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Introduction There are no clear guidelines for deciding between endoscopic sinus surgery and tooth extraction for the treatment of odontogenic sinusitis. Furthermore, tooth extraction does not necessarily improve sinusitis and eventually results in additional endoscopic sinus surgery.

BackgroundNivolumab paved a new way in the treatment of patients with recurrent or metastatic (RM) head and neck squamous cell carcinoma (RM-HNSCC). However, the limited rates of long-term survivors (< 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and provides a biological clue to develop effective therapies for a majority of non-survivors.MethodsPre-treatment plasmas (N = 104) of RM-HNSCC patients were subjected to comprehensive PEX mRNA analyses for prognostic marker discovery and validation. In parallel, paired treatment-naïve tumor and plasma samples (N = 20) were assayed to elucidate biological implications of the PEX mRNA signature.ResultsAssays for pre-treatment blood samples (N = 104) demonstrated that a combination of 6 candidate PEX mRNAs plus neutrophil-to-lymphocyte ratio precisely distinguished non-survivors from >2-year survivors (2-year OS; 0% vs 57.7%; P = 0.000124) with a high hazard ratio of 2.878 (95% CI 1.639-5.055; P = 0.0002348). Parallel biological assays demonstrated that in the paired treatment-naïve HNSCC tumor and plasma samples (N = 20), PEX HLA-E mRNA (a non-survivor-predicting marker) was positively corelated with overexpression of HLA-E protein (P = 0.0191) and the dense population of tumor-infiltrating NK cells (P = 0.024) in the corresponding tumor, suggesting that the HLA-E-NKG2A immune checkpoint may inhibit the antitumor effect of PD-1blockade.ConclusionThe PEX mRNA signature could be useful as a companion diagnostic of nivolumab. The combination of an anti-NKG2A antibody (i.e., monalizumab) and nivolumab may serve as a treatment option for non-survivors predicted by a RT-qPCR-based pre-treatment measurement of PEX mRNAs.

Introduction: Immune-related adverse events (irAEs) from nivolumab can affect any organ, but renal impairment is less common than effects on other organs. We encountered a case in which a renal irAE was difficult to diagnose due to mild renal dysfunction. Case Presentation: We report the case of a 65-year-old man with hypopharyngeal carcinoma treated with radiotherapy and cisplatin. Histopathological examination after reconstructive surgery showed extranodal invasion. Two months after completing treatment, computed tomography showed multiple lung metastases. We determined that the tumors were platinum-resistant and initiated treatment with nivolumab. Pyuria, worsening renal function, and elevation of C-reactive protein (CRP) to 16 mg/dL were observed 203 days after the first dose and nivolumab was discontinued. We considered the possibility of renal irAE but did not perform renal biopsy because creatinine was not highly elevated. We administered antibiotics for urinary tract infection, but CRP rose to 20 mg/dL and his general condition gradually worsened. Arthralgia in both knees and elbows appeared around the same time and gallium scintigraphy showed polyarticular accumulations. After diagnosing irAE arthritis, 20 mg of prednisolone was administered. Arthralgia and inflammatory responses improved, along with urinary findings and tubular markers. Retrospectively, pyuria, mild renal dysfunction, and elevated CRP were considered to reflect renal irAE. Conclusion: In some cases of mild renal dysfunction, as in the present case, biopsy may not be performed and the diagnosis may be missed. Renal irAEs should be kept in mind when abnormal urinalysis results and renal dysfunction are observed.

BackgroundIn 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. MethodsThe study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing.ResultsOf 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. ConclusionNivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.

Introduction: Head and neck photoimmunotherapy (HN-PIT) uses a combination of drugs and laser illumination to specifically destroy tumor cells. Lemierre’s syndrome is an infectious disease with severe systemic symptoms caused by prior infection in the pharyngeal region, leading to thrombophlebitis. Here, we report a case of Lemierre’s syndrome that developed after HN-PIT for recurrent nasopharyngeal carcinoma. Case Presentation: A 68-year-old male with nasopharyngeal carcinoma (squamous cell carcinoma) underwent HN-PIT after local recurrence with chemoradiation therapy. Three months after HN-PIT, the patient developed fever and neck pain, which led to a diagnosis of Lemierre’s syndrome. The patient was treated with antibiotics and anticoagulants for at least 1 month. The patient’s general condition and inflammatory findings on blood sampling showed gradual improvement, and a follow-up cervicothoracic computed tomography imaging showed that the venous thrombus had been obscured and the patient was doing well. Conclusion: HN-PIT is a high-risk procedure for the development of Lemierre’s syndrome due to irradiation-induced mucositis, and anticipating the development of Lemierre’s syndrome during HN-PIT is important.

Introduction: Head and neck photoimmunotherapy (HN-PIT) has been conditionally approved by the Japanese government for the treatment of unresectable locally advanced or locally recurrent head and neck cancer since January 2021. HN-PIT makes local treatment of locally recurrent disease possible in cases where systemic drug therapy would have previously been the only option. However, when treatment is ineffective and the disease progresses, it is necessary to shift to conventional drug therapies. We report a case in which an immune checkpoint inhibitor (ICI) was successfully administered to a patient with advanced disease following HN-PIT. Case Presentation: A 75-year-old male patient presented with local recurrence of mandibular gingival cancer. The primary treatment consisted of mandibular segmentectomy and reconstruction with a scapulohumeral and vastus lateralis skin valve. Post-operative radiotherapy was administered. Local recurrence was found in the mid-pharynx adjacent to the reconstruction. HN-PIT was performed for the local recurrence. After three cycles of HN-PIT, the local lesion increased, and the disease was evaluated as advanced. Therefore, the patient was switched to pembrolizumab, an ICI. Conclusion: The recurrent lesions disappeared 2 months after the first dose of pembrolizumab, and the patient remained in clinical remission at 1 year. To the best of our knowledge, there are no other reports of successful ICI therapy after HN-PIT.

Transoral robotic surgery (TORS) and transoral videolaryngoscopic surgery (TOVS) are minimally invasive procedures for early-stage head and neck cancers. However, due to its unique nature, transoral resection often leads to skeletal and anatomical disorders. We describe a case in which TORS was used in a 71-year-old man with a skeletal disorder, spastic stridor, and a T2N1M0 stage I p16-positive oropharyngeal carcinoma. Prior to the procedure, he underwent right cervical dissection (levels II–IV). Although he had an oblique neck, the right side of his neck was naturally hyperextended because the dissection was performed on the right side. The right facial, lingual, and external carotid arteries were ligated in preparation for TORS. Postoperative pathological examination revealed no extranodal involvement of the metastatic lymph nodes. A two-stage TOVS procedure was performed for the oropharyngeal tumor, in which the surgeon was required to be positioned at the patient’s head to allow direct manipulation. This makes the neck and oral cavity more susceptible to the skeletal effects. In contrast, in TORS, the da Vinci insertion angle can be set to match the angle of the neck, allowing surgeons to operate with less skeletal influence. TORS is more useful in this setting.

Malignant otitis externa (skull base osteomyelitis) can be fatal and long-term antibiotic therapy is recommended. Despite being potentially fatal, this infection causes minor changes in inflammatory biomarkers (white blood cell count and C-reactive protein levels) upon blood testing. Computed tomography and magnetic resonance imaging changes persist over a long period. Therefore, it is difficult to determine the optimal time for the discontinuation of antibiotics. We present a 77-year-old male whose medical history included type 2 diabetes mellitus who suffered from chronic otitis media with Pseudomonas aeruginosa infection. His condition did not improve with proper treatment, and imaging revealed malignant otitis media. Intravenous cefepime treatment was administered. Antibiotic treatment was de-escalated to oral levofloxacin treatment after Gallium-67 scintigraphy showed less accumulation after 6 weeks of Cefepime administration; accumulation almost disappeared after 1 year. In this report, we describe the usefulness of gallium scintigraphy in the evaluation of malignant otitis externa.

Abstract Background Salivary duct carcinoma (SDC) is a high‐grade adenocarcinoma with a 5‐year survival rate of 40%. Although drug therapy has improved patients' prognosis, the impact of brain metastasis (BM) remains poorly understood. We aimed to retrospectively examine the incidence of BM in patients with SDC (n = 464) and develop a tool to estimate their prognoses. Methods We retrospectively examined 464 patients with SDC enrolled in a multicenter study. We investigated the incidence of BM, overall survival (OS) rates, and factors affecting prognosis in patients with BM. We also developed an SDC‐graded prognostic assessment (GPA) score for disease prognostication. Results Sixty‐five (14%) patients had BM. The median OS (mOS) was 13.1 months. On univariate and multivariate analyses, factors such as Eastern Cooperative Oncology Group Performance Status >1, human epidermal growth factor receptor 2‐negative status, and locoregional uncontrolled disease were associated with poor OS. SDC‐GPA scores according to the prognostic factors were 0, 1, 2, and 3 points, and mOS estimates were 50.5, 16.1, 3.9, and 1.2 months, respectively (p

Abstract This sentinel node (SN) biopsy trial aimed to assess its effectiveness in identifying predictive factors of micrometastases and to determine whether elective neck dissection is necessary in oral squamous cell carcinoma. This retrospective study included 55 patients from three previous trials, with positive SNs. The relationship between the sizes of the metastatic focus and metastasis in non-sentinel node (NSN) was investigated. Four of the 55 largest metastatic focus were isolated tumor cells, and the remaining 51 were ranged from 0.2 to 15 mm, with a median of 2.6 mm. The difference of prevalence between 46 negative- and 9 positive-NSN was statistically significant with regard to age, long diameter of primary site and number of cases with regional recurrence. In comparing the size of largest metastatic focus dividing the number of positive SN, with metastaic focus range of

Abstract Lysosomes are single-membraned organelles that mediate the intracellular degradation of macromolecules. Various stress can induce lysosomal membrane permeabilization (LMP), translocating intralysosomal components, such as cathepsins, to the cytoplasm, which induces lysosomal-dependent cell death (LDCD). This study reports that p53 regulates LMP in response to DNA-damaging drugs. Treating wild-type TP53 A549 cells with DNA-damaging drugs (namely, doxorubicin, carboplatin, and etoposide) induced LMP and accelerated cell death more rapidly than treating TP53-knockout (KO) A549 cells. This suggested p53-dependent LMP and LDCD induction in response to DNA damage. LMP was induced by p53-dependent BID upregulation and activation, followed by translocation of truncated BID to lysosomes. Simultaneously, autophagy for damaged lysosome elimination (lysophagy) was activated via the p53–mTOR–TEFB/TFE3 pathways in response to DNA damage. These data suggested the dichotomous nature of p53 for LMP regulation; LMP induction and repression via the p53–BID axis and p53–mTOR–TFEB/TFE3 pathway, respectively. Blocking autophagy with hydroxychloroquine or azithromycin as well as ATG5 KO enhanced LMP and LDCD induction after exposure to DNA-damaging drugs. Furthermore, lysosomal membrane stabilization using U18666A, a cholesterol transporter Niemann-Pick disease C1 (NPC1) inhibitor, suppressed LMP as well as LDCD in wild-type TP53, but not in TP53-KO, A549 cells. Thus, LMP is finely regulated by TP53 after exposure to DNA-damaging drugs.

Abstract Molecular targets and predictive biomarkers for prognosis in salivary duct carcinoma (SDC) have not been fully identified. We conducted comprehensive molecular profiling to discover novel biomarkers for SDC. A total of 67 SDC samples were examined with DNA sequencing of 464 genes and transcriptome analysis in combination with the clinicopathological characteristics of the individuals. Prognostic biomarkers associated with response to combined androgen blockade (CAB) treatment were explored using mRNA expression data from 27 cases. Oncogenic mutations in receptor tyrosine kinase (RTK) genes or genes in the MAPK pathway were identified in 55 cases (82.1%). Alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway were identified in 38 cases (56.7%). Interestingly, patient prognosis could be predicted using mRNA expression profiles, but not genetic mutation profiles. The risk score generated from the expression data of a four-gene set that includes the ADAMTS1, DSC1, RNF39, and IGLL5 genes was a significant prognostic marker for overall survival in the cohort (HR = 5.99, 95% confidence interval (CI) = 2.73–13.1, p = 7.8 × 10−6). Another risk score constructed from the expression of CD3E and LDB3 was a strong prognostic marker for progression-free survival for CAB treatment (p = 0.03). Mutations in RTK genes, MAPK pathway genes, and PI3K/AKT pathway genes likely represent key mutations in SDC tumorigenesis. The gene expression profiles identified in this study may be useful for stratifying patients who are good candidates for CAB treatment and may benefit from additional systemic therapies.

Abstract Backgrounds The pharynx has no muscularis mucosae, so it is unclear whether diagnostic techniques used for the esophagus can be applied to the pharynx. This study investigated the usefulness of magnifying endoscopy with narrowband imaging using the Japan Esophageal Society (JES) classification for predicting the depth of invasion and lymph node metastasis (LNM) in pharyngeal cancer. Methods A total of 123 superficial pharyngeal carcinoma lesions that had been observed preoperatively with magnifying endoscopy with narrowband imaging between January 2014 and June 2021 were analyzed. Predictors of subepithelial invasion (SEP) and LNM were sought based on endoscopic findings, including microvascular morphology, using the JES classification. Results The lesions were divided into carcinoma in situ (n = 41) and SEP (n = 82). Multivariate analysis identified B2–B3 vessels (odds ratio [OR] 6.54, 95% confidence interval [CI] 1.74–24.61, p = 0.005) and a middle/large avascular area (OR 4.15, 95% CI 1.18–14.62, p = 0.027) as independent predictors of SEP. Significant predictors of LNM were protruding type, B2–B3 vessels, middle/large avascular area, SEP, venous invasion, lymphatic invasion, and tumor thickness > 1000 μm. Median tumor thickness increased significantly in the order of B1

Photoimmunotherapy (PIT) targets and destroys tumor cells through irradiation with 690-nm red light after the administration of cetuximab sarotalocan sodium, which contains IRDye700DX bound to cetuximab. In Japan, PIT is a new treatment that is covered by insurance only for unresectable head and neck cancers. However, this treatment has conditional early approval. There have been no case reports describing the efficacy of this treatment in a real-world setting thus far. We report our experience with PIT for head and neck cancer. A 76-year-old man with laryngeal cancer underwent radiation therapy and surgery. Skin involvement in the right submandibular region was subsequently noted. We diagnosed local recurrence and performed PIT for this lesion. Partial response was achieved after the first PIT session, and progressive disease was diagnosed after the second session. Many aspects of PIT remain unclear and should, therefore, be clarified in further research. Despite this uncertainty, PIT may become an effective treatment strategy for head and neck cancer if the patient selection criteria are delineated.

Abstract Nivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.

Laryngeal cryptococcosis is a rare condition. While there is no reliable evidence regarding the treatment of laryngeal cryptococcosis, oral fluconazole was successful in most previous cases. We experienced a case where we could not continue fluconazole because of adverse drug effects. An 88-year-old female was referred to our department with a 5-month history of sore throat and cough. She had used oral steroids and a corticosteroid inhaler for poorly controlled asthma. Flexible laryngoscopy showed leukoplakia of the vocal cords and subglottic mucosa, and biopsy revealed cryptococcal infection. We started the treatment with fluconazole but changed to itraconazole because of adverse events. Since laryngoscopy performed 6 months later was unremarkable and drug interactions had occurred, we stopped the itraconazole use at 6 months. Our experience suggests that itraconazole is also useful for treating laryngeal cryptococcosis.

Sternotomy is indicated when a goiter cannot be resected via a cervical incision, such as in the case of a substernal goiter extending beyond the aortic arch. In this article, we report a case of a large substernal goiter that was successfully removed using the cervical approach only. This is a case of a 68-year-old woman, diagnosed with goiter 20 years ago, who complained of a neck mass enlargement with associated cough. Pathological examination revealed no malignancy. Computed tomography (CT) scan showed an 11-cm thyroid mass reaching the level of the aortic arch. Preoperatively, we evaluated the substernal extent of the goiter via CT in the extended neck position to decide whether sternotomy was necessary. With the patient’s neck extended, the goiter withdraws cranially above the aortic arch. The mass was then removed via the cervical approach without sternotomy. Preoperative CT in the extended neck position was thus deemed helpful in deciding whether or not sternotomy was required.

ObjectiveBasal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC.Materials and methodsThis study involved 47 patients with HNSmCC from 10 participating institutions. Eight patients were excluded for whom no pathological specimens were available (n = 2) and for discrepant central pathological judgements (n = 6). The remaining 39 patients were processed for data analysis.ResultsAs pretreatment examinations, computed tomography (CT) was performed for the brain (n = 8), neck (n = 39), and chest (n = 32), magnetic resonance imaging (MRI) for the brain (n = 4) and neck (n = 23), positron emission tomography-CT (PET-CT) in 23 patients, bone scintigraphy in 4, neck ultrasonography in 9, and tumor markers in 25. Primary sites were oral cavity (n = 1), nasal cavity/paranasal sinuses (n = 16), nasopharynx (n = 2), oropharynx (n = 4), hypopharynx (n = 2), larynx (n = 6), salivary gland (n = 3), thyroid (n = 2), and others (n = 3). Stages were II/III/IV-A/IV-B/IV-C/Not determined = 3/5/16/6/5/4; stage IV comprised 69%. No patient had brain metastases. First-line treatments were divided into 3 groups: the chemoradiotherapy (CRT) group (n = 27), non-CRT group (n = 8), and best supportive care group (n = 4). The CRT group included concurrent CRT (CCRT) (n = 17), chemotherapy (Chemo) followed by radiotherapy (RT) (n = 5), and surgery (Surg) followed by CCRT (n = 5). The non-CRT group included Surg followed by RT (n = 2), Surg followed by Chemo (n = 1), RT alone (n = 2), and Chemo alone (n = 3). The 1-year/2-year overall survival (OS) of all 39 patients was 65.3/53.3%. The 1-year OS of the CRT group (77.6%) was significantly better compared with the non-CRT group (31.3%). There were no significant differences in adverse events between the CCRT group (n = 22) and the Chemo without concurrent RT group (n = 9).ConclusionNeck and chest CT, neck MRI, and PET-CT would be necessary and sufficient examinations in the diagnostic set up for HNSmCC. CCRT may be recommended as the first-line treatment. The 1-year/2-year OS was 65.3%/53.3%. This study would provide basal data for a proposing the diagnostic and treatment algorithms for HNSmCC.

Background: The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown. Methods: Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC. Results: Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p

Abstract Background Carnitine is related to malaise, and cisplatin is associated with decreased carnitine. The purpose of this study was to elucidate the effects of one course of induction chemotherapy (IC) for head and neck cancer on blood carnitine levels, focusing on free carnitine (FC). Methods This single-center prospective study investigated 20 patients diagnosed with primary head and neck cancer who underwent IC with cisplatin, docetaxel, and 5-fluorouracil. FC, acylcarnitine (AC), and total carnitine (TC) levels were measured before starting therapy and on Days 7 and 21 after starting IC. In addition, malaise was evaluated before and after therapy using a visual analog scale (VAS). Results All subjects were men and the most common primary cancer site was the hypopharynx (9 patients). FC levels before starting therapy and on Days 7 and 21 were 47.7 ± 2.2 μM/mL, 56.7 ± 2.2 μM/mL, and 41.1 ± 1.9 μM/mL, respectively. Compared with the baseline before starting therapy, FC had significantly decreased on Day 21 (p = 0.007). AC levels before starting therapy and on Days 7 and 21 were 12.5 ± 1.2 μM/mL, 13.6 ± 1.4 μM/mL, and 10.7 ± 0.7 μM/mL, respectively. TC levels before starting therapy and on Days 7 and 21 were 60.2 ± 2.5 μM/mL, 70.2 ± 3.3 μM/mL, and 51.7 ± 2.3 μM/mL, respectively. No significant differences in AC, TC or VAS were seen before the start of therapy and on Day 21. Conclusions After IC, a latent decrease in FC occurred without any absolute deficiency or subjective malaise.

Abstract Background Cytomegalovirus (CMV) is an important pathogen among immunocompromised hosts. Typically, CMV in human immunodeficiency virus (HIV) infection causes diseases of the retina, digestive tract, lungs and liver, but there are few cases of CMV infection of the pharynx and larynx. Case presentation A 57-year-old man with HIV infection was admitted because of pharyngeal pain. Before and after admission, pharyngeal biopsies guided by laryngeal endoscopy were performed four times, but pathological examination showed nonspecific inflammation, and the cause of pharyngeal ulceration was unclear. Additionally, the ulceration deteriorated after initiation of retroviral therapy. Laryngomicrosurgery was conducted under general anesthesia to remove tissue, and pathological diagnosis confirmed CMV infection. Pathological features included enlargement of the cytoplasm and nucleus in infected cells, and intranuclear bodies called owl’s eye inclusions. Ganciclovir dramatically improved the symptoms and laryngoscopic findings. Conclusions This case was diagnosed as pharyngitis and pharyngeal ulceration caused by CMV infection, related to immune reconstitution inflammatory syndrome. In previous reports of CMV-induced pharyngeal or laryngeal ulceration in HIV infection, we found six cases similar to our present case. All cases were diagnosed by biopsy. The present case indicates the importance of biopsy for definitive diagnosis. CMV infection should be considered as a differential diagnosis of pharyngeal ulceration in patients with HIV infection.

Abstract Cochlear implants (CIs) are generally considered useful in the treatment of hereditary hearing loss with progressive deafness. Early CI can be beneficial for maintaining social activities in POU4F3 mutation patients.

Abstract Background There is increasing evidence that immunotherapy with nivolumab, an anti‐programmed death 1 monoclonal antibody, is effective in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the predictive role of hematological inflammatory markers such as neutrophil‐to‐lymphocyte ratio (NLR) and the modified Glasgow prognostic score (mGPS) in patients with R/M SCCHN treated with nivolumab remains unclear. Methods We conducted a multi‐institutional cohort study to evaluate the impact of pretreatment NLR and mGPS on overall survival (OS) and progression‐free survival (PFS) in patients with R/M SCCHN treated with nivolumab in Japan. From 2012 to 2013, 102 patients were eligible, of whom 88 were finally included in the analysis. mGPS was calculated as follows: mGPS of 0, C‐reactive protein (CRP) ≤1.0 mg/dL; 1, CRP > 1.0 mg/dL; and 2, CRP > 1.0 mg/dL and albumin

ObjectiveSalivary duct carcinoma (SDC) is a highly aggressive and uncommon tumor arising not only de novo but also in pleomorphic adenoma. Androgen receptor (AR)- and HER2-targeted therapy have recently been introduced for SDC as promising treatment options; however, no predictive biomarkers have yet been established. EZH2 and H3K27me3 are closely linked to the development and progression of various cancers, and EZH2 is also expected to be a desirable therapeutic target. We therefore explored the clinicopathological and prognostic implications of EZH2 and H3K27me3 in a large cohort of SDC patients, focusing on their impact on the therapeutic efficacy of AR- or HER2-targeted therapy.Materials and MethodsThe EZH2 and H3K27me3 immunohistochemical expression and EZH2 Y646 gain-of-function mutation status were examined in 226 SDCs, and the relationship with the clinicopathological factors as well as clinical outcomes were evaluated within the three groups depending on the treatment: AR-targeted (combined androgen blockade with leuprorelin acetate and bicalutamide; 89 cases), HER2-targeted (trastuzumab and docetaxel; 42 cases), and conventional therapy (112 cases).ResultsEZH2 and H3K27me3 were variably immunoreactive in most SDCs. A positive correlation was found between the expression of EZH2 and H3K27me3. The EZH2 expression in the SDC component was significantly higher than that in the pre-existing pleomorphic adenoma component. EZH2 Y646 was not identified in any cases. EZH2-high cases more frequently had an advanced clinical stage and aggressive histological features than EZH2-low cases. An EZH2-high status in patients treated with AR-targeted therapy was associated with a significantly shorter progression-free and overall survival as well as a lower objective response rate and clinical benefit rate. In addition, a H3K27me3-high status in patients treated with AR-targeted therapy was related to a shorter overall survival. Conversely, there was no association between the EZH2 and H3K27me3 expression and the clinical outcomes in the conventional or HER2-targeted therapy groups.ConclusionsA high expression of EZH2 and H3K27me3 in SDC might be a predictor of a poor efficacy of AR-targeted therapy. Our data provide new insights into the role of EZH2 and H3K27me3 in therapeutic strategies for SDC.

As the laryngopharynx is closely related to swallowing, speech, and phonation, it is necessary to consider not only disease control but also a minimally invasive approach for the treatment of laryngopharyngeal cancer. Transoral surgery has been reported to be a minimally invasive method for treating these diseases. Transoral videolaryngoscopic surgery (TOVS) and endoscopic laryngo-pharyngeal surgery (ELPS) have been developed in Japan and recently emerged as treatments for patients with early stage pharyngeal and laryngeal cancers. However, securing an appropriate field of view and a narrow operating space during TOVS or ELPS are critical issues to be resolved for these surgeries. The clinical significance and safety of transoral robotic surgery (TORS) using the da Vinci Surgical System have been widely reported to provide surgeons with increased visualization and magnification, resulting in precise surgical margins and rapid functional recovery. In this context, a multi-institutional clinical study was conducted to evaluate the treatment outcomes of TORS for the treatment of laryngopharyngeal cancer in Japan, and the da Vinci Surgical System for oral robot-assisted surgery for these diseases was approved by the Pharmaceutical Affairs Agency in August 2018. This review provides an overview of the therapeutic effects of TOVS, ELPS, and TORS, with a particular focus on these therapeutic results in Japan.

Acquired ear canal stenosis can be caused by trauma, inflammation, postoperative scar formation, or tumors. There is a risk of cholesteatoma formation because of keratinized deposits in the closed space, with a reduction in quality of life because of conductive hearing loss. A cholesteatoma that has grown in a closed external auditory canal is difficult to find because of its location and the original hearing loss because of ear canal stenosis. Regarding imaging for cholesteatoma, CT absorption values are nonspecific, but MRIs are said to be effective. In an MRI, diffusion-weighted images are useful for distinguishing cholesteatoma. In surgery for ear canal stenosis, it is important to adopt strategies that will prevent post-operative restenosis and re-closure. If a cholesteatoma is also present, besides excising it, the ear canal should be enlarged. It is also important to follow-up patients with traumatic ear canal stenosis. We present a case of cholesteatoma associated with traumatic ear canal stenosis discovered 50 years after injury. Here, the cholesteatoma was diagnosed by MRI, and the external ear canal was enlarged during surgery. No postoperative recurrence was observed during follow-up.

Amyloidosis rarely occurs in the head and neck region and is extremely rare in the nasopharynx (3%). We encountered a case of nasopharyngeal amyloidosis discovered because of exudative otitis media. The patient presented to a local otolaryngology department with complaints of hearing loss, right exudative otitis media, and a nasopharyngeal mass. She was referred to our department for consultation. A diagnosis of AA type amyloidosis was made based on a biopsy of the mass. In a detailed systemic examination in internal medicine, there were no findings suggestive of systemic amyloidosis or the presence of a primary disease, leading to a diagnosis of localized nasopharyngeal amyloidosis. Surgical resection was difficult. However, in outpatient follow-up, no signs of a change to the systemic type were observed. If amyloid deposition is discovered in a particular organ, the prognosis is good if it is localized. It is however imperative to check whether it has a systemic nature through a detailed systemic examination. In addition, as the AA type may be secondary to rheumatoid arthritis or collagen disease, it is important to determine if there is a primary disease through a detailed examination. Since the transformation of localized amyloidosis to the systemic type has been reported, stringent follow-up is important.

Herein, we report a case of an occult thyroid cancer that was not detected as a primary tumor on preoperative ultrasonography or postoperative pathological examination, although a diagnosis of papillary thyroid carcinoma metastasis was made owing to the presence of a mass in the right upper neck. Needle biopsy of the mass in the right upper neck revealed positive results for thyroglobulin and TTF-1 on immunostaining, and a papillary thyroid carcinoma was observed with papillary and follicular patterns. We suspected papillary thyroid carcinoma (T0N1bM0) or ectopic papillary thyroid carcinoma. Accordingly, we performed total thyroidectomy, central lymph node dissection, right lateral neck dissection, and resection of the superficial lobe of the right parotid. A postoperative pathological examination of 5-mm slices of the specimen revealed no primary tumor in the thyroid. However, a hyalinized image of the thyroid indicated that a micropapillary thyroid carcinoma might have spontaneously disappeared. As there was no normal thyroid tissue in the metastasis to the superior internal jugular lymph node, the tumor was unlikely to be an ectopic papillary thyroid carcinoma. Therefore, we made a diagnosis of a papillary thyroid carcinoma (pT0N1bM0). After surgery, we determined that the tumor belonged to a high-risk group of papillary thyroid carcinomas and a poor-prognosis group of symptomatic papillary thyroid microcarcinomas; accordingly, ablation was performed with 30 mCi iodine-131. There was no recurrence or metastasis 24 months after the first surgery.

Tyrosine kinase inhibitors (TKIs) induce autophagy in many types of cancer cells. We previously reported that gefitinib (GEF) and imatinib (IMA) induce autophagy in epidermal growth factor receptor (EGFR) knock-out A549 and non-BCR-ABL-expressing leukemia cell lines, respectively. This evidence suggests that TKI-induced autophagy is independent of the original target molecules. The present study compared the autophagy-inducing abilities of various TKIs, regardless of their targets, by quantitative autophagy flux assay. We established stable clones expressing the GFP-LC3-mCherry-LC3ΔG plasmid in A549, PC-9, and CAL 27 cell lines and assessed autophagy inducibility by monitoring the fluorescent ratios of GFP-LC3 to mCherry-LC3ΔG using an IncuCyte live cell imaging system during exposure to TKIs viz; GEF, osimertinib (OSI), lapatinib (LAP), lenvatinib (LEN), sorafenib (SOR), IMA, dasatinib (DAS), and tivantinib (TIV). Among these TKIs, DAS, GEF, and SOR exhibited prominent autophagy induction in A549 and PC-9 cells. In CAL 27 cells, IMA, SOR, and LEN, but not GEF, TIV, or OSI, exhibited autophagy induction. In the presence of azithromycin (AZM), which showed an inhibitory effect on autophagy flux, TKIs with prominent autophagy inducibility exhibited enhanced cytotoxicity via non-apoptotic cell death relative to effects of TKI alone. Therefore, autophagy inducibility of TKIs differed in the context of cancer cells. However, once induced, they appeared to have cytoprotective functions. Thus, blocking TKI-induced autophagy with AZM may improve the therapeutic effect of TKIs in cancer cells.

When performing thyroplasty, local anesthesia is better to check patient’s voice. However, some cases need general anesthesia for various reasons. To evaluate limitations of arytenoid adduction (AA) under general anesthesia. We report five cases of AA performed under general anesthesia. Four cases were treated AA only and one case was performed nerve-muscle pedicle implantation with AA. Voice was evaluated by maximum phonation time (MPT), mean air flow rate (MFR), and auditory impression using four score levels (0–3) for grade (G), roughness (R) and breathiness (B). Improvements in MPT and MFR were seen all patients. However, glottal gap remained post-surgery with G (1) voice in four AA alone patients. Another patient who underwent AA with nerve-muscle pedicle implantation achieved excellent voice with G (0). AA under general anesthesia improve patient’s voice but sometimes insufficient. Combined treatment with nerve-muscle implantation should be considered.

BACKGROUND:Chemoradiotherapy (CRT) has improved organ preservation or overall survival (OS) of locoregionally advanced head and neck squamous cell cancer (LAHNSCC), but in clinical trials of conventional CRT, increasing CRT intensity has not been shown to improve OS. In the Adjuvant ChemoTherapy with S-1 after curative treatment in patients with Head and Neck Cancer (ACTS-HNC) phase III study, OS of curative locoregional treatments improved more with adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) than with tegafur/uracil (UFT). ACTS HNC study showed the significant efficacy of S-1 after curative radiotherapy in sub-analysis. We explored the efficacy of S-1 after curative CRT in a subset of patients from the ACTS-HNC study. METHODS:Patients with stage III, IVA, or IVB LAHNSCC were enrolled in this study to evaluate the efficacy of S-1 compared with UFT as adjuvant chemotherapy after curative CRT in the ACTS-HNC study. Patients received S-1 at 80-120 mg/day in two divided doses for 2 weeks, followed by a 1-week rest, or UFT 300 or 400 mg/day in two or three divided doses daily, for 1 year. The endpoints were OS, disease-free survival, locoregional relapse-free survival, distant metastasis-free survival (DMFS), and post-locoregional relapse survival. RESULTS:One hundred eighty patients (S-1, n = 87; UFT, n = 93) were included in this study. Clinical characteristics of the S-1 and UFT arms were similar. S-1 after CRT significantly improved OS (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22-0.93) and DMFS (HR, 0.50; 95% CI, 0.26-0.97) compared with UFT. CONCLUSION:As adjuvant chemotherapy, S-1 demonstrated better efficacy for OS and DMFS than UFT in patients with LAHNSCC after curative CRT and may be considered a treatment option following curative CRT. For this study was not preplanned in the ACTS-HNC study, the results is hypothesis generating but not definitive.

In nonocclusive mesenteric ischemia (NOMI), mesenteric ischemia and intestinal necrosis occur despite the absence of organic blockage in mesenteric blood vessels. As abdominal pain is often absent and few characteristic findings are seen in blood biochemistry, imaging diagnosis or other examinations, discovery is often delayed. With a mortality rate of 56–79%, NOMI is a very serious disease. However, few reports have described this pathology in association with chemotherapy regimens such as those used for malignant head and neck tumors. We encountered a case of NOMI during induction therapy combining cisplatin, docetaxel, and 5-fluorouracil. The patient was a 74-year-old man receiving chemotherapy for T2N2bM0 stage IVA oropharyngeal carcinoma. Febrile neutropenia appeared on treatment day 8. An antibacterial agent and a granulocyte colony-stimulating factor were administered, but septic shock developed and he was transferred to the intensive care unit. Abdominal distension was present and contrast-enhanced computed tomography of the abdomen suggested NOMI. Emergency surgery on day 9 resected the necrotized small intestine and created a single-hole ileostomy. The patient subsequently recovered with 2 weeks of continuous hemodiafiltration and other intensive therapies. Otolaryngological surgeons seldom encounter intestinal diseases, which are thus easily overlooked. The present case report may help in achieving early diagnosis.

We report a rare case of hypopharyngeal squamous cell carcinoma occurring synchronously with extramedullary plasmacytoma (EPM) of the oropharynx in which radiotherapy was used as the curative treatment. A 73-year-old man presented with a sore throat that had persisted for 6 months. Examination revealed a superficial, smooth tumorous lesion at the base of his tongue with a red hue in the oropharynx. In addition, a protruding tumor was observed on the mucosal surface in the right piriform recess of the hypopharynx, and computed tomography revealed thickening of the pharyngeal wall at the right tongue base and in the right piriform recess of the hypopharynx. Because no definitive diagnosis could be reached for the lesion at the base of the tongue, the entire tongue-base tumor was resected by transoral surgery under endoscopy. Proliferation of plasma cells in the tumor was detected, and a bone marrow puncture test ruled out multiple myeloma leading to a definitive diagnosis of Stage I (cT1N0M0) squamous cell carcinoma in the right piriform recess of the hypopharynx and primary extramedullary plasmacytoma in the oropharynx. Radiotherapy was selected for curative treatment with a complete response for both cancers. No recurrences have been observed as of 12 months postoperatively.

Objective. In most cases, about the voice of the patient with female-to-male/gender identity disorder (FTM/GID), hormone therapy makes the voice low-pitched. In success cases, there is no need for phonosurgery. However, hormone therapy is not effective in some cases. We perform type 3 thyroplasty in these cases. Method. Hormone therapy was started in 2008 but did not lower the speaking fundamental frequencies (SFFs). We therefore performed TP3 under local anesthesia. Results. In our case, the SFF at the first visit was 146 Hz. The postoperative SFF was 110 Hz. Conclusions. TP3 was performed under local anesthesia in a patient with FTM/GID in whom hormone therapy proved ineffective. With successful conversion to a lower-pitched voice, the patient could begin to live daily life as a male. QOL improved significantly with TP3. If hormone therapy proves ineffective, TP3 may be selected as an optional treatment and appears to show few surgical complications and was, in this case, a very effective treatment.

Background. Thyroid carcinoma complicated by hemiagenesis is very rare, and previous reports have not described this cancer on the side of the absent lobe. Methods and Results. We report the case of a 64-year-old woman in whom left thyroid hemiagenesis was discovered incidentally during investigations of abnormal sensation during swallowing. A tumorous 1.4 cm lesion was also found on the side of the absent lobe, left of the isthmus. Fine-needle aspiration biopsy revealed class V papillary carcinoma, but no lymph node metastases. Total thyroidectomy was performed for stage cT1bN0M0 carcinoma. Histopathology revealed normal thyroid tissues in the right lobe and isthmus, while the left lobe was absent. The mostly papillary carcinoma was adjacent to the truncated thyroid tissue, with a portion histologically consistent with poorly differentiated carcinoma. Conclusions. All previously reported cases of thyroid cancer complicated by hemiagenesis have represented carcinoma occurring within the present lobe. This case is extremely rare.

Autophagy, a self-digestive system for cytoplasmic components, is required to maintain the amino acid pool for cellular homeostasis. We previously reported that the macrolide antibiotics azithromycin (AZM) and clarithromycin (CAM) have an inhibitory effect on autophagy flux, and they potently enhance the cytocidal effect of various anticancer reagents in vitro. This suggests that macrolide antibiotics can be used as an adjuvant for cancer chemotherapy. Since cancer cells require a larger metabolic demand than normal cells because of their exuberant growth, upregulated autophagy in tumor cells has now become the target for cancer therapy. In the present study, we examined whether macrolides exhibit cytotoxic effect under an amino acid-starving condition in head and neck squamous cancer cell lines such as CAL 27 and Detroit 562 as models of solid tumors with an upregulated autophagy in the central region owing to hypovascularity. AZM and CAM induced cell death under the amino acid-depleted (AAD) culture condition in these cell lines along with CHOP upregulation, although they showed no cytotoxicity under the complete culture medium. CHOP knockdown by siRNA in the CAL 27 cells significantly suppressed macrolide-induced cell death under the AAD culture condition. CHOP-/- murine embryonic fibroblast (MEF) cell lines also attenuated AZM-induced cell death compared with CHOP+/+ MEF cell lines. Using a tet-off atg5 MEF cell line, knockout of atg5, an essential gene for autophagy, also induced cell death and CHOP in the AAD culture medium but not in the complete culture medium. This suggest that macrolide-induced cell death via CHOP induction is dependent on autophagy inhibition. The cytotoxicity of macrolide with CHOP induction was completely cancelled by the addition of amino acids in the culture medium, indicating that the cytotoxicity is due to the insufficient amino acid pool. These data suggest the possibility of using macrolides for "tumor-starving therapy".

BACKGROUND:We conducted a phase III study to evaluate S-1 as compared with UFT as control in patients after curative therapy for stage III, IVA, or IVB squamous-cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS:Patients were randomly assigned to the UFT group (300 or 400 mg day-1 for 1 year) or the S-1 group (80, 100, or 120 mg day-1 for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were relapse-free survival, overall survival (OS), and safety. RESULTS:A total of 526 patients were enrolled, and 505 were eligible for analysis. The 3-year DFS rate was 60.0% in the UFT group and 64.1% in the S-1 group (HR, 0.87; 95%CI, 0.66-1.16; p = 0.34). The 3-year OS rate was 75.8% and 82.9%, respectively (HR, 0.64; 95% CI, 0.44-0.94; p = 0.022). Among grade 3 or higher adverse events, the incidences of leukopenia (5.2%), neutropenia (3.6%), thrombocytopenia (2.0%), and mucositis/stomatitis (2.4%) were significantly higher in the S-1 group. CONCLUSIONS:Although DFS did not differ significantly between the groups, OS was significantly better in the S-1 group than in the UFT group. S-1 is considered a treatment option after curative therapy for stage III, IVA, IVB SCCHN. TRIAL REGISTRATION:ClinicalTrials.gov NCT00336947 http://clinicaltrials.gov/show/NCT00336947.

Parotid gland carcinoma is extremely rare in children. We report a case of pediatric parotid gland carcinoma with extensive infiltration into surrounding tissues including the skin and temporomandibular joint capsule at initial examination. Total resection of the parotid gland was conducted together with skull base surgery and mandibular dissection. The patient was a 14-year-old girl. In addition to the skin and temporomandibular joint, infiltration into the anterior wall of the external auditory meatus and masseter muscle was also seen, and T4N0M0 stage IV parotid carcinoma was diagnosed. Skin was resected together with the pinna, and temporal craniotomy and skull base surgery were performed to resect the temporomandibular joint capsule and external auditory meatus en bloc, and mandible dissection was conducted. Facial nerves were resected at the same time. Level I to level IV neck dissection was also conducted. A latissimus dorsi myocutaneous flap was used for reconstruction. The postoperative permanent pathology diagnosis was high-grade mucoepidermoid carcinoma with a low-grade component. Postoperatively, radiotherapy at 50 Gy alone has been conducted, with no recurrence or metastasis observed for over 4 years.

Background. Small cell carcinoma (SmCC) in the nasal cavity and paranasal sinuses is very rare, and definitive therapies have not yet been established. Methods. Chemoradiotherapy comprised 60 Gy of external radiation, with the administration of irinotecan intravenously at 60 mg/m2 on days 1, 8, and 15 and cisplatin at 60 mg/m2 on day 1. Results. Case 1 involved a 66-year-old woman with stage III cancer. Adverse events included decreased white blood cells, anemia, and oral mucositis, all Grade 2. The patient remained free of cancer as of 3 years and 6 months after completing the treatment. Case 2 involved a 60-year-old man with stage IV cancer. He also experienced adverse events of decreased white blood cells, anemia, and oral mucositis, all Grade 2. He died after 11 months due to metastases throughout the body. Conclusions. The results suggest that this regimen may be tolerable as a therapy for this type of carcinoma.

Primary submandibular gland oncocytic carcinoma is a rare pathology, with only 10 cases being reported to date. We encountered a case of primary submandibular gland oncocytic carcinoma and report it herein. The patient was a 69-year-old man who came to our hospital with right submandibular cancer as the main complaint. Based on the results of computed tomography and magnetic resonance imaging, submandibular gland tumor was diagnosed. Preoperative cytodiagnosis suggested class III oncocytic carcinoma. Resection of the right submandibular tumor was performed along with right neck dissection. Postoperative histopathological diagnosis was oncocytic carcinoma. As of 3 years following surgery, no recurrence has been identified.

Malignant melanoma of the sphenoid sinus is a very rare disease, and only 6 cases have previously been reported. The present case involved a 74-year-old woman who was examined for visual disturbance of the left eye. Computed tomography revealed a soft tissue shadow, but only mucosal hypertrophy was found on opening the sphenoid sinus under general anesthesia. One month postoperatively, visual disturbance of the right eye and paresis of cranial nerve III appeared. Malignant melanoma was diagnosed from biopsy. Multiple bone metastases were identified, but the patient declined active treatment. As a result, palliative care was provided and she died 3 months later. When there is no improvement in postoperative visual acuity as in this case, in consideration of the possibility of neoplastic lesions, rigorous followup including monitoring for neurological symptoms is warranted.

Background/Aim: Locally advanced squamous cell carcinoma of the head and neck (L/A SCCHN) is typically treated with surgery or chemoradiation therapy (CRT), whereas salvage surgery is considered for residual disease post-CRT. However, salvage surgery after radiation therapy presents challenges due to tissue fibrosis. Planned neck dissection (ND) combined with CRT, as well as positron emission tomography after CRT, have been proposed strategies, but no definitive consensus has been reached. Therefore, this study aimed to investigate the utility of "upfront ND" performed prior to CRT to enhance local control and reduce complications. Patients and Methods: We retrospectively reviewed 121 patients who underwent primary CRT for oropharyngeal, hypopharyngeal, or laryngeal cancer at Tokyo Medical University Hospital from January 2015 to September 2021. Patients without cervical lymph node metastasis or with unresectable nodes were excluded. All patients underwent pre-treatment imaging and staging. CRT consisted of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy. Selective ND or modified radical neck dissection was performed based on lymph node involvement. Results: Overall, 35 patients underwent upfront ND, whereas 54 did not. The upfront ND group exhibited significantly better 2-year locoregional recurrence-free survival than the group without upfront ND (93.7% vs. 71.0%). No significant differences were noted in adverse events between groups. Conclusion: The findings highlight upfront ND before CRT as a viable option for locally advanced head and neck cancer, particularly beneficial in cases with extranodal extension. This approach enhances local control and may reduce the need for salvage surgery, thus improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background/Aim: Nuclear protein in testis (NUT) carcinoma is extremely rare, occurs in the midline of the body, progresses rapidly and is refractory to treatment; most patients die within a year. Here, we describe a case of maxillary sinus NUT carcinoma presenting with epistaxis and nasal obstruction that was treated as a standard head and neck carcinoma. Case Report: The patient was a 41-year-old male with a left buccal swelling; the diagnosis was made of primary NUT carcinoma of the left maxillary sinus and bone metastasis in the cervical spine. After induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil, the tumor decreased in size, and the patient was further treated with cisplatin and radiation therapy. One month after that, the tumor remained small, however, lung metastasis was observed. Therefore, nivolumab was administered. Cetuximab and paclitaxel were administered after the lung metastasis worsened, but the patient developed progressive disease and died 11 months after diagnosis. Conclusion: Effective treatments for NUT carcinoma have not yet been established. However, early testing to establish the diagnosis may provide useful insights to guide clinical decisions to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background/Aim: First bite syndrome (FBS) is a symptom of severe pain at the beginning of a meal that lessens as the meal progresses. It is a common postoperative complication of parapharyngeal space tumors and is rarely reported as the first symptom of parotid carcinoma. The parapharyngeal space is considered a difficult area for approach; hence, preoperative histopathology is often challenging. However, there are hardly any reports on the approach of performing biopsies under computerized tomography (CT) guidance. Case Report: A 28-year-old woman presented to our hospital with the chief complaint of pain in the left parotid region since the past year. Contrastenhanced magnetic resonance imaging of the parotid gland revealed a 10-mm high-signal area on T2-weighted images extending from the deep lobe of the left parotid gland to the parapharyngeal space, which could not be visualized on ultrasound. She was suspected to have a malignant tumor because of the presence of a parotid tumor with FBS. Therefore, she underwent CT-guided fine-needle aspiration cytology (FNAC) and was diagnosed with adenoid cystic carcinoma. The patient underwent left parotid tumor resection and left cervical dissection, and her pain during feeding improved postoperatively. Conclusion: In a patient with parotid tumor extending into the parapharyngeal space with FBS as the initial symptom, CT-guided FNAC was successfully used to diagnose parotid carcinoma. Symptoms of pain, including FBS, should be considered in cases of malignancy. CT-guided FNAC is effective for lesions that cannot be visualized by ultrasound, such as those in the parapharyngeal space. [ABSTRACT FROM AUTHOR]

Background/Aim: Head and neck photoimmunotherapy (HN-PIT) has been an insured treatment in Japan for approximately three years. The number of treatments has gradually increased to over 350 cases. However, there are still various questions in actual clinical practice, including laryngeal edema. Therefore, it is vital to carefully explain in advance to patients the possibility of laryngeal edema occurring and obtaining consent for tracheostomy as a prophylactic or emergency measure. At our institution, 44 HN-PIT cycles were performed in 23 patients between January 2021 and October 2023. Of these, we experienced two cases in which preventive tracheostomy was not performed because the risk of laryngeal edema was considered low; however, laryngeal edema developed after treatment, and an emergency tracheostomy had to be performed. Case Report: Case 1 was a patient in his 70s with a local recurrence of mandibular gingival carcinoma. HN-PIT using cylindrical diffusers was performed on the target lesion, extending from the lateral wall of the oropharynx to the soft palate. Case 2 was also a patient in his 70s with carcinoma of the mid-pharynx. HN-PIT was performed using a frontal diffuser to target lesions extending from the soft palate to the buccal mucosa. Notably, both patients developed laryngeal edema after HN-PIT, and an emergency tracheostomy had to be performed. Conclusion: HN-PIT treatment is still being established through a trial-and-error method and is still incomplete. [ABSTRACT FROM AUTHOR]