Search

Background We conducted a comparative study to evaluate the efficacy of poloxamer 407-based ropivacaine hydrogel at the wound site (Gel) and continuous thoracic paravertebral block (On-Q) for postoperative pain following thoracoscopic pulmonary resection. Methods This prospective, randomized, noninferiority study included 89 patients randomized into the two groups; Gel (poloxamer 407-based 0.75% ropivacaine, 22.5 mg) and On-Q (0.2% ropivacaine, 4 mg/hour for 48 hours). The primary outcome measure was total fentanyl consumption and secondary outcome measures were the need for rescue analgesia and pain intensity using the numeric rating scale (NRS). Results There was no significant difference in total fentanyl consumption between the Gel group and the On-Q group (1504.29 ± 315.72 mcg vs 1560.32 ± 274.81 mcg, p = 0.374). Pain intensity using the NRS between the Gel group and the On-Q group demonstrated no statistical differences (6 hours: 3.56 vs 3.55, p = 0.958; 24 hours: 3.21 vs 3.00, p = 0.250; 48 hours: 2.75 vs 2.49, p = 0.233; and 72 hours: 2.39 vs 2.33, p = 0.811), and there was no significant difference in the frequency of analgesic rescue medication use (3.70 vs 3.33, p = 0.417). Conclusions We confirm the noninferiority of Gel compared with On-Q for acute postoperative pain following thoracoscopic pulmonary resection. Considering a technical simplicity and low systemic toxicity of the local injection of Gel, this analgesic modality may be worthy of further research and is thus considered to have potential as a viable alternative to On-Q for regional analgesia.

Supplementary Data from Prediction of Recurrence-Free Survival in Postoperative Non–Small Cell Lung Cancer Patients by Using an Integrated Model of Clinical Information and Gene Expression

Purpose: One of the main challenges of lung cancer research is identifying patients at high risk for recurrence after surgical resection. Simple, accurate, and reproducible methods of evaluating individual risks of recurrence are needed.Experimental Design: Based on a combined analysis of time-to-recurrence data, censoring information, and microarray data from a set of 138 patients, we selected statistically significant genes thought to be predictive of disease recurrence. The number of genes was further reduced by eliminating those whose expression levels were not reproducible by real-time quantitative PCR. Within these variables, a recurrence prediction model was constructed using Cox proportional hazard regression and validated via two independent cohorts (n = 56 and n = 59).Results: After performing a log-rank test of the microarray data and successively selecting genes based on real-time quantitative PCR analysis, the most significant 18 genes had P values of CALB1, MMP7, SLC1A7, GSTA1, CCL19, and IFI44). Two pathologic variables, pStage and cellular differentiation, were developed. Validation by two independent cohorts confirmed that the proposed model is significantly accurate (P = 0.0314 and 0.0305, respectively). The predicted median recurrence-free survival times for each patient correlated well with the actual data.Conclusions: We have developed an accurate, technically simple, and reproducible method for predicting individual recurrence risks. This model would potentially be useful in developing customized strategies for managing lung cancer.

Identification of molecular markers often leads to important clinical applications such as early diagnosis, prognosis, and drug targeting. Lung cancer, the leading cause of cancer-related deaths, still lacks reliable molecular markers. We have combined the bioinformatics analysis of the public gene expression data and clinical validation to identify biomarker genes for non–small-cell lung cancer. The serial analysis of gene expression and the expressed sequence tag data were meta-analyzed to produce a list of the differentially expressed genes in lung cancer. Through careful inspection of the predicted genes, we selected 20 genes for experimental validation using semiquantitative reverse transcriptase-PCR. The microdissected clinical specimens used in the study consisted of three groups: lung tissues from benign diseases and the paired (cancer and pathologic normal) tissues from non–small-cell lung cancer patients. After extensive statistical analyses, seven genes (CBLC, CYP24A1, ALDH3A1, AKR1B10, S100P, PLUNC, and LOC147166) were identified as potential diagnostic markers. Quantitative real-time PCR was carried out to additionally assess the value of the seven identified genes leading to the confirmation of at least two genes (CBLC and CYP24A1) as highly probable novel biomarkers. The gene properties of the identified markers, especially their relationship to lung cancer and cell signaling pathway regulation, further suggest their potential value as drug targets as well. [Cancer Res 2007;67(15):7431–8]

Supplementary Tables 1-8 from Clinical Validity of the Lung Cancer Biomarkers Identified by Bioinformatics Analysis of Public Expression Data

We present an in-depth single cell atlas of in vitro multi-culture systems on human primary airway epithelium derived from normal and diseased lungs of 27 individual donors. Our large-scale single cell profiling identifies new cell states and differentiation trajectories of rare airway epithelial cell types in human distal lungs. By integrating single cell datasets of human lung tissues, we discover immune primed subsets enriched in lungs and organoids derived from patients with chronic respiratory disease. To demonstrate the full potential of our platform, we further illustrate transcriptomic responses to various respiratory virus infections in in vitro airway models. Our work constitutes a single-cell roadmap for the cellular and molecular characteristics of human primary lung cells in vitro and their relevance to human tissues in vivo.

Background Patients with N1 or N2 non-small cell lung cancer exhibit prognostic heterogeneity. To refine the current N staging system, new N stages were proposed by the International Association for the Study of Lung Cancer. However, those proposed new N stages have not been validated. Purpose To evaluate the prognostic performance of the proposed N descriptors for clinical staging. Materials and Methods Participants with non-small cell lung cancer without distant metastasis from January 2010 to December 2014 were retrospectively included. Each patient's clinical N (cN) stage was assigned to one of seven categories (cN0, cN1a, cN1b, cN2a1, cN2a2, cN2b, cN3). The 5-year overall survival rates were estimated with the Kaplan-Meier method. The adjusted hazard ratios (HRs) and their 95% CIs were estimated by using a multivariable Cox proportional hazard model. Ad hoc analyses according to lymph node (LN) size were performed. Results A total of 1271 patients (median age, 66 years; interquartile range, 59-73 years; 812 men) were included. The 5-year overall survival rates were 77.3%, 53.7%, 36.0%, 29.2%, 34.4%, 18.0%, and 12.4% for stages cN0, cN1a, cN1b, cN2a1, cN2a2, cN2b, and cN3, respectively. Patients with cN2b disease had a worse prognosis than patients with cN2a disease (HR, 1.53; 95% CI: 1.06, 2.22; P = .02). There was no prognostic difference between cN1b and cN1a (HR, 1.13; 95% CI: 0.61, 2.09; P = .71); however, there was a difference between cN1 subgroups when stratified by LN size (≥2 cm; HR, 2.26; 95% CI: 1.16, 4.44; P = .02). Within cN2a disease, there were no differences between cN2a1 and cN2a2 (HR, 0.98; 95% CI: 0.61, 1.56; P = .93) or between subgroups according to LN size (HR, 0.74; 95% CI: 0.40, 1.37; P = .34). Conclusion A survival difference was observed between single- and multistation involvement among cN2 disease. The number of involved lymph node stations in patients with cN1 disease and the presence of skip metastasis in patients with cN2 disease were not associated with survival differences. © RSNA, 2021 Online supplemental material is available for this article.

Tumor spread through air spaces (STAS) is an invasive pattern of lung cancer that was recently described. In this study, we investigated the association between the extent of STAS and clinicopathological characteristics and patient outcomes in resected non-small cell lung cancers (NSCLCs). STAS has been prospectively described from 2008 and graded its extent with a two-tiered system (STAS I

The purpose of this study was to assess the clinicopathologic implications of tumor spread through air spaces (STAS) in patients with stage IA part-solid lung adenocarcinoma after sublobar resection.Medical records of patients with stage IA part-solid adenocarcinoma who underwent curative pulmonary resection between February 2009 and December 2016 were retrospectively reviewed. The clinicopathological features of STAS and its influence on postoperative recurrence and survival were investigated.Among the 115 patients with stage IA part-solid adenocarcinoma who underwent wedge resection, 20 (17.4 %) had STAS. The multivariable analysis showed presence of STAS [HR (hazard ratio), 9.447; p = 0.002) and a larger invasive component size (HR, 1.097; p = 0.034) were independent risk factors for recurrence. The 5-year freedom from recurrence rates were 62.4 % and 97.9 % in cases with and without STAS, respectively (p 0.001), and the 5-year disease-free survival rates were 58.5 % and 97.9 % in cases with and without STAS, respectively (p 0.001). The presence of STAS was associated with old age (p = 0.030), male gender (p = 0.023), acinar predominant histologic pattern (p = 0.004), presence of micropapillary pattern (p 0.001), lymphovascular invasion (p 0.001) and larger invasive component (p 0.001).STAS could be an important prognostic factor in patients with stage IA part-solid lung adenocarcinoma after sublobar resection. Effective preoperative evaluation and postoperative surveillance may help improve the outcome of patients with small part-solid nodules, particularly when accompanied by STAS.

Subsolid lung adenocarcinoma with cystic airspaces (LACA) is a unique manifestation of lung cancer. This study was conducted to establish a radiologic disease progression model of LACA and to explore its association with the clinical course and clinicopathologic features of LACA. Sixty patients with LACA who underwent surgery at our center between 2004 and 2017 were retrospectively reviewed. The morphological changes of LACA over time on 98 serial computed tomography scans from 27 of 60 patients were tracked to establish a radiologic disease progression model. Associations between this model and the clinicopathologic characteristics of LACA were investigated. The following stepwise progression model of LACA was developed: in phase I, cystic airspaces (CAs) appear in the middle of non-solid nodules; in phase II, the CAs grow; in phase III, a solid component appears on the border of the CAs; and in phase IV, the solid component gradually surrounds the CAs and becomes thicker, and the CAs shrink. In total, 10 (17%), 33 (55%), and 17 (28%) LACA patients were classified as belonging to phases II, III, and IV at the time of surgery, respectively. More advanced phases were associated with higher pathologic T and N staging, lymphovascular invasion, visceral pleural invasion, spread through air spaces, and solid/micropapillary subtype. In the multivariate analysis, our model demonstrated a good discrimination capability for cancer recurrence risk. The stepwise disease progression model of LACA based on radiologic findings developed in this study represented its natural clinical course and clinicopathologic features well.

BACKGROUND: The aim of this study was to investigate the clinical outcomes of sublobar resections and compare these with those of lobectomies in early-stage lung adenocarcinoma patients. METHODS: We retrospectively reviewed medical records of 871 patients who underwent lobectomies or sublobar resections for early-stage lung adenocarcinomas. Two hundred thirty-five (27.0%) patients underwent sublobar resections (wedge and segmentectomies), and 636 (73.0%) underwent lobectomies. Propensity score matching resulted in 2 groups each with 219 patients. Survival analysis was performed. RESULTS: Mean age of matched patients was 61.9 (± 10.38, range of 21 to 91) years, mean follow-up period was 50.8 (± 27.57, range of 6.1 to 128.9) months, and mean tumor size was 15.2 (± 6.49, range of 3.0 to 45.0) mm. Overall recurrence rate was 9.4% (41 patients), and it was 8.7% (19 patients) in sublobar resection patients and 9.6% (21 patients) in lobectomy patients. Rates and sites of recurrence were not significantly different between the two surgical groups (p = 0.500 and 0.401, respectively). Overall 5-year survival and recurrence-free survival of sublobar resection patients were 90.6 and 89.5%, respectively, whereas those of lobectomy patients were 91.9 and 88.3%, respectively. No significant differences in overall 5-year survival rate or recurrence-free survival rate were found between the two groups (p = 0.636 and p = 0.975, respectively). CONCLUSIONS: Prognosis of early-stage lung adenocarcinoma treated with sublobar resection was not inferior to that treated with lobectomy in carefully selected cases. Further investigations, including randomized controlled trials, are needed to identify the equivalent oncologic efficacy of sublobar resections.

OBJECTIVES The purpose of this study was to analyse the prognostic significance of the dominant features of ground-glass opacities (GGOs) in part-solid node-negative adenocarcinomas with invasive components of similar sizes. METHODS From 2004 to 2017, a total of 544 patients with a diagnosis of part-solid pathological node-negative adenocarcinoma with an invasive component RESULTS Propensity score matching produced 92 patients in each group for the prognostic analysis. The mean size of the solid part was 8.8 mm in the GGO-dominant group and 9.0 mm in the solid-dominant group (P = 0.34); the mean size of the total lesion was 22.2 mm in the GGO-dominant group and 14.9 mm in the solid-dominant group (P CONCLUSIONS Although the total sizes of the GGO-dominant lesions were larger than those of the solid-dominant lesions, the prognosis of patients with GGO-dominant lesions was not significantly different from that of patients with solid-dominant lesions in node-negative adenocarcinomas with a similar invasive component size

Background Video-assisted thoracic surgery sleeve resection with bronchial anastomosis or bronchoplasty is a technically demanding procedure. Three-dimensional endoscopic surgery has been reported to be helpful in decreasing operation time and improving spatial perception with less surgical errors, but there have been rare reports about relatively difficult thoracoscopic procedures utilizing 3D thoracoscope. We performed this study to evaluate early clinical outcomes of thoracoscopic sleeve resection and bronchoplasty utilizing 3D thoracoscope. Methods Data from a total of 36 patients who underwent thoracoscopic sleeve lobectomy or bronchoplasty at our institution from December 2015 to October 2017 were retrospectively reviewed. Three-port approach with one utility incision was used with a 10 mm, 30° three-dimensional thoracoscope. Twenty-three patients (81%) were male, and mean age was 65.9 ± 9.4 years. Fourteen patients (38.9%) underwent sleeve resection with bronchial anastomosis, 22 (61.1%) underwent wedge or simple bronchoplasty, and one patient received concomitant PA procedure. Bronchial anastomosis sites were not covered with viable tissue flaps. Results There was no (0%) suture needle injury from spatial misperception during bronchoplasty or sleeve anastomosis. There was no (0%) operative mortality. The pathologic report revealed squamous cell carcinoma (63.9%), adenocarcinoma (19.4%), carcinoid (6.9%), adenosquamous carcinoma (3.4%), and sarcomatoid carcinoma (2.8%). One (2.8%) late mortality was due to systemic recurrence of sarcomatoid carcinoma. There was no (0.0%) anastomotic failure. The mean number of dissected lymph nodes were 27.4 ± 13.2, and mean operation time was 216.8 ± 60.0 min. Median postoperative 24-h drain amount was 315 mL. Median chest tube days and hospital days were 4 and 6, respectively. Two patients (5.6%) had complications greater than Clavien-Dindo grade II—one case of ARDS, and the other case of a delayed bronchopleural fistula. Conclusions Thoracoscopic sleeve resection and bronchoplasty utilizing HD 3D thoracoscope is a safe and effective procedure with excellent early clinical outcomes. Further investigation for long-term outcomes will be needed.

There is limited evidence for the effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC). This study aimed to assess whether adjuvant capecitabine and cisplatin improve survival compared to surgery alone among patients with locally advanced ESCC. This is a multicenter randomized controlled trial. Patients were eligible if they underwent curative resection for ESCC staged T2–4 or N1 and M0 according to the TNM cancer staging system sixth edition. The intervention group received four cycles of adjuvant chemotherapy (capecitabine: 1,000 mg/m 2 b.i.d for 14 days, and intravenous cisplatin: 75 mg/m2 at day 1, every 3 weeks). A total of 136 patients were randomly assigned to either the adjuvant chemotherapy group (n = 68) or surgery-alone group (n = 68). Seven patients who rejected chemotherapy after randomization were excluded from the final analysis. The cumulative incidence of recurrence within 18 months after surgery was significantly lower in the adjuvant chemotherapy group than in the surgery-alone group (hazard ratio [HR]: 0.49; 95% confidence interval (CI): 0.25–0.95]. However, the 5- and 10-year disease-free survival did not differ between treatment groups (HR: 0.84; 95% CI: 0.53–1.34 and HR: 0.76; 95% CI: 0.50–1.18, respectively). Adjuvant chemotherapy after curative resection in patients with locally advanced ESCC reduced early recurrence but had no statistically significant increase in the long-term disease-free survival. Due to the limited sample size of this study, additional randomized controlled trials with larger sample sizes are necessary.

There is limited evidence for effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma. We conducted a multi-center randomized controlled trial to assess whether adjuvant Capecitabine and Cisplatin improve survival compared with surgery only among patients with resectable esophageal squamous cell carcinoma. Methods This is a multicenter randomized controlled trials conducted at five hospitals in Korea from Mar 2005 to Dec 2018. Patients were eligible if they underwent curative resection for esophageal squamous cell carcinoma and diagnosed with pathologic T2–3 or N1 stage, according to 6th edition of TNM cancer staging system. Patients who were diagnosed with cervical esophageal cancer, had previous history of cancer, or received neoadjuvant therapy were excluded. Intervention group received 4 cycles of adjuvant chemotherapy (Capecitabine 1,000 mg/m2 b.i.d for 14 days and intravenous Cisplatin 75 mg/m2 at Day1, every 3 weeks). The primary endpoint was disease free survival. Results 136 patients were randomly assigned to adjuvant chemotherapy group (n = 68) or surgery alone group (n = 68). Seven patients who rejected chemotherapy after randomization were excluded from the final analysis. The cumulative incidence of recurrence within 18 months after surgery was significantly lower in the adjuvant chemotherapy group compared to the surgery alone group (Hazard Ratio (HR), 0.45; 95% Confidence Interval (CI), 0.22–0.91). After long-term follow-up (median 3.3 years, maximum 14 years), disease free survival and overall survival were not different between two groups. (HR, 0.77; 95% CI, 0.49–1.18 and HR, 0.85; 95% CI, 0.55–1.34, respectively.) Conclusion Adjuvant chemotherapy after curative resection in patients with esophageal squamous cell carcinoma reduced early recurrence but this does not extend to long-term disease free and overall survival due to limited sample size. Additional randomized controlled trials with larger sample would be necessary to confirm the effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma.

Although the video-assisted thoracic surgery (VATS) approach has been accepted as a safe and effective alternative to lobectomy, its advantage remains unclear in advanced-stage lung cancer. This study is aimed to evaluate the feasibility and long-term outcomes of VATS in lung cancer with clinical N1 (cN1) disease.We retrospectively reviewed the records of 1149 consecutive patients who underwent lobectomy for cN1 disease from 2006 to 2016. Perioperative outcomes and long-term survival rates were compared using a propensity score-based inverse probability of treatment weighting (IPTW) technique.We performed VATS and open thoracotomy for 500 and 649 patients, respectively. All preoperative characteristics became similar between the two groups after IPTW adjustment. Compared to thoracotomy, VATS was associated with shorter hospitalization (7.7 days vs. 9.2 days, p0.001), earlier adjuvant chemotherapy (41.7 days vs. 46.6 days, p = 0.028), similar complete resection rates (95.2 % vs. 94.0 %, p = 0.583), and equivalent dissected lymph nodes (27.5 vs. 27.8, p = 0.704). On IPTW-adjusted analysis, overall survival (OS) (59.4 % vs. 60.3 %, p = 0.588) and recurrence-free survival (RFS) (59.2 % vs. 56.9 %, p = 0.651) at 5 years were also similar between the two groups. Multivariable Cox analysis revealed that VATS was not a significant prognostic factor for cN1 disease (p = 0.764 for OS and p = 0.879 for RFS).VATS lobectomy is feasible for patients with cN1 disease, providing comparable perioperative outcomes, oncologic efficacy, and long-term outcomes as open thoracotomy.

BACKGROUND: Computed tomography (CT) screening for lung cancer has led to frequent findings of small anterior mediastinal masses. It is very hard to distinguish small thymomas from thymic cysts. The objective of this study was to develop a clinical model for predicting small thymomas (

Background This study aimed to determine whether adjuvant therapy improves survival in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) after neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery. Methods We retrospectively reviewed 467 consecutive patients with stage IIIA-N2 NSCLC who received neoadjuvant CCRT followed by surgery between 2004 and 2013. From these, we identified 398 eligible patients and their clinical outcomes were compared according to whether adjuvant therapy was provided. Results In total, 296 patients (74%) received adjuvant therapy consisting of chemotherapy alone (n=71) radiotherapy alone (n=118) and both chemotherapy and radiotherapy (n=107). Adjuvant therapy was not given to remaining 102 patients. Patients who receiving adjuvant therapy were significantly younger (P=0.001), and predominantly male (P=0.014) compared to patients who did not receive adjuvant therapy. Regarding to the pathologic response, the adjuvant therapy group had a significantly poor pathologic response. However, the 5-year overall survival (OS) rate did not significantly differ between the groups (adjuvant therapy group, 52.9%; no adjuvant therapy group, 54.9%; P=0.369). After adjusting for age, sex, type of operation, cell type and yp stage, adjuvant therapy was significantly associated with better OS (hazard ratio =0.59; 95% CI, 0.38-0.92; P=0.019) and disease free survival (hazard ratio =0.62; 95% CI, 0.44-0.87; P=0.006). Conclusions Our data indicate that adjuvant therapy is more often given to patients with poor pathologic findings. Adjuvant treatment after trimodal therapy is a significant predictor of survival after adjustment of clinical variables.

Tumor spread through air spaces (STAS) is an invasive pattern of lung cancer that was recently described. In this study, we investigated the association between the extent of STAS and clinicopathological characteristics and patient outcomes in resected non-small cell lung cancers (NSCLCs). STAS has been prospectively described from 2008 and graded its extent with a two-tiered system (STAS I:2500 μm [one field of ×10 objective lens] from the edge of tumor and STAS II: ≥2500 μm from the edge of tumor) from 2011 in Seoul National University Bundang Hospital. We retrospectively analyzed the correlations between the extent of STAS and clinicopathologic characteristics and prognostic significance in 1869 resected NSCLCs. STAS was observed in 765 cases (40.9%) with 456 STAS I (24.4%) and 309 STAS II (16.5%). STAS was more frequently found in patients with adenocarcinoma (ADC) (than squamous cell carcinoma), pleural invasion, lymphovascular invasion, and/or higher pathologic stage. In ADC, there were significant differences in recurrence free survival (RFS), overall survival (OS), and lung cancer specific survival (LCSS) according to the extent of STAS. In stage IA non-mucinous ADC, multivariate analysis revealed that STAS II was significantly associated with shorter RFS and LCSS (p 0.001 and p = 0.006, respectively). In addition, STAS II was an independent poor prognostic factor for recurrence in both limited and radical resection groups (p = 0.001 and p = 0.023, respectively). In conclusion, presence of STAS II was an independent poor prognostic factor in stage IA non-mucinous ADC regardless of the extent of resection.

BackgroundIdiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, its effect on recurrence after curative surgery remains unclear.ObjectivesThis study aimed to determine the impact of IPF on recurrence-free survival following curative surgical resection of stage I-III non-small cell lung cancer (NSCLC) and investigate the effects of patient and surgical factors on the risk of recurrence.MethodsWe reviewed retrospectively collected data of patients with surgically resected stage I-III NSCLC from two tertiary care hospitals in South Korea. By propensity score matching, patients with IPF (LC with IPF) were matched to those without IPF (LC without IPF).ResultsIn total, 3416 patients underwent surgical resection, and 96 were diagnosed with underlying IPF. In the LC with IPF group, 89.6% patients were men, and the average age was 69.7 years. Sublobar resection was performed more frequently in the LC with IPF group than in the LC without IPF group, while the rate of mediastinal lymph node dissection and dissected node number were lower in the former group. The 5-year recurrence-free survival rate was significantly lower in the LC with IPF group (49.2%) than in the LC without IPF group (69.1%; PConclusionsIPF may increase the risk of recurrence after curative surgical treatment for NSCLC. Close surveillance for recurrence is mandatory for patients with underlying IPF.

Objectives We evaluated the differential prognostic impact of spread through air spaces (STAS) in early-stage lung adenocarcinoma after lobectomy according to the pT descriptor. Methods The study population included 506 patients who underwent lobectomy with mediastinal lymph node dissection for pT1b, pT1c, and pT2a adenocarcinoma between 2011 and 2016. We divided the study population into 2 groups according to STAS status, ie, STAS (+) versus STAS (–), and stratified them according to the pT descriptor. A Cox proportional hazard model and inverse probability of treatment weight–adjusted Kaplan–Meier curves were used to evaluate the prognostic impact of STAS on recurrence-free survival (RFS) and its independency in each stratum. Results Multivariable Cox proportional hazard regression analysis demonstrated that in pT1b and pT1c strata, STAS (+) patients had a 7.02-fold and 2.89-fold greater risk of recurrence than STAS (–) patients, respectively. However, in the pT2a stratum, STAS did not affect RFS. And the RFS of the STAS (+) pT1b/c strata was similar to that of the pT2a stratum. In the pT1b/c strata, inverse probability of treatment weighting-adjusted Kaplan-Meier curves also showed that RFS was significantly worse when STAS was present. Furthermore, the risks for locoregional and distant recurrence were both greater when STAS was present. Conclusions The presence of STAS increased the risk of recurrence independently from other poor prognostic factors in patients with pT1b/cN0M0 adenocarcinoma who underwent lobectomy, but not in pT2a patients. The presence of STAS in pT1b/cN0M0 adenocarcinoma was associated with a similar risk of recurrence to that of pT2aN0M0 adenocarcinoma.

Some metastatic colorectal cancer (mCRC) patients receive conversion surgery (CS), including metastasectomy after palliative chemotherapy. Although targeted agents significantly improved the outcomes, the clinical outcome of CS in the targeted agent era has not yet been thoroughly investigated. We analyzed the clinical data of 96 mCRC patients who initially had unresectable liver- and/or lung-limited metastases and underwent first-line cetuximab or bevacizumab plus FOLFIRI between January 2013 and June 2017. Liver-limited metastasis was seen in 44 patients (45.8%), lung-limited metastases in 21 patients (21.9%), and both liver and lung metastases in 31 patients (32.3%). Among them, 37 patients (38.5%) received cetuximab, and 59 patients (61.5%) received bevacizumab plus FOLFIRI. Overall response rate was 63.9% and 40.7%, respectively (p = 0.035). After median 8.7 (range 2.5–27.3) months, CS was performed in 11 patients (29.7%) in cetuximab group and 15 patients (25.4%) in bevacizumab group (p = 0.646). Median overall survival has not been reached in R0-resected patients (n = 23), during the median follow-up period of 22.5 (range 9.8–54.5) months. Median disease-free survival was 7.1 (95% CI 2.5–11.7) months: 11.0 (95% CI 3.1–19.0) months in cetuximab group and 3.2 (95% CI 0.0–7.8) months in bevacizumab group (p = 0.422). There was no progression after 18.5 months and disease-free survival reached a plateau at 19.9%. A substantial proportion of patients could receive CS after cetuximab or bevacizumab plus FOLFIRI chemotherapy. R0-resected patients had excellent overall survival, although 80.1% of them eventually experienced recurrence. Some patients could achieve durable disease-free state.

OBJECTIVES Carcinoembryonic antigen (CEA) is a well-known tumour marker for lung adenocarcinoma (AC). This study was conducted to evaluate the clinical characteristics and prognosis of patients with pathological node-negative lung AC who have a high preoperative level of CEA. METHODS Among 2124 patients with lung AC between 2003 and 2016, 858 patients were enrolled. CEA levels were dichotomized as normal (≤5 ng/ml) or high (>5 ng/ml). According to the levels of CEA between 6 and 12 months after surgery, patients were divided into a normalized and a remained-high group. Propensity score matching was used to compare 80 patients without adjuvant chemotherapy (ACT) with 39 patients with ACT. Kaplan–Meier survival analysis with the log-rank test and Cox proportional hazards regression analysis were performed for recurrence-free survival (RFS) and overall survival (OS). RESULTS The multivariable analysis showed that high maximum standardized uptake value and T2 stage were more common in patients with high levels of CEA. The median follow-up period was 52.8 months (range 6–169 months). The 5-year RFS and OS rates were 89.3% and 68.9% and 92.8% and 77.2% in normal patients and patients with high levels of CEA, respectively, with a statistically significant difference. The 5-year RFS was 79.4% and 39.2% in the normalized and remained-high groups after surgery, respectively (P = 0.011). The 5-year RFS and OS rates were 68.9% and 62.2% and 80.1% and 82.9% in patients without and with ACT, respectively. After propensity score matching, RFS was not significantly different between patients without and with ACT (P = 0.500); however, OS was significantly better in patients with ACT than in those without ACT (P = 0.001). CONCLUSIONS The clinicopathological characteristics, RFS and OS of patients with lung AC might be well discriminated by preoperative CEA levels. In patients with node-negative disease and high CEA levels, those with normalized CEA levels had a significantly better prognosis than those with persistently high CEA levels.

Subsolid lung adenocarcinoma with cystic airspaces (LACA) is a unique manifestation of lung cancer. This study was conducted to establish a radiologic disease progression model of LACA and to explore its association with the clinical course and clinicopathologic features of LACA.Sixty patients with LACA who underwent surgery at our center between 2004 and 2017 were retrospectively reviewed. The morphological changes of LACA over time on 98 serial computed tomography scans from 27 of 60 patients were tracked to establish a radiologic disease progression model. Associations between this model and the clinicopathologic characteristics of LACA were investigated.The following stepwise progression model of LACA was developed: in phase I, cystic airspaces (CAs) appear in the middle of non-solid nodules; in phase II, the CAs grow; in phase III, a solid component appears on the border of the CAs; and in phase IV, the solid component gradually surrounds the CAs and becomes thicker, and the CAs shrink. In total, 10 (17%), 33 (55%), and 17 (28%) LACA patients were classified as belonging to phases II, III, and IV at the time of surgery, respectively. More advanced phases were associated with higher pathologic T and N staging, lymphovascular invasion, visceral pleural invasion, spread through air spaces, and solid/micropapillary subtype. In the multivariate analysis, our model demonstrated a good discrimination capability for cancer recurrence risk.The stepwise disease progression model of LACA based on radiologic findings developed in this study represented its natural clinical course and clinicopathologic features well.

Background Accurate clinical staging of tumors with a small solid portion is essential for developing an appropriate treatment plan. This study evaluated predictive factors for lymph node (LN) metastasis in patients with clinical stage I part-solid lung adenocarcinoma. Methods Medical records of patients with clinical stage I part-solid adenocarcinoma who underwent anatomic pulmonary resection with systematic node evaluation between January 2009 and June 2018 were retrospectively reviewed. To identify predictive factors for LN metastasis, univariate and multivariable logistic regression analyses were performed. Results Among the 593 patients in this study, the overall prevalence of LN metastasis was 3.7% (n = 22), which included 3.0% (n = 18) of patients with N1 LN metastasis and 1.5% (n = 9) of patients with N2 LN metastasis. Combined N1 and N2 nodal involvement was observed in 5 patients. Nodal metastasis was not observed in tumors with a solid portion sized 1.1 cm or smaller. The nodal metastasis rates in cT1b, cT1c, and cT2a tumors were 5.5% (13 of 237), 7.1% (6 of 84), and 13.6% (3 of 22), respectively. According to the multivariable analysis, predictive factors included the size of the solid portion (P = .015) and the high maximum standardized uptake value (SUVmax) of the primary tumor (P = .044). Conclusions Large solid portion and high SUVmax of the primary tumor were predictive factors of LN metastasis in patients with clinical stage I part-solid lung adenocarcinoma. Systematic LN evaluation should be performed, especially in those who have a large solid portion and high SUVmax of the primary tumor.

The aim of this study was to investigate the prognostic factors for post-recurrence survival (PRS) in patients with completely resected Stage III (N2) non-small-cell lung cancer.A number of clinicopathological factors were evaluated to identify the prognostic factors for recurrence-free survival using Cox proportional hazards models in 245 patients who underwent complete resection of pathological Stage III (N2) non-small-cell lung cancer. Additional post-recurrence data were evaluated, including the presence of symptoms of recurrence, the recurrence pattern, the treatment modality and the recurrence-free interval (RFI). The prognostic effects of clinicopathological factors before recurrence and the additional post-recurrence data on PRS were analysed.A total of 124 patients experienced recurrence during a median follow-up period of 39.8 months. Twenty-one patients were symptomatic at the time of initial recurrence, and the mean RFI was 14.0 months. Loco-regional recurrence was observed in 38 (31%) patients, distant metastasis in 33 (27%) patients and both in 53 (42%) patients. The initial treatment modality was surgery in 17 (14%) patients, chemotherapy in 66 (53%) patients, radiotherapy in 17 (14%) patients and chemoradiotherapy in 18 (15%) patients. The median duration of PRS was 30.5 months (range 1-109 months), and the 1-, 3- and 5-year PRS rates were 72%, 43% and 23%, respectively. A shorter RFI and radiotherapy for the treatment of recurrence were found to be independent prognostic factors for PRS in the multivariable analysis.The prognostic factors for recurrence-free survival were not associated with PRS, and a shorter RFI and radiotherapy for the treatment of recurrence were found to be negative prognostic factors for PRS.

Objective: Multimodal treatments that include preoperative platinum-based chemotherapy are fundamental to the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the predictive value of DNA repair protein expression in surgically resected NSCLCs in terms of prognosis and responses to platinum-containing chemotherapy. Methods: This retrospective study included 136 patients with NSCLC who were treated with preoperative platinum-based chemotherapy, followed by curative lung resection. ATM, RAD51, LKB1, H2AX, and SIRT1 expression levels were analyzed in resected tumor specimens via immunostaining and were used to classify patients and compare survival and responses to chemotherapy. Results: SIRT1 expression correlated significantly with improved responses to platinum-based chemotherapy (odds ratio, 2.28; p = 0.024), progression-free survival (hazard ratio [HR], 0.74; p = 0.036), overall survival (HR, 0.63; p = 0.006), and tumor-bearing survival (HR, 0.62; p = 0.014). After adjusting for clinical variables, the HR of SIRT1 expression remained significant for overall survival (HR, 0.59; p = 0.039) but not for progression-free survival (HR, 0.74; p = 0.183). No prognostic stratification was observed for the other 4 markers. Conclusion: Patients with SIRT1-expressing NSCLC had superior responses to chemotherapy and longer survival durations than those with SIRT1-negative cancer.

Background and Objectives This study evaluated the relationship between the maximum standardized uptake value (SUVmax) of preoperative positron emission tomography/computed tomography (PET/CT) and the characteristics of lung adenocarcinoma featuring ground-glass opacity nodules (GGN). Methods The association of the SUVmax of preoperative PET/CT with ground-glass opacity (GGO) proportion on CT, subtypes of adenocarcinoma (minimally invasive adenocarcinoma, invasive adenocarcinoma), predominant types of invasive adenocarcinoma, and size of the total and invasive components of pathology were evaluated in 190 patients who underwent resection for lung adenocarcinoma featuring GGN. Results The mean SUVmax of non-solid GGN and partly solid GGN were 0.53 and 1.32, respectively (P = 0.029). The mean SUVmax of the main masses in 38 patients with MIA and 152 with invasive adenocarcinoma were 0.86 and 1.36, respectively (P = 0.029). The mean SUVmax of acinar, lepidic, papillary, and solid tumors were 1.61, 0.87, 0.98, and 1.60, respectively. The mean SUVmax of invasive components measuring ≤10 mm, 11-20 mm, and >20 mm were 0.84, 1.66, and 2.09, respectively (P

BACKGROUND Histological heterogeneity is thought to be important for prognosis of lung adenocarcinoma. We investigated to determine pathological features with prognostic value for recurrence of early stage lung cancer. METHODS A total of 368 patients who underwent curative surgical resection for early stage lung adenocarcinoma between 2009 and 2012 were enrolled. Pathologic characteristics including the presence of visceral pleural invasion, micropapillary patterns, aerogenous spread, lymphovascular invasion, perineural invasion and necrosis were examined. The correlations between pathological factors and clinical outcomes were analysed to determine prognostic significance. RESULTS Mean follow-up was 43.0 months (±14.56, ranging from 0.0 to 73.9 months). Three-year overall survival was 95.2% and disease-free survival was 89.8%. The recurrence rate was 9.0% (33 patients) and the mortality rate was 6.0% (22 patients). The presence of a micropapillary pattern (P

Objectives In the 7th edition of the tumour, node and metastasis staging system, a primary tumour size larger than 5 cm was shifted to Stage II. Therefore, we aimed to evaluate the characteristics and prognostic factors of node-negative non-small cell lung cancer (NSCLC) larger than 5 cm. Methods We included 109 patients who underwent curative resection and had pathologically confirmed node-negative NSCLC >5 cm (Group 1). We compared the clinicopathological characteristics and prognosis of these patients with 85 patients with node-positive NSCLC >5 cm (Group 2) and 383 patients who had node-positive NSCLC ≤5 cm (Group 3). Results Compared with Group 2, old age and absence of lymphovascular invasion was significantly more common in Group 1. Compared with Group 3, frequency of non-adenocarcinoma type and visceral pleural invasion were significantly higher in Group 1; however, the frequency of lymphovascular invasion was higher in Group 3. A Cox proportional hazards model showed that the maximized standardized uptake value and visceral pleural invasion was a statistically worse prognostic factor. Compared with Group 2, Group 1 showed significantly longer overall survival; however, there was no difference in recurrence-free survival. Compared with Group 3, there was no significant difference in recurrence-free survival and overall survival. In Group 1, recurrence in the contralateral lung was the most common recurrence pattern, and there was no metastasis in the mediastinal lymph nodes. Conclusions Patients with node-negative NSCLC >5 cm had a lower incidence of lymphovascular invasion and a more common contralateral recurrence than patients with node-positive NSCLC, and visceral pleural invasion was identified as independent prognostic factors.

The KIT inhibitor, imatinib, has shown promising efficacy in patients with KIT-mutated melanoma; however, acquisition of resistance to imatinib occurs rapidly in the majority of patients. The mechanisms of acquired resistance to imatinib in melanoma remain unclear. We analyzed biopsy samples from paired baseline and post-treatment tumor lesions in one patient with KIT-mutated melanoma who had had an initial objective tumor regression in response to imatinib treatment followed by disease progression 8 months later. Targeted deep sequencing from post-treatment biopsy samples detected an additional mutation in CTNNB1 (S33C) with original KIT L576P mutation. We examined the functional role of the additional CTNNB1 S33C mutation in resistance to imatinib indirectly using the Ba/F3 cell model. Ba/F3 cell lines transfected with both the L576P KIT mutation and the CTNNB1 S33C mutation demonstrated no growth inhibition despite imatinib treatment, whereas growth inhibition was observed in the Ba/F3 cell line transfected with the L576 KIT mutation alone. We report the first identification of the emergence of a CTNNB1 mutation that can confer acquired resistance to imatinib. Further investigation into the causes of acquired resistance to imatinib will be essential to improve the prognosis for patients with KIT-mutated melanoma.

// Hyojin Kim 1 , Jeong Mi Yang 1 , Yan Jin 1 , Sanghoon Jheon 2 , Kwhanmien Kim 2 , Choon Taek Lee 3 , Jin-Haeng Chung 1 , Jin Ho Paik 1 1 Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea 2 Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea 3 Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Correspondence to: Jin Ho Paik, email: paikjh@snu.ac.kr Jin-Haeng Chung, email: chungjh@snu.ac.kr Keywords: microRNA, lung cancer, adenocarcinoma, miR-342-3p, ALK Received: May 30, 2016 Accepted: December 01, 2016 Published: December 27, 2016 ABSTRACT Lung adenocarcinoma has distinctive clinicopathological features that are related to specific genetic alterations, including EGFR and KRAS mutations and ALK rearrangement. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate many important biological processes and influence cancer phenotypes. This study retrospectively investigated microRNA expression profiles, and their clinicopathological implications, in lung adenocarcinoma according to genetic status ( EGFR , KRAS , ALK , and triple negative). A total of 72 surgically resected lung adenocarcinoma specimens (19 EGFR- mutated, 17 KRAS -mutated, 16 ALK -rearranged, and 20 triple negative cancers) were screened for 23 microRNAs using quantitative real-time reverse transcriptase polymerase chain reaction. We then evaluated the associations between the microRNA expressions and the cancers’ genetic and clinicopathological features. Eight microRNAs were associated with clinicopathological features, such as male sex and ever-smoker status (high miR-373-3p, miR-1343-3p, miR-138-1-3p, and miR-764; low miR-27b-3p) and vascular invasion (high miR-27b-3p; low miR-1343-3p and miR-764). Clustering and discriminant analyses revealed that the microRNA expression patterns in the ALK group were different from those in the EGFR and KRAS groups. Five microRNAs (high miR-1343-3p; low miR-671-3p, miR-103a-3p, let-7e, and miR-342-3p) were especially distinctive in the ALK group, compared to the EGFR and KRAS groups. Moreover, a significant association was observed between ALK -rearrangement, decreased miR-342-3p expression, and immunohistochemical loss of E-cadherin. Therefore, microRNA expression profiles appear to have distinctive clinicopathological implications in ALK- rearranged lung adenocarcinoma. Furthermore, the association of ALK rearrangement, decreased miR-342-3p expression, and E-cadherin loss might indicate that miR-342-3p is involved in the ALK -associated phenotypes and epithelial-mesenchymal transition.