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.

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.

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.

Background/Aims: The incidence of eosinophilic esophagitis (EoE) has been increasing recently. The role of regulatory T cells (Tregs) and correlations with other inflammatory cells in EoE remain unknown. We aim to clarify the role of Tregs and their correlations with inflammatory cells in EoE patients. Methods: Biopsies from controls and EoE patients before and after treatments were analyzed. Eosinophil infiltration was evaluated by hematoxylin and eosin staining. Immunohistochemical staining was performed to examine infiltration of T cells, Tregs, and mast cells.Gene expressions of chemokines were evaluated by reverse transcription-quantitative polymerase chain reaction. Results: Tregs and mast cells were increased in the esophageal epithelial layers of EoE patients. After treatments, Tregs and mast cells were decreased when histologic remission was achieved. Infiltration of Tregs correlated significantly with numbers of eosinophils and mast cells. Filaggrin mRNA was decreased in patients with EoE before treatment and upregulated after treatment, even when histologic remission was not achieved. Conclusions Tregs were increased in esophageal epithelium of patients with EoE, and correlated with mast cell infiltration.

Background/Aims: Non-cardiac chest pain (NCCP) is defined as recurring angina-like retrosternal chest pain of non-cardiac origin. Information about the epidemiology of NCCP in Japan is lacking. We aim to determine the prevalence and characteristics of NCCP in the Japanese general population. Methods: Two internet-based surveys were conducted among the general population in March 2017. Questions investigated the characteristics of symptoms associated with chest pain and consultation behavior. Quality of life, anxiety, depression, and gastroesophageal reflux disease were analyzed. Results: Five percent of the survey respondents reported chest pain. Subjects with chest pain showed higher frequencies of anxiety and depression and lower quality of life. Among subjects with chest pain, approximately 30% had sought medical attention for their symptoms. Among all consulters, 70% were diagnosed with NCCP. Females were less likely to seek consultations for chest pain than males. Further, severity and frequency of chest pain, lower physical health component summary score, and more frequent gastroesophageal reflux disease were associated with consultation behavior. Subjects with NCCP and cardiac chest pain experienced similar impacts on quality of life, anxiety, and depression. Among subjects with NCCP, 82% visited a primary-care physician and 15% were diagnosed with reflux esophagitis. Conclusions The prevalence of chest pain in this sample of a Japanese general population was 5%. Among all subjects with chest pain, less than one-third consulted physicians, approximately 70% of whom were diagnosed with NCCP. Sex and both the severity and frequency of chest pain were associated with consultation behavior.

Background/Aims: Diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms frequently occur in patients with quiescent Crohn’s disease (CD). To investigate the factors underlying IBS-D-like symptoms in patients with quiescent CD, we performed a comprehensive analysis of the clinical features and intestinal environment in those patients. Methods: We performed a prospective observational study of 27 patients with quiescent CD (CD activity index [CDAI] ≤ 150; C-reactive protein ≤ 0.3 mg/dL). The presence and severity of IBS-D-like symptoms, health-related quality of life, disease-specific quality of life, andstatus of depression and anxiety were evaluated. The level of intestinal permeability, fecal calprotectin and organic acids and the profiles of gut microbiome were analyzed. Results: Twelve of the 27 patients with quiescent CD (44.4%) had IBS-like symptoms, and these patients showed a significantly higher CDAI, IBS severity index and anxiety score than those without. The inflammatory bowel disease questionnaire score was significantly lower in the patients with IBS-D-like symptoms. There were no significant differences in small intestinal/colonic permeability or the levels of organic acids between the patients with and without IBS-D-like symptoms. Fusicatenibacter was significantly less abundant in the patients with IBS-D-like symptoms whereas their fecal calprotectin level was significantly higher (384.8 ± 310.6 mg/kg) than in patients without (161.0 ± 251.0 mg/kg). The receiver operating characteristic curve constructed to predict IBS-D-like symptoms in patients with quiescent CD using the fecal calprotectin level (cutoff, 125 mg/kg) showed a sensitivity and specificity of 73.3% and 91.7%, respectively. Conclusion Minimal inflammation is closely associated with the development of IBS-D-like symptoms in patients with quiescent CD.

Background/Aims: Herbal medicine is an important complementary therapy for functional dyspepsia (FD). However, its effect against gastric hypersensitivity in patients with FD has rarely been evaluated. Yokukansan (YKS), a traditional Japanese herbal medicine, is effective against neuropathic and inflammatory pain. This study aims to use a maternal separation (MS) stress-induced FD model to investigate the effects of YKS against gastric hypersensitivity, gastric motility, and duodenal micro-inflammation. Methods: The MS stress model was established by separating newborn Sprague-Dawley rats from their mothers for 2 hours a day from postnatal days 1 to 10. At the age of 7-8 weeks, the rats were treated with YKS at a dose of 5 mL/kg (1 g/kg) for 7 consecutive days. AfterYKS treatment, electromyographic activity in the acromiotrapezius muscle by gastric distention and the gastric-emptying rate were assessed. Immunohistochemical analysis of eosinophils in the duodenum and phosphorylated extracellular signal-regulated kinase(p-ERK) 1/2 in the spinal cord was performed. Results: YKS treatment suppressed MS stress-induced gastric hypersensitivity and decreased the elevated levels of p-ERK1/2 in the spinal cord.In the gastroduodenal tract, YKS inhibited eosinophil-associated micro-inflammation but did not improve gastric dysmotility. Conclusions YKS treatment improved gastric hypersensitivity by alleviating eosinophil-associated micro-inflammation in the gastroduodenal tract.This treatment may be considered an effective therapeutic option for epigastric pain and micro-inflammation in patients with FD.

BACKGROUND/AIMS: Magnesium oxide (MgO) has been frequently used as a treatment for chronic constipation (CC) since the 1980s in Japan. The aim of this study is to evaluate its therapeutic effects of MgO in Japanese CC patients. METHODS: We conducted a randomized, double-blind placebo-controlled study. Thirty-four female patients with mild to moderate constipation were randomly assigned to either placebo (n = 17) or MgO group (n = 17) 0.5 g × 3/day for 28 days. Primary endpoint was overall improvement over the 4-week study period. Secondary endpoints were changes from baseline in spontaneous bowel movement (SBM), response rates of complete spontaneous bowel movement (CSBM), stool form, colonic transit time (CTT), abdominal symptom, and quality of life. RESULTS: One patient failed to complete the medication regimen and was omitted from analysis: data from 16 placebo and 17 MgO patients were analyzed. The primary endpoint was met by 25.0% of placebo vs 70.6% of MgO group (P = 0.015). MgO significantly improved SBM changes compared to placebo (P = 0.002). However, MgO did not significantly improved response rates of CSBM compared to placebo (P = 0.76). In addition, MgO significantly improved Bristol stool form scale changes (P < 0.001) and significantly improved CTT compared to the placebo group (P < 0.001). MgO significantly improved the Japanese version of the patient assessment of constipation quality of life (P = 0.003). CONCLUSION: Our placebo-controlled study demonstrated that MgO was effective treatment for improving defecation status and shortened CTT in Japanese CC patients with mild to moderate symptoms.
Asian Continental Ancestry Group ; Colon ; Constipation ; Defecation ; Double-Blind Method ; Female ; Humans ; Japan ; Magnesium Oxide ; Magnesium ; Quality of Life ; Therapeutic Uses

BACKGROUND/AIMS: When a person is experiencing stress, corticotropin-releasing hormone (CRH) can modulate gut physiologies, such as visceral sensation or gastrointestinal motility, and its intravenous administration mimics stress-induced physiological changes. However, the influence of CRH on the esophagus is yet unknown. Accordingly, we investigated whether intravenous CRH administration increases esophageal sensitivity to electrical stimulation in healthy Japanese subjects. METHODS: Twenty healthy subjects were recruited. We quantified the initial perception threshold (IPT) every 15 minutes after CRH injection. Venous blood was collected with a cannula, and both plasma adrenocorticotropic hormone (ACTH) and cortisol were measured at pre-stimulation, 0, 30, 60, 90, and 120 minutes. The results from each time point were compared against a baseline IPT obtained before electrical stimulation was initiated. RESULTS: When compared to the baseline IPT value (16.9 ± 4.5), CRH significantly decreased electrical threshold of the esophagus at 30, 45, 60, 75 minutes (14.1 ± 4.2, 13.1 ± 5.0, 12.1 ± 5.7, 14.0 ± 5.8 minutes, P < 0.01, respectively) after CRH injection, suggesting that CRH increased esophageal sensitivity to the electrical stimulus. CRH also significantly increased plasma ACTH levels at 30 minutes (50.3 ± 17.7, P < 0.01), and cortisol levels at 30 minutes (22.0 ± 6.7 minutes, P < 0.01) and 60 minutes (20.3 ± 6.7 minutes, P < 0.01) after CRH injection, when compared to the pre-stimulation ACTH and cortisol values. CONCLUSION: Intravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity.
Administration, Intravenous ; Adrenocorticotropic Hormone ; Asian Continental Ancestry Group ; Catheters ; Corticotropin-Releasing Hormone* ; Electric Stimulation ; Esophagus ; Gastrointestinal Motility ; Healthy Volunteers ; Humans ; Hydrocortisone ; Plasma ; Sensation

BACKGROUND/AIMS: Gastric motility abnormalities have been considered to be pathophysiological features of functional dyspepsia (FD) that are closely related to dyspepsia symptoms, especially postprandial distress syndrome (PDS). The aims of this study are to (1) investigate the prevalence of gastric motility disorders and (2) evaluate the association between gastric motility abnormalities and dyspeptic symptoms using gastric scintigraphy in the PDS type of FD. METHODS: Forty healthy subjects and 94 PDS type FD patients were enrolled in the study. The volunteers and patients ingested a radiolabeled (technetium-99m) solid test meal, and scintigraphic images were recorded. Gastric accommodation and emptying were assessed by scintigraphic imaging. The patients’ dyspeptic symptoms were also explored using self-completed symptom questionnaires with 10 variables (4 scales, 0–3 points) at the same time. RESULTS: In 94 Japanese FD patients, the prevalence of impaired gastric accommodation and delayed emptying were 14.9% (14/94) and 10.6% (10/94), respectively. Gastric motility abnormalities were seen in 25.5% (24/94) of FD patients. There was no association between gastric motility abnormalities and dyspeptic symptoms. CONCLUSIONS: Gastric motility abnormalities were seen in 25.5% of Japanese PDS type FD patients. However, there was no association between gastric motility abnormalities and dyspeptic symptoms on gastric scintigraphy.
Asian Continental Ancestry Group ; Dyspepsia* ; Healthy Volunteers ; Humans ; Meals ; Prevalence* ; Radionuclide Imaging ; Stomach ; Volunteers ; Weights and Measures