embryonic stage of membranous labyrinth development. Due to the inherent difficulty in clinically assessing the status of the membranous labyrinth, these malformations are diagnosed with radiographic imaging, based on the morphological characteristics of the bony labyrinth. While extensive research has elucidated the intricacies of membranous labyrinth development in mouse models, comprehensive investigations into the developmental trajectory of the bony labyrinth, especially about its calcification process, have been notably lacking. One of the most prominent types of inner ear malformations is known as incomplete partition (IP), characterized by nearly normal external cochlear appearance but pronounced irregularities in the morphology of the modiolus and inter-scalar septa. IP type II (IP-II), also known as Mondini dysplasia, is generally accompanied by an enlargement of the vestibular aqueduct and is primarily attributed to mutations in the SLC26A4 gene. In the case of IP-II, the modiolus and inter-scalar septa of the cochlear apex are underdeveloped or missing, resulting in the manifestation of a cystic structure on radiographic imaging. In this overview, we not only explore the normal development of the bony labyrinth in mice but also present our observations on otolith mineralization. Furthermore, we investigated the specifics of bony labyrinth and otolith mineralization in Slc26a4-deficient mice, which served as an animal model for IP-II. We ensured that these findings promise to provide valuable insights for the establishment of therapeutic interventions, optimal timing, targeted sites, and preventive measures when considering the management of this condition.

Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort.

The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice.

High fluence in laser stapedotomy aggravates transient subjective dizziness.

BACKGROUND: Laser fenestration in stapedotomy has thermal effect to the vestibule. AIMS/OBJECTIVES: To evaluate the role of energy density (fluence) in the severity of postoperative vestibular symptoms. MATERIALS AND METHODS: The retrospective chart-review study included 84 patients with otosclerosis that underwent primary laser stapedotomy. Surgical outcomes, including nystagmus, and subjective vestibular symptoms during one-month follow-up, were compared between potassium titanyl phosphate (KTP) and CO2 laser. According to this study and literature, we assessed the relationship between laser parameters and the incidence of persistent vestibular symptoms lasting more than one week after surgery. RESULTS: The KTP and CO2 laser group included 48 and 36 patients, respectively. Fluence was different between the KTP (637 J/cm2) and CO2 (141 J/cm2) laser (p < .001). The KTP group showed gradual decrease in dizziness during one-month observation period, while the CO2 group exhibited a steep recovery curve in the first postoperative week (9 and 4 d of duration, respectively). The incidence of persistent vestibular symptoms was correlated with both fluence (r = 0.80, p = .01) and spot size (r = -0.74, p = .01). CONCLUSIONS AND SIGNIFICANCE: Appropriate setting of parameters with lower fluence is desirable for the efficiency and safety of laser stapedotomy.Abbreviations: ABG: air-bone gap; SD: standard deviation.

Combined genetic polymorphisms of the GSTT1 and NRF2 genes increase susceptibility to cisplatin-induced ototoxicity: A preliminary study.

OBJECTIVE: The genotype-phenotype relationship in cisplatin-induced ototoxicity remains unclear. By assessing early shifts in distortion product otoacoustic emission (DPOAE) levels after initial cisplatin administration, we aimed to discriminate patients' susceptibility to cisplatin-induced ototoxicity and elucidate their genetic background. STUDY DESIGN: A prospective cross-sectional study. SETTING: Tertiary referral hospital in Japan. PATIENTS: Twenty-six patients with head and neck cancer were undergoing chemoradiotherapy with three cycles of 100 mg/m2 cisplatin. INTERVENTIONS: Repetitive pure-tone audiometry and DPOAE measurements, and blood sampling for DNA extraction were performed. Patients were grouped into early ototoxicity presence or absence based on whether DPOAE level shifts exceeded the corresponding reference limits of the 21-day test interval. MAIN OUTCOME MEASURES: Hearing thresholds after each cisplatin cycle, severity of other adverse events, and polymorphisms in cisplatin-induced ototoxicity-associated genes were compared. RESULTS: Early ototoxicity was present in 14 and absent in 12 patients. Ototoxicity presence on DPOAEs was associated with greater progression of hearing loss in frequencies ≥2 kHz throughout therapy and with higher ototoxicity grades compared with ototoxicity absence. Ototoxicity was further associated with grade ≥2 nausea. Ototoxicity presence was genetically associated with the GSTT1 null genotype and G-allele of NFE2L2 rs6721961, whereas ototoxicity absence was associated with the GSTM1 null genotype. Dose-dependent progression of hearing loss was the greatest in the combined genotype pattern of GSTT1 null and the T/G or G/G variants of rs6721961. CONCLUSION: Early DPOAE changes reflected genetic vulnerability to cisplatin-induced ototoxicity. Hereditary insufficiency of the antioxidant defense system causes severe cisplatin-induced hearing loss and nausea.

Advanced Magnetic Resonance Imaging Sheds Light on the Distinct Pathophysiology of Various Types of Acute Sensorineural Hearing Loss.

OBJECTIVE: To compare the findings of magnetic resonance imaging (MRI) with advanced protocols in patients with various types of acute sensorineural hearing loss (ASNHL). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Two hundred eighty-seven patients with ASNHL. INTERVENTIONS: All patients underwent MRI scanning, including heavily T2-weighted three-dimensional fluid-attenuated inversion recovery before and 4 hours after the intravenous administration of gadolinium contrast medium (delayed 3D-FLAIR). A hybrid of the reversed image of the positive endolymph signal and the native image of the perilymph signal image was constructed to visualize the endolymphatic space. RESULTS: The detection rates of abnormal MRI findings vary significantly among different types of ASNHL. A hyperintense signal on delayed 3D-FLAIR was observed in all patients with intralabyrinthine schwannoma or vestibular schwannoma and 20.5% of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) but was rarely observed in definite Ménière's disease (MD, 2.6%). In contrast, endolymphatic hydrops (EH) was frequently observed in patients with definite MD (79.5%) but was observed much less frequently in patients with ISSNHL (11.0%). In patients with cochlear MD and ALHL, detection rates of cochlear EH were similar to those with definite MD, whereas detection rates of vestibular EH were significantly lower than in patients with definite MD. CONCLUSIONS: The significantly different detection rates of abnormal MRI findings among various types of ASNHL shed light on the distinct pathophysiology of each disorder. A diagnosis based on MRI findings with advanced protocols may help select treatment strategies and provide prognostic information for patients.

Cholesteatoma has an altered microbiota with a higher abundance of Staphylococcus species.

Objective: To compare the microbiota between cholesteatoma and chronic suppurative otitis media (COM) and to identify potential pathogens that explain the relevant phenotypes of cholesteatoma. Study Design: Prospective cohort study. Methods: Surgical specimens collected from 20 cholesteatomas and nine COMs were treated to dissolve biofilms and subjected to 16S ribosomal RNA (rRNA) gene sequencing and amplicon sequence variant-level analysis for microbiota profiling and quantitative comparison. Correlations between the relative abundance of potential pathogens and the volume of the primary resected cholesteatomas were examined. Results: Differences in bacterial composition (beta diversity) were observed between cholesteatomas and COM (p = .002), with a higher abundance of Staphylococcus in cholesteatomas than in COM (p = .005). Common genera in the external auditory canal (EAC) flora, such as Staphylococcus, Corynebacterium, and Cutibacterium, were predominant in both cholesteatoma and COM; Staphylococcus aureus and Pseudomonas aeruginosa were increased in both diseases compared with the EAC flora. Furthermore, coagulase-negative staphylococci (CoNS) were more abundant in cholesteatomas than in COM (p = 0.002). Linear discriminant analysis coupled with effect size measurements (LEfSe) identified four CoNS as potential biomarkers for cholesteatoma. The relative abundance of S. aureus, a potential pathogen, was positively correlated with cholesteatoma volume (r = .60, p = .02). Conclusion: The microbiota of cholesteatoma and COM originated from EAC flora, but the bacterial composition was largely altered. Our results suggested that S. aureus infection is involved in cholesteatoma progression. Level of Evidence: 3b.

Application of a virtual and mixed reality-navigation system using commercially available devices to the lateral temporal bone resection.

BACKGROUND: Lateral temporal bone resection (LTBR) is performed for stage T1-2 external ear malignant tumors and requires spatial anatomical knowledge of the rare surgical field. OBJECTIVE: This paper presents a novel virtual reality (VR) based surgical simulation and navigation system using only commercially available display device and an online software, to assist in the understanding of the anatomy pre and intraoperatively. RESULT AND CONCLUSION: VR model created by 3D Slicer modules and visualized on head mounted display enabled users to simulate and learn surgical techniques of a rare surgical case. 3D hologram through HoloLens assisted the surgeon in comprehending the spatial relationship between crucial vital structures and the pathological lesion during the operation. This platform does not require the users to possess specific programming skill or knowledge, and is therefore applicable in daily clinical usage.

Cochlear Pathomorphogenesis of Incomplete Partition Type II in Slc26a4-Null Mice.

Incomplete partition type II (IP-II) is frequently identified in ears with SLC26A4 mutations. Cochleae with IP-II are generally observed to have 1½ turns; the basal turns are normally formed, and the apical turn is dilated or cystic. The objective of this study was to characterize the pathomorphogenesis of the IP-II cochlear anomaly in Slc26a4-null mice. Otic capsules were dissected from Slc26a4Δ/+ and Slc26a4Δ/Δ mice at 1 and 8 days of age and at 1 and 3 months of age. X-ray micro-computed tomography was used to image samples. We used a multiplanar view and three-dimensional reconstructed models to calculate the cochlear duct length, cochlear turn rotation angle, and modiolus tilt angle. The number of inner hair cells was counted, and the length of the cochlear duct was measured in a whole-mount preparation of the membranous labyrinth. X-ray micro-computed tomography mid-modiolar planar views demonstrated cystic apical turns in Slc26a4Δ/Δ mice resulting from the loss or deossification of the interscalar septum, which morphologically resembles IP-II in humans. Planes vertical to the modiolus showed a similar mean rotation angle between Slc26a4Δ/+ and Slc26a4Δ/Δ mice. In contrast, the mean cochlear duct length and mean number of inner hair cells in Slc26a4Δ/Δ mice were significantly smaller than in Slc26a4Δ/+ mice. In addition, there were significant differences in the mean tilt angle and mean width of the modiolus. Our analysis of Slc26a4-null mice suggests that IP-II in humans reflects loss or deossification of the interscalar septum but not a decreased number of cochlear turns.

Four-Hour Delayed Gadolinium-Enhanced 3D-FLAIR MR Imaging Highlights Intralabyrinthine Micro-Schwannomas.

OBJECTIVE: To demonstrate the clinical significance of 4-hour delayed gadolinium-enhanced three-dimensional fluid-attenuated inversion recovery (delayed 3D-FLAIR) in patients with intralabyrinthine schwannoma (ILS). PATIENTS: Three patients who were clinically diagnosed with ILS. INTERVENTIONS: All patients underwent audiological examinations and magnetic resonance imaging (MRI) scans. The MR-protocol included axial MR cisternography, immediate gadolinium-enhanced T1-weighted sequence, and heavily T2-weighted 3D-FLAIR prior to and 4 hours after the intravenous administration of gadolinium contrast medium. MAIN OUTCOME MEASURES: All MR images were visually inspected. RESULTS: In all three patients with ILS, delayed 3D-FLAIR MRI demonstrated a strong signal of cochlear fluid surrounding the tumor, which highlighted a tumor region that lacked signals. CONCLUSIONS: Delayed 3D-FLAIR MRI may serve as a novel diagnostic tool for the early detection of intralabyrinthine micro-schwannoma. The findings also shed light on the pathophysiology of ILS.

Patient-specific virtual and mixed reality for immersive, experiential anatomy education and for surgical planning in temporal bone surgery.

OBJECTIVE: The recent development of extended reality technology has attracted interest in medicine. We explored the use of patient-specific virtual reality (VR) and mixed reality (MR) temporal bone models in anatomical teaching, pre-operative surgical planning and intra-operative surgical referencing. METHODS: VR and MR temporal bone models were created and visualized on head-mounted display (HMD) and MR headset respectively, by a novel webservice that allows users to convert computed tomography images to VR and MR images without specific knowledge of programming. Eleven otorhinolaryngology trainees and specialists were asked to manipulate the healthy VR temporal bone model and to assess its validity by filling out a questionnaire. Additionally, VR and MR pathological models of petrous apex cholesteatoma were utilized for surgical planning pre-operatively and for referring to the anatomy during the surgery. RESULTS: Most participants were favorable about the VR model and considered HMD as superior to a flat computer screen. 91% of the participants agreed or somewhat agreed that VR through HMD is cost effective. In addition, the VR pathological model was used for planning and sharing the surgical approach during a pre-operative surgical conference. The MR headset was worn intra-operatively to clarify the relationship between the pathological lesion and vital anatomical structures. CONCLUSION: Regardless of the participants' training level in otorhinolaryngology or VR experience, all participants agreed that the VR temporal bone model is useful for anatomical education. Furthermore, the creation of patient-specific VR and MR models using the webservice and their pre- and intra-operative usages indicated the potential of innovative adjunctive surgical instrument.

Indications for and extent of elective neck dissection for lymph node metastasis from external auditory canal carcinoma.

OBJECTIVES: We aim to clarify the frequency of lymph node metastasis of external auditory canal (EAC) carcinoma, including susceptible locations, adequate extent of elective neck dissection, and the relationship between the tumor infiltration site and lymph node metastasis. PATIENTS AND METHODS: From 2003 to 2018, 63 patients with EAC carcinoma at Tokyo Medical and Dental University Hospital were enrolled in this study. The T and N stages, locations of clinically positive lymph nodes, prognoses, and anatomic site of tumor infiltration were analyzed after treatment. RESULTS: Clinically positive lymph node metastasis (cN+) was detected in 18 patients (28.6%), consisting of T1, T2, T3, and T4 disease in 1 (6%), 2 (22%), 8 (38%), and 7 (41%) patients, respectively. The metastatic locations were at level II in 10 patients, parotid gland nodes in 7, preauricular nodes in 5, level Ib in 3, level Va in 3, level III in 1, and superficial cervical nodes in 1. Neck recurrence was determined in two of 45 patients with clinically negative lymph nodes (cN0), with the metastatic locations being levels II, Ib, and III. Among 18 cN+ cases, neck recurrence was noted in 2 of 9 patients who underwent neck dissection. Neck lesions were found to be manageable in all five patients who underwent docetaxel, cisplatin, 5-fluorouracil, and radiation therapy (TPF-RT). No relationship was noted between the tumor infiltration site and lymph node metastasis among T3/4 canrcinoma patients. CONCLUSIONS: Elective neck dissection could be indicated only in T3/4 patients with free flap reconstruction. Levels Ib to III are considered appropriate for elective neck dissection in cN0 cases. Levels Ib to III and Va indicated favorable sites, even in cases with metastasis in the parotid gland or preauricular area. Furthermore, TPF-RT could be a useful option even in cN+ cases.

Denosumab-induced osteonecrosis of external auditory canal.

Denosumab is the world's first human monoclonal antibody for the treatment of osteoporosis and shares an active pathway with bisphosphonates, strongly suppressing osteoclast activities. This is the first case report describing a possible relationship between the development of osteonecrosis of external auditory canal and denosumab administration. We herein report an 81-year-old woman diagnosed with left osteonecrosis of external auditory canal who had a history of denosumab administration. She underwent left radical mastoidectomy due to being refractory to conservative treatment. No major complications or recurrence were observed in the left ear after surgery, but bone erosion in the right ear has continued to progress slowly despite the cessation of denosumab administration. Otolaryngologists should be aware of the association between osteonecrosis of external auditory canal and denosumab administration and consider performing long-term observation even after cessation.

Enhanced fallopian canal as a potential marker for temporal bone vasculitis.

OBJECTIVES: This study aimed to test the hypothesis that contrast-enhanced 3D MRI with gradient-echo sequences (CE-3D-GRE) can detect signs of vasculitis in the fallopian canal, which may cause otologic involvement, in four patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: CE-3D-GRE acquired at 3.0 Tesla was performed on four patients diagnosed with granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis, at onset or relapse of the disease, and in remission. Clinical correlations between otologic symptoms and radiological findings were examined for each patient. Furthermore, signal intensity of the mastoid segment of the fallopian canal was compared between the ears with active disease (n = 3) and those in remission or without vasculitis (n = 3). RESULTS: Intense enhancement in the tympanic and mastoid segments of the fallopian canal was associated with development of external otitis, otitis media, and sensorineural hearing loss, and was unrelated to the presence of facial paresis. Maximal intensity projection images visualized the close relationship between the enhanced fallopian canal and middle ear inflammation. The findings were absent in remission. Signal intensity of the mastoid segment of the fallopian canal was higher in ears with active disease than in normal ears (P < .001) and decreased to normal levels during remission (P = .597). CONCLUSION: CE-3D-GRE can demonstrate vasculitis in the temporal bone, reflecting disease activity and the severity of otologic manifestations, including cochlear involvement, in AAV patients. Intense enhancement of the fallopian canal on CE-3D-GRE can be a potential marker for vasculitis of the temporal bone. LEVEL OF EVIDENCE: 5.

Genetic Hearing Loss Associated With Autoinflammation.

Sensorineural hearing loss can result from dysfunction of the inner ear, auditory nerve, or auditory pathways in the central nervous system. Sensorineural hearing loss can be associated with age, exposure to ototoxic drugs or noise, or mutations in nuclear or mitochondrial genes. However, it is idiopathic in some patients. Although these disorders are mainly caused by dysfunction of the inner ear, little of the pathophysiology in sensorineural hearing loss is known due to inaccessibility of the living human inner ear for biopsy and pathological analysis. The inner ear has previously been thought of as an immune-privileged organ. We recently showed that a missense mutation of the NLRP3 gene is associated with autosomal-dominant sensorineural hearing loss with cochlear autoinflammation in two unrelated families. NLRP3 encodes the NLRP3 protein, a key component of the NLRP3 inflammasome that is expressed in immune cells, including monocytes and macrophages. Gain-of-function mutations of NLRP3 cause abnormal activation of the NLRP3 inflammasome leading to IL-1ß secretion in a spectrum of autosomal dominant systemic autoinflammatory phenotypes termed cryopyrin-associated periodic syndromes. The affected subjects of our two families demonstrated atypical phenotypes compared with those reported for subjects with cryopyrin-associated periodic syndromes. These observations led us to test the hypothesis that macrophage/monocyte-like cells in the cochlea can mediate local autoinflammation via activation of the NLRP3 inflammasome. The inflammasome can indeed be activated in macrophage/monocyte-like cells of the mouse cochlea, with secretion of IL-1ß. The macrophage/monocyte-like cells in the cochlea were also found to be associated with hearing loss in a Slc26a4-insufficient mouse model of human deafness. This review addresses our understanding of genetic hearing loss mediated by autoinflammation and macrophage/monocyte-like cells in the cochlea.

Potential Confounding Factors May Influence the Association Between Configurations of the Vertebrobasilar System and the Incidence of Idiopathic Sudden Sensorineural Hearing Loss and Canal Paresis.

OBJECTIVE: To investigate the impact of configurations of the vertebrobasilar system on the incidence of idiopathic sudden sensorineural hearing loss (ISSNHL) and canal paresis (CP). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Two hundred and forty-eight consecutive patients diagnosed with ISSNHL and 152 patients with unilateral CP of an uncertain cause who were managed between January 2011 and December 2017. The contralateral side of 144 patients with Bell's palsy or cerebellopontine angle tumor served as a control. INTERVENTIONS: All patients underwent magnetic resonance cisternography. CP was diagnosed based on caloric testing. MAIN OUTCOME MEASURES: 1) Branching patterns of the anterior/posterior inferior cerebellar artery (AICA/PICA) in the cerebellopontine angle area. 2) The direction of the basilar artery (BA) curvature. 3) Vertebral artery (VA) dominance. RESULTS: The incidence of vascular loops of the AICA/PICA entering the internal acoustic canal was significantly higher on both the affected and unaffected sides in patients with ISSNHL and CP in comparison to controls (p < 0.05). The curved BA was observed more frequently in the ISSNHL and CP groups than in the control group (p < 0.05), whereas the direction of the BA curvature was not associated with the laterality of ISSNHL or CP. The incidence of asymmetric VA in CP patients was significantly higher than that in controls (p = 0.0304), while no significant difference was observed between ISSNHL patients and controls. Remarkably, while the incidence rate of irregular vascular configurations was high in both the ISSNHL and CP groups, there was no marked difference between the affected and unaffected ears of the ISSNHL and CP groups. CONCLUSIONS: Our results indicate that the vascular configurations of the vertebrobasilar system do not directly cause ISSNHL and CP. Instead, they suggest the presence of confounding factors that influence the vascular configurations and the development of ISSNHL and CP.

Increased expression of pendrin in eosinophilic chronic rhinosinusitis with nasal polyps / Expressão aumentada de pendrina na rinossinusite crônica eosinofílica com pólipos

Abstract Introduction: Chronic rhinosinusitis with nasal polyps is a heterogeneous disease and appropriate diagnostic algorithms in individual cases are necessary for effective medical treatment. Objective: The purpose of this study was to clarify the relationship between the pendrin expression of nasal polyps and clinical and pathological characteristic features of eosinophilic chronic rhinosinusitis. Methods: A total of 68 patients were classified into eosinophilic chronic rhinosinusitis or non-eosinophilic chronic rhinosinusitis groups according to the degree of eosinophilic infiltration into the nasal polyps. Clinical, hematological, and immunohistochemical analyses were performed and statistically compared between both groups. Results: Thirty-eight were classified into eosinophilic chronic rhinosinusitis and 30 into non-eosinophilic chronic rhinosinusitis groups. There were no significant differences in age distribution, sex ratio, prevalence of asthma, or any other complications between the groups. The mean Lund-Mackay score and the number of serum eosinophils was significantly higher in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. The pendrin expression was more frequently detected in the epithelial surface layer of nasal polyps in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. In addition, mucin 5AC was more widely expressed in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis. Conclusion: Increased expression of pendrin and mucin 5AC in the nasal polyps would be associated with development of eosinophilic chronic rhinosinusitis. This finding could allow the development of a novel therapeutic agent targeted specifically to patients with eosinophilic chronic rhinosinusitis.

Resumo Introdução: A rinossinusite crônica com pólipos nasais é uma doença heterogênea e algoritmos diagnósticos apropriados em casos individuais são necessários para um tratamento médico eficaz. Objetivo: O objetivo deste estudo foi esclarecer a relação entre a expressão da pendrina de pólipos nasais e propriedades clínicas e patológicas características da rinossinusite crônica eosinofílica. Método: Um total de 68 pacientes foram classificados como tendo rinossinusite crônica eosinofílica ou rinossinusite crônica não eosinofílica de acordo com o grau de infiltração eosinofílica nos pólipos nasais. Análises clínicas, hematológicas e imunohistoquímicas foram realizadas e comparadas estatisticamente entre os dois grupos. Resultados: Entre os pacientes, 38 apresentavam rinossinusite crônica eosinofílica e constituíram o grupo 1; 30 tinham rinossinusite crônica não eosinofílica e constituíram o grupo 2. Não houve diferenças significantes na distribuição etária, razão entre os sexos, prevalência de asma ou qualquer outra complicação entre os grupos. O escore médio de Lund-Mackay e o número de eosinófilos séricos foram significantemente maiores no grupo com rinossinusite crônica eosinofílica do que no grupo com rinossinusite crônica não eosinofílica. A expressão da pendrina foi mais frequentemente detectada na camada epitelial superficial dos pólipos nasais na rinossinusite crônica eosinofílica do que no grupo com rinossinusite crônica não eosinofílica. Além disso, mucina 5AC foi mais amplamente expressa na rinossinusite crônica eosinofílica do que na rinossinusite crônica não eosinofílica. Conclusão: O aumento da expressão da pendrina e mucina 5AC nos pólipos nasais estaria associado ao desenvolvimento de rinossinusite crônica eosinofílica. Esse achado pode permitir o desenvolvimento de um novo agente terapêutico voltado especificamente para pacientes com rinossinusite crônica eosinofílica.

The quantitative analysis of the human papillomavirus DNA load in submandibular gland lesions with droplet digital polymerase chain reaction.

BACKGROUND: The relationship between infection with human papillomavirus (HPV) and tumorigenesis of salivary gland remains controversial. OBJECTIVES: This study explored the relationship between HPV and salivary gland lesions as well as that of the HPV infection status and p16INK4A immunoreactivity. The HPV DNA loads were also quantitatively evaluated. MATERIALS AND METHODS: Tissue samples from 31 submandibular gland lesions were evaluated. p16INK4A immunohistochemical (IHC) staining, nested polymerase chain reaction (PCR), DNA sequencing, and droplet digital PCR (ddPCR) were performed. RESULTS: Non-neoplastic lesion, benign tumors, and malignant tumors were noted in 9, 16, 6 cases, respectively. p16INK4A immunoreactivity was higher in malignant tumors than in benign tumors (50.0% vs. 6.3%). Single PCR with MY09/11 found that all samples were negative. Nevertheless, nested PCR revealed a high HPV-DNA positivity rate of 96.8%. No relationship between the HPV status and p16INK4A immunoreactivity was shown. HPV-18 was the only subtype identified in this study. ddPCR showed significantly lower HPV-18 DNA loads in submandibular gland lesions than in oropharyngeal cancers. CONCLUSIONS: HPV-DNA positivity and p16INK4A-immunoreactivity were not correlated in submandibular gland lesions. The loads of HPV DNA detected in this study were small. HPV positivity therefore may not be associated with tumorigenesis of the submandibular gland.