The impact of adjuvant surgical treatment of nontuberculous mycobacterial pulmonary disease on prognosis and outcome.

BACKGROUND: Lung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has been reported to be associated with favorable outcomes. However, little is known regarding the risk and prognostic factors for refractory and recurrent cases. We aimed to evaluate the overall impact and benefit of adjuvant lung surgery by comparing NTM-PD patients who underwent adjuvant lung resection with those treated exclusively with antibiotics. We also investigated the efficacy of serum IgA antibody against glycopeptidolipid (GPL) core antigen (GPL core antibody) to monitor disease activity and predict the recurrence of disease after adjuvant lung resection. METHODS: We retrospectively evaluated the clinical characteristics and surgical outcomes of 35 patients surgically treated for NTM-PD. Furthermore, we compared surgically treated patients and control patients treated exclusively with antibiotics who were matched statistically 1:1 using a propensity score calculated from age, sex, body mass index, and radiologic features of disease. RESULTS: In the surgically treated patients, the median age was 58 (interquartile range, 47-65) years and 65.7% were female. Twenty-eight patients had Mycobacterium avium complex. Operations comprised four pneumonectomies, two bilobectomies, one bilobectomy plus segmentectomy, 17 lobectomies, two segmentectomies, and nine lobectomies plus segmentectomies. Postoperative complications occurred in seven patients (20%), there were no operative deaths, and 33 (94.3%) patients achieved negative sputum culture conversion. Refractory and recurrent cases were associated with remnant bronchiectasis, contralateral shadows, and positive acid-fast bacilli staining or culture. Of 28 statistically matched pairs, long-term sustained negative culture conversion was observed in 23 (82.2%) surgical group patients and in 14 (50.0%) non-surgical group patients (0.0438). The mortality rate was lower in the surgical group, but did not reach statistical significance (one in the surgical group and four in the non-surgical group, p = 0.3516). GPL core antibody was correlated with disease activity and recurrence. CONCLUSIONS: NTM-PD patients who underwent adjuvant lung resection experienced overall favorable outcomes and achieved sputum culture conversion more frequently. Long-term mortality may have been reduced by this procedure, and the level of GPL core antibody was shown to be a good clinical indicator of disease activity after surgery.

Human airway trypsin-like protease enhances interleukin-8 synthesis in bronchial epithelial cells by activating protease-activated receptor 2.

Human airway trypsin-like protease (HAT) localizes at human bronchial epithelial cells (HBECs). HAT enhanced release of interleukin-8 (IL-8) from HBECs at 10-100 mU/mL and the enhanced release was almost completely abolished by 50 µM leupeptin, a serine protease inhibitor. Previous reports suggested that HAT displays its physiological functions via protease-activated receptor 2 (PAR2). In the present study, we examined the mechanism whereby HAT upregulates IL-8 synthesis in HBECs with a focus on PAR2. Northern blot analysis revealed that HAT enhanced IL-8 mRNA expression at concentrations of 10-100 mU/mL. PAR2 activating peptide (PAR2 AP) also enhanced IL-8 release and IL-8 mRNA expression in HBECs at 50-1,000 µM at similar levels as HAT. Knockdown of PAR2 mRNA by siRNA methods showed that PAR2 mRNA expression was significantly depressed in primary HBECs, and both HAT- and PAR2 AP-induced IL-8 mRNA elevation was significantly depressed in PAR2 siRNA-transfected HBECs. Additionally, HAT cleaved the PAR2 activating site (R36-S37 bond) of synthetic PAR2 N-terminal peptide. These results indicate that HAT stimulates IL-8 synthesis in airway epithelial cells via PAR2 and could help to amplify inflammation in chronic respiratory tract disease.

Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.

Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

Collagen gel droplet-embedded culture drug sensitivity test for adjuvant chemotherapy after complete resection of non-small-cell lung cancer.

PURPOSE: We conducted a prospective clinical study to individualize adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC), based on the drug sensitivity test. METHODS: Patients with resectable c-stage IB-IIIA NSCLC were registered between 2005 and 2010. We performed the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) on a fresh surgical specimen to assess in vitro chemosensitivity and evaluated the prognostic outcome after adjuvant chemotherapy with carboplatin/paclitaxel based on the CD-DST. RESULTS: Among 92 registered patients, 87 were eligible for inclusion in the analysis. The success rate of CD-DST was 86% and chemosensitivity to carboplatin and/or paclitaxel was evident in 57 (76%) of the 75 patients. Adjuvant chemotherapy was completed in 22 (73%) of 30 patients. The 5-year overall survival rates were 71, 73, and 75% for all, CD-DST success, and chemosensitive patients, respectively. The 5-year disease-free survival and overall survival rates of the chemosensitive patients who completed adjuvant chemotherapy using carboplatin/paclitaxel were 68 and 82%, respectively. The 5-year disease-free survival and overall survival rates of the patients with stage II-IIIA chemosensitive NSCLC were 58 and 75%, respectively. Comparative analyses of the chemosensitive and non-chemosensitive/CD-DST failure groups showed no significant survival difference. CONCLUSIONS: CD-DST can be used to evaluate chemosensitivity after lung cancer surgery; however, its clinical efficacy for assessing individualized treatment remains uncertain.

Long-Term Impact of Postoperative Complications on Cancer Recurrence Following Lung Cancer Surgery.

BACKGROUND: Postoperative complications are associated with poor cancer-specific survival in various types of cancer surgery. Recent studies suggest that systemic inflammation induced by surgical trauma can accelerate the adhesion of circulating tumor cells to the vascular endothelium of distant organs, resulting in early cancer recurrence. We investigated the impact of postoperative cardiopulmonary complications on cancer recurrence following lung cancer surgery. METHODS: From a prospective database of 675 consecutive patients who underwent curative surgery for lung cancer between 2007 and 2012, the incidence of postoperative cardiopulmonary complications, white blood cell counts, and C-reactive protein levels were evaluated in the acute phase after surgery. Four patients had both cardiovascular and respiratory complications. The remaining 671 patients were divided into 3 groups: patients without cardiopulmonary complications; those with cardiovascular complications; and those with respiratory complications. The incidence of cancer recurrence was compared among the three groups. RESULTS: Postoperative cardiovascular or respiratory complications were identified in 94 (14%) or 25 (4%) patients, respectively. Postoperative white blood cell counts and C-reactive protein levels were significantly higher in those with postoperative respiratory complications than in those without. There was a significantly higher incidence of cancer recurrence in those with postoperative respiratory complications than in those without (48.0 vs. 16.8%; p < 0.0001). Multiple regression analysis adjusted for age, sex, and pathological staging showed that the incidence of postoperative respiratory complications was a significant predictor of cancer recurrence. CONCLUSIONS: The presence of respiratory complications following lung cancer surgery was a significant predictor of cancer recurrence.

B-type natriuretic peptide-guided risk assessment for postoperative complications in lung cancer surgery.

BACKGROUND: Since lung cancer surgery is still associated with a high complication rate, it is important to efficiently identify patients at high risk for postoperative complications following lung cancer surgery. We previously reported that elderly patients with elevated preoperative B-type natriuretic peptide (BNP) levels (>30 pg/mL) have an increased risk for postoperative atrial fibrillation and cardiopulmonary complications following lung cancer surgery. The objective of this study was to evaluate the clinical utility of BNP-guided risk classification for postoperative complications after lung cancer surgery. METHODS: A total of 675 consecutive patients who underwent curative surgery for lung cancer in two specialized thoracic centers between 2007 and 2011 were included in this retrospective study. We evaluated the association between the incidence of postoperative complications and preoperative BNP levels. RESULTS: Univariable and multivariable stepwise logistic regression analyses revealed that an elevated preoperative BNP level was the most significant predictor of postoperative complications. All patients were classified by their preoperative BNP levels into a normal group (<30 pg/mL), a mildly elevated group (30-100 pg/mL), and a severely elevated group (>100 pg/mL). The incidence of postoperative complications was significantly higher in the severely and mildly elevated groups than in the control group (85 % and 47 % vs. 11 %, P < 0.0001). Furthermore, there were more severe complications and a higher mortality rate in the severely elevated group. CONCLUSIONS: Risk assessment using preoperative BNP levels was clinically useful for the identification of patients at high risk for postoperative complications.

Impact of cardiopulmonary complications of lung cancer surgery on long-term outcomes.

PURPOSE: The impact of postoperative cardiopulmonary complications on long-term outcomes has not been established. We investigated the effects of acute postoperative cardiopulmonary complications not only on cancer recurrence, but also on cardiovascular or respiratory events in the chronic phase after lung cancer surgery. METHODS: From a prospective single-institution database of 496 consecutive patients, who underwent lung cancer surgery between August, 2008 and December, 2011, medical records, including information about cardiovascular or respiratory events and cancer recurrence in the chronic phase (>6 months) after surgery, were analyzed retrospectively. Results were compared between patients with vs. those without postoperative cardiopulmonary complications in the acute phase. RESULTS: Postoperative cardiopulmonary complications were identified in 90 (20%) patients. There were significantly more cardiovascular or respiratory events in the chronic phase after lung cancer surgery in the patients who had suffered postoperative cardiopulmonary complications in the acute phase than in those who had not (23 vs. 5%; p < 0.0001). CONCLUSIONS: Postoperative cardiopulmonary complications in the acute phase were associated with a higher incidence of cardiovascular or respiratory events in the chronic phase after lung cancer surgery. CLINICAL TRIAL REGISTRATION NUMBER: JPRN-UMIN2370.

Inhaled tiotropium to prevent postoperative cardiopulmonary complications in patients with newly diagnosed chronic obstructive pulmonary disease requiring lung cancer surgery.

PURPOSE: A new diagnosis of chronic obstructive pulmonary disease is often made during the evaluation of patients requiring lung cancer surgery. The objective of the present study was to evaluate the clinical effects of inhaled tiotropium on the postoperative cardiopulmonary complications in patients with untreated chronic obstructive pulmonary disease requiring lung cancer surgery. METHODS: A retrospective study involving 104 consecutive patients with moderate to severe chronic obstructive pulmonary disease who underwent a lobectomy for lung cancer at two specialized thoracic centers between April 2008 and October 2011 was performed. The results were compared between patients who did and did not receive inhaled tiotropium during the perioperative period. The primary endpoint was the incidence of postoperative cardiopulmonary complications. The postoperative white blood cell counts and C-reactive protein levels as biomarkers of inflammation were also examined. RESULTS: The incidence of postoperative cardiopulmonary complications was significantly lower in the tiotropium group than in the control group (18 vs. 48 %, P = 0.001). Patients in the tiotropium group also showed significantly lower white blood cell counts and C-reactive protein levels postoperatively. CONCLUSIONS: Inhaled tiotropium treatment during the perioperative period had a prophylactic effect on postoperative cardiopulmonary complications in patients with newly diagnosed chronic obstructive pulmonary disease requiring lung cancer surgery.

Association of cigarette smoking with the expression of nuclear survivin in pathological Stage IA lung adenocarcinomas.

Survivin is expressed in the cytoplasm and/or nucleus of various types of malignant tumor cells. Cytoplasmic survivin functions as an apoptosis inhibitor, while nuclear survivin is indispensable for complete mitosis completion. To investigate the effect of cigarette smoking on the survivin expression in lung adenocarcinomas at the early developmental stage, we examined the expression of nuclear and cytoplasmic survivin in pathological Stage IA lung adenocarcinomas resected from 38 non-smokers and 44 smokers (current smokers and ex-smokers) using an immunohistochemical method. Labeling indices of nuclear survivin in tumors of smokers were significantly greater than those of non-smokers. The labeling index of nuclear survivin was above 3 % in only 1 (2.6 %) of the 38 tumors of the non-smokers, while the labeling indices in 19 (43.2 %) of 44 tumors of the smokers were above 3 % with a significantly greater frequency. There was no significant difference in the labeling index of nuclear survivin between current smokers and ex-smokers. There was no significant difference in the labeling index of cytoplasmic survivin between tumors of the non-smokers and the smokers. The present results show that cigarette smoking is associated with the higher nuclear surviving expression in lung adenocarcinomas at the early stage, suggesting that cigarette smoking affects the nuclear survivin expression in lung adenocarcinomas at the early developmental stage.

Mixed squamous cell and glandular papilloma of the lung increased in twelve years -A case report.

We report the case of a 55-year-old man presented with a nodule in the right middle lung on computed tomography. The size of the nodule had increased at 12 years after the first visit. Consequently, the patient was diagnosed with a Mixed squamous cell and glandular papilloma (MSGP) by surgical resection. To our knowledge, there are no previous studies that MSGP in the lung which had been observed for 12 years before surgery. This study reports the case of a patient who underwent surgical resection of a MSGP.

Yellow nail syndrome with thoracic empyema: report of a case.

We report a rare case of yellow nail syndrome (YNS) complicated by thoracic empyema. The patient was a 75-year-old man with yellow nails and a history of respiratory illnesses. Initially he presented with recurrent pleural effusion, which developed into empyema within 3 years. This case serves to reinforce that recurrent pleural effusions should be initiated in the early stage of YNS to prevent the development of empyema.

Detection of lymph node metastasis in non-small cell lung cancer using the new system of one-step nucleic acid amplification assay.

INTRODUCTION: The prognosis of non-small cell lung cancer greatly depends on the presence of lymph node metastasis, which limits the need for surgery and adjuvant therapy for advanced cancer. One-step nucleic acid amplification of cytokeratin19 (CK19) mRNA was used to detect lymph node metastasis. Automated Gene Amplification Detector RD-200 and the LYNOAMP CK19 gene amplification reagent as components of the new one-step nucleic acid amplification system, which has increased gene amplification efficiency by improving the reagent composition, have shorter preprocessing and measurement times than conventional systems. We aimed to compare the clinical performance of the new system with that of histopathology and the conventional system. MATERIALS AND METHODS: 199 lymph nodes from 58 non-small cell lung cancer patients who underwent lymph node dissection were examined intraoperatively using the new system, conventional system, and histopathology. RESULTS: Lymph node metastasis was diagnosed in 32, 42, and 44 patients using histopathological analysis, the new system, and the conventional system, respectively. Compared with histopathological analysis, the concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value of the new system were 92.0%, 90.6%, 92.2%, 69.0%, and 98.1%, respectively, and compared with the conventional system, the values were 95.0%, 86.4%, 97.4%, 90.5%, and 96.2%, respectively. CONCLUSION: The clinical performance of the new one-step nucleic acid amplification system in detecting lymph node metastasis of lung cancer is comparable to that of histopathology and the conventional system; its performance was sufficient for determining the appropriate clinical treatment. The new rapid system can be effectively utilized during lung cancer treatment intraoperatively and postoperatively.

Efficacy of pleural coverage with polyglycolic acid sheet after bullectomy for postoperative recurrence of spontaneous pneumothorax in young patients: a multi-institutional cohort study.

OBJECTIVE: Various surgical procedures have been performed to decrease the recurrence of primary spontaneous pneumothorax after video-assisted thoracic surgery. This study aimed to examine the efficiency of pleural coverage for the prevention of postoperative recurrence in relatively young patients. METHODS: Between January 2008 and December 2012, a total of 357 cases of 345 patients (age 15-29 years) with primary spontaneous pneumothorax who underwent bullectomy at 13 institutions were enrolled in this multi-institutional retrospective cohort study. A concurrent bilateral operation was counted as two cases. Polyglycolic acid sheets were used in 238 cases, and oxidized regenerated cellulose sheets were used in 37 cases to cover the visceral pleura, with no pleural coverage in 82 cases. The average observation period was 4.2 ± 2.0 years. RESULTS: Postoperative recurrence was observed in 50 cases (14.0%) after video-assisted thoracic surgery. Twenty-six cases (10.9%) in the polyglycolic acid group, eight (21.6%) in the oxidized regenerated cellulose group, and sixteen (19.5%) in the non-coverage group experienced postoperative recurrence. Kaplan-Meier analysis revealed that the rate of freedom from postoperative recurrence in the polyglycolic acid group was significantly higher than that in the non-coverage group. Multivariate analysis showed that age ≥ 20 years and coverage with polyglycolic acid sheets were associated with reduced risk factors for postoperative recurrence. CONCLUSION: Pleural coverage with a polyglycolic acid sheet is suggested to be effective in preventing postoperative recurrence of pneumothorax compared with non-coverage in relatively young patients.

Analysis of pulmonary nodules caused by nontuberculous mycobacteriosis in 101 resected cases: multi-center retrospective study.

BACKGROUND: Solitary pulmonary nodules caused by nontuberculous mycobacteriosis are included as a category of pulmonary nontuberculous mycobacterium disease. Clinical characteristics, treatments and prognosis are not fully known because there are a few related reports. METHODS: This was a multi-center retrospective study of 101 cases diagnosed as solitary nodular type of nontuberculous mycobacteriosis from January 2000 to March 2017 that underwent resection at 9 related facilities belonging to the Thoracic Surgery Study Group of Osaka. RESULTS: The most common pathogen was Mycobacterium avium complex (n=77, 87.5%), followed by Mycobacterium kansasii (n=8, 9.1%). Chest computed tomography results showed subpleural locations that were difficult to distinguish from lung cancer. Fluorodeoxyglucose positron emission tomography/computed tomography was performed in 58 cases and positive results were obtained in 35 (60.3%), with an average maximum standardized uptake value of 3.87. The purpose of resection in most cases was for diagnosis. The surgical procedure was wedge resection in 87, segmentectomy in 3, and lobectomy in 11, while 77 underwent thoracoscopic surgery. Postoperative complications occurred in 7 cases, though no infections caused by nontuberculous mycobacteriosis were noted. The median observation period was 27 months. A worsened condition occurred in 10 (9.9%) with Mycobacterium avium complex, though none had local recurrence. CONCLUSIONS: Solitary pulmonary nodules due to nontuberculous mycobacteriosis is difficult to diagnose based on preoperative examination results or distinguish from lung cancer. Among the present cases, none had local complications or recurrence, even in those that underwent a wedge resection, thus postoperative chemotherapy was not considered necessary if a complete resection was performed. On the other hand, some cases showed reinfection after a long period following resection, thus patients should be informed of that future possibility.

Impact of somatic mutations on prognosis in resected non-small-cell lung cancer: The Japan Molecular Epidemiology for lung cancer study.

BACKGROUND: To report the follow up data and clinical outcomes of the JME study (UMIN 000008177), a prospective, multicenter, molecular epidemiology examination of 876 surgically resected non-small-cell lung cancer (NSCLC) cases, and the impact of somatic mutations (72 cancer-associated genes) on recurrence-free survival (RFS) and overall survival (OS). METHODS: Patients were enrolled between July 2012 and December 2013, with follow up to 30th November 2017. A Cox proportional hazards model was used to assess the impact of gene mutations on RFS and OS, considering sex, smoking history, age, stage, histology, EGFR, KRAS, TP53, and number of coexisting mutations. RESULTS: Of 876 patients, 172 had ≥2 somatic mutations. Median follow-up was 48.4 months. On multivariate analysis, number of coexisting mutations (≥2 vs 0 or 1, HR = 2.012, 95% CI: 1.488-2.695), age (≥70 vs <70 years, HR = 1.583, 95% CI: 1.229-2.049), gender (male vs female, HR = 1.503, 95% CI: 1.045-2.170) and pathological stage (II vs I, HR = 3.386, 95% CI: 2.447-4.646; ≥III vs I, HR = 6.307, 95% CI: 4.680-8.476) were significantly associated with RFS, while EGFR mutation (yes vs no, HR = 0.482, 95% CI: 0.309-0.736), number of coexisting mutations (≥2 vs 0 or 1, HR = 1.695, 95% CI: 1.143-2.467), age (≥70 vs <70 years, HR = 1.932, 95% CI: 1.385-2.726), and pathological stage (II vs I, HR = 2.209, 95% CI: 1.431-3.347; ≥III vs I, HR = 5.286, 95% CI: 3.682-7.566) were also significant for OS. CONCLUSION: A smaller number of coexisting mutations, earlier stage, and younger age were associated with longer RFS and OS, while EGFR mutations were significantly associated with improved OS.

Feasibility of postoperative adjuvant chemotherapy using carboplatin plus S-1 in completely resected non-small cell lung cancer patients.

Feasibility is one of the major concerns during adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. A phase II clinical trial of adjuvant chemotherapy with four courses of carboplatin (AUC 5 at day 1) and S-1 (80 mg/m2/day for 2 weeks followed by a 2-week rest) was performed to evaluate the feasibility (UMIN 9101). The primary endpoint was the completion rate and the secondary endpoints were adverse events, 2-year overall survival and disease-free rates. Thirty-five non-small cell lung cancer patients were enrolled. The adjuvant chemotherapy completion rate was 85.3% (29/34); 17/34 (50%) patients completed 4 courses without dose reduction. There were no treatment-related deaths, and Grade 3/4 adverse events included neutropenia (38.2%), leukocytopenia (14.7%), anemia (20.6%), thrombocytopenia (20.6%), anorexia (5.9%), fatigue (5.9%), and oral mucositis (2.9%). Two-year overall and disease-free survival rates were 96.3% and 53.3%, respectively. Adjuvant chemotherapy with carboplatin plus S-1 is safe and feasible.

Thoracoscopic segmentectomy for intralobar sequestration in adult: a case report.

BACKGROUND: Surgical resection is the first choice for intralobar sequestration (ILS). A lobectomy is often performed, though we consider that a segmentectomy may be sufficient for benign cases if the sequestration is completely included within a segment. CASE PRESENTATION: We treated a 36-year-old female diagnosed with ILS. Chest computed tomography (CT) revealed several cystic lesions with niveau formation and consolidation in left segment (S)10 without communication of the bronchus and abnormal artery branching from the descending aorta. We performed a sublobar resection of left S10 including sequestration through a thoracoscopic minimally sized incision. The sequestration had dark red appearance and was completely included in the S10. The boundary line of S10 was clear with inflation of the lung after cutting bronchus 10. The postoperative course was uneventful. Chest CT findings at 2 years after surgery showed good expansion of the residual left lower lobe with no consolidation and respiratory function were nearly the same as the preoperative condition. CONCLUSIONS: A thoracoscopic segmentectomy for ILS is a feasible and useful procedure for qualified cases, even in adult patients who had repeated inflammation.

Upfront surgery in patients with clinical skip N2 lung cancer based on results of modern radiological examinations.

BACKGROUND: Direct lymphatic drainage from a primary tumor to the right paratracheal or aortic window lymph nodes is often noted in pN2 disease. This multi-institutional retrospective study investigated the outcomes of upfront surgery in patients with clinical skip N2 disease (N2 disease without N1 disease) and a tumor in the right upper lobe or left upper segment based on results of modern radiological examinations, including positron emission tomography (PET). METHODS: We identified 143 patients with cN2 disease who underwent upfront surgery in 12 institutions under the Thoracic Surgery Study Group of Osaka University between January 2006 and December 2013. Among 143 patients, 94 who underwent PET were analyzed. We classified these patients into Group A (n=39; clinical skip N2 disease and a tumor in the right upper lobe or left upper segment) and Group B (n=55; other). RESULTS: The median follow-up was 56.5 months. Among the 94 patients, 50 (53.2%) had skip N2 disease and 65 (69.1%) had a tumor in the right upper lobe or left upper segment. The 5-year overall survival (OS) rates of the 94 patients with cN2 disease was 47.9%. The 5-year OS rates for the cN2pN0/1 (n=22) and cN2pN2 (n=70) groups were 74.9% and 41.2%, respectively (P=0.034). The univariate analysis of OS revealed no significant differences in age, sex, histology, carcinoembryonic antigen (CEA) level, tumor size, PET findings, and number of metastatic lymph nodes when these parameters were dichotomized. A significantly better 5-year OS rate was observed in Group A than in Group B (64.0% vs. 37.0%; P=0.039). The multivariate analysis of OS revealed that Group A was a significantly prognostic factor (P=0.030). CONCLUSIONS: Patients with cN2 disease in Group A had a more favorable prognosis. Upfront surgery may be a treatment option for such selected patients with non-small lung cancer in the specific group.