Comparative analyses of short- and long-term outcomes between endoscopic submucosal dissection and endoscopic laryngo-pharyngeal surgery for superficial pharyngeal carcinomas.

Objectives: Endoscopic treatment of superficial pharyngeal carcinomas includes endoscopic submucosal dissection (ESD; usually performed by endoscopists), and endoscopic laryngo-pharyngeal surgery (ELPS; primarily performed by otolaryngologists). Few studies have compared the efficacy of the two techniques in treating superficial pharyngeal carcinomas. In this study, we compared the outcomes of these two techniques to determine the advantages. Methods: We retrospectively examined the short- and long-term outcomes of 93 consecutive patients with superficial pharyngeal carcinoma who either underwent an ESD or ELPS between August 2008 and December 2021. Results: There were 35 lesions among 29 patients and 93 lesions among 71 patients in the ESD and ELPS groups, respectively. The ELPS group had a significantly shorter procedure time (121.2 ± 97.4 min vs. 54.7 ± 40.2 min, p<0.01), greater procedure speed (0.10 ± 0.06 min/min vs. 0.30 ± 0.23 min/min, p<0.01), and less laryngeal edema than that of the ESD group. There were no significant differences in the 3-year overall, relapse-free, or disease-specific survival rates between the two groups. Intervention with ESD during ELPS was most commonly required when it was difficult to secure the visual field. Conclusions: There were no differences in batch resection rates or long-term prognoses between the two groups; nevertheless, the ELPS group had a shorter treatment time and less laryngeal edema than the ESD group. However, the treatment of narrow areas, such as the esophageal inlet patch, is a technical limitation of ELPS; thus, ELPS should be combined with ESD techniques.

First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE­048.

BACKGROUND: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up. METHODS: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. RESULTS: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2-81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13-1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34-1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27-1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27-2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56-2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57-2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. CONCLUSION: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. CLINICAL TRIAL REGISTRATION: NCT02358031.

Baseline eosinophil proportion is a useful predictor of immune-related adverse events following immune checkpoint inhibitor treatment for recurrent metastatic head and neck cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs. However, predictors of irAEs remain unidentified. OBJECTIVES: We evaluated the predictors of irAEs and compared the outcomes of ICIs with and without irAEs in patients with recurrent/metastatic head and neck cancers (R/M HNCs). MATERIALS AND METHODS: We retrospectively analyzed 157 patients with R/M HNCs who were administered an anti-PD-1 antibody between September 2014 and December 2022. We examined whether various pretreatment factors were associated with irAEs. The overall survival (OS) and progression-free survival (PFS) in patients with and without irAEs were analyzed. RESULTS: Overall, 44 patients (28.0%) developed irAEs. The survival curve estimated for patients with and without irAEs showed a significant difference in PFS (p = 0.018), but not in OS (p = 0.208). Multivariate analysis revealed significant differences in relative eosinophil counts (p < 0.001), TP (p = 0.014), and NLR (p = 0.002), which may be independent predictors of irAEs. CONCLUSION: IrAEs may be associated with higher efficacy of ICIs and longer PFS. The relative eosinophil count may be predictors of irAEs and useful in routine medical practice. Using these biomarkers to predict irAEs will help predict ICI effects and manage irAEs.

Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008.

BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

Clinical, genomic and immune microenvironmental determinants of nivolumab response in head and neck squamous cell carcinoma.

Background: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. Methods: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing. Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. Conclusion: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.

Severe Type 2 Inflammation Leads to High Platelet-Activating-Factor-Associated Pathology in Chronic Rhinosinusitis with Nasal Polyps-A Hierarchical Cluster Analysis Using Bulk RNA Barcoding and Sequencing.

Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator that triggers various inflammatory conditions, including eosinophil activation and recruitment. This study aimed to evaluate the expressions of PAF-metabolism-associated genes, namely genes coding the enzymes involved in PAF synthesis (LPCAT1, LPCAT2, LPCAT3, and LPCAT4), PAF degradation (PAFAH1B2, PAFAH1B3, and PAFAH2), and the gene for the PAF receptor (PTAFR) in subtypes of CRSwNP classified by clinical- or hierarchal-analysis-based classifications. Transcriptomic analysis using bulk RNA barcoding and sequencing (BRB-seq) was performed with CRSwNP, including eosinophilic CRS (ECRS) (n = 9), nonECRS (n = 8), ECRS with aspirin-exacerbated respiratory disease (Asp) (n = 3), and controls with a normal uncinate process mucosa (n = 6). PTAFR was only upregulated in ECRS and nonECRS. In the hierarchical cluster analysis with clusters 1 and 2 reflecting patients with low-to-moderate and high levels of type 2 inflammation, respectively, cluster 1 exhibited a significant downregulation of LPCAT2 and an upregulation of PTAFR expression, while cluster 2 showed an upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. Understanding this strong PAF-associated pathophysiology in the severe type 2 inflammation group could provide valuable insights into the treatment and management of CRSwNP.

Transoral robotic surgery (TORS) in Japan: procedures, advantages and current status.

Transoral robotic surgery (TORS), introduced by Weinstein et al. in 2005, has been widely adopted as a minimally invasive procedure, particularly for the treatment of patients with early stage oropharyngeal cancer. TORS is typically performed using the da Vinci Surgical System, similar to robot-assisted surgeries for other malignancies. The main difference between TORS and these other robot-assisted surgeries is that it is performed through the natural orifice of the mouth, which limits the surgical working space, and that it progresses from the lumen of the pharynx to the deeper tissues. The advantages of TORS are mainly due to the benefits of using the da Vinci Surgical System, such as three-dimensional high-definition images, magnification, multiple forceps articulation, tremor-stabilization function and motion scale function. To date, many big data and meta-analyses have shown that TORS is superior to conventional surgeries, such as open surgery, in terms of oncological outcomes, post-operative functionality and quality of life. In Japan, TORS is expected to spread across the country, as it has been covered by health insurance since April 2022. This review highlights the procedures of TORS, its unique aspects, its unparalleled advantages as a minimally invasive surgery for treating laryngeal and pharyngeal cancers, and its current status in Japan.

Extent of thyroidectomy and paratracheal lymph node dissection in total pharyngolaryngectomy for pyriform sinus cancer, and recurrence, survival, and postoperative hypoparathyroidism: A multicenter retrospective study.

BACKGROUND: Total pharyngolaryngectomy (TPL) is standard treatment for hypopharyngeal cancer. However, extensive thyroidectomy and paratracheal nodal dissection (PTND) can cause hypoparathyroidism. We sought to determine the optimum extent of resection. METHODS: We analyzed the clinicopathological information of 161 pyriform sinus cancer patients undergoing TPL from 25 Japanese institutions. Rates of recurrence and risk factors for hypoparathyroidism, as well as incidence of pathological contralateral level VI nodal metastasis and stomal recurrence, were investigated. RESULTS: The extent of thyroidectomy and nodal dissection were not independent risk factors for recurrence. Incidences of contralateral level VI nodal involvement and stomal recurrence were 1.8% and 1.2%, respectively. Patients undergoing hemithyroidectomy/ipsilateral PTND did not develop stomal recurrence and had the lowest incidence of hypoparathyroidism. Prognosis in patients without tracheostomy prior to hemithyroidectomy/ipsilateral PTND was comparable to that with more extensive resections. CONCLUSIONS: Hemithyroidectomy/ipsilateral PTND may be sufficient for pyriform sinus cancer cases without tracheostomy.

Dose-Finding and Efficacy Confirmation Trial of the Superselective Intra-arterial Infusion of Cisplatin and Concomitant Radiation Therapy for Locally Advanced Maxillary Sinus Cancer (JCOG1212): Results of the Efficacy Confirmation Phase in Patients with T4aN0M0.

PURPOSE: Locally advanced maxillary sinus cancers require radical surgery as a standard treatment, but this often results in significant disfigurement and impairment of function. JCOG1212 seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of cisplatin and concomitant radiation therapy (RADPLAT) for T4aN0M0 and T4bN0M0 maxillary sinus squamous cell carcinomas. We herein report the results of the efficacy confirmation phase in the T4a cohort. METHODS AND MATERIALS: Patients received 100 mg/m2 cisplatin intra-arterially weekly for 7 weeks with concomitant radiation therapy (total 70 Gy) as determined by the results of the preceding dose-finding phase. The trial aimed to evaluate the primary endpoint of 3-year overall survival (OS), comparing RADPLAT with the historical control for 3-year OS in surgery (80%). RESULTS: From April 2014 to August 2018, 65 patients were registered in the T4a cohort from 18 institutions, consisting of 54 men and 11 women with a median age of 64 years (range, 40-78 years) and Eastern Cooperative Oncology Group performance status 0/1 (58/7). After excluding 1 ineligible patient, 64 patients were included in the primary analysis of efficacy and safety. The median follow-up was 4.5 years in all eligible patients, and the primary endpoint for 3-year OS was 82.8% (90% CI, 73.4%-89.2%). With regard to acute adverse events, mucositis (grade ≥3), neutropenia (grade ≥3), increased creatinine (grade ≥2), hearing impairment (grade ≥2), and stroke (grade ≥2) were observed in 20.3%, 14.1%, 3.1%, 3.1%, and 1.6% of patients, respectively. One treatment-related death due to a thromboembolic event was reported. CONCLUSIONS: We demonstrated that RADPLAT showed favorable results for patients with T4aN0M0 maxillary sinus squamous cell carcinomas compared with the historical control for 3-year OS in surgery, which was from an earlier period, and showed some specific toxicities. Therefore, RADPLAT, as well as surgery, can be regarded as a possible treatment option for these patients.

Artificial intelligence-based diagnosis of the depth of laryngopharyngeal cancer.

OBJECTIVE: Transoral surgery (TOS) is a widely used treatment for laryngopharyngeal cancer. There are some difficult cases of setting the extent of resection in TOS, particularly in setting the vertical margins. However, positive vertical margins require additional treatment. Further, excessive resection should be avoided as it increases the risk of bleeding as a postoperative complication and may lead to decreased quality of life, such as dysphagia. Considering these issues, determining the extent of resection in TOS is an important consideration. In this study, we investigated the possibility of accurately diagnosing the depth of laryngopharyngeal cancer using radiomics, an image analysis method based on artificial intelligence (AI). METHODS: We included esophagogastroduodenoscopic images of 95 lesions that were pathologically diagnosed as squamous cell carcinoma (SCC) and treated with transoral surgery at our institution between August 2009 and April 2020. Of the 95 lesions, 54 were SCC in situ, and 41 were SCC. Radiomics analysis was performed on 95 upper gastrointestinal endoscopic NBI images of these lesions to evaluate their diagnostic performance for the presence of subepithelial invasion. The lesions in the endoscopic images were manually delineated, and the accuracy, sensitivity, specificity, and area under the curve (AUC) were evaluated from the features obtained using least absolute shrinkage and selection operator analysis. In addition, the results were compared with the depth predictions made by skilled endoscopists. RESULTS: In the Radiomics study, the average cross-validation was 0.833. The mean AUC for cross-validation calculated from the receiver operating characteristic curve was 0.868. These results were equivalent to those of the diagnosis made by a skilled endoscopist. CONCLUSION: The diagnosis of laryngopharyngeal cancer depth using radiomics analysis has potential clinical applications. We plan to use it in actual surgery in the future and prospectively study whether it can be used for diagnosis.

Oncostatin M's Involvement in the Pathogenesis of Chronic Rhinosinusitis: Focus on Type 1 and 2 Inflammation.

OBJECTIVES: The cytokine oncostatin M (OSM) elicits pathogenic effects involving disruption of the epithelial barrier function as a part of immunological response networks. It is unclear how these integrated cytokine signals influence inflammation and other physiological processes in the pathology of chronic rhinosinusitis (CRS). We investigated the expression and distribution of OSM and OSM receptor (OSMR) in CRS patients' sinonasal specimens, and we compared the results with a panel of inflammatory cytokine levels and clinical features. PATIENTS AND METHODS: We classified CRS patients as eosinophilic (ECRS, n = 36) or non-eosinophilic (non-ECRS, n = 35) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis phenotypic criteria and compared their cases with those of 20 control subjects. We also examined OSM's stimulatory effects on cytokine receptor expression levels using the human bronchial epithelium cell line BEAS-2B. RESULTS: RT-PCR showed that the OSM mRNA levels were significantly increased in the CRS patients' ethmoid sinus mucosa. The OSM mRNA levels were positively correlated with those of TNF-α, IL-1ß, IL-13, and OSMR-ß. In BEAS-2B cells, OSM treatment induced significant increases in the OSMRß, IL-1R1, and IL-13Ra mRNA levels. CONCLUSIONS: OSM is involved in the pathogenesis of CRS in both type 1 and type 2 inflammation, suggesting the OSM signaling pathway as a potential therapeutic target for modulating epithelial stromal interactions.

Swallowing Exercise Evaluated Using High-Density Surface Electromyography in Patients with Head and Neck Cancer: Supplementary Analysis of an Exploratory Phase II Trial.

Background and Objectives: Muscle strength evaluation using high-density surface electromyography (HD-sEMG) was recently developed for the detailed analysis of the motor unit (MU). Detection of the spatial distribution of sEMG can detect changes in MU recruitment patterns resulting from muscle-strengthening exercises. We conducted a prospective study in 2022 to evaluate the safety and feasibility of transcutaneous electrical sensory stimulation (TESS) therapy using an interferential current device (IFCD) in patients with head and neck squamous cell carcinoma (HNSCC) undergoing chemoradiotherapy (CRT), and reported the safety and feasibility of TESS. We evaluated the efficacy of swallowing exercises in patients with HNSCC undergoing CRT and determined the significance of sEMG in evaluating swallowing function. Materials and Methods: In this supplementary study, the patients performed muscle-strengthening exercises five days a week. The association of the effects of the exercises with body mass index, skeletal muscle mass index, HD-sEMG, tongue muscle strength, and tongue pressure were evaluated. Results: We found significant correlations between the rate of weight loss and skeletal muscle mass index reduction and the rate of change in the recruitment of the MU of the suprahyoid muscle group measured using HD-sEMG. Conclusions: We believe that nutritional supplementation is necessary in addition to muscle strengthening during CRT.

Exhaled Nitric Oxide and Olfactory Dysfunction in Patients with Asthma: Association with Chronic Rhinosinusitis.

Objectives: Olfactory dysfunction is a clinical sign that is important to detect with coexistent upper airway comorbidities in patients with asthma. This study aimed to investigate the etiology of olfactory dysfunction in patients with asthma and the relationship between fractional exhaled nitric oxide (FeNO) levels. Materials and Methods: This study included 47 asthma patients who were evaluated for olfactory dysfunction at Hiroshima University Hospital between 2012 and 2020. The etiologies of olfactory dysfunction were evaluated, and they were classified according to the FeNO levels of patients with asthma. Results: Olfactory dysfunction was observed in 30 patients with asthma, with chronic rhinosinusitis (77%) being the most prevalent etiology. Eosinophilic chronic rhinosinusitis (ECRS) was the most prevalent etiology of olfactory dysfunction in asthma patients with high FeNO levels (≥25 ppb), while non-eosinophilic chronic rhinosinusitis (NCRS) was the most prevalent etiology in asthma patients with low FeNO levels (<25 ppb). Additionally, the prevalence of ECRS was significantly higher in asthma patients with olfactory dysfunction and high FeNO levels (74%) than in those with either high FeNO levels or olfactory dysfunction and those with low FeNO levels and no olfactory dysfunction (12% and 9%, respectively). Conclusions: We found that ECRS was the predominant cause of olfactory dysfunction in patients with high FeNO levels, while NCRS was more common in those with low FeNO levels. The present study showed that both ECRS and NCRS are common etiologies of olfactory dysfunction in patients with asthma. Additionally, this study supports the link between upper and lower airway inflammation in patients with asthma complicated with olfactory dysfunction.

Head and neck cancer patients show poor oral health as compared to those with other types of cancer.

PURPOSE: Several studies have found associations between periodontitis and various types of cancer. Since the site of head and neck cancer (HNC) has contiguity or proximity to the oral cavity, it may be particularly influenced by oral inflammation. This study aimed to determine whether HNC patients have poor oral health as compared to those with other types of cancer. METHODS: This study retrospectively examined oral environmental factors including periodontal inflamed surface area (PISA), a new periodontal inflammatory parameter. A total of 1030 cancer patients were divided into the HNC (n = 142) and other cancer (n = 888) groups. Furthermore, the HNC group was divided into high (n = 71) and low (n = 71) PISA subgroups, and independent risk factors affecting a high PISA value were investigated. RESULTS: Multivariate logistic regression analysis showed that number of missing teeth (odds ratio 1.72, 95% CI 1.15-2.56, P < 0.01), PISA (odds ratio 1.06, 95% CI 1.03-1.06, P < 0.05), and oral bacterial count (odds ratio 1.02, 95% CI 1.01-1.03, P < 0.01) were independent factors related to HNC. In addition, multivariate logistic regression analysis indicated that current smoker (odds ratio 7.51, 95% CI 1.63-34.71, P < 0.01) and presence of untreated dental caries (odds ratio 3.33, 95% CI 1.23-9.00, P < 0.05) were independent risk factors affecting high PISA values in HNC patients. CONCLUSION: HNC patients have higher levels of gingival inflammation and poor oral health as compared to patients with other types of cancer, indicating that prompt oral assessment and an effective oral hygiene management plan are needed at the time of HNC diagnosis.

Efficacy of Supportive Care for Radiodermatitis in Patients with Head and Neck Cancer: Supplementary Analysis of an Exploratory Phase II Trial.

Self-care demonstrated efficacy in preventing severe acute radiation dermatitis among patients with head and neck squamous cell carcinoma undergoing chemoradiotherapy (CRT). This prospective trial aimed to confirm the feasibility and safety of transcutaneous electrical sensory stimulation while examining the relationship between changes in self-care behavior through supportive care interventions and the severity of acute radiation dermatitis during CRT. Patients underwent assessments for dermatitis grading (Grades 1 to ≥3) and were interviewed regarding self-care practices. The self-care questionnaires comprised six items, and a point was deducted for each task that the patient could not perform independently. Statistical analysis was performed to determine the association between G3 radiation dermatitis and the lowest self-care behavior scores. Of the 10 patients enrolled, three experienced G3 dermatitis. During CRT, six patients maintained their initial scores and did not develop ≥G3 dermatitis. Meanwhile, three of four patients with decreased scores exhibited ≥G3 dermatitis. The group with ≥G3 dermatitis had significantly lower scores than those with ≤G2 dermatitis, suggesting that the inability of patients to perform self-care routinely may lead to severe acute radiation dermatitis. Further prospective studies are needed to confirm the potential of self-care interventions in preventing severe dermatitis.

Evaluation of the Safety of Percutaneous Sensory Nerve Stimulation in Patients with Head and Neck Cancer Receiving Chemoradiotherapy.

Chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck cancer; however, CRT may cause post-treatment dysphagia. Transcutaneous electrical sensory stimulation (TESS), developed in recent years for swallowing rehabilitation, is used at many medical facilities. Although TESS has been used for dysphagia in several fields, its safety and efficacy in patients with head and neck cancer remain to be clarified. Therefore, this study evaluated the safety of TESS in ten patients with head and neck cancers undergoing CRT. Swallowing rehabilitation intervention and TESS implementation were performed for all patients during CRT. Non-blood-toxicity adverse events (AEs), such as dermatitis and mucositis, occurred during CRT; however, the severity was less than grade 3. No patient experienced pain due to TESS. As survival time analysis using the Kaplan-Meier method for interferential current device implementation rates revealed a feasibility of 100% for up to 60 Gy and a feasibility of 78% for up to 70 Gy, TESS may be feasible until 70 Gy. This study confirmed the feasibility and safety of TESS in the head and neck region during CRT. Although the precise mechanism of TESS on dysphagia remains unclear, its continued use has great potential for improving sensory disturbance.

Functional Alteration and Differential Expression of the Bitter Taste Receptor T2R38 in Human Paranasal Sinus in Patients with Chronic Rhinosinusitis.

The bitter taste receptors (T2Rs) expressed in human sinonasal mucosae are known to elicit innate immune responses involving the release of nitric oxide (NO). We investigated the expression and distribution of two T2Rs, T2R14 and T2R38, in patients with chronic rhinosinusitis (CRS) and correlated the results with fractional exhaled NO (FeNO) levels and genotype of the T2R38 gene (TAS2R38). Using the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) phenotypic criteria, we identified CRS patients as either eosinophilic (ECRS, n = 36) or non-eosinophilic (non-ECRS, n = 56) patients and compared these groups with 51 non-CRS subjects. Mucosal specimens from the ethmoid sinus, nasal polyps, and inferior turbinate were collected from all subjects, together with blood samples, for RT-PCR analysis, immunostaining, and single nucleotide polymorphism (SNP) typing. We observed significant downregulation of T2R38 mRNA levels in the ethmoid mucosa of non-ECRS patients and in the nasal polyps of ECRS patients. No significant differences in T2R14 or T2R38 mRNA levels were found among the inferior turbinate mucosae of the three groups. Positive T2R38 immunoreactivity was localized mainly in epithelial ciliated cells, whereas secretary goblet cells generally showed lack of staining. The patients in the non-ECRS group showed significantly lower oral and nasal FeNO levels compared with the control group. There was a trend towards higher CRS prevalence in the PAV/AVI and AVI/AVI genotype groups as compared to the PAV/PAV group. Our findings reveal complex but important roles of T2R38 function in ciliated cells associated with specific CRS phenotypes, suggesting the T2R38 pathway as a potential therapeutic target for promotion of endogenous defense mechanisms.

Determining Invasion Depth in Superficial Pharyngeal Carcinoma by Transoral Ultrasonography.

OBJECTIVES: To examine the clinical usefulness of transoral ultrasonography (US) in determining the invasion depth of superficial pharyngeal carcinoma (SPC). Determining the invasion depth of SPC is crucial for transoral surgery including determining treatment strategy. This study aimed to examine the usefulness of transoral US in determining the invasion depth of SPC. METHODS: Forty-six patients with 51 lesions who underwent both magnifying endoscopy with narrow-band imaging (ME-NBI) and transoral US were included. The primary outcomes were the sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of ME-NBI and transoral US findings for pathological tumor depth in SPCs. RESULTS: The accuracy (82.4%), sensitivity (85.2%), PPV (82.1%), and NPV (82.6%) rates of US for subepithelial propria (SEP) were higher than those of ME-NBI and macroscopic classification, indicating that transoral US is superior to ME-NBI in determining the invasion depth. All cases where the SEP was clearly invaded (SEP deep) could be diagnosed as SEP by transoral US. CONCLUSIONS: Transoral US may be useful in determining the invasion depth of SPCs. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2192-2197, 2023.

Severe multiple simultaneous immune-related adverse events in a patient with head and neck cancer.

Nivolumab, an immune checkpoint inhibitor (ICI) against the programmed death-1 pathway, has been used for the treatment of recurrent metastatic head and neck cancer. However, the management of immune-related adverse events (irAEs), a unique side effect of ICI therapy, can be problematic. Although severe irAEs have been reported to result from multi-ICI therapy, we report a case of multiple severe irAEs caused by single-agent nivolumab treatment. Nivolumab was administered to treat a case of hypopharyngeal cancer recurrence. However, when first-line chemotherapy of nivolumab was replaced with a second chemotherapeutic agent because of insufficient effectiveness, the patient showed anorexia, dermatitis, and mucositis; upper gastrointestinal endoscopy yielded a diagnosis of irAEs. Additional examinations revealed simultaneous multiple irAEs, including hypothyroidism, dermatitis, eyelid conjunctivitis, tracheal mucositis, upper gastrointestinal ulcer, and type 1 diabetes. Since all symptoms improved after steroid treatment, the patient was treated with subsequent chemotherapy. However, he died from uncontrolled cancer recurrence. Thus, even a single ICI agent can cause life-threatening irAEs. Moreover, the management of irAEs requires early recognition and close multidisciplinary collaboration in accordance with the countermeasure manual.

Effectiveness of Expanded Instantaneous Input Dynamic Range Adjustment on Speech Perception.

Instantaneous input dynamic range (IIDR), as defined by Cochlear Ltd. (Sydney, Australia), refers to the acoustic level of short-term input dynamic range (IDR). Our aim was to evaluate the efficacy of expanding IIDR to improve speech understanding. We enrolled 11 unilateral Cochlear Ltd. patients with post-lingual hearing loss. The two types of IIDR settings (T-SPL/C-SPL of 25/65 dB (default IIDR) and 25/80 dB (wide IIDR)) were blindly assigned, and only one IIDR setting selected according to their preference was used for at least three months. Each IIDR group was evaluated with both default and wide IIDR conditions using the recorded word and sentence test materials of the Japanese CD speech discrimination scoring system (CI-2004 test) in quiet and noise with a signal-to-noise ratio (SNR) of +10 dB, presented at 65/80 dB SPL. Wide IIDR significantly improved speech perception in all tests, except for sentences in quiet conditions at a presentation level of 65 dB. Improvements during loud conversations in noisy environments were obtained without any adaptation period. Wide IIDR should become a new individual configuration setting method in Cochlear Ltd. devices to improve hearing in loud conversations and noisy environments.