OBJECTIVES: Many patients with lung cancer have been cured by surgical intervention. However, the long-term effects of lung resection on pulmonary function are unclear. Therefore, we investigated long-term pulmonary function after surgery. METHODS: We retrospectively reviewed the medical records of patients who underwent surgery for lung cancer between 2001 and 2009. A total of 445 patients who had survived more than 5 years since the surgery were included. The patients were divided into lobectomy, segmentectomy and partial resection groups. The time-dependent changes in pulmonary function were investigated. RESULTS: The percentages of the vital capacity and forced expiratory volume in 1 second (FEV₁) at postoperative year (POY) 1 vs preoperative values were 92.9 ± 11.1% and 91.3 ± 13.0% in the lobectomy group, 95.9 ± 9.0% and 93.8 ± 10.5% in the segmentectomy group and 97.8 ± 7.3% and 98.1 ± 8.3% in the partial resection group, respectively. The values in the lobectomy group were significantly lower than those in the segmentectomy and partial resection groups. The percentages of vital capacity and FEV₁ at POY 5 vs preoperative values were 90.0 ± 11.5% and 86.2 ± 11.9% in the lobectomy group, 93.4 ± 9.8% and 91.1 ± 9.8% in the segmentectomy group and 94.3 ± 8.8% and 94.0 ± 8.0% in the partial resection group, respectively. The decrease in the rates from POY 1 to POY 5 were not significantly different among the procedures. CONCLUSIONS: Pulmonary function declined with pulmonary resection. After the patient recovered from the operation, pulmonary function decreased with time regardless of the surgical procedure.

Purpose: In performing surgery for lung cancer, emphysema is a risk factor related to postoperative respiratory complications (PRC). However, few studies have addressed the risk of radiological emphysematous volume affecting PRC. The aim of this study was to investigate the relationship between emphysematous volume as measured on 3-dimensional computed tomography and PRC. Patients and Methods: We reviewed 342 lung cancer patients undergoing lobectomy between 2013 and 2018. The percentage of low attenuation area (LAA%) was defined as the percentage of the lung area showing attenuation of − 950 Hounsfield units or lower. Preoperative factors including age, sex, body mass index, smoking index, respiratory function, tumour histology, and LAA% were evaluated. PRC included pneumonia, atelectasis, prolonged air leakage, empyema, hypoxia, ischemic bronchitis, bronchopleural fistula, and exacerbation of interstitial pneumonia. Uni- and multivariable analyses were performed to investigate the relationship between independent clinical variables and postoperative adverse events. Results: Median LAA% was 5.0% (range, 0– 40%) and PRC was observed in 50 patients (14.6%). Patients who presented with PRC showed significantly high LAA% compared to those without complications (median: 8.1% vs 3.8%; p < 0.001). Based on univariable analysis, age, sex, smoking index, percentage of forced expiratory volume in 1 s (FEV_1.0%), histology, and LAA% were significant predictors for PRC. Multivariable analysis revealed higher LAA% as a significant risk factor for PRC (odds ratio = 1.040; 95% confidence interval, 1.001– 1.080; p = 0.046). Conclusion: In addition to respiratory function with spirometry, LAA% can be used as a predictor of PRC.

Background Hyponatremia is the most common electrolyte disorder and is a negative prognostic factor in several kinds of cancer. However, few reports have referred to hyponatremia in non-small cell lung cancer (NSCLC). In the present study, the authors examined the influence of preoperative serum sodium concentration on survival in completely resected NSCLC. Methods A total of 386 completely resected NSCLC patients were retrospectively analyzed. Results Kaplan-Meier survival curves showed that serum sodium concentration was a significant prognostic factor, and the log-rank statistical value was maximum (9.173, p = 0.002) when the cutoff value of serum sodium concentration was 139 mEq/L. The overall 5-year survival rate of the high-serum sodium concentration group (> 139 mEq/L) was 74.8% and that of the low-serum sodium concentration group (≤ 139 mEq/L) was 59.7%. Clinicopathological factors showed significant differences between the two groups for leukocyte count, neutrophil count, C-reactive protein, tumor size, and pleural invasion. Conclusions Low-serum sodium concentration, which was associated with tumor status and inflammation, had negative prognostic influence in completely resected NSCLC.

MAFB is a basic leucine zipper (bZIP) transcription factor specifically expressed in macrophages. We have previously identified MAFB as a candidate marker for tumor-associated macrophages (TAMs) in human and mouse models. Here, we analyzed single-cell sequencing data of patients with lung adenocarcinoma obtained from the GEO database (GSE131907). Analyzed data showed that general macrophage marker CD68 and macrophage scavenger receptor 1 (CD204) were expressed in TAM and lung tissue macrophage clusters, while transcription factor MAFB was expressed specifically in TAM clusters. Clinical records of 120 patients with lung adenocarcinoma stage I (n = 57), II (n = 21), and III (n = 42) were retrieved from Tsukuba Human Tissue Biobank Center (THB) in the University of Tsukuba Hospital, Japan. Tumor tissues from these patients were extracted and stained with anti-human MAFB antibody, and then MAFB-positive cells relative to the tissue area (MAFB⁺ cells/tissue area) were morphometrically quantified. Our results indicated that higher numbers of MAFB⁺ cells significantly correlated to increased local lymph node metastasis (nodal involvement), high recurrence rate, poor pathological stage, increased lymphatic permeation, higher vascular invasion, and pleural infiltration. Moreover, increased amounts of MAFB⁺ cells were related to poor overall survival and disease-free survival, especially in smokers. These data indicate that MAFB may be a suitable prognostic biomarker for smoker lung cancer patients.

Pulmonary neuroendocrine carcinoma (NEC), including small cell carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC), is highly aggressive and has a poor prognosis. The molecular subtyping of NECs has recently attracted attention, and we identified a new NEC subtype, the hepatocyte nuclear factor 4α (HNF4α) subtype. HNF4α, a transcription factor associated with gastrointestinal differentiation, and TTF-1 are mutually and exclusively expressed in lung adenocarcinomas; however, the characteristics of HNF4α-high NEC and TTF-1-high NEC have yet to be compared. We immunohistochemically examined the characteristics of HNF4α-high NEC in 83 surgically resected specimens (37 SCLCs and 46 LCNECs) and revealed that HNF4α-high and TTF-1-high NEC accounted for 15% (12/83) and 47% (39/83), respectively. In SCLCs, HNF4α-high cases (n = 3) and TTF-1-high cases (n = 20) were almost confined to the neuroendocrine phenotype with high ASCL1 expression, and the expressions of HNF4α, TTF-1, and POU2F3 were mutually exclusive. Similar results were obtained for LCNECs; however, some HNF4α-high cases were positive for TTF-1 or YAP1, possibly due to the heterogeneity of LCNEC. Therefore, we investigated the heterogeneity of LCNEC and performed a spatial transcriptome analysis of 1 HNF4α-high LCNEC case, which revealed a mutually exclusive mixture of different subgroups characterized by HNF4A and NKX2-1 (TTF-1) expressions. A whole-genome analysis of 10 LCNECs showed that NFE2L2/KEAP1 mutations were characteristic of HNF4α-positive LCNECs. A prognostic analysis revealed a significantly worse prognosis in HNF4α-high LCNECs than in HNF4α-low LCNECs. A cell line analysis showed that TTF-1-high-expressing (Lu139/H889/H510A) and HNF4α-high-expressing (VMRC-LCD/H810) lines were consistent with ASCL1-high-expressing lines. HNF4α knockdown/knock-in experiments in VMRC-LCD and SBC5 (HNF4α-negative) revealed that HNF4α promoted cell proliferation by inhibiting apoptosis. The HNF4α-subtype of pulmonary NEC is a unique subtype, characterized by a neuroendocrine phenotype with high ASCL1 expression and mutual exclusivity with the TTF-1/POU2F3 subtypes. NFE2L2/KEAP1 mutations and HNF4α itself are potential therapeutic targets for this subtype.