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Background : Based on results from the Japan Clinical Oncology Group (JCOG) 9204 and JCOG 9907 trials, neoadjuvant-CF (cisplatin+5-fluorouracil) followed by esophagectomy with extended lymphadenectomy is the standard treatment for patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC) in Japan. Recently, however, results from the JCOG 1109 trial revealed that neoadjuvant-DCF (docetaxel+cisplatin+5-fluorouracil) provides significantly better overall survival (OS) than neoadjuvant-CF, whereas neoadjuvant chemoradiotherapy (NACRT) did not produce significantly better outcomes than neoadjuvant-CF.Methods : We retrospectively identified 225 ESCC patients treated between December 2008 and December 2021 who received esophagectomy at Akita University Hospital. These patients were divided into neoadjuvant-CF (NAC, n=30) and NACRT (NACRT, n=195) groups before esophagectomy. Using the Kaplan-Meier method, we compared OS and disease-specific survival (DSS) between the two groups.Results : The pathological response to treatment was significantly better in the NACRT than the NAC group. Although 5-year OS and DSS were better in the NACRT than NAC group, these differences did not reach statistical significance.Conclusion : Among patients with locally advanced thoracic ESCC, NACRT produced a significantly better pathological response than NAC. However, NACRT did not produce significantly better long-term survival than NAC, which is consistent with the results of JCOG 1109.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Additional file 2: Table S1. Perioperative management protocol for COVID-19 patients in our hospital.

BACKGROUND End-diastolic opening of the pulmonary valve and subsequent antegrade diastolic pulmonary artery flow (ADPAF) reflect restrictive right ventricular (RV) physiology in children. However, this has attracted little attention in adults. PURPOSE To clarify the clinical implications of ADPAF in adults. METHODS AND RESULTS The study population consisted of 23,049 consecutive adult patients who underwent echocardiography in our hospital between 2008 and 2015. ADPAF was found in 17 patients (0.07%). The simultaneous recording of RV and pulmonary artery pressures revealed marked elevation of RV diastolic pressure, which exceeded pulmonary artery pressure at the time of atrial contraction. These results suggested that ADPAF implies RV restriction. Based on the level of tricuspid annular plane systolic excursion (TAPSE), we classified these patients into two groups: reduced RV function (R-RVF) group (12 patients with TAPSE

Human epidermal growth factor receptor 2 (HER2)-targeted agents are effective treatment for patients with HER2-positive breast cancer. However, the lack of survival benefit in HER2-negative patients as well as the toxic effects and high cost of these drugs highlight the need for accurate and prompt assessment of HER2 status. Our aim was to evaluate the clinical utility of a novel one-step, fully automated in-situ hybridization (Auto-RISH) method developed to facilitate hybridization. This method takes advantage of the non-contact mixing effect of an alternating current electric field. Eighteen specimens from patients diagnosed with primary breast cancer identified immunohistochemically as HER2 (2+) or (3+) were used. The specimens were all tested using DISH with an automated slide stainer (DISH-ASS), fluorescence in-situ hybridization, and Auto-RISH. With RISH the HER2 test was completed within 6 h, as compared to 20-22 h needed for the standard protocol. We found 88.8% agreement between standard DISH-ASS and Auto-RISH based on the status of the HER2 signals, and both methods stained nearly all samples from HER2-IHC 3+ patients equally well. These findings suggest Auto-RISH could potentially serve as an automated clinical tool for prompt determination of HER2 status in breast cancer samples.

Purpose : To evaluate the usefulness of the CT angiogram sign for solid lung masses on dynamic contrast-enhanced, thin-slice CT.Methods : Between January 2010 and March 2014, 300 patients’ lung masses were surgically resected at our institution. Of these patients, we excluded 177 patients because the CT was not obtained at our institution ; ground-glass opacity component was present ; or neoadjuvant chemotherapy was administered. The CT images were obtained in both arterial and delayed phases at 1.25-mm and 5-mm sections. We evaluated presence of the CT angiogram sign, CT value, and presence of hypo-enhanced areas.Results : Included 123 patients were 89 men and 34 women, with median age of 72 years (range, 38-86). Neither the presence of the CT angiogram sign nor contrast-enhanced pattern had significant correlation with pathologic findings.Conclusions : In our study, the CT angiogram sign was not useful in evaluating solid lung masses on dynamic contrast-enhanced, thin-slice CT.

Background Given the extent of the surgical indications for pulmonary lobectomy in breathless patients, preoperative care and evaluation of pulmonary function are increasingly necessary. The aim of this study was to assess the contribution of preoperative pulmonary rehabilitation (PR) for reducing the incidence of postoperative pulmonary complications in non‐small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD). Methods The records of 116 patients with COPD, including 51 patients who received PR, were retrospectively analyzed. Pulmonary function testing, including slow vital capacity (VC) and forced expiratory volume in one second (FEV 1), was obtained preoperatively, after PR, and at one and six months postoperatively. The recovery rate of postoperative pulmonary function was standardized for functional loss associated with the different resected lung volumes. Propensity score analysis generated matched pairs of 31 patients divided into PR and non‐PR groups. Results The PR period was 18.7 ± 12.7 days in COPD patients. Preoperative pulmonary function was significantly improved after PR (VC 5.3%, FEV 1 5.5%; P

C-reactive protein (CRP) is widely used as a biomarker of inflammation, though its functions are not fully understood. In the present study, we hypothesized that CRP reduces cancer cell invasion and migration by enhancing the expression of E-cadherin. NR-S1M cells, a murine squamous cell carcinoma line, were incubated for 48 h or 72 h with or without 10 or 50 μg/ml recombinant mouse CRP. Subsequent counts of viable cells showed that CRP had no significant effect on NR-S1M cell proliferation, nor did it affect invasion by the cells across a basement membrane matrix in Boyden chamber assays. By contrast, wound healing assays showed that CRP significantly weakened the migration potential of the cells. Moreover, Western and immunohistochemical analyses showed that CRP induced a corresponding increase in E-cadherin expression. These findings suggest that CRP may inhibit cancer cell migration, and thus metastasis, by strengthening cell-cell adhesion through increased E-cadherin expression.

Nodal micrometastasis in non-small cell lung cancer (NSCLC) is associated with a poorer survival rate than node-negative disease. Furthermore, lymph node micrometastasis often cannot be detected using conventional hematoxylin and eosin staining of frozen sections ; detection requires additional time-consuming immunohistochemical (IHC) analysis of paraffin-embedded tissue. We previously developed and reported a device that enables us to complete IHC analyses within 11 minutes. In the present study, we used this rapid-IHC protocol with an anti-cytokeratin antibody and analyzed 205 mediastinal lymph nodes dissected during surgery for NSCLC. Although we modified the original rapid-IHC procedure to block endogenous peroxidase activity, which could potentially cause misdiagnosis, the staining was still completed within 19 min. On the basis of conventional histological examination, 7 lymph nodes from 3 patients were deemed positive for micrometastasis. By contrast using hematoxylin and eosin staining, 13 lymph nodes from 7 patients were diagnosed positive on the basis of cytokeratin-detection using routine-IHC, and the same 13 nodes were diagnosed positive on the basis of rapid-IHC. That is, all nodes deemed positive with the routine-IHC procedure were also positive with the rapid-IHC procedure. Assuming the results of the routine-IHC are correct, the sensitivity, specificity and accuracy of rapid-IHC are 100%, 100% and 100%, respectively. These findings demonstrate the utility of our rapid-IHC analysis for intraoperative diagnosis of micrometastasis. However, our findings are limited by the fact that we tested the method using a single antibody at a single institute. Further investigation in multicenter studies will be needed to confirm the utility of this method.

Some cases of post-surgical acute respiratory distress syndrome (ARDS) may be an acute exacerbation of idiopathic pulmonary fibrosis (IPF) including subclinical IP, and pathological interstitial pneumonia (IP) is a predictor of the ARDS high-risk group. Although one-lung-ventilation (OLV) has become established procedure during thoracic surgery, there is little data on the re-expansion of pulmonary edema after surgery. In the present study, we evaluated the possibility that occult lung injury occurs in pathological IP patients during the early phase of thoracic surgery. [Methods] Study was performed in 22 patients who underwent pulmonary resection at our institute. Plasma levels of interleukin (IL)6, IL8 and high mobility group box protein1 (HMGB1) were measured during the pre-, peri-and postoperative periods. [Results] Serum levels of IL-6 and IL-8 increased after surgery ; however, there were no significant differences between the IP and non-IP groups. Meanwhile, serum levels of HMGB1 were significantly higher at 30 min after OLV in IP group, and those in IP group were continuously higher during the peri-and postoperative periods. [Conclusions] This study suggests that elevation of HMGB1, which might influence occult lung injury, occurred during OLV in IP group, and that it already existed before lung re-expansion.