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Introduction: We analyzed the association between postoperative weight loss (WL), preoperative body mass index (BMI), and prognosis in patients with lung cancer who underwent lobectomy using minimally invasive approaches., Methods: Weight change in 325 patients who underwent radical lobectomy for non-small cell lung cancer was assessed at 3, 6, and 12 months postoperatively and compared to preoperative weight. Patients were divided into three groups according to their preoperative BMI interquartile range: low BMI ≤20.3 kg/m 2 , middle BMI 20.4-24.4 kg/m 2 , and high BMI ≥24.5 kg/m 2 . Postoperative WL ≥5% was evaluated with reference to frailty., Results: There were no significant differences in pathological findings, postoperative complications, or postoperative hospital stay among the three groups. Thirty all-cause deaths and 39 cancer recurrences occurred. Within the first year after surgery, WL of any grade was observed in 229 patients (70.5%) and WL ≥5% in 86 patients (26.5%). Postoperative WL of any grade within 1 year after surgery was not associated with OS and RFS (both p > .05). However, WL ≥5% within 1 year after surgery was associated with worse OS and RFS (p = .007 and .006, respectively). WL ≥5% within 1 year after surgery was more common in the low BMI group (p = .045). There was no difference in OS and RFS among the BMI groups in patients with WL ≥5% and those without WL ≥5% (all p > .05)., Conclusion: WL ≥5% was associated with poor prognosis after lobectomy via minimally invasive approaches. Weighing is a useful prognostic marker that can be easily self-checked., (© 2023 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: Renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) are representative malignancies that respond well to immune checkpoint inhibitors (ICIs). Research has been conducted to identify biomarkers, such as programmed death ligand-1 (PD-L1), that would allow the response to ICI therapy to be predicted; however, the complex tumor immune system consisting of both host and tumor factors may also exert an influence., Case Presentation: Computed tomographic imaging (CT) incidentally revealed a left renal mass, and a left pulmonary nodule with multiple lymph node metastases (LNMs). Firstly, video-assisted thoracic surgery revealed a lung tumor invading the chest wall. Histologically, the findings of the tumor were consistent with squamous cell carcinoma (SCC), and immunohistochemistry (IHC) showed positive PD-L1 expression. The renal tumor was excised by robotic-assisted partial nephrectomy (RAPN). Histologically, the renal tumor showed the features of clear cell carcinoma (CCC). Four months after the RAPN, CT revealed left hydronephrosis caused by an enhancing ureteral tumor. Then, multiple right lung metastases appeared, and the left lung tumor increased. Following treatment including atezolizumab, the primary lung SCC and the multiple LNMs almost disappeared completely, while the ureteral and right lung metastases showed progression. The ureteral metastasis was resected by left open nephroureterectomy. Histology of the ureteral tumor revealed features consistent with CCC. Histological examination of the multiple right lung metastases that were resected by partial lobectomy via a small thoracic incision also revealed features consistent with CCC. Two months after nephroureterectomy, a solitary left lung metastasis was treated by nivolumab and ipilimumab. Six months after nephroureterectomy, the patient died of RCC. Further studies of specimens revealed that the tumor cells in the primary RCC and the ureteral and lung metastases showed negative results of IHC for PD-L1., Conclusions: The responses to ICI therapy of concomitant RCC and NSCLC were quite different. The PD-L1 expression status in individual tumors in cases of multiple primary malignancies (MPMs) may directly predict the response of each malignancy to ICI therapy, because the host immune system, which may affect the response to ICI therapy, could be the same in MPMs., (© 2023. The Author(s).)

Background: Understanding the mechanisms of non-T cell inflamed tumor microenvironment (TME) and their modulation are important to improve cancer immunotherapies such as immune checkpoint inhibitors. The involvement of various immunometabolisms has recently been indicated in the formation of immunosuppressive TME. In this study, we investigated the immunological roles of stearoyl-CoA desaturase 1 (SCD1), which is essential for fatty acid metabolism, in the cancer immune response., Methods: We investigated the roles of SCD1 by inhibition with the chemical inhibitor or genetic manipulation in antitumor T cell responses and the therapeutic effect of anti-programmed cell death protein 1 (anti-PD-1) antibody using various mouse tumor models, and their cellular and molecular mechanisms. The roles of SCD1 in human cancers were also investigated by gene expression analyses of colon cancer tissues and by evaluating the related free fatty acids in sera obtained from patients with non-small cell lung cancer who were treated with anti-PD-1 antibody., Results: Systemic administration of a SCD1 inhibitor in mouse tumor models enhanced production of CCL4 by cancer cells through reduction of Wnt/β-catenin signaling and by CD8 + effector T cells through reduction of endoplasmic reticulum stress. It in turn promoted recruitment of dendritic cells (DCs) into the tumors and enhanced the subsequent induction and tumor accumulation of antitumor CD8 + T cells. SCD1 inhibitor was also found to directly stimulate DCs and CD8 + T cells. Administration of SCD1 inhibitor or SCD1 knockout in mice synergized with an anti-PD-1 antibody for its antitumor effects in mouse tumor models. High SCD1 expression was observed in one of the non-T cell-inflamed subtypes in human colon cancer, and serum SCD1 related fatty acids were correlated with response rates and prognosis of patients with non-small lung cancer following anti-PD-1 antibody treatment., Conclusions: SCD1 expressed in cancer cells and immune cells causes immunoresistant conditions, and its inhibition augments antitumor T cells and therapeutic effects of anti-PD-1 antibody. Therefore, SCD1 is an attractive target for the development of new diagnostic and therapeutic strategies to improve current cancer immunotherapies including immune checkpoint inhibitors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: First-line chemoimmunotherapy (CIT) has improved overall survival (OS) and progression-free survival (PFS) outcomes among patients with non-small cell lung cancer (NSCLC). The immunological and nutritional statuses of patients fluctuate during treatment using immune checkpoint inhibitors, and are closely related to treatment outcomes. However, it is unclear whether these markers are significant in patients who are receiving CIT., Methods: This retrospective single-center study evaluated 34 consecutive Japanese patients with NSCLC who were treated using first-line CIT. Previously reported markers that reflect immunological and nutritional statuses were evaluated at three time points: at the start of CIT, after three weeks, and at the end of induction therapy., Results: The median PFS was 7.2 months (95% confidence interval: 6.3 months-not reached) and the median OS was not reached (95% confidence interval: 9.6 months-not reached). The PFS duration was significantly associated with the baseline neutrophil-to-lymphocyte ratio and the three-week values for the modified Glasgow prognostic score, C-reactive protein-albumin ratio, prognostic nutrition index, and advanced lung cancer inflammation index. The OS duration was significantly associated with the pre-treatment values for the neutrophil-to-lymphocyte ratio and advanced lung cancer inflammation index, as well as the prognostic nutrition index at the end of induction therapy., Conclusions: Immunological and nutritional markers could be useful for predicting the outcomes of CIT for Japanese patients with advanced non-small cell lung cancer. The timing of their evaluation may also be important., Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Overall survival in patients receiving first-line chemoimmunotherapy for advanced lung cancer were associated with pretreatment values of neutrophil-to-lymphocyte ratio, advanced lung cancer inflammation index, and the prognostic nutrition index at the end of induction therapy., What This Study Adds: Repetitive evaluation of immunological and nutritional markers may be useful for guiding prognostication and treatment selection for Japanese patients with advanced lung cancer., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Minimally invasive thoracoscopic lobectomy is the recommended surgery for clinical stage I non-small cell lung cancer (NSCLC). The purpose of this study was to identify the risk factors, including sarcopenia, for postoperative complications in patients undergoing a complete single-lobe thoracoscopic lobectomy for clinical stage I NSCLC, as well as the impact of complications on disease-free survival., Methods: We retrospectively investigated 173 patients with pathologically-diagnosed NSCLC who underwent curative thoracoscopic lobectomies between April 2013 and March 2018. Sarcopenia was assessed using the psoas muscle index calculated from preoperative computed tomography images at the third lumbar vertebral level., Results: Complications developed in 38 (22%) patients, including 21 with prolonged air leak. In univariate analysis, the significant risk factors for complications were advanced age, male sex, higher Charlson Comorbidity Index (CCI) score, lower cholinesterase, lower albumin, higher creatinine level, pleural adhesion, operative time ≥ five hours, nonadenocarcinoma cancer, and larger tumor size. Multivariate analysis showed that age ≥ 75 years (P = 0.002) and pleural adhesion (P = 0.026) were significant independent risk factors for complications. Compared with the patient group without complications, postoperative complications were independently associated with shorter disease-free survival (P = 0.01)., Conclusions: Advanced age and pleural adhesion were independent risk factors for complications after complete single-lobe thoracoscopic lobectomies for clinical stage I NSCLC, and postoperative complications were statistically associated with poor prognosis. Surgical teams should ensure an experienced surgeon leads the operation for patients at higher risk to avoid prolonged postoperative hospitalization and a possible poor prognosis., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Postoperative complications are reportedly related to poor prognosis following lung cancer surgery; however, the difference in the prognostic impact according to immune-nutritional status is unknown., Methods: In 411 patients with completely resected non-small cell lung cancer, the relationship between severe postoperative complications (SPCs; Clavien-Dindo grade III or higher) and survival was retrospectively analyzed, with special reference to preoperative immune-nutritional status based on the prognostic nutritional index (PNI), which was calculated using serum albumin level and total lymphocyte count., Results: A total of 52 (12.7%) patients had SPCs. The most common SPC was air leak (n = 39), atelectasis/sputum (n = 4), pneumonia (n = 2), pyothorax (n = 2), and bleeding (n = 2). The 5-year overall survival (OS) rates in patients with and without SPCs were 63.8% and 80.1%, respectively (p = 0.007). A multivariate Cox proportional hazard model revealed SPCs had a negative prognostic impact on patients with preserved immune-nutritional status (PNI ≥ 48.3; first to third quartile), but not on those with poor immune-nutritional status (PNI < 48.3; fourth quartile), with statistically significant interaction. Further analysis focused on 309 patients with preserved immune-nutritional status. The OS and relapse-free survival (RFS) rates were significantly worse in patients with SPCs than in those without (p < 0.001). After controlling for potential confounders, SPCs remained significantly associated with worse OS (adjusted hazard ratio [HR] 2.49, 95% confidence interval [CI] 1.21-4.83; p = 0.015) and RFS (adjusted HR 2.02, 95% CI 1.10-3.53; p = 0.025)., Conclusion: Severe complications following lung cancer surgery could negatively impact prognosis, particularly in patients with preserved immune-nutritional status.

Background: The prognostic nutritional index (PNI), an immune nutritional marker based on serum albumin levels and total lymphocyte count, predicts postoperative complications in various types of malignancies. However, the clinical significance of the PNI for postoperative complications following lung cancer surgery is uncertain., Methods: Patients with resected non-small cell lung cancer (n = 515) were retrospectively analyzed and the relationship between the preoperative PNI and postoperative complications was evaluated., Results: Multivariate logistic regression analysis revealed that a preoperative low PNI was a significant independent predictor of postoperative complications of Clavien-Dindo Grade ≥ II (odds ratio: 1.06 per unit decrease, 95.0% confidence interval 1.01-1.11). Patients were divided into three groups according to the preoperative PNI: normal (≥ 50; n = 324), mildly low (< 50, ≥ 45; n = 134), and severely low (< 45; n = 57). The incidence of postoperative complications of Grade ≥ II and Grade ≥ III in the normal, mildly low, and severely low PNI groups was 22.2, 39.6, and 42.1% and 7.1, 16.4, and 22.8%, respectively. The incidence of postoperative complications of Grade ≥ II and Grade ≥ III was significantly higher in the mildly low and severely low PNI groups than in the normal PNI group (p < 0.001 and p < 0.001, respectively). The incidence of air leak, pneumonia, and extrapulmonary infection, but not arrhythmia, was significantly higher in the mildly low and severely low PNI groups than in the normal PNI group., Conclusions: The PNI could be a useful marker to predict the risk of postoperative complications after lung cancer surgery.

Objective: Sublobar resection is practically indicated in poor-risk patients compromised cardiopulmonary reserve or for small ground-glass opacity-dominant adenocarcinomas. The aim of this study was to clarify the surgical outcomes of wide wedge resection in poor-risk patients with clinical-N0 non-small cell lung cancers., Methods: Sixty-two poor-risk patients, who underwent wedge resection for clinical-N0 lung cancer, were retrospectively reviewed. We defined the ratio of the maximum diameter of the consolidation to the maximum tumour diameter as the consolidation-to-tumour ratio using high-resolution computed tomography., Results: The 5-year overall, recurrence-free, and lung cancer specific survivals of all patients were 56.4, 46.6, and 81.1%, respectively, while other malignancies were frequently found as causes of death. Overall and recurrence-free survivals were favourable in patients with tumour size ≤3 cm, consolidation-to-tumour ratio ≤0.50, solid tumour size ≤1.2 cm, carcinoembryonic antigen level <5.0 ng/mL and adenocarcinoma. Multivariate Cox proportional hazard model revealed that solid tumour size ≤1.2 cm and consolidation-to-tumour ratio ≤0.50 were independent prognostic factors. CT-guided lipiodol marking was applied in 20 patients to identify the tumour location had no recurrence., Conclusions: Wide wedge resection could be radical treatment option in poor-risk patients with clinical-N0 non-small cell lung cancer, though careful follow-up might be necessary for other malignancies. Patients with solid tumour ≤1.2 cm or ground-glass-dominant lesion are good candidates for wedge resection. CT-guided lipiodol marking is a useful option to identify the location and safe surgical tumour margin in wedge resection.

Background: The prognostic nutritional index (PNI), calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (cells/mm 3 ), can reportedly predict postoperative complications and prognosis for various types of malignancy. However, the clinical significance and prognostic value of the PNI for both short- and long-term outcomes remains uncertain in patients with lung cancer., Methods: We retrospectively reviewed 248 patients with completely resected non-small cell lung cancer (NSCLC). Clinicopathologic characteristics were evaluated according to the PNI, and the prognostic significance for postoperative outcomes was assessed using Cox proportional regression analysis. The survival rate was calculated using the Kaplan-Meier method., Results: An optimal cutoff of 48 for recurrence-free survival (RFS) was determined using the minimum p value approach. Old age, low body mass index, large tumor size, and elevated C-reactive protein levels correlated significantly with low PNI. Logistic regression analysis demonstrated that low PNI status was statistically related to postoperative complications (Clavien-Dindo grade ≥II) and pulmonary air leakage. Five-year overall survival (OR) rates in the high- and low-PNI groups were 80.6% and 58.5%, respectively (p = 0.002). Five-year RFS rates were 73.6% and 48.6%, respectively (p < 0.001). Furthermore, PNI was identified as an independent prognostic factor for OS (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.08-4.21) and RFS (HR, 2.57; 95% CI, 1.46-4.38) by multivariate analysis., Conclusions: The PNI could represent a useful biomarker to predict postoperative complications and survival in patients with completely resected NSCLC., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

In order to clarify the mechanisms of resistance to paclitaxel in lung cancer, three human lung cancer cell lines which exhibit different sensitivity to paclitaxel were investigated from the following viewpoints: overexpression of ATP-binding cassette, sub-family B, member 1 (ABCB1), mutations on paclitaxel binding site of β-tubulin genes, quantity of polymerized tubulin and the intracellular localization of paclitaxel. ABCB1 expression was evaluated by real-time RT-PCR. No correlations were noted between the ABCB1 expression in the sensitive and resistant cell lines at the mRNA level. No mutations on the paclitaxel binding site of the β-tubulin genes were detected in either the resistant or sensitive cells. Live cell images obtained by confocal laser microscopy revealed that the resistant cell line, RERF-LC-KJ, had more accumulation of Oregon Green® 488 conjugated paclitaxel in the lysosomal and extra-lysosomal compartments of cytoplasm than other cell lines. The results obtained in this study indicated that the changes in the subcellular localization could contribute to the production of paclitaxel resistance in lung cancer cell lines. Further studies should be conducted to elucidate the molecular mechanisms that differentiate the intracellular localization of paclitaxel.