Development of a Remote Examination of Deglutition Based on Consensus Surveys of Clinicians (Part II): Reliability and Validity in Healthy Elderly Individuals and Oral Cancer Patients.

In our prior published study, we extracted evaluation items suitable for remote administration, and made a relatively simple Remote Examination of Deglutition (RED). This study aimed at verifying the reliability and validity of RED. The participants were 21 healthy elderly individuals and 72 postoperative oral cancer (OC) patients. OC patients underwent videofluoroscopic dysphagia examination, and severity was judged on the dysphagia severity scale (DSS). Reliability and validity of RED were examined in all participants under face-to-face conditions, in comparison with the Mann Assessment of Swallowing Ability (MASA). Reliability and validity of remote administration of RED were examined in 40 participants. ROC curves were used to find cut-off RED scores to predict aspiration and deglutition disorders. The Cronbach's alpha coefficient for the items was 0.882. There was a high correlation between the total score of RED and MASA in the face-to-face condition. When RED score was compared among different severity groups (DSS1-4, DSS5-6, and DSS7), the total and oral preparatory stage scores revealed significant group differences. The area under the curve (AUC) for aspiration based on the ROC curve was 0.913, with a sensitivity/specificity of 0.80/0.98. The AUC for deglutition disorders was 0.819, with a sensitivity/specificity of 0.74/0.67. In both face-to-face and remote conditions, the reliability of RED was good.The reliability and validity of RED were confirmed. RED has shown the potential to assess the likelihood of aspiration and deglutition disorders in OC patients remotely as an initial assessment tool.

Effects of Bolus Types and Swallowing Maneuvers on Laryngeal Elevation: Analysis of Healthy Young Adult Men and Healthy Older Men.

Peak velocity, distance, and time of laryngeal elevation during swallowing were measured with a laryngeal motion measurement system in eight healthy young adult men in their 20 and 30 s (33.0 ± 4.3 years) and ten healthy older men in their 60 and 70 s (74.0 ± 3.9 years). The participants performed swallowing five times each for a total of eight conditions: two bolus types (saliva and water) and four swallowing methods (normal swallow, effortful swallow, super-supraglottic swallow, and Mendelsohn maneuver). When the bolus type was saliva, peak velocity and distance increased more for swallowing maneuvers (effortful swallow, super-supraglottic swallow, and Mendelsohn maneuver) than for normal swallow. On the other hand, when the bolus type was water, there was no difference in peak velocity or distance between normal swallow and swallowing maneuvers. In healthy older men, distance was greater with Mendelsohn maneuver than with normal swallow, and peak velocity was increased with swallowing maneuvers than with normal swallow. Healthy young adult men had increased peak velocity and distance with water rather than saliva. The increase in peak velocity and distance obtained by swallowing maneuvers was influenced by age and bolus, suggesting that the subjects and conditions used are important in terms of promoting safer oral intake.

Development of a Remote Examination of Deglutition Based on Consensus Surveys of Clinicians (Part I): Selection of Examination Items.

In order to ensure appropriateness and feasibility of examination items for remote evaluation for deglutition disorders, a questionnaire based on the Delphi method was administered to 122 speech-language-hearing therapists (STs), and a set of examination items was selected. The participants were instructed to view a video recording of a remote assessment situation and answer a 30-item questionnaire. Of 19 items ensuring the appropriateness for deglutition disorders detection, 13 items ultimately met the consensus criteria for remote feasibility. Factor analysis extracted three factors: 'oral observation,' 'overall evaluation,' and 'perceptual voice judgment.' In free-text responses, "quality and stability of the voice that may be heard through the device" were the most common concerns, followed by "the need to correct of the camera angle, magnification, and targets that should be projected," "concerns about the technical aspects of the assistants and their role in relation with the examiner/ST," and "the need for palpation as well as visual confirmation." The proposed 13-item examination is considered to capture the characteristics of deglutition disorders, while items that appeared difficult to implement remotely were excluded. The fact that some items could be influenced by the video calling experience when judging the feasibility of remote implementation, the acceptability of such items, is likely to increase in the future.

Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis.

The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically. The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.

[Report of Multidisciplinary Treatment for Sisters with Li-Fraumeni Syndrome].

Li-Fraumeni syndrome(LFS)is a hereditary cancer disorder caused by germline variant in TP53 and characterized by various malignancies. Multidisciplinary treatment is needed for tumors of LFS, however, radiation therapy is a relative contraindication because of frequent development of secondary malignancy such as sarcoma in the irradiated field. Case 1: A 22- year-old woman who was diagnosed with LFS by genetic test when she developed upper rectal cancer. Her rectal tumor with marked bilateral lateral lymph node dissection was successfully removed by low anterior resection with extensive lateral lymph node dissection. She underwent resection for ovarian metastasis followed by chemotherapy and radiotherapy but subsequently died by the disease 32 months postoperatively. Case 2(elder sister of Case 1): A brain tumor was identified in the left high frontal lobe to the parietal lobe because of consciousness disorder, after the genetic diagnosis of LFS. The brain tumor was successfully resected. Histological examination revealed diffuse astrocytoma(WHO grade Ⅱ). Local recurrence was observed 46 months later, and radiation therapy was performed. Six months have passed since radiation therapy, no exacerbation of local recurrence has been observed.

[Idea of Treatment Method for Upper and Lower Rectal Cancer Avoiding Irradiation to Internal and External Sphincter].

BACKGROUND: Preoperative chemoradiotherapy(CRT)followed by total mesorectal excision(TME)is used for locally advanced rectal cancer, but it can induce postoperative anorectal function. The primary objective of this study is to confirm the efficacy and safety of preoperative CRT and TME without irradiation to the internal and external sphincter muscles. SUBJECTS AND METHODS: Patients were eligible for this study if they met the following inclusion criteria: histologically proven rectal cancer, clinical T3T4N0-2 disease, and a distance between anal margin of tumor and the rental line is more than 2 cm. Twelve patients who underwent preoperative CRT and TME between 2013 and 2017 were enrolled. The primary endpoint was completion rate of sphincter-preserving surgery. RESULTS: All patients completed preoperative CRT without Grade 3 or higher adverse effect. Sphincter-preserving surgery was performed in all cases. The 5-year disease-free survival rate was 46.7%, and the local recurrence-free survival rate was 75%, and the overall survival rate was 90.9%. CONCLUSION: It is suggested that preoperative CRT and TME without irradiation to the internal and external sphincter muscles is effective and safe therapy for locally advanced rectal cancer.

Evaluation of geometrical uncertainties on localized prostate radiotherapy of patients with bilateral metallic hip prostheses using 3D-CRT, IMRT and VMAT: A planning study.

OBJECTIVE: Since most radiation treatment plans are based on computed tomography (CT) images, which makes it difficult to define the targeted tumor volume located near a metal implant, this study aims to evaluate and compare three treatment plans in order to optimally reduce geometrical uncertainty in external radiation treatment of localized prostate cancer. METHODS: Experimental subjects were three prostate patients with bilateral hip prosthesis who had undergone radical radiotherapy. The treatment plans were five-field three-dimensional conformal radiation therapy (3D-CRT), fixed 5-field intensity-modulated radiation therapy (IMRT) using similar gantry angles, and single-arc volumetric modulated arc therapy (VMAT). The monitor units (MUs), dose volume histograms (DVHs), the dose indices of planning target volume (PTV), clinical target volume (CTV) and rectum were compared among the three techniques. The geometrical uncertainties were evaluated by shifting the iso-center (2- 10 mm in the anterior, posterior, left, right, superior, and inferior directions). The CTV and rectum dose indexes with and without the iso-center shifts were compared in each plan. RESULTS: The Conformity Index of PTV were 1.35 in 3D-CRT, 1.12 in IMRT, and 1.04 in VMAT, respectively. The rectum doses in 3D-CRT are also higher than those in IMRT and VMAT. The iso-center shift little affected the CTV dose when smaller than the margin size. The rectum dose increased especially after a posterior shift. Additionally, this dose increase was larger in the VMAT plan than in the 3D- CRT plan. However, the VMAT achieved a superior rectum DVH to that of 3D- CRT, and this effect clearly exceeded the rectum-dose increase elicited by the iso-center shift. CONCLUSION: For radiotherapy treatment of localized prostate cancer in patients with hip prosthesis, the dose distribution was better in the VMAT and Metal Artifact Reduction (MAR)-CT image methods than the conventional methods. Because the anatomical structure of the male pelvic region is relatively constant among individuals, we consider that VMAT is a valid treatment plan despite analyzing just three cases.

Simple index for validity of the evaluation point for dosimetric verification results of intensity-modulated radiation therapy using a Farmer-type ionization chamber.

PURPOSE: Based on a retrospective analysis, this study aims to develop a simple index for validity of the evaluation point for the dosimetric verification of intensity-modulated radiation therapy (IMRT). METHODS: The results for the dosimetric verifications of a total of 69 IMRT plans were analyzed in this study. A Farmer-type ion chamber was used as a dose detector, and a solid water-equivalent phantom was used. Index values were obtained by dividing the difference between the maximum and minimum dosages by the mean dosage of the 69 plans, and the values were classified into five groups with index value <4, 4-8, 8-12, 12-16, and >16. A t-test was used to assess the statistical significance of the mean differences of the absolute values of the relative errors among these groups. RESULTS: We found that there was no significant difference between the groups with index value <4 and 4-8 (p = 0.152); however, there were significant differences between the other groups (p < 0.01). In addition, when the index values were smaller than 8, the pass ratio of 3% tolerance was 96.2% and the pass ratio of 5% tolerance was 99.9%. We observed that the smaller the index value, the smaller the uncertainty of the dose measurement. CONCLUSIONS: The results obtained in this study may prove to be useful for accurate dosimetric verifications of IMRTs when ion chambers are used.

[Trial of Micro CT Scanner SKYSCAN1176 for the Imaging of the Guinea Pig Cochlea in vivo].

The usefulness of the micro CT scanner system SKYSCAN1176 was evaluated for the study of the guinea pig cochlea. Each slice of the section was 9 µm and we were able to identify each ossicles, modiolus, upper, middle, and basal turn of the cochlea. This scanner enables us to observe inner ear structure repeatedly in vivo.

Tepotinib-induced hand-foot skin reaction.

Tepotinib may cause hand-foot skin reactions with keratotic changes. When such changes are observed in the hands or toes after starting tepotinib treatment, its side effects should be considered, and corticosteroid ointment or withdrawal of tepotinib should be considered if necessary.

A case report of immune checkpoint inhibitor-related myositis and cholangitis induced by pembrolizumab.

Key Clinical Message: Rare but severe, immune-related adverse events such as myositis and sclerosing cholangitis can occur with immune checkpoint inhibitors in lung cancer treatment. This case report highlights their co-occurrence after pembrolizumab treatment, indicating the need for vigilance and management strategies in immune checkpoint inhibitors therapy. Abstract: Immune checkpoint inhibitors (ICI) are used in advanced treatment of lung cancer but can lead to immune-related adverse events. ICI-related myositis and cholangitis are rare, and their combination has not been previously reported. Here, we report the first case of ICI-related myositis and sclerosing cholangitis. A patient with stage IV lung adenocarcinoma who received one cycle of pembrolizumab with cisplatin and pemetrexed developed myositis. Treatment with prednisolone improved the myositis, but the patient subsequently developed cholangitis. The patient did not respond to a regimen of prednisolone, mycophenolate mofetil, and azathioprine, and eventually died due to worsening lung cancer. An autopsy confirmed the presence of ICI-related myositis and sclerosing cholangitis.

Outpatient Treatment of Mild Dysphagia in Ear-Nose-and-Throat Clinics.

OBJECTIVE: Many reports on inpatient dysphagia rehabilitation in acute and convalescent rehabilitation hospitals exist, but there are a few reports on outpatient treatments. Otolaryngologists still take a trial-and-error approach when treating dysphagia. Here, we explore the effectiveness and limitations of outpatient treatment in ear-nose-and-throat (ENT) clinics. METHODS: Sixty-four patients (41 males and 23 females) aged 27-101 years (mean 78 years) visited an outpatient clinic specialising in feeding and swallowing conditions (the Fukuyo ENT Clinic). All were able to perform the activities of daily living (ADL) to the extent that outpatient visits were possible; no home visits were made. The weekly outpatient day was staffed by an otolaryngologist and a speech-language-hearing therapist (SLHT). All patients were subjected to fibreoptic endoscopic evaluation of swallowing (FEES), followed by appropriate training as revealed by the examinations. RESULTS: Salivary retention in the glottis valley and piriform sinuses improved (both p < 0.05) in 30 patients who underwent repeat FEES; we compared the initial and final figures. In 14 cases in whom maximal tongue pressure (TP) was measured, this was higher at the final than at the first examination (p < 0.01). CONCLUSION: Outpatient treatment at ENT clinics for patients who are able to maintain their ADLs to the extent that they are able to walk to a hospital is an option for the treatment of age-related dysphagia. For severe cases, however, house calls and collaboration with the home and nursing care sector will be necessary and should be considered in the future.

A case of allergic bronchopulmonary mycosis: 3D-CT Findings led to successful multidisciplinary treatment with dupilumab and cryoprobe.

The present case involved a 78-year-old woman with repeated recurrences of allergic bronchopulmonary mycosis (ABPM) who presented to our outpatient clinic with a chief complaint of dyspnoea with respiratory failure. Computed tomography (CT) of the chest showed atelectasis of the lower lobes due to mucus plugs. Blood and biochemical tests showed a high peripheral blood eosinophil count (1330/µL) and elevated immunoglobulin E (15,041 IU/mL; normal, < 361 IU/mL). Recurrent ABPM was diagnosed. The patient also showed chronic lower respiratory tract infection associated with Mycobacterium avium complex and Pseudomonas aeruginosa. First, we removed the mucus plug with a cryoprobe to avoid administering corticosteroids. However, subsequent 3-dimensional CT showed residual mucus plugs, so we administered dupilumab as an additional treatment. After initiating dupilumab, mucus plugs disappeared and respiratory failure resolved. We were able to implement multidisciplinary treatment that did not rely on corticosteroids.

Effects of Food Properties and Aging on External Auditory Canal Movements Associated With Mastication.

Few objective evaluations of external auditory canal movement during mastication have been conducted. This study investigated the extent to which age and physical properties influence such movement. The effects of food properties and aging on ear canal movement during mastication were investigated using an earable reliable chewing-count measurement device. We used such a device to study the effects of food properties and aging on ear canal movement associated with mastication. A main effect of the difference in hardness between the foods (F = 8.3405, p = 0.0071) was found. No interaction (F = 1.3558, p = 0.2534) or main effect of age (F = 1.1206, p = 0.2982) was found. The values for peanuts were higher than those for pudding. Age had no significant effect. For both pudding and peanuts, there was a trend toward greater ear canal movement in young adults than in older adults. We suggest that external auditory canal movement during mastication decreases as muscle function declines with aging, but any effect may be less than that exerted by food properties.

A Potential Novel Treatment for Chronic Cough in Long COVID Patients: Clearance of Epipharyngeal Residual SARS-CoV-2 Spike RNA by Epipharyngeal Abrasive Therapy.

A major target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the epipharyngeal mucosa. Epipharyngeal abrasive therapy (EAT) is a Japanese treatment for chronic epipharyngitis. EAT is a treatment for chronic epipharyngitis in Japan that involves applying zinc chloride as an anti-inflammatory agent to the epipharyngeal mucosa. Here, we present a case of a 21-year-old man with chronic coughing that persisted for four months after a diagnosis of mild coronavirus disease 2019 (COVID-19), who was treated by EAT. We diagnosed chronic epipharyngitis as the cause of the chronic cough after the SARS-CoV-2 infection. SARS-CoV-2 spike RNA had persisted in the epipharyngeal mucosa of this Long COVID patient. EAT was performed once a week for three months, which eliminated residual SARS-CoV-2 RNA and reduced epipharyngeal inflammation. Moreover, a reduction in the expression of proinflammatory cytokines was found by histopathological examination. We speculate that the virus was excreted with the drainage induced by EAT, which stopped the secretion of proinflammatory cytokines. This case study suggests that EAT is a useful treatment for chronic epipharyngitis involving long COVID.

Association Between Oral Health and Swallowing Function in the Elderly.

Objective: Although the oral environment significantly affects the risk of pneumonia, there have been few studies regarding its relation with swallowing. There is no doubt that there is a significant link between the oral environment and the development of pneumonia; however, there have been few comparative studies of swallowing using video endoscopy (VE) and video fluorography (VF) as indicators to determine the actual availability of oral intake and the choice of food form. This study was performed to examine whether the oral environment or swallowing function contributes more to the development of pneumonia in the elderly. Methods: The study population consisted of 24 patients (7 men and 17 women; age range: 64-97 years; average age: 86 years) assessed using the Oral Health Assessment Tool (OHAT), VE and VF at Fukuoka Dental College Hospital. The most common disease was pneumonia (17 patients), followed by cerebral infarction (5 patients), pyelonephritis (4 patients), bronchitis (2 patients), Parkinson's disease (2 patients), scleroderma (1 patient), diabetes (1 patient), eosophageal cancer (1 patient) and Parkinson's syndrome> (1 patient). Some patients had multiple diseases. Oral intake was possible in 20 patients (80%), whereas tube feeding and gastric banding were required in 4 patients. Results: The OHAT score was not correlated with either the VE or VF score. Furthermore, the OHAT score was not significantly different between the multiple- and no/single-pneumonia episode groups. The group with multiple episodes of pneumonia had lower VE and VF scores than those with no or only a single episode of pneumonia. Conclusion: Oral assessment, VE and VF are necessary to evaluate swallowing in patients with suspected dysphagia. Swallowing function, especially as assessed by VE and VF, is more important than examination of the oral environment for evaluating risk of recurrent aspiration pneumonia in the elderly. In addition, multiple factors contribute to recurrent pneumonia in patients with a good oral environment, including subclinical aspiration, pharyngeal clearance and delayed activation of the gag reflex.

A Retrospective Study of Patients Undergoing Palliative Radiotherapy for Airway Obstruction due to Lung Cancer.

BACKGROUND/AIM: In advanced stage lung cancer, bulky tumors can cause serious symptoms such as malignant airway obstruction (MAO). Prompt response to airway obstruction might be essential to improve quality of life and prolong life expectancy. Palliative external beam radiotherapy (EBRT) is a less invasive and highly safe treatment method that can alleviate symptoms and at the same time treat lung cancer. However, there are few reports on the results of palliative radiotherapy performed for improving airway obstruction and obstructive pneumonia. Therefore, this study retrospectively examined the effectiveness of palliative radiotherapy. PATIENTS AND METHODS: We reviewed 38 lung cancer patients with MAO who underwent EBRT. Patients were treated with a median dose of 37.5 Gy (range=30-40 Gy) in 10-20 fractions. Whether a patient was a responder or non-responder was assessed by whether the bronchus that was obstructed before EBRT reopened or improvement of obstructive pneumonia was observed on follow-up chest X-ray or computed tomography after EBRT. RESULTS: The median survival time was 135 days (range=31-469 days) for the responders to EBRT and 45 days (range=23-355 days) for non-responders; this difference was statistically significant (p=0.03). One-year overall survival rate was 18.5% and 0% for the responders to EBRT and non-responders, respectively. CONCLUSION: Palliative EBRT might be an important option for non-curative lung cancer patients with MAO.

Ototoxicity of Burow solution on the guinea pig cochlea.

PURPOSE OF THE STUDY: The aim of the present study was to evaluate the ototoxicity of Burow solution. PROCEDURES: Compound action potentials (CAPs) of the eighth nerve were measured before and 30 minutes after the application of the Burow solution in the middle ear cavity. RESULTS: Use of the original Burow solution (pH 3.5) for 30 minutes caused a significant reduction of click sounds. A 2-fold diluted Burow solution (pH 4.4) for 30 minutes caused no reduction in CAP threshold. Burow solution, pH adjusted to 4.5, caused no changes in CAP threshold at 30 minutes. At 24 hours, Burow solution (pH 3.5) caused complete abolition of CAP. CONCLUSIONS: Burow solution is ototoxic in the guinea pig when applied in the middle ear cavity for 30 minutes or longer. In the clinical settings, it is advisable to avoid allowing the solution to contact the round window for extended times.

Dramatic Response to Alectinib in a Critically Ill Elderly Patient with Lung Adenocarcinoma Due to Trousseau Syndrome and Disseminated Intravascular Coagulation.

Lung cancer complicated with Trousseau syndrome (TS) or disseminated intravascular coagulation (DIC) has a severe prognosis. We herein report an elderly lung cancer patient who presented with a critically ill condition due to concomitant TS and DIC and responded dramatically to alectinib. There are no rules regarding treatment indications based on the age or severity of critically ill patients. If the patient's cancer cells are positive for anaplastic lymphoma kinase rearrangement, alectinib is worthwhile to administer, even in a critically ill condition. In our patient, anticoagulation failed to suppress the TS complications. We also report how to prevent the recurrence of TS.

Epipharyngeal Abrasive Therapy Down-regulates the Expression of SARS-CoV-2 Entry Factors ACE2 and TMPRSS2.

BACKGROUND: The epipharynx, with its high expression of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), is a primary target for SARS-CoV-2 replication in the early stage of Coronavirus Disease 19 (COVID-19). Epipharyngeal abrasive therapy (EAT) is a treatment for epipharyngitis in Japan which involves applying zinc chloride to the epipharyngeal mucosa. In this study, we evaluated the expression patterns of ACE2 and TMPRSS2 in tissue samples from patients before and after EAT. PATIENTS AND METHODS: The study subjects were seven patients that had not been treated with EAT and 11 patients that had. For immunohistochemical assessment of the epipharyngeal mucosa, the staining intensity of ACE2 and TMPRSS2 was described as an immunohistochemical score (IHC score). RESULTS: The IHC scores for ACE2 and TEMPRSS2 in the EAT-treated group were 3.40-fold and 1.81-fold lower, respectively, than those in the non-treated group (p=0.0208 and p=0.0244, respectively). CONCLUSION: EAT down-regulates the expression of SARS-CoV-2 entry factors ACE2 and TMPRSS2. Thus, EAT has potential as a novel COVID-19 preventative method.