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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

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.

Pure high-grade fetal adenocarcinoma of the lung (H-FLAC) is a very rare tumor. An annual check-up revealed an abnormal shadow in the left middle lung field of a 63-year-old Japanese man. Chest computed tomography (CT) showed a 3.6 × 2.8 cm pulmonary lesion with clear boundary in the left upper lobe. A transbronchial lung biopsy revealed non-small cell carcinoma. A left upper lobectomy and mediastinal lymph node dissection were performed. Histologically, the tumor consisted of solid proliferation of atypical cell with clear cytoplasm. Another histological component and morulae were not contained. Immunohistochemically, the tumor was focally positive for alpha-fetoprotein (AFP) and beta-catenin in the cell membrane. Accordingly, we made the diagnosis of pure H-FLAC, pT2aN2M0, stage IIIA. Two courses of adjuvant chemotherapy (cisplatin and vinorelbine) were administered but then the treatment was discontinued due to the patient’s adverse reaction. At 25 months after the surgery, the patient had relapsed. We report a very rare case of pure H-FLAC. This histology has been considered to predict an extremely poor prognosis; therefore, the elucidation of genetic abnormalities and effective treatment is awaited.

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

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.

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.

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.

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

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.

Minimally-invasive surgeries including video-assisted thoracoscopic surgery and robot-assisted thoracoscopic surgery are used throughout the world and are one of the standard approaches to primary lung cancer and other chest diseases. The clinical utility of those surgeries has improved owing to advances in thoracoscopic instruments and techniques; however, it is also increasingly important for thoracic surgeons to know how to manage unexpected intraoperative bleeding during these surgeries, particularly thoracoscopic surgeries. In this review, we outline the essentials to perform safe thoracoscopic surgery, showing specific methods for controlling bleeding and repairing the injured vessels. In addition, we discuss indications and timings of conversion to open thoracotomy and show the algorithm of management for unexpected intraoperative bleeding during video-assisted thoracoscopic surgery.

Introduction The aim of this study was to radiologically identify early lung adenocarcinoma in clinical T1bN0M0 lung cancer, based on pathological findings and long-term prognosis. Methods In this study, we reviewed lung nodules findings on thin-section computed tomography in 173 patients with clinical T1bN0M0 lung adenocarcinoma who underwent surgery between 2003 and 2007. The ratio of the size of solid attenuation to the maximum tumor dimension (consolidation/tumor [C/T] ratio) was calculated. We defined two groups of patients by C/T ratio cutoff levels of 0.00, 0.25, 0.50, 0.75, and 1.00 and compared the rates of pathological nonaggressive lung adenocarcinoma, overall survival, and recurrence rates between the groups. The percentages of predominant histological subtypes were compared between two groups divided by the optimal cutoff level. Various clinical factors were analyzed by univariate and multivariate analyses to predict pathological lymph node involvement. Results The median follow-up period was 62 months. All patients with C/T ratios of 0.5 or less were diagnosed as having pathological nonaggressive adenocarcinomas, and there was no recurrence; their 5-year overall survival rate was 97.4%, which was significantly better than that for patients with C/T ratios of greater than 0.5 (76.2%). None of the ground-glass opacity–predominant tumors were predominantly solid adenocarcinoma with mucin. The C/T ratio of 0.5 or more was an independent predictor of lymph node involvement. Conclusion In patients with clinical T1bN0M0 disease, the C/T ratio of 0.5 or less identified early lung adenocarcinoma. In patients with the identified early disease, a feasibility study of limited surgery may be warranted.

Although the optimal treatment strategy for locally advanced thymic carcinomas has yet to be determined, complete resection of the tumor after induction chemoradiotherapy (CRT) can sometimes provide a good chance of being cured. A 61-year-old woman was diagnosed with locally advanced primary thymic carcinoma, which invaded bilateral brachiocephalic veins and superior vena cava with intraluminal tumor thrombus. Induction CRT was performed, and a partial response to the treatment was achieved. Subsequent radical surgery was successfully performed by the median full sternotomy with a right transmanubrial osteomuscular sparing approach (TMA). The patient is currently alive and has remained disease-free for a year. The TMA is useful for extensive surgery of locally advanced thymic carcinoma because it can provide good exposure of the operative field without post-operative functional limitation of upper limbs.

The solid component of lung ground-glass nodules on thin-section computed tomography (TSCT) reflects cancer cell progression and invasiveness. The purpose of this study was to clarify the cut-off value of preoperative TSCT findings in treating a lesion suspected of being adenocarcinoma and to recognize the timing of surgical resection for lung nodules. We reevaluated the TSCT findings in 392 patients with clinical stage IA lung adenocarcinoma who underwent surgical resection between 2003 and 2007. We identified the clinical parameters that were most useful for predicting recurrence and identified a cut-off level for each parameter. Recurrence was observed in 75 (19 %) of 392 patients (median follow-up: 7 years). The size of internal consolidation of a lung nodule (SCL) and the ratio of the SCL to the maximum tumor diameter (C/T ratio) were extracted as independent factors that predicted recurrence. Only 1 (0.3 %) patient each with a lung nodule C/T ratio ≤0.5 and SCL ≤10 mm recurred. These conditions were associated with a significantly better overall survival and recurrence-free survival. In patients with clinical stage I lung adenocarcinoma with a C/T ratio ≤0.5 and/or SCL ≤10 mm on TSCT, surgery is extremely likely to achieve a cure.

Non-small cell lung cancer (NSCLC) accounts for >85% of incidences of lung cancer, for which the predicted 5-year survival rates are low and recurrence rates remain high. Although it has been reported that the patients with SCLC cells that possess the cluster of differentiation (CD) 117 marker exhibited poor prognosis and poor response to chemotherapy, no studies concerning the association of CD117 expression with prognosis of the patients with NSCLC have been reported. An in vitro study reportedly revealed that CD117-positive cell populations in NSCLC cell lines exhibited cancer stem cell (CSC) phenotypes including self-renewal and chemoresistance. Therefore, the present study hypothesized that if CD117-positive cells are CSC-like cells, CD117 positivity may be associated with the prognosis of patients with NSCLC. To confirm this hypothesis, the association between CD117 expression in patients with NSCLC and clinicopathological characteristics was investigated. CD177 expression was examined by immunohistochemistry in 99 patients with NSCLC who underwent curative surgical resection. Tumor samples in the present study included 73 samples of adenocarcinoma and 26 of squamous carcinoma. The associations of CD177 expression with clinicopathological features and prognosis were examined. The lymph node metastasis and rates of recurrence were significantly associated with overall survival rates through multivariate analysis (P

We performed robot (da Vinci)-assisted thoracoscopic extended thymectomy (rThx) for myasthenia gravis with thymoma. The patient was a 66-year-old woman who complained of palpebral heaviness. Robotic operation was performed in the supine position by placing four ports in the right chest wall under 10 mmHg CO(2) insufflation using three arms and one assist port. Compared with conventional video-assisted thoracic surgery (VATS), the bilateral upper horns, fat around the diaphragm, and aortopulmonary window could be resected more easily. The tumor measured 41 mm maximum diameter and was diagnosed as type AB noninvasive thymoma. The operating time was 298 min, console operating time was 203 min, and the amount of bleeding was small. The postoperative course was uneventful with no complications. This is a report of the first Japanese case of rThx for myasthenia gravis. rThx is a promising technique, and further improvement in the procedure is expected.

Geminin is an important molecule which plays a role in cell cycle regulation, and this has been considered to be a useful biomarker of cell proliferation. The purpose of this study was to evaluate the pathological and prognostic significance of geminin expression in small lung adenocarcinoma (AC). We performed Western blot analysis of five human lung AC cell lines and immunohistochemistry on 100 surgically resected specimens of lung AC with a diameter less than 3 cm. We counted the number of positively stained tumor cells, and calculated the labeling indices (LIs). Geminin proteins were variably detected in all five cell lines examined on Western blotting. The mean LIs for geminin, Ki-67, and MCM7 were 7.5%, 12.3%, and 18.5%, respectively. The geminin LIs were associated with some clinicopathological profiles including gender, histological grade, subtypes, N-status, p-factor, and tumor stage. A significantly worse prognosis was noted in the higher geminin LIs group than in the lower group (p < 0.01). Multivariate Cox regression analysis also confirmed that geminin LIs was an independent prognostic marker in stage IA lung AC patients. These results suggest that geminin is overexpressed in small lung ACs, and geminin LIs might be a useful prognostic indicator in patients with lung AC.

A 29-year-old man had been diagnosed with an anterior mediastinal cyst 6 years earlier and was undergoing follow-up. At a follow-up visit, a newly developed cystic lesion was found in the middle mediastinum; therefore, the anterior mediastinal cyst and the middle mediastinal cyst were resected by thoracoscopic surgery. It was observed that the middle mediastinal cyst originated from the thoracic duct, and the thoracic duct was clipped. Pathologically, the diagnosis was a thymic cyst of the anterior mediastinum and a thoracic duct cyst of the middle mediastinum. The patient developed chylothorax after surgery, and a second thoracoscopic operation was performed. It revealed that part of the clipping of the caudal thoracic duct was incomplete, and leakage of chyle was observed. Hence, the clipping was performed again. The course after the second surgery was good. Thoracic duct cysts are rare even among mediastinal cysts and thus require caution due to their tendency to expand.

This report presents a rare case of lung adenocarcinoma accompanied by partial spontaneous regression (SR). A 69-year-old woman with an abnormal shadow on chest X-ray was admitted to the hospital. She was diagnosed to have lung adenocarcinoma with right adrenal metastasis based on a thorough examination. However, a month after the diagnosis, the primary and metastatic lesions markedly shrank on the following computed tomography scan and (18)F-fluorodeoxyglucose positron emission tomograph. This was thought to be a partial SR of the cancer, and she was treated with a surgical procedure. She has since remained free of disease for 14 months after the surgery.

Background and objective: The Japanese Respiratory Society recently proposed ‘lung age’ as an easily understood concept of respiratory function. In this study, we evaluated whether ‘lung age’ could be a useful predictor of post-operative respiratory complications and survival patients with lung cancer treated surgically. Methods: The study recruited 308 patients who underwent surgery for primary non-small-cell lung cancer. All patients had preoperative pulmonary function testing. ‘Lung age’ was determined using the methods advocated by the Japanese Respiratory Society. Based on the difference between ‘real age’ (R) and ‘lung age’ (L), patients were classified into five groups: group A: R−L > 15 (n = 37), B: 5 R−L (n = 94). Clinicopathological factors, post-operative respiratory complications and survival were compared between the groups. Results: Gender, smoking status and index, histology, operative approach and FEV1 were significantly associated with the group classification. The incidence of complications was significantly higher in group E compared with other groups (P = 0.003). Multivariate analysis showed that the group classification by ‘lung age’ was an independent predictor of post-operative respiratory complications (P = 0.02). Overall survival differed significantly between the groups (P = 0.03). Conclusions: ‘Lung age’ could be useful for the prediction of post-operative respiratory complications and survival in patients with lung cancer treated surgically.

We examined the clinicopathological features of four mediastinal lymph node carcinomas from an unknown primary site.Four patients with mediastinal lymph node carcinoma from an unknown primary site were treated at our hospital during the past 6 years.All of the patients were men, with an average age of 74.0 years (range 70-78 years). Histologically, one lesion was poorly differentiated adenocarcinoma, two were poorly differentiated squamous cell carcinoma, and one was undifferentiated carcinoma. Radical resection of the mediastinal tumor and radiotherapy were performed in two patients, both of whom were still alive with no evidence of recurrence at 44 and 82 months, respectively, after the operation. Thoracoscopic biopsy was performed in two patients, and both underwent chemoradiotherapy. These two patients were alive at 24 and 33 months, respectively, after the biopsies.Radical resection of mediastinal lymph node carcinoma with an unknown primary site has the possibility of a good prognosis. In nonradical cases, it is important to perform a biopsy to make an accurate diagnosis and then administer radiotherapy and/or chemotherapy postoperatively.

A 69-year-old woman was admitted to our hospital with the complaint of a right breast mass. As a result of thorough examinations, she was diagnosed with breast cancer and underwent breast-conserving surgery. The pathological findings of the resected specimen showed that the tumor consisted of intermingled carcinomatous and sarcomatous components with a transition zone. On immunohistochemical study, the sarcomatous cells in this transition zone showed partial positive staining for CD10, the myoepithelial marker, suggesting that the myoepithelial cells had transformed into sarcoma, and then this biphasic tumor was formed. Finally, she was diagnosed with biphasic metaplastic sarcomatoid carcinoma of the breast. Biphasic metaplastic sarcomatoid carcinoma of the breast is a relatively rare but aggressive disease. The pathological diagnosis is often controversial, requiring detailed immunohistochemical analysis. We report our experience with a case of biphasic metaplastic sarcomatoid carcinoma of the breast.

To study the effects of smoking on the postoperative outcome of lung cancer surgery.The subjects were 571 patients who underwent surgery for primary lung cancer. The patients were divided into the following groups according to their smoking history: a nonsmoker group (n = 218), a former smoker group (n = 140), and a current smoker group (n = 213).The 5-year survival rates were 56.2%, 40.9%, and 34.0% in the nonsmoker, former smoker, and current smoker groups, respectively. These differences were significant. According to a multivariable analysis, smoking was a significant factor affecting the postoperative prognosis of patients undergoing surgery for lung cancer. In analyzing the causes of death, there were more deaths caused by other diseases such as multiple organ cancer, respiratory disorder, cardiovascular disease, and surgery-related events in the former smoker and current smoker groups than in the nonsmoker group.Smoking was significantly predictive of a poor prognosis after lung cancer surgery.

Aims Maspin is known to be a tumour suppressor protein, and its prognostic significance in patients with several types of cancer, including lung squamous cell carcinoma (SCC), has been reported. However, its prognostic impact on lung SCC has been controversial. We explored the prognostic value of maspin expression with particular reference to its subcellular localization in patients with lung SCC. Methods and results Paraffin-embedded tissue samples from 101 curatively resected patients with lung SCC were analysed immunohistochemically using an antibody for maspin. Maspin positivity was defined as strong expression in only the cytoplasm and observed in 25 patients (24.6%). It correlated significantly with the presence of lymph node metastasis (P = 0.006) and higher pathological stage (P = 0.003). The patients were followed-up for 2-119 months (median: 50 months), and the maspin-positive group had shorter disease-free survival (DFS) and disease-specific survival (DSS) by log-rank test (P = 0.002, P = 0.016, respectively). Multivariate analysis revealed that the status of maspin was the only independent prognostic factor for DFS and DSS (P = 0.017, P = 0.047, respectively). Conclusions Cytoplasmic expression of maspin could be an independent unfavourable prognostic indicator in patients with lung SCC.

We describe a successful surgical case of a 78-year-old man with a squamous cell carcinoma of the lung invaded to the esophagus. Chest computed tomography on admission showed a tumor mass shadow in the left lower lobe (S(6)). The tumor was adjacent to the esophagus, which was a strongly suspected lung cancer with esophageal invasion. We performed the transesophageal endoscopic ultrasound (EUS) for a detailed evaluation of the degree of invasion, and we obtained the findings of localized tumor invasion into the muscular coat of the esophagus. The tumor invaded to the esophagus perioperatively, and we could remove all the involved area with enough surgical margin. We believe that the preoperative evaluation using EUS is a useful procedure, if we suspect the lung cancer with esophageal invasion.

A 58-year-old woman visited our hospital with the chief complaint of an abnormal chest shadow. Chest CT showed an 18-mm ground-glass opacity in the right upper lobe, which became enlarged over time, and lung cancer was suspected. At the same time, a tracheal bronchus originating directly from the trachea was observed. She underwent thoracoscopic right upper lobectomy and mediastinal lymph node dissection. During surgery, in addition to the tracheal bronchus, a pulmonary vein variation was seen running dorsal to the pulmonary artery. Her postoperative course was uneventful. Tracheal bronchus is a rare anomaly, with an incidence of 0.1%-5%. Since tracheal bronchus is often accompanied by pulmonary vessel variations and may be associated with repeated previous infections, care should be taken when performing thoracoscopic lung resection.

We report a case of thoracoscopic resection of mediastinal parathyroid adenomas using methylene blue to localize the tumors during the operation. After methylene blue 4 mg/kg was injected intravenously, we easily identified methylene blue-stained parathyroid glands and successfully resected them with sufficient surgical margins. The use of methylene blue for detection of parathyroid adenoma is a useful technique.

Herein, we report a patient with a rare disease, intrapulmonary schwannoma. The patient was a 61-year-old woman who had a 20 mm × 18 mm nodule, with a clear boundary and homogeneous content, on the central side of S4 in the right lung on chest CT. On PET with 18- fluorodeoxyglucose scanning, 18-fluorodeoxyglucose accumulations with a maximal standardized uptake value of 2.5 and 3.3 were observed in the early and late phases, respectively, suggesting a malignant tumor. A thoracoscopic right middle lobectomy was performed because the tumor was present in the segmental bronchial region of the middle lobe. Intrapulmonary schwannoma accounts for 0.2% of lung tumor cases, and cases involving patients who have undergone preoperative PET with 18- fluorodeoxyglucose scanning have rarely been reported.

Pulmonary epithelioid hemangioendothelioma (PEH) is a relatively uncommon neoplasm of vascular origin with a low or intermediate grade of malignancy. We present a case of a 28-year-old female with multiple pulmonary nodules which were diagnosed as PEH by video-assisted thoracoscopic surgery (VATS) biopsy. In addition, we performed an immunohistochemical analysis for placenta growth factor (PlGF) and a strong positivity for PlGF observed, suggesting that the PlGF may play some role in the tumorigenesis of PEH.

The patient was a 47-year-old male with the chief complaints of right shoulder pain and fever. A 10-cm mass was found to be present in the right pulmonary apical region on chest X-ray examination. The mass was diagnosed as a G-CSF-producing invasive apical cancer and the patient underwent chemoradiotherapy followed by right upper lobectomy with combined resection of the chest wall, and lymph node dissection. A very small nodule was noted in the right frontal lobe on brain MRI before surgery, and the final diagnosis was pT3N0M1, stage IV lung adenocarcinoma. For the brain metastasis, gamma knife treatment and chemotherapy were performed after surgery, and there was no recurrence during 16 months after surgery. The prognosis for G-CSF-producing lung cancer and invasive apical cancer is poor. This was a rare and difficult case of lung cancer showing both characteristics of lung cancer.

We report a rare case of left lung cancer in a patient with a right aortic arch. A 65-year-old woman was diagnosed to have an adenocarcinoma in the left upper lobe (S3) in addition to a right aortic arch (type II), with the left subclavian artery originating from the descending aorta. Left upper lobectomy and lymph node dissection was performed by video-assisted thoracic surgery (VATS). For the mediastinal dissection, the upper mediastinal lymph nodes were easily resected after verifying the location of the arterial ligament and the recurrent laryngeal nerve (RLN). This is the first report of using VATS to remove a lung cancer from a patient with a right aortic arch.

The patient was a 62-year-old male who underwent wide resection and radiotherapy for right scapular chondrosarcoma 12 years ago. An abnormal shadow was detected in the right upper lung field included in the irradiated field on chest X-ray. Since the nodule tended to enlarge, a malignant lung tumor was suspected, and surgery was performed. On histological examination, spindle cells densely proliferated in a bundle pattern. Vimentin, bcl-2 protein, and CD99 were positive, and CD34, cytokeratin, AE1/AE3, and EMA were partially positive on immunohistochemical staining. The SYT-SSX (synaptotagmin- synovial sarcoma X) fusion gene was detected employing RT-PCR, based on which primary synovial sarcoma of the lung was diagnosed. The findings also matched the diagnostic criteria of radiation-induced sarcoma, suggesting radiation-induced primary synovial sarcoma of the lung. Primary synovial sarcoma of the lung is a rare tumor. It is difficult to diagnose based on cellular findings, and immunohistochemical and genetic investigations are essential. Radiation-induced sarcoma may develop through a long-term course, as seen in this patient, for which long-term follow-up after radiotherapy is important.

Cell cycle-related molecules play crucial roles in maintaining genomic stability, and can also serve as biomarkers of cell cycle phase distribution at the same time. In this study, we used multiparameter analysis of various biomarkers to investigate their utility for the evaluation of tumor proliferation activities and the prognosis of patients with small-size lung adenocarcinoma. We performed immunohistochemical analysis using five cell cycle-related biomarkers (MCM7, Ki-67, Geminin, Aurora A and H3S10ph) for 102 surgically resected small-size lung adenocarcinomas. We classified them into three phenotypes based on the dominant cell cycle phase distribution of the tumor cell population, and evaluated whether these phenotypes were associated with clinicopathological factors and survival. Phenotype I (MCM7-negative tumors; n=56) was correlated with high or moderate differentiation and reduced local invasiveness (pleural and lymphovascular invasion) compared with phenotype II (MCM7-, Ki-67- and Geminin-positive tumors; n=23) and phenotype III (MCM7-, Aurora A- and H3S10ph-positive tumors; n=17). Five-year survival rates of phenotypes I, II and III were 89.8, 55.4 and 38.6%, respectively, with a significant difference between them (p

Background Video-assisted thoracoscopic surgery (VATS) for clinical stage I non-small cell lung cancer (NSCLC) has been widely used as a less invasive surgical procedure, but the resection method is still controversial. We retrospectively compared the surgical outcomes of lobectomy, segmentectomy and wedge resection. Patients and methods A total of 411 patients with clinical stage I NSCLC who underwent VATS (218 males and 193 females, aged 69.3 years; 345 adenocarcinomas, 57 squamous cell carcinomas, and 9 others) were investigated. The surgical procedure was lobectomy in 289, segmentectomy in 38, and wedge resection in 84. Surgical outcomes were compared among these 3 groups. Results Demographic characteristics showed that the rate of elderly and male patients was higher in the wedge resection group. The 5-year survival rates for the lobectomy, segmentectomy, and wedge resection groups were 82.1, 87.2, and 55.4%, respectively. In the wedge resection group, the 5-year survival rate was 83.3% in patients undergoing intentional low-risk operations for small tumors with ground glass opacity, and 41.1% in those undergoing conservative high-risk operations because of comorbidities. Using Cox's proportional multivariate analysis and sex differences, histology, and tumor size as co-influential factors, the surgical procedure was found to be a significantly poor prognostic factor, and the hazard ratio of wedge resection relative to lobectomy was 4.30. Conclusion The outcomes of VATS lobectomy and segmentectomy procedures for clinical stage I NSCLC were equivalent, while the outcome for VATS wedge resection was inferior. VATS wedge resection for clinical stage I NSCLC should be carefully indicated and requires adequate patient selection.