The efficacy of adjuvant chemotherapy with capecitabine and cisplatin after surgery in locally advanced esophageal squamous cell carcinoma: a multicenter randomized phase III trial.

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.

Application of N Descriptors Proposed by the International Association for the Study of Lung Cancer in Clinical Staging.

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): prognostic significance of grading in non-small cell lung cancer.

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.

Correction to: Stepwise Disease Progression Model of Subsolid Lung Adenocarcinoma with Cystic Airspaces.

In the original article there are errors in Fig. 3. Following is the corrected figure.

Stepwise Disease Progression Model of Subsolid Lung Adenocarcinoma with Cystic Airspaces.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: The stepwise disease progression model of LACA based on radiologic findings developed in this study represented its natural clinical course and clinicopathologic features well.

Endoscopic Vacuum Therapy in the Management of Postoperative Leakage After Esophagectomy.

BACKGROUND: Postoperative leakage after esophagectomy is associated with significant life-threatening complications. Recently, endoscopic vacuum therapy (EVT) was introduced and has been successfully used as a new treatment option. The purpose of this study was to evaluate the safety and efficacy of EVT for the management of postoperative leakage after esophagectomy. METHODS: A total of 22 patients were treated with either intraluminal or intracavitary EVT for the management of postoperative leakage from May 2012 to April 2018. The location of leakage was intrathoracic in 17 patients and cervical in five patients. The outcomes of EVT were analyzed retrospectively. RESULTS: Complete postoperative leakage closure was achieved in 19 of 22 patients. The median duration of EVT application was 14 days (range 2-103), and a median number of three EVT systems (range 1-14) were used. In 19 patients who were successfully managed with EVT, oral feeding was possible a median of 15 days after the first day of treatment. There were no cases of mortality related to postoperative leakage. CONCLUSIONS: EVT is a well-tolerated and effective therapeutic option for the treatment of various types of postoperative leakage after esophagectomy.

Predictive Factors of Thoracic Lymph Node Metastasis Accompanying Pulmonary Metastasis from Colorectal Cancer.

BACKGROUND: The aim of this study was to identify the factors predicting thoracic lymph node (LN) metastases for pulmonary resection from colorectal cancer (CRC). METHODS: The records of 160 patients who underwent pulmonary metastasectomy for CRC were retrospectively reviewed. Clinicopathologic factors were analyzed with chi-square test or t-test and logistic regression to identify predictable factors for LN metastases. RESULTS: Sixty patients (37.5%) underwent LN dissection during pulmonary metastasectomy, and LN metastases were found in five patients. Twenty-three patients had LN recurrence among the 100 patients (62.5%) without LN dissection during the follow-up period. Twenty-eight patients out of 160 (17.5%) had LN metastases. By multivariate analysis, the number of pulmonary metastasis and metastasis from colon cancers were independent factors predicting LN metastases. CONCLUSION: The number of pulmonary metastasis and metastasis from colon cancers were independent factors predicting LN metastases. LN sampling should be performed especially in cases with strong predictive factors to improve staging and help guide further treatment.

Prognostic Impact of DNA Repair Protein Expression in Non-Small Cell Lung Cancers Treated with Platinum-Based Chemotherapy and Subsequent Curative Lung Resection.

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.

Long-Term Oncologic Outcomes for Patients Undergoing Volatile Versus Intravenous Anesthesia for Non-Small Cell Lung Cancer Surgery: A Retrospective Propensity Matching Analysis.

Propofol-based total intravenous anesthesia (TIVA) has been reported to improve long-term outcome following cancer surgery, when compared with inhalation agents. However, such investigational reports are still controversial, and no studies have been conducted in relation to non-small cell lung cancer (NSCLC) surgery. The present study aimed to compare the favorable effects of TIVA versus inhalation agents on recurrence-free survival and overall survival after curative resection of NSCLC. This retrospective cohort study examined medical records of the patients who were diagnosed with NSCLC and underwent curative resection at Seoul National University Bundang Hospital from August 2003 to July 2012. The primary outcome included the comparison of postoperative overall survival and recurrence-free survival in both groups. To balance the 2 groups for analysis, a propensity matching method was used, and stratified Cox proportional hazard models were used for statistical analysis. This study included 943 cases of NSCLC for final analysis, and the cases were divided into the TIVA group (n = 749) and inhalation group (n = 194). Propensity matching produced 196 patients in each group. The final analysis revealed no significant difference in the hazard ratio (HR) for recurrence between the TIVA and inhalation groups ( P = .233). The HR for death between the 2 groups was not significantly different either ( P = .551). In this study, we found no benefit of propofol-based TIVA for long-term oncologic outcome after NSCLC surgery, relative to inhalation agents.

Impact of Statin Use on Recurrence or Survival After Surgical Curative Resection of Non-Small Cell Lung Cancer.

Statins are known for their anticancer effects, and many studies have shown the effectiveness of statins for cancer prevention and improvement of cancer-related long-term oncologic outcome. However, their effectiveness on recurrence or survival of non-small cell lung cancer (NSCLC) after curative resection remains unknown. This was a retrospective cohort study that assessed the medical records of patients who were diagnosed with NSCLC and treated with curative resection at a tertiary care hospital between August 2003 and July 2012. The primary outcome was the comparison of postoperative overall survival (OS) and recurrence-free survival (RFS) between the statin group of patients, who were administered statins at least 1 month before the surgery and continued it after the surgery, and the nonstatin group of patients, who were not administered statins. Propensity score (PS) matching was used to balance the 2 groups, and the analysis was performed using a Cox proportional hazards model. In total, 994 patients with NSCLC were included in the final analysis: 135 patients in the statin group and 859 patients in the nonstatin group. After PS matching, there was no significant difference in postoperative recurrence ( P = .862) or death ( P = .074) between the statin group and the nonstatin group. Similarly, there was no significant difference in postoperative RFS ( P = .862) and OS ( P = .072) between the 2 groups after PS matching. This study demonstrated that statin administration had no significant association with recurrence or survival after NSCLC treatment.

The maximum standardized uptake value of preoperative positron emission tomography/computed tomography in lung adenocarcinoma with a ground-glass opacity component of less than 30 mm.

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 < 0.001). CONCLUSIONS: The SUVmax of lung adenocarcinoma featuring GGN can vary depending on the GGO proportion. A higher SUVmax can be expected in invasive adenocarcinoma than in MIA, and solid and acinar-predominant invasive adenocarcinoma showed a higher SUVmax.

Tumor Size-Dependent Anticancer Efficacy of Chlorin Derivatives for Photodynamic Therapy.

Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and N-methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as well as in A549 tumor-bearing mice in vivo. Cell viability, microscopy, and fluorescence-activated cell sorting (FACS) analyses were performed for the in vitro studies. MPPa and NMPi showed high phototoxicity in vitro, which was dependent on the concentration of the photosensitizers as well as the light irradiation time. In the animal study, tumor volume change, tumor surface alterations, and hematoxylin & eosin (H&E) and terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL) staining analyses were performed and compared between small (tumor volume of 50 mm³) size of initial tumors. MPPa and NMPi showed high anticancer efficacy against small-size tumors, indicating that early treatment with PDT is effective. Especially, repeated two times PDT with NMPi allowed almost complete eradication against small-size tumors. However, MPPa and NMPi were not effective against large-size tumors. In conclusion, the two chlorin derivatives, MPPa and NMPi, show good anticancer efficacy as promising photosensitizers for PDT in vitro and in vivo. Moreover, their activity in vivo was significantly dependent on the initial tumor size in mice, which confirms the importance of early cancer treatment.

Learning curve of single-incision thoracoscopic surgery for primary spontaneous pneumothorax.

BACKGROUND: Single-incision thoracoscopic surgery (SITS) requires extensive time and practice to achieve satisfactory technical skills. The aim of this study was to evaluate the learning curves of SITS for primary spontaneous pneumothorax (PSP). METHODS: This study included a total of 274 consecutive patients who underwent PSP surgery by a single operator between May 2011 and February 2014. During this period, SITS was applied as a routine approach. Learning curves were made by the cumulative sum (CUSUM) method using the number of cases and four surgical technique-related factors, including operation time, postoperative complication, non-SITS rate, and ipsilateral PSP recurrence. RESULTS: Among the 274 patients, 16 patients who were presented with a previous 3-port wound scar or inadequate chest tube site before surgery were not eligible for SITS. Hence, SITS was attempted on 258 patients and performed successfully in 251 patients. For these successful SITS patients, the mean age was 22.9 ± 8.1 years, the mean operation time was 65.6 ± 22.2 min, the mean chest tube indwelling time was 1.5 ± 1.1 days, and the mean postoperative hospital stay was 1.7 ± 1.1 days. The mean operation time decreased from 84.0 to 47.6 min when a comparison was made between patients operated in the initial 6 months and the last 6 months of the study period. As revealed by the CUSUM technique, more than 50 % of the cases experienced an operation time of <70 min after the first 92 cases. After 57 cases, the postoperative complication rate was maintained at <5 %. The non-SITS rate was achieved to be lower than 5 % after 112 cases. The ipsilateral PSP recurrence rate was maintained at below 8 % after 102 cases. CONCLUSIONS: Although PSP is the most applicable scenario for the beginner of SITS, at least 100 cases of experience are needed to achieve optimal technical level.

Prognostic factors after pulmonary metastasectomy of colorectal cancers: influence of liver metastasis.

BACKGROUND: Our objective was to evaluate the influence of liver metastasis on survival after pulmonary metastasectomy in patients with colorectal cancer (CRC). METHODS: We retrospectively reviewed a total of 524 patients and were classified into two groups based on the presence of liver metastasis. Group HM + PM (n = 106) included patients who previously received a hepatic metastasectomy and then received pulmonary metastasectomy. Group PM (n = 418) included patients who only received pulmonary metastasectomy with no liver metastasis. RESULTS: There were more male patients (70 vs. 57 %; P = 0.02) and more patients with colon cancer (60 vs. 42 %, P = 0.001) in group HM + PM than in group PM. Otherwise, there was no significant difference between the two groups in clinicopathologic characteristics and extent of surgery. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 58 and 31 %, respectively. There was no significant difference in OS (group HM + PM, 54 % vs. group PM, 59 %; P = 0.085) and in DFS (group HM + PM, 28 % vs. group PM, 32 %; P = 0.12). For the entire patient cohort, a multivariate analysis revealed that the presence of liver metastasis, CRC T and N stages, disease-free interval, and number and size of lung metastases were significantly associated with OS and DFS. CONCLUSIONS: Our findings suggest that previous or present liver metastasis should not exclude a patient from pulmonary metastasectomy. When lung metastasis is detected in patients with a history of hepatic metastasectomy, pulmonary metastasectomy is still a viable treatment option especially in patients with a long disease-free interval and a small number of lung metastases.

Recurrence Risk-Scoring Model for Stage I Adenocarcinoma of the Lung.

PURPOSE: The aim of this retrospective, multicenter study was to develop a recurrence risk-scoring model in patients with curatively resected stage I lung adenocarcinoma (ADC). METHODS: Clinicopathologic and outcome data for a development cohort of 1,700 patients with pathologic stage I ADC from four institutions resected between January 2000 and December 2009 were evaluated. A phantom study was performed for correction of inter-institutional differences in positron emission tomography-standardized uptake value (PET-SUV). A nomogram for recurrence prediction was developed using Cox proportional hazards regression. This model was validated in a cohort of 460 patients in two other hospitals. The recurrence rate was 21.0 % for the development cohort and 22.1 % for the validation cohort. RESULTS: In multivariable analysis, three independent predictors for recurrence were identified: pathologic tumor size (hazard ratio [HR] 1.03, 95 % CI 1.017-1.048; p < 0.001), corrected PET-SUV (HR 1.08, 95 % CI 1.051-1.105; p < 0.001), and lymphovascular invasion (HR 1.65, 95 % CI 1.17-2.33; p = 0.004). The nomogram was made based on these factors and a calculated risk score was accorded to each patient. Kaplan-Meier analysis of the development cohort showed a 5-year recurrence-free survival (RFS) of 83 % (95 % CI 0.80-0.86) in low-risk patients and 59 % (95 % CI 0.54-0.66) in high-risk patients with the highest 30 percentile scores. The concordance index was 0.632 by external validation. CONCLUSIONS: This recurrence risk-scoring model can be used to predict the RFS for pathologic stage I ADC patients using the above three easily measurable factors. High-risk patients need close follow-up and can be candidates for adjuvant chemotherapy.

Central Lung Cancer Management: Impact of Bronchial Resection Margin Length.

PURPOSE: The purpose of this study was to analyze the clinical impact of bronchial resection margin length in centrally located, non-small cell lung cancer. MATERIALS AND METHODS: A total of 1,854 pulmonary resections were performed between January 1994 and December 2005. Central lung cancer was defined as a tumor that was confirmed by bronchoscopy or a malignancy proven by bronchoscopic washing. Cases with neoadjuvant treatment that could alter the malignancy on the margin and those without documentation of margin length were excluded. To divide the study group into two groups, the cutoff value for the margin length was calculated by the minimum p-value approach. Clinical variables were then compared between the two groups and prognostic factors for survival were analyzed. RESULTS: A total of 573 patients were included. The patients were divided into two groups based on margin length, short (< 19 mm) and long (≥ 19 mm). Overall survival and disease-free survival were superior in the short length group by univariate analysis (p = 0.03, 0.02). With multivariate analysis, advanced age (p < 0.00, 0.00), pneumonectomy (p < 0.00, 0.00), advanced pathologic stage (p < 0.00, 0.00), and no adjuvant chemotherapy (p < 0.00, 0.01) were poor prognostic factors for survival; however, bronchial resection margin length was not a statistically significant factor (p = 0.90, 0.96). CONCLUSION: A long bronchial resection margin length may not guarantee better oncologic outcomes in central lung cancer patients. Rather, avoiding pneumonectomy and the application of adjuvant chemotherapy should be considered to survival.

Cytoplasmic YAP expression is associated with prolonged survival in patients with lung adenocarcinomas and epidermal growth factor receptor tyrosine kinase inhibitor treatment.

BACKGROUND: Yes-associated protein (YAP) has been reported to be associated with the prognosis of various cancers and also to affect epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) activity in ovarian cancer cell lines. However, few studies have evaluated YAP protein expression in lung cancer, and the results have lacked consistency. METHODS: YAP expression was evaluated in a total of 205 curatively resected lung adenocarcinomas and 36 cases of EGFR-mutated TKI-treated patients. Correlations between the expression of YAP and clinicopathologic features, response to EGFR-TKI treatment, and prognostic significance were analyzed. RESULTS: High cytoplasmic YAP expression was positively correlated with the clinicopathologic parameters that have been associated with favorable prognosis. Multivariate analysis revealed that high cytoplasmic YAP expression was an independent prognostic factor in lung adenocarcinomas (progression-free survival: hazard ratio [HR] 0.659; 95 % confidence interval [CI] 0.431-1.010; p = 0.050; overall survival: HR, 0.474; 95 % CI 0.263-0.854; p = 0.013) and EGFR-TKI-treated patients with EGFR mutation (progression-free survival: HR, 0.346; 95 % CI 0.146-0.818; p = 0.016; overall survival: HR, 0.291; 95 % CI 0.125-0.676; p = 0.004). CONCLUSIONS: High cytoplasmic YAP expression predicted a good clinical outcome for patients with lung adenocarcinoma and in EGFR-TKI-treated patients. Therefore, YAP may play a role in EGFR-TKI-treated lung cancer, and YAP targeting may enhance therapeutic effects in combination with other cancer drugs.

Surgical resection of nodular ground-glass opacities without percutaneous needle aspiration or biopsy.

BACKGROUND: Percutaneous needle aspiration or biopsy (PCNA or PCNB) is an established diagnostic technique that has a high diagnostic yield. However, its role in the diagnosis of nodular ground-glass opacities (nGGOs) is controversial, and the necessity of preoperative histologic confirmation by PCNA or PCNB in nGGOs has not been well addressed. METHODS: We here evaluated the rates of malignancy and surgery-related complications, and the cost benefits of resecting nGGOs without prior tissue diagnosis when those nGGOs were highly suspected for malignancy based on their size, radiologic characteristics, and clinical courses. Patients who underwent surgical resection of nGGOs without preoperative tissue diagnosis from January 2009 to October 2013 were retrospectively analyzed. RESULTS: Among 356 nGGOs of 324 patients, 330 (92.7%) nGGOs were resected without prior histologic confirmation. The rate of malignancy was 95.2% (314/330). In the multivariate analysis, larger size was found to be an independent predictor of malignancy (odds ratio, 1.086; 95% confidence interval, 1.001-1.178, p =0.047). A total of 324 (98.2%) nGGOs were resected by video-assisted thoracoscopic surgery (VATS), and the rate of surgery-related complications was 6.7% (22/330). All 16 nGGOs diagnosed as benign nodules were resected by VATS, and only one patient experienced postoperative complications (prolonged air leak). Direct surgical resection without tissue diagnosis significantly reduced the total costs, hospital stay, and waiting time to surgery. CONCLUSIONS: With careful selection of nGGOs that are highly suspicious for malignancy, surgical resection of nGGOs without tissue diagnosis is recommended as it reduces costs and hospital stay.

Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements in lung cancer with nodular ground-glass opacity.

BACKGROUND: Nodular ground-glass opacities (nGGO) are a specific type of lung adenocarcinoma. ALK rearrangements and driver mutations such as EGFR and K-ras are frequently found in all types of lung adenocarcinoma. EGFR mutations play a role in the early carcinogenesis of nGGOs, but the role of ALK rearrangement remains unknown. METHODS: We studied 217 nGGOs resected from 215 lung cancer patients. Pathology, tumor size, tumor disappearance rate, and the EGFR and ALK markers were analyzed. RESULTS: All but one of the resected nGGOs were adenocarcinomas. ALK rearrangements and EGFR mutations were found in 6 (2.8%) and 119 (54.8%) cases. The frequency of ALK rearrangement in nGGO was significantly lower than previously reported in adenocarcinoma. Advanced disease stage (p = 0.018) and larger tumor size (p = 0.037) were more frequent in the ALK rearrangement-positive group than in ALK rearrangement-negative patients. nGGOs with ALK rearrangements were associated with significantly higher pathologic stage and larger maximal and solid diameter in comparison to EGFR-mutated lesions. CONCLUSION: ALK rearrangement is rare in lung cancer with nGGOs, but is associated with advanced stage and larger tumor size, suggesting its association with aggressive progression of lung adenocarcinoma. ALK rearrangement may not be important in early pathogenesis of nGGO.