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We describe a rare case of newly discovered pulmonary metastases and surgical confirmation 12 years after initial surgery for a pheochromocytoma. A 61-year-old asymptomatic man was referred because of an abnormal shadow in the right lung field upon chest radiography. Computed tomography (CT) showed two well-demarcated tumors in the basal segment of the right lung. Twelve years previously, he underwent right adrenalectomy and was pathologically diagnosed as having a benign pheochromocytoma. Thereafter, he received a medical check-up annually. To confirm the diagnosis of two pulmonary tumors, video-assisted thoracic surgery was done and wedge resection of the right lower lobe completed. Pathology studies revealed these tumors as pulmonary metastases from the pheochromocytoma, which indicated that the true diagnosis was a malignant pheochromocytoma. Patients with a benign pheochromocytoma should continue to undergo careful monitoring for a long time after the initial surgical procedure. Thoracic surgeons should be aware of the possibility of pulmonary metastases even if >10 years have passed since initial resection of a benign pheochromocytoma.

Immune checkpoint inhibitors with chemotherapy have been shown to exhibit remarkable efficacy for advanced non‐small‐cell lung carcinoma and are under investigation as an induction therapy. However, the significance of preoperative therapy with pembrolizumab + chemotherapy for surgically resectable non‐small‐cell lung carcinoma still remains unclear. Here, we report a case of stage IIIB non‐small‐cell lung carcinoma that underwent salvage surgery after three cycles of pembrolizumab + carboplatin + nab‐paclitaxel. Computed tomography revealed the remarkable decrease in tumor volume by 81%. A pathological examination showed that viable neoplastic cells were observed in, Significance of preoperative therapy with pembrolizumab + chemotherapy for surgically resected non‐small‐cell lung carcinoma still remains unclear. This regimen showed a drastic response in a case of stage IIIB non‐small‐cell lung carcinoma that underwent salvage surgery after three cycles. A pathological examination showed that viable neoplastic cells were observed in

IntroductionImmunotherapy is the fourth leading therapy for lung cancer following surgery, chemotherapy and radiotherapy. Recently, several studies have reported about the potential association between the gut microbiome and therapeutic response to immunotherapy. Nevertheless, the specific composition of the gut microbiome or combination of gut microbes that truly predict the efficacy of immunotherapy is not definitive.Methods and analysisThe present multicentre, prospective, observational study aims to discover the specific composition of the gut microbiome or combination of gut microbes predicting the therapeutic response to immunotherapy in lung cancer using artificial intelligence. The main inclusion criteria are as follows: (1) pathologically or cytologically confirmed metastatic or postoperative recurrent lung cancer including non-small cell lung cancer and small cell lung cancer; (2) age≥20 years at the time of informed consent; (3) planned treatment with immunotherapy including combination therapy and monotherapy, as the first-line immunotherapy; and (4) ability to provide faecal samples. In total, 400 patients will be enrolled prospectively. Enrolment will begin in 2021, and the final analyses will be completed by 2024.Ethics and disseminationThe study protocol was approved by the institutional review board of each participating centre in 2021 (Kyushu Cancer Center, IRB approved No. 2021-13, 8 June 2021 and Kyushu Medical Center, IRB approved No. 21-076, 31 August 2021). Study results will be disseminated through peer-reviewed journals and national and international conferences.Trial registration numberUMIN000046428.

OBJECTIVES The prognostic nutritional index (PNI) is an indicator of systemic immune-nutritional condition and is a well-known prognostic biomarker in lung cancer patients. Tumour-infiltrating lymphocytes (TILs) is a specific histological feature of cancers, influencing an individual’s immunological tumour responses. However, whether PNI can reflect lung cancer patients’ prognosis through local immunity such as TIL is unclear. METHODS We selected 64 lung squamous cell carcinoma patients who underwent curative operations. We investigated the significance of preoperative PNI level and evaluated the relationship between PNI and immune cells surrounding the lung cancer tissue using immunohistochemical analysis of a cluster of differentiation (CD)3, CD4, CD8 and CD68. RESULTS A low-PNI level was significantly associated with a worse postoperative prognosis (P = 0.042). The PNI (hazard ratio 2.768, 95% confidence interval 1.320–5.957; P = 0.007) was an independent prognostic factor. The low-PNI group had a significantly shorter recurrence-free survival and overall survival (P = 0.013 and P = 0.002, log-rank test) compared with the high-PNI group. A significant positive correlation between PNI components including preoperative peripheral blood lymphocyte count and serum albumin concentration, and TILs, was observed. Absolute numbers of TILs in the preoperative high-PNI group were significantly increased compared with those in the preoperative low-PNI group (CD3+ cells; P = 0.002, CD4+ cells; P = 0.049 and CD8+ cells; P = 0.024). CONCLUSIONS The preoperative PNI level was strongly associated with the postoperative outcome in lung cancer patients. Considering the positive relationship between preoperative PNI level and TIL status, preoperative immune-nutritional condition may influence lung cancer patients’ postoperative prognosis through local immunity as well as systemic immune response.

BACKGROUND: Robot-assisted thoracic surgery (RATS) lobectomy for lung cancer is now performed all around the world. The camera and robotic devices are generally inserted from a low position via the thorax. We previously reported our original anterior approach (AA) for performing RATS lobectomy with a camera and robotic devices inserted via the anterior chest wall. However, whether AA is comparable or superior to the conventional approach (CA) remains unclear. METHODS: A total of 108 patients who underwent RATS lobectomy were included in the current study. We compared the AA with the CA for performing RATS lobectomy in terms of the operative and postoperative features, such as total operation/console time, blood loss and postoperative complications. RESULTS: Eighty-seven and 21 patients underwent the AA and CA in RATS lobectomy, respectively. The console and total operation time were significantly shorter in the AA group than in the CA group for RATS lobectomy (median console time: AA vs. CA, 112 vs. 148 min, P=0.0001; median total operation time: AA vs. CA, 193 vs. 243 min, P=0.0002), especially left upper lobectomy. Intraoperative blood loss and the frequency of postoperative complications were significantly reduced in the AA group compared with the CA group (median intraoperative blood loss: AA vs. CA, 20 vs. 105 mL, P

Background: Complete blood cell count (CBC)-derived inflammatory biomarkers are widely used as prognostic parameters for various malignancies, but the best predictive biomarker for early-stage non-small-cell lung cancer (NSCLC) is unclear. We retrospectively analyzed early-stage NSCLC patients to investigate predictive effects of preoperative CBC-derived inflammatory biomarkers. Patients and Methods: We selected 311 consecutive patients with pathological stage IA NSCLC surgically resected from April 2006 to December 2012. Univariate and multivariate Cox proportional analyses of recurrence-free survival (RFS) were used to test the preoperative systemic immune inflammation index (SII), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), and monocyte–lymphocyte ratio (MLR). Results: Preoperative high MLR levels were significantly associated with patient sex, smoking status, and postoperative recurrence (p 2 cm had significantly shorter RFS than other subgroups (p = 0.0289). Conclusions: The preoperative MLR level is the optimal predictor of recurrence in patients with pathological stage IA NSCLC.

Background Elderly non-small-cell lung cancer (NSCLC) patients are increasing. In general, elderly patients often have more comorbidities and worse immune-nutritional condition. Patients and methods In total, 122 NSCLC patients aged 75 years or older, underwent thoracic surgery between January 2007 and December 2010. In all, 99 of 122 patients (81.1%) who had preoperative comorbidities were retrospectively analyzed. We evaluated the preoperative immune-nutritional condition using the controlling nutritional status (CONUT) score. Results We decided the best cutoff value for CONUT score was 1; as a result, 42 of 99 patients (42.4%) had abnormal preoperative CONUT score. Univariate analyses showed sex (P = 0.0099), smoking status (P = 0.0176), pathological stage (P = 0.0095), and preoperative CONUT score (P = 0.0175) significantly affected overall survival (OS). In multivariate analysis, pathological stage (relative risk (RR): 2.12; 95% confidence interval (CI): 1.10-3.90; P = 0.0268) and preoperative CONUT score (RR: 2.10; 95% CI: 1.20-3.67; P = 0.0094) were shown to be independent prognostic factors. In Kaplan-Meier analysis of OS, the preoperative abnormal CONUT score group had significantly shorter OS than did the preoperative normal CONUT score group (P = 0.0152, log-rank test); however, there were no statistical differences both in disease-free survival (DFS) and cancer-specific survival (CSS; P = 0.9238 and P = 0.8661, log-rank test, respectively). In total, 22 patients (46.8%) were dead caused by other diseases such as pneumonia or other organs malignancies. Conclusion Preoperative abnormal CONUT score is a poor prognostic factor for the elderly NSCLC patients with preoperative comorbidities and might predict poor postoperative outcome caused by not primary lung cancer but other diseases.

Spread through air spaces (STAS) was proposed as a new form of cancer invasion by the World Health Organization in 2015. Since the definition of STAS, a number of studies on STAS have been reported and revealed the clinical significance of STAS in various histological subtypes of lung cancer.

Cancer immunotherapy including immune checkpoint inhibitors (ICI) has revolutionized non-small cell lung cancer (NSCLC) therapy. Recently, the microbiome status before initiation of ICI therapy has been emphasized as a predictive biomarker in patients undergoing ICI therapy. However, the microbiome diversity and composition during ICI therapy is unknown. This multicenter, prospective observational study analyzed both saliva and feces from 28 patients with NSCLC. We performed 16S ribosomal RNA gene sequencing, then analyzed associations of oral and gut microbiome diversity or composition with ICI response. Seventeen patients (responders) had a partial ICI response, and the remaining 11 patients (non-responders) had stable or progressive disease. At the genus level, the alpha diversity of the gut microbiome was significantly greater in ICI responders than in non-responders (Chao 1, p = 0.0174; PD whole tree, p = 0.0219; observed species, p = 0.0238; Shannon, p = 0.0362), while the beta diversity of the gut microbiome was significantly lower in ICI responders (principal coordinates analysis, p = 0.035). Compositional differences in the gut microbiome were observed between the two groups; in particular, Blautia was enriched in ICI responders, whereas RF32 unclassified was enriched in ICI non-responders. There were no significant differences between groups in the oral microbiome. This study revealed a strong association between gut microbiome diversity and ICI response in Japanese NSCLC patients. Moreover, specific gut microbiome compositions may influence the ICI response. These findings might be useful in identifying biomarkers to predict ICI response, as well as in developing biotic therapies to enhance the ICI response.

Background Smoking cessation is a highly important preparation before thoracic surgery. We examined the effects of short-term smoking cessation intervention before pulmonary resection on postoperative pulmonary complications (PPCs). Methods A retrospective analysis of prospectively collected data was performed for 753 patients who underwent curative surgical resection for thoracic malignancy at 3 institutions. Patients with a smoking history were instructed to quit smoking. After confirming smoking cessation by at least four weeks before surgery, surgical resection was performed. Subjects were classified into three groups based on their smoking status: abstainers (anyone who had stopped smoking for at least 4 weeks but less than 2 months), former smokers (anyone who had abstained from smoking for more than two months prior to surgery), and never smokers (those who had never smoked). We examined the relationship between the preoperative smoking status and PPCs. Results Surgery was performed for 660 primary lung cancers and 93 metastatic lung tumors. The smoking statuses were classified as follows: abstainers (n=105, 14%), former smokers (n=361; 48%) and never smokers (n=287, 38%). The incidence of PPCs among abstainers, former smokers and never smokers was 15%, 8% and 6%, respectively (P=0.01). The mean duration of post-operative chest tube drainage among abstainers, former smokers and never smokers was 3.2, 2.2 and 2.2 days, respectively (P=0.04). The mean post-operative hospital stay among abstainers, former smokers and never smokers was 12.1, 10.6 and 10.2 days, respectively (P=0.07). There was no 30-day mortality in the cohort. Conclusions Short-term smoking cessation intervention did not enough reduce the PPCs as much as in former or never smokers.

Stroke is a major cause of morbidity or death after lung operations. Carotid artery screening (CAS) is useful for detecting carotid artery stenosis, which is one of the causes of stroke. This study investigated the frequency of and risk factors for preoperative carotid artery stenosis to determine whether CAS with ultrasonography contributes to preventing postoperative stroke or cardiovascular comorbidities in lung cancer patients.This retrospective study included 1,676 consecutive lung cancer patients who underwent surgical resection.Of the 1,342 patients who underwent CAS, 173 (12.9%) had carotid artery stenosis. Significant associations with carotid artery stenosis were found for older patients (p0.0001), men (p0.0001), smoking history (p 0.0001), history of stroke (p = 0.0037), cardiovascular diseases (p0.0001), hypertension (p = 0.0353), diabetes mellitus (p = 0.0037), and peripheral vascular diseases (p 0.0001). Patients with the three independent risk factors of age, male sex, and history of cardiovascular diseases had a 6.43-fold higher prevalence of carotid artery stenosis (odds ratio, 6.43; 95% confidence interval, 3.80 to 10.89) than those with none of these factors. Propensity score-matched analysis showed that incidences of postoperative stroke and cardiovascular comorbidities were both lower in patients who underwent CAS and received appropriate anticoagulant therapy than in those who did not (p = 0.0619 and p = 0.0319, respectively).Preoperative CAS is a simple and useful tool for detecting carotid artery stenosis. Administration of perioperative anticoagulant therapy to preoperative patients with lung cancer and carotid artery stenosis identified by CAS may prevent postoperative stroke and cardiovascular events.

Although several studies have suggested that primary spontaneous pneumothorax (PSP) might occur in clusters, only a few studies have found seasonal variations in PSP occurrence. Some meteorological parameters might be related to the occurrence of PSP occurrence, however, the effects of weather variations on the onset of PSP are still controversial.We examined seasonal differences in the occurrence of PSP and the meteorological risk factors for PSP. All PSP patients aged40 years who were admitted to Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers from April 2007 through March 2013 were included in the study.The incidence rates of PSP were 16.7 and 2.1 per 100,000 person-years in men and women, respectively. The frequency of PSP days among months and seasons was significantly different with a peak in September and autumn. Daily changes in maximum wind speed had positive associations with PSP days [crude OR =1.11 (95% CI: 1.02-1.21) per 1 m/s, P=0.02; multivariable-adjusted OR =1.11 (95% CI: 1.00-1.23) per 1 m/s, P=0.05].PSP tends to cluster seasonally. Increased wind speed may play a role in the development of PSP.

Lung cancer is the leading cause of death due to cancer worldwide. Surgery, chemotherapy, and radiotherapy have been the standard treatment for lung cancer, and targeted molecular therapy has greatly improved the clinical course of patients with non-small-cell lung cancer (NSCLC) harboring driver mutations, such as in epidermal growth factor receptor and anaplastic lymphoma kinase genes. Despite advances in such therapies, the prognosis of patients with NSCLC without driver oncogene mutations remains poor. Immunotherapy targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has recently been shown to improve the survival in advanced NSCLC. The PD-L1 expression on the surface of tumor cells has emerged as a potential biomarker for predicting responses to immunotherapy and prognosis after surgery in NSCLC. However, the utility of PD-L1 expression as a predictive and prognostic biomarker remains controversial because of the existence of various PD-L1 antibodies, scoring systems, and positivity cutoffs. In this review, we summarize the data from representative clinical trials of PD-1/PD-L1 immune checkpoint inhibitors in NSCLC and previous reports on the association between PD-L1 expression and clinical outcomes in patients with NSCLC. Furthermore, we discuss the future perspectives of immunotherapy and immune checkpoint factors.

Objectives It was reported that programmed cell death-ligand 1 (PD-L1) expression is associated with smoking and wild-type epidermal growth factor receptor (EGFR) in lung adenocarcinoma. However, the association between PD-L1 expression and EGFR mutation site in EGFR mutation-positive lung adenocarcinoma is unclear. Materials and methods We retrospectively examined the relationship between PD-L1 expression and EGFR status in 441 surgically resected primary lung adenocarcinomas. Membrane PD-L1 expression on tumor cells was evaluated by immunohistochemical analysis using a PD-L1 antibody (clone SP142) and defined by tumor proportion scores (TPSs) of 0%, 1–4%, 5–49%, and ≥50%, respectively. Results Two hundred and eighteen (49.4%) patients had wild-type EGFR, and 223 (50.6%) had mutant EGFR—98 (44.0%) with exon 19 deletion, 116 (52.0%) with exon 21 L858R point mutation, and nine (4.0%) with another EGFR mutation. Overall, Fisher’s exact test showed that PD-L1 positivity was associated with wild-type EGFR, and there was only one case with PD-L1 TPS ≥50% among the cases with mutant EGFR. The analysis of cases with mutant EGFR indicated no significant association between EGFR mutation site and PD-L1 expression. However, the prevalence of PD-L1 TPS 5–49% was higher among patients with EGFR exon 19 deletion than with EGFR exon 21 L858R point mutation. Conclusions PD-L1 expression was significantly associated with wild-type EGFR, and PD-L1 TPS ≥50% seldom overlaps with presence of driver oncogene EGFR. There was no significant difference in PD-L1 expression among the EGFR mutation sites

Background Little is known about the programmed death-ligand 1 (PD-L1) expression in multifocal lung cancer, such as the expression in multiple primary lung cancer and pulmonary metastasis. In this translational study, we investigated PD-L1 expression and its relationship with the epidermal growth factor receptor ( EGFR ) mutation status in resected multifocal lung cancer. Methods The PD-L1 expression in 152 samples of multifocal lung cancer from 59 patients was evaluated by an immunohistochemical analysis. Results Among the 152 lung cancer lesions of 59 patients, PD-L1 expression was observed in 29 lesions (19.1%) of 20 patients (33.9%). Among 43 patients with 112 multiple primary lung cancer lesions, 15 lesions (13.4%) of 13 patients (30.2%) were PD-L1 positive; and among 16 patients with 40 pulmonary metastatic lesions, 14 lesions (35.0%) of 7 patients (43.8%) were PD-L1-positive. Among 43 patients with multiple primary lung cancer, there was disagreement of PD-L1 expression in 12 patients (27.9%, κ = 0.104). On the contrary, among 16 patients with pulmonary metastasis, disagreement of PD-L1 expression was observed only in 1 patient (6.3%, κ = 0.871). In pulmonary metastatic lesions, the frequency of PD-L1 positivity among lesions with wild-type EGFR was significantly higher than among lesions with mutated EGFR (66.7% versus 0%: p Conclusions This study provides important evidence of higher levels of agreement of PD-L1 expression in pulmonary metastasis compared with in multiple primary lung cancer, and high positivity of PD-L1 expression in pulmonary metastatic lesions with wild-type EGFR in an Asian population.

The CXCR4/CXCR7/CXCL12 chemokine axis plays important roles in the migration of tumor cells during cancer development by modulating site‐specific distant metastasis including to regional lymph nodes. We investigated the correlation of these chemokine expressions to prognosis in lymph‐node‐positive non‐small‐cell lung cancer (NSCLC) patients. A total of 140 surgically resected specimens of primary site (PS) and metastatic lymph nodes (MLN) of NSCLC involving hilar and/or mediastinal lymph nodes (N1‐2) were collected. CXCR4, CXCR7 and CXCL12 expressions were evaluated. Cox regression analysis was performed to determine whether these chemokines were independent prognostic factors in N1‐2 NSCLC. High expression of CXCR4 in PS and CXCL12 in MLN was associated with poor overall survival (OS) (P = .025 and .033, respectively). Significant correlations between CXCR4 expression in PS and CXCL12 expression in MLN were observed (P = .040). There was significant difference in OS between 2 groups according to expressions of CXCR4 in PS and CXCL12 in MLN (P = .0033). Expression of CXCL12 in MLN was identified as an independent prognostic factor (HR 1.79, 95% CI 1.08‐3.04, P = .023). CXCL12 in MLN was mainly expressed by tumor cells compared with stromal cells (56% vs 25%, respectively, P < .0001). CXCR4/CXCL12 may play roles in tumor progression in MLN and is associated with poor prognosis of lymph‐node‐positive NSCLC patients.

Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have been identified as novel targets of immunotherapy of lung cancer. In present study, we evaluated the metabolic characteristics of lung cancer by using 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) with regard to PD-L1 protein expression. PD-L1 protein expression was evaluated by immunohistochemistry with the antibody clone SP142 in 579 surgically resected primary lung cancer patients. Cases with less than 5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 protein expression and the maximum standardized uptake value (SUVmax) in preoperative 18 F-FDG PET/CT. The cut-off values for SUVmax were determined by receiver operating characteristic curve analyses. The SUVmax was significantly higher in nonsmall cell lung cancer (NSCLC) patients with PD-L1 protein expression compared with those without PD-L1 protein expression (P

A tracheal metastasis (TM) from non-pulmonary malignancy is extremely rare, and there are very few reports regarding TM. Here, we report a case of the successful tracheal resection of TM of colorectal cancer. A 36-year-old man underwent a surgical resection for the rectal cancer. Approximately 5 years after the surgical resection of the primary rectal cancer, an isolated TM was identified. The patient was successfully treated with a tracheal resection. In conclusion, the current case suggested that the best treatment of the isolated TM might be a surgical resection.

The oxidized purine nucleoside triphosphatase, mutT homolog 1 (MTH1), physiologically sanitizes 8-oxo-dGTP in the nucleotide pool. Previous studies indicated that MTH1 is associated with tumor proliferation and invasion in non-small cell lung cancer (NSCLC) cell lines; however, the role of MTH1 in patients with NSCLC remains unclear.Two patient cohorts that underwent surgery for NSCLC in our institution were investigated retrospectively. In one cohort consisting of 197 patients, the associations between MTH1 expression and clinicopathological factors or prognosis were analyzed. In another cohort consisting of 41 patients, the relationship between MTH1 expression in the tumors and serum oxidative stress levels (evaluated by the diacron-reactive oxygen metabolites [d-ROMs] test) or antioxidant capacity in the patients (evaluated by the biological antioxidant potential (BAP) test) was analyzed. A total of 238 patients were assessed for MTH1 protein levels using immunohistochemistry.Among the 197 patients in the former cohort, 111 (56.3%) exhibited high MTH1 expression, while 86 (43.7%) exhibited low MTH1 expression. Male sex, smoking habit of ≥20 pack-years, squamous cell carcinoma, pathological stage ≥ II, tumor diameter ≥30mm, lymph node metastases, pleural invasion, lymphatic permeation and vascular infiltration were significantly associated with high MTH1 expression (p0.05). The high MTH1 expression group had a significantly worse prognosis than that of the low MTH1 expression group (5-year overall survival: 81.6% vs. 92.3%, p=0.0011; 5-year disease-free survival: 55.0% vs. 83.7%, p=0.0002). d-ROMs and BAP test values were significantly higher in the high than in the low MTH1 expression group (p0.05).This study showed that MTH1 protein expression was closely related to factors associated with a high malignant potential and poor patient survival. MTH1 may be a novel therapeutic target for NSCLC.

Malignant pleural mesothelioma (MPM) is a devastating neoplasm; however, some patients exhibit a good response to chemotherapy or multidisciplinary therapy, including surgery and chemotherapy. It is therefore important to discover the factors that can be used to select patients who will benefit from such treatment. Although the Controlling Nutritional Status (CONUT) score has been used to predict the prognosis in other types of malignancy, its utility in patients with MPM is unknown. The aim of this study was to clarify the clinical significance of the CONUT in patients with MPM.The data of 83 patients, who were treated with surgery, chemotherapy, or multidisciplinary therapy, were analyzed in the present study. A cut-off CONUT score of 2 was used to classify all of the patients into low or high CONUT groups.Fifty-two of the 83 patients were classified into the low CONUT group. A high CONUT score was significantly correlated with chemotherapy alone (P = .011). The high CONUT group had significantly poorer overall survival (OS) (P .001) and disease- or progression-free survival (DFS/PFS) (P .001). The clinical stage and the CONUT score were found to be independent predictive factors for the OS: clinical stage, I/II and III/IV; P = .001 and CONUT score, ≥ 3 and ≤ 2; P = .011, respectively. The clinical stage and the CONUT score were also independent predictive factors for DFS/PFS: clinical stage, I/II and III/IV; P = .006 and CONUT score, ≥ 3 and ≤ 2; P = .013, respectively.The CONUT score was an independent predictor of a poor prognosis in the patients with MPM. This score provides useful information for selecting patients who will benefit from the treatment.

Background De novo malignancy, including primary lung cancer, is one of the limitations to long-term survival after liver transplantation. The purpose of this study was to describe patients who developed de novo lung cancer after living-donor liver transplantation (LDLT) and investigate their clinicopathological features as well as the feasibility of surgical resection. Patients and methods We investigated 554 patients who underwent LDLT. Results De novo lung cancer after LDLT was observed in five (0.9%) out of 554 studied patients: four men and one woman, aged 61-78 years (mean=67 years). All four men had a smoking history. Clinical stages of de novo lung cancer were stage IA in three patients, and stage IB and IV in one patient each. Three out of five patients underwent pulmonary lobectomy and pathological stage was IA in two patients and IIA in one. All patients who underwent surgery stopped immunosuppressive therapy 1 day preoperatively and restarted on postoperative day 1. There were no serious postoperative complications. All three patients are still alive without any recurrence, with survival ranging from 8 to 29 months, with an average of 16.3 months after diagnosis of lung cancer. Conclusion Although the study population was small, these results suggest that pulmonary lobectomy of de novo lung cancer after LDLT, even under immunosuppressive conditions, is a feasible procedure and may yield a survival benefit.

Background The usefulness of the controlling nutritional status (CONUT) score for preoperative nutritional assessment has been reported in resected colorectal and esophageal cancer, but not in lung cancer with obstructive lung disease. Patients and methods We retrospectively reviewed 109 patients with adenocarcinoma with obstructive pulmonary disease. We set 1 as the cut-off value for the CONUT score and classified patients into high (≥1) and low (0) CONUT groups. Results Among 109 patients, 35 (32.1%) had low CONUT scores, and 74 (67.8%) had high CONUT scores. The high-CONUT group was significantly associated with a lower body mass index (p=0.025) and wild-type epidermal growth factor receptor mutation status (p=0.011). A multivariate analysis showed that the CONUT score was independently associated with disease-free and overall survival. Conclusion The results of this study suggest that the CONUT score was an independent prognostic factor for disease-free and overall survival in patients with lung adenocarcinoma with obstructive lung disease.

AIM The purpose of this study was to investigate the biological role of DNA damage-response genes and chromosomal instability in primary lung adenocarcinoma. MATERIALS AND METHODS We investigated 60 surgically-resected lung adenocarcinomas. Levels of checkpoint kinase 2 gene (CHEK2) and breast cancer type 1 susceptibility protein gene (BRCA1) mRNA expression were evaluated by polymerase chain reaction (PCR). Epidermal growth factor receptor (EGFR) mutations (exon 19 deletion and exon 21 mutation) were detected by the PCR clamp method. Mutations in Kirsten rat sarcoma viral oncogene homolog gene (KRAS) and TP53 were examined by direct sequencing. Expression levels of p27 and p16 proteins were assessed by immunohistochemistry. Chromosomal aberrations (CA) were examined in 20 samples with single-nucleotide polymorphism-comparative genomic hybridization. RESULTS CHEK2 mRNA levels were significantly increased in tumor tissues compared to normal tissues (p=0.0123, paired t-test), whereas BRCA mRNA levels were not increased. TP53 mutation positivity and BRCA1 mRNA expression were positively associated with CHEK2 mRNA expression status (p=0.022 and p=0.0008). High CHEK2 mRNA expression was associated with poor recurrence-free survival (p=0.028). CHEK2 mRNA levels were higher in samples with a high CA frequency than in those with a low CA frequency (averages: 0.326 vs. 0.185; p=0.0129). CONCLUSION The CHEK2 mRNA expression level was found elevated in lung adenocarcinoma and was related to a poor prognostic outcome. The CHEK2 pathway may be important for the proliferation of lung adenocarcinoma, especially in tumors with chromosomal instability.

BACKGROUND/AIM Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in the pathogenesis of lung cancer. We evaluated the metabolic characteristics of non-small cell lung cancer (NSCLC) in patients with and without expression of EZH2 using 18F-fluorodeoxyglucose positron-emission tomography/ computed tomography (18F-FDG PET/CT). MATERIALS AND METHODS The EZH2 protein expression of 268 patients with resected NSCLC, whose preoperative 18F-FDG PET/CT information was available, was evaluated by immunohistochemistry with clone 6A10 antibody; cases with Allred score ≥3 were considered positive. RESULTS Maximized standard uptake values in cases of EZH2-positive NSCLC and adenocarcinoma were significantly higher in comparison to EZH2-negative cases (p

A 69-year-old man with locally advanced squamous cell lung cancer in the left hilum underwent left upper sleeve lobectomy following neoadjuvant chemoradiotherapy with an S-1/cisplatin regimen. On postoperative day (POD) 5, the chest X-ray findings deteriorated, and computed tomography (CT) images showed pulmonary congestion of the left residual lung. We then performed emergent left completion pneumonectomy. Although the Postoperative course after re-operation was uneventful, and the patient was scheduled to be discharged on POD 12 when the serum creatinine level and plasma D-dimer level increased to 1.34 mg/dL and 17.4 µg/mL respectively. CT images revealed a giant thrombus in the left superior pulmonary vein (LSPV) stump, and we immediately started anticoagulant therapy of apixaban at 10 mg/day. We confirmed that the thrombus was reduced in size on POD 30, and the patient was discharged without any further complications. The elevated plasma D-dimer level was a key finding in this case for diagnosing pulmonary vein stump thrombosis (PVT) after left lung surgery. The 23 reported cases of PVT were found incidentally through follow-up CT scan or after serious complications occurred. This is the first case reporting the utility of the plasma D-dimer test for diagnosing PVT after surgical resection of the left lung. Early detection of PVT by a plasma D-dimer test may therefore positively contribute to better outcomes in the postoperative course of surgical resection of the left lung.

In 2015, a newly defined cancer growth pattern was identified. Classified as spread through air spaces (STAS) by The World Health Organization (WHO), STAS is best understood as a new form of cancer invasion.

Objectives Immune checkpoint inhibitors (ICIs) have been established as a novel strategy for non-small cell lung cancer (NSCLC) therapy. However, a definitive biomarker that can predict response to ICI therapy remains unestablished. The prognostic nutritional index (PNI) is used to assess immune-nutritional conditions and is a prognostic factor in patients with various malignancies; however, its usefulness as a biomarker of response to ICI therapy and survival outcomes in NSCLC patients is unknown. Thus, we retrospectively analyzed the clinicopathological features of advanced-stage or recurrent NSCLC patients treated with ICI therapy to identify predictors of response to ICI therapy and investigate the effects of pretreatment PNI levels on survival after ICI therapy. Materials and methods We selected 102 consecutive NSCLC patients who were treated with ICI therapy from November 2015 to February 2019. We measured their pretreatment PNI levels and performed univariate and multivariate Cox regression analyses of progression-free survival (PFS) or overall survival (OS) after ICI therapy. Results Pretreatment PNI levels were significantly associated with response to ICI therapy (objective response rate:P = 0.0131; disease control rate: P = 0.0002), PFS (P = 0.0013), and OS (P = 0.0053). In univariate and multivariate analyses of the associations between PNI, C-reactive protein (CRP) or neutrophil-lymphocyte ratio (NLR) and PFS or OS, NLR and PNI, but not CRP, are independent prognostic factors for PFS (NLR: relative risk [RR]=1.655, 95% confidence interval [CI]: 1.012–2.743, P = 0.0449, PNI: RR=1.704, 95% CI: 1.039–2.828, P = 0.0346). Only PNI showed a trend towards being an independent prognostic factor for OS (RR=1.606, 95% CI: 0.952–2.745, P = 0.0761). Conclusion The pretreatment PNI has the potential to be a simple and novel predictive biomarker of ICI response in NSCLC patients and might help to identify patients who will obtain a survival benefit from ICI therapy.

Skeletal muscle depletion, referred to as sarcopenia, has recently been identified as a risk factor for poor outcomes in various malignancies. However, the prognostic significance of sarcopenia in patients with NSCLC after surgery has not been adequately determined. This study investigated the impact of sarcopenia in patients undergoing pulmonary resection for lung cancer.This retrospective study consisted of 328 patients with pathologically confirmed NSCLC who underwent curative resection between January 2005 and April 2017. Preoperative computed tomography imaging at the third lumbar vertebrae level was assessed to measure the psoas muscle mass index (PMI, cmThe median patient age was 71 years and 59% were male. Sarcopenia was present in 183 (55.8%) and was significantly related with increasing age (p0.001), being male (p0.001), smoking habit (p0.001), lower body mass index (p0.001), and postoperative major complication (Clavien-Dindo grade ≥3, p = 0.036). The prevalence of sarcopenia was higher in men than in women, and the prevalence increased with age in men, whereas the prevalence did not increase in females older than 70 years. The 5-year survival rate was 61% in patients with sarcopenia and 91% in those without. Multivariate analysis revealed that sarcopenia was an independent unfavorable prognostic factor (p = 0.019).Sarcopenia as determined using preoperative computed tomography could be used to predict postoperative major complication and prognosis in patients with resected NSCLC. Our results may provide some important information for preoperative management.

Red blood cell distribution width (RDW) is a parameter measured in blood sample tests that reflects the variation in the volume of erythrocytes and used to differentiate an anemic state. The RDW has been used to predict a poor survival in various types of cancer; however, the prognostic impact of the RDW in resected pathologic stage I nonsmall cell lung cancer (NSCLC) patients remains to be elucidated. A total of 273 patients with resected pathologic stage I NSCLC were included in this study. The cut-off value of RDW was set at 14.5, which was the upper limit of the normal range of the RDW. The controlling nutritional status (CONUT) score, which was calculated by the albumin, cholesterol, and the lymphocyte count, was also investigated. Among 273 patients, 34 (12.5%) were RDW-high, while 239 (87.5%) were RDW-low. RDW-high was significantly associated with a lower body mass index (P0.01), a lower level of hemoglobin (P0.01), a higher level of C-reactive protein (P0.01), and a high CONUT score (P = 0.03) than RDW-low. Patients with RDW-high exhibited significantly shorter recurrence-free and overall survivals (RFS and OS, respectively) than those with RDW-low (P0.01 and P0.01, respectively). Multivariate analyses showed that the RDW was an independent prognostic factor for both the RFS and OS (RFS, hazard ratio [HR]: 2.16, 95% confidence interval [CI]: 1.14-3.95, P = 0.02; OS, HR: 2.44, 95% CI: 1.28-4.49, P0.01). The RDW was shown to be associated with a worse long-term prognosis in resected pathologic stage I NSCLC patients.

BACKGROUND The prognostic Controlling Nutritional Status (CONUT) score is used to evaluate immuno-nutritional conditions and is a predictive factor of postoperative survival in patients with digestive tract cancer. We retrospectively analyzed clinicopathological features of patients with pathological stage I non-small cell lung cancer (NSCLC) to identify predictors or prognostic factors of postoperative survival and to investigate the role of preoperative CONUT score in predicting survival. PATIENTS AND METHODS We selected 138 consecutive patients with pathological stage I NSCLC treated from August 2005 to August 2010. We measured their preoperative CONUT score in uni- and multivariate Cox regression analyses of postoperative survival. RESULTS A high CONUT score was positively associated with preoperative serum carcinoembryonic antigen level (p=0.0100) and postoperative recurrence (p=0.0767). In multivariate analysis, the preoperative CONUT score [relative risk (RR)=6.058; 95% confidence interval (CI)=1.068-113.941; p=0.0407), increasing age (RR=7.858; 95% CI=2.034-36.185; p=0.0029), and pleural invasion (RR=36.615; 95% CI=5.900-362.620; p