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Background Smoking is a known risk factor for postoperative mortality and morbidity. However, the significance of cumulative smoking dose in preoperative risk assessment has not been established. We examined the influence of preoperative cumulative smoking dose on surgical outcomes after lobectomy for primary lung cancer. Methods A total of 80,989 patients with primary lung cancer undergoing lobectomy from 2014 to 2016 were enrolled. Preoperative cumulative smoking dose was categorized by pack-years (PY): nonsmokers, PY = 0; light smokers, 0 < PY < 10; moderate smokers, 10 ≤ PY < 30; and heavy smokers, 30 ≤ PY. The risk of short-term outcomes was assessed according to PY by multivariable analysis adjusted for other covariates. Results Postoperative 30-day mortality, as well as pulmonary, cardiovascular, and infectious complications, increased with preoperative PY. Multivariable analysis revealed that the odds ratios (ORs) for postoperative mortality compared with nonsmokers were 1.76 for light smokers (P = .044), 1.60 for moderate smokers (P = .026), and 1.73 for heavy smokers (P = .003). The ORs for pulmonary complications compared with nonsmokers were 1.20 for light smokers (P = .022), 1.40 for moderate smokers (P < .001), and 1.72 for heavy smokers (P < .001). Heavy smokers had a significantly increased risk of postoperative cardiovascular (OR, 1.26; P = .002) and infectious (OR, 1.39; P = .007) complications compared with nonsmokers. Conclusions The risk of mortality and morbidity after lung resection could be predicted according to preoperative cumulative smoking dose. These findings contribute to the development of strategies in perioperative management of lung resection patients.

Adhesiolysis is often necessary in intrathoracic adhesion during ipsilateral repeat lung resection. This procedure has a risk of surgical complications, including unintentional intraoperative damage of the pulmonary vessels or lung parenchyma. We used an oxidized regenerated cellulose (ORC) sheet to prevent intrathoracic adhesion after lung resection in 55 patients. The sheet was placed on the surface of the resected region and on the lung surface under the wound. No major postoperative complications were observed. Three cases underwent ipsilateral thoracic surgery for the treatment of lung malignancies, and there were no intrathoracic adhesions around the ORC sheet-covered area.

Managing thoracic empyema with massive air leakage can be challenging. We present a case with thoracic empyema with multiple bronchopleural fistulae and extensive lung parenchymal necrosis due to drain injury. Emergency surgery was performed for respiratory distress due to massive air leakage. As direct sutures could not be achieved due to extensive parenchymal necrosis, polyglycolic acid and oxidized regenerated cellulose sheets were packed into the lesion. Although open-window thoracostomy was required for bronchopleural fistulae, the stoma closure was achieved via vacuum-assisted closure therapy. The dual sheet coverings contributed to the successful recovery by resolving multiple bronchopleural fistulae.

Background Fibrous bands (FBs) are one of the histological features in tumors which can be confirmed by hematoxylin and eosin (H&E)‐stained slides. FBs have been reported to correlate with malignancy in various tumors. This study aimed to investigate whether the presence of FBs is associated with malignancy in thymoma. Methods A total of 123 consecutive patients with thymoma who underwent microscopically complete resections from January 2000 to December 2018 were enrolled into this study. H&E‐stained slides of all thymoma patients were re‐examined. Study patients were classified into two groups: with FBs (n = 36) and without FBs (n = 87). Clinicopathological characteristics, overall survival (OS), and recurrence‐free survival (RFS) were compared between the two groups. Furthermore, multivariate analyses were performed to identify whether the presence of FBs was associated with higher Masaoka stage and poor prognosis in patients with thymoma. Results The Masaoka stage was found to be higher and recurrence more likely in thymoma patients with FBs than in those without. RFS was significantly poorer in thymoma patients with FBs than in those without, although no significant difference was observed in OS between them. The presence of FBs was significantly associated with higher Masaoka stage in the multivariate analysis using logistic regression. Additionally, the presence of FBs was an independent prognostic factor for poor RFS in multivariate analysis using Cox's proportional hazards model. Conclusions The presence of FBs in patients with thymoma was associated with higher Masaoka stage, higher recurrence rate, and poorer RFS. Key points Significant findings of the study Fibrous bands (FBs) are bands of fibrosis dividing tumors into different‐sized irregular islands. The presence of FBs is associated with higher Masaoka stage and poor recurrence‐free survival in patients with thymoma. What this study adds The presence of fibrous bands might be associated with the malignant behavior of thymoma. Confirming the presence or absence of FBs may result in personalized medication for patients with thymoma., • Fibrous bands (FBs) are bands of fibrosis dividing tumors into different‐sized irregular islands. • The presence of FBs is associated with the malignant behavior of thymomas. • Confirmation of FBs might lead to individualized medications in patients with thymoma.

Purpose Caspase recruitment domain-containing protein 9 (CARD9) is expressed at high levels in bone marrow cells and has a crucial role in innate immunity. Current studies indicate that CARD9 also plays a key role in tumor progression, but there are few reports on the role of CARD9 in lung cancer. The aim of this study was to clarify the role of CARD9 in lung adenocarcinoma. Patients and methods Lung adenocarcinoma tumor samples from 74 patients who underwent complete resection at Kobe University Hospital from January 2014 to December 2014 were analyzed by immunohistochemistry. The role of CARD9 in cancer cells was analyzed using lung cancer cell lines treated with CARD9 siRNA. Results High expression of CARD9 was observed in 32.4% of tumors, and compared to low expression of CARD9, high expression was associated with poorer overall survival (P = 0.0365). Univariate and multivariate analyses showed that high expression of CARD9 was an independent prognostic factor. Knockdown of CARD9 in lung adenocarcinoma cells inhibited proliferation but did not increase apoptosis. In addition, CARD9 activated the NF-κB pathway in a lung adenocarcinoma cell line. Conclusion CARD9 was shown to be an independent prognostic factor of poor outcome for lung cancer and may represent a molecular target for treatment.

Background Cisplatin (CDDP) and vinorelbine as an adjuvant chemotherapy improve the overall survival of patients with completely resected non‐small cell lung cancer (NSCLC). However, the treatment completion rate is low due to severe adverse events (AEs). Pemetrexed (PEM) has been used in advanced NSCLC due to its high safety and efficacy. Additionally, the safety of a short hydration method for CDDP administration has been previously reported. Here, we investigated the feasibility of CDDP plus PEM with a short hydration method as adjuvant chemotherapy. Methods A total of 21 completely resected nonsquamous NSCLC patients with pathological stage IIA to IIIA disease were enrolled into the study. Adjuvant chemotherapy consisted of four cycles of CDDP (75 mg/m2) plus PEM (500 mg/m2) every three weeks with a short hydration method. The primary endpoint was the treatment completion rate, and the secondary endpoints included toxicity, the two‐year relapse‐free survival (RFS) rate, and the outpatient treatment rate. Results A total of 21 patients (median age: 66 years; 12 males) were enrolled in two centers. All cases were adenocarcinoma with PS0 (71.4%) or PS1 (28.6%). A total of 81.0% of the patients received four cycles of therapy as scheduled and the primary endpoint was met. The rate of outpatient chemotherapy completion after the second cycle was 90.5%. The grade 3 or higher toxicities were anorexia (n = 2) and pulmonary thromboembolism (n = 1). No grade 3/4 hematological toxicities or creatinine level elevations were observed. The two‐year RFS rate was 57.3%. Conclusions CDDP and PEM with a short hydration is well tolerated in the outpatient setting with limited toxicity. Key points Significant findings of the study CDDP plus PEM adjuvant therapy with a short hydration method is well tolerated in the outpatient setting with limited toxicity. What this study adds CDDP plus PEM with a short hydration method has the potential to be one of the options of adjuvant therapy in the future., CDDP plus PEM adjuvant therapy with a short hydration method is well tolerated in the outpatient setting with limited toxicity.

BackgroundAlthough COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported.MethodsWe investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination.ResultsAnti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063-1.205] and 0.161 [0.07-0.857] vs 0.644 [0.259-1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups.ConclusionAlthough there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.Mini abstractTiters of anti-S1 antibody after the second dose of BNT162b2 were significantly lower in patients with solid tumors undergoing active anticancer treatment than in the healthy volunteers.

Purpose Adjuvant chemotherapy with cisplatin (CDDP) plus vinorelbine is the standard regimen for the treatment of non-small cell lung cancer (NSCLC). However, CDDP elicits severe toxic effects, including emesis, neurotoxicity, and renal damage; carboplatin (CBDCA) may be a feasible alternative for CDDP-unfit patients. CBDCA plus paclitaxel (PTX) adjuvant chemotherapy showed a survival benefit for patients with stage IB tumors >4 cm in size, while CBDCA plus nanoparticle albumin-bound (nab)-PTX showed greater efficacy and lower neurotoxicity than CBDCA plus PTX in advanced NSCLC. Here, we investigated the feasibility of using CBDCA plus nab-PTX as adjuvant chemotherapy for NSCLC. Patients and methods Patients with completely resected stage II or III NSCLC, with an Eastern Cooperative Oncology Group performance status of 0-1 and adequate kidney function, received four cycles of postoperative adjuvant chemotherapy with CBDCA (AUC=5 mg/mL/min, on day 1) and nab-PTX (100 mg/m2, on days 1, 8, and 15) administered every 4 weeks within 8 weeks after surgery. The study was designed as a prospective, single-center, Phase II study. The primary endpoint was the completion rate of chemotherapy; secondary endpoints were two-year relapse-free survival (RFS) and safety. The expected completion rate was 80%, with a 50% lower limit. Results Of 21 enrolled patients, 18 (85.7%) were CDDP-unfit owing to age (≥75 years old [n=11, 52.4%]) or mild renal impairment (n=7, 33.3%). Nineteen of the 21 enrolled patients were assigned to the intervention. The most common grade 3 or 4 adverse events were neutropenia (n=15, 78.9%) and anemia (n=3, 15.8%). The completion rate for the four cycles was 63.2% (95% CI, 38.4-83.7). Two-year RFS was 56.8% (95% CI, 29.7-76.9). Conclusion The completion rate for CBDCA plus nab-PTX as adjuvant chemotherapy for CDDP-unfit NSCLC patients did not reach treatment feasibility. Further dose modifications may be required in future studies.

Background Partner of Sld five 3 (Psf3) is a member of the heterotetrameric complex that consists of SLD5, Psf1, Psf2, and Psf3. We have shown in previous studies that high Psf3 expression was a poor prognostic marker for pulmonary adenocarcinoma. Here, we statistically evaluated the relationship between clinicopathologic factors and Psf3 expression in stage I pulmonary adenocarcinoma. Methods A total of 583 patients who had undergone complete resection of stage I pulmonary adenocarcinoma from January 2002 to December 2009 were included in the study. Tissue microarrays were performed, and the resected tumors were divided into groups according to Psf3 expression. Results Of 583 patients, high expression of Psf3 was observed in 211 (36.2%) and low expression of Psf3 observed in 372 (63.8%) patients. Among stage I patients, the five-year survival rate was 76.7% in the Psf3 high expression group and 90.9% in the Psf3 low expression group (P < 0.0001). On multivariate analysis, Psf3 was found to be the independent prognostic factor. Among stage I patients in the Psf3 high expression group, a significantly greater five-year survival rate was observed in patients who received postoperative chemotherapy with tegafur-uracil than in those who underwent surgery alone (P < 0.0001). In contrast, among stage I patients in the Psf3 low expression group, no difference was found in the five-year survival, regardless of the presence or absence of tegafur-uracil (P = 0.873). Conclusion The Psf3 expression was an independent prognostic factor and could be a biomarker of adjuvant tegafur-uracil for stage I pulmonary adenocarcinoma. Key points Significant findings of the study: The Psf3 expression could be a biomarker of adjuvant tegafur-uracil administration for stage I pulmonary adenocarcinoma. What this study adds: Appropriate patients of adjuvant chemotherapy for stage I pulmonary adenocarcinoma using Psf3 expression could be selected.

Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining. However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.

Background The aim of this study was to identify subgroups with good or bad prognosis in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) based on immunostaining patterns with neuroendocrine markers and compare them with small cell lung carcinoma (SCLC). Methods From January 2001 to December 2017, of all patients with resected LCNEC and SCLC, we selected patients whose pathological tumor sizes were ≤30 mm in diameter (defined as small‐sized tumors) and who underwent complete resection with lymphadenectomy. We classified patients with small‐sized LCNEC (sLCNEC) into two subgroups based on immunostaining patterns with three neuroendocrine markers (chromogranin A, synaptophysin, and NCAM) and compared them to small‐sized SCLC (sSCLC). Results A total of 48 patients with sLCNEC and 39 patients with sSCLC were enrolled. Of 48 patients with sLCNEC, 21 were categorized as the small‐sized triple‐positive group (sTP), whose patients were positive for the three neuroendocrine markers, and 27 patients were categorized as the small‐sized nontriple‐positive group (sNTP), whose patients were not positive for all three neuroendocrine markers. The percentage of lymph node metastasis was significantly lower in sNTP than in sTP and sSCLC. There was no significant difference in overall survival, but recurrence‐free survival (RFS) and tumor‐specific survival (TSS) were significantly poorer in sTP and sSCLC than in sNTP. Multivariate analysis revealed sTP and sSCLC were independent prognostic factors for poorer RFS and TSS than those of sNTP. Conclusions The sNTP subgroup had a good prognosis and the sTP subgroup a poor prognosis. There were some similarities in clinicopathological features between sTP and sSCLC.

Background: The efficacy of diaphragmatic plication (DP) has been proven in many studies. However, there are few reports on DP for patients with severe respiratory conditions requiring mechanical ventilation. The study aim was to demonstrate the efficacy of DP for patients with severe respiratory insufficiency after cardiothoracic surgeries. Methods: We retrospectively reviewed 10 patients who underwent DP for severe respiratory insufficiency due to postoperative diaphragmatic paralysis; eight of them required mechanical ventilation, and two needed high-flow oxygen therapy prior to DP. The symptoms, lung function, and elevation of the diaphragm were assessed before and after DP. Results: All patients were successfully withdrawn from mechanical ventilation after DP and discharged without the need for oxygen therapy. The mean perioperative Medical Research Council (MRC) dyspnea scale (ATS/ERS 2004) score improved in 30 days (from 4 to 1.8) and in 90 days (from 4 to 0.6) after DP. Lung dynamic compliance was also ameliorated (mean improvement: 41.9 to 60.7 mL/cmH 2 O). Radiography revealed improved elevation of the diaphragm (mean improvement of 1.8 intercostal spaces, range, 1–2). Mean hospital stay after DP was 65.5 days (range, 25–187 days). One patient who underwent DP with endostapler-only suturing required re-operation because of staple line ruptures. Conclusions: DP was found to be an effective form of treatment for patients with severe respiratory insufficiency after cardiothoracic surgery.

Background: Large-cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are categorized as high-grade neuroendocrine carcinoma (HGNEC). We analyzed the efficacy of perioperative chemotherapy for HGNEC and the prognostic factors. Methods: We retrospectively reviewed the medical records of patients who underwent tumor resection and were diagnosed with HGNEC between January 2001 and December 2014. The overall survival (OS) was estimated by the Kaplan-Meier method. Propensity score matching was performed to compare the OS between the treatment groups. Multivariate analyses using a Cox proportional hazards model were performed to search for prognostic factors for HGNEC. Results: We analyzed 146 HGNEC patients (LCNEC n=92, SCLC n=54) without synchronous multiple cancers, who underwent complete resection. Seventy patients (LCNEC n=31, SCLC n=32) received perioperative chemotherapy and all of them received a platinum-based anticancer drug. Perioperative chemotherapy significantly improved the 5-year OS rates of HGNEC patients (all stages: 74.5% vs. 34.7%, P

Objectives This study aimed to assess the effect of home-based preoperative pulmonary rehabilitation (HBPPR) on the incidence of postoperative complications, length of stay (LOS), and duration of intercostal catheterization in non-small cell lung cancer (NSCLC) patients who underwent lung resection. Materials and methods In this retrospective cohort study, 144 patients who underwent lung resection were recruited, 51 of whom received HBPPR, comprising respiratory muscle training and was supervised (for patients undergoing it for the first time). Patients continued these programs for 2-4 weeks during the preoperative waiting period, in their homes. Data on postoperative complications graded according to the Clavien-Dindo classification, LOS, and intercostal catheterization duration were collected from medical records. These outcomes were compared between the HBPPR and non-HBPPR groups using Fisher’s exact test and Wilcoxon rank sum test, after 1:1 propensity score matching to avoid selection bias. Results Forty-nine matched pairs were extracted using propensity score matching. HBPPR reduced the onset of postoperative complications (p = 0.04), with the relative ratio (RR) for Clavien-Dindo Class I postoperative complications showing a significant difference (RR 0.55, 95% CI 0.30¬-1.02; p = 0.05), whereas RRs for the other Clavien-Dindo classes were not statistically significant. There was no significant difference in LOS or the duration of intercostal catheterization. Conclusion HBPPR reduced the incidence of Clavien-Dindo Class I postoperative complications after lung resection. Implementing HBPPR practices in a clinical setting would benefit patients unable to receive supervised preoperative pulmonary rehabilitation due to access barriers, time, and financial constraints.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease, occasionally accompanied by malignant tumors. Immunosuppressive therapy is the mainstay treatment for idiopathic NMOSD; no guidelines have been published for paraneoplastic NMOSD because it is rarely reported in the literature. We report a rare case of a 67-year-old man with paraneoplastic NMOSD associated with thymic carcinoid whose cells expressed aquaporin-4 antibody. After surgical resection, the patient's symptoms improved, and serum aquaporin-4 autoantibody turned negative. We believe that radiographic examination for mediastinal tumors in patients with NMOSD is necessary because thymic epithelial tumors could have a role in the pathogenesis of paraneoplastic NMOSD. After mediastinal tumor has been detected, they should be surgically resected to improve neurological symptoms.

Background: The gut microbiome plays an important role in the immune system and has attracted attention as a biomarker of various diseases, including cancer. As such, we examined the relationship between the gut microbiome and lung cancer progression. In addition, we assessed the correlation between the gut microbiome and epidermal growth factor receptor (EGFR) mutation status.Methods: Female never-smokers diagnosed with lung adenocarcinoma were consecutively and prospectively enrolled between May 2018 and August 2019. Fecal samples were collected within 1 month before or after diagnosis and before administration of any lung cancer treatment. Principal coordinate analyses were retrospectively performed using Bray-Curtis distance matrices to investigate the effects of clinical variables (age, body mass index, Tumor-Node-Metastasis stage, T category, N category, M category, primary tumor size, performance status, and EGFR mutation status) on the gut microbial community. A correlation analysis was also performed to determine the strength of association between the dominant taxonomy (comprising ≥1% of the relative abundance of bacterial DNA sequences) and clinical variables.Results: A total of 37 patients were enrolled. T category and primary tumor size were significantly correlated with the gut microbial community (p=0.018 and 0.041, respectively). At the genus level, a significant positive correlation was observed between the relative abundance of Faecalibacterium and both T category (correlation coefficient, R=0.51, p=0.0013) and primary tumor size (R=0.37, p=0.024), whereas a significant negative correlation was observed between the relative abundances of Fusicatenibacter and Bacteroides and T category (R=−0.35, p=0.034 and R=−0.32, p=0.05, respectively) and primary tumor size (R=−0.36, p=0.029 and R=−0.41, p=0.012, respectively). EGFR mutation status had no statistically significant effect on the gut microbial community (p=0.11). However, the relative abundances of Bifidobacterium and Faecalibacterium were significantly higher in EGFR mutation–negative patients than EGFR mutation–positive patients (p=0.012 and 0.041), whereas the relative abundance of Blautia was significantly lower in EGFR mutation–negative patients (p=0.036).Conclusions: This is the first study identifying the gut microbiome as a promising biomarker of lung cancer progression. Further elucidation of the role of the gut microbiome in lung cancer progression could facilitate development of new treatments for lung cancer.

A 63‐year‐old man suspected of having lung cancer underwent right upper lobectomy and was diagnosed with large cell neuroendocrine carcinoma (LCNEC). Eleven months after surgery, he developed an oligorecurrence in the adrenal gland and underwent left adrenalectomy. The specimen revealed LCNEC metastasis. Forty‐one months after surgery, enlargement of a lesion near the surgical site was seen. Biopsy showed LCNEC metastasis and he is currently undergoing radiotherapy for the recurrent lesion. We report a case of LCNEC with adrenal gland oligorecurrence treated by adrenalectomy, which led to long‐term survival., We report a case of large cell neuroendocrine carcinoma (LCNEC) with adrenal gland oligorecurrence treated by adrenalectomy, which led to long‐term survival.

A 14-year-old girl was diagnosed with hemothorax associated with pulmonary arteriovenous fistula rupture, and emergency surgery was performed. One week before her surgery, her mother at 32 weeks of gestation underwent emergency surgery for hemothorax caused by pulmonary arteriovenous fistula rupture. Both were diagnosed with hereditary hemorrhagic telangiectasia. The indications for treatment of pulmonary arteriovenous fistulas in young patients remain controversial because the risk of complications concerning pulmonary arteriovenous fistula is lower in young patients than in adult patients. We recommend that aggressive treatment should be performed for pulmonary arteriovenous fistulas in patients with hereditary hemorrhagic telangiectasis with a family history of pulmonary arteriovenous fistula rupture even if the patient is asymptomatic and young, because such patients may have a high risk of pulmonary arteriovenous fistula rupture.

Backgrounds and objectives Recent studies have suggested that insulinoma-associated protein 1 (INSM1) is a useful marker for pathological diagnosis of pulmonary neuroendocrine tumors. In the present study, we investigated the association between INSM1 expression and prognosis in patients with pulmonary high-grade neuroendocrine carcinomas (HGNEC) and assessed the usefulness of INSM1 as a prognostic biomarker in these patients. Methods Seventy-five consecutive patients with HGNEC who underwent complete surgical resections from January 2000 to December 2018 were enrolled in this study. We classified these patients into two groups: the INSM1-positive group (n = 59) and INSM1-negative group (n = 16). We compared the clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) between the groups. In addition, we performed univariate and multivariate analyses to identify the prognostic factors associated with postoperative survival. Results Significant differences in tumor diameter and vascular invasion between the groups were found. OS and RFS were significantly poorer in the INSM1-positive group than in the INSM1-negative group. Univariate and multivariate analyses revealed that INSM1 expression was the strongest predictor of poor prognosis for OS and RFS. Conclusions INSM1 expression had the greatest influence on the prognosis in patients with HGNEC and may be a prognostic biomarker in these patients.

Background: Advances in the development of staplers for pulmonary vessels have contributed to safe and convenient procedures in thoracic surgery. However, adverse events (AEs) can occur during vascular stapling and cause fatal hemorrhage. We aimed to assess the risk level of using the vessel stapling procedure to reduce such AEs. Methods: First, an animal experiment using pig cardiopulmonary blocks was conducted. Pulmonary arteries were closed with staplers under stressful conditions such as lifting or twisting; vessel stump endurance was analyzed through different methods. Second, AEs associated with clinical stapler use for pulmonary vessels were retrospectively reviewed by studying clinical videos of 263 patients. Results: In the animal experiment, the pressure resistance was significantly lower in the twisted group than in the no strain group (no strain vs. lifting: P=0.2008, no strain vs. twisting: P=0.002, no strain vs. twisting and lifting: P

Mediastinal leiomyosarcoma is an aggressive tumor that primarily occurs in the posterior mediastinum. A bronchogenic cyst is a benign lesion that often develops in the mediastinum close to the thoracic trachea and has been reported to be the origin of certain malignancies. The present study reports an extremely rare case of an anterior mediastinal leiomyosarcoma that was considered to have originated from a bronchogenic cyst. An 82‑year‑old woman complained of chest pain, presenting an abnormal 70 mm mass shadow in the anterior mediastinum of a chest CT scan. Mediastinal tumor resection was performed and the tumor was diagnosed as a leiomyosarcoma. As the tumor was located adjacent to a bronchogenic cyst, it was considered to have originated from the remnant tissue of the cyst. Recurrent lesions were noted in the right lower lobe on CT scan 24 months after surgery.

OBJECTIVES During video-assisted thoracoscopic surgery (VATS), blood oozing from the surface of the access port wound can hamper the surgical view. Although this oozing is difficult to prevent, it can be decreased by placing a wound edge protector with oxidized regenerated cellulose (ORC) on the surface of the access port wound, thereby improving the surgical outcomes and safety of VATS. METHODS We conducted a prospective, single-centre, open-label, randomized clinical trial to evaluate the operative outcomes of VATS when using the ORC (ORC group) compared with operative outcomes without using the ORC (non-ORC group). The primary end point was interruption of the operation as a result of blood oozing from the surface of the access port wound. The secondary end points were the other intraoperative and postoperative outcomes. RESULTS A total of 108 patients were divided into the ORC group (n = 54) and the non-ORC group (n = 54). Compared with the non-ORC group, the ORC group had fewer patients with an interruption in the operation (11.1% vs 51.8%; P CONCLUSION The use of an ORC sheet around a wound edge protector for haemostasis can ensure a clear view during VATS. Clinical trial registration number UMIN000031112.

We thank Dr. Marcin and Dr. Dragan and colleagues for their valuable comment on our article (1,2).

Objectives Partner of Sld five (Psf) 3 is a member of the evolutionarily conserved heterotetrameric complex GINS (Go-Ichi-Ni-San). We previously reported that Psf3 could serve as a biomarker of poor prognosis in lung adenocarcinoma. Here, we used tissue microarrays to analyse Psf3 expression in lung adenocarcinoma and investigated whether its expression is associated with survival outcomes. Methods The study included 864 consecutive patients with lung adenocarcinoma who underwent complete resection at Hyogo Cancer Center between January 2002 and December 2009. Tissue microarrays were prepared, and Psf3 was detected using mouse antihuman Psf3 primary monoclonal antibodies. The status of Psf3 expression was determined using these microarrays. Results Of the 864 patients, 375 had high-positive Psf3 expression and 489 had low-positive expression. Psf3 expression was significantly associated with age, sex, T factor, lymph node metastasis, stage and P factor. The 5-year disease-free survival (DFS) rate was significantly lower in patients with high-positive Psf3 expression than in those with low-positive expression, and Psf3 expression, sex, age, T factor and lymph node metastasis were identified as independent and significant prognostic determinants. Among patients with Stage I adenocarcinoma, the 5-year DFS rate was significantly lower in those with high-positive Psf3 expression than in those with low-positive expression, and Psf3 expression was the most powerful survival predictor. Conclusions The present findings strengthened our previous data demonstrating that high Psf3 expression in primary lung adenocarcinoma plays an important role in disease progression and is a prognostic indicator, particularly in early-stage adenocarcinoma.

Invasion has a significant role in cancer progression, including expansion to surrounding tissue and metastasis. Previously, we assessed the invasive ability of cancer cells using an easy-to-prepare double-layered collagen gel hemisphere (DL-CGH) method by which cancer cell invasion can be easily visualized. The present study examined multiple lung adenocarcinoma and malignant pleural mesothelioma (MPM) cell lines using the DL-CGH method and identified inherently invasive cell lines. Next, by comparing gene expression between invasive and non-invasive cells by cDNA microarray, the potential candidate gene brain-expressed x-linked protein 1 (Bex1) was identified to be involved in cancer invasion, as it was highly expressed in the invasive cell lines. Downregulation of Bex1 suppressed the invasion and proliferation of the invasive tumor cell lines. The findings of the present study suggested that Bex1 may promote metastasis in vivo and could be a potential oncogene and molecular therapeutic target in lung adenocarcinoma and MPM.

Extraskeletal osteosarcoma (ESOS) arising from the mediastinum is a rare malignant tumor and associated with a poor prognosis. We present the case of a 73-year-old man with a hoarseness. Imaging studies revealed a large calcified tumor of the median mediastinum. Surgery was performed, but complete resection was impossible and approximately two thirds of the tumor was excised. The tumor was diagnosed pathologically as ESOS. Proton beam therapy has been performed on the remaining lesion, and the patient is alive without tumor regrowth after 29 months. This case report documents a mediastinum ESOS successfully treated successfully with surgery and postoperative proton therapy.

Aim We examined the advantages of thoracoscopy over thoracotomy in terms of perioperative outcomes and toleration of adjuvant chemotherapy. Methods Between April 2010 and March 2013, 657 patients with non-small-cell lung cancer who underwent lobectomy were classified into thoracoscopy (308 patients) and thoracotomy (349 patients) groups and compared. Results The thoracoscopy group had less blood loss compared to the thoracotomy group ( p Conclusions These results indicate that totally thoracoscopic lobectomy is the more beneficial surgical approach with regard to the incidence of postoperative complications and toleration of adjuvant chemotherapy.

The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation.

Positive pleural lavage cytology (PLC) findings are considered to be predictive of a poor prognosis in patients with non-small-cell lung cancer (NSCLC). We investigated the clinical benefit of adjuvant chemotherapy for lung adenocarcinoma patients with positive PLC findings.We retrospectively reviewed the medical records of lung adenocarcinoma patients who underwent tumour resection and had positive PLC findings between January 2000 and December 2009.Fifty-three patients (4.8%) of 1114 patients with lung adenocarcinoma had positive PLC findings. The median follow-up period was 33.6 months. Adjuvant chemotherapy was administered to 24 patients (adjuvant chemotherapy group); 7, 8 and 9 patients had pathological Stage I, II and III, respectively . The surgery-alone group comprised 29 patients; 12, 8 and 9 patients had pathological Stage I, II and III, respectively. The 5-year recurrence-free survival (RFS) rates were 34.6 and 15.7% (P0.01) in adjuvant chemotherapy and surgery-alone groups, respectively. The rate of distant recurrence was significantly reduced in the adjuvant chemotherapy group (25.0 and 58.6%; P = 0.01). Even for Stage I cases, adjuvant chemotherapy tended to improve the 5-year RFS rate compared with surgery alone (60.1 and 29%; P = 0.11). Multivariate analysis for RFS revealed that adjuvant chemotherapy [hazard ratio (HR), 0.45; P = 0.03], tumour size30 mm (HR, 2.23; P = 0.02) and lymph node metastasis (HR, 2.67; P0.01) were significant independent prognostic factors for recurrence.Adjuvant chemotherapy for lung adenocarcinoma patients with positive PLC findings significantly improved recurrence-free survival.

ROS proto-oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer is rare and comprises only 1% of lung adenocarcinoma cases. It has recently been reported to have good response to crizotinib, a tyrosine kinase inhibitor of anaplastic lymphoma kinase. Driver oncogene mutations with approved therapies seldom coexist with a high expression of Programmed death-ligand 1 (PD-L1). The present case report describes a rare case of ROS1 rearrangement with high-PD-L1-expressing occult lung adenocarcinoma. A 32-year-old woman presented with chest pain and a prolonged cough. Chest computed tomography (CT) revealed a 57×36-mm tumor in the mediastinum, with no tumors detected in other regions. Positron emission tomography (PET)-CT showed a strong fluorodeoxyglucose accumulation in the tumor (SUVmax 13.2). Mediastinal tumor resection was completely resected using a video-assisted thoracic surgery approach. Pathological examination showed the tumor cells were positive for thyroid transcription factor 1, Napsin-A, ROS1, and PD-L1 (tumor proportion score >99%). ROS1 rearrangement was confirmed by fluorescence in situ hybridization. The mediastinal tumor was diagnosed as mediastinal lymph node metastasis of ROS1-rearranged PD-L1 high-expression undifferentiated lung adenocarcinoma (pathological stage 3, TxN2M0). Two months after the operation, the CT scan showed multiple mediastinum lymph nodes metastases with rapid tumor growth. The patient achieved a complete response after three cycles of S-1 plus cisplatin with concurrent radiotherapy 60 Gy/30 Fr.

A 59-year-old woman presented with a 1-year history of dysphagia. She suffered from a large mediastinal mass obstructing trachea and bilateral main bronchus, which led to dyspnea and disturbed consciousness. Immediate intubation and surgery was required. A solid tumor that included esophagus and right vagal nerve, and adhered to the membranous part of the bronchus was found. However, the tumor could be resected en bloc and the patient has been free from recurrence. Pathologically, the tumor exhibited proliferative spindle cells and was diffusely positive for S-100 protein. It was therefore diagnosed as a benign esophageal schwannoma. To our knowledge, this is the first report of tracheal obstruction from a benign esophageal schwannoma, which we successfully treated with emergency subtotal esophagectomy.

Radical resection for thoracic malignancies that invade the great vessels or heart structure is an uncommon, high-risk operation. To help surgeons determine therapeutic strategy, we reviewed the patient characteristics and outcomes of combined thoracic and cardiovascular surgery for thoracic malignancies. Surgical resections of lung cancer, mediastinal tumor and pulmonary artery sarcoma invading great vessels or heart structures were reviewed from the literature. Pneumonectomy was often performed for lung cancer invading the aorta, superior vena cava, and left atrium. Complete resection (R0), no mediastinal lymph node metastasis and without using cardiopulmonary bypass led to a good prognosis. Induction therapy was often performed for complete resection. Regarding mediastinal tumors, thymic epithelial tumors or germ cell tumors occasionally invaded the great vessels or heart structures. For these malignancies, multimodality therapy was often performed, and complete resection could be one of the prognostic factors. The resection of primary pulmonary artery sarcoma (PPAS) is also a combined thoracic and cardiovascular surgery. The primary treatment for PPAS is surgical resection; specifically, pulmonary endarterectomy and pneumonectomy, because PPAS has substantial resistance to chemotherapy or radiotherapy. The prognosis of PPAS is poor, but surgical resection has potential for long-term survival. Although these surgeries are uncommon and invasive for the patients, selecting appropriate patients, aggressive multimodality therapy, and performing combined thoracic and cardiovascular surgery can contribute to a good outcome.

Objectives We evaluated the clinical benefit of segmentectomy for patients with cT1bN0M0 lung cancer. Methods We retrospectively reviewed the medical records of 178 patients who underwent lobectomy or segmentectomy for cT1bN0M0 lung adenocarcinoma and squamous cell carcinoma from January 1995 to December 2005. We investigated the association of surgical outcomes with the presence of pathological invasion. Results The median follow-up period was 93.4 months. Of 178 patients, 37 were scheduled for segmentectomy, but 6 of these patients were switched to receive lobectomy due to surgical N1 or N2 in 3 patients and insufficient surgical margins in 3 patients. In total, 31 patients underwent segmentectomy, and 147 underwent lobectomy. The 5-year overall survival (OS) was similar between the patients who underwent lobectomy (5-year OS, 81.6%) and segmentectomy (5-year OS, 77.4%, P = 0.73). Among pN0 patients without pathological invasion, there was no difference in OS between patients who underwent lobectomy (5-year OS, 89.9%) and segmentectomy (5-year OS, 88.9%, P = 0.80). In contrast, among pN0 patients with pathological invasion, OS was greater in patients who underwent lobectomy (5-year OS, 80.9%) than in those who underwent segmentectomy (5-year OS, 54.6%; P = 0.19). Moreover, a significantly higher rate of local and local + distant recurrence was observed in patients who underwent segmentectomy (45%) than in those who underwent lobectomy (15%) in this group (P = 0.02). Conclusions The results of our study suggest that segmentectomy may not be recommended for cT1b tumours if pathological invasion is suspected before surgery.