Supersulfide formation in the sinus mucosa of chronic rhinosinusitis.

Objectives: Disruption of the oxidative stress defense system is involved in developing various diseases. Sulfur compounds such as glutathione (GSH) and cysteine (CysSH) are representative antioxidants in the body. Recently, supersulfides, including reactive persulfide and polysulfide species, have gained attention as potent antioxidants regulating oxidative stress and redox signaling. However, their involvement in the pathogenesis of chronic rhinosinusitis (CRS) remains unclear. Methods: To clarify the changes in sulfur compounds within the sinus mucosa of each CRS subtype, we measured sulfur compound levels in the sinus mucosa of control individuals (n = 9), patients with eosinophilic CRS (ECRS) (n = 13), and those with non-ECRS (nECRS) (n = 11) who underwent sinus surgery using mass spectrometry. Results: GSH and CysSH levels were significantly reduced, and the glutathione disulfide (GSSG)/GSH ratio, an oxidative stress indicator, was increased in patients with ECRS. Despite the absence of notable variations in supersulfides, patients with ECRS and nECRS exhibited a significant reduction in glutathione trisulfide (GSSSG), which serves as the precursor for supersulfides. Conclusions: This study is the first quantitative assessment of supersulfides in normal and inflamed sinus mucosa, suggesting that sulfur compounds contribute to the pathogenesis of CRS. Level of Evidence: N/A.

Expression of Periostin in Benign Salivary Gland Tumors.

Parotid tumors present a wide range of histological features, from benign to malignant. Periostin, an extracellular matrix protein specifically expressed in the periosteum and periodontal ligament, is isolated from osteoblast cell lines. It regulates fibrosis and collagen deposition and plays an important role in myocardial repair after myocardial infarction. It is also known to be involved in otorhinolaryngological-diseases. This study included 36 patients [38 specimens; 16 men and 20 women, mean age 59.2 (range 26-82) years] who underwent parotid tumor resection at the Division of Otorhinolaryngology, Tohoku Medical and Pharmaceutical University, between April 2017 and March 2022 and were clinically and pathologically diagnosed as having benign parotid tumors. Formalin-fixed, paraffin-embedded sections from the surgical specimens were autoclaved and immunostained with anti-periostin antibodies to evaluate the expression and distribution of periostin. Histologically, the tumors were diagnosed as pleomorphic adenomas in 15 cases (15 specimens), Warthin's tumors in 13 cases (15 specimens), basal cell adenomas in 2 cases (2 specimens), oncocytomas in 4 cases (4 specimens), and myoepitheliomas in 2 cases (2 specimens). An increased expression of periostin was found in 32 of 38 samples (84.2%) in the stroma of benign parotid tumors. Four distinct patterns of periostin expression were observed in benign parotid gland tumors: negative, superficial, infiltrative, and diffuse. Statistically significant differences were found between periostin expression patterns and histological classification of the tumors. Our results suggest that periostin may be involved in the pathogenesis of benign parotid tumors and could serve as a new biomarker for these tumors.

Immunohistochemical localization of CD31, CD34, and periostin in vocal fold polyps.

BACKGROUND: Long-term voice-abuse or sudden vocal fold microvascular disruption can lead to injury and subsequent repair/remodeling of the vocal fold mucosa. Periostin is known to be involved in airway remodeling and in various otolaryngological diseases. In ischemic heart disease, increased CD31 expression has been observed around cardiomyocytes during remodeling, and endothelial proliferation has been reported to occur at these sites. OBJECTIVES: We investigated the expression and the roles of CD31, CD34, and periostin in the formation of vocal fold polyps. MATERIALS AND METHODS: Fifty-seven samples of vocal fold polyps were investigate histopathologically and immunohistochemically. RESULT: Expression of CD31 and CD34 was detected in 41 (71.9%) and 53 (93.0%) samples, respectively, obtained from patients with vocal fold polyp. Expression of periostin was detected in 41 (71.9%) samples obtained from patients with vocal polyps. The vocal polyp samples could be classified into three histological subtypes. Three patterns of CD31 and CD34 expression were observed in the vocal polyp. Four patterns of periostin expression were observed in vocal polyps. An association was observed between the CD31 expression pattern and the histological subtype of vocal fold polyps. CONCLUSION AND SIGNIFICANCE: In vocal fold polyps, evaluation of vascular endothelial markers may be useful for staging.

Immunohistochemical Localization of D-ß-Aspartic Acid and Periostin in Vocal Fold Polyps.

Long-term voice abuse or sudden vocal fold microvascular disruption may lead to injury and subsequent repair/remodeling in the vocal fold mucosa. Periostin is known to be involved in airway remodeling and also in various otolaryngological diseases. D-ß-aspartic acid is the major isomer of D-aspartic acid found in elderly tissue. In this study we investigated the expression and the role of D-ß-aspartic acid and periostin in the formation of vocal fold polyps. The expression patterns of D-ß-aspartic acid and periostin in 36 surgical specimens of vocal fold polyps from 36 patients were investigated immunohistochemically. In the epithelium of vocal polyps, D-ß-aspartic acid was expressed in all cases. Expression of D-ß-aspartic acid was detected in 25 samples obtained from patients with vocal fold polyps stroma. Expression of periostin was detected in 28 samples obtained from patients with vocal fold polyps. Two patterns of D-ß-aspartic acid expression were observed in vocal fold polyps stroma: positive type and negative type. The following four patterns of periostin expression were observed in vocal fold polyps: negative type, superficial type, infiltrative type, and diffuse type. An association was observed between D-ß-aspartic acid expression patterns and periostin expression patterns. From these findings we speculate that periostin and D-ß-aspartic acid participate in certain pathological changes in vocal fold polyps, such as extracellular matrix accumulation, local fibrosis, and the formation and development of vocal fold polyps.

The functional role and the clinical application of periostin in chronic rhinosinusitis.

INTRODUCTION: Chronic rhinosinusitis (CRS) comprises several heterogenous groups, now classified based on endotype more often than on phenotype. A number of studies aimed at finding a useful biomarker for type 2 CRS suggest that periostin is a promising surrogate. AREAS COVERED: A comprehensive overview of the clinical significance of tissue periostin expression and serum periostin in CRS patients is provided. The effects of comorbid asthma on serum periostin and samples other than serum in which periostin can be detected in CRS patients are also discussed. Moreover, the functional roles of periostin in CRS pathogenesis are summarized. EXPERT OPINION: The position of periostin as a signature biomarker of type 2 CRS has been well established, enabling us to classify CRS patients by endotyping. Serum periostin is useful not only for endotyping CRS patients, but also for estimating disease severity, comorbidity, prognosis, and response to treatment, and in particular, predicting recurrence after surgery. However, it remains to be addressed how we apply serum periostin to using biologics for CRS patients. Further studies aimed at showing periostin to be a therapeutic target for CRS are awaited.

A facelift procedure for resection of a branchial cleft cysts.

OBJECTIVES: Branchial cleft cysts (BCCs) are common in daily practice, however, BCC patients suffer aesthetic problems due to postoperative scars on visible parts after surgery. To analyze the feasibility, surgical outcomes and possible risks and complications encountered during a facelift procedure for patients with BCC. METHODS: This retrospective analysis examined patients who had undergone surgery for branchial cleft cyst using a facelift procedure (n = 16) or conventional transcervical resection (n = 20) at our institutes between April 2015 and August 2021. RESULTS: There was no significant difference between the groups that underwent the facelift procedure or conventional transcervical resection as to the average size of the cysts, operating time, bleeding, drain out, or recurrence. None of the patients needed to switch from the facelift procedure to conventional transcervical resection. In all the patients in the facelift procedure group, postoperative scars were fully concealed by the auricle and hair. However, four patients in the facelift procedure group experienced a transient auricular complication after surgery. CONCLUSION: The facelift procedure provides adequate visualization, workspace and excellent cosmetic results in suitably selected cases with BCC.

Periostin is an aggravating factor and predictive biomarker of eosinophilic chronic rhinosinusitis.

BACKGROUND: Patients with eosinophilic chronic rhinosinusitis (ECRS) respond poorly to many treatment modalities. Overproduction of periostin in the nasal mucosa is reported to contribute to polyp formation. This study examined periostin levels in patients with ECRS in comparison with levels in patients with non-ECRS. METHODS: Fifty-nine patients with chronic rhinosinusitis were grouped into those with ECRS and those with non-ECRS. We compared the relationships between peripheral blood eosinophil level, serum periostin level, histopathological findings, clinical and laboratory findings, nose findings, diagnostic score of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study, and postoperative recurrence of nasal polyps in each group. RESULTS: In the ECRS group, a positive correlation was found between peripheral blood eosinophil level and serum periostin level (rs = 0.49, P < 0.01: Spearman's rank correlation coefficient). ROC curve analysis was used to evaluate the serum periostin level that could predict postoperative recurrence of nasal polyps in the ECRS group: the area under the curve (AUC) was 0.95, sensitivity was 92%, and specificity was 100%; the serum periostin cutoff value for postoperative recurrence of nasal polyps was 130 ng/ml. In ROC curve analysis to evaluate peripheral blood eosinophil level, the AUC was 0.73, sensitivity was 69.2%, and specificity was 85.0%; the cutoff value was 8.8%. CONCLUSIONS: periostin was implicated in the pathophysiology of ECRS. Periostin shown to be a more useful biomarker than eosinophils in ECRS. Periostin was shown to likely be an important biomarker for pathological severity of ECRS and postoperative recurrence of nasal polyps.

Executive summary: Japanese guidelines for allergic rhinitis 2020.

The Practical Guideline for the Management of Allergic Rhinitis, the fist guideline for allergic rhinitis in Japan, was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 9th edition was published in 2020 and is widely used today. The most recent collection of evidence from the literature was supplemented to the revised guideline to incorporate evidence-based medicine. The revised guideline includes updated epidemiology of allergic rhinitis in Japan, a figure representing the mechanisms of allergic rhinitis in both the onset and sensitization phases with the introduction of regulatory T cells and type 2 innate lymphoid cells, practical assessment for diagnosis, new pharmacotherapy agents such as anti-IgE mAb and a new drug delivery system for antihistamines, sublingual immunotherapy for children, dual sublingual immunotherapy for house dust mites and Japanese cedar pollen extract, new classification for surgery for allergic rhinitis, and treatment and prescriptions for older adults. An evidence-based step-by-step strategy for treatment is also described.

Immunohistochemical localization of d-ß-aspartic acid in congenital and acquired middle ear cholesteatoma.

Objective/Hypothesis: Middle ear cholesteatoma is characterized by abnormal growth of the keratinizing squamous epithelium of the temporal bone. d-ß-aspartic acid is the major isomer of d-aspartic acid found in elderly tissue. We assessed the immunoreactivity to k-ß-aspartic acid of congenital and acquired middle ear cholesteatomas. Study Design: Case-control studies. Material and Methods: Tissue samples were collected from 21 patients comprising 21 ears with congenital middle ear cholesteatoma and 26 patients comprising 29 ears with acquired type. Their clinical and histopathological features were investigated. We divided the middle ear cholesteatoma samples into three layers: the perimatrix, matrix, and cystic contents. The patterns of immunoreactivity to d-ß-aspartic acid expression were then assessed immunohistochemically. Results: Two patterns of immunoreactivity to d-ß-aspartic acid were detected in middle ear cholesteatoma: infiltrative and diffuse. In congenital middle ear cholesteatoma, d-ß-aspartic acid expression was observed throughout all the layers (perimatrix, matrix, and cystic contents), and immunoreactivity to d-ß-aspartic acid was dramatically strong in all layers. The expression levels of d-ß-aspartic acid to the cystic content and perimatrix were significantly higher in congenital middle ear cholesteatoma than in the acquired type. Conclusions: This study showed the expression levels of d-ß-aspartic acid in middle ear cholesteatoma to differ significantly between congenital and acquired middle ear cholesteatoma. Our results indicate that overexpression of d-ß-aspartic acid is likely to be involved in the pathogenesis of cholesteatoma, and we speculate that d-ß-aspartic acid could be a novel biomarker for, and a therapeutic target in, congenital and acquired middle ear cholesteatoma. Level of Evidence: 4.

Expression of Periostin in Vocal Fold Polyps.

Long-term voice abuse or sudden vocal fold microvascular disruption may lead to injury and subsequent repair/remodeling in the vocal fold mucosa. Periostin is known to be involved in airway remodeling and also in various otolaryngological diseases. The aim of this article was to investigate the expression and the role of periostin in the formation of vocal fold polyps. The expression patterns of periostin in 59 surgical specimens of vocal fold polyps from 54 patients were investigated immunohistochemically. Normal vocal fold mucosa specimens from 5 patients who had undergone total laryngectomy were used as the control group. Retrospective study with planned data collection was conducted at Tohoku Medical and Pharmaceutical University. Expression of periostin was detected in 43 (72.9%) samples and four patterns of periostin expression were observed in vocal fold polyps: negative type, superficial type, infiltrative type, and diffuse type. An association was observed between periostin expression patterns and the histological subtypes of vocal fold polyps. The infiltrative pattern of periostin expression was significantly dominant in vascular-hyaline types. Expression of transforming growth factor-ß (TGF-ß) was also detected in the vocal fold polyps. Our results confirmed that periostin might be involved in certain pathological changes in vocal fold polyps, such as extracellular matrix accumulation, local fibrosis, and formation and development of vocal fold polyps.

OK-432 Treatment of Ranula Intruding into the Cervical Region.

OBJECTIVES: Plunging ranula intruding into the cervical region is rare and a standard therapy has not yet been consolidated. This paper investigates the outcomes and side effects of OK-432 treatment in patients with a ranula extending into the cervical region. METHODS: The study design and setting consisted of a planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Eight patients with ranula extending into the cervical region received OK-432 treatment between January 2016 and February 2019. OK-432 treatment was performed for patients with ranula extending into the cervical region. RESULTS: In all patients, a total shrinkage and marked reduction in lesions were observed without local scars or deformations after OK-432 treatment. Complications were local swelling and mild fever (37.5-38.5 °C), which lasted a few days in half of the patients. CONCLUSIONS: OK-432 treatment is straightforward, secure, and efficacious and can be substituted for surgery in the treatment of ranula extending into the cervical region.

Cervical Liposarcoma Revisited: A Case Report and Scoping Literature Review.

The commonest sites for liposarcoma are the retroperitoneum and lower extremities. Liposarcoma of the head and neck region is a rare and potentially life-threatening malignancy. Tumors originating in the right cervical space cause special diagnostic and therapeutic difficulties. In the present report, we describe a case of differentiated liposarcoma of the right cervical region. The tumor continued to grow slowly over 3 years before a definitive diagnosis was established. Extended extirpation of the tumor was performed and proved efficacious in that no recurrence has been observed for 4 years. Recommendations for earlier and accurate diagnosis and treatment of this rare neoplasm are discussed.

Dupilumab efficacy in chronic rhinosinusitis with nasal polyps from SINUS-52 is unaffected by eosinophilic status.

BACKGROUND: The human monoclonal antibody dupilumab blocks interleukin (IL)-4 andIL-13, key and central drivers of type 2 inflammation. Dupilumab, on background mometasone furoate nasal spray (MFNS), improved outcomes in the phase III SINUS-52 study (NCT02898454) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). This posthoc analysis of SINUS-52 examined whether eosinophilic status of CRSwNP was a predictor of dupilumab efficacy. METHODS: Patients were randomized 1:1:1 to dupilumab 300 mg every 2 weeks (q2w) until week 52; dupilumab 300 mg q2w until Week 24, then 300 mg every 4 weeks until week 52; or placebo (MFNS) until week 52. Coprimary endpoints were change from baseline in nasal polyps score (NPS), nasal congestion (NC), and Lund-Mackay score assessed by CT (LMK-CT) at week 24. Patients (n = 438) were stratified by eosinophilic chronic rhinosinusitis (ECRS) status according to the Japanese Epidemiological Survey of Refractory Eosinophilic Rhinosinusitis algorithm. RESULTS: Dupilumab significantly improved NPS, NC, and LMK-CT scores versus placebo at week 24 in all ECRS subgroups (p < 0.001), with improvements maintained or increased at week 52 (p < 0.001). There was no significant interaction between ECRS subgroup (non-/mild or moderate/severe) and dupilumab treatment effect for all endpoints at weeks 24 and 52 (p > 0.05), except LMK-CT at week 24 (p = 0.0275). Similar results were seen for the secondary endpoints. Dupilumab was well tolerated across all ECRS subgroups. CONCLUSION: Dupilumab produced consistent improvement in symptoms of severe CRSwNP irrespective of ECRS status. Therefore, blood eosinophil level may not be a suitable biomarker for dupilumab efficacy in CRSwNP.

Endoscopic Treatment of Sinonasal Leiomyosarcoma: A Case Report in Light of the Literature.

A 49-year-old Japanese man presented with a rare case of sinonasal leiomyosarcoma with left nasal bleeding for 12 months. He had no history of irradiation or malignancies, including retinoblastoma. Preoperative histological examination suggested vascular leiomyoma. Complete resection with endoscopic surgery was performed. Histological examination during the operation suggested that the tumor was a leiomyoma. However, immunohistochemical staining for α smooth muscle actin and desmin were helpful in establishing a definitive diagnosis of sinonasal leiomyosarcoma. The resection margins were positive for tumor cells. Staging with CT of the neck and thorax, ultrasound of the abdomen, and MRI of the head ruled out metastases. Second endoscopic tumor resection surgery was performed for positive resection margins. The patient's condition was successfully managed with additional excision, and he remains well with no evidence of recurrence and metastasis 36 months after treatment. Endoscopic management should be considered in suitable cases.

A global phylogenetic analysis of Japanese tonsil-derived Epstein-Barr virus strains using viral whole-genome cloning and long-read sequencing.

Epstein-Barr virus (EBV) establishes lifelong latent infection in the majority of healthy individuals, while it is a causative agent for various diseases, including some malignancies. Recent high-throughput sequencing results indicate that there are substantial levels of viral genome heterogeneity among different EBV strains. However, the extent of EBV strain variation among asymptomatically infected individuals remains elusive. Here, we present a streamlined experimental strategy to clone and sequence EBV genomes derived from human tonsillar tissues, which are the reservoirs of asymptomatic EBV infection. Complete EBV genome sequences, including those of repetitive regions, were determined for seven tonsil-derived EBV strains. Phylogenetic analyses based on the whole viral genome sequences of worldwide non-tumour-derived EBV strains revealed that Asian EBV strains could be divided into several distinct subgroups. EBV strains derived from nasopharyngeal carcinoma-endemic areas constitute different subgroups from a subgroup of EBV strains from non-endemic areas, including Japan. The results could be consistent with biased regional distribution of EBV-associated diseases depending on the different EBV strains colonizing different regions in Asian countries.

Altered Immune Regulation of Dendritic Cells and Enhanced Cytokine Production of T Cells in the Pathogenesis of Eosinophilic Chronic Rhinosinusitis.

INTRODUCTION: Eosinophilic chronic rhinosinusitis (ECRS) is a refractory chronic disease defined by recurrent nasal polyps with severe eosinophilic infiltration. This is mainly due to enhanced type 2-dominant immune responses, but the underlying mechanism is still not fully understood. OBJECTIVE AND METHODS: In the present study, we aimed to determine the characteristics of dendritic cells (DCs) and cytokine profiles of T cells in the peripheral blood of individuals with ECRS and age- and sex-matched healthy controls (HC). RESULTS AND CONCLUSION: The ratios of myeloid (m)DC1s to DCs and PD-L1+ mDC1s to mDC1s were higher in ECRS patients than in HC. The proportions of plasmacytoid (p)DCs in DCs, and human leukocyte antigen-DR+ pDCs and ILT3+ pDCs in pDCs were lower in ECRS patients than in HC. In a characterization of T cells, IL-4+CD4+, IFN-γ+CD4+, IL-4+IFN-γ+CD4+, IL-4+Foxp3+CD4+, IFN-γ+Foxp3+CD4+, IFN-γ+IL-4-Foxp3-CD4+, IL-4+CD8+, IL-4+IFN-γ+CD8+, and IL-4+Foxp3+CD8+ T-cell populations were significantly higher in ECRS patients than in HC. These results suggest that the enhanced immune regulation of mDC1, diminished capacity of pDCs, and increased proportion of the T-cell phenotypes in peripheral blood might be factors in ECRS pathogenesis.

OK-432 treatment of pediatric patients with recurrent thyroglossal duct cyst after surgery.

<b>Introduction:</b> Recurrent thyroglossal duct cyst after surgery is not a rare condition and first-line treatment has not been established yet.<br/><br/> <b>Aim:</b> Evaluation of outcomes and complications of OK-432 treatment in patients with recurrent thyroglossal duct cyst after surgery. <br/><br/> <b>Material and methods:</b> This study is designed as a case series with planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Five patients with recurrent thyroglossal duct cyst after surgery received this therapy between January 2014 and February 2020 on an outpatient basis, without hospitalization. OK-432 solution was injected into the lesion using an 18- or 27-gauge needle, depending on the location and size of the lesion, as well as on possible complications.<br/> <br/> <b>Results:</b> Lesions showed marked reduction or total shrinkage in all patients, with no local scarring or deformity at the injection site. Side effects manifested as local pain at the site of injection and fever (37.5-38.5°C) observed in three patients, but the symptoms resolved within a few days.<br/> <br/> <b>Conclusions:</b> Since OK-432 therapy is simple, easy, safe and effective, it can be used as an alternative to surgery in the treatment of recurrent thyroglossal duct cyst after surgery.

Treatment of oral ranula in HIV-positive patient.

HIV-associated salivary gland disease refers to the pathology in head and neck lesions such as ranula, salivary gland swelling, xerostomia, and benign lymphoepithelial cysts in the parotid gland. Here, we present a unique case of the ranula patient with HIV infection treated with OK-423 sclerotherapy. Case report: The patient was a 42-year-old Japanese male with a few months history of oral floor swelling. Computed tomography (CT) showed a low-density area limited within the right floor of the mouth. Magnetic resonance imaging (MRI) revealed a distinct T2-high intensity area localized on the same location. The puncture fluid was bloody mucus, and the cytology was no malignancy. We diagnosed a simple ranula. He was, however, found to be HIV-antibody positive at the examination before treatment by chance. He was referred to the department of infectious diseases and definitively diagnosed HIV infection by western blot. We chose OK-432 sclerotherapy because of its minimally invasive and the risk of HIV infecting medical staff. Two times OK-432 injection made the lesion disappear. Conclusion: The case indicated that OK-432 sclerotherapy could be effective for ranula related to HIV.

Systematic Review of Surgical Outcomes Following Repair of Patulous Eustachian Tube.

OBJECTIVE: To perform a systematic review and meta-analysis of surgical outcomes following repair of patulous Eustachian tube (PET). DATA SOURCES: Analysis of cases collected from studies published between January 1990 and December 2018 and identified using PubMed, Google Scholar, and Cochrane databases. STUDY SELECTION: Articles addressing interventions to treat PET were selected. DATA EXTRACTION: The database was searched using the keywords "patulous Eustachian tube treatment" and yielded 1,370 studies. Twenty studies were eligible for inclusion. DATA SYNTHESIS: A total of 914 cases were evaluated for surgical approach, patient outcomes, and complications. The reported techniques were categorized by the procedure type, including ventilation tube insertion, mass loading of the tympanic membrane, ET injection, plug surgery, shim surgery, tuboplasty, and ET closure. Overall PET symptom improvement were reported for ventilation tube insertion (79 cases, mean: 58%, 95% CI: 47-69%), mass loading of the tympanic membrane (43 cases, mean: 50%, 95% CI: 32-69%), ET injection (139 cases, mean: 47%, 95% CI: 38-56%), plug surgery (386 cases, mean: 81%, 95% CI: 77-85%), shim surgery (122 cases, mean: 62%, 95% CI: 53-70%), tuboplasty (105 cases, mean: 41%, 95% CI: 31-51%), and ET closure (40 cases, mean: 66%, 95% CI: 49-80%). A low incidence of minor complications was reported. CONCLUSIONS: This systematic review describes clinical outcome data following surgical management of PET. Plug surgery and shim surgery show relatively high effectiveness and safety. Further prospective studies that compare surgical approaches for PET are needed.