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Background: Although the positive rate of preresection pleural lavage cytology (PLC) is low, it is an important indicator of poor prognosis for non-small-cell lung cancer patients with frequent pleural dissemination (PD) recurrence. Thin-section computed tomography (TSCT) can reveal relationships between a primary tumor and the pleura at 1 to 2 mm intervals, and this is associated with visceral pleural invasion (VPI). However, its association with PLC remains unclear. Therefore, we aimed to improve PLC efficiency and predict PD recurrence by understanding the relationship between PLC and preoperative TSCT findings., Patients and Methods: Between January 2014 and December 2018, we reviewed 978 patients with non-small-cell lung cancer who underwent PLC tests during complete resection surgery. Preoperative TSCT findings were evaluated, and factors with the highest specificity (proportion of patients with radiologically to pathologically diagnosed positive PLC) were investigated. We also evaluated their relationships with VPI and PD recurrence., Results: PLC positive was identified in 55 (5.6%) of the 978 patients. The two TSCT findings predicting PLC results, "the absence of pleural findings," ie, tumor not attached to pleura or without pleural tag, and "consolidation-to-tumor ratio ≤0.5", had a specificity of 100% (95% confidence interval: 90.4%-100%); additionally, all cases with these findings were VPI negative and had no PD recurrence. And 24% of the cohort had either of these findings., Conclusion: The absence of pleural findings and/or consolidation-to-tumor ratio ≤0.5 of primary tumor on preoperative TSCT can predict PLC negativity with very high probability; therefore, PLC can be omitted for such patients., Competing Interests: Disclosure The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In the treatment of nonsmall cell lung cancer (NSCLC), a disease-free survival of 5 years is a criterion for cure. This study aimed to evaluate the characteristics and outcomes of patients with brain metastases of NSCLC after a disease-free survival of 5 years (late recurrent brain metastasis [LRBM])., Methods: We reviewed 1281 consecutive patients with brain metastasis of lung cancer at a single institute between November 2014 and December 2022. Relevant articles were retrieved from PubMed. Only peer-reviewed journals published in English were included., Results: Six patients (0.47%) showed LRBM. Three were male. The median age at lung cancer diagnosis was 45 years. The histological diagnosis of all patients was adenocarcinoma. Driver gene mutations were observed in five patients. The median latency period from lung cancer treatment to the development of brain metastasis was 13 years. All patients had no metastasis to any other organs and underwent craniotomies. The median follow-up duration after craniotomy was 3.5 years. No local intracranial recurrences were observed. Three patients had distant intracranial recurrences at 7, 2, and 0.6 years after craniotomy. Five patients survived for 8, 4, 3, 2, and 0.3 years after craniotomy. One patient experienced re-recurrence in the lung 4 years after craniotomy and died 3.7 years later. In our systematic review, only six studies described LRBM of NSCLC., Conclusions: LRBM is rare in patients with NSCLC. In our institution, many of these patients harbored driver gene mutations, and achieved long-term survival with aggressive local therapy. Multicenter analysis is mandatory., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: We investigated the incidence of late recurrence beyond 5 years after pulmonary resection and aimed to identify candidates for long-term surveillance., Methods: We retrospectively reviewed the medical records of 978 non-small-cell lung cancer patients who underwent pulmonary resection between 2002 and 2015 and survived without recurrence for 5 years. Clinicopathological factors associated with recurrence-free survival beyond 5 years after surgery were investigated using univariate and multivariate analyses. The development of late metachronous malignancies was also investigated., Results: The median follow-up period from 5 years post-surgery was 27 months in the whole cohort. Late recurrence occurred in 37 (3.8%) patients. Late metachronous malignancies were diagnosed in 116 patients (11.9%), including 57 (5.8%) with lung cancer. One-, three-, and five-year recurrence-free survival rates beyond 5 years after surgery were 97.6%, 94.7%, and 94.7%, respectively. The recurrence-free survival of patients with pN1-2 was significantly poorer than that of patients with pN0 disease. Multivariate analysis revealed that adenocarcinoma and pN1-2 status were significantly associated with poor recurrence-free survival beyond 5 years post-surgery (P = 0.009 and 0.007, respectively)., Conclusions: Non-adenocarcinoma histology and pN0 status were significant favorable factors for recurrence-free survival beyond 5 years post-surgery. The efficacies of long-term surveillance for the detection of late recurrence were considered limited for these populations. Twelve percent of the patients experienced late metachronous malignancies after pulmonary resection., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Objective: Positive pleural lavage cytology (PLC +) is a poor prognostic factor for non-small cell lung cancer (NSCLC). However, data on the impact of intraoperative rapid diagnosis of PLC (rPLC) are lacking. Therefore, we evaluated the efficacy of rPLC before resection during surgery., Methods: A total of 1,838 patients who underwent rPLC for NSCLC between September 2002 and December 2014 were studied retrospectively. We assessed the clinicopathological factors between rPLC findings and the impact on survival of patients with curative resection., Results: The rPLC + status was observed in 96 (5.3%) among 1,838 patients. The rPLC + group had more unsuspected N2 (30%) than the rPLC- group (p < 0.001). The 5-year overall survival (OS) of patients who underwent lobectomy or more extensive resection with rPLC + , negative rPLC (rPLC-), and microscopic pleural dissemination (PD) and/or malignant pleural effusion (PE) were 67.3, 81.3, and 11.0%, respectively. In the rPLC + group, the prognosis of patients with pN2 was equal to that of pN0-1 (5-year OS: 77.9% vs. 63.4%, p = 0.263). Undetectable dissemination in the first evaluation immediately after starting surgery was found in 9% of rPLC + patients by additional evaluation of the thoracic cavity., Conclusions: Patients with rPLC + have more favorable survival than those with microscopic PD/PE after surgery. Curative resection should be performed in patients with rPLC + , even if N2 is detected during surgery. However, the rPLC + group often has N2 upstaging; therefore, systematic nodal dissection should be performed in rPLC + patients for exact staging. rPLC may contribute to preventing oversight PD by re-evaluation during surgery., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background: Pathological N2 (pN2) non-small cell lung cancer (NSCLC) is diverse; its treatment depends on the clinical N (cN) status. We aimed to determine the efficacy of upfront surgery for cN2pN2 NSCLC., Methods: The study included 43 cN2pN2 NSCLC patients who underwent upfront surgery at the Shizuoka Cancer Center between 2002 and 2017. Survival outcome, focusing on cN2 status, was retrospectively investigated. Mediastinal lymph nodes were pre-operatively evaluated using computed tomography and positron emission tomography. Surgical eligibility criteria included single-station cN2. N2 with N1 and skip N2 were defined as N2 with and without ipsilateral hilar lymph node metastasis, respectively. A platinum-doublet regimen was used for adjuvant chemotherapy. Survival curves were analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model., Results: Clinical-skip N2 and cN2 with N1 cases included 22 and 21 patients, respectively. Twenty-three patients received adjuvant chemotherapy. The median follow-up duration was 73 months. Clinical-skip N2 had a significantly better 5-year recurrence-free survival (RFS) than cN2 with N1 (58.3 vs 28.6%, P = 0.038) and was an independent favorable RFS predictor. Recurrence within 18 months occurred in 71% of cN2 with N1 cases. Five-year overall survival and RFS rates in patients receiving adjuvant chemotherapy vs those without adjuvant chemotherapy were 82.2 vs 41.9% (P = 0.019) and 56.5 vs 28.0% (P = 0.049), respectively., Conclusions: Clinical-skip N2 had an excellent prognosis, and upfront surgery was acceptable. Conversely, upfront surgery followed by chemotherapy is not recommended for cN2 with N1 patients because of early recurrence., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Lobe-specific nodal dissection (LND) is increasingly used for non-small cell lung cancer (NSCLC) in Japan; however, its treatment validity remains unclarified. Since 2013, LND has been used as a standard procedure for clinical stage-I (c-stage-I) NSCLC at our institution. We aimed to evaluate its validity using intraoperative frozen section analysis (FSA) for c-stage-I NSCLC., Methods: The participants comprised patients with NSCLC who underwent LND between 2013 and 2016 (n = 307) or systematic nodal dissection (SND) between 2002 and 2013 (n = 367) for c-stage-I disease. FSA was routinely performed in LND to examine at least three stations. Outcomes were compared between the LND and SND groups. Patients in whom LND was converted to SND due to metastasis on FSA of the sampled lymph node were still categorized into the LND group, i.e., intention-to-treat analysis. The prognostic impact was compared using propensity score matching., Results: The rate of conversion from LND to SND was 10.4%. Of the patients converted to SND, 12.5% had metastases outside the LND area. False-negative N2 results were detected in only 0.7% of the LND group patients after FSA. After matching, each group had 220 patients. There were no significant between-group differences in the lymph-node recurrence rate (7% vs. 6%), 5-year recurrence-free survival (80.1% vs. 79.0%), and overall survival (90.4% vs. 90.3%)., Conclusions: LND with intraoperative FSA is a valid modality that could serve as a standard surgical procedure for c-stage-I NSCLC. Intraoperative FSA may lower the residual lymph-node metastasis risk in LND., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background: A significant number of non-small cell lung cancer (NSCLC) patients develop osteogenic metastases (OMs) and/or brain metastases (BMs) after surgery, however, routine chest computed tomography (CT) sometimes fails to diagnose these recurrences. We investigated the incidence of BMs and OMs after pulmonary resection and aimed to identify candidates who can benefit from brain magnetic resonance imaging (MRI) and 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in addition to CT., Methods: We retrospectively reviewed medical records of 1099 NSCLC patients who underwent pulmonary resection between 2002 and 2013. Clinicopathological factors associated with OM and/or BM were investigated using univariate and multivariate analyses., Results: Postoperative recurrence occurred in 344 patients (32.6%). OMs were diagnosed in 56 patients (5.6%) with 93% within 3 years. BMs were identified in 72 patients (6.6%) with 91.1% within 3 years. Multivariate analysis revealed that poorly differentiated tumor and the presence of pathological nodal metastases were significantly associated with postoperative BM (p = 0.037, < 0.001), preoperative serum carcinoembryonic antigen (CEA) level of 5 ng/mL or higher and the presence of pathological nodal metastases were significantly associated with OM (p = 0.034, < 0.001). The prevalence of OM and/or BM in 5 years was as high as 25.9% in patients with pathological nodal metastases., Conclusions: We identified significant predictive factors of postoperative BM and OM. Under patient selection, the effectiveness of intensive surveillance for the modes of recurrence should be investigated with respect to earlier detection, maintenance of quality of life, and survival outcomes., (© 2021. Japan Society of Clinical Oncology.)

Background: Positive preresection pleural lavage cytology (PLC + ) is a poor prognostic factor in non-small cell lung cancer (NSCLC). This study evaluated the prognostic value of PLC + for the different pathologic stages (p-stages) of NSCLC., Methods: A retrospective analysis was conducted of all 1293 staged patients who underwent curative resection in the Shizuoka Cancer Center Hospital, Shizuoka, Japan, for NSCLC to evaluate the impact of PLC + on survival, specifically in patients with p-stage I NSCLC. The survival rate between patients with and without PLC + was compared using the Kaplan-Meier method with the log-rank test for comparison., Results: PLC + was identified in 50 of the 1293 patients (3.9%) and was correlated with lymph node metastasis (P < .001), a pathologic tumor size larger than 3 cm (P = .033), the presence of pleural invasion (P < .001), and adenocarcinoma (P = .038). In patients with PLC + , the 5-year disease-free survival (DFS) was 31.1%, compared with 75.7% for patients with a negative PLC (PLC - ) (P < .001). On multivariate analysis, the PLC + status was an independent prognostic factor of DFS (hazard ratio 1.70; P = .013). Among the 818 patients with p-stage I NSCLC, PLC + was identified in 22, with a 5-year DFS of 40.4%. The prognosis in patients with p-stage I NSCLC with PLC + was equal to that in patients with p-stage IIIA NSCLC with PLC - (5-year DFS, 40.4% and 39.0%)., Conclusions: PLC is an independent prognostic factor in early-stage NSCLC. Therefore, it may be appropriate to up-stage an NSCLC diagnosis in the presence of PLC + , especially for patients with p stage I., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The current nodal staging for lung cancer is defined only by the anatomical site of metastasis. However, the International Association for the Study of Lung Cancer (IASLC) proposed further subdivisions of the N descriptor that considers the locations and numbers of involved lymph node stations. This study aimed to test the new IASLC categories and compare their prognostic abilities to those of our proposed model that considers only the number of involved lymph node stations instead of the sites of metastasis., Methods: Between September 2002 and December 2016, 1581 patients who underwent complete resection for pathologically diagnosed Tis-4N0-2M0 non-small cell lung cancer were retrospectively analyzed. We evaluated the survival rates according to the patients' N classification as recently proposed by the IASLC and by the number of involved lymph node stations, and determined the optimal N classification., Results: The 5-year survival rates for patients with IASLC stages N1a, N1b, N2a1, N2a2, and N2b were 71.5%, 49.9%, 73.7%, 62.1%, and 46.9%, respectively. These results showed relatively good categorizations; however, some prognostic overlaps existed and not all differences were significant. After redefining the number of involved stations as Nα for 1, Nβ for 2-3, and Nγ for ≥ 4 without considering the metastasis sites, the 5-year survival rates for patients in these categories were 72.1%, 58.3%, and 29.6%, respectively; the differences between them were significant., Conclusion: The number of involved lymph node stations is a more accurate prognostic indicator in patients with completely resected non-small cell lung cancer.

Background and Objective: The efficacy expectation of immune checkpoint inhibitors against NSCLC in patients with ILD seems to be high because these populations are supposed to have high TMB. However, information about the characterization of TMB in patients with NSCLC and ILD is limited. Therefore, this study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence TMB values., Methods: The medical records of patients with NSCLC who underwent thoracic surgery at our institution between January 2014 and January 2017 were retrospectively reviewed. Whole-exome sequencing with an Ion Proton system and gene expression profiling of fresh surgical specimens were performed., Results: Among 367 patients with NSCLC, 62 (16.9%) were diagnosed with ILD. All samples were collected from primary tumours with a median TMB of approximately 2.1 (range: 0.1-64.4) mutation/Mb. Among 81 squamous cell carcinomas, we compared 27 tumours with concomitant ILD and 54 tumours without ILD. Univariate analyses revealed that tumours with concomitant ILD showed lower TMB values than those without ILD. Multivariate analysis revealed that concomitant ILD was significantly associated with low TMB values. Conversely, no difference was noted in the TMB value of adenocarcinoma between patients with and without ILD., Conclusion: Squamous cell carcinoma and adenocarcinoma with ILD do not have high TMB values. Therefore, considering the risk of severe pneumonitis, immune checkpoint inhibitors should not be used routinely against patients with NSCLC and ILD based on the expectation of high TMB values., (© 2019 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: There is no standard therapeutic approach for local recurrence of non-small cell lung cancer (NSCLC) after complete resection. We investigated the outcomes of radiotherapy (RT) for patients with local recurrence., Methods: We reviewed 46 patients who underwent curative-intent RT for local recurrence after lobectomy or pneumonectomy accompanied with mediastinal lymph node dissection between 2002 and 2014. We analyzed overall survival (OS), progression-free survival (PFS), local control, tumour response and the re-recurrence pattern., Results: Among the 46 patients, 16 received concurrent chemotherapy. The median follow-up period was 48 months. The response rate was 91%. The 5-year OS and local control rates were 47.9 and 65.3%, respectively, and the 5-year PFS rate was 22.8%. Female sex and complete response to radiation were favourable prognostic factors. Of the 33 patients with recurrence after radiation, 32 (97%) had distant metastasis., Conclusions: Although RT for local recurrence has high efficacy, distant relapse after radiation remains a major issue. Therefore, combination systemic therapy for local recurrence at any site should be further investigated. Since it is difficult to achieve a radical cure for local recurrence using RT, further study, for the administration of post-operative adjuvant therapy, is recommended., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: Tumor-associated macrophages (TAMs) are believed to influence tumor progression and the prognosis of patients. The purpose of this study was to clarify the correlation between the TAM density or location and the clinicopathological features of non-small-cell lung cancer (NSCLC) as well as to explore the prognostic impact of TAMs in NSCLC., Materials and Methods: CD68- and CD204-positive macrophages were detected in tumor islets, tumor stroma and alveolar space in 297 patients with NSCLC using immunochemistry. The clinicopathological and genetic factors surveyed were the disease-free survival, age, gender, smoking status, histological type, disease stage, histological grade, pleural invasion, lymph node metastasis, EGFR gene mutations and ALK rearrangements., Results: There were significantly more CD68-positive macrophages than CD204-positive macrophages in each location of the tumor islets, tumor stroma and alveolar spaces, and they were strongly correlated (P < 0.0001 each). Factors such as male gender, being a smoker, an advanced disease stage and histological grade, positive pleural invasion and node status and wild-type EGFR gene status were significantly correlated with a higher density of CD68- and CD204-positive TAMs in tumor stroma (P < 0.05 each). In contrast, the age of patients was not correlated with CD68- and CD204-positive TAMs (P > 0.05 each). Furthermore, survival analysis revealed that a high number of CD68- and CD204-positive TAMs in tumor stroma, but not in tumor islets or alveolar space, was a significant prognostic factor for the disease-free survival time of NSCLC (P < 0.05, respectively). Moreover, both univariate and multivariate analyses confirmed that higher numbers of CD204-positive TAMs in tumor stroma were an independent worse prognostic predictor for adenocarcinoma., Conclusion: The tumor stroma is the most suitable intratumoral area for the evaluation of TAMs in the setting of the prognostic prediction of NSCLC patients. CD204-positive TAMs are the preferable marker for prognostic prediction in NSCLC, especially in lung adenocarcinoma., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A 56-year-old man presented with a chest computed tomography (CT) finding of a right upper lobe nodule, which was diagnosed using brush cytology as adenocarcinoma stage IB (cT2aN0M0). Repeat CT scan for preoperative evaluation revealed a small, slightly hypodense spot in the pancreatic body, which was diagnosed as pancreatic metastasis from lung cancer using endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB). Because of the presence of distant metastasis, surgical resection was deferred and chemotherapy was chosen instead. Pancreatic metastasis from non-small-cell lung cancer (NSCLC) is rare and might present with few symptoms when the tumor is small. EUS-FNAB is a useful modality for detecting and providing accurate histological diagnosis of pancreatic tumors. Although pancreatic metastasis from NSCLC is rare, appearance of a new lesion in the pancreas should immediately warrant EUS-FNAB.

Background: Given the extent of the surgical indications for pulmonary lobectomy in breathless patients, preoperative care and evaluation of pulmonary function are increasingly necessary. The aim of this study was to assess the contribution of preoperative pulmonary rehabilitation (PR) for reducing the incidence of postoperative pulmonary complications in non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD)., Methods: The records of 116 patients with COPD, including 51 patients who received PR, were retrospectively analyzed. Pulmonary function testing, including slow vital capacity (VC) and forced expiratory volume in one second (FEV 1 ), was obtained preoperatively, after PR, and at one and six months postoperatively. The recovery rate of postoperative pulmonary function was standardized for functional loss associated with the different resected lung volumes. Propensity score analysis generated matched pairs of 31 patients divided into PR and non-PR groups., Results: The PR period was 18.7 ± 12.7 days in COPD patients. Preoperative pulmonary function was significantly improved after PR (VC 5.3%, FEV 1 5.5%; P < 0.05). The FEV 1 recovery rate one month after surgery was significantly better in the PR (101.6%; P < 0.001) than in the non-PR group (93.9%). In logistic regression analysis, predicted postoperative FEV 1 , predicted postoperative %FEV 1 , and PR were independent factors related to postoperative pulmonary complications after pulmonary lobectomy (odds ratio 18.9, 16.1, and 13.9, respectively; P < 0.05)., Conclusions: PR improved the recovery rate of pulmonary function after lobectomy in the early period, and may decrease postoperative pulmonary complications., (© 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Purpose: miR-451 is a tumor suppressive microRNA with several target genes, including Macrophage migration inhibitory factor (MIF). As little is known about the expression and clinicopathological significance of mir-451 in NSCLC, we performed a clinicopathological study of 370 NSCLC cases to clarify them. Cell biological experiments were also performed on NSCLC cell lines to confirm the tumor-suppressive role of miR-451 and whether or not MIF is targeted by miR-451., Methods: We analyzed 370 NSCLC cases for the miR-451 expression by quantitative real-time polymerase chain reaction and the MIF expression by immunohistochemistry. Eighty-four background lung tissue samples were also evaluated for the miR-451 expression. The clinicopathological and genetic factors surveyed were the disease-free survival, smoking status, histological type, disease stage, EGFR gene mutations and ALK rearrangements. In 286 adenocarcinoma cases, the invasive status (adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma) was also evaluated. Five NSCLC cell lines (H23, H441, H522, H1703, and H1975) were cultured and evaluated for their miR-451 and MIF expression. The cell lines with lower miR-451 and higher MIF expressions were then selected and transfected with miR-451-mimic to observe its effects on MIF expression, Akt and Erk status, cell proliferation, and cell migration., Results: The miR-451 expression was down-regulated in cancer tissues compared with background lung tissues (P<0.0001). Factors such as advanced disease stage, positive pleural invasion and nodal status and being a smoker were significantly correlated with a lower expression of miR-451 (P<0.05 each), while EGFR gene mutations and ALK rearrangements were not. In adenocarcinoma, invasive and minimally invasive adenocarcinoma showed lower expression of miR-451 than adenocarcinoma in situ (P<0.0005, respectively). A survival analysis showed that a lower expression of miR-451 was an independent predictor of a poor prognosis for NSCLC (P<0.05). The MIF expression was inversely correlated with the miR-451 expression. Out of 5 NSCLC cell lines examined, H441 and H1975 showed higher MIF and lower miR-451 expressions. After the transfection of miR-451-mimic, the MIF expression and phosphorylated Akt expression of these cell lines was suppressed, as were cell proliferation and cell migration., Conclusion: This clinicopathological study of 370 NSCLC cases and the cell biological studies of NSCLC cell lines clarified the tumor-suppressive role of miR-451 and its prognostic value. We also validated MIF as a target of miR-451 in NSCLC.

Background: The aim of the present study was to use surgical and histological results to develop a simple noninvasive technique for improving nodal staging using preoperative PET/CT in patients with resectable non-small cell lung cancer (NSCLC)., Methods: Preoperative PET/CT findings (163 patients) and pathological diagnoses after surgical resection were evaluated. Using PET/CT images, lymph node section area (SA), the maximum standardized uptake value (SUV max ), SA of SUV ≥2.5 and ≥3.0 were drawn freehand and measured using caliper software. Receiver operating characteristic (ROC) curves were then used to analyze those data., Results: Based on ROC analyses, the cut-off values for SA of SUV ≥2.5, SA of SUV ≥3.0, SUV ≥2.5 SA/node SA and SUV ≥3.0 SA/node SA for diagnosis of lymph node metastasis were 200 mm 2 , 30 mm 2 , 1.0 and 0.4. SUV ≥2.5 SA/node SA ≥1.0 had the highest negative predictive value, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of nodal staging were 61.1, 73.4, 36.7, 88.2 and 70.9%., Conclusions: When diagnosing nodal staging based a lymph node SUV ≥2.5 SA/node SA ratio of ≥1.0, it can be an effective criterion for use to determine surgical indications.

Purpose: Lymphatic spread of lung carcinoma to the mediastinum is a key determinant of prognosis. The lymph flow often carries metastases from the pulmonary segment directly into the mediastinal lymph nodes, without passing through the hilar nodes. This phenomenon is termed as "skip metastasis." This study investigated the subpleural lymphatic flow to the mediastinum using indocyanine green (ICG) with a near-infrared fluorescence imaging system., Methods: Seventeen patients with lung cancer were enrolled in this study. A 0.3 ml sample of solution containing the fluorescent dye ICG (5 mg/ml) was injected into subpleural sites near the primary tumor. Fluorescence imaging was used to monitor the flow of ICG-containing lymph from the injection site for 5 min. The relationship between the anatomical segment of the primary tumor and the lymphatic flow was assessed., Results: The lymphatic vessels draining from the injection site were revealed by the bright ICG fluorescence in 14 of the patients (82.4 %). A direct lymphatic flow to the mediastinum was confirmed in 3 of those 14 (21.4 %)., Conclusions: These findings confirm the direct flow of lymph to the mediastinum without passage through the hilum pulmonis intraoperatively. These preliminary results may provide a valuable clue for further investigations of the mechanisms underlying skip metastasis.

Since locally advanced non-small-cell lung cancer(NSCLC)treated by surgical therapy alone has a poor prognosis, the efficacy of preoperative chemotherapy for improving postoperative survival in patients with NSCLC is controversial. A 69-year-old female was referred to our hospital for Stage IIIA(cT3bulkyN2M0)adenocarcinoma of the right lung. Computed tomography(CT)revealed a small nodule, 21mm in diameter, in the right S6, with isolated pulmonary metastasis in the same lobe and bulky subcarinal lymph node swelling. She received two courses of a combination of carboplatin(CBDCA AUC5), paclitaxel(PTX 200mg/m2)and bevacizumab(15mg/kg)as induction therapy, and showed no serious adverse effects. CT after induction therapy revealed a minor radiographic response. She underwent right lower lobectomy with node dissection 2a in 2011. An intercostal muscle flap was used for the bronchial stump. Histopathological examination revealed adenocarcinoma pT1aN0M0 of Stage I A, and showed that the pulmonary metastasis had disappeared even though the effect of induction chemotherapy was Ef2. Induction chemotherapy with carboplatin, paclitaxel and bevacizumab may be useful for treatment of locally advanced lung cancer.

Zinc Finger Homeobox 3 (ZFHX3) was first identified as a suppressor of alpha-fetoprotein gene and is a good candidate for the 16q22 tumor suppressor. In this study we investigated the relationship between tumoral ZFHX3 mRNA expression and the clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). We used semi-quantitative real time reverse transcription polymerase chain reaction to assess expression of ZFHX3 mRNA in tumor samples from 140 patients with NSCLC. We found that the 5-year overall survival rate among patients weakly expressing ZFHX3 was significantly poorer than among those expressing higher levels of ZFHX3 (P< 0.0001 by log-rank test). Multivariate logistic regression analysis revealed being lower ZFHX3 expression are independent predictors of lymph node metastasis. With low-ZFHX3 tumors, there was a significantly (P=0.009) greater (7.39-fold higher) risk of lymph node metastasis. Multivariate Cox proportional hazard analyses revealed that being lower ZFHX3 expression (Hazard ratio, 4.42; 95% CI, 2.09-8.92; p=0.0002) were independent factors affecting 5-year overall survival. Ratio of ZFHX3 mRNA in tumor against normal lung in low-ZFHX3 tumor was lower than in high-ZFHX3 tumor. In conclusion, suppression of ZFHX3 expression in tumor cells decreases the survival rate among patients with NSCLC.