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Thoracic injuries are significant causes of morbidity and mortality in trauma patients. Traumatic pulmonary contusion and/or laceration are often observed in patients with chest trauma, explosion injuries or a shock wave associated with penetrating trauma. A pulmonary contusion is an injury to the lung parenchyma without actual structural damage. As a result of damage to alveoli and capillaries, it results in leakage of blood and other interstitial fluids across the alveolar-capillary membrane into lung tissue and alveolar space. Since oxygenated air can not enter into fluid-filled alveoli, hypoventilation and decreased perfusion by reflux vasoconstriction result in hypoxemia and hypercapnia. Pulmonary laceration is a lung injury with disruption of the architecture of the lung, while pulmonary contusion does not. There is almost always concurrent pulmonary contusion, and pneumothorax, hemothorax, or hemopneumothorax. In addition, pulmonary laceration can be a cause of forming a cyst or hematoma, which usually disappears over a period of weeks or months. However, pneumatocele can occur in some cases when lacerations are enlarged with air-filled cavity. It is important for thoracic surgeons to understand pathophysiology of traumatic lung injury, and to know the diagnosis and treatment.

The use of the white-light thoracoscopy is hampered by the low contrast between oncologic margins and surrounding normal parenchyma. As a result, many patients with in situ or micro-infiltrating adenocarcinoma have to undergo lobectomy due to a lack of tactile and visual feedback in the resection of solitary pulmonary nodules. Near-infrared (NIR) guided indocyanine green (ICG) fluorescence imaging technique has been widely investigated due to its unique capability in addressing the current challenges; however, there is no special consensus on the evidence and recommendations for its preoperative and intraoperative applications. This manuscript will describe the development process of a consensus on ICG fluorescence-guided thoracoscopic resection of pulmonary lesions and make recommendations that can be applied in a greater number of centers. Specifically, an expert panel of thoracic surgeons and radiographers was formed. Based on the quality of evidence and strength of recommendations, the consensus was developed in conjunction with the

Intraoperative complications, especially unexpected bleeding, are of great concern in the safety of thoracoscopic surgery. We investigated the hemostatic efficacy and safety of positive intrapleural pressure (PIP) with carbon dioxide insufflation by assessing the amount of blood loss in a pulmonary arterial hemorrhage model.An ex vivo experimental model of saline flow into a swine vessel was created in a container simulating a chest cavity. From the results, in vivo experiments (swine model) were conducted to compare the pulmonary arterial bleeding volume while applying PIP.In the ex vivo experiment, regardless of the incision type, the outflow volumes did not significantly differ at flow pressures of 20, 30, and 40 mmHg. At each flow pressure, the outflow volumes at 10, 15, and 20 mmHg of positive pressure in the container were significantly smaller than those of the control (p = 0.027, p = 0.002, and p = 0.005, respectively). Similarly, the in vivo experiments showed that bleeding decreased as intrapleural pressure increased (slope = -0.22, F = 55.13, p0.0001).It may be possible to temporarily suppress pulmonary arterial bleeding by increasing the intrapleural pressure to 10 to 20 mmHg using carbon dioxide insufflation. This method may be an adjunctive hemostatic maneuver for intraoperative bleeding.

Intraoperative identification of small pulmonary nodules has been an important technical issue. We aimed to develop a new localization method which is much safer and simple procedure compared with conventional methods.This was a retrospective study including patients with resected peripheral pulmonary nodules between November 2017 and April 2021 at Teikyo University School of Medicine, and Saitama Cardiovascular and Respiratory Center. All surgical procedure was wedge resection, and the tumor size was equal to or less than 20 mm which were detected by cone-beam computed tomography (CBCT; Philips Allura Xper FD 20, Philips). Some metal clips were put on several places of visceral pleura, where the target lesion was sandwiched by marking clips (sandwich marking technique). CBCT detected both the target lesion and metal clips, and video-assisted thoracoscopic surgery (VATS) was performed. Radiological and pathological findings were analyzed, and the correlation coefficient of tumor size was examined among pre-, intra-, and post-operative tumor sizes.The average age of 90 patients was 65.2 years, and 47 were male (52.2%). All procedure was wedge resection including twelve bi-wedge resections, and one hundred nine peripheral pulmonary lesions were obtained by sandwich marking technique. The detection rate was 100%, and there was no marking-related complication.All small peripheral pulmonary lesions were successfully detected and resected by using CBCT with no marking-related complication. Sandwich marking technique was demonstrated to provide safe, reliable, and simple localization procedure for small peripheral pulmonary lesions.

Several methods for chest drainage after pulmonary resection of malignant lung tumors exist, but consensus on the ideal method has not been reached.We conducted a multicenter prospective observational study. We enrolled 2200 patients who underwent lung resection for lung tumors. Of the 1470 patients who underwent anatomic resection, 347 showed air leak on the morning of postoperative day 1. They were assigned to 3 groups according to the chest drainage method on postoperative day 1.Of 347 patients with postoperative air leaks, 107 (30.8%), 179 (51.6%), and 61 (17.6%) were assigned to water seal, continuous suction, and digital drainage, respectively. The median postoperative air leak duration was significantly longer with digital drainage (4.0 days) than with either water seal (2.5 days) or continuous suction (3.0 days; P = .009). Chest tubes were required for significantly more days on average with digital drainage (6.0 days) than with water seal (4.0 days) or continuous suction (4.0 days; P = .003). Prolongation of air leak duration was significantly more likely to occur in patients with body mass index18.5 kg/mWater seal was associated with significantly shorter duration of postoperative air leak and chest drainage compared with continuous suction and digital drainage.

OBJECTIVES For the technical management of tracheal anastomosis, developing new and simple methods is required to relieve anastomotic tension. This study aimed to investigate whether basic fibroblast growth factor (bFGF) only once injected immediately before anastomosis promotes cartilage regeneration at the tracheal anastomosis and whether the regenerated cartilage has the effect of reinforcing the anastomosis in a rabbit model. METHODS New Zealand white rabbits were anaesthetized, and the cervical trachea was exposed through a cervical midline incision, followed by resection of the 10th tracheal cartilage. The rabbits were categorized into 2 groups: the bFGF group (n = 6) and the control group (n = 6). In the former group, bFGF (25 μg) was administered into the submucosal layer of the cartilage using a 27-G needle immediately before tracheal anastomosis. The animals were sacrificed 4 weeks later. Histological, mechanical and biochemical evaluations were performed on this anastomosed trachea. RESULTS At 4 weeks of age, the anastomoses were spindle-shaped and displayed maximum diameter at the injection site compared with those in the control group. Histological evaluation showed that cartilage tissue had regenerated between the 9th and 11th tracheal cartilage rings. Tensile test showed that the anastomoses displayed a significantly high strain/stress ratio (P = 0.035). The collagen type II and glycosaminoglycan levels were significantly increased, and the collagen type I level was significantly decreased (P = 0.019, P = 0.013 and P = 0.045, respectively). CONCLUSIONS A new wound-healing concept of airway anastomosis could be provided by the results that single injection of bFGF regenerated tracheal cartilage in rabbits and strengthened the anastomosis by bridging the regenerated and well-matured cartilage. Further investigation of this method will lead to potential clinical applications for reinforcement of tracheal anastomoses.

Background Surgical outcomes of pneumonectomy for lung cancer differ based on various therapeutic strategies. Methods One hundred and fifty-one patients who underwent pneumonectomy were divided into three groups based on patients' therapeutic conditions: a primary pneumonectomy group (no preoperative treatment, n=137), an induction group (planned surgery after induction chemotherapy or chemoradiotherapy, n=10), and a salvage group (surgery for residual or enlarged lesions after radical non-operative therapies, n=4). Results Multivariate analysis showed that completeness of resection (P=0.003), subcategorization of whether there was no invasion, infiltration only to the main bronchus or pleura, or invasion of other deeper structures (P=0.008), and the presence or absence of mediastinal lymph node metastasis (P=0.033) were significant prognostic factors. Severe postoperative complications occurred in 5.1% (7/137), 20% (2/10), and 0% (0/4) in the primary pneumonectomy, induction, and salvage groups, respectively. Among patients with pN0-1 disease, the 3-year overall survival rate was 58.7% in the primary pneumonectomy group, 100% and 40% in cases with high and low pathological effects in the induction group, respectively, and 50% in the salvage group. Among patients with pN2 disease, this rate was 41.4% in the primary pneumonectomy group, and no patients survived for postoperative 2 years in the other groups. Conclusions For patients undergoing pneumonectomy, subcategorization based on the invasion status (none/bronchus/pleura or other deeper structures) is a crucial prognostic factor. To consider pneumonectomy in the induction or salvage setting, selecting patients with pN0-1 disease may be mandatory.

Postoperative complications of thoracic wall resection include respiratory complications, skin necrosis and infection. The aim of the present study was to examine postoperative complications in patients who required combined thoracic wall resection during the surgical removal of a tumor. The present study included 68 patients; there were 50 patients with lung tumors and 18 patients with musculoskeletal tumors. The clinical factors associated with complications were compared between the two groups. Preoperative and postoperative pulmonary function tests were performed to examine the residual pulmonary function in 16 patients. Thoracic cage reconstruction was performed in 46 patients. Postoperative complications occurred in 30 (44.1%) patients, and one patient died from postoperative pneumonitis. Compared with the pulmonary function preoperative test results, the postoperative results revealed a decrease in the mean vital capacity percentage and an increase in the mean forced expiratory volume within 1 sec as a percent of the forced vital capacity. In patients with lung tumors, pneumonectomy can result in an increased rate of complications following thoracic wall resection. Residual pulmonary function is affected by impaired thoracic cage expansion and removal of the lung. However, the results of the present study demonstrated that these complications can be somewhat stabilized by thoracic wall reconstruction.

BACKGROUND One of the known risk factors for non-small cell lung cancer (NSCLC) is somatic mutation in the Kirsten rat sarcoma (KRAS) gene. The relationship with smoking is well known. METHODS We retrospectively studied the data of 92 patients who underwent pulmonary resection January 2003 and June 2012 and were diagnosed as KRAS-mutated pathological stage I adenocarcinoma. RESULTS Among them, 33 patients who were non to light smoker (NLS) (smoking index, 0 to 400) were compared with 59 middle to heavy smoker (MHS) (> 400). The 5-year overall survival (OS) was significantly better in NLS (96.9%) than in MHS (80.0%); however, no significant difference was observed compared with wild-type KRAS (92.8%) (p= 0.66). The presence of p53 was significantly associated with smoking history (p< 0.01). The 5-year OS for NLS with p53-negative KRAS codon 12-mutated NSCLC (n= 28) was significantly better (96.3%) than that for MHS with both p53-positive and -negative KRAS mutation (p= 0.03 and p< 0.03, respectively). CONCLUSIONS A non to light smoking habit might contribute to an improvement in prognosis that is equivalent to that of wild-type KRAS, and p53 mutation did not affect survival in smokers harboring KRAS codon 12.

Hiroaki Kuroda,1 Yusuke Sugita,1 Yuko Ohya,2 Tatsuya Yoshida,2 Takaaki Arimura,1 Noriaki Sakakura,1 Toyoaki Hida,2 Yasushi Yatabe,3 Yukinori Sakao1 1Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan; 2Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; 3Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan Introduction: The natural history of consolidation on computed tomography (CT) rarely includes invasive cancers, and evidence of the ideal timing for surgical intervention via long-term follow-up studies remains unknown. Methods: Between January 2012 and June 2017, pulmonary resection was undertaken in 293 clinical IA patients who were followed-up for > 6 months after the first detection of potential non-small-cell lung cancer (NSCLC) opacities. We evaluated the corresponding HRs and compared the recurrence risk with the CT follow-up duration. Results: HRs calculated for the longest intervals were compared between two patient subsets: a shorter-interval surgery group (SISG: 41.3%; mean follow-up interval, 13.5±5.3 months) and a longer-interval surgery group (58.7%; mean follow-up interval, 54.9±25.6 months). On Cox multivariate regression analyses, CT consolidation (ratio >0.5), an abnormal carcinoembryonic antigen and a triple-negative mutation showed an independent association with an unfavorable prognosis, as measured by disease-free survival after the first detection of potential NSCLC opacities. The longer-interval surgery group fared significantly better than the SISG in terms of 5-year overall survival after the first detection (99.3% vs 93.1%, P

Objectives The lung was recently re-discovered as a hematopoietic organ for platelet production in mice. However, evidence for the role of the lung in thrombopoiesis in humans is still limited. In this study, we examined megakaryocytes in the pulmonary and systemic circulation, specifically in pulmonary arterial blood (PAB), venous blood (PVB) and peripheral blood using a newly developed microfluidic platform for rare cell isolation. Materials and methods We analyzed 23 lung cancer patients who underwent surgery in our institute. PAB and PVB were obtained from the resected lung immediately after surgery. Blood samples were size-selected using a filtration-based microfluidic device and enriched rare cells on glass slide specimens were stained with Papanicolaou (Pap), immunocytochemistry (ICC), and immunofluorescence (IF). Lung tissues were also analyzed by immunohistochemistry. Results Pap/ICC/IF showed the presence of abundant CD61+/cytokeratin- giant cells with a megakaryocyte lineage in PAB, but only a few in PVB. These megakaryocytes were found to consist of CD61+/CD41+ immature megakaryocytes and CD61+/CD41- mature megakaryocytes with the potential to produce platelets. These findings were confirmed by the conventional hematological analysis of blood smears stained with Giemsa. In analysis of lung cancer, CD61+ megakaryocytes were observed exclusively in the capillaries of non-cancerous tissue, whereas platelets were selectively observed in the tumor blood vessels of cancerous tissue. Conclusions These results indicate that numerous megakaryocytes migrate from systemic bone marrows to accumulate in PAs and arrest of mature megakaryocytes in the capillaries of normal lung, suggesting the possibility that the lung plays a physiological role in the systemic thrombopoiesis in lung cancer patients.

Spontaneous regression (SR) of cancer implies the partial or complete disappearance of malignant disease without or with adequate medical treatment. Typically, SR of cancer is a sporadic event, especially in non-small cell lung cancer (NSCLC). Although the underlying mechanism of SR remains unknown, stimulation of an immunological response has been proposed. Herein, we report the case of a 56-year-old woman exhibiting SR of NSCLC with a mediastinal disease. Despite regression of the primary site after a lung biopsy, simultaneous progression of mediastinal lymph node metastasis occurred. Specimens obtained by surgical resection pathologically confirmed both primary and metastatic sites. Reportedly, primary and metastatic tumors shrink synchronously in SR of metastatic NSCLCs. Thus, the fact that the SR of NSCLC can present inconsistent development in primary and metastatic sites should be considered, and direct intervention is recommended if physicians diagnose this phenomenon.

BACKGROUND/AIM The aim of this study was to evaluate the safety and efficacy of osimertinib for elderly patients, since the data remain limited. PATIENTS AND METHODS A total of 77 patients with advanced non-small cell lung cancer (NSCLC) harboring the epidermal growth factor receptor (EGFR) T790M mutation and treated with osimertinib were reviewed. Efficacy and safety indicators, such as EGFR-tyrosine kinase inhibitor (TKI)-related adverse events (AEs) and osimertinib-associated hematotoxicity, were evaluated in elderly patients (elderly group, EG; age, ≥75 years) by comparing them with younger patients (non-EG; aged

Open thoracotomy continues to be the gold standard approach for thoracic surgery despite the recent developments in thoracoscopic and robot-assisted procedures. Vertical muscle-sparing thoracotomy (VMST) is a well-established technique (1-3) that has not attracted much attention in recent years.

Our previous report suggested that fluorescence thoracoscopic anatomical segmentectomy (TAS) using intravenous (IV) indocyanine green (ICG) injection is safe, feasible, and efficacious for identifying segmental boundaries. However, contrast visualization in the conventional indocyanine green mode (CIM) remains relatively obscure in smoking-related comorbidities. Our aim was to evaluate the safety and efficacy of recently released Spectra-A with CIM by simultaneous observation.We postoperatively analyzed captive imaging using histogram counts in 29 patients who underwent TAS and previously reported that Δ indicates the index of visualization obtained by subtraction from its representative illuminated signal quantities of maximum pixels so that light-shade, intensity-removed image signals are obtained.Sixteen (55.2%) patients were male, and 13 (44.8%) were female. Segmental boundaries were successfully visualized in all patients (100%). The histogram count widths in dim and bright segments with CIM were 13.3 ± 3.8 and 52.5 ± 12.2, and those with Spectra-A were 19.4 ± 6.1 and 118.1 ± 37.4, respectively. The mean value was 4.3-fold higher for ΔSpa-A (61.4 ± 33.2) than for ΔCIM (14.2 ± 8.5) (P 0.01). In 14 (48.3%) patients, the segmental boundary could not be clearly visualized using CIM but was explicitly identified using Spectra-A.Spectra-A is a safe and promising noninvasive alternative like CIM, and more effective because of overcoming the limitation of CIM, but its use should be studied further to determine its usefulness in identifying segmental boundaries.

Objectives There have been few studies that have fully elucidated the relationship between genomic mutations in pulmonary adenocarcinomas and occult lymph node (LN) metastases (pN1-2) despite a preoperative clinical N0 stage (cN0). It is well known that anaplastic lymphoma kinase (ALK) rearrangements are more likely to occur in younger patients with high grade tumors. The aim of this study was to investigate the genomic status, examine the clinicopathologic features, and evaluate whether ALK mutations are associated with occult LN metastases. Materials and methods We retrospectively evaluated 459 Japanese patients who underwent pulmonary resection of cN0 adenocarcinomas between January 2012 and December 2015. The clinicopathologic characteristics, including age, sex, smoking index, tumor maximum diameter and consolidation/tumor ratio on computed tomography (CT), maximum standardized uptake value on positron emission tomography (PET) and gene mutations (epidermal growth factor receptor [EGFR], ALK, and kirsten ras genes (KRAS), were evaluated. Results ALK and EGFR and KRAS mutations were all mutually exclusive. Among 324 patients found to have mutations, ALK was involved in 19 (5.9%), EGFR in 266 (82.1%), and KRAS in 39 (12.0%). The incidence of occult LN metastases did not differ significantly between those with or without mutations (p=0.27). On univariate and multivariate analyses, tumors with ALK were more likely to have occult LN metastases (p=0.03). In cN0 tumors with ALK, pN1 was diagnosed in 26.3% and pN2 in 10.5%, whereas pN1 or pN2 stage was found in

Katsutoshi Seto,1 Hiroaki Kuroda,1 Tatsuya Yoshida,2 Shozo Sakata,1 Tetsuya Mizuno,1 Noriaki Sakakura,1 Toyoaki Hida,2 Yasushi Yatabe,3 Yukinori Sakao1 1Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan; 2Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; 3Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan Objectives: There have been few studies that have fully elucidated the relationship between genomic mutations in pulmonary adenocarcinomas and occult lymph node (LN) metastases (pN1-2) despite a preoperative clinical N0 stage (cN0). It is well known that anaplastic lymphoma kinase (ALK) rearrangements are more likely to occur in younger patients with high grade tumors. The aim of this study was to investigate the genomic status, examine the clinicopathologic features, and evaluate whether ALK mutations are associated with occult LN metastases. Materials and methods: We retrospectively evaluated 459 Japanese patients who underwent pulmonary resection of cN0 adenocarcinomas between January 2012 and December 2015. The clinicopathologic characteristics, including age, sex, smoking index, tumor maximum diameter and consolidation/tumor ratio on computed tomography (CT), maximum standardized uptake value on positron emission tomography (PET) and gene mutations (epidermal growth factor receptor [EGFR], ALK, and kirsten ras genes (KRAS), were evaluated. Results: ALK and EGFR and KRAS mutations were all mutually exclusive. Among 324 patients found to have mutations, ALK was involved in 19 (5.9%), EGFR in 266 (82.1%), and KRAS in 39 (12.0%). The incidence of occult LN metastases did not differ significantly between those with or without mutations (p=0.27). On univariate and multivariate analyses, tumors with ALK were more likely to have occult LN metastases (p=0.03). In cN0 tumors with ALK, pN1 was diagnosed in 26.3% and pN2 in 10.5%, whereas pN1 or pN2 stage was found in

Thoracoscopic surgery (TS) is a less invasive procedure than open thoracotomy because it involves less postoperative pain, a lower complication rate, a shorter time to ambulation, and shorter hospitalization. Clinically, patients who undergo TS do not always harbor mild-to-moderate postoperative pain.

Thoracoscopic surgery is becoming more widely used in thoracic surgery and has an increasingly important role to play. However, its use for locally advanced carcinoma (clinical stage T3-4) remains controversial. We adapted our procedure by combining thoracoscopy and open chest surgery (combination surgery) with the aim of reducing invasiveness while ensuring that the operation is safe and curative. Here we describe our experience. Case 1 was a man in his 60s who underwent induction chemoradiotherapy (cisplatin plus vinorelbine plus 40 Gy radiotherapy) followed by radical surgery for a left apical lung carcinoma with chest wall invasion. Case 2 was a woman in her 70s who repeatedly had pneumonia and who underwent radical surgery for left apical adenocarcinoma that was expected to have strong adhesions to the thoracic wall. A thoracotomy incision may be required in cases of stage T3-4 lung cancer to access the hilar region and dissect the resected tumor and surrounding organs. In such cases, adding thoracoscopy to either one of these procedures may enable the use of a smaller incision in the chest wall. In both cases, complete resection with no residual tumor or complications was achieved, with the patients being discharged 3-8 days postoperatively. Cases 1 and 2 both remain recurrence free after 1.5 and 3 years, respectively). This suggests that having a thorough understanding of the features of both thoracoscopic and open chest surgery and integrating the two may enable surgery to be safely and less invasively performed while ensuring a curative effect.

// Hiroaki Kuroda 1 , Shnsuke Mori 2 , Hirotaka Tanaka 3 , Tatsuya Yoshida 4 , Tetsuya Mizuno 1 , Noriaki Sakakura 1 , Yasushi Yatabe 2 , Hiroshi Iwata 3 and Yukinori Sakao 1 1 Department of Thoracic Surgery, Aichi Cancer Center Hospital, Aichi, Japan 2 Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Aichi, Japan 3 East Nagoya Radiological Diagnosis Foundation, Aichi, Japan 4 Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan Correspondence to: Hiroaki Kuroda, email: h-kuroda@aichi-cc.jp. Keywords: three-dimensional; mediastinal size; invasive size; positron emission tomography; adenocarcinoma Received: September 16, 2016 Accepted: November 12, 2017 Published: December 18, 2017 ABSTRACT Background: We previously proposed measuring tumor size using mediastinal window setting on high-resolution computed tomography (CT) as a simple and useful modality for preoperative prognostication of small adenocarcinoma. Hence, the importance of tumor volume and positron emission tomography (PET) for preoperative prognostication of clinical stage IA (cIA) adenocarcinoma was studied. Materials and Methods: We retrospectively evaluated total 324 patients who underwent pulmonary resection of cIA adenocarcinoma between July 2008 and August 2015. Reconstructed three-dimensional (3D) images from 1–1.5 mm-sliced CT were evaluated for whole tumor volume including ground grass opacity, consolidation volume on lung window setting, and mediastinal window volume (MWV). The values examined by PET were total lesion glycolysis (TLG), and maximum standardized uptake (SUV max) and mean. Pathologic status was evaluated according to tumor maximum size, invasive size (IS), lymphatic and vascular vessels, pleural invasion (ly/v/pl), and TNM staging. Results: According to ly/v/pl invasion and lymph node positivity, no variables were superior to IS. We used Mean/MWV (SUV mean x MWV) to evaluate tumor quality and quantity in the role of surrogate TLG. Mean/MWV were superior to IS. Additionally, Mean/MV was associated with lymph node metastases. Among the various histologic subtypes, solid-predominant had the highest expression of Mean/MV. The higher Mean/MV significantly contributed to unfavorable disease-free survival in cIA adenocarcinomas, but not to overall survival. Conclusions: The mean/MWV value determination on 3D-reconstructed CT images was a simple and useful preoperative modality for predicting invasive facet in cIA adenocarcinoma. However, higher values didn’t significantly affect overall survival.

To evaluate the possibility of pathologic diagnosis and genetic analysis of percutaneous core-needle biopsy (CNB) lung tumor specimens obtained immediately after radiofrequency ablation (RFA). Patients who underwent CNB of lung tumors immediately after RFA from May 2013 to May 2016 were analyzed. There were 19 patients (8 men and 11 women; median age, 69 years; range, 52–88 years) and 19 lung tumors measuring 0.5–2.6 cm (median, 1.6 cm). Thirteen tumors were solid, and 6 were predominantly ground-glass opacity (GGO) on computed tomography. All specimens were pathologically examined using hematoxylin and eosin (H&E) staining and additional immunostaining, as necessary. The specimens were analyzed for EGFR and KRAS genetic mutations. The safety and technical success rate of the procedure and the possibility of pathologic diagnosis and genetic mutation analysis were evaluated. Major and minor complication rates were 11% (2/19) and 53% (10/19), respectively. Tumor cells were successfully obtained in 16 cases (84%, 16/19), and technical success rate was significantly lower for GGO-dominant tumors (50%, 3/6) compared with solid lesions (100%, 13/13, p = 0.02). Pathologic diagnosis was possible in 79% (15/19) of cases based on H&E staining alone (n = 12) and with additional immunostaining (n = 3). Although atypical cells were obtained, pathologic diagnosis could not be achieved in 1 case (5%, 1/19). Both EGFR and KRAS mutations could be analyzed in 74% (14/19) of the specimens. Pathologic diagnosis and genetic analysis could be performed even for lung tumor specimens obtained immediately after RFA.

// Yuko Oya 1 , Tatsuya Yoshida 1 , Hiroaki Kuroda 2 , Masashi Mikubo 3 , Chiaki Kondo 1 , Junichi Shimizu 1 , Yoshitsugu Horio 1 , Yukinori Sakao 2 , Toyoaki Hida 1 and Yasushi Yatabe 3 1 Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan 2 Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan 3 Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan Correspondence to: Tatsuya Yoshida, email: t.yoshida@aichi-cc.jp Keywords: nivolumab, non-small cell lung cancer, programmed cell death-1(PD-1), programmed cell death-ligand 1 (PD-L1) Received: June 27, 2017 Accepted: September 21, 2017 Published: October 07, 2017 ABSTRACT Background: Nivolumab offers a superior survival benefit over docetaxel in patients with advanced, previously treated non-small-cell lung cancer (NSCLC). An association between programmed cell death ligand-1 (PD-L1) expression and the efficacy of nivolumab has been reported in many studies. However, the association between the clinical parameters and efficacy of nivolumab remains unclear in advanced NSCLC patients. Results: Among 124 patients, 108 (88%) were performance status (PS) 0 to 1. PD-L1 expression was assessed in 89 patients, with 51 (57%) patients having PD-L1 positive expression. In all patients, the objective response rate (ORR) in patients with elevated CRP levels (≥ 1 mg/dl) was significantly worse than those without elevated CRP levels (< 1 mg/dl) (8.3 vs 23.4%, p = 0.0180). The PS (≥ 2), smoking index (< 400), CRP levels (≥ 1 mg/dl) and LDH (≥ 245 IU/L) were significantly associated with a shorter PFS and OS in patients treated with nivolumab. Multivariate analyses showed that the PS (≥ 2), smoking index (< 400), CRP levels (≥ 1 mg/dl) and LDH (≥ 245 IU/L) and PD-L1 expression were significant factors associated with a longer PFS of nivolumab. Materials and Methods: We retrospectively analyzed 124 patients who received nivolumab as a subsequent treatment. The patient characteristics, laboratory data at baseline (C-reactive protein [CRP] and lactate dehydrogenase [LDH]), PD-L1 expression, nivolumab response, progression-free survival (PFS), and overall survival (OS) were evaluated. Conclusions: Clinical parameters, such as PS, serum CRP, serum LDH, and smoking status, were significantly associated with the response duration and survival in patients treated with nivolumab.

Non-small cell lung cancer (NSCLC) patients at cN1 have unfavorable outcomes. It has been reported that a substantial proportion of cN1 patients have occult mediastinal disease, and treatment guidelines suggest invasive preoperative mediastinal evaluation. However, the population that would most benefit from invasive staging has not been defined. The aims of this study are to identify factors predicting mediastinal metastasis and outcomes in cN1 NSCLC patients to select appropriate candidates for invasive mediastinal evaluation. We retrospectively studied 164 patients with radiologically diagnosed cN1 NSCLC. Clinicopathological factors including radiological nodal findings were reviewed. Factors predicting the pN2 status, disease-free survival (DFS), and overall survival (OS) were investigated. Among 164 patients with cN1 disease, pN2 was diagnosed in 43 (26.4%). This pN2 subgroup included a higher proportion of cases with adenocarcinoma (AD) histology than the pN0/1 subgroup (60.5 vs. 38.8%, p = 0.012). Logistic regression analyses revealed AD as an independent predictor of the pN2 status, while radiological nodal findings were unrelated. Cox regression analyses identified lower preoperative serum CEA, non-AD, and pN0/1 status as favorable factors of DFS and adjuvant therapy to be associated with OS. Five-year DFS was much lower in the pN2 subgroup than the pN0/1 subgroup of AD patients (p

Objectives Thoracoscopic surgery for lung metastasectomy remains controversial. The study aimed at determining the efficacy of thoracoscopic surgery for lung metastasectomy. Methods This was a multi-institutional, retrospective study that included 1047 patients who underwent lung metastasectomy for colorectal cancer between 1999 and 2014. Prognostic factors of overall survival were compared between the thoracoscopic and open thoracotomy groups using the multivariate Cox proportional hazard model. The propensity score, calculated using the preoperative covariates, included the era of lung surgery as a covariate. A stepwise backward elimination method, with a probability level of 0.15, was used to select the most powerful sets of outcome predictors. The difference between the radiological tumour number and the resected tumour number (delta_num) was also evaluated. Results The c -statistics and the P -value of the Hosmer-Lemeshow Chi-square of the propensity score model were 0.7149 and 0.1579, respectively. After adjusting for the propensity score, the thoracoscopy group had a better survival rate than the open group (stratified log-rank test: P = 0.0353). After adjusting for the propensity score, the most powerful predictive model for overall survival was that which combined thoracoscopy [hazard ratio (HR): 0.468, 95% CI: 0.262-0.838, P = 0.011] and anatomical resection (HR: 1.49, 95% CI: 1.134-1.953, P = 0.004). Before adjusting for the propensity score, the delta_num was significantly greater in the open group than in the thoracoscopy group (thoracoscopy: 0.06, open: 0.33, P = 0.001); however, after adjustment, there was no difference in the delta_num (thoracoscopy: 0.04, open: 0.19, P = 0.114). Conclusions Thoracoscopic metastasectomy showed better overall survival than the open approach in this analysis. The thoracoscopic approach may be an acceptable option for resection of pulmonary metastases in terms of tumour identification and survival outcome in the current era.

Background We previously reported the clinical application of powered vascular staple (PVS) for closure of subsegmental or segmental bronchus (SSB). This study aimed to measure breakdown pressure in experiment and to investigate bronchopleural fistula (BPF) after thoracoscopic segmentectomy (TS). Methods Part 1: a total of 30 cadaveric pigs were used, and bronchi were categorized into the following four groups: small [S, bronchial outer diameter (BOD) of 4-8 mm, n=8], medium (M, 9-10 mm, n=9), and large (L, >10 mm, n=13). We additionally added a single additional suture to compensate for weak sites with large BOD (group R, n=6). The pressure was slowly increased, and stump breakdown was observed. Part 2: we investigated the morbidity of BPF formation at follow-up of at least 6 months in a total of 217 patients. Results Part 1: the mean leak pressure was the highest in M, followed by groups S, R and L'. However, the significant difference was not found between S and R. Part 2: no BPF was observed, clinically. Conclusions Based on experimental results and clinical experience, the proper selection of PVS should contribute to the safety, feasibility, and success as SSB closure.

Objectives: Acute exacerbation of interstitial lung disease (AEILD) is a severe complication after pulmonary resection. This study investigates whether 2-[18]-fluoro-2-deoxy-D-glucose (18F-FDG) uptake on positron emission tomography (PET) in ILD areas is a predictor of AEILD. Methods: We enrolled 200 non-small cell lung cancer (NSCLC) patients with smoke exposures. Ten (5.0%) developed AEILD of whom seven were diagnosed as severe AEILD requiring medication. Patients were classified into either heterogeneity (HET, presence of ILD and non-ILD areas) or homogeneity (HOM, only non-ILD) according to the 18F-FDG uptake at diaphragm level. Results: The average maximum 18F-FDG uptake by NSCLC and in non-ILD was in HOM comparable to that in HET (p = 0.86 and p = 0.14, respectively); however; it was 2.8-fold higher in ILD than in non-ILD within HET (p < 0.01). Multivariate analyses revealed that only HET was independent factors for AEILD and severe AEILD (p < 0.01, and p = 0.03, respectively). Among HET, honeycombing or a triad of reticulation, consolidation, and ground-glass attenuation on high-resolution computed tomography (n = 21) associated with higher complication rate regarding AEILD and worse prognosis (both p < 0.01). Conclusions: Presurgical 18F-FDG uptake on normal lung areas may predict AEILD in smoke exposures. Synopsis: Heterogeneity consisted of normal lung area and interstitial lung disease area according to 18FFDG uptake. The average maximum 18F-FDG uptake was 2.8-fold higher in interstitial lung area than in normal area within heterogeneity. honeycombing or plenty of distinctive findings of interstitial lung disease on high-resolution computed tomography associated with higher complication rate regarding acute exacerbation of interstitial lung disease and worse prognosis.

To investigate the prognostic impact of 4L lymph node (LN) dissection in left lung cancer and to analyze the relative risk factors for 4L LN metastasis.We retrospectively collected data from 657 patients with primary left lung cancer who underwent surgical pulmonary resection from January 2005 to December 2009. One hundred thirty-nine patients underwent 4L LN dissection (4LThe metastasis rate of station 4L was 20.9%, which was significantly higher than those of station 7 (14.0%; P = .048) and station 9 (9.8%; P.001). Station 4L metastasis was associated with most other LN station metastases in univariate analysis, but only station 10 LN metastasis was an independent risk factor for 4L LN metastasis (odds ratio, 0.253; 95% CI, 0.109 to 0.588; P = .001) in multivariate logistic analysis. The 4LStation 4L LN involvement is not rare in left lung cancer, and dissection of the 4L LN station seems to be associated with a more favorable prognosis as compared with those who did not undergo this dissection.