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The mutation status of tumor tissue DNA (n = 389) of resected stage II‐III non‐squamous non–small‐cell lung cancer (Ns‐NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG‐TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation‐positive status had a significantly shorter recurrence‐free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22‐2.21; P = .0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30‐2.44; P = .0003 for disease stage; and HR, 1.57; 95% CI, 1.15‐2.16; P = .0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II‐III Ns‐NSCLC patients. This result supports a role for mandatory molecular diagnosis of early‐stage Ns‐NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum‐based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237)., Mutation status of stage II‐III Ns‐NSCLC (n = 389) was analyzed using targeted deep sequencing. Patients with an EGFR mutation‐positive status had a significantly shorter recurrence‐free survival (RFS). Both the pathological stage and EGFR mutation status were independent prognostic factors for RFS.

Background A thymoma with chest pain and multilocular thymic cysts (MTCs) is very rare. Case presentation A 49-year-old man presented to another hospital complaining of an anterior chest pain. Chest computed tomography (CT) showed an anterior mediastinal tumor 60 × 30 × 55 mm in size. The boundary with the pericardium or left brachiocephalic vein seemed to be partially unclear while enhanced by the contrast medium, and so the tumor could have invaded them. No definitive diagnosis of myasthenia gravis was made although the serum anti-acetylcholine receptor antibody count was high. We performed an extended thymectomy with combined partial resection of left brachiocephalic vein, left upper lobe, and left phrenic nerve. He was discharged with no chest pain and no complications post-surgery. The tumor was pathologically type B2 thymoma with hemorrhage necrosis and MTCs, and we diagnosed Masaoka stage II because of no histological infiltration to the organs. Conclusions We speculated that hemorrhagic necrosis due to infarction in tumor caused the inflammation to spread to the surrounding organs, which was related to the chest pain and the development of MTCs.

Robot-assisted thoracoscopic surgery (RATS) for primary lung cancer has been spreading rapidly in Japan. While RATS has various technical advantages over video-assisted thoracoscopic surgery (VATS), the quality of surgery from an oncologic viewpoint must be maintained, and the evaluation of medium- to long-term survival outcomes is momentous. This study included 299 patients with primary lung cancer (VATS, n = 246; RATS, n = 53) who underwent lobectomy and mediastinal lymph node dissection at our hospital. We reviewed and compared perioperative factors, the number of dissected lymph nodes, and postoperative recurrence between the VATS and RATS groups. We also compared the postoperative survival rates among 98 patients (49 patients in each group) whose background factors were adjusted by propensity score matching (PSM). After PSM, a significant difference was found in the total operative time between the two groups (p

To establish the prognostic significance of C-reactive protein (CRP) and albumin in octogenarians with non-small cell lung cancer (NSCLC) based on the study of the Japanese Association for Chest Surgery (JACS 1303).A total of 618 octogenarians with pathological stage I NSCLC, who underwent pulmonary resection, were included in the analysis. We conducted multivariable Cox regression analysis to evaluate the CRP to albumin ratio (CAR) as a potential prognostic factor. Other clinicopathological factors were also evaluated.The median age was 82 years. Operations included lobectomy (n = 388; 62.8%) segmentectomy (n = 95; 15%), and wedge resection (n = 135; 22%). Pathological stage IA was diagnosed in 380 (61.5%) patients. The 3-year (OS) and cancer-specific survival (CS) rates were 86.7% and 94.6%, respectively. OS was significantly higher for patients with low CAR ( 0.106) than for those with high CAR (≥ 0.106) (hazard ratio = 3.13, 95% confidence interval: 1.99-4.93, p 0.0001). Univariate analysis identified sex, poor performance status, smoking status, comorbidity, solid tumor, histology, high Glasgow prognostic scale, and high CAR as significant prognostic factors. Multivariate analysis identified only the CAR as a significant prognostic factor for both OS and CS.Our analysis of the nationwide data demonstrated that the CAR is a useful prognostic factor for elderly patients with stage I NSCLC.

Lung adenocarcinoma (LUAD) shows heterogeneous morphological features and the stepwise progression from adenocarcinoma in situ to minimally invasive adenocarcinoma to invasive LUAD. Although multiple genetic alterations have been linked to the progression, the differences between the gene expression profiles of non-invasive lesions (non-ILs) and adjacent histologically normal lung (aNL) tissues within invasive LUAD have not been investigated. Herein, we analyzed differentially expressed genes (DEGs) specific to early-stage carcinogenesis in LUAD. Invasive LUAD tissue samples containing both non-ILs and aNL tissues were obtained from seven patients with pathological stage I LUAD, and each component was subjected to microdissection. Gene expression profiles of each component were determined using targeted RNA-sequencing. In total, 2536 DEGs, including 863 upregulated and 1673 downregulated genes, were identified in non-ILs. In non-ILs, the expression of SLC44A5, a choline transporter-like protein-coding gene, was significantly upregulated, and that of TMEM100, a gene encoding a transmembrane protein, was significantly downregulated. Reportedly, SLC44A5 plays an important role in the development and progression of hepatocellular carcinoma, whereas TMEM100 functions as a tumor suppressor in non-small cell lung cancer. Gene set enrichment analysis showed that DEGs in non-ILs were negatively enriched in cell death and immune response. Immunohistochemical analysis revealed that increased SLC44A5 expression and decreased TMEM100 expression were maintained in ILs. A protein-protein interaction (PPI) network analysis identified several upregulated and downregulated hub genes with high degrees in non-ILs. In conclusion, several new DEGs and key PPI network hub genes were identified in non-ILs, contributing to understanding of early-stage carcinogenesis in LUAD.

Personalized Induction Therapy-1 is a multicenter, randomized phase II selection design trial of the efficacy and safety of platinum-doublet induction chemotherapy plus angiogenesis inhibitors/concurrent thoracic radiotherapy (TRT) followed by surgery for stage IIIA (N2) nonsquamous non-small cell lung cancer (NSCLC).Patients with pathologically proven stage IIIA (N2) nonsquamous NSCLC were assigned at random to 1 of 2 arms. Patients received (1:1) induction therapy with pemetrexed 500 mg/mEighty-two patients were treated, including 42 in the bevacizumab arm and 40 in the TRT arm. Thirty-eight patients (90%) in the bevacizumab arm and 37 patients (93%) in the TRT arm underwent surgery. The objective response rates in the 2 groups were 50% and 60%, respectively (P = .36). The 2-year PFS and overall survival rates were 37% (95% confidence interval [CI], 22.4%-51.2%) and 50% (95% CI, 33.8%-64.2%) (hazard ratio [HR], 1.34; P = .28), respectively, and 81% (95% CI, 64.7%-89.7%) and 80% (95% CI, 64.0%-89.5%) (HR, 1.10; P = .83), respectively. Although grade 5 toxicity did not occur during induction therapy, 2 patients in the bevacizumab arm died due to bronchopleural fistula.Although not significant, the 2-year PFS rate was higher in the TRT arm than in the bevacizumab arm. Fatal surgical complications were observed only in the bevacizumab arm. Therefore, pemetrexed-cisplatin with concurrent TRT was chosen as the investigational induction treatment strategy for future phase III trials.

The prognostic significance of mediastinal lymph node dissection (MLND) in elderly patients with non-small cell lung cancer (NSCLC) remains unclear. This post hoc analysis of a nationwide multicenter cohort study (JACS1303) evaluated the prognostic significance of MLND in octogenarians with NSCLC.We included 622 octogenarians with NSCLC who underwent lobectomy. The median follow-up duration was 41.1 months. We compared survival and perioperative outcomes between patients who did and did not undergo MLND.In total, 414 (67%) patients underwent MLND (ND2 group), whereas 208 (33%) did not undergo MLND (ND0-1 group). The disease stage was more advanced in the ND2 group than in the ND0-1 group. Disease-free survival was slightly greater in the ND0-1 group with marginal significance (P= .079). In the matched cohort (N = 228), which mainly consisted of patients with clinical stage I disease (96%), there was no significant difference between the 2 groups regarding overall and disease-free survival (P= .908 and P = .916, respectively). Operative time and blood loss were significantly lower in the ND0-1 group than in the ND2 group in the entire cohort (P.001 and P = .050, respectively) and in the matched cohort (P = .003 and P= .046, respectively).Based on a nationwide prospective database, we found limited prognostic impact of MLND, suggesting that MLND can be omitted for octogenarians with early-stage NSCLC.

OBJECTIVES Lymph node dissection (LND) with robot-assisted thoracoscopic surgery (RATS) in lung cancer surgery has not been fully evaluated. The aim of this study was to compare LND surgical results between video-assisted thoracoscopic surgery (VATS) and RATS. METHODS We retrospectively compared perioperative parameters, including the incidence of LND-associated complications (chylothorax, recurrent and/or phrenic nerve paralysis and bronchopleural fistula), lymph node (LN) counts and postoperative locoregional recurrence, among 390 patients with primary lung cancer who underwent lobectomy and mediastinal LND by RATS (n = 104) or VATS (n = 286) at our institution. RESULTS The median total dissected LN numbers significantly differed between the RATS and the VATS groups (RATS: 18, VATS: 15; P CONCLUSIONS In this comparison, it was suggested that more LNs could be dissected using RATS than VATS, especially in bilateral superior mediastinum and hilar regions. Accumulation of more cases and longer observation periods are needed to verify whether RATS can provide the acceptable quality of LND and local control of lung cancer.

The JIPANG study is a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) versus vinorelbine/cisplatin (Vnr/Cis) for completely resected stage II‐IIIA non‐squamous non‐small cell lung cancer (Ns‐NSCLC). This study did not meet the primary endpoint (recurrence‐free survival, RFS) but Pem/Cis had a similar efficacy to Vnr/Cis with a better tolerability. Tumor mutation burden (TMB) is thought to have a predictive value of immune checkpoint inhibitors. However, the relevance of TMB to cytotoxic chemotherapy remains unknown. This exploratory study investigates the relationship between tumor mutation profiles and clinical outcome of Pem/Cis. Formalin‐fixed, paraffin‐embedded tumor tissues (n = 389) were obtained from the patients. Mutation status of tissue DNA was analyzed by targeted deep sequencing. Epidermal growth factor receptor (EGFR) mutations were detected frequently in Ns‐NSCLC (139/374). Patients without any EGFR mutations experienced longer RFS in the Pem/Cis arm versus Vnr/Cis arms. Pem/Cis in patients with high TMB (≥12‐16 mut/Mb) tended to have improved survival. In patients with wild‐type EGFR, TMB ≥ 12 mut/Mb was significantly associated with improved RFS with Pem/Cis versus Vnr/Cis (not reached vs 52.5 months; hazard ratio (HR) 0.477). It could be proposed that TMB was predictive of RFS benefit with Pem/Cis versus Vnr/Cis in Ns‐NSCLC. Further investigation is required to determine whether TMB combined with EGFR mutation status could be used as a predictive biomarker., Tumor mutation burden (TMB) is a predictor of immune checkpoint inhibition therapy. When combined with EGFR mutation status, TMB could be a predictive biomarker of postoperative adjuvant chemotherapy with pemetrexed plus cisplatin for patients with non‐squamous non‐small cell lung cancer. Personalized adjuvant therapy will continue to advance.

Objectives Solid predominant adenocarcinoma is considered an independent predictor of an unfavorable prognosis in patients with stage I lung adenocarcinoma (LUAD). Furthermore, solid minor components are related to poor prognosis in patients with stage I LUAD. Therefore, it is imperative to elucidate the molecular determinants of the malignant potential of solid components (SC). Several studies reported the gene expression profiling specific for lepidic predominant adenocarcinoma or solid predominant adenocarcinoma, however; there is no report identifying the differentially expressed genes (DEGs) between SC and acinar component (AC) within the same tumor tissue in pathological (p)-stage I LUAD patients. Materials and Methods LUAD tissue samples containing both SC and AC were obtained from 8 patients with p-stage I LUAD and each component was microdissected. Targeted RNA sequencing was performed by a high-throughput chip-based approach. Results In total, 1272 DEGs were identified, including 677 upregulated genes and 595 downregulated genes in SC compared with AC. The most highly upregulated gene was TATA binding protein associated factor 7 (TAF7) and the most highly downregulated gene was homeobox B3 (HOXB3), which acts as a metastasis suppressor. A protein–protein interaction (PPI) network analysis of upregulated genes in SC identified ribosomal protein S27a (RPS27a) as a hub gene with the highest degree. First neighbors of RPS27a included PSMA6, which is a highly promising target for lung cancer. The subnetwork of PD-L1 had 10 first neighbors, including CMTM6, which enhances the ability of PD-L1-expressing tumor cells to inhibit T cells. The staining score for PD-L1 in SC was significantly higher than that in AC by immunohistochemistry (p = 0.001). Conclusion Our results revealed several new DEGs and key PPI network in SC compared to AC, contributing to understanding the biological features of SC and providing therapeutic targets for early-stage LUAD with SC in the future.

OBJECTIVES Although some retrospective studies have reported clinicopathological scoring systems for predicting postoperative complications and survival outcomes for elderly lung cancer patients, optimized scoring systems remain controversial. METHODS The Japanese Association for Chest Surgery (JACS) conducted a nationwide multicentre prospective cohort and enrolled a total of 1019 octogenarians with medically operable lung cancer. Details of the clinical factors, comorbidities and comprehensive geriatric assessment were recorded for 895 patients to develop a comprehensive risk scoring (RS) system capable of predicting severe complications. RESULTS Operative (30 days) and hospital mortality rates were 1.0% and 1.6%, respectively. Complications were observed in 308 (34%) patients, of whom 81 (8.4%) had Grade 3-4 severe complications. Pneumonia was the most common severe complication, observed in 27 (3.0%) patients. Five predictive factors, gender, comprehensive geriatric assessment75: memory and Simplified Comorbidity Score (SCS): diabetes mellitus, albumin and percentage vital capacity, were identified as independent predictive factors for severe postoperative complications (odds ratio = 2.73, 1.86, 1.54, 1.66 and 1.61, respectively) through univariate and multivariate analyses. A 5-fold cross-validation was performed as an internal validation to reconfirm these 5 predictive factors (average area under the curve 0.70). We developed a simplified RS system as follows: RS = 3 (gender: male) + 2 (comprehensive geriatric assessment 75: memory: yes) + 2 (albumin

8543 Background: A multicenter phase II study, PIT-2 (Personized Induction Therapy-2), was performed to investigate the efficacy and safety of S-1 plus cisplatin and concurrent thoracic radiation therapy (TRT) followed by surgery in patients with stage IIIA (N2) lung squamous cell carcinoma (LSCC). To date, no clinical trials on the use of induction therapy prior to surgery have focused solely on the treatment of N2 LSCC. Methods: Eligible patients were 20 to 75 years old and had stage IIIA (pathologically proven N2) LSCC, performance status of 0-1, and no prior treatment. The patients received induction therapy consisting of three cycles of S-1 and cisplatin plus concurrent TRT (45 Gy in 25 fractions) followed by surgery. S-1 was administered orally at 40 mg/m2 twice per day, on days 1 through 14 along with an intravenous infusion of cisplatin (60 mg/m2) on day 1. The treatment cycles were repeated every four weeks. The primary endpoint was 2-year progression-free survival (PFS) rate and key secondary endpoints included overall survival (OS), the objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumors version 1.1, pathological complete remission (pCR) rate, feasibility, and toxicity. Results: Of the 45 patients registered between December 2013 and September 2018, 43 received induction therapy. Of the 43 patients, 39 (91%) underwent surgery (25 lobectomies, 10 bilobectomies, three pneumonectomies, and one wedge resection). The complete resection rate was 95% (37/39). Median follow-up time was 35.7 months. The 2-year PFS and OS rates were 67% (90% CI: 54-78%) and 70% (95% CI: 53-81%), respectively. The ORR and pCR rates were 86% (37/43, 95% CI: 76-96%) and 39% (15/39, 95% CI: 23-54%), respectively. Grade (G) 3 or 4 toxicities during the induction therapy in 43 patients included neutropenia (40%), anemia (9%), thrombocytopenia (7%), and hyponatremia (7%). Severe surgical complications in 39 patients included G3/4 pneumonia (5%), G3 bronchopleural fistula (5%), and G3 pleural effusion (5%). No G3/4 intraoperative adverse events occurred. There was no 30-day postoperative mortality and one 90-day postoperative mortality in a patient who underwent right pneumonectomy and developed pneumonia after discharge. Conclusions: Induction therapy using S-1 plus cisplatin and concurrent TRT followed by surgery is a promising treatment for patients with stage IIIA (N2) LSCC. Clinical trial information: 000012413.

Background/Aim: Podoplanin is a candidate cancer stem cell marker in squamous cell carcinoma (SCC). Several studies have reported the prognostic value of podoplanin expression in tumor cells in lung SCC but few have focused on its expression in cancer-associated fibroblasts (CAFs). The aim of this study was to analyze the prognostic significance of podoplanin expression, with special reference to the expression pattern in both tumor cells and CAFs. Patients and Methods: Immunohistochemical analyses using anti-podoplanin antibody were performed on 126 resected specimens of lung SCC. When more than 10% of tumor cells or CAFs showed immunoreactivity with podoplanin levels as strong as those of the positive controls, the specimens were classified as a podoplanin-positive. Results: Podoplanin-positive status in tumor cells (n=54) was correlated with a lower incidence of lymphatic invasion (p=0.031) but there were no significant differences in disease-free survival (DFS) and disease-specific survival (DSS) by the log-rank test. Podoplanin-positive status in CAFs (n=41) was correlated with more advanced stage (p=0.008), higher frequency of pleural invasion (p=0.002) and both shorter DFS (p=0.006) and DSS (p=0.006). In Cox's multivariate analysis, podoplanin-positive status in CAFs was an independent negative prognostic factor for DFS (p=0.027) and DSS (p=0.027). Conclusion: Podoplanin expression in CAFs might be an independent unfavorable prognostic indicator in patients with lung SCC, irrespective of the expression status of tumor cells.

Background At the end of 2016, robot-assisted thoracoscopic surgery (RATS) was still not covered by Japanese national health insurance. Therefore, few institutions in Japan perform RATS and even fewer have reported procedures as they occurred earlier. So, we decided to focus on the initial results of RATS for primary lung cancer. Methods We retrospectively reviewed 44 patients who underwent RATS for primary lung cancer from January 2011 to August 2016. After mastering the initial procedure, we introduced a completely portal robotic pulmonary resection procedure using a carbon dioxide insufflation system. Cases were divided into 2 groups: the early period (20 cases) and the later period (24 cases). Results There was no case of conversion to video-assisted thoracoscopic surgery or thoracotomy. In the 44 cases of primary lung cancer, median operating time was 239.5 min, console time was 179 min, blood loss was 10 mL, drainage period was 2 days, morbidity of Grade 2 or more (Clavien-Dindo classification) was 18.2%, morbidity of Grade 3 or more was only 4.6%, and there was no 30-day mortality. Median operating and console times were significantly shorter in the later period (215 min and 159.5 min, respectively) than in the initial period (300.5 min and 228 min, respectively). Median blood loss was significantly lower in the later period (5 mL) than in the initial period (50 mL). Five-year overall and disease-free survival rates were 100% and 88.9%, respectively. Conclusion RATS for primary lung cancer is feasible and safe, has a faster learning curve, and provides satisfactory. Studies with longer follow-ups and larger numbers of cases are necessary.

There are 2 surgical approaches to secure and treat interlobar pulmonary artery in severe insufficient interlobar fissure of the lung. One is an interlobar approach which is called "fissure first technique". This approach is standard, but sometimes difficult to secure interlobar artery safely. So, lung parenchyma injury and accidental bleeding from the pulmonary artery become troublesome problems. On the other hand, hilar approach without contacting to interlobar fissure which called "hilar first technique" is very useful to avoid lung parenchyma injuries. There are some knack and pitfalls in every lobe of the lung. The key of this approach is to be familiar with the anatomical position of pulmonary artery running by confirming preoperative 3-dimensional computed tomography( 3D-CT). In the final step of this technique cutting the interlobar line exactly is more important to prevent atelectasis and congestion of residual lung. It is very important for thoracic surgeons to know the details of both approaches in the surgical treatment of severe insufficient interlobar fissure of the lung.

Although patients with non-small cell lung cancer exhibiting EGFR mutations generally respond to tyrosine kinase inhibitors (TKIs), the majority of patients acquire resistance ~1 year after treatment. EGFR T790M mutations, MET or HER2 amplifications and phenotypic transformations contribute to the mechanism of EGFR-TKI resistance. The transformation of small cell lung cancer frequently occurs, although few convert to squamous cell carcinoma associated with the administration of EGFR-TKIs. The current study reports a case of EGFR-mutated adenocarcinoma of the lung that transitioned to squamous cell carcinoma in association with long-term EGFR-TKIs administration.

In addition to conventional video-assisted thoracic surgery(VATS)as minimallyinvasive surgeryfor lung cancer, medical insurance system of robot-assisted thoracoscopic surgery(RATS)byusing da Vinci Surgical System®(DVSS)is just adapted from this spring. Although VATS is widelydiffused in clinical practice, it is recommended as grade C1(considerable)in the latest lung cancer medical guideline. On the other hand, it has been noticed that RATS is attractive and expected to cover the disadvantages of conventional VATS. In the comparison of both VATS and RATS lobectomyfor lung cancer, theyhave been reported to be comparable in safetyand efficacy, but RATS is superior at the viewpoint of good operabilityand faster learning curve. However, high costs and the longer operative time in RATS are of a concern. Experience of RATS is still in the initial phase, however from now on RATS is graduallyinfiltrating and expected to demonstrate the improvement of perioperative outcome. Especially, manyinstitutes have just began to introduce robotic surgeryin general thoracic field after the adaption of medical insurance. So, safetyand sure spread of RATS is an urgent and important issue in our field. Of course, while coexisting with VATS, it is important to verifythe efficacyof RATS.

We investigated the efficiency of the Simplified Comorbidity Score (SCS) for predicting postoperative complications and prognosis in elderly patients undergoing video-assisted thoracoscopic surgery (VATS) for lung cancer. We reviewed 216 patients aged 75 years or older, who underwent pulmonary resection by VATS for lung cancer between January, 2005 and December, 2012. The SCS assigns different scores to patients’ comorbidities; namely, smoking (n = 7); diabetes mellitus (n = 5); renal insufficiency (n = 4); and respiratory, neoplastic, and cardiovascular comorbidities or alcoholism (n = 1 each). Patients were divided into a high SCS group (SCS ≥ 9; n = 154) and a low SCS group (

Background/aim We aimed to analyze the clinical impact of solid and micropapillary components in a series of Japanese patients resected for ≤3 cm lung adenocarcinoma. Patients and methods A total of 115 patients with ≤3 cm lung adenocarcinomas were reviewed and classified according to the American Thoracic Society and the European Respiratory Society classification. The presence of solid (S+) or micropapillary component (MP+) was defined when the component constituted ≥1% of the entire tumor. The impact of these components on disease-free (DFS) and disease-specific (DSS) survival was analyzed. Results Thirty (26.1%) cases with S+ and 27 (23.5%) with MP+ were identified, and multivariate analysis indicated that S+ status significantly reduced the duration of DFS and DSS. In 86 patients of acinar- and papillary-predominant subgroups, S+ and/or MP+ had the most significant effect on DFS and DSS by multivariate analysis. Conclusion S+ and/or MP+ status predict worse prognosis in patients with acinar- and papillary-predominant lung adenocarcinoma.

Background Ectopic ACTH-producing thymic carcinoid tumors are rare, but often behave aggressively with local invasion and distant metastasis. We herein report a case of ACTH-producing thymic typical carcinoid tumor with lymph node metastasis treated by surgery and postoperative radiation therapy. Case presentation A 61-year-old woman was admitted to be evaluated for hypoglycemia and hypokalemia. Laboratory data revealed elevation of serum cortisol and ACTH levels. Overnight administration of 8 mg dexamethasone did not suppress plasma ACTH. Chest CT demonstrated a tumor of 30 mm in diameter and enlargement of the lymph node at the anterior mediastinum. Ectopic ACTH syndrome was suspected and total thymectomy and lymph node dissection were performed. The histopathological examination indicated typical carcinoid tumor and mediastinal lymph node metastasis, and immunohistochemical staining was positive for ACTH. The plasma ACTH level decreased immediately after surgery. She received postoperative radiation therapy of 60 Gy. Conclusion Ectopic ACTH-producing thymic typical carcinoid tumors are rare, and it is important to consider this disease and perform appropriate treatment.

Background/aim Maspin is a tumor-suppressor protein and its prognostic value in lung adenocarcinoma has been reported. However, little is known about the clinical impact of subcellular localization of maspin in early-stage lung adenocarcinoma. We aimed to evaluate the clinical significance of subcellular localization of maspin in patients with pathological stage (p-stage) IA lung adenocarcinoma categorized by the new eighth edition TNM classification. Patients and methods We immunohistochemically analyzed 181 tissue samples from p-stage IA1 (n=37), IA2 (n=92) and IA3 (n=52) lung adenocarcinomas using antibody for maspin. Results The 181 cases fell into five predominant subtypes: lepidic (n=32), acinar (n=97), papillary (n=30), solid (n=20) and micropapillary (n=2). The frequencies of maspin staining were: cytoplasmic-only in 24.9%; pancellular (nuclear and cytoplasmic) in 8.8%; nuclear-only in 0.6%; no staining in 65.7%. Cytoplasmic-only staining significantly correlated with high pathological T-classification (p=0.039), lymphatic invasion (p=0.002) and poorer tumor differentiation (p=0.002). The patients were followed-up for 12-151 months (median=74 months), and the cytoplasmic-only staining significantly correlated with shorter disease-free survival (DFS) (p=0.034) and disease-specific survival (DSS) (p=0.036) by log-rank tests. In Cox's multivariate analysis, lymphatic invasion had the most significant effect on shorter DFS and DSS. Conclusion The expression of maspin in the cytoplasm alone could be useful for predicting unfavorable prognoses in patients with p-stage IA lung adenocarcinoma.

As surgical robots have widely spread, verification of their usefulness in the general thoracic surgery field is required. The most favorable advantage of robot-assisted surgery is the markedly free movement of joint-equipped robotic forceps under 3-dimensional high-vision. Accurate operation makes complex procedures straightforward and may overcome weak points of previous thoracoscopic surgery. Robot-assisted surgery for lung cancer and mediastinal disease have been safely introduced and initial results have shown favorable. It is still at the stage of clinical research, but recently a lot of merits of robot-assisted thoracic surgery are proved. Although safety management, education and significant cost are also important issues, the robotic-assisted thoracoscopic surgery will become one of the surgical options in minimally invasive surgery.

Background The aim of this study is to evaluate cases with locoregional recurrence after video-assisted thoracoscopic surgery (VATS) for primary lung cancer. Methods We reviewed 248 patients with primary lung cancer who underwent lobectomy or segmentectomy with mediastinal lymph node dissection by VATS between January 2005 and December 2011. Locoregional recurrence is defined as per its occurrence in (1) bronchial stump or lung parenchymal cut end, (2) ipsilateral pleura, and (3) ipsilateral hilar and mediastinal lymph nodes, and we analyzed recurrence rate and significant associated factors for locoregional recurrence by logistic regression analysis. Results There were 47 cases of postoperative recurrence, which consisted of 26 distant, 6 locoregional and distant, and 15 locoregional recurrences. The locoregional recurrence rate was 6.0%. Of the 15 locoregional recurrence cases, there were two cases of bronchial stump and lung parenchyma cut end (0.4%), five cases of ipsilateral pleura (2.0%), and eight cases of ipsilateral hilar and mediastinal lymph nodes (3.2%). Pleural and lymphovascular invasion and advanced stages were significant associated factors in univariate analysis. Multivariate analysis revealed that advanced stages were only a significant associated factor for locoregional recurrence (p < 0.01, odds ratio: 3.3). Conclusion Although locoregional recurrence rates of our surgical treatments for primary lung cancer by VATS might be acceptable, we should explore more effective modalities against pathologically proven local advanced lung cancer for preventing not only distant but also locoregional recurrences.

BackgroundThe aim of this study is to elucidate the optimal candidate of selective lymph node dissection (LND) that reduces the extent of mediastinal LND according to clinical information including radiological evaluation in primary non–small-cell lung cancer (NSCLC) patients.MethodsEight hundred and seventy-six patients with clinical(c)-stage I NSCLC (adenocarcinoma and squamous cell carcinoma), who underwent complete surgical resection between January 2003 and December 2009 were included in this study. We elucidated the lymph node metastatic incidence and distribution according to the primary tumor lobe location and extracted the associated clinicopathological factors, especially thin-section computed tomographic findings, with mediastinal lymph node involvement.ResultsThe total incidence of mediastinal lymph node metastasis was 9.1%. There were no cases with hilar and mediastinal lymph node metastasis in ground glass opacity-predominant tumors. There was no significant association of clinical factors with subcarinal lymph node metastasis in right upper-lobe and left upper-division adenocarcinoma. An elevated preoperative serum carcinoembryonic antigen level (p < 0.001) showed significant associations with upper mediastinal lymph node metastasis in the patients with bilateral lower-lobe primary lung adenocarcinoma.ConclusionsIt would be acceptable to perform selective LND in patients with c-stage I NSCLC with ground glass opacity- predominant tumor. Elevated serum carcinoembryonic antigen was associated with upper mediastinal lymph node involvement in lower-lobe primary lung adenocarcinoma with radiologically solid-predominant tumor. We should be careful when applying selective LND to patients with solid-predominant tumor, especially located in the lower lobe.

Aims Maspin is known to be a tumour suppressor protein, and few studies focused upon its prognostic significance in patients with small-size lung adenocarcinoma have been reported; however, its clinical significance remains controversial. We explored the prognostic value of maspin with particular reference to its subcellular localization in patients with resected lung adenocarcinoma measuring

At the end of 2016, robot-assisted thoracoscopic surgery (RATS) was still not covered by Japanese national health insurance. Therefore, few institutions in Japan perform RATS and even fewer have reported procedures as they occurred earlier. So, we decided to focus on the initial results of RATS for primary lung cancer.We retrospectively reviewed 44 patients who underwent RATS for primary lung cancer from January 2011 to August 2016. After mastering the initial procedure, we introduced a completely portal robotic pulmonary resection procedure using a carbon dioxide insufflation system. Cases were divided into 2 groups: the early period (20 cases) and the later period (24 cases).There was no case of conversion to video-assisted thoracoscopic surgery or thoracotomy. In the 44 cases of primary lung cancer, median operating time was 239.5 min, console time was 179 min, blood loss was 10 mL, drainage period was 2 days, morbidity of Grade 2 or more (Clavien-Dindo classification) was 18.2%, morbidity of Grade 3 or more was only 4.6%, and there was no 30-day mortality. Median operating and console times were significantly shorter in the later period (215 min and 159.5 min, respectively) than in the initial period (300.5 min and 228 min, respectively). Median blood loss was significantly lower in the later period (5 mL) than in the initial period (50 mL). Five-year overall and disease-free survival rates were 100% and 88.9%, respectively.RATS for primary lung cancer is feasible and safe, has a faster learning curve, and provides satisfactory. Studies with longer follow-ups and larger numbers of cases are necessary.

As the use of robotic surgery has widely spread, its usefulness in the field of general thoracic surgery needs to be verified. The biggest advantage of robotic surgery is the remarkably free movement of joint-equipped robotic forceps under 3-dimensional high vision. An accurate operation makes complex procedures straightforward and may overcome the disadvantages of previous thoracoscopic surgery. Robotic surgery for lung cancer has been safely introduced, and the initial results have been favorable. While still at the stage of clinical research, it is expected to be useful in hilar exposure, lymph node dissection, and suturing of lung parenchyma or bronchus. We considered robotic surgery for lung cancer surgery because of its ability to facilitate both thoracotomy and minimally invasive video-assisted thoracic surgery. Robotic thoracic surgery has not been sufficiently examined for its usefulness, and other major issues such as safety management, education, and significant cost need to be addressed. However, it may become an extension of thoracoscopic surgery, and studies showing its usefulness for primary lung cancer have been increasing. Two urgent issues are its use in advanced medical care and national heal th insurance coverage.