Faculty Profiles - Ando Mizuo

Papers - Ando Mizuo

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Primary Thyroid Lymphoma: Clinical Factors Predicting the Possibility of Diffuse Large B-Cell Lymphoma. Reviewed International journal

Akifumi Kariya, Tomoyasu Tachibana, Yasushi Hiramatsu, Yoji Wani, Jun-Ya Matsumoto, Chieko Furukawa, Asuka Sato, Yuto Naoi, Yorihisa Orita, Yasuharu Sato, Mizuo Ando

Ear, nose, & throat journal 1455613231218130 - 1455613231218130 2023.12

Language：English Publishing type：Research paper (scientific journal)

Aims: Among primary thyroid lymphomas (PTLs), diffuse large B-cell lymphoma (DLBCL) has a poorer prognosis than other indolent lymphomas such as mucosa-associated lymphoid tissue (MALT) or follicular lymphoma (FL). However, the clinical differences between DLBCL and indolent lymphoma remain unclear. Therefore, this retrospective study on PTL was aimed at investigating the clinical differences between DLBCL and indolent lymphomas and identifying the factors differentiating DLBCL from indolent lymphomas. Materials and Methods: Medical records of 28 patients diagnosed with PTL and treated at our institution between 2005 and 2022 were retrospectively analyzed. Data on the following clinical variables were extracted: sex, age, symptoms (pain and dysphagia), ultrasonographic appearance patterns, the presence of airway stenosis on computed tomography and laryngeal endoscopy, blood test results, disease stage, and pathological diagnosis. Results: In all, 13 patients were histologically diagnosed with DLBCL, 12 with MALT lymphoma, and 3 with FL. Significant differences in disease-specific survival rates were evident between the DLBCL and indolent lymphoma groups (68.2 vs 100%, P = .043). High lactate dehydrogenase levels (>230 U/mL) and airway stenosis were observed only in patients with DLBCL. Multivariate analysis identified that the presence of a linear echoic strand pattern and the absence of an echoic nodular pattern on ultrasound were independently associated with DLBCL (P = .0497 and .012, respectively). Conclusion: DLBCL can cause airway stenosis. The linear echogenic strand pattern and the absence of a nodular pattern should be recognized as predictive factors of DLBCL.

DOI： 10.1177/01455613231218130

Ultra-high combined positive score and high serum albumin are favorable prognostic biomarkers for immune checkpoint inhibitors in head and neck squamous cell carcinoma. Reviewed International journal

Yuki Saito, Kenya Kobayashi, Osamu Fukuoka, Toshihiko Sakai, Koji Yamamura, Mizuo Ando, Kenji Kondo

Head & neck 2023.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Biomarkers that predict response to immune checkpoint inhibitor (ICI) in recurrent metastatic squamous cell carcinoma of the head and neck (RMHNSCC) are not well known. METHODS: We prospectively measured the combined positive score (CPS) and administered ICI to patients with RMHNSCC. RESULTS: Of 51 patients, 23 patients had a CPS <20 and 12 patients (23.5%) had a CPS ≥90. CPS showed a negative correlation with serum albumin. Survival analysis showed a 2-year survival rate of 24.1%. In multivariate analysis, CPS ≥90 (HR 0.3026, p = 0.02614) and albumin >3.5 (HR 0.3463, p = 0.01354) were the significant factors and plus chemotherapy (HR 0.4648, p = 0.07632) was not significant. Seven patients (14%) with CPS ≥90 and albumin >3.5 showed a 2-year survival rate of 66. 7%. CONCLUSIONS: CPS ≥90 and albumin >3.5 cases are a subgroup of RMHNSCC that respond extremely well to ICI.

DOI： 10.1002/hed.27576

Cochlear Implantation in the Poorer-Hearing Ear Is a Reasonable Choice. Reviewed

Ryotaro Omichi, Shin Kariya, Yukihide Maeda, Kunihiro Fukushima, Yuko Kataoka, Akiko Sugaya, Kazunori Nishizaki, Mizuo Ando

Acta medica Okayama 77 ( 6 ) 589 - 593 2023.12

Language：English Publishing type：Research paper (scientific journal)

Choosing the optimal side for cochlear implantation (CI) remains a major challenge because of the lack of evidence. We investigated the choice of the surgery side for CI (i.e., the better- or poorer-hearing ear) in patients with asymmetric hearing. Audiological records of 74 adults with a unilateral hearing aid who had undergone surgery at Okayama University Hospital were reviewed. The definition of 'better-hearing ear' was the aided ear, and the unaided ear was considered the poorer-hearing ear. We performed a multiple regression analysis to identify potential predictors of speech recognition performance after unilateral CI in the patients. Fifty-two patients underwent CI in the poorer-hearing ear. The post-Ci bimodal hearing rate was far higher in the poorer-ear group (77.8% vs. 22.2%). A multivariate analysis revealed that prelingual hearing loss and the patient's age at CI significantly affected the speech recognition outcome (beta coefficients: 24.6 and -0.33, 95% confidence intervals [11.75-37.45] and [-0.58 to -0.09], respectively), but the CI surgery side did not (-6.76, [-14.92-1.39]). Unilateral CI in the poorer-hearing ear may therefore be a reasonable choice for adult patients with postlingual severe hearing loss, providing a greater opportunity for postoperative bimodal hearing.

DOI： 10.18926/AMO/66150

p16 status and high-risk human papilloma virus infection in squamous cell carcinoma of the nasal vestibule. Reviewed International journal

Koji Yamamura, Yuki Saito, Kenya Kobayashi, Toshiyuki Mukai, Osamu Fukuoka, Ken Akashi, Masafumi Yoshida, Mizuo Ando, Tatsuya Yamasoba

Auris, nasus, larynx 50 ( 6 ) 942 - 947 2023.12

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The status of human papilloma virus (HPV) and p16 overexpression for nasal vestibule squamous cell carcinoma (NVSCC) is unclear. The purpose of this retrospective study was to analyze the presence of HPV and the role of p16 overexpression as a surrogate marker in cases of NVSCC. METHODS: Retrospective analysis was performed on patients who were diagnosed and treated for NVSCC at the University of Tokyo Hospital, Japan. p16 immunohistochemistry was considered positive with at least moderate staining intensity and diffuse staining (≥75% of tumor cells), according to the 8th edition of the American Joint Commission on Cancer. HPV-DNA testing was performed using multiplex polymerase chain reaction. RESULTS: Five patients were included in the study. Ages ranged from 55 to 78 years; there were two men and three women; two had T2N0, and three had T4aN0. Surgery was performed in one case, surgery plus radiation therapy (RT) in one case, and chemoradiation therapy (CRT) in three cases. Four of the five tumors showed p16 overexpression. One of five cases had an HPV-16 genotype. The mean follow-up period was 73 months, and all the patients survived. One patient with p16-negative carcinoma had local recurrence and underwent salvage surgery. Of the four patients with p16-positive carcinoma, one with CRT and one with surgery plus RT, each had delayed cervical lymph node metastasis, which was salvaged with neck dissection subsequent RT. CONCLUSIONS: In NVSCC, four of the five cases were p16-positive, and one was high-risk HPV infection.

DOI： 10.1016/j.anl.2023.03.008

Risk Factors for Anterior Skull Base Injury in Endoscopic Sinus Surgery Reviewed International journal

Seiichiro Makihara, Kensuke Uraguchi, Tomoyuki Naito, Aiko Shimizu, Aya Murai, Takaya Higaki, Yohei Noda, Shin Kariya, Mitsuhiro Okano, Mizuo Ando

Cureus 15 ( 11 ) e49273 2023.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Objectives This retrospective study aimed to investigate the relationships between the Keros classification, the Gera classification, the vertical height of the posterior ethmoid roof (ER), and anterior ethmoidal artery (AEA) types in Japanese patients. Methods We investigated the computed tomography (CT) slices of paranasal sinuses (120 sides) of 60 patients; measured the cribriform plate (CP) depth, lateral lamella CP angle (LLCPA), and vertical height of the lateral ER from the hard palate (LERHP) at the coronal plane of the posterior ethmoidal artery (PEA); and reviewed the AEA types, whether floating or non-floating. Results CP depth was positively correlated with LLCPA (r=0.63; p<0.01) and the height of LERHP (r=0.19; p<0.05). The height of the LERHP in females was significantly lower than that in males. With increased CP depth, floating AEAs became prevalent (p<0.001). Conclusion In females, low height of the posterior ethmoid sinus roof, where cerebrospinal fluid (CSF) leaks occurred while penetrating the basal lamella, often existed; the heights positively correlated with the Keros classification in Japanese patients. The Keros and Gera classifications, AEA type, and posterior ER height do not individually constitute a complete risk assessment but may correlate, preventing major complications, such as CSF leak and orbital hemorrhage.

DOI： 10.7759/cureus.49273

Revision cochlear implant surgery in adults and children is a safe and effective technique: a retrospective single faculty study in Okayama University Hospital, Japan. Reviewed International journal

Akiko Sugaya, Shin Kariya, Kunihiro Fukushima, Ryotaro Omichi, Mizuo Ando

Acta oto-laryngologica 1 - 5 2023.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Cochlear implant (CI) surgery is a safe surgical technique, although some patients require revision CI surgery. AIMS/OBJECTIVES: This study investigated the cause and underlying reason of revision CI surgery as well as hearing outcomes in a single institution. PATIENTS AND METHODS: This retrospective study evaluated patients who underwent CI surgery between April 2006 to March 2022 (n = 351). Sex, aetiology of hearing loss (HL), age and period from initial CI surgery to reimplantation, cause of revision, and related factors were examined. RESULTS: Twelve patients (8 males, 4 females) received CI reimplantation. The revision surgery rate was 2.59% (3.15% children, 1.69% adults); the period from initial surgery to reoperation was 8.60 ± 6.56 years for 9 children with congenital HL and 15.27 ± 5.72 years for 3 adults with progressive HL. Device failure was the most common cause (n = 8), followed by infections (n = 2), advanced facial irritation symptoms (n = 1), and electrode slip-out (n = 1). Mean preoperative and postoperative CI thresholds were 44.0 ± 9.46 dBnHL and 39.19 ± 8.89 dBnHL (p < .068), respectively. CONCLUSION AND SIGNIFICANCE: Caregiver education, surgical technique advances, flap design, and extensive antibiotic use may decrease the revision surgery rate. The lack of post-revision deterioration of the hearing threshold contributed to well-being in patients with CI.

DOI： 10.1080/00016489.2023.2270701

Nasopharyngeal low-grade papillary schneiderian carcinoma with cervical metastasis. Reviewed International journal

Kensuke Uraguchi, Kenji Nishida, Takuma Makino, Seiichiro Makihara, Masahiro Tabata, Shin Kariya, Mizuo Ando

Auris, nasus, larynx 50 ( 5 ) 821 - 826 2023.10

Language：English

Low-grade papillary Schneiderian carcinoma (LGPSC) is a rare and newly described type of cancer arising from the Schneiderian epithelium. Owing to cellular atypia, it is difficult to differentiate this type from other papillomas and malignancies. Although this condition remains unclear, it is associated with mortality and recurrence. Therefore, treating physicians should be aware of the possibility of LGPSC for prompt diagnosis and treatment. In this article, we present an additional case of nasopharyngeal LGPSC with cervical lymph node metastasis and reviewed the 14 cases reported thus far in the literature. A 76-year-old female was referred to our department for detailed examination of nasopharyngeal and cervical lymph node tumors detected by positron emission tomography-computed tomography. Based on the biopsy of the nasopharyngeal tumor, we suspected LGPSC. Considering the clinical course and pathological findings, the patient was diagnosed with cervical lymph node metastasis through neck dissection. We performed radiotherapy for the primary lesion of the nasopharynx, which led to the disappearance of the tumor. After 13 months following the radiotherapy, the patient died from a recurrence of retroperitoneal liposarcoma without the recurrence of LGPSC.

DOI： 10.1016/j.anl.2022.12.010

Near-infrared photoimmunotherapy for salivary duct carcinoma. Reviewed International journal

Takuma Makino, Yasuharu Sato, Kensuke Uraguchi, Yuto Naoi, Yujiro Fukuda, Mizuo Ando

Auris, nasus, larynx 2023.9

Language：English

In Japan, near-infrared photoimmunotherapy (NIR-PIT) was introduced in 2021 as a treatment option for unresectable recurrent head and neck cancer. The treatment targets the epidermal growth factor receptor (EGFR), which is overexpressed in 80-90 % of head and neck squamous cell carcinoma (HNSCC). NIR-PIT should theoretically show therapeutic efficacy if EGFR is expressed, even in nonsquamous cell carcinomas (non-SCC). To the best of our knowledge, there are no case reports of NIR-PIT for non-SCC. We performed NIR-PIT in a patient with non-SCC of the head and neck region. After performing two NIR-PIT treatments, small free clusters of residual tumor cells were observed. Immunostaining in this specimen revealed EGFR expression in residual tumor cells. The residual tumor cells had been irradiated sufficiently to achieve necrosis. It is suggested that not only laser irradiation and expression of EGFR but also other factors are involved in the efficacy of this treatment. Further investigation for these other factors is warranted.

DOI： 10.1016/j.anl.2023.09.006

Summary of Japanese clinical practice guidelines for head and neck cancer - 2022 update edited by the Japan society for head and neck cancer. Reviewed International journal

Akihiro Homma, Mizuo Ando, Nobuhiro Hanai, Hiroyuki Harada, Yoshitaka Honma, Tomonori Kanda, Satoshi Kano, Daisuke Kawakita, Naomi Kiyota, Yoshiyuki Kizawa, Masahiro Nakagawa, Takenori Ogawa, Hirotaka Shinomiya, Takeshi Shinozaki, Motoyuki Suzuki, Tetsuya Tsuji, Koichi Yasuda, Sadamoto Zenda, Takeshi Kodaira, Tadaaki Kirita, Ken-Ichi Nibu

Auris, nasus, larynx 2023.7

Language：English Publishing type：Research paper (scientific journal)

The aim of the "Japanese Clinical Practice Guidelines for Head and Neck Cancer - 2022 Update" is to review the latest evidence regarding head and neck cancer and to present the current standard approaches for diagnosis and treatment. These evidence-based recommendations were created with the consensus of the Guideline Committee, which is composed of otorhinolaryngologists and head and neck surgeons, together with radiologists, radiation oncologists, medical oncologists, plastic surgeons, dentists, palliative care physicians, and rehabilitation physicians. These guidelines were created by the Clinical Practice Guideline Committee of the Japan Society for Head and Neck Cancer based on the "Head and Neck Cancer Treatment Guidelines 2018 Edition," and the revised draft was compiled after evaluation by the Assessment Committee and public comments. The 'Clinical questions and recommendations' section consists of 13 categories, and 59 clinical questions are described in total. Here we describe 6 clinical questions specific to other sets of guidelines with recommendations and comments.

DOI： 10.1016/j.anl.2023.07.003

Genome Doubling Shapes High-Grade Transformation and Novel EWSR1::LARP4 Fusion Shows SOX10 Immunostaining in Hyalinizing Clear Cell Carcinoma of Salivary Gland. Reviewed International journal

Kenya Kobayashi, Masahito Kawazu, Seiichi Yoshimoto, Toshihide Ueno, Go Omura, Yuki Saito, Mizuo Ando, Eigitsu Ryo, Airi Sakyo, Akihiko Yoshida, Yasushi Yatabe, Hiroyuki Mano, Taisuke Mori

Laboratory investigation; a journal of technical methods and pathology 103 ( 10 ) 100213 - 100213 2023.7

Language：English Publishing type：Research paper (scientific journal)

Hyalinizing clear cell carcinoma (HCCC) is a rare indolent malignant tumor of minor salivary gland origin with EWSR1::ATF1 rearrangement. Pathologically, the tumor cells possess a clear cytoplasm in a background of hyalinized stroma. Generally, the tumor cells are positive for p63 and p40 and negative for s100 and α-smooth muscle actin, suggesting that they differentiate into squamous epithelium and not into myoepithelium. In this study, we performed a detailed histopathological and genomic analysis of 6 cases of HCCC, including 2 atypical subtypes-a case of "high-grade transformation" and 1 "possessing a novel partner gene for EWSR1." We performed a sequential analysis of the primary and recurrent tumor by whole-exome sequencing, RNA sequencing, Sanger sequencing, and fluorescence in situ hybridization to investigate the effect of genomic changes on histopathology and clinical prognosis. A fusion gene involving the EWSR1 gene was detected in all cases. Five cases, including the "high-grade transformation," harbored a known EWSR1::ATF1 fusion gene; however, 1 case harbored a novel EWSR1::LARP4 fusion gene. This novel EWSR1::LARP4-fused HCCC has a SOX10-positive staining, which is different from the EWSR1::ATF1-fused HCCC. According to whole-exome sequencing and fluorescence in situ hybridization analysis, the "whole-genome doubling" and focal deletion involving CDKN2A, CDKN2B, and PTEN were detected in HCCC with "high-grade transformation." Conclusively, we identified a novel partner gene for EWSR1, LARP4, in indolent HCCC. Importantly, "high-grade transformation" and poor prognosis were caused by whole-genome doubling and subsequent genomic aberrations.

DOI： 10.1016/j.labinv.2023.100213

Association between handwashing and gargling education for children and prevention of respiratory tract infections: a longitudinal Japanese children population-based study Reviewed International journal

Kensuke Uraguchi, Toshiharu Mitsuhashi, Naomi Matsumoto, Soshi Takao, Seiichiro Makihara, Mizuo Ando, Takashi Yorifuji

European Journal of Pediatrics 182 ( 9 ) 4037 - 4047 2023.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

PURPOSE: A longitudinal study was conducted to examine the effects of handwashing and gargling education for children on the prevention of respiratory tract infections (RTIs) in children in Japan. METHODS: The study included 38,554 children born in 2010 who were enrolled in a longitudinal study. Information on children's hygiene education regarding handwashing and gargling was collected in a survey at the age of 3.5 years. Based on parents' reports of doctors' diagnoses, airway infections and influenza events in the 12-month duration before the survey were evaluated for RTIs at the ages of 4.5 and 9 years. Poisson regression with robust variance was performed to examine the effects of hygiene education on RTIs prevention. The supplementary analysis was stratified by household income. RESULTS: Children were categorized into different groups: 38% in the handwashing and gargling group, 29% in the handwashing group, 0.1% in the gargling group, and 9.7% in the no-education group. Exclusions were made for non-respondent children (23%) and those in the gargling group. Hygiene education was associated with decreased influenza at the age of 4.5 years in the handwashing (adjusted RR [aRR] = 0.8; 95% CI, 0.8-0.9) and handwashing and gargling groups (aRR = 0.8; 95% CI, 0.8-0.9) compared with no education. However, no preventive effects on airway infections at the age of 4.5 and 9, influenza at the age of 9, or hospitalization between the ages of 3.5 and 9 years were detected. Handwashing and gargling could significantly prevent influenza in low-income households (aRR = 0.7; 95% CI, 0.6-0.8). Conclusions: Gargling education was widespread and mostly combined with handwashing education in Japan. Hygiene education significantly affected prevention of influenza infections at the age of 4.5 years, especially in low-income households. WHAT IS KNOWN: • Previous intervention studies showed handwashing and gargling are effective in preventing respiratory tract infections. WHAT IS NEW: • We conducted a longitudinal study on handwashing and gargling education in Japanese children and found that handwashing and gargling were widely practiced together. • Handwashing and gargling education were related to a reduction in influenza, particularly in low-income households.

DOI： 10.1007/s00431-023-05062-5

Other Link： https://link.springer.com/article/10.1007/s00431-023-05062-5/fulltext.html

Endolymphatic Hydrops on Magnetic Resonance Imaging May Be an Independent Finding on Aging in Neurotologic Patients. Reviewed International journal

Yukihide Maeda, Katsuhide Kojima, Soshi Takao, Ryotaro Omichi, Shin Kariya, Mizuo Ando

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 44 ( 7 ) 737 - 741 2023.7

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To clarify whether age impacts the development of endolymphatic hydrops (ELH) in neurotologic patients. Documentation of ELH in living patients on magnetic resonance imaging (MRI) allows analysis of patient age and formation of ELH, which is impossible by means of postmortem temporal bone pathology. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Fifty patients (100 ears) with top 3 diagnoses of definite Menière's disease, delayed ELH, or probable Menière's disease. INTERVENTIONS: Endolymph MRI after intravenous gadolinium injection and pure-tone audiometry. MAIN OUTCOME MEASURES: Cochlear and vestibular ELH confirmed by MRI. RESULTS: The prevalences of ears showing both cochlear and vestibular ELH were similar among age groups <30 years (30%), 30-59 years (25.9%), and ≥60 years (34.4%; p > 0.05; χ2 test). Using logistic regression modeling, mean hearing level at the six frequencies was positively associated with a higher risk of cochlear ELH (odds ratio, 1.3; 95% confidence interval, 1.1-1.5 per 10-dB increment). In the same regression model, age did not impact the outcome of cochlear ELH (odds ratio, 1.0; 95%confidence interval, 0.7-1.4 per 10-year increment). Age did not differ among ears with no ELH (mean ± standard deviation age, 48.6 ± 14.4 yr), ears with only cochlear ELH (59.3 ± 10.7 yr), ears with only vestibular ELH (50.4 ± 16.9 yr), or ears with both cochlear and vestibular ELH (51.5 ± 18.4 yr; p > 0.05, analysis of variance). CONCLUSION: Chronological age was not associated with the formation of ELH. Aging per se may not be associated with the development of ELH in neurotologic patients.

DOI： 10.1097/MAO.0000000000003945

Efficacy of Chemotherapy After Immune Checkpoint Inhibitor Discontinuation in Head and Neck Cancer. Reviewed International journal

Osamu Fukuoka, Yuki Saito, Toshiyuki Mukai, Takaaki Hayashi, Koji Yamamura, Toshihiko Sakai, Kenya Kobayashi, Ken Akashi, Masafumi Yoshida, Mizuo Ando, Tatsuya Yamasoba

The Laryngoscope 134 ( 1 ) 228 - 235 2023.6

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Immune checkpoint inhibitors (ICI) have become widely used becuse of their effectiveness and relatively low rate of severe adverse events. However, active treatment should be continued after discontinuation of ICI as response rates are lower than that of conventional cytotoxic chemotherapy. The purpose of the present study was to determine the efficacy of treatment after ICI discontinuation. METHODS: This was a retrospective study from hospital charts of 99 consecutive cases treated with ICI at our facility since 2017. Of these, 79 cases of squamous cell carcinoma which had already discontinued ICI were enrolled in the present study. RESULTS: After discontinuation of ICI, 40 cases received active treatment with salvage chemotherapy (SCTx; 33 cases) or surgery or radiotherapy (seven patients) and 39 cases received nonactive treatment. SCTx comprising paclitaxel and cetuximab (PTX-Cmab) was administered to 15 cases and other SCTx regimens to 18 cases. A significant increase in overall survival (OS) was observed with active treatment compared with nonactive treatment. No significant differences in OS or progression-free survival (PFS) were observed between SCTx regimens; however, there was a trend toward increased survival with PTX-Cmab. Univariate analysis of overall response rate (ORR) demonstrated significant differences in the site of disease at ICI and SCTx regimens. A significant difference in disease control rate was observed between SCTx regimens. Multivariate analysis of ORR demonstrated a significant correlation with PTX-Cmab treatment. CONCLUSION: Active treatment after ICI discontinuation and the use of PTX-Cmab as SCTx may increase OS in head and neck squamous cell carcinoma. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2023.

DOI： 10.1002/lary.30851

Macroarray expression analysis of cytokines and prostaglandin metabolism-related genes in chronic rhinosinusitis Reviewed International journal

Aiko Oka, Kengo Kanai, Takaya Higaki, Seiichiro Makihara, Yohei Noda, Shin Kariya, Mizuo Ando, Wataru Nishimura, Mitsuhiro Okano

Journal of Allergy and Clinical Immunology: Global 2 ( 3 ) 100123 - 100123 2023.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

BACKGROUND: Chronic rhinosinusitis (CRS) can be divided into endotypes by functional or pathophysiologic findings. OBJECTIVE: The aim of this study was to analyze the expression of cytokines, prostaglandin (PG) synthases, and their receptors related to the pathogenesis of CRS, especially those contributing to nasal polyp (NP) formation. METHODS: NPs and uncinate tissue (UT) samples were collected from 90 patients who underwent endoscopic sinus surgery. They included 75 patients with CRS (including 45 with eosinophilic CRS [eCRS] and 30 with non-eCRS) and 15 patients without CRS. A total of 30 genes were selected for our original DNA array plate to analyze the levels of expression of 10 cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-13, IL-17A, IL-22, IL-25, IL-33, and TSLP), 4 prostaglandin synthases (prostaglandin D2 [PGD2] synthase, prostaglandin E2 synthase, COX-1, and COX-2), and their 16 receptors. Clustering analysis was performed according to the expression results, and clinical findings of patients from each cluster were investigated. RESULTS: The samples could be divided into 3 clusters. Cluster 1 showed elevated levels of expression of IL4, IL5, IL13, TSLP, IL1RL1 (ST2 [an IL-33 receptor]), HPGDS, and GPR44 (CRTH2, a PGD2 receptor); cluster 2 showed elevated levels of expression of IL17A and PTGES; and cluster 3 showed an elevated level of expression of IL25. Regarding clinical features, the main characteristics of each cluster were as follows: NPs from patients with eCRS for cluster 1, NPs and/or UT samples from patients with non-eCRS for cluster 2, and UTs from patients with non-CRS for cluster 3. CONCLUSION: The results suggest that there are associations between type 2 inflammation/PGD2 and eCRS and also between type 3 inflammation/prostaglandin E2 and non-eCRS.

DOI： 10.1016/j.jacig.2023.100123

Risk factors for incomplete resection with pharyngeal endoscopic submucosal dissection and long-term prognosis after resection. Reviewed International journal

Yoshiki Sakaguchi, Yuki Saito, Mizuo Ando, Masafumi Yoshida, Osamu Fukuoka, Kenya Kobayashi, Dai Kubota, Daisuke Ohki, Hiroya Mizutani, Keiko Niimi, Yosuke Tsuji, Mitsuhiro Fujishiro, Tatsuya Yamasoba

Surgical endoscopy 37 ( 5 ) 3593 - 3601 2023.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Advances in endoscopic imaging technology have led to an increase in detection of superficial pharyngeal squamous carcinoma. Endoscopic submucosal dissection (ESD) has been reported to be effective for the treatment of these lesions, however there is still insufficient evidence on the long-term results of pharyngeal ESD. METHODS: This is a single-center retrospective study of all cases of superficial pharyngeal cancer that underwent ESD as primary treatment between January 2010 and May 2022. A total of 83 lesions in 63 patients were analyzed. RESULTS: The en bloc resection rate was 100%, and R0 resection rate was 59.0%, with an adverse event rate of 6.0%. During a mean observation period of 1134 days, there were 0 cases of disease-specific metastasis or death. However, the 5-year cumulative incidence of metachronous head and neck cancer after resection was 27.1% and the 5-year overall survival and 10-year overall survival after pharyngeal ESD were 87.0% and 69.6%, respectively. Of the 34 cases with non-R0 resection, local recurrence occurred in 8.8%. Location of lesion (p = 0.011), disparity between demarcation of the lesion with NBI and iodine staining (p = 0.026), and non-effective laryngeal elevation (p = 0.080) were risk factors for non-R0 resection. CONCLUSION: Pharyngeal ESD is effective and safe. Further studies are needed to improve and standardize indications and strategies for pharyngeal ESD.

DOI： 10.1007/s00464-022-09820-8

A Case of Radiation-Induced Osteosarcoma with RB1 Gene Alteration Treated by Skull Base Surgery and Craniofacial Reconstruction. Reviewed

Yuki Matsuda, Yoshihiro Otani, Takao Yasuhara, Mizuo Ando, Takaya Higaki, Takuma Makino, Hiroshi Matsumoto, Tadashi Oyama, Hisakazu Nishimori, Isao Date

Acta medica Okayama 77 ( 1 ) 85 - 90 2023.2

Language：English

A 35-year-old female presented with headache, photophobia and developed sudden loss of vision after having undergone right-side ophthalmectomy and radiochemotherapy for retinoblastoma in infancy. A neoplastic lesion was found in the left middle cranial fossa and was surgically removed. The diagnosis was radiation-induced osteosarcoma with RB1 gene alteration. Although she received chemotherapy for the residual tumor, it progressed 17 months later. Maximal surgical resection with craniofacial reconstruction was required. We utilized two three-dimensional models for surgical planning. She was discharged without neurological deficits other than loss of light perception subsequent to left ophthalmectomy. In cases where retinoblastoma is treated with radiotherapy, long-term follow-up is necessary to monitor for radiation-induced tumor development.

DOI： 10.18926/AMO/64367

A Case of Relapsing Polychondritis Localized to the Nasal Septum Which Showed Spontaneous Healing Reviewed

Tomoyasu Tachibana, Yoji Wani, Hidetoshi Kagawa, Yasutoshi Komatsubara, Kazunori Kuroda, Akifumi Kariya, Yuto Naoi, Mizuo Ando

Practica Oto-Rhino-Laryngologica 116 ( 6 ) 573 - 577 2023

Publishing type：Research paper (scientific journal)

We present the case of a 77-year-old male patient with relapsing polychondritis localized to the nasal septum, who presented with a history of recurrent epistaxis and nasal pain. After definitive confirmation of the diagnosis of relapsing polychondritis by biopsy, the patient was kept under observation and the lesion healed spontaneously, without steroid administration; the patient was followed up for 5 years, with no signs of recurrence. Careful follow-up might be an option for patients with localized relapsing polychondritis without systemic symptoms.

DOI： 10.5631/jibirin.116.573

A Case of Cerebrospinal Fluid Rhinorrhea of the Clivus Reviewed

Tomoyasu Tachibana, Shohei Kohno, Yasutoshi Komatsubara, Kazunori Kuroda, Akifumi Kariya, Yuto Naoi, Mizuo Ando

Practica Oto-Rhino-Laryngologica 116 ( 9 ) 881 - 885 2023

Publishing type：Research paper (scientific journal)

We present the case of a 63-year-old woman with cerebrospinal fluid (CSF) rhinorrhea of the clivus. She presented with a 6-week history of left-sided watery nasal discharge. RI cisternography showed evidence of a CSF leak in the sphenoid sinus at the previous institution, so the patient was referred to our hospital for further examination. CT and MR imaging revealed fluid collection in the left-sided sphenoid sinus and a clival bone defect. Transnasal endoscopic repair was performed using autologous grafts of her abdominal fat and fascia, and a mucosal flap from the nasal septum. Histological examination showed no evidence of tumor. We made the final diagnosis of idiopathic CSF rhinorrhea. There were no signs of a CFS leak or any new lesion at the clivus at the 2-year follow-up. Reconstruction with a mucosal flap from the nasal septum is considered as being useful for CSF rhinorrhea in the clivus.

DOI： 10.5631/jibirin.116.881

Tumor-stroma ratio can predict lymph-node metastasis in cT1/2N0 oral tongue squamous cell carcinoma independent of tumor budding grade. Reviewed

Toshihiko Sakai, Yuki Saito, Yoko Tateishi, Sho Yamazawa, Osamu Fukuoka, Kenya Kobayashi, Go Omura, Ken Akashi, Masafumi Yoshida, Mizuo Ando, Yasuhiro Ebihara, Tatsuya Yamasoba

International journal of clinical oncology 27 ( 12 ) 1818 - 1827 2022.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: cT1/2 oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. However, predicting neck lymph-node metastasis (NLM) remains challenging. Pathomorphological evaluation of tumor budding grade (TBG) and tumor-stroma ratio (TSR) reportedly can predict lymph-node metastases. Hence, this study aimed to evaluate TBG and TSR in OTSCC and investigate their relationship to occult NLM and cancer relapse. METHODS: Clinicopathological data of patients with cT1/2N0 OTSCC treated at the University of Tokyo Hospital between 2007 and 2017 were collected. TBG and TSR were evaluated using hematoxylin-eosin staining and cytokeratin AE1/AE3 immunostaining. RESULTS: Out of 70 patients, 16 underwent elective neck dissection in addition to primary-tumor resection, whereas 54 did not. During follow-up, NLM was found in 35 patients. NLM correlated with the pathological depth of invasion (pDOI) (p < 0.001), TBG (p = 0.008), and TSR (p < 0.001) in univariate analysis and pDOI (p = 0.01) and TSR (p = 0.02) in multivariate analysis. The 5-year recurrence-free survival rate (RFS) was 78% for patients with a pDOI ≤ 5 mm and stroma-poor tumors and 33% for patients with a pDOI > 5 mm and stroma-rich tumors. CONCLUSION: Patients with a pDOI > 5 mm and stroma-rich tumors have a high risk for cancer relapse. TSR and pDOI may be promising NLM predictors in cT1/2N0 OTSCC.

DOI： 10.1007/s10147-022-02249-y

Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling. Reviewed International journal

Shinji Kohsaka, Yuichiro Tada, Mizuo Ando, Masato Nakaguro, Yukina Shirai, Toshihide Ueno, Shinya Kojima, Hideaki Hirai, Natsuki Saigusa, Satoshi Kano, Kiyoaki Tsukahara, Takafumi Togashi, Hiroyuki Ozawa, Takahito Kondo, Kenji Okami, Hideaki Takahashi, Daisuke Kawakita, Chihiro Fushimi, Takayoshi Suzuki, Akira Shimizu, Isaku Okamoto, Takuro Okada, Yuichiro Sato, Yorihisa Imanishi, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Yukiko Sato, Makoto Urano, Yoshitaka Honma, Keisuke Yamazaki, Yushi Ueki, Toyoyuki Hanazawa, Yuki Saito, Tomotaka Shimura, Toshitaka Nagao, Hiroyuki Mano

NPJ precision oncology 6 ( 1 ) 82 - 82 2022.11

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1038/s41698-022-00324-1

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