Postoperative pulmonary function of patients with lung cancer and interstitial lung abnormalities.

OBJECTIVE: We investigated the impact of radiological interstitial lung abnormalities on the postoperative pulmonary functions of patients with non-small cell lung cancer. METHODS: A total of 1191 patients with clinical stage IA non-small cell lung cancer who underwent lung resections and pulmonary function tests ≥ 6 months postoperatively were retrospectively reviewed. Postoperative pulmonary function reduction rates were compared between patients with and without interstitial lung abnormalities and according to the radiological interstitial lung abnormality classifications. Surgical procedures were divided into wedge resection, 1-2 segment resection, and 3-5 segment resection groups. RESULTS: No significant differences in postoperative pulmonary function reduction rates 6 months after wedge resection were observed between the interstitial lung abnormality [n = 202] and non-interstitial lung abnormality groups [n = 989] [vital capacity [VC]: 6.82% vs. 5.00%; forced expiratory volume in 1 s [FEV1]: 7.05% vs. 7.14%]. After anatomical resection, these values were significantly lower in the interstitial lung abnormality group than in the non-interstitial lung abnormality group [VC: 1-2 segments, 12.50% vs. 9.93%; 3-5 segments, 17.42% vs. 14.23%; FEV1: 1-2 segments: 13.36% vs. 10.27%; 3-5 segments: 17.36% vs. 14.39%]. No significant differences in postoperative pulmonary function reduction rates according to the radiological interstitial lung abnormality classifications were observed. CONCLUSIONS: The presence of interstitial lung abnormalities had a minimal effect on postoperative pulmonary functions after wedge resections; however, pulmonary functions significantly worsened after segmentectomy or lobectomy, regardless of the radiological interstitial lung abnormality classification in early-stage non-small cell lung cancer.

Lessons from short chest drain management for primary spontaneous pneumothorax.

OBJECTIVES: Video-assisted thoracic surgery (VATS) bullectomy is the mainstay treatment for primary spontaneous pneumothorax (PSP) but we encounter patients with pain due to chest tube. This study investigated the postoperative outcomes of shortened silicone drain as a chest tube after VATS bullectomy to reduce pain. METHODS: The current study included patients aged < 30 years who underwent VATS bullectomy for PSP. Patients with normal intrathoracic lengths of the silicone drain placed in a loop at the apex toward the diaphragm were categorized as Group L, whereas those with the silicone drain shortened to approximately 10 cm and placed toward the apex were classified as Group S. Postoperative pain evaluated using a numerical rating scale (NRS) and other perioperative outcomes were compared between the groups. RESULTS: Altogether, 43 patients were included, with 22 in Group L and 21 in Group S, respectively. The NRS before chest tube removal was significantly lower in Group S (mean, 2.1) than in Group L (4.4; p = 0.001). In Group L, 4 patients (p = 0.017) required early chest tube removal than expected due to severe pain whereas none in Group S required this intervention; additionally, more patients needed additional analgesics than in Group S (p = 0.003). CONCLUSION: In VATS bullectomy for PSP, the pain intensity could be reduced by shortening the intrathoracic length of the silicone drain, compared to a longer intrathoracic length of the silicon drain. Our findings contribute to the establishment of optimal postoperative management of general thoracic surgery.

Differences in postoperative prognosis between early-stage lung adenocarcinoma and squamous cell carcinoma.

BACKGROUND: Although prognosis and treatments differ between small-cell- and nonsmall-cell carcinoma, comparisons of the histological types of NSCLC are uncommon. Thus, we investigated the oncological factors associated with the prognosis of early-stage adenocarcinoma and squamous cell carcinoma. METHODS: We retrospectively compared the clinicopathological backgrounds and postoperative outcomes of patients diagnosed with pathological stage I-IIA adenocarcinoma and squamous cell carcinoma primary lung cancer completely resected at our department from January 2007 to December 2017. Multivariable Cox regression analysis for overall survival and recurrence-free survival was performed. RESULTS: The median follow-up duration was 55.2 months. The cohort consisted of 532 adenocarcinoma and 96 squamous cell carcinoma patients. A significant difference in survival was observed between the two groups, with a 5-year overall survival rate of 90% (95% confidence interval 86-92%) for adenocarcinoma and 77% (95% CI 66-85%) for squamous cell carcinoma (P < 0.01) patients. Squamous cell carcinoma patients had worse outcomes compared to adenocarcinoma patients in stage IA disease, but there were no significant differences between the two groups in stage IB or IIA disease. In multivariate analysis, invasion diameter was associated with overall survival in adenocarcinoma (hazard ratio 1.76, 95% confidence interval 1.36-2.28), but there was no such association in squamous cell carcinoma (hazard ratio 0.73, 95% confidence interval 0.45-1.14). CONCLUSIONS: The importance of tumor invasion diameter in postoperative outcomes was different between adenocarcinoma and squamous cell carcinoma. Thus, it is important to consider that nonsmall-cell carcinoma may have different prognoses depending on the histological type, even for the same stage.

Utility of 4 K three-dimensional endoscopic system in performing video-assisted thoracoscopic surgery lobectomy: initial results of the first year after installation.

OBJECTIVES: With the evolution of technology in the field of thoracoscopy, three-dimensional (3D) endoscopic systems with 4 K resolution have recently come into use. This study aimed to determine perioperative outcomes of video-assisted thoracoscopic surgery (VATS) lobectomy performed a year after the 4 K three-dimensional (3D) endoscopic system installation and compare them with those of the high-definition (HD) 3D endoscopic system. METHODS: We included patients who underwent complete VATS (cVATS) lobectomy for primary lung cancer using an HD3D endoscopic system (HD3D group, June 2015-September 2021, n = 251) or 4K3D endoscopic system (4K3D group, October 2021-September 2022, n = 47). The perioperative outcomes were compared between the two groups. RESULTS: The operation time was significantly shorter in the 4K3D group (mean, 189.5 min) than in the HD3D group (208.5 min; p = 0.021), and the 4K3D group did not require conversion to thoracotomy or transfusion. The 4K3D group had less blood loss volume (4K3D group: mean, 24.0 mL vs. HD3D group: 43.3 mL; p = 0.105) and shorter chest drainage duration (4K3D group: mean, 2.3 days vs. HD3D group: 3.1 days; p = 0.115) and hospitalization period (4K3D group: mean, 7.9 days vs. HD3D group:10.0 days; p = 0.226) than the HD3D group, with no significant difference. No difference was observed in the incidence of ≥ Grade IIIa complications (p = 0.634). CONCLUSION: The 4K3D endoscopic system significantly shortened the duration of cVATS lobectomy. It is useful for lung resection and may replace other endoscopy systems.

Significance of the Goddard Score in Predicting Complications Related to Air Leak After Lobectomy.

BACKGROUND: Postoperative air leakage is a frequent complication after lung resection, and emphysema is a risk factor. However, no study has investigated the relationship between emphysema severity and postoperative complications related to air leak by the Goddard score (GS), a visual evaluation method of radiologic emphysema using computed tomography. METHODS: This study included patients who underwent lobectomy for non-small cell lung cancer between April 2009 and March 2022. The utility of GS in predicting complications related to air leak (air leak prolonged for ≥5 days, pleurodesis, and reoperation for air leak) was investigated by receiver operating characteristic curve analysis and multivariable analysis with a logistic regression model. RESULTS: This study included 477 patients. The GS was a significant predictor of complications related to air leak (area under the curve, 0.696; P < .001). Based on the receiver operating characteristic curve analysis, GS of 6 points was used as the cutoff point for multivariable analysis. In the multivariable analysis, GS of ≥6 points was a significant predictor of complications related to air leak (odds ratio, 2.719; P = .007). In the subgroup analysis of patients with emphysema, GS of ≥6 points was a significant predictor of complications related to air leak (P = .014). CONCLUSIONS: The GS was useful in predicting complications related to air leak. Patients with radiologic findings of emphysema with GS of ≥6 points should be recognized as a high-risk group for complications related to air leak.

Pleural plaque identification in computed tomography and intraoperative thoracic findings: Correspondence and prognosis comparison in patients with resection of non-small cell lung cancer.

BACKGROUND: We previously reported that intraoperative findings of pleural plaques were worse prognostic factors of resected non-small cell lung cancer (NSCLC). However, differences in the presence of pleural plaques detected either intraoperatively or by CT findings have not been addressed. METHOD: We included 121 patients who underwent resection for NSCLC with intraoperatively detected pleural plaques. We investigated preoperative CT findings and compared the prognosis between patients with or without evidence of pleural plaque on CT. RESULTS: Only 43% of patients with pleural plaques on intrathoracic findings had pleural plaques detected on preoperative CT. There were no differences in prognosis between patients with or without pleural plaque evidences on preoperative CT. CONCLUSION: The rate of detection of pleural plaques on preoperative CT is low even if they are present intraoperatively, and patients with intraoperative findings of pleural plaques have equally poor prognosis regardless of their evidences on preoperative CT.

Usefulness of serum S100A4 and positron-emission tomography on lung cancer accompanied by interstitial pneumonia.

BACKGROUND: The S100 calcium-binding protein A4 (S100A4) and the accumulation of [18F]-fluoro-2-deoxy-D-glucose (FDG) in noncancerous interstitial pneumonia (IP) area are predictors of postoperative acute exacerbation (AE) of IP after pulmonary resection for lung cancer with IP. However, the significance of combining these markers for predicting short-term outcome and long-term prognosis is not known. METHODS: Patients diagnosed with IP on preoperative high-resolution computed tomography and who had undergone pulmonary resection for primary lung cancer between April 2010 and March 2019 at Hiroshima University were included in this study. Predictive factors for the cumulative incidence of death from other than lung cancer (CIDOL) were investigated using the Fine and Gray model. CIDOL, perioperative outcome, and cumulative incidence of all death (CIAD) were retrospectively compared based on serum S100A4 and FDG accumulation. RESULTS: A total of 121 patients were included in this study. High S100A4 (hazard ratio [HR], 2.541; p = 0.006) and FDG accumulation (HR, 3.199; p = 0.038) were significant predictors of CIDOL. AE of IP occurred only in patients with high S100A4/FDG (+). CIDOL of patients with high S100A4/FDG (+) was higher than those with high S100A4/FDG (-) or low S100A4/FDG (+) (p < 0.001), and CIAD of patients with high S100A4/FDG (+) was also higher than those with high S100A4/FDG (-) or low S100A4/FDG (+) patients (p = 0.021). CONCLUSIONS: Serum S100A4 and FDG accumulation in the noncancerous IP area were significant predictors of CIDOL after lung resection for lung cancer with IP and may help decide the treatment strategy.

Segmentectomy for clinically early-stage primary squamous cell carcinoma of the lung.

BACKGROUND: Squamous cell carcinoma of the lung-the second most common subtype of lung cancer-has a poorer prognosis than lung adenocarcinoma. However, in contrast to lobectomy, the oncological outcomes after segmentectomy for primary squamous cell carcinomas remain unknown; hence, this study investigated these outcomes. METHODS: Patients who underwent lobectomy or segmentectomy for clinically node-negative primary lung squamous cell carcinoma with a whole tumor size of ≤ 30 mm on preoperative computed tomography scan during April 2010 to December 2020 were included in this study. The cumulative incidence of recurrence (CIR) among all included patients and propensity score-matched patients were compared using the Gray method. Multivariate analysis using propensity scores and surgical procedures was performed using the Fine and Gray method. RESULTS: Overall, 230 patients were included in this study; of these, 172 (74.8%) underwent lobectomy and 58 (25.2%) underwent segmentectomy. No significant differences were observed in the CIR between patients who underwent lobectomy and those who underwent segmentectomy (5-year rate 18.1% vs. 14.2%; p  = â€Š0.787). Moreover, no significant differences in CIR were observed between the propensity score-matched patients who underwent lobectomy (n = 43) and those who underwent segmentectomy (n   = â€Š43) (8.6% vs. 8.0%; p = 0.571). Multivariable analysis was performed for CIR using the propensity score; it revealed that segmentectomy was not a significant predictor of worse CIR (hazard ratio, 0.987; p = â€Š 0.980). CONCLUSIONS: Segmentectomy may be feasible for treating clinically early-stage lung squamous cell carcinoma; its oncological outcomes are similar to those of lobectomy.

Prognosis of resected non-small cell lung cancer with pleural plaques on intrathoracic findings.

BACKGROUND: The prognosis of patients with lung cancer who demonstrate pleural plaques intraoperatively, which may be associated with exposure to asbestos, is unclear. Here, we compared the clinicopathological characteristics and prognosis of these patients to those of patients without pleural plaques. METHODS: We included patients who underwent curative-intent resection for non-small cell lung cancer. We retrospectively investigated the relationship of intrathoracic findings of pleural plaques with clinicopathological features and prognosis. RESULTS: Pleural plaques were found in 121/701 patients (17.3%) during surgery. The incidence of squamous cell carcinoma (P < 0.001) and the pathological stage (P = 0.021) were higher in patients with pleural plaques. Overall survival was significantly worse in patients with pleural plaques (5-year rate; 64.5% vs. 79.3%; P < 0.001), and the same finding was noted in clinical stage I patients (5-year rate; 64.8% vs. 83.4%; P < 0.001). In multivariable analysis, the presence of pleural plaques was a significant predictor of overall survival in patients with clinical stage I (hazard ratio, 1.643; P = 0.036). In the analysis among patients with emphysema more severe than Goddard score 5 points or interstitial pneumonia, overall survival was significantly worse in those with pleural plaques than in those without pleural plaques (5-year rate; 66.3% vs. 49.5%; P < 0.001). CONCLUSIONS: Patients with non-small cell lung cancer who underwent resection and demonstrated pleural plaques intraoperatively had a significantly worse prognosis. It is important to recognize the presence of pleural plaques intraoperatively, and our findings will be useful in determining the treatment and follow-up strategy for such patients with lung cancer and pleural plaques on intrathoracic examination.

Oncological outcome of segmentectomy for early-stage non-small-cell lung cancer with invasive characteristics: a multicentre study.

OBJECTIVES: Segmentectomy can provide oncologically acceptable results for small-sized non-small-cell lung cancer (NSCLC). However, in cases of NSCLC with pathological invasive characteristics such as lymphatic invasion (LY), vascular invasion (V), pleural invasion (PL) and/or lymph node metastasis, the feasibility of segmentectomy is not known. METHODS: The patients included in the study (i) underwent lobectomy or segmentectomy for NSCLC with invasive characteristics such as LY, V, PL or pathological lymph node metastasis; (ii) presented with a node-negative, solid component-predominant tumour (consolidation tumour ratio >50%) on preoperative computed tomography; (iii) had a whole-tumour size of 2 cm or less; and (iv) presented between January 2010 and December 2019 to one of the 3 institutions. Cumulative incidences of recurrence (CIRs) after segmentectomy and lobectomy were compared. RESULTS: A total of 321 patients were included. Segmentectomy and lobectomy were performed in 80 (24.9%) and 241 (75.1%) patients, respectively. There was no significant difference in CIR between segmentectomy (5-year CIR rate, 17.2%) and lobectomy patients (5-year CIR rate, 27.8%, P = 0.135). In the propensity score-matched cohort, there was no significant difference in CIR between segmentectomy (5-year CIR rate, 19.1%) and lobectomy patients (5-year CIR rate, 19.2%; P = 0.650). In the multivariable analysis using inverse probability of treatment weighting and surgical method, segmentectomy was not a significant predictor of worse CIR (P = 0.920). CONCLUSIONS: Segmentectomy is feasible for clinically early-stage NSCLC irrespective of the presence of LY, V, PL or lymph node metastasis.

Segmentectomy versus wedge resection for radiological solid predominant and low metabolic non-small cell lung cancer.

OBJECTIVES: The prognosis of segmentectomy and wedge resection for solid predominant early-stage non-small cell lung cancer with low metabolic activity is unclear. METHODS: This study aimed to assess patients who underwent segmentectomy or wedge resection with curative intent for clinically node-negative non-small cell lung cancer presenting as a solid predominant tumour (consolidation tumour ratio >50%) with a whole size ≤3 cm and [18F]-fluoro-2-deoxy-D-glucose accumulation weaker than that of the mediastinum tissue (Deauville score, 1 or 2) on positron emission tomography/computed tomography. The cumulative incidence of recurrence (CIR) was compared using the Gray method, and the predictive factor of CIR was analysed using the Fine and Gray method. RESULTS: Of 140 patients included in this study, 93 (66.4%) underwent segmentectomy and 47 (33.6%) underwent wedge resection. No significant difference in the clinical stage was found between the 2 groups. The CIR was higher with wedge resection than with segmentectomy (P = 0.004). Recurrence after wedge resection was noted in 4 (8.5%) patients, 2 of whom had a recurrent site containing lung parenchyma of the preserved lobe and hilum lymph node, which would have been resected if segmentectomy had been performed. In the multivariable analysis for CIR using inverse probability of treatment weighting and the procedure, wedge resection was a significantly worse predictive factor (hazard ratio, 12.280; P = 0.025). CONCLUSIONS: Segmentectomy rather than wedge resection should be considered for solid predominant, small-size non-small cell lung cancer even if [18F]-fluoro-2-deoxy-D-glucose accumulation is low.

Segmentectomy versus lobectomy for solid predominant cN0 lung cancer: analysis using visual evaluation of positron emission tomography.

OBJECTIVES: Prognosis after segmentectomy for early-stage non-small cell lung cancer (NSCLC) with a high consolidation tumour ratio (CTR) and [18F]-fluoro-2-deoxy-d-glucose (FDG) accumulation on positron emission tomography/computed tomography is unclear. METHODS: Participants of this study were 465 patients who underwent lobectomy or segmentectomy for clinical N0 NSCLC presenting solid component predominant tumour (CTR >50%) with a whole size ≤3 cm. Accumulations of FDG on positron emission tomography/computed tomography scans were scored according to the Deauville criteria, a 5-point visual evaluating method (Deauville score). The correlations between Deauville score, prognosis, and procedures were analysed. RESULTS: Characteristics of pathological invasiveness, such as lymphatic invasion (P < 0.001), vascular invasion (P < 0.001) and pleural invasion (P < 0.001), and non-adenocarcinoma histologies (P < 0.001) were more common in patients with Deauville scores of 3-5. The cumulative incidence of recurrence (CIR) was higher in patients with Deauville scores of 3-5 (P < 0.001). The CIR after lobectomy and segmentectomy did not differ significantly among patients with Deauville scores of 1 or 2 (P = 0.598) or those with Deauville scores of 3-5 (P = 0.322). In the analysis of propensity score matched cohort, the CIR after lobectomy and segmentectomy did not differ significantly between patients with Deauville scores of 1 or 2 and Deauville scores of 3-5. CONCLUSIONS: Segmentectomy may be feasible for NSCLC with high CTR (>50%) and accumulation of FDG. This finding should be confirmed in larger prospective studies.

Role of Soluble Receptor for Advanced Glycation End Products in Postoperative Fibrotic Lung Injury.

BACKGROUND: In lung cancer patients with interstitial lung disease (ILD) postoperative acute exacerbation can be fatal. However the predictive biomarkers for postoperative exacerbation of ILD have not been fully elucidated. The soluble receptor for advanced glycation end products is a lung-derived antiinflammatory protein that can prevent acute lung injury. This study aimed to elucidate its role in this fatal complication, especially focusing on the predictive potential of serum levels of soluble receptor for advanced glycation end products. METHODS: We retrospectively enrolled 152 patients with lung cancer and ILD who underwent lung resection and had blood samples collected before surgery. Independent predictors of postoperative acute exacerbation were evaluated in all patients and in subgroups based on the surgical procedure. Additionally serial changes in soluble receptor levels in these subgroups were evaluated. RESULTS: Seventeen patients (11.2%) developed postoperative acute exacerbation. Receiver operating characteristic curve analysis revealed 547.4 pg/mL as the optimal soluble receptor level cutoff value. Univariate and multivariate logistic regression analyses revealed a significant association between soluble receptor serum levels (≤547.4 pg/mL) and postoperative acute exacerbation. In the subgroup analysis this independent association was observed only in the lobectomy group. Additionally lobectomy caused a significant reduction in postoperative soluble receptor levels. CONCLUSIONS: Decreased baseline levels of circulatory soluble receptor might be a potential risk factor for postoperative acute exacerbation in patients with lung cancer and ILD. Moreover additional reduction in the levels of this antiinflammatory protein occurs because of lung resection.

Pathological high malignant grade is higher risk of recurrence in pN0M0 invasive lung adenocarcinoma, even with small invasive size.

INTRODUCTION: Tumor size is an absolute recurrence risk in lung cancer. Although morphological features also reflect recurrence risk, its significance among lower-risk cases characterized by small size is unknown. We aimed to evaluate the relationship between pathological invasive tumor size and morphological features, and their prognostic impact by considering them simultaneously in lung adenocarcinoma. PATIENTS AND METHODS: We retrospectively reviewed 563 pN0M0 patients with pathological invasive size of ≤40 mm. The patients were classified by pathological invasive size and pathological malignant grading using the proportion of subhistological components. The prognostic impact was evaluated using recurrence-free survival (RFS) and overall survival (OS). The impact on prognosis was evaluated using uni- and multivariate analyses. RESULTS: The proportion of histological grade changed according to invasive tumor size. Patients with high malignant grade (G3) showed worse RFS than those with low and intermediate malignant grade (G1+2) with invasive size ≤20 mm. The 5-year RFS (G1+2 vs. G3) in 5-10 mm was 96.0% vs. 83.3% (HR = 5.505, 95% CI = 7.156-1850, p < 0.001) and in 10-20 mm was 87.8% vs. 67.1% (HR = 2.829, 95% CI = 4.160-43.14, p < 0.001). G3 patients were significantly bigger in invasive size and included more pleural/lymphatic/vascular invasion and recurrence. Multivariate analysis indicated pathological G3 status was significantly associated with worse RFS (HR = 2.097, 95% CI = 1.320-3.333, p = 0.002). CONCLUSIONS: Invasive tumor size and pathological malignant grade overlap in invasive adenocarcinoma. G3 patients are more likely to have pleural/lymphatic/vascular invasion and significantly worse RFS compared to G1/G2 cases, even with a small invasive size of ≤20 mm.

Utility of Newly Proposed Grading System From International Association for the Study of Lung Cancer for Invasive Lung Adenocarcinoma.

INTRODUCTION: The International Association for the Study of Lung Cancer proposed a new grading criteria for invasive adenocarcinoma. However, its utility has not been validated. METHODS: Patients who underwent complete resection of lung adenocarcinoma were included in this study. Then, they were divided into the following three groups on the basis of the criteria recently proposed by the International Association for the Study of Lung Cancer: grade 1, lepidic predominant tumor, with less than 20% of high-grade patterns; grade 2, acinar or papillary predominant tumor, with less than 20% of high-grade patterns; and grade 3, any tumor with greater than or equal to 20% of high-grade patterns. RESULTS: Recurrence-free survival (RFS) was significantly different among the proposed grades (p < 0.001). The RFS of patients upgrading from current grade 2 (papillary or acinar predominant tumor) to proposed grade 3 (5-y RFS, 65.2%) was significantly worse than that of patients with proposed grade 2 (77.1%, hazard ratio = 1.882, 95% confidence interval: 1.236-2.866) but not significantly different from that of patients with grade 3 in both the current (micropapillary or solid predominant tumor) and proposed criteria (53.2%, hazard ratio = 0.761, 95% confidence interval: 0.456-1.269). Among patients with pathologic stage 0 or I, RFS was well stratified by the new grading system (p < 0.001) but not among patients with stage II or III (p = 0.334). In the multivariable analysis, the new grading was not a predictive factor of RFS. CONCLUSIONS: Although the proposed grading system well stratified RFS in patients with pathologic stage 0 or I lung adenocarcinoma, there is room for improvement.

Systemic Inflammatory Score Predicts Response and Prognosis in Patients With Lung Cancer Treated With Immunotherapy.

AIM: This study aimed to investigate useful prognostic factors of immunotherapy in patients with lung cancer. PATIENTS AND METHODS: We retrospectively observed 73 patients who underwent immunotherapy (nivolumab, pembrolizumab, and atezolizumab) for lung cancer. The systemic inflammatory score (SIS) was calculated as the sum of the following factors scored one point each: Hemoglobin <12.5 g/dl and serum albumin <3.6 g/dl, resulting in scores of 0-2. We examined the correlation between the SIS and initial tumor response and progression-free and overall survival with other existing markers, namely tumor programmed death-ligand 1 (PD-L1) expression level; neutrophil-to-lymphocyte ratio (NLR); modified Glasgow prognostic score; and prognostic nutritional index, etc. Results: SIS ≤1 was significantly associated with better initial tumor response. In multivariate analysis, PD-L1 expression ≥50% (p=0.010), SIS ≤1 (p=0.028) and NLR <5.6 (p=0.047) were significantly associated with longer progression-free survival, and SIS ≤1 (p=0.030) and NLR <5.6 (p=0.037) were associated with longer overall survival. CONCLUSION: SIS is a useful marker of the efficacy of immunotherapy that can be obtained via routine blood tests.

Serum S100 calcium-binding protein A4 as a novel predictive marker of acute exacerbation of interstitial pneumonia after surgery for lung cancer.

BACKGROUND: Acute exacerbation (AE) of interstitial pneumonia (IP) is the most fatal complication after lung resection for lung cancer. To improve the prognosis of lung cancer with IP, the risk factors of AE of IP after lung resection should be assessed. S100 calcium-binding protein A4 (S100A4) is a member of the S100 family of proteins and is a known marker of tissue fibrosis. We examined the usefulness of S100A4 in predicting AE of IP after lung resection for lung cancer. METHODS: This study included 162 patients with IP findings on preoperative high-resolution computed tomography scan who underwent curative-intent lung resection for primary lung cancer between April 2007 and March 2019. Serum samples were collected preoperatively. Resected lung tissue from 76 patients exhibited usual IP (UIP) pattern in resected lung were performed immunohistochemistry (IHC). Relationship between S100A4 and the incidence of AE of IP and short-term mortality was analyzed. RESULTS: The receiver operating characteristic area under the curve for serum S100A4 to predict postoperative AE of IP was 0.871 (95% confidence interval [CI], 0.799-0.943; P < 0.001), with a sensitivity of 93.8% and a specificity of 75.3% at the cutoff value of 17.13 ng/mL. Multivariable analysis revealed that a high serum S100A4 level (> 17.13 ng/mL) was a significant risk factor for AE of IP (odds ratio, 42.28; 95% CI, 3.98-449.29; P = 0.002). A 1-year overall survival (OS) was significantly shorter in patients with high serum levels of S100A4 (75.3%) than in those with low serum levels (92.3%; P = 0.003). IHC staining revealed that fibroblasts, lymphocytes, and macrophages expressed S100A4 in the UIP area, and the stroma and fibrosis in the primary tumor expressed S100A4, whereas tumor cells did not. CONCLUSIONS: Serum S100A4 had a high predictive value for postoperative AE of IP and short-term mortality after lung resection.

Predictive role of circulatory HMGB1 in postoperative acute exacerbation of interstitial lung disease in lung cancer patients.

Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29-11.70] ng/mL vs. 3.55 [2.07-5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy.