1.Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya NISHIOKA ; Tae HATA ; Tadaaki YAMADA ; Yasuhiro GOTO ; Akihiko AMANO ; Yoshiki NEGI ; Satoshi WATANABE ; Naoki FURUYA ; Tomohiro OBA ; Tatsuki IKOMA ; Akira NAKAO ; Keiko TANIMURA ; Hirokazu TANIGUCHI ; Akihiro YOSHIMURA ; Tomoya FUKUI ; Daiki MURATA ; Kyoichi KAIRA ; Shinsuke SHIOTSU ; Makoto HIBINO ; Asuka OKADA ; Yusuke CHIHARA ; Hayato KAWACHI ; Takashi KIJIMA ; Koichi TAKAYAMA
Cancer Research and Treatment 2025;57(2):412-421
Purpose:
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods:
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results:
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
2.Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya NISHIOKA ; Tae HATA ; Tadaaki YAMADA ; Yasuhiro GOTO ; Akihiko AMANO ; Yoshiki NEGI ; Satoshi WATANABE ; Naoki FURUYA ; Tomohiro OBA ; Tatsuki IKOMA ; Akira NAKAO ; Keiko TANIMURA ; Hirokazu TANIGUCHI ; Akihiro YOSHIMURA ; Tomoya FUKUI ; Daiki MURATA ; Kyoichi KAIRA ; Shinsuke SHIOTSU ; Makoto HIBINO ; Asuka OKADA ; Yusuke CHIHARA ; Hayato KAWACHI ; Takashi KIJIMA ; Koichi TAKAYAMA
Cancer Research and Treatment 2025;57(2):412-421
Purpose:
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods:
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results:
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
3.Impact of TTF-1 Expression on the Prognostic Prediction of Patients with Non–Small Cell Lung Cancer with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs. Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya NISHIOKA ; Tae HATA ; Tadaaki YAMADA ; Yasuhiro GOTO ; Akihiko AMANO ; Yoshiki NEGI ; Satoshi WATANABE ; Naoki FURUYA ; Tomohiro OBA ; Tatsuki IKOMA ; Akira NAKAO ; Keiko TANIMURA ; Hirokazu TANIGUCHI ; Akihiro YOSHIMURA ; Tomoya FUKUI ; Daiki MURATA ; Kyoichi KAIRA ; Shinsuke SHIOTSU ; Makoto HIBINO ; Asuka OKADA ; Yusuke CHIHARA ; Hayato KAWACHI ; Takashi KIJIMA ; Koichi TAKAYAMA
Cancer Research and Treatment 2025;57(2):412-421
Purpose:
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non–small cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods:
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results:
This study included 283 of 624 patients. TTF-1–positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI), 5.0 to 9.4] vs. 4.1 months [95% CI, 2.7 to 6.1], p=0.03; OS: 17.9 months [95% CI, 15.2 to 28.1] vs. 9.4 months [95% CI, 6.3 to 17.0], p < 0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1–positive and –negative groups (PFS: 7.6 months [95% CI, 6.4 to 11.0] vs. 6.0 months [95% CI, 3.6 to 12.6], p=0.59; OS: 25.0 months [95% CI, 18.0 to 49.2] vs. 21.3 months [95% CI, 9.8 to 28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
4.Modulation of Nicotine-Associated Behaviour in Rats By μ-Opioid Signals from the Medial Prefrontal Cortex to the Nucleus Accumbens Shell.
Feng ZHU ; Hirosato KANDA ; Hiroyuki NEYAMA ; Yuping WU ; Shigeki KATO ; Di HU ; Shaoqi DUAN ; Koichi NOGUCHI ; Yasuyoshi WATANABE ; Kazuto KOBAYASHI ; Yi DAI ; Yilong CUI
Neuroscience Bulletin 2024;40(12):1826-1842
Nicotine addiction is a concern worldwide. Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects. However, no effective therapeutic treatment has been established. Nicotine addiction is reinforced by environments or habits. We demonstrate the neurobiological basis of the behavioural aspect of nicotine addiction. We utilized the conditioned place preference to establish nicotine-associated behavioural preferences (NABP) in rats. Brain-wide neuroimaging analysis revealed that the medial prefrontal cortex (mPFC) was activated and contributed to NABP. Chemogenetic manipulation of µ-opioid receptor positive (MOR+) neurons in the mPFC or the excitatory outflow to the nucleus accumbens shell (NAcShell) modulated the NABP. Electrophysiological recording confirmed that the MOR+ neurons directly regulate the mPFC-NAcShell circuit via GABAA receptors. Thus, the MOR+ neurons in the mPFC modulate the formation of behavioural aspects of nicotine addiction via direct excitatory innervation to the NAcShell, which may provide new insight for the development of effective therapeutic strategies.
Animals
;
Nucleus Accumbens/drug effects*
;
Prefrontal Cortex/drug effects*
;
Nicotine/pharmacology*
;
Receptors, Opioid, mu/metabolism*
;
Male
;
Rats
;
Rats, Sprague-Dawley
;
Tobacco Use Disorder/metabolism*
;
Neurons/drug effects*
;
Neural Pathways/drug effects*
5.The dynamic movement for global health ─Hot topics on migrants and refugee health!, Supports for refugees─call for empowerment, Living conditions of refugees in Japan, Tragedy of Afghanistan: ─what the international society should do now?─, The role of international NGOs in the health sector in humanitarian crises: experiences of supporting the Thai-Myanmar border in chronic emergency situations, National Institute of Population and Social Security Research/Committee for Migration and Health, JAIH
Azusa IWAMOTO ; Yasuhide NAKAMURA ; Yukie KAN ; Khaled RESHAD ; Jun KOBAYASHI ; Yuka MAEKAWA ; Yoko FUCHIGAMI ; Masumi TANAKA ; Aya TABATA ; Tomoko KAMIYA ; Chika SATO ; Koichi IKEMURA ; Ryoko TOYAMA ; Miwa SAWABE ; Tadashi TAKEUCHI ; Toshiyuki WATANABE ; Tsubasa NAKAZATO ; Hiromi NISHIO ; Nanae ARITAKA ; Reiko HAYASHI
Journal of International Health 2022;37(3):113-131
6.A large sublingual glandular branch of the lingual nerve: a rare case report
Aaron ALBUCK ; Yuto HAIKATA ; Koichi WATANABE ; R. Shane TUBBS ; Joe IWANAGA
Anatomy & Cell Biology 2022;55(3):380-383
While the route, location, and pathology of the lingual nerve has been detailed extensively in reports in the literature, its terminal branch to the sublingual gland is often overlooked. It is known, via both gross and histological observation, that the sublingual glandular branch terminates at the posterior aspect of the sublingual gland. Upon routine cadaveric dissection of a male cadaver, one of the lingual nerve branches was found to terminate at the anteroinferior portion of a herniated sublingual gland. This specific course has not previously been discussed or reported via gross or histological observation. Therefore, a timely review of the lingual nerve’s terminal sublingual glandular branch’s anatomy and clinical significance pertaining to this case is warranted. Surgeons who treat patients with submental masses should be aware of the anatomy of this nerve and the potential variance described here in order to avoid postprocedural complications.
7.Heartburn, Functional Dyspepsia, Anxiety/Depression, and Sleep Disturbances Are Associated With Clinically Significant Belching
Yasuhiro FUJIWARA ; Masatsugu OKUYAMA ; Yasuaki NAGAMI ; Koichi TAIRA ; Hirotaka ISHIZU ; Osamu TAKAISHI ; Hiroshi SATO ; Toshio WATANABE
Journal of Neurogastroenterology and Motility 2021;27(4):581-587
Background/Aims:
Belching is the act of expelling gas from the stomach or esophagus noisily through the oral cavity. Although it is a physiological phenomenon, belching may also be a symptom of upper gastrointestinal diseases such as reflux esophagitis and functional dyspepsia (FD). A detailed epidemiology of belching has not yet been reported. The aim of this study is to examine the prevalence and clinical characteristics of clinically significant belching (CSB) in adults.
Methods:
We analyzed 1998 subjects who visited the hospital for annual health checkups. Belching was evaluated by a simple question “Do you burp a lot?” and scored as 0 (never), 1 (occasionally), 2 (sometimes), 3 (often), or 4 (always). Subjects with CSB were defined ashaving scores ≥ 3. We also collected the clinical parameters, endoscopic findings, and data according to the Athens Insomnia Scale, Rome IV questionnaire, and Hospital Anxiety and Depression Scale (HADS).
Results:
Of the 1998 subjects, 121 (6.1%) had CSB. Subjects with CSB had FD more commonly than reflux esophagitis, but presence of heartburn was high (10.7% vs 3.1%). In addition, the HADS and Athens Insomnia Scale scores in subjects with CSB were significantly higher than those in subjects without CSB. Presence of heartburn (OR, 2.07; 95% CI, 1.05-4.09), presence of FD (OR, 2.12; 95% CI, 1.33-3.36), anxiety/depression (OR, 2.29; 95% CI 1.51-3.45), and sleep disturbances (OR, 1.73; 95% CI, 1.14-2.61) were significantly associated with CSB.
Conclusion
The detailed epidemiology of belching in the general adult population was clarified.
8.Heartburn, Functional Dyspepsia, Anxiety/Depression, and Sleep Disturbances Are Associated With Clinically Significant Belching
Yasuhiro FUJIWARA ; Masatsugu OKUYAMA ; Yasuaki NAGAMI ; Koichi TAIRA ; Hirotaka ISHIZU ; Osamu TAKAISHI ; Hiroshi SATO ; Toshio WATANABE
Journal of Neurogastroenterology and Motility 2021;27(4):581-587
Background/Aims:
Belching is the act of expelling gas from the stomach or esophagus noisily through the oral cavity. Although it is a physiological phenomenon, belching may also be a symptom of upper gastrointestinal diseases such as reflux esophagitis and functional dyspepsia (FD). A detailed epidemiology of belching has not yet been reported. The aim of this study is to examine the prevalence and clinical characteristics of clinically significant belching (CSB) in adults.
Methods:
We analyzed 1998 subjects who visited the hospital for annual health checkups. Belching was evaluated by a simple question “Do you burp a lot?” and scored as 0 (never), 1 (occasionally), 2 (sometimes), 3 (often), or 4 (always). Subjects with CSB were defined ashaving scores ≥ 3. We also collected the clinical parameters, endoscopic findings, and data according to the Athens Insomnia Scale, Rome IV questionnaire, and Hospital Anxiety and Depression Scale (HADS).
Results:
Of the 1998 subjects, 121 (6.1%) had CSB. Subjects with CSB had FD more commonly than reflux esophagitis, but presence of heartburn was high (10.7% vs 3.1%). In addition, the HADS and Athens Insomnia Scale scores in subjects with CSB were significantly higher than those in subjects without CSB. Presence of heartburn (OR, 2.07; 95% CI, 1.05-4.09), presence of FD (OR, 2.12; 95% CI, 1.33-3.36), anxiety/depression (OR, 2.29; 95% CI 1.51-3.45), and sleep disturbances (OR, 1.73; 95% CI, 1.14-2.61) were significantly associated with CSB.
Conclusion
The detailed epidemiology of belching in the general adult population was clarified.
10.Administration of Corticosteroids Is Effective for Hyperactive Delirium Due to Intravascular Large B-cell Lymphoma: A Case Report
Rika KIHARA ; Yumi YAMAZOE ; Yasuyuki ASAI ; Yoshiya ADACHI ; Kyoko KUWABARA ; Masahiko FUJINO ; Satoru SABURI ; Takuya ODAGIRI ; Koichi WATAMOTO ; Hiroaki WATANABE
Palliative Care Research 2020;15(3):199-204
Introduction: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of non-Hodgkin lymphoma. Patients with IVLBCL frequently have neurological symptoms associated with cerebrovascular infarction or central nervous system involvement of malignant lymphoma. Case: A 67-year-old man consulted the Department of Hematology at our hospital because of fever of unknown origin, anemia and increased serum lactate dehydrogenase. Although IVLBCL was strongly suspected, no lymphoma cells were found by multiple bone marrow aspirations and skin biopsies. Two months later, he developed hyperactive delirium, which was difficult to manage using antipsychotic agents. Brain MRI revealed multiple hyper-intense infarct-like lesions on diffusion-weighted images. After assessment of bone marrow aspiration and skin biopsies, he was administered an enough dose of prednisolone to manage malignant lymphoma. Hyperactive delirium rapidly improved. Discussion: In patients with IVLBCL, corticosteroids may be useful to manage hyperactive delirium due to cerebrovascular infarction or central nervous system involvement of IVLBCL.


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