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.Two Cases of Orthostatic Dysregulation Successfully Treated with Shakanzoto
Takashi NISHIMOTO ; Naoki OKADA ; Shinji NISHIDA
Kampo Medicine 2024;75(2):132-137
		                        		
		                        			
		                        			Orthostatic dysregulation arises primarily from venous pooling in the lower extremities due to abnormal regulation of the autonomic nervous system. This leads to altered central blood volume, which reduces cardiac output and circulating blood volume, resulting in difficulties in rising, dizziness, fatigue, nausea, and palpitations. The treatment of orthostatic dysregulation typically involves non-pharmacological measures such as salt and water supplementation, as well as pharmacological interventions including midodrine hydrochloride. Here, we present two cases of orthostatic dysregulation that were effectively treated with shakanzoto, a Kampo medicine. Case 1 was a 15-year-old boy who had been experiencing fatigue, difficulty in rising, and palpitations in the morning for two years, resulting in his inability to attend school for six months. He was diagnosed with orthostatic dysregulation in accordance with the Japan Clinical Guidelines on Psychosomatic Diseases in Childhood and was administered shakanzoto, after which his symptoms were resolved by day 14 of the follow-up visit, enabling him to attend school. Case 2 involved a 14-year-old girl who had been experiencing fatigue, nausea, dizziness, and palpitations in the morning for five years and was also diagnosed with orthostatic dysregulation in accordance with the aforementioned guidelines. She was administered shakanzoto and her symptoms resolved by the fourth day, allowing her to return to school. To date, the effectiveness of shakanzoto for the treatment of orthostatic dysregulation has not been reported. Nonetheless, shakanzoto may be considered as a potential addition to the treatment for orthostatic dysregulation.
		                        		
		                        		
		                        		
		                        	
5.Mitral Valve Repair for Failed MitraClip: a Case Report
Shintaro KUWAUCHI ; Mitsuharu HOSONO ; Tomohiko UETSUKI ; Masato OHNO ; Hideki SAKASHITA ; Takayuki OKADA ; Nobuya ZEMPO ; Naoki MINATO ; Kohei KAWAZOE
Japanese Journal of Cardiovascular Surgery 2023;52(6):396-400
		                        		
		                        			
		                        			The patient was an 89-year-old male who underwent transcatheter edge-to-edge repair to the mitral valve using MitraClip for severe degenerative mitral regurgitation (MR) one year earlier. Although two clips were implanted, grade III/IV MR still remained. As his heart failure progressed, he was referred to us for surgery. The patient also had aortic stenosis. He underwent mitral valve repair and aortic valve replacement. The postoperative course was uneventful. He was transferred to the referring hospital on postoperative day 14. When performing MitraClip for degenerative MR, it is important to consider carefully not only the operative risk for open surgery but also the anatomical adequacy of MitraClip. When MitraClip fails to control MR, early surgical intervention should be considered.
		                        		
		                        		
		                        		
		                        	
6.Two Cases of Chronic Cough Successfully Treated with Kumibinroto
Tomoe FUKUNAGA ; Daizo KISHINO ; Seiichiro USUKI ; Naoki OKADA ; Kentaro IWATA ; Takashi NISHIMOTO
Kampo Medicine 2020;71(1):77-81
		                        		
		                        			
		                        			Cough-variant asthma is the most common cause of chronic cough. It may progress to classic asthma and therefore requires adequate treatment intervention. We experienced two cases of cough-variant asthma that was refractory to standard drug therapy but improved after additional administration of kumibinroto. In Case 1, the patient was a 46-year-old woman receiving hormone therapy after breast cancer surgery. She developed cough-variant asthma 5 years ago, and though she has received drug therapy, the symptoms aggravated. Cough continued to appear at night without improvement of asthma symptoms. However, the symptoms improved with subsequent administration of kumibinroto. In Case 2, the patient was a 47-year-old woman who developed cough-variant asthma after childbirth, which repeatedly worsened and improved. The cough-variant asthma aggravated after change of workplace and did not improve with drug therapy. However, asthma symptoms improved with oral administration of kumibinroto and hangekobokuto, and subsequent administration of kumibinroto alone. In both patients, the asthma was seasonal. These cases suggest that kumibinroto administration may contribute to the improvement of cough-variant asthma.
		                        		
		                        		
		                        		
		                        	
7.Use of VIABAHN Stent Graft for Subclavian Artery Injury due to Inadvertent Catheter Placement
Shintaro KUWAUCHI ; Nobuya ZEMPO ; Hideki SAKASHITA ; Tomohiko UETSUKI ; Naoki TANIGUCHI ; Takayuki OKADA ; Mitsuharu HOSONO ; Shinya KANEMOTO ; Kohei KAWAZOE ; Naoki MINATO
Japanese Journal of Cardiovascular Surgery 2020;49(2):86-89
		                        		
		                        			
		                        			A 77-year-old man presenting with uremic acidosis was referred to our department for a misplaced vascular access catheter. Computed tomography revealed the catheter was passing through the subclavian artery and terminating in the ascending aorta. Under angio-fluoroscopic monitoring, a VIABAHN stent graft was deployed immediately after removing the catheter. The patient had no hemorrhagic complication although continuous hemodiafiltration was started just after surgery. His postoperative course was uneventful.
		                        		
		                        		
		                        		
		                        	
8.A “Back Light System” for Identification of Sites for Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Solid Pancreatic Masses: A Prospective, Randomized Study with a Crossover Design
Ryo HARADA ; Hironari KATO ; Soichiro FUSHIMI ; Hirofumi INOUE ; Daisuke UCHIDA ; Yutaka AKIMOTO ; Takeshi TOMODA ; Kazuyuki MATSUMOTO ; Yasuhiro NOMA ; Naoki YAMAMOTO ; Shigeru HORIGUCHI ; Koichiro TSUTSUMI ; Hiroyuki OKADA
Clinical Endoscopy 2019;52(4):334-339
		                        		
		                        			
		                        			BACKGROUND/AIMS: We applied a back light system (BLS) with a magnifying glass to improve the ability to assess the adequacy of specimen sampling using endosonography. We conducted this study to evaluate the efficacy of the BLS in sampling of specimens by endoscopic ultrasound-guided fine needle aspiration of solid pancreatic masses. METHODS: This was a prospective, randomized, crossover, single-center clinical trial. An endosonographer evaluated adequacy on gross visual inspection and identified whitish specimen sampling sites with and without the BLS according to a randomization sequence in the first and second passes with a 25-G needle. On cytological evaluation, the presence of well-defined pancreatic ductal epithelium was evaluated by a cytopathologist who was blinded to any clinical information. RESULTS: A total of 80 consecutive patients were eligible during the study period. Adequacy was observed for 52 specimens (65%) with the BLS and 54 (68%) without the BLS (p=0.88). In assessment of specimen adequacy on gross examination, only fair agreement was observed both with and without BLS (kappa score 0.40 and 0.29, respectively). CONCLUSIONS: The BLS did not influence the ability to identify specimen sampling sites or reliable assessment of specimen site adequacy using gross visual inspection.
		                        		
		                        		
		                        		
		                        			Biopsy, Fine-Needle
		                        			;
		                        		
		                        			Cross-Over Studies
		                        			;
		                        		
		                        			Endoscopic Ultrasound-Guided Fine Needle Aspiration
		                        			;
		                        		
		                        			Endosonography
		                        			;
		                        		
		                        			Epithelium
		                        			;
		                        		
		                        			Glass
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Needles
		                        			;
		                        		
		                        			Pancreatic Ducts
		                        			;
		                        		
		                        			Pancreatic Neoplasms
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Random Allocation
		                        			
		                        		
		                        	
9.Depression Promotes the Onset of Irritable Bowel Syndrome through Unique Dysbiosis in Rats
Takeshi TAKAJO ; Kengo TOMITA ; Hanae TSUCHIHASHI ; Shingo ENOMOTO ; Masaaki TANICHI ; Hiroyuki TODA ; Yoshikiyo OKADA ; Hirotaka FURUHASHI ; Nao SUGIHARA ; Akinori WADA ; Kazuki HORIUCHI ; Kenichi INABA ; Yoshinori HANAWA ; Naoki SHIBUYA ; Kazuhiko SHIRAKABE ; Masaaki HIGASHIYAMA ; Chie KURIHARA ; Chikako WATANABE ; Shunsuke KOMOTO ; Shigeaki NAGAO ; Katsunori KIMURA ; Soichiro MIURA ; Kunio SHIMIZU ; Ryota HOKARI
Gut and Liver 2019;13(3):325-332
		                        		
		                        			
		                        			BACKGROUND/AIMS: Although studies using conventional animal models have shown that specific stressors cause irritable bowel syndrome (IBS), it is unclear whether depression itself causes IBS. Our aim was to establish a rat model to determine if depression itself promotes the onset of IBS and to elucidate the role of gut microbiota in brain-gut axis pathogenesis during coincident depression and IBS. METHODS: Rat models of depression were induced using our shuttle box method of learned helplessness. Visceral hypersensitivity was evaluated by colorectal distension (CRD) to diagnose IBS. Gut microbiota compositions were analyzed using high-throughput sequencing. In the subanalysis of rats without depression-like symptoms, rats with posttraumatic stress disorder (PTSD) were also examined. RESULTS: The threshold value of CRD in depressed rats was significantly lower than that in control rats. Microbial community analysis of cecal microbiota showed that the relative abundance of Clostridiales incertae sedis, the most prevalent microbe, was significantly lower in depressed rats than in control rats. The distribution pattern of the microbiota clearly differed between depressed rats and control rats. Neither visceral hypersensitivity nor the composition of gut microbiota was altered in rats with PTSD-like phenotypes. CONCLUSIONS: Our rat model of depression is useful for clarifying the effect of depression on IBS and suggests that depression itself, rather than specific stressors, promotes the onset of IBS. Further, we provided evidence that various psychiatric diseases, viz., depression and PTSD, are associated with unique gut microbiota profiles, which could differentially affect the onset and progression of coincident IBS.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Clostridiales
		                        			;
		                        		
		                        			Depression
		                        			;
		                        		
		                        			Dysbiosis
		                        			;
		                        		
		                        			Gastrointestinal Microbiome
		                        			;
		                        		
		                        			Helplessness, Learned
		                        			;
		                        		
		                        			Hypersensitivity
		                        			;
		                        		
		                        			Irritable Bowel Syndrome
		                        			;
		                        		
		                        			Methods
		                        			;
		                        		
		                        			Microbiota
		                        			;
		                        		
		                        			Models, Animal
		                        			;
		                        		
		                        			Phenotype
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Stress Disorders, Post-Traumatic
		                        			
		                        		
		                        	
10.A Study about “YARIGAI” : What Makes Work Worth Doing for the Community Pharmacists Who Participated in a Workshop of the COMPASS Project
Masaki Shoji ; Mitsuko Onda ; Hiroshi Okada ; Yukio Arakawa ; Naoki Sakane
Japanese Journal of Social Pharmacy 2014;33(1):2-7
		                        		
		                        			
		                        			Objective : By extracting and modeling the component factors that community pharmacists have for “YARIGAI”—a Japanese colloquial expression commonly defined as “something worthwhile doing”—and by re-defining “YARIGAI,” we sought to help improve the quality of work lives of community pharmacists. Methods : All of 139 employee pharmacists participated in a workshop of the COMPASS Project (May 2011) were surveyed using a self-administered questionnaire. Responses were collected on the scene. The seventeen, 6-point-scale questions focused on the “patient-pharmacist relationship,” which may be related to “YARIGAI.” Then “YARIGAI” factors were extracted using factor analysis, and modeled using covariance structure analysis. IBM SPSS (ver. 20) and Amos 5.0J were used for the analyses. Results : To the item “I feel ‘YARIGAI’ with pharmacy work,” 12.2% of the 139 respondents said, “Strongly agree”, followed by “Agree” (41.0%) and “Somewhat agree” (33.8%). A factor analysis extracted three factors related to “YARIGAI” (knowledge, patient counseling management, and sense of personal growth). After modeling (AGFI : 0.903, RMSEA : 0.048) with these factors as latent variables and items in them as observable variables, a positive correlation was indicated for all the following factor pairs : “knowledge” and “patient counseling management”, “knowledge” and “sense of personal growth”, and “sense of personal growth” and “patient counseling management” (standardized points of estimate : 0.71, 0.55, and 0.42, respectively). Standardized coefficients for all latent and observable variables were 0.7 or higher, showing a good fit. Conclusion : “YARIGAI” of pharmacists employed by community pharmacies can consist of “knowledge,” “patient counseling management,” and “sense of personal growth”. Our results suggest that the improvement of communication skills and knowledge can lead to improvement of “YARIGAI” of pharmacists working for community pharmacies.
		                        		
		                        		
		                        		
		                        	
            

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