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Concurrent chemoradiation therapy (CRT) is the standard of care for patients with unresectable stage II/III lung cancer. However, systemic chemotherapy is required for patients who are ineligible for radical radiation therapy. There is little evidence to date for the safety and efficacy of CRT administered after treatment with immune checkpoint inhibitors (ICIs). The cases reported here had inoperable stage III lung cancer (non‐small cell lung cancer and small cell lung cancer) and were ineligible for radical radiation therapy. They were administered ICIs plus chemotherapy and subsequently underwent late concurrent CRT. Because of the remarkable tumor shrinkage achieved by the ICIs plus chemotherapy, adverse events of CRT were tolerable. They were alive without tumor progression as of this report, over 1 year after CRT was terminated. CRT is administered with curative intent, while the intent of immunochemotherapy is palliative. Late concurrent CRT after immunochemotherapy is probably effective and tolerable. After treatment with systemic chemotherapy in patients judged ineligible for radical radiation therapy, radiation therapy should be reconsidered because of its importance once tumor shrinkage has been achieved., Late concurrent chemoradiation therapy following systemic therapy (immunotherapy or immunochemotherapy) should be considered as an important treatment option for patients initially judged ineligible for definitive chemoradiation therapy.

Taichi Matsubara, Takashi Seto, Shinkichi Takamori, Takatoshi Fujishita, Ryo Toyozawa, Kensaku Ito, Masafumi Yamaguchi, Tatsuro Okamoto Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, JapanCorrespondence: Taichi MatsubaraDepartment of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, 3-1-1, Notame, Minami-Ku, Fukuoka, 811-1395, JapanTel +81-92-541-3231Fax +81-92-551-4585Email t_matsu@med.kyushu-u.ac.jpPurpose: Anti-programmed death 1 (PD-1) antibodies have emerged as frontline treatments for patients with advanced non-small cell lung cancer (NSCLC) on the basis of global Phase III trials. However, current data regarding responses to anti–PD-1 therapy in older patients with NSCLC or those with poor performance status (PS) are limited. Therefore, we examined the therapeutic effect of anti PD-1 antibody in these patients.Patients: We retrospectively examined consecutive patients treated with anti–PD-1 monotherapy (pembrolizumab or nivolumab) from January 2016 to September 2018.Results: We enrolled 125 patients (median age, 60 years), 80.8% of whom were men. Patients aged ≥ 75 years were considered older patients (n = 15), and those with PS 2– 3 were regarded as having poor PS (n = 11). The objective response and disease control rates were 15.4% and 46.2%, respectively, in older patients and 9.1% and 27.3%, respectively, in those with poor PS. Progression-free survival (PFS) and overall survival (OS) did not significantly differ between older and younger patients. However, poor PS was significantly associated with poor survival. High programmed death ligand 1 (PD-L1) expression in tumor specimens (≥ 50%) was associated with favorable survival in the entire cohort as well as patients with poor PS. Safety analyses demonstrated no significant difference in the occurrence of any adverse event, including grade ≥ 3 adverse events, between patients with poor PS or older age and the remaining patients.Conclusion: Anti–PD-1 therapy had similar efficacy in older and younger patients with NSCLC, whereas survival was significantly worse in patients with poor PS. However, immune checkpoint inhibitors may be considered for patients with poor PS harboring positive PD-L1 expression.Keywords: immunotherapy, non-small cell lung cancer, lung cancer, prognosis

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.

Pneumonitis can be triggered by anti-cancer therapies: cytotoxic chemotherapy, tyrosine kinase inhibitors, and immune checkpoint inhibitors. There are few treatment options for patients who develop such pneumonitis and their treatment including chemotherapy is generally difficult thus would limit patient’s prognosis. In this study, we investigated the clinical course of patients with lung cancer who developed anti-cancer therapy-related pneumonitis. We retrospectively examined data of patients who had developed pneumonitis triggered by anti-cancer agents and required hospitalization from January 2014 to March 2019 and analyzed their subsequent clinical course and prognosis. The median age of the 58 study patients was 68 years and 82.8% were men. The median interval between first receiving the responsible agent and drug-induced pneumonitis was 7.4 weeks. Approximately 38% of patients were subsequently able to receive some anti-cancer therapy. The median post-pneumonitis overall survival (OS) from commencement of anti-cancer treatment was 13.2 months. No significant differences were found in survival time between treatment agents. However, patients who received some anticancer therapy after pneumonitis had significantly longer survival times than those did not (HR = 4.11, p = 0.0003) and patients who took longer to develop pneumonitis had a longer survival (HR = 2.28, p = 0.0148). Multivariate analysis revealed that short interval to onset and no post-pneumonitis anticancer therapy were independent predictors of short survival. Although patients who developed pneumonitis had relatively short survival times, the interval between initial therapy and pneumonitis had survival impact. Survival can be prolonged by administering further cancer treatment after resolution of pneumonitis.

Three immune-nutritional parameters exist for malignant tumors using serum C-reactive protein (CRP) and albumin: the Glasgow prognostic score (GPS), the modified GPS (mGPS), and the CRP-albumin ratio (CAR). However, it remains unclear which of the three parameters is the most predictive of prognosis. Therefore, this study compared the clinical and prognostic significance of these parameters for non-small cell carcinoma (NSCLC). The study retrospectively enrolled 596 NSCLC patients who underwent surgical resection at the authors’ institution from January 2010 to December 2015 and investigated the clinicopathologic significance of GPS, mGPS, and CAR. The optimal cutoff value for CAR was determined by a receiver operating curve (ROC). The median age of the patients was 69 years. Lymph node metastases were identified in 99 patients, and 455 patients had a diagnosis of stage 1 disease. The positivity for GPS was 7.6%, and that of mGPS (score, 1 or 2) was 12.2%. Of the 596 patients, 480 patients (80.5%) were classified in the high CAR group. In univariate survival analyses, all three parameters were associated significantly with postoperative survival. The multivariate analyses showed CAR to be an independent prognostic factor. Additionally, survival analyses of the stage 1 subgroup were performed because CAR was higher for patients with an advanced stage of disease or lymph node metastases. In these subgroup analyses, CAR also was an independent prognostic factor. As the most prognostic index, CAR may be useful among the immunonutritional parameters using CRP and albumin for resected NSCLC.

Immunotherapy targeting programmed death‐1 or programmed death‐ligand 1 has become the standard of care for advanced non‐small cell lung cancer (NSCLC). Several recent clinical trials have investigated the efficacy of immune checkpoint inhibitors (ICIs) as neoadjuvant treatment for early NSCLC. However, the safety and feasibility of pulmonary resection after ICIs remain unclear. We herein report a patient in whom cohesion between the left main pulmonary artery and left upper bronchus was found during left upper lobectomy following neoadjuvant ICI combined with chemotherapy. After both central and peripheral sides of the left main pulmonary artery were clamped with the aim of controlling hemorrhage in case of vascular injury, the left main pulmonary artery and left upper bronchus were divided and individually cut with staplers. The thoracoscopic procedure was otherwise uneventful. The patient was discharged from our hospital with no postoperative complications. Thoracic surgeons should anticipate the possible need for management of cohesion between a pulmonary artery and bronchus in patients who have received immune checkpoint inhibitors preoperatively., We herein report a patient in whom cohesion between the left main pulmonary artery and left upper bronchus was found during left upper lobectomy following neoadjuvant immune checkpoint inhibitor combined with chemotherapy. The left main pulmonary artery and left upper bronchus were successfully divided and individually cut with staplers. Thoracic surgeons should anticipate the possible need for management of cohesion between a pulmonary artery and bronchus in patients who have received immune checkpoint inhibitors preoperatively.

Molecular drugs targeting mutated or rearranged oncogene drivers have become one of the standard recognized treatments in patients with advanced and recurrent non-small cell lung cancer. RET is located in the long arm of human chromosome 10 and encodes a receptor tyrosine kinase protein, and RET fusion-positive lung adenocarcinoma occurs in 1%–2% of cases. Clinical trials of multikinase inhibitors, including cabozantinib, vandetanib, sorafenib, and lenvatinib, that inhibit RET oncogene activity have shown their antitumor efficacy. Recently, RET inhibitors such as pralsetinib and selpercatinib that are specialized for RET kinase have also been developed, and their efficacy was investigated in previous clinical trials (BLU-667 and LOXO-292). In this review, we summarized the effects and adverse events of multikinase and selective RET inhibitors and the various diagnostic techniques for RET gene fusion. In the perspective part, we focused on the unsolved issues on treatment for RET fusion-positive lung cancer and future developments.

Immune checkpoint inhibitors (ICIs) have become one of the standard therapies in non-small-cell lung cancer (NSCLC). Although inflammatory indices, including Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and C-reactive protein/albumin ratio (CAR) were reported to be reliable predictors for survival in cancer patients, their clinical utility in NSCLC patients treated with ICIs is unknown.Advanced or recurrent NSCLC patients (n = 304) treated with ICI monotherapy at the National Hospital Organization Kyushu Cancer Center and Kyushu University Hospital between January 2016 and December 2019 were analyzed. Information on patient demographics, GPS, mGPS, and CAR at diagnosis were collected. The time-dependent area under curves (AUCs) of receiver operating characteristic curves for the prediction of overall survival (OS) for each factor were compared.Of the three indices, GPS was the most significantly correlated with the degree of disease control rate (DCR) (DCR of GPS of 0, 1, and 2: 63.6 %, 49.4 %, and 41.4 %, respectively). The time-dependent AUC values of GPS for the prediction of OS were superior to those of mGPS and CAR (time-dependent AUC values of GPS, mGPS, and CAR for the prediction of 1-year OS: 0.7005, 0.6736, and 0.6565, respectively). GPS was significantly correlated with performance status (PS) (P 0.0001) and clinical stage (P = 0.0139). GPS in combination with PS effectively predicted survival at 1 year ranging from 83.5 % (GPS = 0, PS = 0) to 25.0 % (GPS = 2, PS = 2, 3). A multivariable analysis revealed that GPS was an independent predictor of PFS and OS (P = 0.0009 and P = 0.0100, respectively).We report for the first time that GPS represents a simple and useful prognostic factor in NSCLC patients treated with ICIs and should be validated prospectively.

Highlights • A myelolipoma is a rare benign tumor comprising adipose tissue and normal hematopoietic cells. • A myelolipoma commonly occurs in the unilateral adrenal gland. • This is the first rare case of multifocal myelolipomas of the mediastinum and adrenal gland., Introduction A myelolipoma is a rare benign tumor that is composed of adipose tissue and hematopoietic elements. Myelolipomas most commonly occur in the unilateral adrenal gland. Posterior mediastinal myelolipomas are extremely rare. We herein present a rare case of a multifocal myelolipoma of the mediastinum that gradually enlarged over a 12-year period after surgical resection of an adrenal myelolipoma. This is the first report of multifocal myelolipomas of the posterior mediastinum and adrenal gland. Presentation of case A posterior mediastinal tumor was incidentally found by chest X-ray and computed tomography (CT) examination of a 74-year-old woman. The patient had a medical history of resection of a myelolipoma of the left adrenal gland 12 years earlier. We performed tumor extirpation under video-assisted thoracic surgery (VATS). The size of the tumor was 4.5 cm, and the postoperative diagnosis was a myelolipoma. Discussion Posterior mediastinal myelolipomas are extremely rare, and only 39 cases of mediastinal myelolipoma have been reported to date. No reports have described a multifocal myelipoma of mediastinal myelolipoma. To our knowledge, this is the first report of multifocal myelipomas of the adrenal gland and posterior mediastinum. Conclusion A differential diagnosis of myelolipoma of the posterior mediastinum is important in patients with a history of myelolipoma of the adrenal gland.

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.

Highlights • A rare intercostal lung herniation occurred one year after previous video-assisted thoracic surgery operation for treatment of primary lung adenocarcinoma. • In spite of adequate chest wall closure, a rare intercostal lung herniation occurred after video-assisted thoracic surgery. • Addition of fixation of the ribs to patch repair is a very effective repair for concurrent lung herniation and rib fractures., Introduction Lung herniation is a rare condition defined as a protrusion of the pleural-covered lung parenchyma through an abnormal defect or weakness in the thoracic wall. Postoperative lung herniation is reported to result from a preceding operation with inadequate closure of the chest wall. Presentation of case A 77-year-old woman was admitted to our hospital for treatment of hemoptysis and nausea. One year previously, she had undergone wedge resection of the right lower lobe (S6) for treatment of primary lung adenocarcinoma. Upon admission, chest radiograph and chest computed tomography showed a right lung herniation through the fifth enlarged intercostal space with right fifth and sixth rib fractures. She underwent surgical closure of the intercostal hernia using synthetic materials with fixation of the fifth and sixth ribs. The patient had developed no recurrence 9 months after surgical repair. Discussion In the present case, adequate closure of the right pleural cavity was ensured by fixation of both fifth and sixth ribs during the preceding video-assisted thoracic surgery for the primary lung carcinoma. Our patient may have had some exacerbation factors for lung herniation, increased intrathoracic pressure, attenuation of chest wall by prolonged coughing and rib fracture, and high abdominal pressure due to her hunched-over posture. Concludion It is important to know some exacerbation factors for postoperative intercostal lung herniation. Addition of monofirament-suture fixation of the ribs to patch repair is very effective for lung herniation repair in patients with concurrent lung herniation and rib fractures.

Objectives The programmed death ligand 1(PD-L1)/programmed cell death protein 1 (PD-1) pathway is one of the most important checkpoint pathways for mediating tumor-induced immune suppression through T-cell exhaustion. Recently, targeted therapies using monoclonal antibodies against components of this pathway have been shown to reduce tumor burden in patients with non–small cell lung cancer (NSCLC). However, the prognostic significance of PD-L1 expression is controversial and the precise mechanisms of PD-L1 gene activation in lung cancer have yet to be clarified. Methods We investigated copy number alterations (CNAs) in the PD-L1 gene by real-time PCR in 94 surgically resected lung cancer samples to find possible associations between PD-L1 CNA and lung cancer biology. Janus kinase 2 gene ( JAK2 ) CNA and its influence on the PD-L1/PD-1 pathway were also assessed. Results Five samples were shown to have PD-L1 gene amplification, whereas 89 samples did not. The patients with PD-L1 amplification had worse prognoses than did those without PD-L1 amplification. Genetic amplification of the PD-L1 gene was correlated with JAK2 gene amplification. The lung cancer cell line HCC4006 was found to harbor both JAK2 and PD-L1 amplification. Flow cytometry analyses revealed the level of PD-L1 protein expression to be higher in HCC4006 cells than in other NSCLC cell lines. Expression of the PD-L1 protein was significantly reduced by the JAK2 inhibitor TG-101348 and the signal transducer and activator of transcription 3 (STAT-3) inhibitor BP-1-102, but not by the STAT1 inhibitor fludarabine. Conclusions Our data suggest that expression of PD-L1 protein is upregulated by the simultaneous amplification of the PD-L1 and JAK2 genes through JAK-STAT signaling in NCSLC.

Background The standard of care for patients with small cell lung cancer (SCLC) is chemotherapy and radiotherapy, even for patients with limited disease. To define the role of surgical resection in patients with limited SCLC, we investigated the outcomes of patients diagnosed with limited-stage disease (LD) SCLC. Methods The records of 57 LD SCLC patients who underwent surgical resection from April 1974 to March 2012 were retrospectively analyzed. Results There were six women and 51 men, with a median age of 63.5 years. The overall five-year survival rate was 28.6% (median, 18.2 months). The p-stage II and III patients had a significantly worse survival than the p-stage I patients (13.4% vs. 43.4%, P = 0.0036). However, the c-stage was not found to correlate with survival. Patients who underwent pneumonectomy had a significantly worse outcome than those who underwent other surgical procedures (0.0% vs. 32.0%, P = 0.0002). In a multivariate Cox proportional hazards analysis, p-stage II or III (hazard ratio [HR] 3.040 P = 0.0017) and pneumonectomy (HR 6.177, P = 0.00159) were significant independent predictors of an adverse survival outcome. Conclusions Surgical treatment can be considered in SCLC patients with pathologically proven N0 status, although pneumonectomy should be avoided.

We experienced a case of the cardiopulmonary arrest due to subglottic stenosis developed on the second day after lung cancer surgery. Case : A 73-year-old female who was diagnosed with primary lung cancer was referred to our department for surgery. The second day after left lung segmentectomy, she showed respiratory discomfort symptoms and exhibited hoarseness and stridor, which were revealed as the subglottic stenosis by bronchoscopy. During the emergency airway management, she went into cardiopulmonary arrest. We performed cardiopulmonary resuscitation and simultaneous urgent tracheotomy.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) inhibitors are effective and useful agents for treating patients who harbor EGFR-TKI-sensitive mutations or EML4-ALK rearrangement. Therefore, the importance of determining the presence of these somatic mutations when treating lung adenocarcinomas is widely accepted. However, genetic mutations are rarely evaluated in patients with adenosquamous cell carcinoma of the lung, a relatively infrequent histologic type of lung cancer, because of limited knowledge and the unclear value of assessing these oncogenic mutations in these patients. Therefore, we investigated the clinical implications of somatic mutations in surgically resected adenosquamous cell carcinoma of the lung in Japanese patients. We retrospectively analyzed 32 patients with adenosquamous cell carcinoma of the lung who underwent surgical resection at two institutes in Japan. EGFR mutations and EML4-ALK rearrangement were assessed in all of the patients. Overall, 7 (21.9 %) of 32 patients had EGFR mutations: three patients had an exon 19 deletion and 4 had an exon 21, L858R mutation. There were no T790 M mutations. The median relapse-free survival was 766 days and the median overall survival was 1,152 days in the total cohort. Relapse-free survival and overall survival were not significantly different between patients with or without EGFR mutations. Detecting EGFR mutations in patients with adenosquamous cell carcinoma is clinically important, especially in patients with disease recurrence because EGFR-TKIs may be effective in this histologic type of lung cancer.

Backgrounds The purpose of this study was to investigate the relationship between the level of tobacco smoking and the clinicopathological features of non-small cell lung cancer (NSCLC) patients, individually for adenocarcinoma (Ad) and squamous cell carcinoma (Sq). Patients and methods We retrospectively reviewed the clinical records of 1825 consecutive lung cancer patients who underwent surgery in our department. Among these, the data sets of 750 Ad patients and 364 Sq patients who received lobectomy or more extensive resection were available. Results In Ad patients, those who had never smoked (never-smokers) ( n =309) were more likely to be female, to have less advanced stage tumors, and to have a significantly better prognosis than those who had ever smoked (ever-smokers) ( n =441) (5-year OS: never-smokers, 67.9%; ever-smokers, 53.7%, p n =15) were more likely to be female than the ever-smokers ( n =349). Among ever-smokers, the light-smokers (PY≤30; n =56) were associated with more female patients, more advanced stage tumors, and significantly worse prognoses than were the heavy smokers (PY>30; n =292) ( p =0.0003). The multivariate survival analysis showed that light smoking was related to a worse prognosis compared with heavy smoking (HR=2.06, 95% CI 1.43–2.98, p =0.0001). Conclusions The never-smokers had a significantly better prognosis than ever-smokers among Ad patients, whereas the light-smokers had a significantly worse prognosis than heavy smokers among Sq patients. There may be factors other than tobacco carcinogens that influence the development of Sq in never and/or light smokers.

Programmed cell death ligand 1 (PD-L1) expression in lung cancer appears to be important in immunotherapy, as its expression can predict responses to programmed cell death-1 (PD-1)-blocking antibodies. However, a definitive antibody and cut-off value for PD-L1 expression are urgently needed.The PD-L1 expression in 40 surgically resected small cell lung cancer (SCLC) specimens was evaluated by immunohistochemistry (IHC) with three different antibodies: clones E1L3N, 28-8, and SP142, and using three different evaluations: the Allred score, 1% cut-off, and 5% cut-off.The percentage of tumors with positive PD-L1 expression was inconsistent in the IHC evaluations using the Allred score and 1% cut-off. However, the IHC evaluations using the 5% cut-off showed similar rates of expression using the three different antibodies.The results of this study provided detailed evidence on the frequency of PD-L1 expression in surgically resected SCLC, which may be a useful reference for identifying patients with PD-L1-expressing SCLC.

Introduction The clinicopathological features of carcinomas expressing programmed death ligand 1 (PD-L1) and their associations with common driver mutations, such as mutations in the EGFR gene, in lung adenocarcinoma are not clearly understood. Here, we examined PD-L1 protein expression in surgically resected primary lung adenocarcinoma and the association of PD-L1 protein expression with clinicopathological features, EGFR mutation status, and patient outcomes. Methods The expression of PD-L1 protein in 417 surgically resected primary lung adenocarcinomas was evaluated by immunohistochemical analysis. The cutoff value for defining PD-L1 positivity was determined according to the histogram of proportions of PD-L1–positive cancer cells. Results Samples from 85 patients (20.4%) and 144 patients (34.5%) were positive for PD-L1 protein expression according to 5% and 1% PD-L1 cutoff values, respectively. Fisher's exact tests showed that PD-L1 positivity was significantly associated with male sex, smoking, higher tumor grade, advanced T status, advanced N status, advanced stage, the presence of pleural and vessel invasions, micropapillary or solid predominant histological subtypes, and wild-type EGFR . Univariate and multivariate survival analyses revealed that patients with PD-L1 positivity had poorer prognoses than those without PD-L1 protein expression at the 1% cutoff value (disease-free survival p p Conclusions PD-L1 protein expression was significantly higher in smoking-associated adenocarcinoma and in EGFR mutation–negative adenocarcinoma. PD-L1 protein expression was associated with poor survival in patients with lung adenocarcinoma. The PD-L1/programmed cell death 1 pathway may contribute to the progression of smoking-associated tumors in lung adenocarcinoma.

The purpose of this study was to investigate the prognostic significance of epidermal growth factor receptor (EGFR) sensitizing mutations in patients with lung adenocarcinoma who underwent complete surgical resection.We retrospectively reviewed the clinical records of 164 patients with lung adenocarcinoma who underwent surgery from 2003 to 2010. Seventy-four patients harbored EGFR mutations; two with exon 18 mutations, 27 with exon 19 mutations, and 45 with exon 21 mutations.There were more female patients and more never-/light smokers among patients with EGFR mutations than among patients without EGFR mutations. Patients with EGFR mutations had a trend for better disease-free survival and overall survival compared to patients without EGFR mutations (p=0.068 and p=0.049, respectively). Patients with exon 21 mutations had significantly better disease-free survival than patients with exon 19 mutations (p=0.027).Adenocarcinomas harboring EGFR exon 21 mutation were less malignant than adenocarcinomas harboring exon 19 mutation.

The most effective treatment for early-stage non-small cell lung cancer (NSCLC) is surgical resection. Nevertheless, up to 20% of patients, even those with stage I NSCLC, relapse after surgery and die. The prognostic nutritional index (PNI) is used to assess immunonutritional conditions or is a predictor of postoperative recurrence in patients with digestive malignancies. However, the usefulness of the PNI for lung cancer is still unknown. We retrospectively analyzed clinicopathological features of stage I NSCLC patients to identify predictors of recurrence and to investigate effects of preoperative PNI levels.We selected 141 consecutive stage I NSCLC patients who were treated from August 2005 to August 2010. We measured their preoperative PNI levels in uni- and multivariate Cox regression analyses of recurrence-free survival.A low PNI was significantly associated with sex (P=0.0117), preoperative serum carcino embryonic antigen levels (P=0.0228), and postoperative recurrence (P0.0001). In multivariate analysis, PNI (RR: 9.243; 95% CI: 3.662-25.823; P0.0001), pleural invasion (RR: 8.664; 95% CI: 2.510-38.056; P=0.0005), and intratumoral blood vessel invasion (RR: 3.151; 95% CI: 1.259-7.681; P=0.0152) were independent prognostic factors. The low-PNI group had a significantly shorter recurrence-free survival than the high-PNI group, regardless of pathological T factors (T1a, P=0.0422; T1b, P0.0001; T2a, P=0.0098).The preoperative PNI level is a simple and novel predictor of recurrence in stage I NSCLC patients, and might help identify patients who will need multimodality therapy such as induction or adjuvant therapy.

Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement often have a better prognosis when they are treated with specific inhibitors than when treated with cytotoxic agents. However, the associations between gene mutations and cytotoxic chemosensitivity are still unclear. The objective of the present study was to identify which clinicopathological factors, including genetic mutations, influence chemosensitivity, determined using the succinate dehydrogenase inhibition (SDI) test in patients with NSCLC.The chemosensitivity of tumor tissues from 96 patients with NSCLC who underwent surgical resection was evaluated using the SDI test.In patients with adenocarcinoma, tumors with EGFR gene mutations were significantly more sensitive to 5-fluorouracil (5-FU) than tumors without EGFR gene mutations (p0.0149).Our data suggest that patients with adenocarcinoma harboring EGFR gene mutations may be susceptible to 5-FU.

A 77-year-old male was referred to our department due to lung cancer (cT3N0M0) of the right lower lobe. During right lower lobectomy, a thin duct structure was recognized in the hilar region between the middle and lower lobes that was identified to be a supernumerary bronchus upon a review of the preoperative chest CT images. Although bronchial anomalies are rare, it is important to carefully view preoperative images for any such anomalies in order to more safely perform surgery.

Background The standard of care for patients with small cell lung cancer (SCLC) is chemotherapy and radiotherapy, even for patients with limited disease. To define the role of surgical resection in patients with limited SCLC, we investigated the outcomes of patients diagnosed with limited-stage disease (LD) SCLC. Methods The records of 57 LD SCLC patients who underwent surgical resection from April 1974 to March 2012 were retrospectively analyzed. Results There were six women and 51 men, with a median age of 63.5 years. The overall five-year survival rate was 28.6% (median, 18.2 months). The p-stage II and III patients had a significantly worse survival than the p-stage I patients (13.4% vs. 43.4%, P = 0.0036). However, the c-stage was not found to correlate with survival. Patients who underwent pneumonectomy had a significantly worse outcome than those who underwent other surgical procedures (0.0% vs. 32.0%, P = 0.0002). In a multivariate Cox proportional hazards analysis, p-stage II or III (hazard ratio [HR] 3.040 P = 0.0017) and pneumonectomy (HR 6.177, P = 0.00159) were significant independent predictors of an adverse survival outcome. Conclusions Surgical treatment can be considered in SCLC patients with pathologically proven N0 status, although pneumonectomy should be avoided.

A 71-year-old male with a history of asbestosis was referred to our department for the treatment of a bilateral pneumothorax. His pulmonary function was severely impaired because of asbestosis and emphysema. Chest computed tomography showed severe emphysema with bilateral multiple bullae. Although chest drainage tubes were placed in the bilateral thorax, the left lung did not completely expand due to a persistent air leak. We performed VATS while retaining the patient's spontaneous respiration under general sedation with regional epidural anesthesia, since one-lung, positive pressure ventilation was considered to be difficult to achieve. After the airway was secured by a laryngeal-mask, the bullae were then thoracoscopically resected. The pneumothorax improved after surgery.