MicroRNA Expression in Plasma of Esophageal Squamous Cell Carcinoma Patients.

BACKGROUND: Patients with esophageal squamous cell carcinoma (ESCC) have a poor prognosis and there are no effective clinical biomarkers. Recently, stable microRNAs detected in the blood have been suggested as potential biomarkers in various cancers. Therefore, we investigated whether plasma microRNAs could be feasible biomarkers for ESCC. METHODS: Peripheral blood samples were obtained from 16 healthy volunteers and 66 ESCC patients before treatment between May 2016 and April 2021. Plasma miR-18b, miR-21, miR-31, and miR-375 expression levels were measured using reverse transcription-quantitative polymerase chain reaction. RESULTS: Compared with those in healthy controls, the expression levels of plasma miR-21 were significantly higher (P = 0.022) and those of plasma miR-31 and miR-375 were significantly lower in ESCC patients (both P < 0.001). Plasma miR-18b expression levels increased in ESCC patients, but the difference was not significant (P = 0.164). The sensitivities and specificities of miR-21, miR-31, and miR-375 for differentiating ESCC patients from healthy controls were 87.5% and 61.9%, 87.5% and 98.4%, and 87.5% and 100%, respectively. There was no difference in expression levels of plasma miR-21, miR-31, and miR-375 according to clinicopathological characteristics of sex, age, tumor size and location, histologic grade, and tumor-node-metastasis stage. CONCLUSION: Our study demonstrated that plasma miR-21, miR-31, and miR-375 could be potential biomarkers for the diagnosis of ESCC. Particularly, plasma miR-31 and miR-375 showed high sensitivity and specificity for differentiating ESCC patients from healthy controls.

Applying Fibrin Glue under Pleurography for Intractable Secondary Spontaneous Pneumothorax.

BACKGROUND: Prolonged air leakage is a problem that can frequently develop in patients with a secondary spontaneous pneumothorax (SSP) or in those who undergo thoracic surgery. However, the management of an air leak is difficult and reoperation might be avoided due to several reasons including adhesions. Herein, we introduce a fibrin glue application under pleurography (FGAP) and short-term outcomes in patients who underwent this procedure. METHODS: FGAP was performed in 20 patients with an intractable persistent air leakage who had poor lung function, comorbidities to undergo general anesthesia and were expected severe adhesions due to previous surgery. All medical records were retrospectively reviewed. RESULTS: Eighteen cases sealed soon after dropping the glue. One patient had a prolonged air leak for 12 days and another patient required an operation to control air leakage 16 days after the procedure. The mean duration of postoperative drainage was 4.17 ± 2.11 days (range: 3-14 days). No postprocedural complications were recorded. The mean duration of follow-up was 12.01 ± 5.02 months (range: 4-22 months). CONCLUSION: FGAP could be a treatment option to seal air leaks, especially in cases with intractable air leakage.

Circulating tumor cells detected using fluid-assisted separation technique in esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is one of the aggressive gastrointestinal tract cancers. Detection of circulating tumor cells (CTCs) in peripheral blood from patients with various malignancies has been reported to have diagnostic, prognostic, and therapeutic implications. We aimed to evaluate CTCs in patients with ESCC and assess the clinical significance of CTCs in the early diagnosis of ESCC. METHODS: Peripheral blood samples for CTCs analyses were prospectively obtained from 73 patients with ESCC prior to treatment between March 2015 and June 2018. CTCs were detected using a centrifugal microfluidic system with a new fluid-assisted separation technique. Blood samples from 31 healthy volunteers were used as controls. RESULTS: After creating a receiver operating characteristic curve to determine the optimal CTC threshold to differentiate patients with ESCC from healthy controls, sensitivity and specificity were most optimized at a CTC threshold of two per 7.5 mL of blood. Among 66 subjects with ≥ 2 CTCs per 7.5 mL of blood, 63 (95.5%) had ESCC. Among 38 subjects with < 2 CTCs per 7.5 mL of blood, 28 (73.7%) were healthy controls. When using this threshold, the sensitivity and specificity for differentiating patients with ESCC from healthy controls were 86.3% and 90.3%, respectively. CTC count was associated with tumor-node-metastasis stage, especially lymph node metastasis, but there was no correlation with any other relevant clinicopathologic variable. CONCLUSIONS: Our results suggest that CTCs detected using fluid-assisted separation technique could be helpful for early diagnosis of ESCC. Further large-scale prospective studies are warranted to validate our findings.

Factors Affecting Postoperative Lung Expansion in Patients with Pyogenic Empyema.

BACKGROUND: In patients with parapneumonic empyema, decortication is usually preferred to ensure functional lung re-expansion. However, there could be patients exhibiting incomplete postoperative lung expansion and inadequate drainage despite decortication. Therefore, we evaluated factors affecting postoperative lung expansion in patients undergoing decortication. METHODS: A total of 221 patients with pyogenic empyema who underwent video-assisted thoracoscopic surgery (VATS) between January and October 2016 in our hospital were reviewed in terms of surgical success. The following factors were evaluated: age; the time between identification of a localized effusion and surgical referral; chest tube drainage durations; any underlying morbidity preoperative blood culture data; and the thickness of the visceral pleura. RESULTS: Several factors that significantly prolonged the postoperative time to lung expansion were evident in patients with diabetes mellitus (DM) and bacteremia; postoperative chest tube drainage was significantly longer in those with DM (p = 0.009) and bacteremia (p = 0.01); and postoperative hospitalization time was significantly longer in patients with bacteremia (p = 0.01). The thickness of the visceral pleura was strongly correlated with postoperative chest tube drainage duration and postoperative hospitalization time (Pearson correlation coefficient, r = 0.245, p = 0.00). CONCLUSIONS: In patients with DM, bacteremia, or thickened pleura, the time to lung expansion after operation was longer. Therefore, stricter pre- and post-operative control of blood-sugar levels and adequate antibiotics are required to facilitate postoperative lung re-expansion. In patients with thickened pleurae, prolonged chest tube placement is unavoidable.

Predicting the invasion depth of esophageal squamous cell carcinoma: comparison of endoscopic ultrasonography and magnifying endoscopy.

OBJECTIVE: Predicting the invasion depth of superficial esophageal squamous cell carcinoma (SESCC) is important when selecting among therapeutic strategies. The aim of this study was to compare magnifying endoscopy with narrow-band imaging (ME-NBI) with endoscopic ultrasonography (EUS) for predicting the depth of tumor invasion in patients with SESCC. METHODS: This study enrolled 51 patients with SESCC (52 SESCC lesions) who underwent both ME-NBI and EUS at Pusan National University Hospital during 2010-2013. We reviewed the patients' medical records and compared ME-NBI and EUS findings with histopathological results according to clinicopathological factors. RESULTS: A total of 46 lesions in 45 patients were included in the final analysis. ME-NBI and EUS had overall accuracies of 76.1% and 84.8%, respectively, in distinguishing mucosal from non-mucosal cancers. There were no differences between ME-NBI and EUS in terms of sensitivities and specificities in distinguishing mucosal from non-mucosal cancers (p = 0.500 and p = 0.688, respectively). When both ME-NBI and EUS suggested a mucosal depth of lesion invasion, the frequency of mucosal cancer in the final histopathology was 94%. However, if either ME-NBI or EUS suggested a non-mucosal depth of invasion, the frequency of mucosal cancer was only 21%. CONCLUSION: ME-NBI and EUS are accurate predictors of SESCC invasion depth. If both methods suggest a mucosal depth of lesion invasion, the accuracy of the prediction is increased. Therefore, when possible, it would be better to evaluate the invasion depth of SESCC using both ME-NBI and EUS before deciding to perform endoscopic resection.

Biomechanical Effectivity Evaluation of Single- and Double-Metal-Bar Methods with Rotation and Equilibrium Displacements in Nuss Procedure Simulations.

Surgical treatment of the pectus excavatum has led to the introduction of the Nuss procedure, a minimally invasive surgical procedure that involves inserting a metal bar under the sternum through a small lateral thoracic incision. An additional metal bar was inserted in patients with pectus excavatum to improve the retention of the restored chest wall after the Nuss procedure. However, a need still exists to analyze the mechanistic advantages and disadvantages of the double-bar method owing to the increased surgical time and proficiency. The purpose of this study is to compare and evaluate the efficiency of single- and double-bar methods using rotational and equilibrium displacement simulations of the Nuss procedure. A finite-element model was constructed for two types of metal bars inserted into the chest wall. Boundary conditions for the rotation and equilibrium displacements were set for the metal bar. The anterior sternal translation, Haller index and maximum equivalent stress and strain owing to the behavior of the metal bar were estimated and compared with the single-bar method and postoperatively acquired patient data. The simulation results showed that the influences of the intercostal muscle and equilibrium after rotation displacement were significant. The stresses and strains were distributed across the two metal bars, and the upper-metal bar was heavily loaded. The double-bar method was advantageous regarding the load distribution effects of the two metal bars on the chest wall. However, mechanical assessments are also important because an excessive load is typically applied to the upper-metal bar.

A novel in silico Nuss procedure for pectus excavatum patients.

The purpose of this study is to suggest a novel in silico Nuss procedure that can predict the results of chest wall deformity correction. Three-dimensional (3D) geometric and finite element model of the chest wall were built from the 15-year-old male adolescent patient's computed tomography (CT) image with pectus excavatum of the mild deformity. A simulation of anterior translating the metal bar (T) and a simulation of maintaining equilibrium after 180-degree rotation (RE) were performed respectively. A RE simulation using the chest wall finite element model with intercostal muscles (REM) was also performed. Finally, the quantitative results of each in silico Nuss procedure were compared with those of postoperative patient. Furthermore, various mechanical indicators were compared between simulations. This confirmed that the REM simulation results were most similar to the actual patient's results. Through two clinical indicators that can be compared with postoperative patient and mechanical indicators, the authors consider that the REM of silico Nuss procedure proposed in this study is best simulated the actual surgery.

Biomechanical validation of novel Nuss procedure simulations for patients with various morphological types of pectus excavatum.

A novel Nuss procedure simulation was developed for patients with pectus excavatum considering the displacement of a metal bar and a chest wall model, including the intercostal muscles. However, this simulation was developed for a typical symmetrical patient among the various morphological types of pectus excavatum. Accordingly, this study aimed to validate and confirm the novel simulation for patients with eccentric and imbalanced types, which are severe types of pectus excavatum, considering factors such as depression depth and eccentricity among others. Three-dimensional models of chest walls and metal bars were created for three different types of patients. The rotation-equilibrium displacement and chest wall with intercostal muscles were set according to the methods and conditions of the novel Nuss procedure simulation. The anterior sternal translation and the Haller index derived from the simulation results were compared and verified using medical data from actual postoperative patients. Additionally, maximum equivalent stresses and strains were derived to confirm the suitability of the novel Nuss procedure for each patient type. The severe types had similar precision to the typical type when compared to the actual postoperative patient. Relatively high maximum equivalent stresses and strains were observed on the metal bars and sternum in the severe type, thereby predicting and confirming the biomechanical characteristics of these types. In conclusion, a novel Nuss procedure simulation for severe types was numerically validated. This underscores the importance of biomechanical evaluation through a novel Nuss procedure simulation when planning actual surgeries for severe types of cases.

Chronic destructive pulmonary tuberculosis: assessment of disease activity by computed tomography.

BACKGROUND: Determination of disease activity of chronic destructive pulmonary tuberculosis (TB) on imaging studies can be difficult because several imaging findings due to disease chronicity such as a residual cavity can be misinterpreted as an active disease. PURPOSE: To evaluate computed tomography (CT) findings to predict active disease in patients with chronic destructive pulmonary TB. MATERIAL AND METHODS: CT findings of 36 patients with chronic active destructive pulmonary TB and 78 patients with chronic inactive destructive pulmonary TB were reviewed and their patterns of lung lesions were compared. Statistical comparisons were performed using chi-square and Student's T tests for univariate analyses, and a stepwise logistic regression method was used for multivariate analysis. RESULTS: Based on univariate analyses, cavitary destruction (P = 0.015), non-branching centrilobular nodules (P < 0.001), tree-in-bud pattern (P < 0.001), airspace nodules (P < 0.001), and cavities in other lobes (P = 0.001) were more frequently seen in chronic active destructive pulmonary TB. A stepwise logistic regression analysis demonstrated that tree-in-bud pattern (odds ratio, 52.3; 95% confidence interval, 6.2-437.2; P < 0.001) were significant CT findings associated with active disease. CONCLUSION: Tree-in-bud pattern were the most characteristic CT findings to predict active disease in patients with chronic destructive pulmonary TB.

Exosomal MicroRNA Analyses in Esophageal Squamous Cell Carcinoma Cell Lines.

Exosomal miRNAs have been studied in various cancers as minimally invasive biomarkers. This study aimed to investigate the potential of exosomal microRNAs (miRNAs) as biomarkers for esophageal squamous cell carcinoma (ESCC). Exosomes were isolated from cultures of esophageal epithelial cell and ESCC cell lines using ExoDisc, and exosomal miRNAs were detected via miRNA sequencing. Of the differentially expressed 14 miRNAs, the top 2 up-regulated miRNAs (miR-205-5p and miR-429) and top 2 down-regulated miRNAs (miR-375-3p and miR-483-3p) were selected as ESCC target miRNAs. Four selected exosomal miRNAs were validated in the plasma of 20 healthy controls (HCs) and 40 ESCC patients via quantitative reverse transcription-polymerase chain reaction. The expression of plasma exosomal miR-205-5p and miR-429 significantly increased, while that of plasma exosomal miR-375-3p was significantly reduced in ESCC patients compared to that in HCs. At cut-off values of 5.04, 2.564, and 0.136, the sensitivity and specificity for the diagnosis of ESCC were 72.5% and 70.0% for miR-205-5p, 60.0% and 60.0% for miR-429, and 65.0% and 65.0% for miR-375-3p, respectively. Based on the exosomal miRNAs identified in ESCC cell lines, our study demonstrated that plasma exosomal miR-205-5p, miR-429, and miR-375-3p could serve as potential biomarkers for ESCC diagnosis.

Localization-adjusted diagnostic performance and assistance effect of a computer-aided detection system for pneumothorax and consolidation.

While many deep-learning-based computer-aided detection systems (CAD) have been developed and commercialized for abnormality detection in chest radiographs (CXR), their ability to localize a target abnormality is rarely reported. Localization accuracy is important in terms of model interpretability, which is crucial in clinical settings. Moreover, diagnostic performances are likely to vary depending on thresholds which define an accurate localization. In a multi-center, stand-alone clinical trial using temporal and external validation datasets of 1,050 CXRs, we evaluated localization accuracy, localization-adjusted discrimination, and calibration of a commercially available deep-learning-based CAD for detecting consolidation and pneumothorax. The CAD achieved image-level AUROC (95% CI) of 0.960 (0.945, 0.975), sensitivity of 0.933 (0.899, 0.959), specificity of 0.948 (0.930, 0.963), dice of 0.691 (0.664, 0.718), moderate calibration for consolidation, and image-level AUROC of 0.978 (0.965, 0.991), sensitivity of 0.956 (0.923, 0.978), specificity of 0.996 (0.989, 0.999), dice of 0.798 (0.770, 0.826), moderate calibration for pneumothorax. Diagnostic performances varied substantially when localization accuracy was accounted for but remained high at the minimum threshold of clinical relevance. In a separate trial for diagnostic impact using 461 CXRs, the causal effect of the CAD assistance on clinicians' diagnostic performances was estimated. After adjusting for age, sex, dataset, and abnormality type, the CAD improved clinicians' diagnostic performances on average (OR [95% CI] = 1.73 [1.30, 2.32]; p < 0.001), although the effects varied substantially by clinical backgrounds. The CAD was found to have high stand-alone diagnostic performances and may beneficially impact clinicians' diagnostic performances when used in clinical settings.

Endosonographic features of esophageal granular cell tumors using a high-frequency catheter probe.

OBJECTIVE: Submucosal tumors (SMTs) are occasionally found in the esophagus during upper endoscopy. Granular cell tumors (GCTs) are reported to be the second most common esophageal mesenchymal tumors, after leiomyomas. Endoscopic ultrasonography (EUS) is an effective tool for predicting the histologic characteristics of SMTs by providing an accurate image of the layering structure of the esophagus, but it is hard to differentiate GCTs from submucosal leiomyomas accurately with conventional EUS. The aim of the present study was to characterize the EUS features of GCTs compared with those of submucosal leiomyomas using a high-frequency catheter probe EUS. MATERIAL AND METHODS: A total of 41 patients with GCTs or submucosal leiomyomas were included. All of the patients underwent EUS before histologic confirmation by endoscopic resection or biopsy. RESULTS: There were 14 GCTs in 12 patients and 30 leiomyomas in 29 patients. GCTs had a white-to-yellow surface color more frequently than leiomyomas. In comparison with the surrounding normal proper muscle layer, the echogenicity of the leiomyomas was similar to that of the surrounding muscle layer, but more than half of the GCTs were hyperechoic compared to the surrounding muscle layer. Unclear borders were observed more frequently in GCTs than in leiomyomas. The presence of at least two of these three features in a given tumor had a sensitivity of 85.7%, a specificity of 96.7%, and an accuracy of 93.2% for predicting GCTs. CONCLUSIONS: High-frequency probe EUS is helpful for differentiating esophageal GCTs from submucosal leiomyomas.

Localization of pulmonary nodules with lipiodol prior to thoracoscopic surgery.

BACKGROUND: Preoperative localization with lipiodol for identifying small or deeply seated pulmonary nodules is simple and useful for thoracoscopic surgery. Although several studies about performance and complication rates of lipiodol localization have been reported, there has been no report about the performance and complication rates of lipiodol localization with regard to the CT appearance of pulmonary nodules. PURPOSE: To evaluate the performance and complication rates of localization of pulmonary nodules with lipiodol prior to video-assisted thoracoscopic surgery with regard to the CT appearance of nodules. MATERIAL AND METHODS: After institutional review board approval and informed consent were obtained, lipiodol marking was performed in 67 patients (33 men and 34 women; mean age 58 years) with 68 nodules. All nodules were marked with 0.4-0.5 mL lipiodol under CT guidance on the day of surgery. The size of the targeted nodule and the shortest distance to the accessible pleural surface were measured. Lipiodol accumulation of a targeted nodule was scored by use of a four-point scale (0: none, 1: within 1 cm around a nodule, 2: partial accumulation within a nodule, 3: total accumulation within a nodule). Any complications after localization of nodules were noted. We analyzed the score of lipiodol accumulation and the presence of complications for the CT appearance of pulmonary nodules using the Mann Whitney U test, Fisher's exact test and the Kruskall Walis test. RESULTS: The average nodule size was 11.4 mm (range 3.0-28.3 mm) and the average distance to the pleural surface was 13.7 mm (range 0-51.4 mm). Lipiodol accumulation scores of nodules were as follows: score 3 (n=19, 28%), score 2 (n=37, 54%), score 1 (n=11, 16%), and score 0 (n=1, 2%). Lipiodol accumulation scores of nodules were different according to the size of nodules (Kruskal Wallis test, p=0.023). Pneumothorax after localization occurred in 20 (29%) patients and the incidence was higher in nodules located in the subpleural area (Mann Whitney U test, p=0.048). Pulmonary hemorrhage along the needle tract occurred in five (7%) patients and was more frequent in patients with deep nodules as compared to shallow nodules (Mann Whitney U test, p < 0.001). CONCLUSION: Lipiodol marking under CT guidance is a useful and safe procedure for the intraoperative localization of pulmonary nodules. Of variable CT findings, lesion size is important to determine the degree of lipiodol accumulation and the lesion depth is the most important feature for the development of postprocedural complications.

Non-conservative Management of Chylothorax.

Chylothorax is caused by lymphatic leakage, which can develop after thoracic surgery and is associated with cancer. Although prospective randomized trials have not been performed, radiological interventions have been performed in several cases with persistent chylothorax, adjunct to 2 weeks of conservative management. The success rate of such interventions is diverse due to anatomical variations, although the results are promising. However, in cases of treatment failure after cycles of interventions, a team approach may be necessary to determine whether surgical management is warranted.

Extralobar Supradiaphragmatic Pulmonary Sequestration Arising from the Retroperitoneum Through a Congenital Diaphragmatic Defect

Here, we report the rare case of a 13-year-old girl with a congenital diaphragmatic hernia (also known as Bochdalek hernia), which was revealed to be an extralobar pulmonary sequestration that was treated using laparoscopic and video-assisted thoracic surgery sequestrectomy and repair of the diaphragm defect after detection of a supradiaphragmatic mass connected with the retroperitoneum. The patient showed no postoperative complications at a 1-month follow-up examination.

Clinical Significance of TWIST-Positive Circulating Tumor Cells in Patients with Esophageal Squamous Cell Carcinoma.

Background/Aims: Unlike other gastrointestinal tract cancers, there are relatively few reports on the clinical significance of circulating tumor cells (CTCs) and TWIST, a marker of epithelial-mesenchymal transition, in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the clinical significance of TWIST expression in CTCs in patients with ESCC. Methods: Peripheral blood samples for CTC analyses were prospectively obtained from 52 patients with ESCC prior to treatment between September 2017 and September 2019. CTCs were detected using a centrifugal microfluidic system based on a fluid-assisted separation technique, and CTCs positive for TWIST on immunostaining were defined as TWIST (+) CTCs. Results: Of the 52 patients with ESCC, CTCs and TWIST (+) CTCs were detected in 44 patients (84.6%) and 39 patients (75.0%), respectively. The CTC and TWIST (+) CTC counts were significantly higher in patients aged >65 years and those who had a large tumor (>3 cm) than in those aged ≤65 years and those who had a small tumor (≤3 cm), respectively. There were no differences in CTC and TWIST (+) CTC counts according to tumor location, histologic grade, or TNM stage. TWIST (+) CTCs were significantly associated with histologic grade; a proportion of TWIST (+) CTCs ≥0.5 was significantly associated with advanced histologic grade. Other clinicopathologic characteristics such as sex, age, tumor location, tumor size, and TNM stages were not significantly associated with TWIST (+) CTCs. Conclusions: Our study showed that TWIST (+) CTCs were frequently detected in patients with ESCC, and a high proportion of TWIST (+) CTCs was associated with poor differentiation.

Numerical investigation of the sternoclavicular joint modeling technique for improving the surgical treatment of pectus excavatum.

It is now common to perform the Nuss procedure as a surgical treatment for pectus excavatum. As several types of detailed surgical methods exist as part of the Nuss procedure, studies are currently being conducted to verify their relative superiority via computerized biomechanical methods. However, no studies have considered the influence of sternoclavicular joints on the simulations of the Nuss procedure. Accordingly, this study aims to demonstrate the influence of these joints by comparing the clinical data with the finite element analysis data. Scenarios were set by classifying the movement of the joints based on the constraints of translation and rotation in the coordinate plane. The analyses were performed by applying the set scenarios to the constructed finite element model of a chest wall. The sternal displacement, Haller index, and equivalent stress were obtained from the analysis, and the data were compared with the data of the postoperative patient. When the translation of the anterior direction on the chest wall was constrained, the result obtained thereof was found to be similar to those obtained in the actual surgery. It is suggested that more accurate results can be obtained if the influence of the sternoclavicular joints is considered.

Renal Clearable Theranostic Nanoplatforms for Gastrointestinal Stromal Tumors.

Advances in molecular imaging modalities have accelerated the diagnosis and treatment of human diseases. However, tumors less than 1 cm in size still remain difficult to localize by conventional means because of the difficulty in specific targeting/delivery to the tumor site. Furthermore, high nonspecific uptake in the major organs and persistent background retention results in low tumor-to-background ratio. The targeting and therapy of gastrointestinal stromal tumors (GIST) using nonsticky and renal clearable theranostic nanoparticles (a.k.a. H-Dots) are demonstrated. H-Dots not only target GIST for image-guided surgery, but also tailor the fate of anticancer drugs such as imatinib (IM) to the tumor site resulting in efficient treatment of unresectable GIST. In addition, H-Dots can monitor targetability, pharmacokinetics, and drug delivery, while also showing therapeutic efficacy in GIST-bearing xenograft mice following surgical resection. More importantly, IM loaded H-Dots exhibit lower uptake into the immune system, improved tumor selectivity, and increased tumor suppression compared to free IM, which accumulates in the spleen/liver. Precisely designed H-Dots can be used as a promising theranostic nanoplatform that can potentially reduce the side effects of conventional chemotherapies.

The prognostic significance of tumor-infiltrating lymphocytes assessment with hematoxylin and eosin sections in resected primary lung adenocarcinoma.

The prognostic significance of tumor-infiltrating lymphocytes has been determined in cancers of the lung, colon and breast, though there is no standardized method for using this prognostic indicator for lung cancer. We applied a modified version of the method proposed by the International Immuno-Oncology Biomarkers Working Group to primary lung adenocarcinoma, which uses histologic findings of hematoxylin and eosin sections. The study included a total cohort of 146 lung adenocarcinoma patients who underwent lobectomy with lymph node dissection at two hospitals between 2008 and 2012. The full-face sections of hematoxylin and eosin-stained slides were reviewed, and we evaluated the level of tumor-infiltrating lymphocytes as a percentage of the area occupied out of the total intra-tumoral stromal area. Histopathologic factors include histologic grade, necrosis, extracellular mucin, lymphovascular invasion, lymph node metastasis, level of tumor infiltrating lymphocytes, tertiary lymphoid structures around the tumor, and the presence of a germinal center in tertiary lymphoid structures. The high level of tumor-infiltrating lymphocytes was found to be significantly correlated with the histologic grade (p = 0.023), necrosis (p = 0.042), abundance of tertiary lymphoid structures(p<0.001) and presence of a germinal center in tertiary lymphoid structures (p = 0.004). A high level of tumor-infiltrating lymphocytes was associated with better progression-free survival (p = 0.011) as well as overall survival (p = 0.049). On multivariable analysis, high tumor-infiltrating lymphocyte levels were a good independent prognostic factor for progression-free survival (Hazard ratio: 0.389, 95% confidence interval: 0.161-0.941, p = 0.036). Histologic evaluation of tumor-infiltrating lymphocytes level in lung adenocarcinoma with H&E sections therefore has prognostic value in routine surgical pathology.