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Background: JCOG1212 is a dose-finding and efficacy confirmatory study of concurrent superselective intra-arterial infusion of cisplatin and radiotherapy (RADPLAT) for locally advanced primary squamous cell carcinoma of the maxillary sinus (cT4a,bN0M0). In this study, we report the results of the final analysis of the efficacy confirmation phase for the T4a cohort with 5-year follow-up data to evaluate the late adverse events and long-term efficacy., Methods: Based on the results of the dose-finding phase, the efficacy confirmation phase consisted of seven weekly intra-arterial infusions of cisplatin 100 mg/m 2 combined with radiotherapy (70 Gy). The 5-year prognosis and late adverse events were evaluated., Results: Between April 2014 and August 2018, 64 patients were included in the analysis (one ineligible patient was excluded); 31 patients were treated with three-dimensional conformal radiation therapy (3D-CRT) and 33 with intensity modulated radiation therapy (IMRT). The 5-year overall survival, event-free survival, and local event-free survival was 71.9, 54.7, and 57.5%, respectively. In terms of late adverse events, grade 3 or higher non-hematologic toxicity was observed in 42.9% of 63 patients (retinopathy: 12, cataract: 10, osteonecrosis of mandible: 4, etc.). Grade 3 and 4 cataracts of affected side appeared in 22.6% (7/31) of the 3D-CRT group compared to 3.1% (1/32) in the IMRT group. Twenty-one patients had died, with 15 from the primary disease, 5 from other causes, and 1 from treatment-related cause., Conclusion: The prognosis of RADPLAT was favorable after 5-year follow-up with acceptable late adverse events and low proportion of treatment related death., Competing Interests: Declarations. Conflict of interest: A.H. reports grants and nonfinancial support from Japan Agency for Medical Research and Development (AMED) and the National Cancer Center Research and Development Fund during the conduct of the study. Y.S. reports personal fee from MSD.K.K. Ethics approval: This study was registered with the UMIN Clinical Trials Registry under trial number UMIN000013706 and the Japan Registry of Clinical Trials (Number: jRCTs031180004), and approved by the institutional review board from each participating institution and National Cancer Center Hospital Certified Review Board (CRB3180008). Consent to participate: Informed consent was obtained from all individual participants included in the study., (© 2025. The Author(s).)

Background: Patients with esophageal squamous cell carcinoma (ESCC) frequently develop synchronous head and neck squamous cell carcinoma (HNSCC). With advances in endoscopic technology and widespread screening of synchronous cancers, the detection of synchronous HNSCC and superficial ESCC (SESCC) is increasing. We aimed to evaluate the impact of preceding HNSCC treatment on synchronous SESCC., Methods: This single-center retrospective study enrolled patients with synchronous HNSCC and SESCC who were treated between January 2010 and December 2023. Tumor size and depth of SESCC before and after HNSCC treatment were evaluated. The factors associated with SESCC progression were investigated., Results: Of the 299 patients with synchronous HNSCC and SESCC, 134 who underwent preceding HNSCC treatment with follow-up esophagogastroduodenoscopy (EGD) for SESCC were evaluated. Chemoradiotherapy was the most common treatment for HNSCC (56.0%), followed by surgery (17.2%), radiotherapy (14.9%), local resection (7.5%), and chemotherapy (4.5%). The tumor size of SESCC increased after HNSCC treatment in 18 patients (13.4%). Multivariate analysis revealed that an EGD interval of ≥ 120 days was significantly associated with increased tumor size in SESCC (odds ratio, 6.64; 95% confidence interval, 1.91-23.1). Tumor regrowth was observed in 70.6% of SESCCs that shrank with HNSCC treatment, mostly within six months. Tumor depth aggravation was rare (2.2%), but progression to advanced ESCC was observed in two patients., Conclusions: Timely endoscopic follow-up, preferably within 120 days, is crucial for managing synchronous SESCC after HNSCC treatment to prevent tumor progression. Tumor regrowth should be monitored when SESCC shrinks with HNSCC treatment., Competing Interests: Declarations. Conflict of interest: Ryu Ishihara has received honoraria from Olympus, FUJIFILM Medical, Daiichi-Sankyo, Miyarisan Pharmaceutical, AI Medical Service, Astra Zeneca, MSD, and Ono Pharmaceutical. Satoki Shichijo has received honoraria from Olympus, EA Pharma, Astra Zeneca, AI Medical Service, Janssen Pharmaceutical, and FUJIFILM Medical. Takashi Kanesaka has received honoraria from Olympus, AstraZeneca, and AI Medical Service. Sachiko Yamamoto has received honoraria from Ono Pharmaceutical and MSD. Noriya Uedo has received honoraria from Olympus, FUJIFILM Medical, Boston Scientific, Daiichi-Sankyo, Takeda Pharmaceutical, EA Pharma, Otsuka Pharmaceutical, AstraZeneca, Miyarisan Pharmaceutical, and AI Medical Service. Takashi Fujii has received honoraria from Merck Biopharma, Taiho Pharmaceutical, Rakuten Medical, MSD, and Medtronic. The other authors have no financial relationships to disclose., (© 2024. Japanese Society of Gastroenterology.)

Competing Interests: T. Kanesaka has received honoraria from Olympus, AstraZeneca, and AI Medical Service. R. Ishihara has received honoraria from Olympus, FUJIFILM Medical, Daiichi-Sankyo, Miyarisan Pharmaceutical, AI Medical Service, Astra Zeneca, MSD, and Ono Pharmaceutical. Y. Tani, K. Higashino, K. Aoki, T. Fujii, and T. Michida declare that they have no conflict of interest.

Background: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up., Methods: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations., Results: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2-81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13-1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34-1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27-1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27-2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56-2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57-2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively., Conclusion: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC., Clinical Trial Registration: NCT02358031., Competing Interests: Declarations. Conflict of interest: Nobuhiko Oridate has received honoraria from MSD, Ono Pharmaceutical, Bristol Myers Squibb Japan, Merck Biopharm Japan, and Taiho Pharmaceutical. Shunji Takahashi has received honoraria from MSD, Eisai, and Ono Pharmaceutical and grants from Taiho Pharmaceutical, Daiichi Sankyo, Novartis, Ono Pharmaceutical, Eisai, BMS, Bayer, and Astra Zeneca. Kaoru Tanaka has received personal fees from Astra Zeneca, Merck Biopharma, Eisai, Bristol Myers Squibb, Ono Pharmaceutical, MSD, Kyowa Kirin, Chugai Pharmaceutical, Takeda Pharmaceutical, Taiho Pharmaceutical, and Novartis Pharma, outside the submitted work. Yasushi Shimizu has received research funding from MSD. Koji Matsumoto has received honoraria from MSD, Kyowa Kirin, Daiichi Sankyo, Eli Lilly, and Chugai Pharmaceutical Co. and received trial fee from Daiichi Sankyo, MSD, Eli Lilly, Gildea Sciences, and Eisai. Tomoya Yokota has received research funding from MSD. Masanobu Takahashi has received lecture fees from Daiichi Sankyo, Ono Pharmaceuticals, Bristol Myers Squibb, Taiho Pharmaceutical Co. and research funding from Ono Pharmaceutical, Chugai Pharmaceutical, and MSD, outside the submitted work. Tsutomu Ueda has received research funding from Lilly and personal fees from Rakuten Medical, Merck Biopharma, Mitsubishi Tanabe Pharma, MSD, and Bristol Myers Squibb. Nobuhiro Hanai has received honoraria from Rakuten Medical K.K. and research funding from MSD K.K. and Adlai Nortye USA Inc. Hiroki Hara has received honoraria from Bristol Myers Squibb, Chugai, Daiichi Sankyo, Lilly, Merck Biopharma, Miyarisan, MSD, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, and Yakult Honsha and research funding from ALX oncology, Amgen, Astellas, Astra Zeneca, Bayer, BioGene, Chugai, Daiichi Sankyo, Janssen, Jazz Pharma, MSD, Ono Pharmaceutical, and Taiho Pharmaceutical. Kenichi Takahashi is an employee of MSD K.K., Tokyo, Japan and owns stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Nijiro Nohata is an employee of MSD K.K., Tokyo, Japan and owns stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Burak Gumuscu is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Nati Lerman is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Makoto Tahara has received honoraria from Eisai, MSD, Merck Biopharma, Lilly and research funding from Bayer, Astra Zeneca, Ono Pharmaceutical, and Pfizer. Yasushi Fujimoto, Tomoko Yamazaki, Hironori Yamaguchi, Tomokazu Yoshizaki Ryuji Yasumatsu, Masahiro Nakayama, Kiyoto Shiga, Takashi Fujii, and Kenji Mitsugi declare they have no conflicts of interest., (© 2024. The Author(s).)

Bradycardia, atrial tachyarrhythmia, heart failure, residual shunts, and pulmonary hypertension (PH) are significant problems after congenital heart disease surgery. We performed His-bundle pacing (HBP) for drug-resistant PH with bradycardia in a woman post-total anomalous pulmonary venous return repair complicated by bradycardia, hypertension, PH, residual atrial shunts, and heart failure. Significant improvement in PH post-HBP was achieved without exacerbation of left ventricular function. We successfully closed the atrial shunts 12 months after HBP., (© 2024 Wiley Periodicals LLC.)

Background and Aim: Effective treatment of lesions that develop in the irradiated area of head and neck squamous cell carcinoma is a major concern. This study aimed to clarify the efficacy and safety of endoscopic resection for such lesions., Methods: Among consecutive patients who underwent endoscopic resection for histologically proven head and neck squamous cell carcinoma between January 2014 and December 2021, those who received definitive radiotherapy/chemoradiotherapy before endoscopic resection were included in this single-center, retrospective study. Short- and long-term outcomes were evaluated., Results: Among 422 patients who underwent endoscopic resection for 615 lesions, 43 patients with 57 lesions were eligible. All 57 lesions were treated with endoscopic submucosal dissection and en bloc resection was achieved in all lesions. Grade 3 of Common Toxicity Criteria for Adverse Events v5.0 occurred in eight (19%) patients (dysphagia, seven; stricture, three; aspiration pneumonia, two; and pharyngeal necrosis, one [some cases overlapped]), but no grade ≥ 4 events occurred. Enteral nutrition by gastrostomy was temporarily required in two patients owing to dysphagia and laryngeal necrosis. During the median follow-up of 40 (interquartile range, 29.5-61) months after endoscopic submucosal dissection for the lesions developed in the irradiated area, local recurrence and metachronous lesions developed in two (5%) and nine (21%) patients, respectively. However, total laryngectomies and tracheostomies were avoided in all patients. The 3-year overall and disease-specific survivals were 81% (95% confidence interval, 64%-91%) and 94% (95% confidence interval, 79%-99%), respectively., Conclusions: Favorable local control and safety of endoscopic submucosal dissection were demonstrated., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Aggressive lipid-lowering therapy is important for secondary prevention of acute myocardial infarction (AMI). The recommended target for low-density lipoprotein cholesterol (LDL-C) of <70 mg/dL is often not achieved. To address this gap, we implemented a clinical pathway in all hospitals that perform percutaneous coronary interventions (PCI) with primary care physicians in Nagasaki and aimed to validate the effectiveness of this pathway in an acute setting., Methods and Results: This retrospective cohort study included medical records extracted from 8 hospitals in Nagasaki, Japan, where PCI was performed for patients with AMI. The index date was defined as the date of hospitalization for AMI between July 1, 2021, and February 28, 2023. The primary outcome was the rate of achieving LDL-C <70 mg/dL at discharge. The median baseline LDL-C level at admission was 121 mg/dL (n=226) in the pre-implementation group and 116 mg/dL (n=163) in the post-implementation group. In the post-implementation group, 131 patients were treated using the clinical pathway. The rate of achieving LDL-C <70 mg/dL at discharge increased significantly from 37.2% before implementation to 54.6% after implementation. Logistic regression analysis revealed a positive correlation between the implementation of the clinical pathway and achieving LDL-C <70 mg/dL., Conclusions: Implementation of a region-wide clinical pathway for LDL-C management significantly improved the rate of intensive lipid-lowering therapy and the achievement of LDL-C targets.

Background and Purpose: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data., Materials and Methods: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism., Results: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V 60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism., Conclusion: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aimed to develop a method to evaluate the quality of bovine in vitro fertilized (IVF) embryos based on gene expression profiling via whole-transcriptome amplification. The expression of 11 developmentally important genes in individual bovine in vivo-derived (IVD) and IVF embryos were examined. Gene expression profiling was conducted by classifying the expression level of each gene in individual embryos as low, medium, or high. The IVF group had a higher (P < 0.01) proportion of embryos with low expression of SOX2, NANOG, and FGF4. In addition, a correlation analysis between the expression levels of each gene in individual embryos demonstrated that the relationship between gene expression differed with respect to IVD and IVF embryos. Our results suggest that the expression profiling of developmentally important genes using IVD embryos as normal controls could be a useful indicator for evaluating the quality of bovine IVF embryos.

Background: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC., Methods: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing., Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53 , CDKN2A , and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses., Conclusion: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles., Competing Interests: TT received lecture honoraria, consulting fees, and grants from Ono Pharmaceutical Co., Ltd. and lecture honoraria from Bristol Myers Squibb, and Merck Sharp & Dohme Corp. KO received grants from Ono Pharmaceutical Co., Ltd. HO and SS were employed by SCREEN Holdings Co., Ltd. YaS received lecture honoraria from Bristol Myers Squibb, Merck Sharp & Dohme Corp, and Ono Pharmaceutical Co., Ltd. RH received lecture honoraria from Rakuten Medical Inc. YuS received grants from Merck Sharp & Dohme Corp. KT received lecture honoraria from Bristol Myers Squibb, Merck Sharp & Dohme Corp, and Ono Pharmaceutical Co., Ltd. NO received lecture honoraria and grants from Ono Pharmaceutical Co., Ltd and lecture honoraria from Bristol-Myers Squibb. NH received lecture honoraria from Bristol Myers Squibb, and Ono Pharmaceutical Co., Ltd. KN received lecture honoraria from Merck Sharp & Dohme Corp, and Ono Pharmaceutical Co., Ltd. SI received lecture honoraria and grants from Ono Pharmaceutical Co., Ltd and lecture honoraria from Bristol Myers Squibb. KI received grants from SCREEN Holdings Co., Ltd. TAs received grants from Ono Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tsujikawa, Ohno, Morita, Saburi, Mitsuda, Yoshimura, Kimura, Morimoto, Ogi, Shibata, Akashi, Kurata, Imoto, Shimizu, Kano, Watanabe, Yamazaki, Asada, Hayashi, Saito, Ozawa, Tsukahara, Oridate, Sano, Horii, Ueki, Maruo, Mukoyama, Hanai, Fukusumi, Iwai, Fujisawa, Fujii, Nibu, Iwae, Ueda, Chikuie, Yasumatsu, Matsuo, Umeno, Ono, Masuda, Toh, Itoh, Hirano and Asakage.)

Objectives: We aimed to identify independent factors for intraoperative endoscopic lens cloudiness during gastric and colorectal endoscopic submucosal dissections, investigate the effectiveness of Cleastay, an endoscope anti-fog solution, and examine factors associated with severe submucosal fat deposition., Methods: A total of 220 patients who underwent gastric or colorectal endoscopic submucosal dissections in two institutions between January 2022 and October 2023 were included. Significant factors related to cloudiness were determined using univariate and multivariate analyses. Patient background and tumor characteristics related to severe submucosal fat deposition were investigated, and the degree of intraoperative endoscopic lens cloudiness and outcomes were compared between the Cleash and Cleastay groups., Results: In the multivariate analysis, factors increasing lens cloudiness included long procedure time (odds ratio [OR], 17.51; 95% confidence interval [CI], 1.52-202.08), stomach (vs. colon; OR, 5.08; 95% CI, 1.99-12.96), and severe submucosal fat deposition (OR, 12.19; 95% CI, 5.02-29.60). Conversely, the use of Cleastay (vs. Cleash; OR, 0.066; 95% CI, 0.021-0.21) was identified as a factor reducing cloudiness. Location analysis revealed that severe submucosal fat deposition was more common in the upper stomach and right colon., Conclusions: It was suggested that Cleastay is more useful for endoscopic submucosal dissection of the upper stomach and right colon, where severe submucosal fat deposition is expected., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Objective: Several scoring systems have been developed to predict prognosis in patients with refractory cancer. We aimed to validate eight scoring systems and determine the best method for predicting the prognosis of head and neck squamous cell carcinoma treated with nivolumab., Methods: This multicentre retrospective study involved 154 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with nivolumab between 2017 and 2020. Oncological outcomes were assessed according to the scoring systems, including MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scores. Objective response, overall survival and progression-free survival were evaluated using logistic regression and Cox proportional hazards analyses. Receiver operating curve analysis was used to calculate the area under the curve and estimate the efficacy of each score., Results: No significant associations were found between the responses and any score. Seven of the eight scoring systems were associated with disease control (odds ratio, 0.26-0.70). Amongst the eight scoring systems, MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio showed the highest area under the curve for predicting response and disease control. Seven scoring systems were prognostic factors for progression-free survival (hazard ratio, 1.22-1.95). All eight scoring systems were prognostic factors for overall survival (hazard ratio, 1.62-3.83). According to the time-dependent receiver operating characteristics analysis for overall survival, the Hammersmith scoring system had the best predictive ability at 3 months, and the MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio scoring system had the highest area under the curve between 6 and 24 months., Conclusions: MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scoring systems were better predictors of prognosis in patients with head and neck squamous cell carcinoma treated with nivolumab., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/purpose: Following the COVID-19 pandemic, there were reports of diagnostic delays and a surge in the prevalence of advanced head and neck cancer (HNC). We conducted a retrospective study on the impact of COVID-19 on the number of newly diagnosed HNC among patients who underwent screening at our center to understand the temporal changes., Materials and Methods: We investigated the Union for International Cancer Control guidelines-TNM classification, presence of subjective symptoms at the time of consultation, and initial treatment from the medical records of first-time patients with HNC who visited our head and neck surgery department during 2019-2021 and compared them with those before (2019) and after (2020-2021) the pandemic., Results: A total of 1245 patients were included in the study. The number of patients were 437, 417, and 391 in 2019, 2020, and 2021, respectively, indicating a downward trend following the pandemic. When the incidence of early (stage 0-II) and advanced (stage III-IV) HNC cancers was compared, the proportion of patients with early-stage cancer declined. Among them, significant primary tumor progression was observed in T classification. The number of patients with no subjective symptoms at initial diagnosis was decreasing significantly., Conclusion: A decrease in the proportion of HNC patients with early-stage cancer and primary tumor progression was observed after the pandemic in 2020 and 2021. The number of early-stage malignancies may have dropped due to patients' unwillingness to visit a doctor., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Aim: C-reactive protein (CRP) is both an inflammatory and prognostic marker in various cancers. This study aimed to elucidate the characteristics of CRP and the prognostic factors in patients who were administered with atezolizumab plus bevacizumab (ATZ + BEV) for unresectable hepatocellular carcinoma (HCC)., Methods: A total of 213 patients who received ATZ + BEV for HCC from November 2020 to March 2023 at 15 hospitals were enrolled in this retrospective study. The prognosis was analyzed by subdividing the patients based on baseline characteristics, radiologic response, and treatment lines. Accuracy of survival prediction was assessed using CRP, alpha fetoprotein (AFP), C-reactive protein and alpha fetoprotein in immunotherapy (CRAFITY), and Glasgow Prognostic Score., Results: Compared with patients with baseline CRP <1 mg/dL, those with baseline CRP ≥1 mg/dL (n = 45) had a significantly higher baseline albumin-bilirubin score and AFP levels, significantly lower disease control rate (62.2%), and significantly shorter median overall survival (hazards ratios 2.292; 95% confidence interval 1.313-5.107; log-rank test, p < 0.001). Multivariate analysis identified CRP ≥1 mg/dL, AFP ≥100 ng/mL, and modified albumin-bilirubin grade as the significant prognostic factors. The baseline CRP, AFP, CRAFITY, and Glasgow Prognostic Score demonstrated higher discrimination for 1-year survival prediction after first-line ATZ + BEV administration, compared with beyond second line, with area under the receiver operating characteristic curves of 0.759, 0.761, 0.805, and 0.717, respectively., Conclusions: CRP was a significant biomarker in patients treated with ATZ + BEV for HCC. Elevated CRP levels may indicate aggressive cancer progression and potential resistance to ATZ + BEV therapy., (© 2023 Japan Society of Hepatology.)

Objective  With the expansion of indications of flow diverter (FD) for cerebral aneurysms, FD placement for posterior communicating artery (Pcom) aneurysms has been approved. However, it is controversial whether Pcom aneurysms should be treated with FD or not. In this study, we report the outcome of FD treatment for Pcom aneurysms in Japan. Materials and Methods  We retrospectively analyzed 36 patients with 38 aneurysms treated with FD placement for Pcom aneurysms between 2015 and 2021 in our hospital. We divided our cases into complete occlusion (CO) and non-CO groups. And we extracted contributing factors to CO using multivariate analysis. We also compared the complications rate among the three types of FDs. Results  CO was obtained in 29 cases (79.3%), and complications were observed in 3 cases (7.9%). Multivariate analysis revealed that the type of Pcom branch from the aneurysmal dome was a significant factor contributing to CO (odds ratio: 0.0052, 95% confidence interval 0.000048-0.584, p  = 0.029). In terms of complications, complication rate was significantly higher in the Flow-Redirection Endoluminal Device (FRED) group ( p  = 0.0491). Conclusion  The outcome for Pcom aneurysms treated by FD was acceptable. When treating, we must pay attention to where Pcom originates. Achieving CO with FD is difficult for aneurysms where the Pcom branches from the dome. Furthermore, when treating Pcom aneurysms with FRED, it is necessary to be careful about thromboembolic complications., Competing Interests: Conflict of Interest H.O. receives donations in the form of research funds to him as an endowed chair of his department from Terumo Co., Ltd., Stryker CO., Ltd., Medtronic CO., Ltd., for consulting fees of over one million yen yearly from each of three companies., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

We experimentally demonstrated the polarization change of femtosecond laser pulses in air by using electric-field-induced second-harmonic generation (E-FISHG) for the first time to our knowledge. The polarization change from linear to elliptical was observed at the laser intensity over the filamentation threshold. These results suggest that the polarization change can occur by the birefringence caused by filamentation. This phenomenon can be used for new applications such as an ultra-fast and precise three-dimensional electric field measurement by E-FISHG. In addition, E-FISHG can be an excellent tool to investigate the characteristics of femtosecond laser propagation such as filamentation.

Purpose: Recently, a novel device, the Woven Endo Bridge (WEB), was developed for wide-neck bifurcation intracranial aneurysms (WNBAs). The aim of this study is to investigate factors that contribute to adequate occlusion (AO) after the operation using detailed radiological images., Methods: The subjects were 29 patients with 29 aneurysms who received WEB implantation for WNBAs between December 2020 and April 2022. We assessed the contributing factors to AO by retrospectively comparing the AO group and non-AO group., Results: The mean age was 64.6 ± 13.1 years, and 18 were female (62.1%). The mean aneurysm dome width, aneurysm height, and aneurysm neck diameter were 4.8 ± 0.6 mm, 5.1 ± 0.6 mm, and 3.7 ± 0.6 mm, respectively. After about 6 months, 22 of 29 patients (75.9%) had AO. Complications were observed in 2 patients (6.9%), renal artery injury in one, and minor cerebral infarction in another, but the modified Rankin scale scores of both patients remained unchanged. Multivariate analysis extracted only WEB shape modification (WSM) as a contributing factor to AO (odds ratio: 0.912, p = 0.0287)., Conclusion: WEB implantation for WNBAs was a treatment modality with acceptable efficacy and safety. WSM was the only significant factor contributing to non-AO after the treatment. We should clarify the mechanisms or causes of WSM to achieve AO after WEB implantation in future., Competing Interests: Declaration of conflicting of interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: H.O. received a donation in the form of a research fund to the endowed chair of his departments and from Terumo Co., Ltd. The other authors have no conflicts of interest to declare.

Here, we investigated the detailed molecular oncogenic mechanisms of a novel receptor tyrosine kinase (RTK) fusion, KLC1-ROS1 , with an adapter molecule, KLC1, and an RTK, ROS1, discovered in pediatric glioma, and we explored a novel therapeutic target for glioma that possesses oncogenic RTK fusion. When wild-type ROS1 and KLC1-ROS1 fusions were stably expressed in the human glioma cell lines A172 and U343MG, immunoblotting revealed that KLC1-ROS1 fusion specifically activated the JAK2-STAT3 pathway, a major RTK downstream signaling pathway, when compared with wild-type ROS1 . Immunoprecipitation of the fractionated cell lysates revealed a more abundant association of the KLC1-ROS1 fusion with JAK2 than that observed for wild-type ROS1 in the cytosolic fraction. A mutagenesis study of the KLC1-ROS1 fusion protein demonstrated the fundamental roles of both the KLC1 and ROS1 domains in the constitutive activation of KLC1-ROS1 fusion. Additionally, in vitro assays demonstrated that KLC1-ROS1 fusion upregulated cell proliferation, invasion, and chemoresistance when compared to wild-type ROS1. Combination treatment with the chemotherapeutic agent temozolomide and an inhibitor of ROS1, JAK2, or a downstream target of STAT3, demonstrated antitumor effects against KLC1-ROS1 fusion-expressing glioma cells. Our results demonstrate that KLC1-ROS1 fusion exerts oncogenic activity through serum-independent constitutive activation, resulting in specific activation of the JAK-STAT pathway. Our data suggested that molecules other than RTKs may serve as novel therapeutic targets for RTK fusion in gliomas.

Objective: The association between the severity of COVID-19 and gastrointestinal (GI) bleeding is unknown. This study aimed to determine whether the severity of COVID-19 is a risk factor for GI bleeding., Design: A multicentre, retrospective cohort study was conducted on hospitalised patients with COVID-19 between January 2020 and December 2021. The severity of COVID-19 was classified according to the National Institute of Health severity classification. The primary outcome was the occurrence of GI bleeding during hospitalisation. The main analysis compared the relationship between the severity of COVID-19 and the occurrence of GI bleeding. Multivariable logistic regression analysis was performed to evaluate the association between the severity of COVID-19 and the occurrence of GI bleeding., Results: 12 044 patients were included. 4165 (34.6%) and 1257 (10.4%) patients had severe and critical COVID-19, respectively, and 55 (0.5%) experienced GI bleeding. Multivariable analysis showed that patients with severe COVID-19 had a significantly higher risk of GI bleeding than patients with non-severe COVID-19 (OR: 3.013, 95% CI: 1.222 to 7.427). Patients with critical COVID-19 also had a significantly higher risk of GI bleeding (OR: 15.632, 95% CI: 6.581 to 37.130). Patients with severe COVID-19 had a significantly increased risk of lower GI bleeding (OR: 10.349, 95% CI: 1.253 to 85.463), but the risk of upper GI bleeding was unchanged (OR: 1.875, 95% CI: 0.658 to 5.342)., Conclusion: The severity of COVID-19 is associated with GI bleeding, and especially lower GI bleeding was associated with the severity of COVID-19. Patients with severe or critical COVID-19 should be treated with caution as they are at higher risk for GI bleeding., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Head and neck cancer (HNC) treatment causes dysphagia, which may lead to aspiration pneumonia (AP). Thickened fluids are widely used to prevent aspiration in patients with dysphagia; however, there is little evidence that they can prevent AP. This study aimed to clarify the differences between restriction of oral intake of fluids (R), only thickened fluids (TF), and no restriction of fluids (NR) for AP in patients with dysphagia after HNC treatment., Methods: We retrospectively studied 654 patients with dysphagia after HNC surgery between 2012 and 2021. Of these, 255 had some restriction of fluids. The development of possible AP and administration of antibacterial drugs were used as outcomes. Multivariate linear regression and propensity score matching analyses were performed., Results: The mean patient age was 64 ± 13, 67 ± 11, and 68 ± 10 years, while the Dynamic Imaging Grade of Swallowing Toxicity score 3-4 was 2.8%, 27.5, and 53.3%% water in NR, TF, and R groups, respectively. AP was diagnosed or suspected after starting oral intake in 37 (9.3%), 11 patients (15.9%), and 45 (17.6%) and antibacterial drugs were administered in 11 (2.8%), 7 patients (10.1%), and 25 (9.8%) in NR, TF, and R groups, respectively. R and TF had significant negative impacts on AP., Conclusions: Fluid restrictions may not reduce the risk of AP or affect the administration of antibacterial drugs. Medical staff should bear in mind that fluid restrictions do not necessarily prevent AP in patients with HNC., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Although neck dissection is an essential technique in the surgical treatment of head and neck carcinoma, arm abduction disorders occurring after neck dissection reduce the patient's quality of life., Methods: We prospectively evaluated the rate of lymph node metastasis in Levels IIB and V in head and neck cancer patients who underwent neck dissection at eight centres in Japan. In addition, post-operative arm abduction disability was classified according to functional assessment values at 1 month post-operatively, and the rate of maintained function at 6 and 12 months was evaluated., Results: Lymph node metastasis occurred in Level IIB in 12 of 242 cases (4.9%) and in Level V in 5 cases (2.1%) during the 12-month post-operative course. In patients with preservation of the ipsilateral accessory nerve, arm abduction function was maintained in 142 of 209 patients (67.9%) at 12 months after surgery. Post-operative radiotherapy and Level V dissection had no statistically significant effect on the recovery of arm abduction function. Level V dissection caused a temporary loss of abduction function post-operatively. A higher arm abduction test score at 1 month post-operatively was associated with a higher rate of subsequent ability to maintain arm abduction function., Conclusions: In patients classified as cN0, metastatic rate at Levels IIB and V was low. In this cohort, omitting Level V dissection may be an option in strategies aimed at maintaining arm abduction function., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We aimed to evaluate the visual measurements of coronary artery calcium (CAC) on nonelectrocardiogram (ECG)-gated chest computed tomography (CT) using a simple scoring method that involves counting the number of CT slices containing CAC. Materials and Methods: We analyzed 163 participants who underwent both coronary and chest CT examinations at six centers within 3 months. Agatston scores were calculated on standard ECG-gated scans and classified as none (0), mild (1-99), moderate (100-400), or severe (>400). Next, chest CT images were reconstructed to standard 5.0 mm axial slices. Then, CAC on chest CT scans was measured using two methods: the Weston score (sum of the assigned score of each vessel, range: 0-12) and number of slices showing CAC (Ca-slice#). Results: When the Weston score and Ca-slice# were divided into four levels according to the optimal divisional levels corresponding to the Agatston score classes, good agreements with the 4-grade Agatston score were observed (kappa value=0.610 and 0.794, respectively). The sensitivity and specificity of Ca-slice# ≥9 to identify severe Agatston scores of >400 were 86% and 96%, respectively. Conclusion: The Ca-slice#, a simple scoring method using chest CT scans, was in good agreement with the ECG-gated Agatston score., Competing Interests: Disclosure StatementShinichiro Fujimoto received grants from HeartFlow Japan G. K., Canon Medical Systems Corporation, and FUJIFILM Corporation, Edwards LifeSciences Ltd. All other authors declare no competing interests., (© 2023 The Editorial Committee of Annals of Vascular Diseases.)

Background: The pipeline embolization device (PED) is the most common flow diverter device in the world. To date, there have been no reports of treatment outcomes specific to intradural internal carotid artery (ICA) aneurysms. The safety and efficacy of the PED treatments for intradural ICA aneurysms are reported., Methods: 131 patients with 133 aneurysms underwent PED treatments for intradural ICA aneurysms. The mean aneurysm dome size and neck length were 12.7 ± 4.3 mm and 6.1 ± 2.2 mm, respectively. We used adjunctive endosaccular coil embolization for 88 aneurysms (66.2%). A total of 113 aneurysms (85%) were angiographically followed up 6 months following the procedure, and 93 aneurysms (69.9%) were followed up for 1 year., Results: The angiographic outcome at 6 months showed that 94 (83.2%) aneurysms had O'Kelly-Marotta (OKM) grade D, 6 (5.3%) had C, 10 (8.8%) had B, and 3 (2.7%) had A. At 1 year, 82 (88.2%) aneurysms had OKM grade D, 6 (6.5%) had C, 3 (3.2%) had B, and 2 (2.2%) had A. Multivariate analysis showed that aneurysm neck size and adjunctive coiling were statistically significant in aneurysm occlusion status. Major morbidity modified Rankin Scale >2 and mortality rates related to procedures were 3.0% and 0%, respectively. Delayed aneurysm ruptures were not observed., Conclusion: These results reveal that PED treatment of intradural ICA aneurysms is safe and efficacious. The combined use of adjunctive coil embolization not only prevents delayed aneurysm ruptures but also contributes to an increase in the rate of complete occlusion., Competing Interests: Hidenori Oishi receives a donation in the form of a research fund to the endowed chair of his departments and about 1 million yen yearly from Medtronic Co., Ltd., (Copyright: © 2023 Surgical Neurology International.)

The flow diverter has been shown to be a safe and effective device for large cerebral aneurysms in the proximal internal carotid artery (ICA). Recently, its indication has been expanded to small- and medium-sized cerebral aneurysms in the distal segment of the ICA. In this study, we report a single-center, retrospective investigation of the safety and efficacy of the Pipeline Flex device to treat these aneurysms. Of the patients who underwent Pipeline implantation for small- and medium-sized ICA aneurysms (≤12 mm) at our hospital between July 2013 and October 2021, 102 patients with 104 aneurysms were included in this study. The mean age of the patients was 57.7 ± 12.1 years, and 94 (90.4%) were female. The mean aneurysmal dome diameter was 9.2 ± 2.3 mm, the mean neck diameter was 5.3 ± 1.6 mm, and the mean dome-to-neck ratio was 1.8 ± 0.5. Twenty-five patients (24.0%) had incorporated vessels from the aneurysm. Complete occlusion of the aneurysms was obtained in 96 patients (92.3%). There were no cases of parent artery stenosis or major stroke after the procedure. Absence of incorporated vessel from the aneurysm dome and adjunctive coil embolization are statistically significant factors indicating complete occlusion in multivariate analysis. The time to complete occlusion was determined earlier with the use of the Pipeline Shield (p = 0.0386) and with adjunctive coils (p = 0.0025). We showed that Pipeline implantation for small- and medium-sized aneurysms was safe and highly effective.

Enarodustat (JTZ-951) is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has been approved and marketed in Japan for patients with anemia with chronic kidney disease (CKD). The pharmacometric approach was applied to assess the relationship between plasma concentrations of enarodustat and hemoglobin (Hb) levels, and to provide information regarding the optimal use of enarodustat in clinical practice by simulations based on the pharmacokinetic and pharmacodynamic (PK/PD) model that was developed. The PK/PD data of enarodusat obtained from phase 2 and phase 3 studies in Japanese patients with CKD were well described by the models: a 1-compartment model with first-order absorption and elimination for PK, and a semimechanistic model based on transit compartment model for PD. Although several factors were identified as statistically significant covariates on the PK/PD of enarodustat, model-based simulations showed that none of them had clinically relevant impacts on the treatment effect (ie, Hb levels) of enarodustat. Hence, enarodustat treatment provides the stable Hb control with the initial dose (hemodialysis-dependent CKD: 4 mg/day, non-dialysis-dependent CKD: 2 mg/day) and maintenance dose (1-8 mg/day) to the patients with varied demographic characteristics., (© 2022, The American College of Clinical Pharmacology.)

Background: In head and neck surgery cases where skin is severely scarred or adhered to surrounding tissue, reconstruction can be difficult to perform using microsurgical tissue or conventional pedicled pectoralis major myocutaneous flap (PMMF) transfer given the risks, which include damage to major vessels when manipulating scarred skin. For such cases, we perform a 2-stage external PMMF transfer, whereby the PMMF is directly sutured to the defect over the neck skin (without manipulation the hardened skin), and the flap division is then performed secondarily., Methods: A total of 30 patients who had histories of radiotherapy (60-70 Gy) and prior neck dissection received the 2-stage external PMMF transfer procedure. Indications for the flaps included pharyngeal fistula closure in 12 patients, reconstruction for mandibular necrosis after radiotherapy in 8 patients, salvage surgery for partial or total necrosis of the free flap in 4 patients, and simultaneous reconstruction after tumor excision in 6 patients. Two patients underwent a second external PMMF transfer from the contralateral side because of postoperative complications, yielding a total of 32 flap transfers., Results: Twenty-nine flaps showed complete flap survival, whereas 3 had partial necrosis. Other complications, despite complete flap survival, included large fistulas requiring additional surgery for fistula closure (1 patient) and small fistulas that were closed without requiring reoperation (7 patients)., Conclusions: External PMMF transfer offers a safe, simple, and effective option in cases where free flap surgery is considered difficult or the risks associated with neck manipulation are high., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Coronary periarteritis with aneurysms has been reported as a cardiovascular manifestation of immunoglobulin G4 (IgG4) -related disease. We report a 10-year clinical observation of a patient with IgG4-related coronary periarteritis (IgG4-rCP) characterized by multiple thickening of periarterial tissue and coronary artery aneurysms (CAAs).A 60-year-old man with a history of IgG4-related autoimmune pancreatitis had an incidental detection of a total of 5 tumor-like lesions surrounding the right and left coronary arteries on coronary computed tomography angiography (CCTA) in 2012. Among them, 3 lesions were located at the middle to the distal portions of the right coronary artery (RCA) and the most proximal lesion was accompanied by a CAA. Although corticosteroid therapy was continued, 4-year follow-up of CCTA in 2016 showed the most proximal lesion gradually increased from 33 to 45 mm and the CAA enlarged from 9 to 22 mm. In order to avoid aneurysmal rupture, the patient underwent resection of the most proximal lesion with an enlarged aneurysm concomitant with coronary artery bypass grafting (CABG). Histopathological findings were coincident with IgG4-rCP. CCTA in 2018, however, showed the remaining distal tumor-like lesion of RCA had slightly enlarged and a new CAA developed despite the corticosteroid therapy. Follow-up CCTA in 2022 revealed the CAA increased to 13 mm, which showed rapid enlargement by 4 mm/year. A second operation through a re-median sternotomy was planned. The residual lesions with the CAA were resected followed by CABG. The other lesions at the left coronary artery remained stable without aneurysmal change, but careful follow-up has been continued.

Background: Brenner tumor is a rare epithelial ovarian neoplasm that accounts for 2-3% of all ovarian neoplasms. Herein, we report the first case of thoracic spinal metastasis of recurrent Brenner tumor without local recurrence.Case Description.A 70-year-old female presented with a feeling of abdominal distension. Computed tomography revealed cystic lesions in her bilateral ovaries. Blood examination revealed high CA-125 [74.9 U/ml]. We excised bilateral ovaries, uterus, and omentum. Borderline Brenner tumor was diagnosed [Ki-67 labeling index: 10 %]. Follow-up abdominal echo and CA-125 examination revealed no local recurrence. 26 months later she developed paraplegia. Magnetic resonance imaging revealed tumor in the 5th-9th thoracic vertebra and compression of spinal cord at the 6th thoracic vertebra level. Her paraplegia was progressive. We performed semi-urgent partial resection of tumor and release of spinal cord compression. Spinal metastasis from Brenner tumor was diagnosed [Ki-67 labeling index: 50-60 %]. She received adjuvant radiation of 30 Gy in 10 fractions to the 4th-10th thoracic vertebra. After radiation and rehabilitation, she was discharged home on foot. She received adjuvant radiation and chemotherapy but died 11 months after spinal surgery. An autopsy has not been performed on her, and the cause of death is unknown., Conclusion: We report the first case of thoracic metastasis of recurrent Brenner tumor without local recurrence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Here, we report the results of the Japanese subgroup of the phase 3 KEYNOTE-048 study of pembrolizumab alone, pembrolizumab plus platinum and 5-fluorouracil (pembrolizumab-chemotherapy), or cetuximab plus platinum and 5-fluorouracil (EXTREME) in previously untreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)., Methods: Primary end points were overall survival (OS) and progression-free survival (PFS). Efficacy was evaluated in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1 and the total Japanese subgroup (n = 67)., Results: At data cutoff (25 February 2019), pembrolizumab led to longer OS versus EXTREME in the PD-L1 CPS ≥ 20 subgroup (median, 28.2 vs. 13.3 months; HR, 0.29 [95% CI 0.09-0.89]) and to similar OS in the total Japanese (23.4 vs. 13.6 months; HR, 0.51 [95% CI 0.25-1.05]) and CPS ≥ 1 subgroups (22.6 vs. 15.8 months; HR, 0.66 [95% CI 0.31-1.41]). Pembrolizumab-chemotherapy led to similar OS versus EXTREME in the PD-L1 CPS ≥ 20 (median, 18.1 vs. 15.8 months; HR, 0.72 [95% CI 0.23-2.19]), CPS ≥ 1 (12.6 vs. 15.8 months; HR, 1.19 [95% CI 0.55-2.58]), and total Japanese subgroups (12.6 vs. 13.3 months; unadjusted HR, 1.10 [95% CI 0.55-2.22]). Median PFS was similar for pembrolizumab and pembrolizumab-chemotherapy versus EXTREME in all subgroups. Grades 3-5 treatment-related adverse events occurred in 5 (22%), 19 (76%), and 17 (89%) patients receiving pembrolizumab, pembrolizumab-chemotherapy, and EXTREME, respectively. One patient receiving pembrolizumab-chemotherapy died because of treatment-related pneumonitis., Conclusion: These results support the use of first-line pembrolizumab and pembrolizumab-chemotherapy for Japanese patients with R/M HNSCC. Clinical trial registry ClinicalTrials.gov, NCT02358031., (© 2022. Merck & Co., Inc., Rahway, NJ, USA and its affiliates.)

Competing Interests: Takashi Kanesaka has received personal fees from Olympus Corporation. Ryu Ishihara has received personal fees from Olympus Corporation and FUJIFILM Medical Co., Ltd. Other authors have no financial relationships to disclose.

Background: Brenner tumor is a rare epithelial ovarian neoplasm that accounts for 2-3% of all ovarian neoplasms. Herein, we report the first case of thoracic spinal metastasis of recurrent Brenner tumor without local recurrence.Case Description.A 70-year-old female presented with a feeling of abdominal distension. Computed tomography revealed cystic lesions in her bilateral ovaries. Blood examination revealed high CA-125 [74.9 U/ml]. We excised bilateral ovaries, uterus, and omentum. Borderline Brenner tumor was diagnosed [Ki-67 labeling index: 10 %]. Follow-up abdominal echo and CA-125 examination revealed no local recurrence. 26 months later she developed paraplegia. Magnetic resonance imaging revealed tumor in the 5th-9th thoracic vertebra and compression of spinal cord at the 6th thoracic vertebra level. Her paraplegia was progressive. We performed semi-urgent partial resection of tumor and release of spinal cord compression. Spinal metastasis from Brenner tumor was diagnosed [Ki-67 labeling index: 50-60 %]. She received adjuvant radiation of 30 Gy in 10 fractions to the 4th-10th thoracic vertebra. After radiation and rehabilitation, she was discharged home on foot. She received adjuvant radiation and chemotherapy but died 11 months after spinal surgery. An autopsy has not been performed on her, and the cause of death is unknown., Conclusion: We report the first case of thoracic metastasis of recurrent Brenner tumor without local recurrence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Inc.)

As of January 2021, the Surpass Streamline (SS) is the most recently approved flow diverter in Japan. A total of 28 Japanese patients, including 9 clinical trial patients, with 28 large or giant unruptured internal carotid artery (ICA) aneurysms, underwent SS embolization at Juntendo University Hospital. Procedural failure occurred in two patients due to the difficulty to navigate the device in the tortuous parent artery. Therefore, 26 patients with 26 aneurysms were available for clinical and anatomical assessments. Patients' mean age was 62.6 years (range 46-86), and 24 patients (92.3%) were female. Mean aneurysm size and neck width were 15.4 mm and 7.7 mm, respectively, with 20 saccular and 6 fusiform aneurysms. Seven aneurysms were symptomatic due to the aneurysmal mass effect. Twenty patients underwent a 6-month follow-up angiography to evaluate the degree of occlusion. Anatomical outcomes were 12 (60%) complete occlusion (CO), 4 (20%) residual neck (RN), and 4 (20%) residual aneurysm. Favorable aneurysm occlusion consisted of CO, and RN was achieved in 16 (80.0%). There were no significant device stenoses. Aneurysmal mass effect improved in one and was unchanged in eight patients. There were three device-related complications, namely, delayed aneurysm rupture, minor ischemic stroke, and device occlusion (11.5%). One patient with minor ischemic stroke fully recovered before 30 days, and our series showed 7.7% risk of major ipsilateral stroke and neurological death at 30 days. The SS embolization for large and giant unruptured ICA aneurysms offers satisfactory anatomical and clinical outcomes with a low risk of device-related complications.

Oral care is important for patients with head and neck cancer who undergo radiotherapy because these patients encounter various symptoms, which decrease their quality of life(QOL). Oral mucositis is considered the major side effect of radiation, and the dose-volume parameters can serve as predictors of the occurrence of severe oral mucositis. Therefore, understanding radiation treatment planning(e. g., prescription dose and irradiated volumes of the organs at risk)and providing oral healthcare before, during, and after radiotherapy are essential for maintaining patients' QOL., Methods: An RT viewer (Climb Medical Systems) was installed into the inhouse hospital information system to provide education regarding radiation treatment planning to medical staff members (dentists and nurses) by medical physicists., Results: Patients can undertake appropriate oral care before radiotherapy, and this intervention has potential for reducing the radiation-related side effect., Conclusion: Education regarding radiation treatment planning by medical physicists using the RT viewer could improve the knowledge of medical staffs regarding the predictors of radiation-induced side effects for. By introducing the appropriate intervention of oral care before radiotherapy, it may be feasible to maintain patients' QOL.

Background: The identification of predictive factors is imperative for identifying patients with optimal responses to nivolumab. We aimed to determine whether body composition parameters can predict treatment outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with nivolumab., Method: We performed a multicenter retrospective chart review of patients with recurrent and/or metastatic HNSCC treated with nivolumab between 2017 and 2020. Computed tomography images and anthropometric measures were used to determine the skeletal muscle index (SMI), subcutaneous adipose index, visceral adipose index (VAI), and body mass index. Objective response, overall survival (OS), progression-free survival (PFS), and severe immune-related adverse events (irAEs) were the main outcomes. Odds ratios (ORs) and hazard ratios (HRs) for low-index groups compared with high-index groups were calculated for these outcomes., Results: Our study comprised 114 patients with a median follow-up period of 23.1 months. Low SMI and low VAI were significantly associated with poor disease control [OR: 0.39, 95% confidence interval (CI): 0.15-0.97] and poor response (OR: 0.38, 95% CI: 0.15-0.94), respectively. Low SMI independently predicted poor OS (HR: 2.06, 95% CI: 1.16-3.67), poor PFS (HR: 1.74, 95% CI: 1.04-2.92), and increased incidence of irAEs (OR: 6.00, 95% CI: 1.04-34.61). Low VAI independently predicted poor PFS (HR 2.07, 95% CI: 1.15-3.73)., Conclusion: The SMI and VAI are predictive factors of nivolumab therapy in patients with HNSCC. Body composition indices should be assessed before nivolumab treatment for achieving optimal responses to nivolumab., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Intracranial germ cell tumors (IGCTs) are rare brain neoplasms that mainly occur in children and adolescents with a particularly high incidence in East Asian populations. Here, we conduct a genome-wide association study (GWAS) of 133 patients with IGCTs and 762 controls of Japanese ancestry. A common 4-bp deletion polymorphism in an enhancer adjacent to BAK1 is significantly associated with the disease risk (rs3831846; P = 2.4 × 10 -9 , odds ratio = 2.46 [95% CI: 1.83-3.31], minor allele frequency = 0.43). Rs3831846 is in strong linkage disequilibrium with a testicular GCTs susceptibility variant rs210138. In-vitro reporter assays reveal rs3831846 to be a functional variant attenuating the enhancer activity, suggesting its contribution to IGCTs predisposition through altering BAK1 expression. Risk alleles of testicular GCTs derived from the European GWAS show significant positive correlations in the effect sizes with the Japanese IGCTs GWAS (P = 1.3 × 10 -4 , Spearman's ρ = 0.48). These results suggest the shared genetic susceptibility of GCTs beyond ethnicity and primary sites., (© 2022. The Author(s).)

Purpose: The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m 2 ). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m 2 ) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown., Patients and Methods: In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m 2 ) or with weekly cisplatin (40 mg/m 2 ) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32., Results: Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [< 1.32], one-sided P for noninferiority = .0027 < .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm., Conclusion: Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients., Competing Interests: Naomi KiyotaHonoraria: Ono Pharmaceutical, Bristol Myers Squibb Japan, Bayer, Chugai Pharma, Merck Serono, MSD, Eisai, AstraZenecaConsulting or Advisory Role: Shift Zero, Ono Pharmaceutical, Ascent Development ServicesSpeakers' Bureau: Ono Pharmaceutical, Bristol Myers Squibb Japan, Merck Serono, Eisai, Bayer, MSD, Chugai PharmaResearch Funding: Ono Pharmaceutical (Inst), Bristol Myers Squibb (Inst), Pfizer (Inst), Roche (Inst), Rakuten Medical (Inst), Adlai Nortye (Inst) Makoto TaharaHonoraria: Merck Serono, Bristol Myers Squibb, Eisai, Ono Pharmaceutical, MSDConsulting or Advisory Role: Ono Pharmaceutical, MSD, Pfizer, Bristol Myers Squibb, Rakuten Medical, Bayer, LillyResearch Funding: Merck Sharp & Dohme (Inst), AstraZeneca (Inst), Ono Pharmaceutical (Inst), Novartis (Inst), Pfizer (Inst), Bristol Myers Squibb (Inst), Rakuten Medical (Inst), Bayer (Inst), GlaxoSmithKline (Inst), Lilly (Inst) Junki MizusawaHonoraria: Chugai Pharma, Taiho Pharmaceutical Takeshi KodairaConsulting or Advisory Role: Ono Pharmaceutical, Chugai PharmaSpeakers' Bureau: Merck Serono, Hitachi, Bristol Myers Squibb Japan, Accuray, Elekta, Ono Pharmaceutical, Canon USA, AstraZeneca, Chugai Pharma Nobuhiro HanaiHonoraria: Ono Pharmaceutical, Bristol Myers Squibb, Merck, MSD K.K, Eisai, Ethicon/Johnson & Johnson, AmcoConsulting or Advisory Role: SanwaResearch Funding: Ono Pharmaceutical, Chugai Pharma, Rakuten Medical, Bristol Myers Squibb/Ono Pharmaceutical, GlaxoSmithKline K.K, MSD K.K Hiroki HaraHonoraria: Chugai Pharma, Taiho Pharmaceutical, Merck Serono, Yakult Honsha, Lilly, Ono Pharmaceutical, Takeda, Bristol Myers Squibb, Sanofi, MSD, Daiichi Sankyo, Kyowa Hakko Kirin, BayerConsulting or Advisory Role: Ono Pharmaceutical, MSD, Lilly, Boehringer Ingelheim, Dainippon SumitomoResearch Funding: AstraZeneca (Inst), Chugai Pharma (Inst), Merck Serono (Inst), MSD (Inst), Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst), Boehringer Ingelheim (Inst), Dainippon Sumitomo Pharma (Inst), Daiichi Sankyo (Inst), Pfizer (Inst), Eisai (Inst), Incyte (Inst), BeiGene (Inst), Astellas Pharma (Inst), Bayer (Inst), Elevar Therapeutics (Inst) Kaoru TanakaHonoraria: AstraZeneca, Merck Serono, Ono Pharmaceutical, Bristol Myers Squibb, Eisai, MSD, Kyowa Kirin Co, Ltd Akihiro HommaConsulting or Advisory Role: Rakuten Medical Japan, Olympus Medical SystemsSpeakers’ Bureau: Bristol Myers Squibb Japan, Mitsubishi Tanabe Pharma, Eisai, Makichie, Merck Serono, MSD K.K, Ono Pharmaceutical, Sanofi, Nobelpharma, BayerResearch Funding: Taiho Pharmaceutical (Inst), Kyorin Pharmaceutical (Inst), Otsuka Pharmaceutical Factory (Inst), Eisai (Inst) Nobuhiko OridateSpeakers' Bureau: Ono Pharmaceutical, Bristol Myers Squibb Japan, Merck Biopharma/Japan, Taiho Pharmaceutical, MSDResearch Funding: Ono Pharmaceutical, Merck biopharma/Japan, Taiho Pharmaceutical, Daiichi Sankyo Japan Tsutomu UedaHonoraria: Mitsubishi Tanabe Pharma, Bayer, Taiho Pharmaceutical, MSD, Ono PharmaceuticalResearch Funding: Ono Pharmaceutical Kenichi NakamuraHonoraria: Bayer Yakuhin, Chugai Pharma, Taiho PharmaceuticalResearch Funding: Astellas Pharma (Inst), Eisai (Inst), Otsuka (Inst), Ono Pharmaceutical (Inst), Kyorin (Inst), Daiichi Sankyo (Inst), Taiho Pharmaceutical (Inst), Takeda (Inst), Chugai/Roche (Inst), Novartis (Inst), Pfizer (Inst), Bayer (Inst), Bristol Myers Squibb Japan (Inst), Boehringer Ingelheim Seiyaku (Inst) Ryuichi HayashiConsulting or Advisory Role: Rakuten Medical JapanNo other potential conflicts of interest were reported.

Optimal regimens using recent radiotherapy (RT) equipment for bleeding gastric cancer (GC) have not been fully investigated yet. We retrospectively reviewed the clinical data of 20 patients who received RT for bleeding GC in our institution between 2016 and 2021. Three-dimensional conformal RT was performed. The effectiveness of RT was evaluated by the mean serum hemoglobin (Hb) level and the number of transfused red blood cell (RBC) units 1 month before and after RT. The median first radiation dose was a BED of 39.9 Gy. The treatment success rate was 95% and the rebleeding rate was 10.5%. There was a significant increase in the mean Hb level (8.0 ± 1.1 vs. 9.8 ± 1.3 g/dL, p = 0.01), and a significant decrease in the mean number of transfused RBC units (6.8 ± 3.3 vs. 0.6 ± 1.5 units, p < 0.01). Severe toxicity was observed in two patients (anorexia [n = 1] and gastrointestinal [GI] perforation [n = 1]). Reirradiation was attempted in three patients (for hemostasis [n = 2] and for mass reduction [n = 1]). The retreatment success rate for rebleeding was 100%. GI perforation occurred in two patients who had received hemostatic reirradiation. Palliative RT for bleeding GC using recent technology had excellent efficacy. However, it may be associated with a risk of GI perforation.

Febrile infection-related epilepsy syndrome (FIRES) is a disease of unknown etiology, characterized by refractory frequent focal seizures, which require prolonged intensive care. We successfully treated a boy with FIRES with anti-inflammatory and immunosuppressive therapy. This case suggests that an autoimmune mechanism may play a role in the development of FIRES., Competing Interests: 6The authors have no conflicts of interest to declare., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Gastrointestinal involvement is a rare manifestation of systemic amyloidosis, and few reports have been published on localized amyloidosis of the colon. Only one case report has been published on the long-term prognosis of localized colorectal amyloidosis, and there are no previous reports on localized colorectal ATTR amyloidosis. Here, we report an 80-year-old male with localized colorectal wild-type ATTR amyloidosis who presented with edematous mucosa with vascular changes throughout the colon. He did not exhibit any symptoms or endoscopic exacerbation for 8 years after diagnosis. However, after 8 years, he developed early stage colorectal cancer and cytomegalovirus-associated ulcer. He was treated with endoscopic submucosal dissection, which was relatively challenging due to his hemorrhagic condition and poor elevation of the submucosa caused by amyloid deposits. Since the tumor was completely resected, he will undergo regular follow-up. Our review of 20 previous cases of localized colorectal amyloidosis revealed its clinical features and long-term prognosis. Specifically, ours is the second case of a diffuse pan-colon type of colorectal localized amyloidosis, which may lead to various complications, such as colorectal cancer, over a long period of time, and thus, regular follow-up is necessary., (© 2022. Japanese Society of Gastroenterology.)

Although hormonal induction of parturition in cattle results in the successful delivery of healthy calves, the risk of retained fetal membrane is significantly increased. In a previous study, a combination of the long-acting glucocorticoid, triamcinolone acetonide, with a high dose of betamethasone partially normalized the placentomal gene expression during parturition; however, the incidence of retained fetal membrane remained high. This study further explored placentomal dysfunction and aimed to elucidate the mechanism of retained fetal membrane in parturition-induced cows. In this study, transcriptome analysis revealed that enhanced glucocorticoid exposure normalized the expression of a substantial fraction of genes in the cotyledons. In contrast, a significant reduction in the multiple signaling pathway activities, including interferon signaling, was found in the caruncles during induced parturition. Real-time PCR showed that the expression of interferon-tau in the caruncles, but not interferon-alpha or interferon-gamma, was significantly lower in induced parturition than spontaneous parturition. Interferon-stimulated gene expression was also significantly decreased in the caruncles during induced parturition. These results indicate that interferon signaling could be important for immunological control in placentomes during parturition. Additionally, this suggests that interferon-tau might be a pivotal ligand for interferon receptors in the caruncles. This study revealed that peripheral blood leukocytes in prepartum cows transcribed interferon-tau. Macrophage infiltration in the placentome is known to participate in the detachment of the fetal membrane from the caruncle. Thus, this study raised the possibility that immune cells migrating into the caruncles at parturition may act as a source of ligands that activate interferon signaling.

Purpose: Among all stents available for neuroendovascular therapy, the low-profile visible intraluminal support stent bears the highest metal coverage ratio. We deployed a low-profile visible intraluminal support stent with a delivery wire or/and microcatheter system push action to shorten the low-profile visible intraluminal support stent and thus achieve a flow diversion effect. We report our single-institution experience with the use of low-profile visible intraluminal support stents for intentionally shortened deployment (shortening group) and non-shortened deployment (non-shortening group) for unruptured intracranial aneurysms., Methods: We retrospectively reviewed the medical records of 130 patients with 131 intracranial aneurysms who were treated with low-profile visible intraluminal support stent-assisted coil embolization from February 2016-January 2019. All perioperative complications were noted. Every 6 months, we re-examined the patients with cerebral angiography or magnetic resonance angiography. The outcomes of aneurysm occlusion were evaluated by the modified Raymond-Roy occlusion classification. We used the finite element method and computational fluid dynamics to investigate the hemodynamics after shortened low-profile visible intraluminal support stent deployment., Results: Immediately after treatment, the modified Raymond-Roy occlusion classification was significantly better in the shortening group than in the non-shortening group ( p <0.05). The latest angiographic outcomes showed the same tendency. Hemodynamic analysis by computational fluid dynamics suggested an adequate flow diversion effect with the use of our intentional shortening method., Conclusions: Stent-assisted coil embolization using this technique showed good results of a high complete occlusion rate and low complication rate. These findings suggest that shortened low-profile visible intraluminal support stent deployment yields a flow diversion effect and may lead to early intra-aneurysmal thrombus formation.

Flow diverter (FD) therapy using Pipeline embolization device (PED) has become an important alternative to treat internal carotid artery (ICA) aneurysms. Herein, we report the long-term outcome for 3 years after FD therapy using PED for ICA aneurysms in Japan. The patients who underwent angiographical and/or clinical follow-up for 3 years after the FD therapy using PED of large or giant unruptured ICA aneurysms from December 2012 at our university hospital are the subjects of this study. We retrospectively reviewed the in- and outpatients' medical charts, and written operative and radiological records. There were 84 patients with 90 aneurysms who could be clinically and/or angiographically followed up for 3 years. Of these, 7 aneurysms were only available for clinical follow-up. Of the remaining 83 aneurysms, 6 aneurysms had vessel occlusion due to stent thrombosis or parent artery occlusion, and 60 of the remaining 77 (77.9%) had complete occlusion. In multivariate analysis, older age (>70 years), wide neck, and non-adjunctive coiling contributed statistically significantly to incomplete occlusion. Of the 84 patients, 2 patients (2.4%) had delayed complications between 6 months and 3 years after the initial FD placement. Three patients (3.6%) had poor outcome due to postoperative major stroke complications, 2 of which were acute complications. The long-term results after FD therapy are good both angiographically and clinically. Endothelialization of the aneurysmal neck and intra-aneurysmal thrombosis contribute to complete occlusion. The primary reason for the somewhat low complete occlusion in Japan may be the patients are generally older.

Background: We have previously reported the effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) in real-world clinical practice in Japan. Here, we report long-term outcomes from this study in the overall population and subgroups stratified by subsequent chemotherapy., Methods: In this multicenter, retrospective observational study, Japanese patients with recurrent or metastatic (R/M) HNC receiving nivolumab were followed up for 2 years. Effectiveness endpoints included overall survival (OS), OS rate, progression-free survival (PFS), and PFS rate. Safety endpoints included the incidence of immune-related adverse events (irAEs)., Results: Overall, 256 patients received a median of 6.0 doses (range: 1-52) of nivolumab over a median duration of 72.5 days (range: 1-736). Median OS was 9.5 months [95% confidence interval (CI) 8.2-12.0] and median PFS was 2.1 months (95% CI 1.8-2.7). A significant difference between 2-year survivors (n = 62) and non-2-year survivors was observed by median age (P = 0.0227) and ECOG PS (P = 0.0001). Of 95 patients who received subsequent chemotherapy, 54.7% received paclitaxel ± cetuximab. The median OS and PFS from the start of paclitaxel ± cetuximab were 6.9 months (95% CI 5.9-11.9) and 3.5 months (95% CI 2.3-5.5), respectively. IrAEs were reported in 17.2% of patients. Endocrine (7.0%) and lung (4.3%) disorders were the most common irAEs; kidney disorder (n = 1) was newly identified in this follow-up analysis., Conclusions: Results demonstrated the long-term effectiveness of nivolumab and potential effectiveness of subsequent chemotherapy in patients with R/M HNC in the real-world setting. Safety was consistent with that over the 1-year follow-up., (© 2021. The Author(s).)

Glioblastomas (GBM) often acquire resistance against temozolomide (TMZ) after continuous treatment and recur as TMZ-resistant GBM (TMZ-R-GBM). Lomustine (CCNU) and nimustine (ACNU), which were previously used as standard therapeutic agents against GBM before TMZ, have occasionally been used for the salvage therapy of TMZ-R-GBM; however, their efficacy has not yet been thoroughly examined. Therefore, we investigated the antitumor effects of CCNU and ACNU against TMZ-R-GBM. As a model of TMZ-R-GBM, TMZ resistant clones of human GBM cell lines (U87, U251MG, and U343MG) were established (TMZ-R-cells) by the culture of each GBM cells under continuous TMZ treatment, and the antitumor effects of TMZ, CCNU, or ACNU against these cells were analyzed in vitro and in vivo. As a result, although growth arrest and apoptosis were triggered in all TMZ-R-cells after the administration of each drug, the antitumor effects of TMZ against TMZ-R-cells were significantly reduced compared to those of parental cells, whereas CCNU and ACNU demonstrated efficient antitumor effects on TMZ-R-cells as well as parental cells. It was also demonstrated that TMZ resistance of TMZ-R-cells was regulated at the initiation of DNA damage response. Furthermore, survival in mice was significantly prolonged by systemic treatment with CCNU or ACNU but not TMZ after implantation of TMZ-R-cells. These findings suggest that CCNU or ACNU may serve as a therapeutic agent in salvage treatment against TMZ-R-GBM., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: Dental implants without proper maintenance may lead to serious consequences, such as peri-implantitis. Peri-implantitis in patients undergoing antitumour chemotherapy can negatively affect the prognosis of treatment. The purpose of this study was to examine the association between the onset of peri-implantitis and the effects of oral hygiene management in patients with dental implants undergoing antitumour chemotherapy., Materials and Methods: Twenty-three patients (n = 23) with dental implants who received oral supportive care during malignancy chemotherapy were included. They were categorised into two groups based on the presence of peri-implantitis and were analysed for oral hygiene conditions, maintenance after implant insertion, and adverse effects such as febrile neutropenia. Statistical analysis was performed using the Fisher's exact test and the Mann-Whitney U-test, with p < 0.05 considered statistically significant., Results: The average number of implants was higher in patients with peri-implantitis; these implants generally did not receive appropriate maintenance. There were statistically significantly fewer peri-implantitis sites in patients receiving continuous implant maintenance therapy than those who did not (p < 0.05). The severity of febrile neutropenia was reduced by dental interventions., Conclusion: Dental intervention before malignancy chemotherapy effectively prevented peri-implantitis and contributed to alleviating febrile neutropenia, even when it was initiated amidst chemotherapy. Dental intervention before chemotherapy seems essential in malignancy patients with dental implants.

Competing Interests: The authors declare that they have no conflict of interest.

Purpose: Leg length discrepancy (LLD) after total hip arthroplasty (THA) prevents functional recovery and reduces patient satisfaction. We investigated impact of changes in patient-perceived LLD on patient satisfaction and walking ability., Methods: one hundred and forty-nine patients with unilateral hip osteoarthritis undergoing THA from 2014 to 2017, (125 women, 24 men; average age, 68.5 years) with an objective LLD < 1 cm were included. Outcome measures included the patient-perceived LLD, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, 10-m walking speed, and affected leg loading rate, assessed preoperatively and at 3 weeks, 3 months, and 1 year postoperatively., Results: The absolute patient-perceived LLD (mean ± SD) (the number of patients with perceived LLD > 5 mm) were 6.4 ± 9.6 mm [88 patients (59%)] preoperatively; and 2.2 ± 4.0 mm [48 (32%); p < 0.001], 0.7 ± 2.3 mm [17 (11%); p < 0.001], and 0.4 ± 1.6 mm [10 (7%); p = 0.095] at 3 weeks, 3 months, and 1 year postoperatively, respectively. All outcome measures improved over time. One year postoperatively, a weak positive correlation between the patient-perceived LLD and WOMAC or 10-m walking speed (r = 0.24, 0.23, respectively) was found. The risk of patient-perceived LLD persisting > 1 year postoperatively was 5.5-fold higher in patients who exhibited it at 3 months and those with a WOMAC score > 10 at 3 months postoperatively, using multivariate logistic regression., Conclusion: Achieving a post-THA objective LLD < 1 cm significantly reduced the patient-perceived LLD up to 3 months postoperatively. The residual patient-perceived LLD at 1 year postoperatively was predicted from the WOMAC score or the presence of patient-perceived LLD at 3 months after THA., Level of Evidence: Therapeutic level IV., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS part of Springer Nature.)

Background: Patients with advanced oral or oropharyngeal cancer sometimes require surgery and adjuvant postoperative radiotherapy (PORT), which may cause dysphagia. However, the efficacy of rehabilitation treatment for PORT-induced dysphagia remains unclear. This study aimed to determine whether rehabilitation treatment during PORT after surgery is effective for dysphagia., Methods: We retrospectively studied 55 patients with oral or oropharyngeal cancer who received PORT. Of these, 25 received rehabilitation treatment for swallowing during PORT. The Functional Oral Intake Scale (FOIS) score at 6 months after treatment was used as the swallowing outcome. We performed multivariate linear regression and stratified analyses using the FOIS score (poor oral intake group: FOIS score <5, good oral intake group: FOIS score ≧5) before PORT., Results: The median (interquartile range) FOIS scores at 6 months post-PORT were 6 (5-6) and 6 (4-7) in the non-rehabilitation and rehabilitation groups, respectively. Multivariate linear regression revealed that rehabilitation treatment was a significant independent factor for a better FOIS score. Stratified analysis of the changes in the FOIS score from pre-PORT values to those obtained 6 months after treatment showed a significant difference in the good oral intake group between the rehabilitation and non-rehabilitation groups. There was no significant difference in the FOIS score from pre-PORT values to those obtained 6 months after treatment between the rehabilitation and non-rehabilitation groups in the poor oral intake group., Conclusion: Rehabilitation treatment during PORT may achieve better swallowing outcomes in patients with advanced oral or oropharyngeal cancer., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

The ongoing development of high-temperature processes with the use of microwaves requires new microwave absorbers that are useful at these temperatures. In this study, we propose Al 4 SiC 4 powders as important and efficient microwave absorbers. We investigated both the behavioural microwave heating and electrical permittivity characteristics of Al 4 SiC 4 powders with various particle sizes at 2.45 GHz. The TE 103 single-mode cavity indicated that Al 4 SiC 4 powder samples yielded different heating behaviours and dielectric constants for each particle size compared with SiC. By microwave heating ∅50 mm × 5 mm disks of Al 4 SiC 4 and SiC, we demonstrate that for specific sizes, Al 4 SiC 4 can be heated at a higher temperature than SiC. Finally, the results of the two-dimensional two-colour thermometer show that an energy concentration appears at the interface of the microwave-heated Al 4 SiC 4 . These phenomena, which are inconsistent in individual physical property values, can be explained without contradicting microwave heating physics.