A Novel Urine Test Biosensor Platform for Early Lung Cancer Detection.

Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection is essential to achieving a better outcome and prognosis. Volatile organic compounds (VOCs) reflect alterations in the pathophysiology and body metabolism processes, as shown in various types of cancers. The biosensor platform (BSP) urine test uses animals' unique, proficient, and accurate ability to scent lung cancer VOCs. The BSP is a testing platform for the binary (negative/positive) recognition of the signature VOCs of lung cancer by trained and qualified Long-Evans rats as biosensors (BSs). The results of the current double-blind study show high accuracy in lung cancer VOC recognition, with 93% sensitivity and 91% specificity. The BSP test is safe, rapid, objective and can be performed repetitively, enabling periodic cancer monitoring as well as an aid to existing diagnostic methods. The future implementation of such urine tests as routine screening and monitoring tools has the potential to significantly increase detection rate as well as curability rates with lower healthcare expenditure. This paper offers a first instructive clinical platform utilizing VOC's in urine for detection of lung cancer using the innovative BSP to deal with the pressing need for an early lung cancer detection test tool.

Using Continuous Flow Data to Predict the Course of Air Leaks After Lung Lobectomy.

Background: Assessments of air leaks are usually performed subjectively, precluding the use of air leaks as an evaluation factor. We aimed to identify objective parameters as predictive factors for prolonged air leak (PAL) and air leak cessation (ALC) from air flow data produced by a digital drainage system. Methods: Flow data records of 352 patients who underwent lung lobectomy were reviewed, and flow data at designated intervals (1, 2, and 3 hours postoperatively [POH] and 3 times a day thereafter [06:00, 13:00, 19:00]) were extracted. ALC was defined by flow less than 20 mL/min over 12 hours, and PAL was defined as ALC after 5 days. Cumulative incidence curves were obtained using Kaplan-Meier estimates of time to ALC. Cox regression analysis was performed to determine the effects of variables on the rate of ALC. Results: The incidence of PAL was 18.2% (64/352). Receiver operating characteristic curve analysis showed cut-off values of 180 mL/min for the flow at 3 POH and 73.3 mL/min for the flow on postoperative day 1; the sensitivity and specificity of these values were 88.9% and 82.5%, respectively. The rates of ALC by Kaplan-Meier analysis were 56.8% at 48 POH and 65.6% at 72 POH. Multivariate Cox regression analysis revealed that the flow at 3 POH (≤80 mL/min), operation time (≤220 minutes), and right middle lobectomy independently predicted ALC. Conclusion: Air flow measured by a digital drainage system is a useful predictor of PAL and ALC and may help optimize the hospital course.

Transcutaneous Carbon Dioxide Monitoring More Accurately Detects Hypercapnia than End-Tidal Carbon Dioxide Monitoring during Non-Intubated Video-Assisted Thoracic Surgery: A Retrospective Cohort Study.

Transcutaneous carbon dioxide (PtcCO2) monitoring is known to be effective at estimating the arterial partial pressure of carbon dioxide (PaCO2) in patients with sedation-induced respiratory depression. We aimed to investigate the accuracy of PtcCO2 monitoring to measure PaCO2 and its sensitivity to detect hypercapnia (PaCO2 > 60 mmHg) compared to nasal end-tidal carbon dioxide (PetCO2) monitoring during non-intubated video-assisted thoracoscopic surgery (VATS). This retrospective study included patients undergoing non-intubated VATS from December 2019 to May 2021. Datasets of PetCO2, PtcCO2, and PaCO2 measured simultaneously were extracted from patient records. Overall, 111 datasets of CO2 monitoring during one-lung ventilation (OLV) were collected from 43 patients. PtcCO2 had higher sensitivity and predictive power for hypercapnia during OLV than PetCO2 (84.6% vs. 15.4%, p < 0.001; area under the receiver operating characteristic curve; 0.912 vs. 0.776, p = 0.002). Moreover, PtcCO2 was more in agreement with PaCO2 than PetCO2, indicated by a lower bias (bias ± standard deviation; -1.6 ± 6.5 mmHg vs. 14.3 ± 8.4 mmHg, p < 0.001) and narrower limit of agreement (-14.3-11.2 mmHg vs. -2.2-30.7 mmHg). These results suggest that concurrent PtcCO2 monitoring allows anesthesiologists to provide safer respiratory management for patients undergoing non-intubated VATS.

Prognostic value of 18F-FDG PET parameters in patients with locally advanced non-small cell lung cancer treated with induction chemotherapy.

AIM: To investigate predictive and prognostic role of metabolic parameters using [18 F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (18 F-FDG PET) in patients with locally advanced non-small cell lung cancer (NSCLC) treated with docetaxel-platinum induction chemotherapy (IC). METHODS: Medical records of 31 patients with pre- and post-IC 18 F-FDG PET were reviewed. Using 18 F-FDG PET, metabolic parameters, including metabolic tumor response, adjusted peak standardized uptake values using lean body mass at baseline (pre-SULpeak ) and after IC (post-SULpeak ), and percentage change of pre- and post-SULpeak (ΔSULpeak ), were assessed. RESULTS: Response rate (RR) was 71%, with a metabolic RR of 83.9%. Nineteen (61.3%) patients underwent surgery, R0 resection was achieved for 17 (89.5%) patients. Median relapse-free survival (RFS) and overall survival (OS) were 8.9 months (95% CI: 4.5-12.1) and 24.1 months (95% CI: 17.1-34.1), respectively. Post-SULpeak  < 2 was identified as a favorable prognostic factor for RFS (hazard ratio [HR]: 0.12; P = .004), while ΔSULpeak ≥60% and R0 resection were found as positive prognostic factors for OS (HR: 0.09 and 0.13; P = .011 and P = .042, respectively). Using a receiver operating characteristics curve, post-SULpeak  > 1.4 could predict recurrence with a sensitivity of 84% and a specificity of 100%. CONCLUSION: In patients with locally advanced NSCLC receiving IC, post-SULpeak and ΔSULpeak showed clinical significance for survival outcome.

Comparison of Uniportal versus Multiportal Video-Assisted Thoracoscopic Surgery Pulmonary Segmentectomy.

BACKGROUND: Uniportal video-assisted thoracoscopic surgery (VATS) has proven safe and effective for pulmonary wedge resection and lobectomy. The objective of this study was to evaluate the safety and feasibility of uniportal VATS segmentectomy by comparing its outcomes with those of the multiportal approach at a single center. METHODS: The records of 84 patients who underwent VATS segmentectomy from August 2010 to August 2018, including 33 in the uniportal group and 51 in the multiportal group, were retrospectively reviewed and analyzed. RESULTS: Anesthesia and operative times were similar in the uniportal and multiportal groups (215 minutes vs. 220 minutes, respectively; p=0.276 and 180 minutes vs. 198 minutes, respectively; p=0.396). Blood loss was significantly lower in the uniportal group (50 mL vs. 100 mL, p=0.013) and chest tube duration and hospital stay were significantly shorter in the uniportal group (2 days vs. 3 days, p=0.003 and 4 days [range, 1-14 days] vs. 4 days [range, 1-62 days], p=0.011). The number of dissected lymph nodes tended to be lower in the uniportal group (5 vs. 8, p=0.056). CONCLUSION: Our preliminary experience indicates that uniportal VATS segmentectomy is safe and feasible in well-selected patients. A randomized, prospective study with a large group of patients and long-term follow-up is necessary to confirm these results.

Does FDG PET/CT have a role in determining adjuvant chemotherapy in surgical margin-negative stage IA non-small cell lung cancer patients?

PURPOSE: To evaluate the prognostic value of FDG PET/CT metabolic parameter compared to clinico-pathological risk factors in surgical margin-negative stage IA non-small cell lung cancer (NSCLC) patients. METHODS: 167 patients with consecutive FDG PET/CT scans from 2009 to 2015 performed for staging of NSCLC stage IA with plans for curative surgery were retrospectively reviewed. Maximum standardized uptake value (SUVmax) of primary tumor and mean SUV of liver were acquired from PET/CT. Tumor-to-liver SUV ratio (TLR) was calculated. Charts were reviewed to obtain basic patient characteristics (age, sex, smoking history, LDH, histologic subtype) and high-risk factors for adjuvant chemotherapy (tumor size, poorly differentiation, vascular invasion, and sub-lobar resection). Patients were dichotomized into two groups using optimal cut-off from receiver operating characteristic curve analysis of TLR to predict recurrence. Statistical analysis was done using Cox regression analysis and Kaplan-Meier method. Factors with P < 0.2 in univariate analysis were included in multivariate analysis. RESULTS: Recurrence rate was 12.6% (21/167). Median disease-free survival (DFS) was 47.2 months while 2-year and 5-year DFS rates were 93% and 86%, respectively. The optimal cut-off for TLR was 2.3. In univariate analysis, P value of sex, vascular invasion, and TLR were less than 0.2. In multivariable analysis, high TLR was the only factor that showed significant association with tumor recurrence (hazard ratio 3.795, P = 0.0048). CONCLUSIONS: TLR was an independent prognostic factor for recurrence and TLR could be an important risk factor to be considered in decision-making for adjuvant chemotherapy, even for those with stage IA NSCLC.

Prognostic role of beclin-1 in locally advanced non-small cell lung cancer in patients receiving docetaxel-platinum induction chemotherapy.

BACKGROUND/AIMS: The outcome of local treatment for advanced non-small cell lung cancer (NSCLC) remains poor, with therapies such as induction chemotherapy (IC) yielding conflicting results. This study aimed to assess the clinicopathologic and prognostic significance of the excision repair cross-complementation group 1 (ERCC1), beclin-1, and glucose-regulated protein of molecular mass 78 (GRP78) in patients with locally advanced NSCLC receiving docetaxel-platinum IC, along with efficacy and safety. METHODS: This is a retrospective observational cohort study. We reviewed medical records of 31 NSCLC patients receiving docetaxel-platinum IC, and conducted immunohistochemical staining of ERCC1, beclin-1, and GRP78. RESULTS: Response rate was 67.8% with 10.7 months of median relapse-free survival (RFS) and 23.1 months of median overall survival (OS), and no treatment-related death was reported. High expression of ERCC1, beclin-1, and GRP78 was identified in 67.7%, 87.1%, and 67.7%, respectively. Expression of ERCC1 and GRP78 did not reveal statistical significance in survival, whereas high beclin-1 expression revealed longer OS (7.6 months vs. 23.2 months; log-rank p = 0.024). In multivariate analysis, histologic differentiation (hazard ratio [HR], 3.48; p < 0.001), stage (HR, 8.5; p = 0.024), and adjuvant treatment (HR, 16.1; p = 0.001) were related to RFS, and in OS, stage (HR, 5.4; p = 0.037), adjuvant treatment (HR, 8.6; p = 0.004), and beclin-1 expression (HR, 8.2; p = 0.011) were identified as significant prognostic factors. CONCLUSION: Our findings suggest that high beclin-1 expression predicts longer survival in locally advanced NSCLC and docetaxel-platinum IC is a treatment option that deserves consideration.

Prognostic Factors of Pathological N1 Non-small Cell Lung Cancer After Curative Resection Without Adjuvant Chemotherapy.

BACKGROUND: The aim of this study was to evaluate the outcomes of patients with pathological N1 non-small cell lung cancer who did not receive adjuvant chemotherapy. We attempted to identify those patients for whom adjuvant chemotherapy would be indispensable. METHODS: Among 132 patients who were diagnosed with pathological N1 lung cancer at a single institution from January 2010 to December 2016 were 32 patients who did not receive adjuvant treatment after curative surgical resection. The surgical and oncological outcomes of these patients were analyzed. Candidate factors for predicting recurrence were analyzed to identify patients at high risk of recurrence. RESULTS: The median follow-up time for all 32 patients was 1044 days. The 5-year recurrence-free survival (RFS) and disease-specific survival rates of the patients without adjuvant therapy were 50.3% and 77.6%, respectively. By multivariate analysis, tumors with a lepidic growth pattern [hazard ratio (HR) 0.119, p = 0.024] and extralobar lymph node metastasis (HR 6.848, p = 0.015) were significant factors predicting recurrence. The difference between the 5-year RFS rates of patients with tumors with or without a lepidic growth pattern was statistically significant (63.5% vs 40.0%, respectively; p = 0.050). The 5-year RFS rates of patients with intralobar lymph node metastasis versus those with extralobar lymph node metastasis were 63.3% and 18.8%, respectively (p = 0.002). CONCLUSIONS: Patients with tumors without a lepidic growth pattern or with extralobar lymph node metastasis who do not receive adjuvant chemotherapy have a high recurrence rate after surgery. Therefore, these patients should be encouraged to undergo adjuvant chemotherapy if their overall condition is not a contraindication for chemotherapy.

Nonintubated Uniportal Video-Assisted Thoracoscopic Surgery: A Single-Center Experience.

BACKGROUND: We report our surgical technique for nonintubated uniportal video-assisted thoracoscopic surgery (VATS) pulmonary resection and early postoperative outcomes at a single center. METHODS: Between January and July 2017, 40 consecutive patients underwent nonintubated uniportal VATS pulmonary resection. Multilevel intercostal nerve block was performed using local anesthesia in all patients, and an intrathoracic vagal blockade was performed in 35 patients (87.5%). RESULTS: Twenty-nine procedures (72.5%) were performed in patients with lung cancer (21 lobectomies, 6 segmentectomies, and 2 wedge resections), and 11 (27.5%) in patients with pulmonary metastases, benign lung disease, or pleural disease. The mean anesthesia time was 166.8 minutes, and the mean operative duration was 125.9 minutes. The mean postoperative chest tube duration was 3.2 days, and the mean hospital stay was 5.8 days. There were 3 conversions (7.5%) to intubation due to intraoperative hypoxemia and 1 conversion (2.5%) to multiportal VATS due to injury of the segmental artery. There were 7 complications (17.5%), including 3 cases of prolonged air leak, 2 cases of chylothorax, 1 case of pleural effusion, and 1 case of pneumonia. There was no in-hospital mortality. CONCLUSION: Nonintubated uniportal VATS appears to be a feasible and valid surgical option, depending on the surgeon's experience, for appropriately selected patients.

Comparison of non-intubated versus intubated video-assisted thoracoscopic lobectomy for lung cancer.

BACKGROUND: Non-intubated, or awake, video-assisted thoracoscopic surgery has been implemented for non-anatomical lung resection and the results obtained were encouraging to consider the approach for anatomical pulmonary resection. This study was conducted to evaluate the perioperative outcomes of the non-intubated and intubated video-assisted thoracoscopic lobectomy in lung cancer in regards to feasibility and safety. METHODS: A retrospective analysis of 62 consecutive video-assisted thoracoscopic lobectomies (31 lobectomies as non-intubated, 31 lobectomies as intubated) performed in Seoul St. Mary's Hospital, The Catholic University of Korea between January and December 2016. RESULTS: Both groups share comparable clinical characteristics including the age, sex, BMI, FEV1, DLCO, smoking history, lung lobes procedure, histological type and pathological staging. There was no difference in the mean of postoperative hospitalization period (6.9 versus 7.6 days, P=0.578) and the total chest tube duration (5.6 versus 5.4 days, P=0.943) between non-intubated and intubated lobectomy respectively. Both groups had a comparable surgical outcome for the anesthesia duration, operative time, blood loss and postoperative complications. The operative time required for lobe-specific surgery was shorter in the non-intubated group except for the LLL (mean 121.7 minutes for non-intubated group versus 118.3 minutes for the intubated group). The only statistically significant surgical outcome was for the number of dissected lymph nodes between both groups (the mean number of nodes for the non-intubated group was 12.6 versus 18.0 nodes for the intubated group, P=0.003). One patient in the non-intubated group required conversion to single lung intubation and mini-thoracotomy because of bleeding with no conversion in the intubated group. No mortality encountered in either group. CONCLUSIONS: The perioperative surgical outcomes for the non-intubated video-assisted thoracoscopic lobectomy are comparable to the intubated technique. Non-intubated video-assisted thoracoscopic lobectomy is safe and is technically feasible. However, further prospective randomized studies are needed for a better comparison between non-intubated and intubated VATS lobectomy.

Non-intubated thoracoscopic surgery: initial experience at a single center.

BACKGROUND: Non-intubated thoracoscopic surgery is an evolving form of minimally-invasive thoracic surgery. We commenced performing non-intubated thoracoscopic surgery at our center in August 2016. We would like to report our initial experience, over a period of 1 year, with this procedure. METHODS: From August 2016 to August 2017, non-intubated thoracoscopic surgery was performed in a series of consecutive patients who underwent thoracoscopic surgery in those who did not meet any of the following exclusion criteria: body mass index (BMI) >30, expected difficult airway, expected extensive pleural adhesion, severe cardiopulmonary dysfunction, persistent cough or excessive airway secretion, high risk of gastric reflux, and underlying neurological disorder. RESULTS: A total of 115 consecutive patients underwent non-intubated thoracoscopic surgery. Of these, 83 (72.2%) of patients had lung cancers that had undergone pulmonary resection and the other 32 (27.8%) patients were diagnosed with pulmonary metastasis, benign lung diseases, thymic tumor or other conditions. The mean time of anesthesia was 172.4 min and time of operation was 130 min. The mean postoperative chest tube duration was 3.9 days and time of hospital stay was 6.0 days. There were 9 conversions (7.8%) to intubation, due to increased respiratory movement with intraoperative hypoxemia or severe pleural adhesion. There were 16 complications (13.9%) following surgery, but all of these were successfully managed during the period of hospital stay. There was no postoperative mortality. In multivariate analysis, old age and high BMI were significant risk factors for conversion to intubation (hazard ratio =1.122, P=0.038; hazard ratio =1.408, P=0.042, respectively). CONCLUSIONS: Non-intubated thoracoscopic surgery can safely be performed in selected patients.

Clinical Characteristics of False-Positive Lymph Node on Chest CT or PET-CT Confirmed by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Lung Cancer.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure to evaluate suspicious lymph node involvement of lung cancer because computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography-CT (PET-CT) have limitations in their sensitivity and specificity. There are a number of benign causes of false positive lymph node such as anthracosis or anthracofibrosis, pneumoconiosis, old or active tuberculosis, interstitial lung disease, and other infectious conditions including pneumonia. The purpose of this study was to evaluate possible causes of false positive lymph node detected in chest CT or PET-CT. METHODS: Two hundred forty-seven patients who were initially diagnosed with lung cancer between May 2009 and December 2012, and underwent EBUS-TBNA to confirm suspicious lymph node involvement by chest CT or PET-CT were analyzed for the study. RESULTS: Of 247 cases, EBUS-TBNA confirmed malignancy in at least one lymph node in 189. The remaining 58 patients whose EBUS-TBNA results were negative were analyzed. Age ≥65, squamous cell carcinoma as the histologic type, and pneumoconiosis were related with false-positive lymph node involvement on imaging studies such as chest CT and PET-CT. CONCLUSION: These findings suggest that lung cancer staging should be done more carefully when a patient has clinically benign lymph node characteristics including older age, squamous cell carcinoma, and benign lung conditions.

Detection of RET (rearranged during transfection) variants and their downstream signal molecules in RET rearranged lung adenocarcinoma patients.

BACKGROUND: We screened resected tumor tissues from patients with lung cancer for EGFR mutations, ALK rearrangements, and rearranged during transfection (RET) gene variants (including RET rearrangements and the Kinesin Family Member 5B (KIF5B)-RET fusion gene) using various methods including reverse transcription polymerase chain reaction (RT-PCR), transcript assays, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). We also examined the protein expression of associated downstream signaling molecules to assess the effect of these variants on patient outcome. METHOD: We constructed a tissue microarray (TMA) comprising 581 resected tumor tissues from patients with lung adenocarcinoma and analyzed the microarray by both FISH (using RET break-apart and KIF5B-RET SY translocation probes) and a commercial RET transcript assay. We evaluated the expression of RET and RET-related signaling molecules, including p-AKT and p-ERK, by TMA -based IHC staining. RESULTS: Among the 581 specimens, 51 (8.8%) specimens harbored RET rearrangements, including 12 cases (2.1%) carrying a KIF5B-RET fusion gene. Surprisingly, RET expression was lower in KIF5B-RET fusion gene-positive than in RET wild-type specimens. We detected activating EGFR mutations in 11 (21.6%) of the 51 RET variant-positive specimens. Among the KIF5B-RET fusion gene-positive specimens, p-ERK expression was significantly lower in the EGFR mutation subgroup showing RET expression than in the EGFR mutation subgroup that did not express RET. Similarly, the RET rearrangement group showed significant variation in the expression level of p-AKT (P = 0.028) and p-ERK, whose expression remarkably increased in specimens not expressing RET. The expression of p-ERK markedly increased in the RET rearrangement group regardless of RET expression. CONCLUSION: This result suggests that a combination of RET and ERK inhibitors may be an effective treatment strategy for lung adenocarcinoma patients harboring RET variants.

Incidence and clinical features of the incidentally found vascular stump thrombus during routine follow up after oncologic lung surgery.

OBJECTIVES: We aimed to evaluate the incidence and clinical features of vascular stump thrombus after oncologic lung surgery. METHODS: A retrospective analysis of records from our institutional database dated between 2009 and 2016 was performed. Data regarding demographics, clinical presentation, medication use, operative findings, pathology, and radiologic findings were retrieved. RESULTS: The study cohort consisted of 648 oncologic surgeries for primary lung cancer. The incidence of thrombus in the entire population was 5.7% (37/648). Most thrombi were incidentally found on follow-up chest computed tomography scans. Univariate Cox proportional hazard analysis showed that age (p = 0.02), adjuvant therapy (p <0.001), neoadjuvant therapy (p = 0.04), left-sided surgery (p = 0.02), complex surgery greater than simple lobectomy or segmentectomy (p <0.001), advanced stages (p <0.001), non-adenocarcinoma (p = 0.003), and thoracotomy approach (p = 0.009) were associated with an increased risk of vascular stump thrombus. There were no embolic events in our cohort, except for a case of pulmonary thromboembolism. During follow-up, 43.2% (16/37) of thrombi had completely resolved, 48.6% (18/37) showed partial regression and stabilization, and 8.1% (3/37) had progressed. CONCLUSIONS: The incidence of vascular stump thrombus in our study was not negligible. The clinical course of stump thrombus appears to be benign in most cases. Anticoagulation may be used with caution based on an individual basis depending on each patient's risk factors.

Lymphatic invasion is a more significant prognostic factor than visceral pleural invasion in non-small cell lung cancer with tumours of 3 cm or less.

BACKGROUND AND OBJECTIVE: Visceral pleural invasion is an upstaging factor that increases cancer staging from stage IA to IB for tumours of 3 cm or less. However, lymphatic invasion has not been associated with the tumour-node-metastasis (TNM) staging system. The purpose of this study was to compare visceral pleural invasion and lymphatic invasion as prognostic factors. METHODS: We retrospectively reviewed 353 consecutive patients who underwent curative resection for stage I non-small cell lung cancer (NSCLC) tumours of 3 cm or less. Patients were divided into three groups and compared. Group A contained no invasions; group B contained visceral pleural invasion only and group C had lymphatic invasion only. RESULTS: Group A patients had stage IA, but group B patients had stage IB tumours. However, group C patients had stage IA tumours. The 5-year recurrence-free survival for the three groups was 86.2%, 71.5% and 48.0%, respectively. There was a significant difference in survival between groups A and C (P = 0.001).Survival was not different between groups A and B (P = 0.547). In a multivariate analysis conducted to determine risk factors for recurrence, lymphatic invasion was a significant independent risk factor for recurrence (hazard ratio = 2.570, P = 0.006). Pleural invasion was not a significant risk factor for recurrence. CONCLUSION: Lymphatic invasion is a more significant prognostic factor than visceral pleural invasion in NSCLC of 3 cm or less.

Clinical Significance of C-MET Overexpression and Epidermal Growth Factor Receptor Mutation in Platinum-Based Adjuvant Chemotherapy Outcome in Surgically Resected Lung Adenocarcinoma.

PURPOSE: We retrospectively assessed the role of C-MET expression and epidermal growth factor receptor (EGFR) mutation on survival following platinum-based adjuvant chemotherapy. The impact of C-MET on survival was also investigated in relation to EGFR mutation status. METHODS: We enrolled 311 patients with resected lung adenocarcinoma (high-risk stage 1B-3A), and performed immunohistochemistry (IHC) using C-MET- and mutant EGFR (EGFRmut)-specific antibodies in tissue microarrays. RESULTS: Adjuvant chemotherapy was administered to 151 patients, 96 of whom relapsed and 85 died by the end of the study. On IHC, C-MET and EGFRmut were positive in 141 (45.3 %) and 88 (28.3 %) cases, respectively. On univariate analysis, adjuvant chemotherapy prolonged relapse-free survival (RFS) and overall survival (OS) in C-MET(+) patients (RFS p = 0.035; OS p = 0.013) but not in C-MET(-) patients. On multivariate analysis, adjuvant chemotherapy was a positive independent prognostic factor in C-MET(+) (RFS p = 0.013; OS p = 0.006) but not in C-MET(-) patients. In addition, univariate analysis showed no effect of EGFRmut status on RFS and OS after chemotherapy, whereas multivariate analysis revealed that adjuvant chemotherapy increased RFS in both EGFRmut(+) and EGFRmut(-) patients [EGFRmut(+) p = 0.033; EGFRmut(-) p = 0.030]. C-MET was a negative prognostic factor for RFS (p = 0.045) and OS (p = 0.007) in the EGFRmut(-) group but not in the EGFRmut(+) group, on multivariate analysis. CONCLUSIONS: Our data indicate that patients with C-MET overexpression should be considered for adjuvant chemotherapy, and that C-MET negatively correlates with survival in patients with wild-type, but not mutant, EGFR.

Clinicopathological characteristics and prognosis of non-lepidic invasive adenocarcinoma presenting as ground glass opacity nodule.

BACKGROUND: Ground glass opacity (GGO) generally associated with the lepidic component of lung adenocarcinoma. However, in some cases, GGO nodules have been associated with invasive adenocarcinomas, where a lepidic component is minimal or absent. The purpose of this study is to evaluate the clinicopathological characteristics and prognosis of non-lepidic invasive adenocarcinoma presenting as GGO nodules. METHODS: We reviewed computed tomography (CT) images from 168 patients diagnosed with non-lepidic invasive adenocarcinoma classified as stage T1N0M0 (≤3 cm) who underwent curative anatomical resection. Tumors were classified according to radiologic features: 31 were GGO predominant (Group A) and 137 were solid predominant (Group B). The clinicopathological findings and recurrence free survival were used as outcome measures. RESULTS: The mean percentages of micropapillary and solid component in tumor was higher in Group B than Group A (P<0.001) Pleural invasion and lymphatic invasion were more frequently seen in Group B. The presence of tumors with a micropapillary component was higher in Group B (P=0.040). The 3-year recurrence-free survival was lower in Group B than Group A (80.4% vs. 100%, P=0.019). Risk factors for recurrence such as presence of a micropapillary component and lymphatic invasion were more frequently seen in Group B. CONCLUSIONS: Non-lepidic invasive adenocarcinoma presenting as GGO has fewer risk factors and better prognosis when compared with those presenting as solid tumors. Therefore, the presence of GGO on chest CT is a good prognostic indicator for lung cancer irrespective of histomorphologic classification.

The effectiveness of mediastinal lymph node evaluation in a patient with ground glass opacity tumor.

BACKGROUND: The prognosis of non-small cell lung cancer (NSCLC) presenting as a ground glass opacity (GGO) nodule is better than other types of lung cancer. The purpose of this study was to evaluate the necessity of mediastinal lymph node evaluation (MLE) in clinical N0 GGO-predominant NSCLC. METHODS: We conducted a retrospective chart review of 358 patients treated for clinical N0 NSCLC that was found by curative resection to be 3 cm or smaller in size. We analyzed clinicopathological findings and survival among three groups with either GGO-predominant or solid-predominant tumor: no mediastinal lymph node evaluation (NoMLE) group, mediastinal lymph node sampling (MLS) group, and mediastinal lymph node dissection (MLND) group. RESULTS: Except for sex, there were no differences in clinicopathological characteristics among the three groups with GGO-predominant tumor or solid-predominant tumor. There was no difference in the 5-year recurrence-free survival (RFS) rate among three groups in the GGO-predominant patients (100%, 92.9%, 93.8%, respectively; P=0.889). However, in the solid-predominant tumor group, the 5-year recurrence free survival of the NoMLE group was lower than in the MLND group (48.6% vs. 73.1%, P=0.007). MLE was not a significant risk factor for recurrence in GGO-predominant tumor [hazard ratio (HR) =1.021; P=0.987]. GGO-predominant tumor [odds ratio (OR) =0.063; P=0.008] was identified as the sole parameter that significantly impacted nodal upstaging. CONCLUSIONS: MLE is not an essential procedure for clinical N0 NSCLC presenting as a 3 cm or smaller GGO-predominant nodule.

Risk factors for recurrence after sublobar resection in patients with small (2 cm or less) non-small cell lung cancer presenting as a solid-predominant tumor on chest computed tomography.

BACKGROUND: Sublobar resection is considered controversial for non-small cell lung cancer (NSCLC) presenting as a solid-predominant nodule. The aim of this study was to identify risk factors related to recurrence in small-sized NSCLC presenting as a solid-predominant nodule. METHODS: We conducted a retrospective chart review of 118 patients who were treated for clinical N0 NSCLC sized ≤2 cm and who underwent sublobar resection with clear resection margins. We assigned them to two groups according to radiologic features: ground glass opacity (GGO)-predominant tumor and solid-predominant tumor. Clinicopathological characteristics and survival were analyzed in both groups. Risk factors for recurrence were analyzed in the solid-predominant tumor group. RESULTS: Seventy-three patients had a GGO-predominant tumor, and 45 patients had a solid-predominant tumor. Five-year recurrence-free survival (RFS) in the solid-predominant tumor and GGO-predominant tumor groups was 64.9% and 95.5%, respectively. A multivariate analysis was performed to determine factors associated with recurrence after sublobar resection in the solid-predominant tumor group; it indicated that SUVmax [hazard ratio (HR) =1.482, 95% confidence interval (CI): 1.123-1.956, P=0.005] and histologic types other than adenocarcinoma (squamous cell carcinoma, HR =8.789, 95% CI: 1.572-49.134, P=0.013; other types, HR =53.569, 95% CI: 2.616-1096.849, P=0.010) were significant risk factors for recurrence. CONCLUSIONS: Risk factors in solid-predominant tumors sized ≤2 cm after sublobar resection are a high SUVmax and histologic types other than adenocarcinoma. Thus, lobectomy should be considered for solid-predominant NSCLC sized ≤2 cm with a high SUVmax or non-adenocarcinoma types.