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.Neonatal Isolation Increases the Susceptibility to Learned Helplessness through the Aberrant Neuronal Activity in the Ventral Pallidum of Rats
Hironori KOBAYASHI ; Manabu FUCHIKAMI ; Kenichi OGA ; Tatsuhiro MIYAGI ; Sho FUJITA ; Satoshi FUJITA ; Satoshi OKADA ; Yasumasa OKAMOTO ; Shigeru MORINOBU
Clinical Psychopharmacology and Neuroscience 2024;22(2):354-363
Objective:
Environmental deprivation, a type of childhood maltreatment, has been reported to constrain the cognitive developmental processes such as associative learning and implicit learning, which may lead to functional and morphological changes in the ventral pallidum (VP) and pessimism, a well-known cognitive feature of major depression. We examined whether neonatal isolation (NI) could influence the incidence of learned helplessness (LH) in a rat model mimicking the pessimism, and the number of vesicular glutamate transporter 2 (VGLUT2)-expressing VP cells and Penk-expressing VP cells.
Methods:
The number of escape failures from foot-shocks in the LH test was measured to examine stress-induced depression-like behavior in rats. The number of VGLUT2-expressing VP cells and Penk-expressing VP cells was measured by immunohistochemistry.
Results:
In NI rats compared with Sham rats, the incidence of LH in adulthood was increased and VGLUT2-expressing VP cells but not Penk-expressing VP cells in adulthood were decreased. VGLUT2-expressing VP cells were decreased only in the LH group of NI rats and significantly correlated with the escape latency in the LH test.
Conclusion
These findings suggest that the aberrant VP neuronal activity due to environmental deprivation early in life leads to pessimistic associative and implicit learning. Modulating VP neuronal activity could be a novel therapeutic and preventive strategy for the patients with this specific pathophysiology.
5.Delphi Method Consensus-Based Identification of Primary Trauma Care Skills Required for General Surgeons in Japan
Kazuyuki HIROSE ; Soichi MURAKAMI ; Yo KURASHIMA ; Nagato SATO ; Saseem POUDEL ; Kimitaka TANAKA ; Aya MATSUI ; Yoshitsugu NAKANISHI ; Toshimichi ASANO ; Takehiro NOJI ; Yuma EBIHARA ; Toru NAKAMURA ; Takahiro TSUCHIKAWA ; Toshiaki SHICHINOHE ; Kazufumi OKADA ; Isao YOKOTA ; Naoto HASEGAWA ; Satoshi HIRANO
Journal of Acute Care Surgery 2023;13(2):58-65
Purpose:
General surgeons at regional hospitals should have the primary trauma care skills necessary to treat critically ill trauma patients to withstand transfer. This study was conducted to identify a consensus on primary trauma care skills for general surgeons.
Methods:
An initial list of acute care surgical skills was compiled, and revised by six trauma experts (acute care surgeons); 33 skills were nominated for inclusion in the Delphi consensus survey. Participants (councilors of the Japanese Society for Acute Care Surgery) were presented with the list of 33 trauma care skills and were asked (using web-based software) to rate how strongly they agreed or disagreed (using a 5-point Likert scale) with the necessity of each skill for a general surgeon. The reliability of consensus was predefined as Cronbach’s α ≥ 0.8, and trauma care skills were considered as primarily required when rated 4 (agree) or 5 (strongly agree) by ≥ 80% participants.
Results:
There were 117 trauma care specialists contacted to participate in the Delphi consensus survey panel. In the 1st round, 85 specialists participated (response rate: 72.6%). In the 2nd round, 66 specialists participated (response rate: 77.6%). Consensus was achieved after two rounds, reliability using Cronbach’s α was 0.94, and 34 items were identified as primary trauma care skills needed by general surgeons.
Conclusion
A consensus-based list of trauma care skills required by general surgeons was developed. This list can facilitate the development of a new trauma training course which has been optimized for general surgeons.
6.Coronal Plane Gap Increases Postoperative Pseudoarthrosis after Lateral Interbody Fusion for Adult Spinal Deformity
Eijiro OKADA ; Mitsuru YAGI ; Yusuke YAMAMOTO ; Satoshi SUZUKI ; Satoshi NORI ; Osahiko TSUJI ; Narihito NAGOSHI ; Nobuyuki FUJITA ; Masaya NAKAMURA ; Morio MATSUMOTO ; Kota WATANABE
Asian Spine Journal 2022;16(3):386-393
Methods:
This study included 42 patients with ASD (two men and 40 women; 112 segments; mean, 68.5±8.4 years; and mean follow-up, 31.6±17.0 months) who underwent LIF and posterior correction surgery. The concave slot of the LIF cage was filled with an autologous iliac crest bone graft (IBG), and the convex slot with a porous hydroxyapatite/collagen (HAp/Col) composite was soaked with bone marrow aspirate. Endplate injury, the gap between vertebral endplate and cage in the coronal or sagittal plane, and fusion status were evaluated using computed tomography multiplanar reconstruction at 12 months after surgery. Moreover, the associated risk factors for pseudoarthrosis were analyzed.
Results:
Fusion at LIF segments were observed in 71.4% segments at 12 months after surgery. Fusion on the concave slot (autologous IBG side), convex slot (porous HAp/Col composite side), and both concave and convex slots were observed in 66.1%, 37.5%, and 36.6% of patients, respectively. Moreover, pseudoarthrosis was observed in 28.6% at 12 months after surgery. Consequently, logistic regression analysis of the fusion at the LIF segment revealed that the gap between the LIF cage and endplate in the coronal plane (p=0.030; odds ratio, 0.183; 95% confidence interval, 0.030–0.183) was significantly associated with pseudoarthrosis at the LIF segments.
Conclusions
ASD surgery fusion rate using LIF cages was 71.4% at 12 months after surgery. The fusion rate was higher on the concave slot filled with autologous IBG than on the convex slot filled with a porous HAp/Col composite. The gap in the coronal plane was a risk factor for pseudoarthrosis at the LIF segment.
7.Effectiveness of Duloxetine for Postsurgical Chronic Neuropathic Disorders after Spine and Spinal Cord Surgery
Osahiio TSUJI ; Shizuko KOSUGI ; Satoshi SUZUKI ; Satoshi NORI ; Narihito NAGOSHI ; Eijiro OKADA ; Nobuyuki FUJITA ; Mitsuru YAGI ; Masaya NAKAMURA ; Morio MATSUMOTO ; Kota WATANABE
Asian Spine Journal 2021;15(5):650-658
Methods:
A total of 24 patients with postsurgical chronic pain and/or numbness Numeric Rating Scale (NRS) scores of ≥4 were enrolled. All patients underwent spine or spinal cord surgery at Keio University Hospital and received daily administration of DLX for more than 3 months. The mean postoperative period before the first administration of DLX was 35.5±57.0 months. DLX was administered for more than 3 months at a dose of 20, 40, or 60 mg/day, and the degree of pain and numbness was evaluated using the NRS before administration and 3 months after administration. Effectiveness was defined as more than a 2-point decrease in the NRS score following administration.
Results:
In terms of the type of symptoms, 15 patients experienced only numbness, eight experienced both pain and numbness, and one experienced only pain. Of the 24 patients, 19 achieved effective relief with DLX. DLX was effective for all patients with postsurgical chronic pain (n=9), and it reduced postsurgical chronic numbness in 18 of 23 patients. No significant difference was observed in background spinal disorders. DLX was not effective for five patients who complained only of postsurgical chronic numbness.
Conclusions
This study reports the effectiveness of DLX for postsurgical chronic neuropathic disorders. Although DLX reduced postsurgical chronic pain (efficacy rate=100%) and numbness (78.3%) in certain patients, further investigation is needed to determine its optimal use.
8.Chronic obstructive pulmonary disease severity in middle-aged and older men with steoporosis associates with decreased bone formation
Manabu TSUKAMOTO ; Toshiharu MORI ; Eiichiro NAKAMURA ; Yasuaki OKADA ; Hokuto FUKUDA ; Yoshiaki YAMANAKA ; Ken SABANAI ; Ke-Yong WANG ; Takeshi HANAGIRI ; Satoshi KUBOI ; Kazuhiro YATERA ; Akinori SAKAI
Osteoporosis and Sarcopenia 2020;6(4):179-187
Objectives:
Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers.
Methods:
We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV1), which reflects COPD severity, and we examined the relationships between %FEV1and serum levels of bone metabolism biomarkers.
Results:
All subjects were diagnosed with osteoporosis based on T-scores. %FEV1 correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV1 moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV1 independent of other factors.
Conclusions
The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.
10.Chronic obstructive pulmonary disease severity in middle-aged and older men with steoporosis associates with decreased bone formation
Manabu TSUKAMOTO ; Toshiharu MORI ; Eiichiro NAKAMURA ; Yasuaki OKADA ; Hokuto FUKUDA ; Yoshiaki YAMANAKA ; Ken SABANAI ; Ke-Yong WANG ; Takeshi HANAGIRI ; Satoshi KUBOI ; Kazuhiro YATERA ; Akinori SAKAI
Osteoporosis and Sarcopenia 2020;6(4):179-187
Objectives:
Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers.
Methods:
We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV1), which reflects COPD severity, and we examined the relationships between %FEV1and serum levels of bone metabolism biomarkers.
Results:
All subjects were diagnosed with osteoporosis based on T-scores. %FEV1 correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV1 moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV1 independent of other factors.
Conclusions
The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.

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