Impact of lymph node dissection on the efficacy of immune checkpoint inhibitors in patients with postoperative recurrence of non-small cell lung cancer.

Background: The effect of lymph node dissection (LND) on the efficacy of immune checkpoint inhibitor (ICI) remains unclear. The purpose of this study was to examine the difference in the effect of ICI between patients with non-small cell lung cancer (NSCLC) according to the extent of LND performed in surgery prior to postoperative recurrence. Methods: A total of 134 patients with postoperative recurrence (surgery group, n=26) or unresectable advanced lung cancer (non-surgery group, n=108) who were treated with ICIs between January 2016 and December 2022 were included for analysis. In the surgery group, 16 patients underwent systematic LND, whereas the remaining 10 patients underwent selective LND. Progression-free survival with ICI treatment (ICI-PFS) and overall survival (OS) were compared between the surgery and non-surgery groups and between the systematic and selective LND groups using the inverse probability of treatment weighting (IPTW) method to adjust for patient background characteristics. Results: In the IPTW-adjusted analysis, the 2-year PFS rate with ICI treatment was 31.2% in the surgery group and 27.3% in the non-surgery group (P=0.19); the corresponding 2-year OS rates were 69.6% and 62.2%, respectively (P=0.10). In the surgery group, the 2-year PFS rates under ICI were 20.0% in the systematic LND group and 45.7% in the selective LND group (P=0.03). Conclusions: IPTW-adjusted analysis indicated no difference in prognosis between patients with postoperative recurrence and those with advanced unresectable lung cancer. However, in patients with postoperative recurrence, the extent of LND was a significant predictor of ICI-PFS. These findings suggest that systematic LND may reduce the efficacy of ICI, indicating that preoperative ICI administration may be warranted.

Salivary metabolomic biomarkers for non-invasive lung cancer detection.

Identifying novel biomarkers for early detection of lung cancer is crucial. Non-invasively available saliva is an ideal biofluid for biomarker exploration; however, the rationale underlying biomarker detection from organs distal to the oral cavity in saliva requires clarification. Therefore, we analyzed metabolomic profiles of cancer tissues compared with those of adjacent non-cancerous tissues, as well as plasma and saliva samples collected from patients with lung cancer (n = 109 pairs). Additionally, we analyzed plasma and saliva samples collected from control participants (n = 83 and 71, respectively). Capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry were performed to comprehensively quantify hydrophilic metabolites. Paired tissues were compared, revealing 53 significantly different metabolites. Plasma and saliva showed 44 and 40 significantly different metabolites, respectively, between patients and controls. Of these, 12 metabolites exhibited significant differences in all three comparisons and primarily belonged to the polyamine and amino acid pathways; N1-acetylspermidine exhibited the highest discrimination ability. A combination of 12 salivary metabolites was evaluated using a machine learning method to differentiate patients with lung cancer from controls. Salivary data were randomly split into training and validation datasets. Areas under the receiver operating characteristic curve were 0.744 for cross-validation using training data and 0.792 for validation data. This model exhibited a higher discrimination ability for N1-acetylspermidine than that for other metabolites. The probability of lung cancer calculated using this model was independent of most patient characteristics. These results suggest that consistently different salivary biomarkers in both plasma and lung tissues might facilitate non-invasive lung cancer screening.

Primary Lung Adenocarcinoma With ALK Gene Rearrangement Mostly Occupied by the Signet-Ring Cell Carcinoma Component: A Case Report.

Primary lung carcinoma tumors possessing a signet-ring cell carcinoma (SRCC) component at varying proportions are rare, while those primarily composed of an SRCC component are much rarer. Reported here is a case of primary lung adenocarcinoma primarily composed of an SRCC component with a scant acinar component that developed in an 81-year-old male. Approximately 95% of the adenocarcinoma was occupied by an SRCC component that was shown to be diastase-resistant based on positive periodic acid-Schiff staining. Immunostaining for ALK and fluorescence in situ hybridization analysis (break-apart assay) showed the presence of an ALK gene rearrangement. Findings in this case indicated a primary lung adenocarcinoma with ALK gene rearrangement, in which an SRCC component accounted for approximately 95% of the tumor.

Surgical technique for preventing lung torsion after right upper and lower bilobectomy.

In cases of right upper and lower bilobectomy, careful manipulation is required to avoid lung torsion, as only the right middle lobe remains in the right thoracic cavity. We report a case of successful right upper and lower bilobectomy with no torsion of the middle lobe. Our technique prevents postoperative lung torsion by fixing the lung to the chest wall and pericardial fat with silk threads. In situations where lung torsion is a concern after lung resection, fixing the remaining lungs with silk thread is effective in preventing lung torsion.

Significance of very-low-voltage coagulation plus coverage with polyglycolic acid sheet after bullectomy for primary spontaneous pneumothorax.

BACKGROUND: The purpose of this study was to clarify the efficacy of the combination of low-voltage coagulation plus staple line coverage with a polyglycolic acid sheet after bullectomy for primary spontaneous pneumothorax to prevent a postoperative recurrence. METHODS: A total of 143 patients who underwent bullectomy for primary spontaneous pneumothorax between January 2014 and December 2019 were enrolled in this study. We classified the patients into two groups based on additional procedures after bullectomy, namely, low-voltage coagulation for the margin of the staple line plus coverage with a polyglycolic acid sheet (Group A) and staple line coverage with a polyglycolic acid sheet alone (Group B). We evaluated perioperative factors and recurrence-free survival after surgery in the two groups. RESULTS: Nine patients in Group B developed postoperative recurrences. In contrast, there was no postoperative recurrence in Group A. According to the Kaplan-Meier curves, the 2-year recurrence-free survival rates of the patients were 100% and 90.3%, in Group A and Group B, respectively. The log-rank test showed a significant difference between the two groups (p = 0.031). CONCLUSION: Low-voltage coagulation for the margin of a staple line plus coverage with a polyglycolic acid sheet is a useful option as an additional technique after bullectomy for primary spontaneous pneumothorax to prevent a postoperative recurrence.

Intrathoracic lipoma in the horizontal fissure of the right lung: a case report.

Lipomas are benign tumors that originate from mesenchymal tissue, such as subcutaneous tissue. Intrathoracic lipomas are rare, and they can occur in the chest wall, mediastinum and bronchi. In the present case, the patient had an intrathoracic lipoma that was located in the horizontal fissure of the right lung. Retrospective review of chest radiographs taken at a previous health checkup confirmed that the tumor was growing. The patient had no symptoms, and computed tomography and magnetic resonance imaging suggested that the tumor was a hamartoma. The tumor was resected by video-assisted thoracic surgery, and was diagnosed by pathological analysis as an intrathoracic lipoma consisting of no atypical fats.

The Correlation Between Fissureless Technique and Prolonged Air Leak for Patients Undergoing Video-Assisted Right Upper Lobectomy.

PURPOSE: We aimed to assess the clinical usefulness of the fissureless technique, which avoided dissection of the lung parenchyma over the pulmonary artery, in preventing prolonged air leak after video-assisted thoracic surgery right upper lobectomy (VATS RUL). METHODS: Perioperative outcomes, including the frequency of prolonged air leak after fissureless technique or traditional fissure dissection technique, which dissected the lung parenchyma through the fissure, were compared in patients who underwent VATS RUL (n = 213) between January 2016 and March 2020. We adopted our fissural grade to evaluate the degree of fused fissure ranging from II (light incomplete fissure) to IV (severe incomplete fissure), which covered all fissural grades in 213 patients. RESULTS: Fifty-four and 159 patients underwent fissureless and traditional techniques, respectively. Significant differences in the incidence of prolonged air leak (p = 0.037), time to air leak cessation (p = 0.047), and duration of chest tube placement (p = 0.017) were observed between fissureless and traditional technique groups. On multivariable analysis, traditional technique (p = 0.005), and greater fissural grade (III vs II, p = 0.020; IV vs II, p = 0.001) were significantly associated with prolonged air leak. CONCLUSIONS: Fissureless technique during VATS RUL can be a superior alternative to the traditional technique to prevent prolonged air leak in treating incomplete fissures.

Clinical usefulness of the 3-tier classification according to the proportion of morphological patterns for patients with pathological stage I invasive lung adenocarcinoma.

OBJECTIVES: We classified pathological stage I invasive lung adenocarcinomas according to our 3-tier classification, which was based on the proportion of invasive morphological patterns as follows: (1) patients with each predominant subtype, (2) those with a minor histological subtype, even not the predominant subtype and (3) those without each invasive component. We aimed to evaluate the classification's clinical impact in survival, recurrence, malignant grade, and epidermal growth factor receptor (EGFR) mutational status. MATERIALS AND METHODS: A total of 1,269 patients with p-stage I lung adenocarcinoma underwent curative surgical resection between January 2008 and December 2017. Of these, 620 patients (48.9%) met the inclusion criteria of this study. RESULTS: Postoperative recurrence was observed in 81 patients (13.1%). Multivariate analysis showed that vascular invasion (hazard ratio, 2.61; p < 0.001) and p-stage IB (hazard ratio, 2.19; p = 0.001) were significantly associated with an unfavorable RFS, while the presence of acinar component (hazard ratio, 1.64; p = 0.052) or solid component (hazard ratio, 1.60; p = 0.074) were marginally significant. The presence of lepidic or papillary component and the absence of acinar or solid component significantly correlated with an increased proportion of lung adenocarcinomas harboring EGFR mutations. CONCLUSION: In patients with p-stage I invasive lung adenocarcinoma, it is beneficial to use not only the predominant subtype but analyzing the extent of each histological component based on our classification to predict patient prognoses and form appropriate postoperative follow-up methods.

Sialadenoma Papilliferum of the Bronchus: An Unrecognized Bronchial Counterpart of the Salivary Gland Tumor With Frequent BRAF V600E Mutations.

Sialadenoma papilliferum (SP) is a rare benign tumor of the salivary glands, and only 3 unequivocal cases of SP arising in the bronchus have been reported. We herein describe the histomorphologic and molecular features of 4 bronchial SP cases and discuss the differential diagnosis of this entity and the relationship with its clinicopathologic mimics, in particular, glandular papilloma and mixed squamous cell and glandular papilloma (GP/MP). We encountered 2 male and 2 female patients with bronchial SP (mean: 66.8 y old). All 4 tumors arose in the central bronchus and were characterized by a combination of surface exophytic endobronchial papillary proliferation and a submucosal multicystic component with complex architecture. The neoplastic epithelium consisted predominantly of nonciliated stratified columnar cells with ciliated, squamous, and mucinous cells present focally. While 2 tumors (50%) harbored a BRAF V600E mutation by molecular and immunohistochemical analysis, similar to GP/MP, no KRAS, HRAS, AKT1, or PIK3CA mutations were detected in any of the cases. Two patients were treated with limited resection, while 2 patients underwent lobectomy based on the diagnosis of adenocarcinoma or possible squamous cell carcinoma in situ in the preoperative biopsy. All survived without recurrence or metastasis for 23 to 122 months after treatment. SP can develop in the central bronchus as the bronchial counterpart of the salivary gland tumor and should be considered in the differential diagnosis of endobronchial tumors. In addition, some histologic resemblance and frequent BRAF V600E mutation raise the possibility of SP and GP/MP being on the same disease spectrum.

Prognostic Significance of Ground-Glass Opacity Components in 5-Year Survivors With Resected Lung Adenocarcinoma.

BACKGROUND: Reports on the prognosis for 5-year survivors with lung adenocarcinoma after resection are sparse. This study aimed to identify factors associated with overall survival (OS) and cancer-specific survival (CSS) for 5-year survivors with completely resected lung adenocarcinoma, and to determine whether preoperative imaging factors, including the presence of ground-glass opacity (GGO) components, affect late recurrence in long-term survivors. METHODS: Complete resection of lung adenocarcinoma was performed for 1681 patients between January 2000 and December 2013. Of these patients, 936 who survived 5 years or longer after surgery were identified, and factors associated with OS and CSS were determined using the Cox proportional hazard model. RESULTS: Multivariable analysis demonstrated that lymph node metastasis (p < 0.01) and absence of GGO components (p < 0.01) were independently associated with OS and CSS for the 5-year survivors. The absence of GGO components was significantly associated with OS (p < 0.01) and CSS (p < 0.01) also for the 5-year survivors with stage 1 disease (n = 782) and for the 5-year survivors without recurrence (n = 809). The incidence of recurrence anytime during the 10-year postoperative follow-up period differed significantly between the 5-year survivors with and without GGO components. CONCLUSIONS: The absence of GGO components was significantly associated with an unfavorable prognosis for the 5-year survivors with completely resected lung adenocarcinoma regardless whether they had recurrences not.

Comparative analysis of the results of video-assisted thoracic surgery lobectomy simulation using the three-dimensional-printed Biotexture wet-lung model and surgeons' experience.

OBJECTIVES: We performed a comparative analysis of the performance of video-assisted thoracic surgery (VATS) lobectomy simulation using three-dimensional-printed Biotexture lung models by surgeons classified according to their level of expertise. The aim of this study was to investigate the association between surgeons' experience and time to complete the VATS lobectomy simulation. METHODS: Participants were divided into 3 groups: group A included those who had no experience of actual VATS lobectomy (n = 11), group B included those who had performed 5-10 VATS lobectomies (n = 12) and group C included those who had performed >100 VATS lobectomies (n = 6). Their performances were assessed based on total procedure time, duration to the exposure of the vessels, ligation of the arteries and stapling of the fissures. After the simulation, a questionnaire survey was performed. RESULTS: The median total procedure time was significantly shorter in the group of surgeons with more experience (A vs B, P < 0.001; B vs C, P = 0.034; A vs C, P < 0.001). Regarding 'the exposure of all the vessels to be resected' and 'ligation of the arteries', group B completed these steps in less time than group A (P = 0.024 and P = 0.012, respectively). In the questionnaire, all groups answered that this simulation was useful for novices to improve their skills. CONCLUSIONS: Although time to complete the VATS lobectomy simulation is only a part of evaluation points for real skills, this model can facilitate basic skill acquisitions for novices.

F-18 fluorodeoxyglucose uptake in lymph nodes and sonographic features on endobronchial ultrasonography predict lymph node metastasis in lung cancer patients.

BACKGROUND: Sonographic findings of lymph nodes on endobronchial ultrasonography (EBUS) images have been reported to be useful to predict lymph node metastasis (LNM) in lung cancer patients. F-18 fluorodeoxyglucose (FDG) uptake in lymph nodes was also found to be useful. In this study, we aimed to clarify whether a combination of sonographic features and maximum standardized uptake values of lymph nodes (LN-SUVmax) is useful for predicting LNM in lung cancer patients. METHODS: From January 2014 to December 2019, a total of 147 lymph nodes from 104 patients with lung cancer, who underwent preoperative EBUS and FDG-positron emission tomography (PET)/computed tomography (CT) followed by surgery were retrospectively assesses. The characteristics of the patients, LN-SUVmax, and sonographic findings of lymph nodes were reviewed. Predictive factors associated with LNM were identified using the logistic regression model. RESULTS: The average size of the lymph nodes was 8.55 (range, 3-22) mm and the average LN-SUVmax was 5.36 (range, 1.79-31.19). The prevalence of nodal metastasis was 26/147 (17.4%), including 22 in mediastinal lymph nodes and 4 in hilar lymph nodes. Multivariate analysis demonstrated four independent predictive factors for LNM; size, round or oval shape, absence of a central hilar structure, and LN-SUVmax. The optimal cutoff value for lymph node size and LN-SUVmax were 10 mm and 6.00, respectively. By combinating of the two modalities, we obtained the results with sensitivity of 76.9%, specificity of 95.1% and accuracy of 93.2%. CONCLUSIONS: A combination of sonographic findings and LN-SUVmax showed a higher diagnostic rate of LNM than either modality alone in lung cancer patients.

Significant prognostic determinants in lung cancers of the superior sulcus: comparable analysis of resected and unresected cases.

OBJECTIVE: In this study, we aimed to identify prognostic determinants and to comparably analyze clinical features of patients with both resected and unresected superior sulcus tumors (SSTs). METHODS: The data of 56 patients who underwent any treatment for an SST from 2004 through 2016 in our hospital were reviewed. Overall survival (OS) rates were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to determine independent prognostic factors for patients with resected and unresected SST separately. RESULTS: The number of patients with resected and unresected SSTs was 24 (43%) and 32 (57%), respectively. Of the 24 patients who underwent surgery, 20 received induction therapy, with 32% achieving pathological complete response. Complete resection (R0) was performed in 22 patients (92%). On multivariate survival analysis, preoperative serum carcinoembryonic antigen (CEA) level (median 8.3 ng/ml, p = 0.021) was identified as the independent determinant of OS in surgical patients; whereas, initial treatment response (complete response or partial response, p = 0.032) was the independent OS indicator in non-surgical patients. The 5-year OS of the patient with resected and unresected SST was 68.8% and 29.1% (p = 0.008), respectively. CONCLUSION: Significant prognostic factors differ among patients stratified by the presence of surgical resection for SSTs. Preoperative CEA level in surgical candidates and initial treatment response in non-surgical patients were the independent factors associated with OS. Surgical candidates are expected to have more favorable survival than patients with unresectable SSTs.

Profiles of Lung Adenocarcinoma With Multiple Ground-Glass Opacities and the Fate of Residual Lesions.

BACKGROUND: We aimed to clarify clinical profiles of patients with adenocarcinoma presenting as multifocal ground-glass opacities (MGGOs) to assess their prognosis and the optimal management method for residual satellite lesions. METHODS: We identified 190 patients with cN0 MGGOs (MGGO cohort) and 1426 patients with solitary lung adenocarcinoma (control cohort) who underwent complete resection between 2004 and 2016. Propensity score matching was performed to adjust for differences in baseline characteristics of both cohorts for survival analyses. MGGOs consist of a main tumor and satellite lesions and were subdivided into 3 groups: the PG group, with multifocal pure GGOs; the GD group, in which the main tumor presented as GGO dominant; and the SD group, where the main tumor presented as solid dominant. RESULTS: No significant differences in recurrence-free survival were observed between the 2 cohorts before and after the propensity score matching. For patients with MGGOs, 22 were in the PG group, 47 in the GD group, and 121 in the SD group. Type of MGGOs was a significant factor for recurrence-free survival recurrence-free survival both in the entire population (SD vs PG-GD, P = .008) and in p-stage I cohorts (P = .004) on multivariable analysis. Among 116 patients (61.1%) with residual satellite lesions, 38 patients had progressed lesions and 69 stable lesions. Although the emergence of new lesions during the follow-up period was an independent predictor for satellite lesion progression, neither progressed lesions nor the emergence of new lesions influenced survival. CONCLUSIONS: Patients with MGGOs and solitary adenocarcinoma had a similar prognosis. The biologic behavior of main tumors dominates clinical outcomes in patients with MGGOs.

A combination therapy of photodynamic therapy (PDT) and airway stent placement using a transparent silicone stent.

The aim of this study was to evaluate the feasibility of a combination therapy of photodynamic therapy (PDT) and airway stent placement using a transparent silicone stent (gold studded stent [GSS]). Laser irradiation (664 nm, continuous wave) was performed through the GSS using a straight and cylindrical fiber 1.0 cm away from a power meter. There are two types of GSS: the TD type for the trachea and the BD type for the bronchus. Laser outputs were set to 150 mW, 180 mW, 210 mW, 240 mW, 270 mW, and 300 mW. The laser powers passing through the both types of GSS were measured three times for each outputs and the averages were calculated. Based on the results, animal experiment was performed using two female pigs. Under general anesthesia, a GSS (BD type) was inserted into trachea of pigs, and PDT using NPe6 as a photosensitizer was performed by 100 J/cm2 laser irradiation on parts of the trachea with and without a GSS. Immediately after and 1 week after PDT, pig tracheas were harvested and histological analysis was performed. Histological analysis of areas with or without the stent showed edematous changes between the cartilage and submucosal layer immediately after PDT, and necrotic changes 1 week later. The effectiveness of NPe6-PDT for pigs' trachea covered by the stent was same as trachea without the stent. The use of a GSS may enable PDT to be effective even in the area covered by the stent.

Ubiquitin C-terminal hydrolase-L1 has prognostic relevance and is a therapeutic target for high-grade neuroendocrine lung cancers.

High-grade neuroendocrine lung cancer (HGNEC), which includes small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is a rapidly proliferating, aggressive form of lung cancer. The initial standard chemotherapeutic regimens of platinum doublets are recommended for SCLC and have been frequently used for LCNEC. However, there are currently no molecularly targeted agents with proven clinical benefit for this disease. The deubiquitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCHL1) is a neuroendocrine cell-specific product that is known as a potential oncogene in several types of cancer, but little is known about the biological function of UCHL1 and its therapeutic potential in HGNEC. In this study, we found that preclinical efficacy evoked by targeting UCHL1 was relevant to prognosis in HGNEC. UCHL1 was found to be expressed in HGNEC, particularly in cell lines and patient samples of SCLC, and the combined use of platinum doublets with selective UCHL1 inhibitors improved its therapeutic response in vitro. Immunohistochemical expression of UCHL1 was significantly associated with postoperative survival in patients with HGNEC and contributed towards distinguishing SCLC from LCNEC. Circulating extracellular vesicles (EV), including exosomes isolated from lung cancer cell lines and serum from early-stage HGNEC, were verified by electron microscopy and nanoparticle tracking analysis. Higher levels of UCHL1 mRNA in EV were found in the samples of patients with early-stage HGNEC than those with early-stage NSCLC and healthy donors' EV. Taken together, UCHL1 may be a potential prognostic marker and a promising druggable target for HGNEC.

Prognostic impact of solid-part tumour volume doubling time in patients with radiological part-solid or solid lung cancer.

OBJECTIVES: The measurement of part-solid and whole tumour sizes in patients with non-small-cell lung cancer (NSCLC) using computed tomography (CT) has been widely accepted for assessing clinical outcomes. Although the volume doubling time (VDT) of a tumour is useful for distinguishing high-risk nodules from low-risk ones, it remains to be clarified whether separate calculation of whole-tumour VDT and solid-part tumour VDT (SVDT) greatly affects the survival rate of patients with radiologically node-negative part-solid or solid NSCLC. METHODS: The study included 258 patients with NSCLC who had radiologically node-negative, part-solid or solid tumours and who had at least 2 preoperative CT scans taken more than 30 days apart followed by radical lobectomy and systemic lymph node dissection between January 2012 and December 2015. Univariable and multivariable analyses of recurrence-free survival were performed using the Cox proportional hazards regression model. RESULTS: The mean whole-tumour VDT and SVDT were 375 and 458 days, respectively. Multivariable analyses demonstrated that whole-tumour VDT (P = 0.003), SVDT (P < 0.001), solid-part tumour size, whole-tumour size and comorbidities significantly affected the recurrence-free survival. Using the receiver operating characteristic curve, the cut-off value of the SVDT for recurrence was 215 days, and the 5-year recurrence-free survival rates for patients with SVDT >215 days and those with SVDT <215 days were 85.7% and 43.0%, respectively (P < 0.001). CONCLUSION: The calculation of SVDT in patients with node-negative, part-solid or solid NSCLC is highly useful for predicting postoperative survival outcomes.

Epidermal growth factor receptor mutation subtype has differential effects on adjuvant chemotherapy for resected adenocarcinoma pathological stages II-III.

The aim of the present study was to investigate epidermal growth factor receptor (EGFR) mutations as a prognostic factor for postoperative patients with positive EGFR mutations treated with postoperative platinum-based adjuvant chemotherapy (PBAC), and whether two common EGFR mutations exhibit different responses to PBAC. A total of 110 patients who underwent complete surgical resection were enrolled, and overall survival (OS) and disease-free survival (DFS) were investigated based on EGFR mutation status and PBAC. The 3 year OS rate in patient groups were as follows: Patients with EGFR mutations (MT) undergoing PBAC, 89.3%; MT patients without PBAC, 83.3%; wild-type (WT) patients with PBAC, 82.3%; and WT patients without PBAC, 62.2%. Statistically significant differences were observed between WT patients based on PBAC (P=0.026). No statistically significant differences were observed between MT patients with PBAC and MT patients without PBAC. On the basis of mutation subtypes, the 3 year OS rate of patient groups were as follows: Patients with in-frame deletions in exon19 (19 del) with PBAC, 92.3%; patients with 19 del without PBAC, 85.7%; patients with the point mutation L858R inexon21 (21L858R) with PBAC, 86.7%; and patients with 21L858R without PBAC, 81.5%; the respective 3-year DFS rates were 53.8, 14.3, 40.2 and 26.9%. Statistically significant differences were observed in the DFS rates in 19 del patients, which was dependent on PBAC (P=0.040). EGFR mutation-positive patients exhibited a decreased benefit from PBAC for increasing in survival rate compared with WT patients. It may be necessary to consider postoperative strategies based on EGFR mutations and their subtype in the future.

Correction to: Successful adjustment for self-expanding metallic stent migration using a flexible bronchoscope with two biopsy forceps technique.

In the original publication of the article, the corresponding author email address was published wrongly.

Computed Tomography Histogram Approach to Predict Lymph Node Metastasis in Patients With Clinical Stage IA Lung Cancer.

BACKGROUND: Quantitative computed tomography (CT) histogram analysis of tumors is reported to help distinguish between invasive and less invasive lung cancers. This study aimed to clarify whether CT histogram analysis of tumors can be used to classify patients with clinical stage 0 to IA non-small cell lung cancer according to pathologic lymph node (pN) status. METHODS: Predictive factors associated with pN metastasis were identified from the derivation dataset including 629 patients with clinical stage 0 to IA non-small cell lung cancer who underwent complete resection with lymph node dissection (surgeries between 2008 and 2013). The validation dataset including 238 patients (surgeries between 2014 and 2015) were subsequently reevaluated. Clinicosurgical factors, including CT histogram analysis of tumors (CT value percentiles 2.5, 25, 50, 75, and 97.5, skewness, and kurtosis) were assessed. RESULTS: Seventy-three patients (12%) in the derivation cohort and 35 patients (15%) in the validation cohort had positive nodes. The pN status significantly affected survival in the entire population: 5-year overall survival of 93.1% vs 71.1% and 5-year disease-free survival of 85.9% vs 43.1% for negative vs positive (both P < .001). On multivariate analysis in the derivation cohort, the 75th percentile CT value (P < .001), age (P = .003), and comorbidities (P = .006) were significantly associated with pN metastasis. The area under the curve and the cutoff level of the 75th percentile CT value relevant to pN metastasis were 0.729 and 1.5 HU, respectively, and the threshold value provided accuracy of 71% for the validation cohort. CONCLUSIONS: Histogram analysis of CT imaging metrics of tumors contributes to noninvasive prediction of pN metastasis in patients with clinical stage 0 to IA non-small cell lung cancer.