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Ryo Uemura,1 Yukihiro Nagatani,1 Masayuki Hashimoto,2,3 Yasuhiko Oshio,3 Akinaga Sonoda,1 Hideji Otani,1 Jun Hanaoka,3 Yoshiyuki Watanabe1 1Department of Radiology, Shiga University of Medical Science, Otsu, Shiga, Japan; 2Department of Thoracic Surgery, Kyoto Medical Center, Kyoto, Kyoto, Japan; 3Division of General Thoracic Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, JapanCorrespondence: Ryo Uemura; Yukihiro Nagatani, Department of Radiology, Shiga University of Medical Science, Seta-tsukinowa-cho, Otsu, Shiga, Japan, 520-2192, Tel/Fax +81-77-548-2536, Email uemurar@belle.shiga-med.ac.jp; yatsushi@belle.shiga-med.ac.jpPurpose: To correlate the ratio of the non-dependent to dependent aspects of the maximal pleural movement vector (MPMVND/D) and gravity-oriented collapse ratio (GCRND/D), and the mean lung field density (MLD) obtained using four-dimensional (4D) dynamic-ventilation computed tomography (DVCT) with airflow limitation parameters and the Brinkman index.Materials and Methods: Forty-seven patients, including 22 patients with COPD, 13 non-COPD smokers, and 12 non-smokers, with no/slight pleural adhesion confirmed using a thoracoscope, underwent 4D-DVCT with 16 cm coverage. Coordinates for the lung field center, as well as ventral and dorsal pleural points, set on the central trans-axial levels in the median and para-median sagittal planes at end-inspiration, were automatically measured (13– 17 frame images, 0.35 seconds/frame). MPMVND/D and GCRND/D were calculated based on MPMV and GCR values for all the included points and the lung field center. MLD was automatically measured in each of the time frames, and the maximal change ratio of MLD (MLDCR) was calculated. These measured values were compared among COPD patients, non-COPD smokers, and non-smokers, and were correlated with the Brinkman index, FEV1/FVC, FEV1 predicted, RV/TLC, and FEF25– 75% using Spearman’s rank coefficients.Results: MPMVND/D was highest in non-smokers (0.819± 0.464), followed by non-COPD smokers (0.405± 0.131) and patients with COPD (− 0.219± 0.900). GCRND/D in non-smokers (1.003± 1.384) was higher than that in patients with COPD (− 0.164± 1.199). MLDCR in non-COPD smokers (0.105± 0.028) was higher than that in patients with COPD (0.078± 0.027). MPMVND/D showed positive correlations with FEV1 predicted (r=0.397, p=0.006), FEV1/FVC (r=0.501, p< 0.001), and FEF25– 75% (r=0.368, p=0.012). GCRND/D also demonstrated positive correlations with FEV1 (r=0.397, p=0.006), FEV1/FVC (r=0.445, p=0.002), and FEF25– 75% (r=0.371, p=0.011). MPMVND/D showed a negative correlation with the Brinkman index (r=− 0.398, p=0.006).Conclusion: We demonstrated that reduced MPMVND/D and GCRND/D were associated with respiratory functional indices, in addition to a negative association of MPMVND/D with the Brinkman index, which should be recognized when assessing local pleural adhesion on DVCT, especially for ventral pleural aspects.Keywords: chronic obstructive pulmonary disease, smoking burden, four-dimensional dynamic-ventilation computed tomography, pleural movement, mean lung density, gravity-oriented distance

Yukihiro Nagatani,1 Masayuki Hashimoto,2 Norihisa Nitta,1 Yasuhiko Oshio,2 Tsuneo Yamashiro,3 Shigetaka Sato,1 Shinsuke Tsukagoshi,4 Hiroshi Moriya,5 Tatsuya Kimoto,6 Tomoyuki Igarashi,2 Noritoshi Ushio,1 Akinaga Sonoda,1 Hideji Otani,1 Jun Hanaoka,2 Kiyoshi Murata1On behalf of investigators of the ACTIve Study Group1Department of Radiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; 2Department of Surgery, Division of General Thoracic Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; 3Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan; 4CT System Division, Canon Medical Systems, Otawara, Tochigi 324-8550, Japan; 5Department of Radiology, Ohara General Hospital, Fukushima, Fukushima 960-8611, Japan; 6Healthcare IT Development Center, Canon Medical Systems, Otawara, Tochigi 324-8550, JapanPurpose: The purpose of this study was to measure changes in lung density and airway dimension in smokers in the lateral position using four-dimensional dynamic-ventilation computed tomography (CT) during free breathing and to evaluate their correlations with spirometric values.Materials and methods: Preoperative pleural adhesion assessments included dynamic-ventilation CT of 42 smokers (including 22 patients with COPD) in the lateral position, with the unoperated lung beneath (dependent lung). The scanned lungs’ mean lung density (MLD) and the bilateral main bronchi’s luminal areas (Ai) were measured automatically (13–18 continuous image frames, 0.35 seconds/frame). Calculations included cross-correlation coefficients (CCCs) between the MLD and Ai time curves, and correlations between the quantitative measurements and spirometric values were evaluated by using Spearman’s rank coefficient.Results: The ΔMLD1.05 (from the peak inspiration frame to the third expiratory frame, 1.05 seconds later) in the nondependent lung negatively correlated with FEV1/FVC (r=-0.417, P

Abstract Introduction Tracheo-brachiocephalic artery fistulae are critical long-term complications after tracheostomy, reported in 0.6% of patients within three to four weeks after the procedure. In 30% to 50% of cases there is some bleeding prior to onset. Since the onset involves sudden massive bleeding, the prognosis is poor; the reported survival rate is 10% to 30%. The direct cause of bleeding is the formation of a fistula with the trachea subsequent to arterial injury by the tracheostomy tube. Endo-tracheal factors are movement of the tracheostomy tube due to body movement and seizures, pressure exerted by the cuff of the tracheostomy tube, tracheostomy at lower levels, and the fragility of blood vessels and the trachea due to steroid or radiation therapy, and malnutrition. Extra-tracheal factors include prior surgery and deformity and shifting of the trachea and major blood vessels due to congenital kyphoscoliosis or thoracic deformity. There has been no report of the usefulness of contrast-enhanced computed tomography studies to identify the anatomical relationship between the trachea and brachiocephalic artery. Case presentation A 27-year-old Mongolian woman with congenital muscular dystrophy who underwent tracheal intubation for airway management due to pneumonia and granulation development developed a tracheo-brachiocephalic artery fistula during the placement of the tracheostomy tube. It was diagnosed by contrast-enhanced chest computed tomography and repaired. About a month later she developed massive airway bleeding during replacement of the tracheostomy tube. Temporary hemostasis was achieved by compression via cuff inflation. A contrast-enhanced chest computed tomography scan demonstrated a narrowed brachiocephalic artery running along and ventral to the tube and a tracheo-brachiocephalic artery fistula was suspected. She underwent brachiocephalic artery resection and aorta, right common carotid artery, and subclavian artery bypass surgery with an innominate vein, tracheoplasty, and partial sternectomy. We noted marked thoracic deformity; the brachiocephalic artery was compressed by the trachea and chest wall resulting in localized wall necrosis and the development of a tracheo-brachiocephalic artery fistula, a fatal complication whose prevention is important. Conclusions We suggest that before tracheostomy, the anatomic relationship between the trachea and brachiocephalic artery must be confirmed by contrast-enhanced chest computed tomography scan.

Patients with lung cancer have a high incidence of tumor recurrence even after curative surgical resection. Some reports indicated that immunosuppressive cells induced by surgical stress could contribute to tumor recurrence after surgery; however, the underlying mechanisms are not fully understood. In this study, we found that increased postoperative blood monocytes served as a risk factor for tumor recurrence in 192 patients with non-small cell lung cancer (NSCLC). We established the lung cancer recurrent mouse model after tumor resection and showed that the surgical stress immediately increased the level of serum monocyte chemoattractant protein-1 (MCP-1), which subsequently increased blood monocytes. These blood monocytes were rapidly recruited into distant micrometastases and became tumor growth-promoting tumor associated macrophages (TAMs). Furthermore, even after the blood MCP-1 and monocytes decreased enough 72 h after tumor resection, TAMs in micrometastases remained rich because the MCP-1 secreted by micrometastases themselves continued to recruit monocytes around the tumor. Consequently, tumor resection triggered the outgrowth of distant metastases via the MCP-1-Monocyte-TAM axis. When we administered the MCP-1 inhibitor to the lung cancer recurrent model mice, blood monocytes decreased after tumor resection, and TAMs in micrometastases also dramatically decreased. Finally, peri- and postoperative treatment with the MCP-1 inhibitor suppressed distant metastases after surgery. Targeting the MCP-1-Monocyte-TAM axis may inhibit surgical stress-induced NSCLC recurrence by attenuating postoperative immunosuppressive monocytes in micrometastases., (© 2024. The Author(s).)

This report details two cases of right upper-lobe lung cancer, of patients aged 62 and 56 years, requiring complex bronchoplasty and thoracoscopic surgeries. In both cases, owing to intraoperative complications, extended thoracotomies were performed to gain access to the right main pulmonary artery. The postoperative courses were uneventful, implying that this approach was safe. Uncomplicated postoperative recoveries underscore the need for adaptable surgical techniques, especially when traditional positioning fails. It emphasizes extending thoracotomy incisions for safer hilar structure access, offering insights for handling similar complex surgeries where standard methods falter., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: In the quantitative assessment of pulmonary blood flow, two different processing algorithms [cross-correlation calculation processing (CCC-pro) and reference frame subtraction processing (RFS-pro)] within dynamic imaging systems have been reported to exhibit high correlations with conventional measurement methods. However, reports still need to evaluate these two processing algorithms regarding the different aspects of pulmonary blood flow. This study aimed to analyze the differences in pulmonary circulation., Methods: We conducted a cross-sectional study to evaluate patients with lung cancer who underwent radical surgery, simultaneous dynamic chest radiography (DCR), and pulmonary perfusion scintigraphy (PPS). We assessed the correlation between PPS and two algorithms (CCC-pro and RFS-pro) regarding calculated blood flow ratio (BFR) using Pearson's correlation and linear regression analysis. Additionally, we evaluated consistency using the Bland-Altman analysis. We compared the pulmonary blood flow distributions across six-division lung fields and evaluated each method's blood flow images and histograms of pixel values., Results: From May 2018 to December 2020, we consecutively enrolled 46 patients with lung cancer who met the inclusion criteria (40 male patients, with a mean age of 72.91 years). In these patients, CCC-pro and RFS-pro were correlated (R=0.718, P<0.01); however, CCC-pro was more strongly correlated with PPS than RFS-pro (R=0.859, P<0.01 vs. R=0.549, P<0.01). The Bland-Altman analysis showed high agreement, although systematic errors were observed in relationships other than RFS-pro to PPS. CCC-pro and RFS-pro showed similar blood flow distributions in the upper and lower lung fields, with RFS-pro being dominant in the middle. RFS-pro showed higher pixel values in the hilar region and a histogram shape similar to PPS; however, posture affected the right upper lung field gradient. RFS-pro showed no difference in the BFR when the pulmonary artery region was symmetric; however, potential inaccuracies existed when it overlapped with the cardiovascular shadow., Conclusions: The CCC-pro algorithm was useful for quantifying BFRs, whereas the RFS-pro algorithm accurately evaluated blood flow distribution in lung fields. Further algorithm development is required to enable versatile pulmonary blood flow analysis., Competing Interests: Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-152/coif). J.H. received a research grant from Konica Minolta Inc. The author has no other conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background and Aim: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue., Methods: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data., Results: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001)., Conclusion: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

There have rarely been reports on the neoplastic transformation in other organs during immunotherapy for lung cancer. We report the case of a 71-year-old man who was diagnosed with advanced pulmonary adenocarcinoma and a thyroid tumor. The patient responded to chemoradiotherapy but developed a recurrence of pulmonary metastasis. Therefore, nivolumab was started, and a complete response for pulmonary metastasis was achieved. After 32 nivolumab cycles, he experienced neck pain, and the thyroid tumor grew rapidly. Histological examination revealed anaplastic thyroid carcinoma. Although rare, immunotherapy for lung cancer has the potential to induce neoplastic transformation in other organs., Competing Interests: No conflict of interest., (© 2024 The Authors. Published by Elsevier Ltd.)

Background/aim: Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy., Methods: From 2000 to 2022, 528 patients with Child-Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated., Results: Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each P < 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each P < 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each P < 0.05)., Conclusion: HCC patients treated by RFA and with a high AD-ON score (≧2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC., (© 2024. Japanese Society of Gastroenterology.)

Introduction Postoperative bile leakage (POBL) has emerged as a complication following hepatectomy. POBL is associated with an elevated risk of liver failure and surgical death. This study aimed to examine risk factors for POBL in primary hepatocellular carcinoma (HCC) patients. Methods A total of 296 patients who had surgical resection for a preoperative diagnosis of primary HCC from January 2013 to December 2022 at Ehime Prefectural Central Hospital were included in this study. The patients were categorized into two groups based on the presence of POBL. The preoperative, operative, and histopathological findings were analyzed between the two groups. Risk factors were determined using multivariable analysis. Results Regarding preoperative findings, statistically significant differences were observed in white blood cell count, platelet count, C-reactive protein (CRP) level, and CRP-to-Albumin ratio (CAR) between the two groups (p = 0.023, p = 0.025, p = 0.011, and p = 0.012, respectively). As for intraoperative variables, only operation time (p = 0.017) was statistically correlated with the risk of POBL. Regarding pathological variables, there were no statistically significant differences between the two groups. The optimal cut-off value of CAR, as determined by ROC curve analysis, was 0.053. This value had a sensitivity of 80.0% and a specificity of 72.8%. Multivariate logistic regression analysis indicated that CAR ≥ 0.053 (p = 0.030) and operation time ≥ 308 min (p = 0.023) were independent potential markers for POBL after hepatectomy. Conclusion A high CAR level can be an effective predictor for POBL following hepatectomy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Utsunomiya et al.)

Background: Heartbeat-based cross-sectional area (CSA) changes in the right main pulmonary artery (MPA), which reflects its distensibility associated with pulmonary hypertension, can be measured using dynamic ventilation computed tomography (DVCT) in patients with and without chronic obstructive pulmonary disease (COPD) during respiratory dynamics. We investigated the relationship between MPA distensibility (MPAD) and respiratory function and how heartbeat-based CSA is related to spirometry, mean lung density (MLD), and patient characteristics., Methods: We retrospectively analyzed DVCT performed preoperatively in 37 patients (20 female and 17 males) with lung cancer aged 70.6 ± 7.9 years (mean ± standard deviation), 18 with COPD and 19 without. MPA-CSA was separated into respiratory and heartbeat waves by discrete Fourier transformation. For the cardiac pulse-derived waves, CSA change (CSAC) and CSA change ratio (CSACR) were calculated separately during inhalation and exhalation. Spearman rank correlation was computed., Result: In the group without COPD as well as all cases, CSACR exhalation was inversely correlated with percent residual lung volume (%RV) and RV/total lung capacity (r = -0.68, p = 0.003 and r = -0.58, p = 0.014). In contrast, in the group with COPD, CSAC inhalation was correlated with MLDmax and MLD change rate (MLDmax/MLDmin) (r = 0.54, p = 0.020 and r = 0.64, p = 0.004) as well as CSAC exhalation and CSACR exhalation., Conclusion: In patients with insufficient exhalation, right MPAD during exhalation was decreased. Also, in COPD patients with insufficient exhalation, right MPAD was reduced during inhalation as well as exhalation, which implied that exhalation impairment is a contributing factor to pulmonary hypertension complicated with COPD., Relevance Statement: Assessment of MPAD in different respiratory phases on DVCT has the potential to be utilized as a non-invasive assessment for pulmonary hypertension due to lung disease and/or hypoxia and elucidation of its pathogenesis., Key Points: • There are no previous studies analyzing all respiratory phases of right main pulmonary artery distensibility (MPAD). • Patients with exhalation impairment decreased their right MPAD. • Analysis of MPAD on dynamic ventilation computed tomography contributes to understanding the pathogenesis of pulmonary hypertension due to lung disease and/or hypoxia in patients with expiratory impairment., (© 2024. The Author(s).)

Objectives: Many studies have demonstrated that sarcopenia among lung cancer predicts poor prognosis due to cancer progression. However, the cytokines that link sarcopenia and lung cancer progression remain unidentified. This study aimed to investigate whether lung cancer producing myostatin, which induces skeletal muscle atrophy, leads to sarcopenia and promotes cancer progression in patients with resected lung cancer., Methods: Tumor tissues were obtained from 148 patients who underwent curative resection for lung cancer. Tumor cells were stained with myostatin and tumor-associated macrophages (TAM) in the tumor microenvironment were stained with CD68. We assessed the association between myostatin expression and the clinicopathological features., Results: High myostatin expression in lung cancer was significantly associated with low skeletal muscle mass. The 5-year overall survival and relapse-free survival were significantly worse among patients with high myostatin expression than those with low expression. A multivariate analysis showed that TAM count was positively correlated with high myostatin expression., Conclusion: Sarcopenia may be induced by myostatin secreted by lung cancer cells. Moreover, myostatin may promote TAM migration into the tumor microenvironment, leading to advance lung cancer. As a result, patients with high myostatin expression had poor prognosis., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Programmed cell death-ligand 1 (PD-L1) on tumor cells can be degraded to soluble form (sPD-L1) and enter circulation, however, the clinical significances of sPD-L1 in peripheral blood remains to be elucidated in non-small-cell lung cancer (NSCLC). We monitored plasma sPD-L1 levels during perioperative periods and evaluated PD-L1-positive cells in tumor tissues in patients with operable NSCLC. Then the correlation between preoperative plasma sPD-L1 levels and relapse-free survival (RFS) was analyzed retrospectively. In patients who underwent radical surgery (n = 61), plasma sPD-L1 levels (median; 63.5 pg/mL) significantly increased 1 month after surgery (72.2 pg/mL, P < 0.001). The combined score of PD-L1-positive cells including tumor cells and tumor-associated macrophages (TAMs) was significantly associated with preoperative plasma sPD-L1 levels. In patients with high levels of preoperative plasma sPD-L1, the probability of 5-year RFS was significantly poor for patients with low PD-L1 expression intensity of tumor cells (tcPD-L1) compared with those with high tcPD-L1 (33.3% vs. 87.5%, respectively, P = 0.016; 95% CI, 0.013-0.964). In former group, PD-L1-positive TAMs were markedly infiltrating compared with those from latter group (246.4 vs. 76.6 counts/mm 2 , respectively, P = 0.003). In NSCLC, plasma sPD-L1 can reflect the accumulation of PD-L1-posotive TAMs, not just PD-L1-positive tumor cells. In patients with high levels of preoperative plasma sPD-L1, the prognoses after surgery depends on which PD-L1-positive cells, tumor cells or TAMs, are the primary source of the sPD-L1. Thus, measuring both plasma sPD-L1 levels and PD-L1 expression status of tumor cells and TAMs is of benefit for assessment of postoperative prognosis in operable NSCLC., (© 2023. The Author(s).)

Background: Surgical intervention for lung resection can cause ventilation-perfusion mismatches and affect gas exchange; however, minimally invasive assessment of blood flow is difficult. This study aimed to evaluate changes in pulmonary blood flow after radical lung cancer surgery using a minimally invasive dynamic digital chest radiography system., Methods: We evaluated 64 patients who underwent radical lobectomies. Postoperative changes in pulmonary blood flow, assessed using dynamic chest radiography-based blood flow ratios (BFRs), were compared with the temporal evolution of both functional lung volumes (FLVs) and estimated lung weight (ELW) derived from computed tomography (CT) volumetry., Results: FLVs on the affected side gradually recovered over time from the lowest value observed 3 months after surgery in all procedures. BFRs on the affected side also showed a gradual recovery from the lowest value 1 month after surgery, except for left upper lobectomies (LULs). In LULs, FLVs and ELWs increased proportionally up to 3 months after surgery, with lung volumes continuing to increase thereafter. The recovery of BFRs differed depending on the resected lobe., Conclusions: A relationship between pulmonary blood flow and FLV was observed in the postoperative period. Despite varying compensatory responses depending on the surgical procedure, FLV recovery coincided with increased pulmonary blood flow., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-986/coif). JH received a research grant from Konica Minolta Inc. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Several studies of early-stage non-small cell lung cancer (NSCLC) have reported a notable therapeutic effect of segmentectomy. However, the secondary benefits of lung volume preservation remain unclear. This study aimed to investigate the potential benefits of segmentectomy, in terms of its impact on postoperative bronchial change., Methods: Patients who underwent left-sided upper lobectomy and upper division segmentectomy for pStage 0-IA2 NSCLC, were retrospectively analyzed. Degree of the left main bronchial deviation was measured by the curvature index (CI), determined using computed tomography. Variables, including CI value and postoperative rate of change in CI were compared for postoperative cough management the lobectomy and segmentectomy groups., Results: Sixty-seven patients were reviewed. Thirty-seven and 30 patients underwent lobectomy and segmentectomy, respectively, without any significant differences in baseline and surgical variables. The 5-year overall survival rates in the lobectomy and segmentectomy groups were 86.7 and 95.2%, respectively (p = 0.437). While there was no significant difference in postoperative complications, the rate of change in CI was significantly higher in the lobectomy group than in the segmentectomy group (113 vs. 106%, p = 0.005). In addition, the analysis based on postoperative cough reveals the rate of change in CI to be significantly higher in patients requiring medical treatment (p = 0.005). Conclusions Left upper division segmentectomy provides satisfactory treatment and relief of postoperative bronchial tortuosity. Our study suggests that there is a possibility the mitigation of environmental changes in the thoracic cavity may reduce symptoms, thus contributing to an improved quality of life., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Epidermal growth factor receptor (EGFR)-mutated (mt) lung adenocarcinoma (LA) is refractory to immune checkpoint inhibitors (ICIs). However, the mechanisms have not been fully elucidated. CD8 + T cell infiltration was significantly lower in EGFR-mt than in EGFR-wild-type LA, which was associated with suppression of chemokine expression. Since this T cell-deserted tumor microenvironment may lead to the refractoriness of ICIs against EGFR-mt LA, we investigated the mechanism by focusing on the regulation of chemokine expression. The expression of C-X-C motif ligand (CXCL) 9, 10 and 11, which constitute a gene cluster on chromosome 4, was suppressed under EGFR signaling. The assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) revealed open chromatin peaks near this gene cluster following EGFR-tyrosine kinase inhibitor (TKI) treatment. The histone deacetylase (HDAC) inhibitor recovered the expression of CXCL9, 10 and 11 in EGFR-mt LA. Nuclear HDAC activity, as well as histone H3 deacetylation, were dependent on oncogenic EGFR signaling. Furthermore, the Cleavage Under Targets and Tagmentation (CUT & Tag) assay revealed a histone H3K27 acetylation peak at 15 kb upstream of CXCL11 after treatment with EGFR-TKI, which corresponded to one of the open chromatin peaks detected by ATAC-seq. The data suggest that EGFR-HDAC axis mediates silencing of the chemokine gene cluster through chromatin conformational change, which might be relevant to the ICI resistance by creating T cell-deserted tumor microenvironment. Targeting this axis may develop a new therapeutic strategy to overcome the ICI resistance of EGFR-mt LA., (© 2023. The Author(s).)

In lung cancer, tumor-associated macrophages (TAMs), especially M2-like TAMs, represent the main tumor progression components in the tumor microenvironment (TME). Therefore, M2-like TAMs may serve as a therapeutic target. The purpose of this study was to investigate the effect of M2-like TAM depletion in the TME on tumor growth and chemotherapy response in lung cancer. The levels of secreted monocyte chemoattractant protein (MCP-1) and prostaglandin E2 (PGE2) in the supernatants of lung cancer cell lines A549 and LLC were evaluated via ELISA. Cell migration assays were performed to assess the recruitment ability of macrophage cell lines THP-1 and J774-1 cells. Differentiation of macrophages was assessed via flow cytometry. Immunohistochemical staining was performed to visualize M2-like TAMs in transplanted lung cancer in mouse. We used the COX-2 inhibitor nimesulide to inhibit the secretion of MCP-1 and PGE2, which promotes macrophage migration and M2-like differentiation. Nimesulide treatment decreased the secretion of MCP-1 and PGE2 from lung cancer cells. Nimesulide treatment suppressed the migration of macrophages by blocking MCP-1. Lung cancer supernatant induced the differentiation of macrophages toward the M2-like phenotype, and nimesulide treatment inhibited M2-like differentiation by blocking MCP-1 and PGE2. In the lung cancer mouse model, treatment with nimesulide depleted M2-like TAMs in the TME and enhanced the tumor inhibitory effect of cisplatin. Our results indicated that blocking the secretion of MCP-1 and PGE2 from tumor cells depleted M2-like TAMs in the TME and the combination therapy with cisplatin considerably suppressed tumor growth in the LLC mouse model., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background/Aim: For intermediate-stage hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC]-B) cases, transarterial chemoembolization (TACE) is recognized as the standard treatment, while systemic therapy is recommended for TACE-unsuitable HCC. However, because the curative potential is not high, this study was conducted to elucidate the potential outcomes of surgical resection (SR) for BCLC-B HCC cases. Materials/Methods: From January 2000 to July 2022, 70 patients with BCLC-B HCC treated with surgery as the initial treatment were enrolled (median age 67.5 years, beyond up-to-7 criteria 44). Forty-five were treated with SR only (SR group), while twenty-five underwent that with complemental radiofrequency ablation (RFA) (Comb group). Recurrence-free survival (RFS) and overall survival (OS) were retrospectively evaluated in both groups. Results: The median albumin−bilirubin (ALBI) score was better in the SR as compared with the Comb group (−2.74 vs. −2.52, p = 0.02), while there were no significant differences between them for median RFS (17.7 vs. 13.1 months; p = 0.70) or median OS (66.6 vs. 72.0 months p = 0.54). As for those beyond up-to-7 criteria, there were no significant differences for median RFS (18.2 vs. 13.0 months; p = 0.36) or median OS (66.5 vs. 72.0 months; p = 0.57). An acceptable five-year cumulative survival rate (>50%) was obtained in both groups (54% vs. 64%). Conclusion: This retrospective study found no significant differences for RFS or OS between the present SR and Comb groups with BCLC-B HCC. When possible to perform, the outcome of SR for BCLC-B is favorable, with a five-year survival rate greater than 50%.

Background: Mediastinal lymph node (LN) dissection during lung resection is essential for accurate staging. Station 4L dissection is anatomically difficult. Therefore, care should be taken to avoid complications. We investigated the importance of mediastinal LN dissection in left upper lobe lung cancer and evaluated intraoperative videos to identify relevant steps during dissection., Methods: We retrospectively reviewed 151 consecutive patients with left upper lobe lung cancer. Finally, 139 patients were enrolled to examine the survival effects of clinical factors of metastatic LN stations. The association between risk factors or surgical procedures and recurrent laryngeal nerve palsy was analyzed., Results: LN dissection of the left upper lobe revealed station 4L LN metastasis in nine patients, three of whom were node-negative on mediastinoscopy. Station 4L LN status was confirmed intraoperatively in 12 of 33 patients. Twenty patients had recurrent laryngeal nerve palsy, four of whom were complicated with aspiration pneumonia. Station 4L LN dissection was an independent risk factor for recurrent laryngeal nerve palsy (P=0.03). The use of an energy device near the recurrent laryngeal nerve was a significant risk factor for recurrent laryngeal nerve palsy. Incidentally, pathological N stage ≥2 was an independent prognostic factor for disease-free survival (DFS) (P=0.005) herein., Conclusions: In patients with left upper lobe lung cancer, pathological N2 disease is an important predictor of recurrence. Therefore, accurate mediastinal LN dissection, including at station 4L, should be performed. We propose to standardize the dissection procedure at each institution to avoid complications, such as recurrent laryngeal nerve palsy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-537/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)