Abstract Morphological abnormalities have been reported in insects following the Fukushima Daiichi Nuclear Power Plant (FNPP) accident. Similar abnormalities were also observed during a feeding experiment using contaminated host plants near the FNPP. However, it is unclear whether these morphological abnormalities were directly caused by radiation, as the relationship between the absorbed doses by insects and radiation effects is ambiguous. Therefore, this study aimed to clarify the direct effects of ionizing radiation on lepidopterans by conducting two independent experiments using silkworms: (1) internal exposure using an artificial diet supplemented with cesium-137 ( 137 Cs), and (2) external exposure using γ-ray irradiation. Abnormalities were evaluated by pupal wing-to-whole-body length ratio and somatic mutations via white spots on the larval integument. The results of the internal exposure showed no significant differences in the ratios between the exposed and control groups. A significant difference in the ratio appeared with 80 Gy irradiation in fifth-instar larvae. Additionally, the development of somatic mutations required at least 1 Gy irradiation of eggs. Therefore, it is strongly suggested that low-dose and low-dose-rate exposure to 137 Cs radiation is unlikely to cause direct radiation effects in lepidopterans, such as morphological abnormalities and somatic mutations.

Background/Purpose Definitive chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) has limitations in advanced disease. Paclitaxel, carboplatin, and cetuximab (PCE) offers a potentially safer induction chemotherapy alternative. This study evaluated the feasibility and outcomes of PCE induction followed by CRT compared with CRT alone among patients with Stage IV HNSCC who received definitive CRT. Materials and Methods This retrospective study included 128 patients with Stage IV HNSCC without distant metastases treated at a single institution (PCE group, n=52; CRT group, n=76). Survival analyses were restricted to the 127 patients who initiated definitive CRT, with time measured from CRT initiation to reduce immortal time bias; CRT completion was analyzed as an outcome, not an eligibility criterion. An adjusted Cox model accounted for baseline imbalances in T classification and Stage. Results Median follow-up was 17.0 months (PCE) and 65.0 months (CRT). The PCE group had more advanced disease (T3-4: 90.4% vs. 65.8%; Stage IVB: 34.6% vs. 15.8%). PCE achieved an 82.7% response rate, CRT completion in 51 of 52 patients (98.1%), and significantly higher cisplatin ≥200 mg/m² achievement (86.5% vs. 59.2%, p=0.002). PFS was longer with PCE in both unadjusted (HR: 0.515, 95% CI:0.271–0.980, p=0.043) and adjusted analysis (adjusted HR: 0.477, 95% CI:0.247–0.924, p=0.028). OS did not differ significantly (adjusted HR: 0.553, p=0.147), and its interpretation is limited by the shorter follow-up in the PCE group. Exploratory inflammatory and nutritional markers showed no reliable prognostic association. Conclusions PCE induction was feasible, with a high rate of CRT completion and acceptable tolerability. PFS was longer in the PCE group after limited adjustment, whereas OS did not differ significantly. Given the retrospective, nonrandomized design, residual confounding, and shorter follow-up in the PCE group, these findings are hypothesis-generating and require confirmation in larger, prospective studies.

BACKGROUND:This study assessed the efficacy of upfront neck dissection (ND) versus concurrent chemoradiotherapy (CRT) in patients diagnosed with T1-3N3b hypopharyngeal carcinoma (HPC). METHODS:This retrospective study enrolled patients with T1-3N3b HPC who had undergone upfront ND followed by CRT (upfront group) or CRT (CRT group). Local control rate, neck control rate (NCR), metastasis-free rate, disease-free survival (DFS), disease-specific survival, and overall survival (OS) were compared between the upfront and CRT groups. Univariate and multivariate analyses using Cox proportional hazards models were performed to identify the survival-related clinical factors. Lymph node status and salvage surgery were also analyzed. RESULTS:Forty-eight patients were enrolled in this study, with 18 in the upfront group and 30 in the CRT group. The groups differed significantly in terms of NCR (p = 0.000121) and DFS (p = 0.0256). The lymph node status was found to be a significant prognostic factor for OS in univariate and multivariate analyses. When comparing the upfront, CRT-R (resectable lymph nodes), and CRT-UR (unresectable lymph nodes) groups, significant differences were observed in NCR (p = 0.0005), DFS (p = 0.0123), DSS (p = 0.0312), and OS (p = 0.0159). The upfront group had better outcomes compared to both CRT-R and CRT-UR. In the analysis considering salvage surgery, a significant difference was found in the NCR between the upfront and CRT ± salvage ND groups (p = 0.003). CONCLUSION:Upfront ND followed by CRT may improve NCR and DFS in patients with stage T1-3N3b HPC compared to CRT. Upfront ND should be considered as a treatment option, provided resectability is feasible.

INTRODUCTION:We evaluated concordance between Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)-based categorization of salivary gland masses/lesions screened by fine-needle aspiration cytology (FNAC) and final histopathologic diagnoses, aiming to identify factors predictive of concordance, with the goal of appropriate case management. METHODS:The study was retrospective and involved 101 cases of salivary mass/lesion examined by FNAC. We compared MSRSGC categories against the final histopathologic classes (non-neoplasm, benign neoplasm, or malignant neoplasm) and calculated diagnostic concordance in each class. Concordance was defined as: MSRSGC categorization of a lesion as a category II lesion and a histopathologic classification as a non-neoplasm; MSRSGC categorization of a lesion as a category IV-A lesion and a histopathologic classification as a benign neoplasm; or MSRSGC categorization of a lesion as a category V or VI lesion and a histopathologic classification as a malignant neoplasm. We then compared clinicopathologic factors between concordant and discordant cases. RESULTS:Diagnostic concordance for non-neoplasms, benign neoplasms, malignant neoplasms, and total cases was 81.8% (9/11), 81.7% (58/71), 66.6% (8/12), and 79.8% (75/94), respectively, with no significant between-class difference. We found the shortest distance from the body surface to the salivary lesion differed significantly between the concordant group and the discordant group (5.35 mm vs. 7.30 mm), and the optimal cutoff was determined to be 8.00 mm (p < 0.01). CONCLUSION:Based on the distance of either <8 mm or ≥8 mm from the body surface to the mass/lesion, we believe our proposed FNAC algorithm of treatment strategies is a reliable guide for otolaryngologists on evaluating salivary gland lesions.

BACKGROUND:Transoral videolaryngoscopic surgery (TOVS) is widely used in Japan, and conventional two-dimensional (2D) endoscopic methods have been established. Three-dimensional (3D) endoscopic surgery offers superior distance perception because it provides stereoscopic views. Recently, we have developed 3D endoscopy for TOVS (3D TOVS). METHODS:This study included 46 patients with pharyngeal cancer who underwent 3D TOVS. The perioperative complications and survival curves were retrospectively analyzed. RESULTS:One patient with oropharyngeal cancer who underwent neck dissection and transoral resection simultaneously experienced postoperative hemorrhage of the neck. Another patient with oropharyngeal cancer underwent hemostasis for postoperative pharyngeal hemorrhage. There was one case of aspiration pneumonia. One patient developed cervical lymph node recurrence; however, there was no local recurrence or primary mortality. The 2-year overall survival, disease-specific survival, local control rates, locoregional control rate, and invasive disease-free survival were 90.9%, 100%, 100%, 97.4%, and 79.9%, respectively. CONCLUSIONS:Three-dimensional endoscopy can be safely applied to TOVS.

BACKGROUND:The abscopal effect is a rare phenomenon in which localized radiation therapy triggers tumor reduction in nontargeted areas. Although this phenomenon has been observed in various cancer types, it remains infrequent and not fully understood.CASE:Two patients with maxillary sinus cancer with distant metastases were treated with radiotherapy after immune checkpoint inhibitor (ICI) therapy. The patients demonstrated abscopal effects following ICI therapy and radiotherapy, showing shrinkage in metastatic areas not directly targeted by radiation.CONCLUSION:This report was reviewed to examine the synergistic effects of ICI and radiotherapy and to identify optimal strategies to enhance the abscopal effect in clinical practice. It has also touched on various ongoing debates and clinical trials aimed at understanding and exploiting this effect to improve cancer treatment. The exact mechanisms and optimal treatment protocols remain areas for future research.

OBJECTIVES:In recent years, there has been a notable increase in syphilis cases in Japan and Western countries. Syphilis, a classic sexually transmitted disease caused by treponemas, presents diagnostic challenges due to its diverse clinical manifestations. This study explores the diagnosis of syphilis in patients treated at our hospital. METHODS:We retrospectively reviewed patients who visited our hospital between April 2015 and March 2024. The review focused on the patients' clinical backgrounds, onset times, symptoms, diagnostic processes, and clinical courses. RESULTS:Our hospital had 45 cases of syphilis. Forty-five cases of syphilis were diagnosed as syphilis in our hospital (13 cases were diagnosed in the Otolaryngology: ENT department). The median age was 40 years, with a significant male predominance (male-to-female ratio of 34:11). The median duration from the onset of subjective symptoms to syphilis diagnosis was 54 days. The timeframe from the initial clinic visit to diagnosis ranged from 1 to 57 days, with a median of nine days. Notably, 47.5% of the patients reported a history of employment or patronage in the sex industry. 73.3% of patients presented to local clinics with any kind of subjective symptoms, but syphilis was often missed in the differential diagnosis. Patients visiting the ENT department were referred to our hospital with a diagnosis of persistent oral ulcer, oropharyngeal carcinoma and neck lymphadenopathy. Histological and cytological evaluation was performed in 33% of patients, but the diagnosis was often difficult to make. Additionally, some patients initially denied using sex services at their first visit but later disclosed this during subsequent visits to the Department of Infectious Diseases, highlighting the critical role of thorough medical history assessments. CONCLUSION:Diagnosing syphilis can be challenging unless the physician specifically suspects it. It is crucial to consider syphilis in cases of pharyngeal mucosal inflammation and neck lymphadenopathy. This study highlights the need for heightened awareness and education regarding the signs and symptoms of syphilis, particularly oropharyngeal and skin findings, to ensure timely diagnosis and treatment.

The prognosis of differentiated thyroid cancers is good, however, there are no established treatment options for patients with radioactive iodine-refractory and unresectable differentiated thyroid cancers. Lenvatinib was approved by the Japan Pharmaceuticals and Medical Devices Agency for the treatment of differentiated thyroid cancers in 2015. However, drug withdrawal or dose reduction is often necessary due to the emergence of adverse effects of these drugs. During the drug discontinuation period, disease progression was frequently observed, and the timing of TKI administration and the management of the adverse events have been discussed.

Background: It is controversial whether transoral resection for early pharyngolaryngeal cancer preserves swallowing function and quality of life. We investigated swallowing function and quality of life before and after transoral videolaryngoscopic surgery (TOVS). Methods: Seventy-three patients with pharyngolaryngeal cancer who underwent TOVS between July 2012 and July 2022 were enrolled in this prospective analysis. The Hyodo score and European Organization for Research and Treatment of Cancer Quality of Life Questionnaires were recorded preoperatively and at three, six, and 12 months postoperatively, in addition to the postoperative functional outcome swallowing scale (FOSS) at six months postoperatively. Results: Although most patients could consume food orally without restrictions with a preferable FOSS score, 23 patients showed impaired Hyodo scores. Age >= 65 years significantly predicted impaired swallowing. Sub -scores of the impaired patient group showed worsening for the glottal closure reflex when the endoscope touched the epiglottis or arytenoid, as well as a reduction in the extent of pharyngeal clearance following the ingestion of blue -dyed water. Conclusion: After TOVS, swallowing function is generally well preserved. Elderly patients, especially those with laryngeal hypoesthesia and poor clearance, are at risk of swallowing dysfunction.

Background: Recurrent or metastatic squamous cell carcinoma of the head and neck (R/MHNSCC) is a challenging malignancy with a poor prognosis and limited treatment options. Nivolumab, an immune checkpoint inhibitor (ICI) targeting the programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) pathway, has emerged as a promising therapy for these patients. However, identifying biomarkers predictive of response to nivolumab remains critical for optimizing treatment strategies. Previous studies have suggested that PD-L1 expression, as determined by the Combined Positive Score (CPS) and other clinical factors, may influence treatment outcome. This study aims to retrospectively examine whether CPS can be a biomarker by staining PD-L1 with 22 C3 antibody in R/MHNSCC patients treated with nivolumab. Methods: This retrospective study reviewed the medical records of R/MHNSCC patients treated with ICIs at Tokai University Hospital from April 2017 to December 2022. We examined the relationship between response rate to ICI therapy, PD-L1 staining, biomarkers, and survival. Statistical analyses included t-test, chi-square test, and Cox regression. Results: This study included 92 nivolumab-treated patients. Combined Positive Score was evaluable in 53 of these patients. Patients with a CPS of 15 or higher had better progression-free survival (PFS) ( P = .0171), with a median PFS) of 13 months. In the Various Definitions analysis, cisplatin-sensitive patients also had good PFS ( P = .0295). The cisplatin-sensitive patient population with a CPS of 15 or higher had the best PFS, with a median of 14 months ( P = .006). There was no significant difference in overall survival (OS) by CPS value. Immune-related adverse events did not affect OS or PFS. Conclusions: CPS ⩾ 15 and cisplatin sensitivity are promising prognostic markers for nivolumab therapy in R/MHNSCC. Considering these biomarkers in patient selection could maximize the therapeutic benefits of nivolumab. This finding may help to optimize ICI therapy strategies.

This case report describes rare concomitant allergic fungal rhinosinusitis (AFRS) and chronic granulomatous invasive fungal sinusitis (CGIFS) in a 34-year-old woman with acute lymphoblastic leukemia and graft-versus-host disease (GVHD) post bone marrow transplantation. Initially presenting with rhinorrhea and nasal obstruction, the patient was diagnosed with AFRS in the right maxillary sinus, followed by a postoperative course of CGIFS in the left nasal cavity, showcasing the unique occurrence. She was not immunocompromised during diagnosis. CGIFS may have occurred because of surgery; however, voriconazole led to significant improvement. This case highlights noninvasive and invasive fungal infections in patients with chronic rhinosinusitis and a history of GVHD and underscores the complexity of diagnosing and managing such cases.

This study aimed to evaluate the clinical effectiveness of chemotherapy following immune checkpoint inhibitors (ICI). The association between inflammatory and nutritional factors and prognosis has also been investigated. We retrospectively reviewed the medical records of recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) patients who received chemotherapy following ICI therapy. The response rate and survival after chemotherapy, and nutritional and inflammatory factors, were examined. The ICI before chemotherapy was nivolumab in 36 patients (70.6

Magnetic resonance imaging (MRI) is a more useful diagnostic modality for detecting paranasal tumors compared with computed tomography (CT). We encountered a case of malignant lymphoma of the maxillary sinus. Although CT findings suggested malignancy, MRI findings indicated an inflammatory disease. The patient was a 51-year-old man with a chief complaint of right maxillary toothache. Edema in the right middle meatus and bloody rhinorrhea were observed. CT revealed r ight maxillary s inus shadow with partial bone loss, suggesting malignancy. However, MRI performed two weeks later showed an internal homogeneous lesion with neither contrast effect, nor invasion outside the maxillary sinus. The patient also had no fever, weight loss, or night sweats. Additionally, no palpable cervical lymphadenopathy was observed. Endoscopic sinus surgery was performed to confirm the diagnosis. Upon opening the maxillary sinus, highly viscous retention and a large amount of yellowish-white debris were observed. Allergic fungal rhinosinusitis was suspected. However, histopathological analysis of the debris established a diagnosis of malignant lymphoma. The debris exhibited pathological findings of necrosis. The patient remained in remission after undergoing radiochemotherapy. Malignant lymphomas of the paranasal sinuses, which have a minimal tendency for invasion but with considerable predominance of necrosis, may be diagnosed as an inflammatory disease, based on MRI findings. In cases in which a thorough physical examination could not rule out malignant lymphomas, an endoscopic biopsy should be immediately considered.

Patients with aortic arch malformations may present with recurrent inferior laryngeal nerve abnormalities that require special attention. Herein, we reported a case of thyroid surgery in a patient with a right aortic arch. The left inferior laryngeal nerve was presumed to be the right inferior laryngeal nerve by confirming the location of the aortic arch and subclavian artery, and the presence of the ductus arteriosus on preoperative computed tomography. Continuous intraoperative nerve monitoring is useful for safe surgery in patients with possible inferior laryngeal nerve abnormalities. Laryngoscope, 2023

This study aimed to determine the prognostic value of inflammatory and nutritional biomarkers of immune checkpoint inhibitor (ICI) therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMHNSCC) and to identify the most useful factor for prognosis assessment. We retrospectively reviewed the medical records of patients with RMHNSCC who received ICI therapy. The response rate for ICI therapy and the relationship between inflammatory and nutritional biomarkers and overall survival were examined. The included biomarkers did not correlate with an objective response rate but were associated with a disease control rate. Univariate analysis showed significant correlations between the serum albumin level, C-reactive protein level, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio (LMR), systemic immune-inflammation index, and controlling the nutritional status score and overall survival; multivariate analysis showed that LMR was significantly correlated with overall survival. LMR was the most important biomarker according to the machine learning model. This study suggests that LMR may be the most useful biomarker for predicting the prognosis of ICI treatment for RMHNSCC.

July 7, 2023. Research Square has removed this preprint due to lack of Institutional Review Board approval for this work at the time of preprint posting.

Abstract Purpose This study assessed the efficacy of upfront neck dissection (ND) versus concurrent chemoradiotherapy (CRT) in patients diagnosed with T1–3N3 hypopharyngeal carcinoma (HPC).Methods This retrospective study enrolled patients with T1–3N3 HPC who had undergone upfront ND followed by CRT (upfront group) or only CRT (CRT group). Local control rate, neck control rate, metastasis-free rate, disease-free survival, disease-specific survival, and overall survival were compared between the upfront and CRT groups. Univariate and multivariate analyses using Cox proportional hazards models were performed to identify the survival-related clinical and systemic factors.Results Forty-eight patients were enrolled in this study, with 18 in upfront group and 30 in CRT group. The groups differed significantly in terms of neck control rate (p = 0.000121) and disease-free survival (p = 0.0256). The upfront CRT group showed a significantly better overall survival (OS) than that of the unresectable CRT group (p = 0.046). Among the various factors, node status, body mass index, and platelet-to-lymphocyte ratio were significantly associated with OS in a univariate analysis.Conclusion Upfront ND can be recommended for T1–3N3 HPC, provided resectability is feasible.

Transoral salvage surgery has the potential to preserve a patient's quality of life. Therefore, we investigated the outcomes, safety, and risk factors for postoperative complications of salvage transoral videolaryngoscopic surgery (TOVS) for recurrent hypopharyngeal carcinoma after radiotherapy (RT) or chemoradiotherapy (CRT).This retrospective analysis enrolled patients with hypopharyngeal cancer who had a history of RT or CRT and underwent TOVS from January 2008 to June 2021. The factors related to postoperative complications, postoperative swallowing functions and survival rates were analyzed.Seven patients (36.8%) of the 19 patients developed complications. Severe dysphagia was the primary complication, and post-cricoid resection was a complication risk factor. The FOSS score was significantly lower in the salvage treatment group. The survival rates were: 3-year overall survival: 94.4%; disease-specific survival: 94.4%; 5-year overall survival: 62.3%; and disease-specific survival: 86.6%.Salvage TOVS for hypopharyngeal cancer was feasible, and oncologically and functionally reasonable. Level of Evidence: 2b.