Proposal of New ypStage Grouping System for Esophageal Squamous Cell Carcinoma Patients who Underwent Neoadjuvant Chemoradiotherapy followed by Surgery.

OBJECTIVE: To propose a new ypTNM grouping system to address these limitations and improve prognostic relevance. SUMMARY BACKGROUND DATA: The current 8th edition of the American Joint Committee on Cancer (AJCC) ypStage system shows unsatisfactory prognostic relevance in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. METHODS: The study cohort included 501 ESCC patients who received nCRT followed by esophagectomy at the Samsung Medical Center in Korea between 1994 and 2018 (development cohort) and 422 patients treated at Asan Medical Center (validation cohort). Recursive partitioning with a tree-structured regression model was used to develop and validate a new ypStage grouping system. RESULTS: In the new ypStage grouping system, ypStage I includes ypT0N0 only; ypStage II includes ypTis-T2N0 or ypT0-T2N1; ypStage III includes ypT3N0-N1; and ypStage IV includes ypT4N0-N1 or ypTanyN2-3. This system adequately addressed the limitations of the existing AJCC classification system, including overlapping and reversal of survival rates. Moreover, the discrimination ability of the new system was higher than that of the existing system [concordance-index (C-index): 61.9%] in the development (C-index: 66.6%) and validation (C-index: 66.0%) cohorts. NRIe was 0.17 [95% confidence interval (CI): 0.09-0.26, P-<0.001) and 0.18 (95% CI: 0.10-0.27, P-<0.001)] in the development and validation cohorts, respectively. CONCLUSIONS: The current study proposes a clear revised version of the 8th edition of the AJCC ypStage grouping system that exhibits superior prognostic stratification in patients with ESCC treated with nCRT followed by esophagectomy.

Comparison of Long-Term Outcomes Between Minimally Invasive Pulmonary Resection With and Without Video-Assisted Mediastinoscopic Lymphadenectomy for Left-Sided Lung Cancer.

BACKGROUND: This study aimed to assess the long-term outcomes of video-assisted mediastinoscopic lymphadenectomy (VAMLA) combined with video-assisted thoracic surgery (VATS) for left-sided lung cancer pulmonary resection. PATIENTS AND METHODS: We retrospectively reviewed 1194 consecutive patients who underwent VATS anatomical resection for left-sided lung cancer between January 2007 and December 2016. Using propensity score-based inverse probability of treatment weighting (IPTW), perioperative outcomes and long-term survival outcomes were compared. RESULTS: Among 1194 patients, 295 (24.7%) underwent additional VAMLA (VATS + VAMLA group) and 899 patients (75.3%) underwent VATS only (VATS group). The proportion of patients with advanced N stage were higher in the VATS + VAMLA group (24.7%) than in the VATS group (18.3%). After IPTW adjustment, all baseline profiles between the two groups became similar. The long-term overall survival (OS) and recurrence-free survival (RFS) rates were similar between the VATS + VAMLA group and the VATS group (5-year OS, 77.8% versus 79.3%, p = 0.957; 5-year RFS, 69.6% versus 70.1%, p = 0.498). However, among patients with borderline pulmonary function (FEV1 ≤ 60% or DLCO ≤ 60%), the VATS + VAMLA group (n = 23) had a better prognosis than the VATS group (n = 36) (5-year OS, 67.4% versus 46.7%, respectively; p = 0.047; 5-year RFS, 74.6% versus 53.5%, respectively; p = 0.027). CONCLUSIONS: VAMLA might be a good complement to VATS for left-sided lung cancer, wherein optimal mediastinal lymph node dissection is not feasible under one-lung ventilation, such as when patients have borderline pulmonary function.

Predicting Postoperative Complications and Long-Term Survival After Lung Cancer Surgery Using Eurolung Risk Score.

BACKGROUND: This study aimed to assess the clinical relevance of the parsimonious Eurolung risk scoring system for predicting postoperative morbidity, mortality, and long-term survival in Korean patients with surgically resected non-small cell lung cancer. METHODS: This retrospective analysis used the data of patients who underwent anatomical resection for non-small cell lung cancer between 2004 and 2018 at a single institution. The parsimonious aggregate Eurolung score was calculated for each patient. The Cox regression model was used to determine the ability of the Eurolung scoring system for predicting long-term outcomes. RESULTS: Of the 7,278 patients in the study, cardiopulmonary complications and mortality occurred in 687 (9.4%) and 53 (0.7%) patients, respectively. The rate of cardiopulmonary complications and mortality gradually increased with the increase in the Eurolung risk scores (all P < 0.001). When risk scores were grouped into four categories, the Eurolung scoring system showed a stepwise deterioration of overall survival with the increase in risk scores, and this association was statistically significant (P < 0.001). Multivariate Cox analysis showed that the Eurolung scoring system, classified into four categories, was a significant prognostic factor of overall survival even after adjusting for covariates such as tumor histology and pathological stage (P < 0.001). CONCLUSION: Stratification based on the parsimonious Eurolung scoring system showed good discriminatory ability for predicting postoperative morbidity, mortality, and long-term survival in South Korean patients with surgically resected non-small cell lung cancer. This might help clinicians to provide a detailed prognosis and decide the appropriate treatment option for high-risk patients with non-small cell lung cancer.

Sublobar Resection in Stage IA Non-Small Cell Lung Cancer: Role of Preoperative CT Features in Predicting Pathologic Lymphovascular Invasion and Postoperative Recurrence.

BACKGROUND. Prognostic factors on preoperative CT in stage IA non-small cell lung cancer (NSCLC) may help select patients for sublobar resection or lobectomy. OBJECTIVE. The purpose of this study was to identify CT features predictive of pathologic lymphovascular invasion (LVI) in stage IA NSCLC and to evaluate the features' prognostic value in patients who undergo sublobar resection. METHODS. This retrospective study included 904 patients (mean age, 62.0 years; 453 men, 451 women) who underwent lobectomy (n = 574) or sublobar resection (n = 330) for stage IA NSCLC. Two thoracic radiologists independently evaluated findings on pre-operative chest CT and then resolved discrepancies. Recurrences were identified from medical record review. Multivariable logistic regression was used to identify independent predictors of pathologic LVI. Multivariable Cox proportional hazards models were used to identify prognostic features. Interreader agreement was assessed. RESULTS. Pathologic LVI was present in 10.2% (92/904) of patients. It was present only in solid-dominant part-solid nodules (PSNs) and solid nodules and only in nodules with a solid portion diameter over 10 mm. Among solid-dominant PSNs and solid nodules with a solid portion diameter over 10 mm, independent (p < .05) predictors of pathologic LVI were peritumoral interstitial thickening (odds ratio [OR], 13.22) and pleural contact (defined as pleural contact measuring over one-quarter of the circumference of the nodule's solid portion) (OR, 2.45). Also among such nodules, peritumoral interstitial thickening achieved 80.4% sensitivity, 76.7% specificity, and 77.4% accuracy; pleural contact achieved 35.9% sensitivity, 82.5% specificity, and 74.3% accuracy; and presence of either feature achieved 90.2% sensitivity, 64.3% specificity, and 68.9% accuracy for predicting pathologic LVI. In patients undergoing sublobar resection, after adjusting for T category and operative type, recurrence-free survival (RFS) was independently (p < .05) predicted by solid-dominant PSN or solid nodule with a solid portion diameter over 10 mm also showing peritumoral interstitial thickening (hazard ratio [HR], 5.37) or also showing either peritumoral interstitial thickening or pleural contact (HR, 6.05). The interreader agreement kappa values were 0.67 for peritumoral interstitial thickening and 0.77 for pleural contact. CONCLUSION. Pathologic LVI occurred only in solid-dominant PSNs and solid nodules with solid portion over 10 mm. Among such nodules, peritumoral interstitial thickening and pleural contact independently predicted pathologic LVI and RFS. CLINICAL IMPACT. CT features may help select patients with stage IA NSCLC for sublobar resection rather than more extensive surgery.

Surgical outcomes of pulmonary metastasectomy in hepatocellular carcinoma patients according to approach method: thoracoscopic versus open approach.

BACKGROUND: The role of surgical intervention as a treatment for pulmonary metastasis (PM) from hepatocellular carcinoma (HCC) has not been established. In this study, we investigated the clinical outcomes of pulmonary metastasectomy. Using propensity score matching (PSM) analysis, we compared the results according to the surgical approach: video-assisted thoracic surgery (VATS) versus the open method. METHODS: A total of 134 patients (115 men) underwent pulmonary metastasectomy for isolated PM of HCC between January 1998 and December 2010 at Seoul Asan Medical Center. Of these, 84 underwent VATS (VATS group) and 50 underwent thoracotomy or sternotomy (open group). PSM analysis between the groups was used to match them based on the baseline characteristics of the patients. RESULTS: During the median follow-up period of 33.4 months (range, 1.8-112.0), 113 patients (84.3%) experienced recurrence, and 100 patients (74.6%) died of disease progression. There were no overall survival rate, disease-free survival rate, and pulmonary-specific disease-free survival rate differences between the VATS and the open groups (p = 0.521, 0.702, and 0.668, respectively). Multivariate analysis revealed local recurrence of HCC, history of liver cirrhosis, and preoperative alpha-fetoprotein level as independent prognostic factors for overall survival (hazard ratio, 1.729/2.495/2.632, 95% confidence interval 1.142-2.619/1.571-3.963/1.554-4.456; p = 0.010/< 0.001/< 0.001, respectively). CONCLUSIONS: Metastasectomy can be considered a potential alternative for selected patients. VATS metastasectomy had outcomes comparable to those of open metastasectomy.

A nomogram for predicting recurrence after complete resection for thymic epithelial tumors based on the TNM classification: A multi-institutional retrospective analysis.

OBJECTIVES: This study aimed to compare the predictive ability between the Masaoka-Koga (M-K) staging system and the 8th TNM staging system for the recurrence of thymic epithelial tumors (TETs). In addition, a nomogram was developed on the basis of the proposed TNM classification to predict individual recurrence rate. METHODS: A retrospective study was performed on 445 patients who underwent complete resection (R0) of TETs between January 2000 and February 2013. Concordance index (C-index) was used as a statistical indicator to quantify the prediction power of the prediction models. RESULTS: In multivariate analysis, tumor stage and WHO classification were independent recurrence factors in a predictive model on the basis of M-K and TNM stage. The TNM model showed higher C-index than the M-K model (0.837 vs 0.817). The nomogram, on the basis of the TNM model, revealed a highly predictive performance, with a bootstrap-corrected C-index of 0.85 (95% CI, 0.76 to 0.93). CONCLUSIONS: A predictive model based on the 8th TNM stage was slightly better than that based on M-K stage with respect to recurrence after R0 of TETs. The proposed nomogram could be applied to estimate the individual recurrence rate and make decisions for proper surveillance.

Recent Trends in Demographics, Surgery, and Prognosis of Patients with Surgically Resected Lung Cancer in a Single Institution from Korea.

BACKGROUND: Over the past few decades, demographics information has changed significantly in patients with surgically resected lung cancer. Herein, we evaluated the recent trends in demographics, surgery, and prognosis of lung cancer surgery in Korea. METHODS: Patients with surgically resected primary lung cancer from 2002 to 2016 were retrospectively analyzed. Multivariable Cox regression analysis was conducted to identify prognostic factors for overall survival. The annual percent change (APC) and statistical significance were calculated using the Joinpoint software. RESULTS: A total of 7,495 patients were enrolled. Over the study period, the number of lung cancer surgeries continued to increase (P < 0.05). The proportion of women to total subjects has also increased (P < 0.05). The proportion of elderly patients (≥ 70 years) as well as those with tumors measuring 1-2 cm and 2-3 cm significantly increased in both genders (all P < 0.05). The proportion of patients with adenocarcinoma, video-assisted thoracic surgery, sublobar resection, and pathological stage I significantly increased (P < 0.05). The 5-year overall survival rate of lung cancer surgery increased from 61.1% in 2002-2006 to 72.1% in 2012-2016 (P < 0.001). The operative period was a significant prognostic factor in multivariable Cox analysis (P < 0.001). CONCLUSION: The mean age of patients with lung cancer surgery increased gradually, whereas tumor size reduced. Prognosis of lung cancer surgery improved with recent increases in the frequency of adenocarcinoma, video-assisted thoracic surgery, sublobar resection, and pathological stage I. The operation period itself was also an independent prognostic factor for overall survival.

Surgical Outcomes after Pulmonary Resection for Non-Small Cell Lung Cancer with Localized Pleural Seeding First Detected during Surgery.

OBJECTIVES: Curative resection is not indicated for non-small cell lung cancer (NSCLC) with pleural seeding, which is classified as stage IV (M1a) disease. However, some patients with a presumably resectable main tumor are diagnosed with localized pleural seeding during surgery. METHODS: A retrospective analysis was performed of 3,975 patients who underwent surgery for NSCLC from 2000 to 2011. Among these cases, 78 (2.0%) patients had unexpected pleural seeding detected during surgery. Exploration with pleural biopsy was performed in 42 of these patients (exploration-only group) and pulmonary resection, including for the main tumor, was performed in 36 cases (resection group; sublobar resection in 12, lobectomy in 21, and pneumonectomy in 3 patients). Survival and cancer progression rates were estimated using the Kaplan-Meier method. Cox proportional hazard regression was used to evaluate prognostic factors associated with survival. RESULTS: Adenocarcinoma was the predominant histological type in both the exploration and resection groups (88.1 and 86.1%, respectively). Epidermal growth factor receptor expression was detected in 22 (52.4%) patients of the exploration group and 21 (58.3%) patients of the resection group. Baseline characteristics including age, sex, comorbidity, pulmonary function, and clinical T/N status were not significantly different between the two groups. There were no postoperative deaths in either group but postoperative complications occurred in two (4.8%) patients of the exploration group and three (8.3%) patients of the resection group. The overall 3- and 5-year survival rates in the exploration group were 41.1 and 15.2%, respectively, with a median survival time (MST) of 33 months, whereas they were 66.7 and 42.7%, respectively, in the resection group, with a 52-month MST (p = 0.012). Local and regional progression-free rates were significantly different (p < 0.001 and p = 0.029, respectively) between groups, whereas no difference was seen in the distant metastasis rates (p = 0.957). In multivariate survival analysis, surgical resection was the only significant prognostic factor (p = 0.01). CONCLUSIONS: Pulmonary resection including the main tumor, regardless of resection extent, may increase long-term survival for NSCLC patients with localized pleural seeding first detected during surgery, without a significant increase in hospital mortality or morbidity.

Clinical impact of postoperative radiotherapy in pIII-N2 non-small cell lung cancer after complete resection followed by adjuvant chemotherapy: a systematic review and meta-analysis.

Background: Theoretically, postoperative radiotherapy (PORT) could reduce the risk of local recurrence and further improve survival outcomes. This study aimed to evaluate the clinical impact of PORT on patients with pIII-N2 non-small cell lung cancer (NSCLC) after complete resection followed by adjuvant chemotherapy. Methods: A systematic literature search was performed in November 2022 to identify randomized controlled trials (RCTs) that compare PORT with observation in patients with pIII-N2 NSCLC using PubMed, Embase, and the Cochrane Central Register of Controlled Trials. This meta-analysis is in accordance with the recommendations of the PRISMA statement. The main outcomes were overall survival (OS), disease-free survival (DFS), and local recurrence rates, which were compared using hazard ratios (HRs). Results: Five RCTs involving 1,138 patients were included: 572 patients in the PORT group and 566 patients in the observation group. The methodological quality of the five RCTs was high. Pooled analysis revealed that PORT decreased local recurrence rate [odds ratio =0.53, 95% confidence interval (CI): 0.40-0.70]. However, PORT did not improve median DFS (HR =0.93, 95% CI: 0.80-1.08) and OS (HR =0.94, 95% CI: 0.78-1.14). Conclusions: Compared to adjuvant chemotherapy alone, additional PORT was significantly associated with a reduced local recurrence rate. However, neither DFS nor OS benefited from PORT in patients with pIII-N2 NSCLC who had undergone complete resection.

Long-Term Outcomes of Colon Conduits in Surgery for Primary Esophageal Cancer: A Propensity Score-Matched Comparison to Gastric Conduits.

Background: In the treatment of esophageal cancer, a gastric conduit is typically the first choice. However, when the stomach is not a viable option, the usual alternative is a colon conduit. This study compared the long-term surgical outcomes of gastric and colon conduits over the same interval and aimed to identify factors influencing the prognosis. Methods: A retrospective review was conducted of patients who underwent esophagectomy followed by reconstruction for primary esophageal cancer between January 2006 and December 2020. Results: The study included 1,545 patients, with a gastric conduit used for 1,429 (92.5%) and a colon conduit for 116 (7.5%). Using propensity-matched analysis, 116 patients were selected from each group for comparison. No significant difference was observed in long-term survival between the gastric and colon conduit groups, irrespective of anastomosis level and pathological stage. A higher proportion of patients in the colon conduit group experienced postoperative complications compared to the gastric conduit group (57.8% vs. 25%, p<0.001). Multivariable analysis revealed that age over 65 years, body mass index below 22.0 kg/m2, neoadjuvant therapy, postoperative anastomotic leakage, and renal failure were risk factors for overall survival in patients with a colon conduit. Regarding conduit-related complications, cervical anastomosis was the only significant risk factor among those with a colon conduit. Conclusion: Despite the association of colon conduits with high morbidity rates relative to gastric conduits, the long-term outcomes of colon conduits were acceptable. More consideration should be given perioperatively to the use of a colon conduit, particularly in cases involving cervical anastomosis.

Validation Study for the N Descriptor of the Newly Proposed Ninth Edition of the TNM Staging System Proposed by the International Association for the Study of Lung Cancer.

INTRODUCTION: The aim of this study was to validate the discriminatory ability and clinical utility of the N descriptor of the newly proposed ninth edition of the TNM staging system for lung cancer in a large independent cohort. METHODS: We retrospectively analyzed patients who underwent curative surgery for NSCLC between January 2004 and December 2019. The N descriptor of patients included in this study was retrospectively reclassified based on the ninth edition of the TNM classification. Survival analysis was performed using the log-rank test and Cox proportional hazard model to compare adjacent N categories. RESULTS: A total of 6649 patients were included in this study. The median follow-up period was 54 months. According to the newly proposed ninth edition N classification, 5573 patients (83.8%), 639 patients (9.6%), 268 patients (4.0%), and 169 patients (2.5%) were classified into the clinical N0, N1, N2a, and N2b categories and 4957 patients (74.6%), 744 patients (11.2%), 567 patients (8.5%), and 381 patients (5.7%) were classified into the pathologic N0, N1, N2a, and N2b categories, respectively. The prognostic differences between all adjacent clinical and pathologic N categories were highly significant in terms of both overall survival and recurrence-free survival. CONCLUSIONS: We validated the clinical utility of the newly proposed ninth edition N classification for both clinical and pathologic stages in NSCLC. The new N classification revealed clear prognostic separation between all categories (N0, N1, N2a, and N2b) in terms of both overall survival and recurrence-free survival.

Adjuvant surgical resection for nontuberculous mycobacterial pulmonary disease: Effectiveness and complications.

BACKGROUND: Standard antibiotic treatment for nontuberculous mycobacteria pulmonary disease (NTMPD) has unsatisfactory success rates. Pulmonary resection is considered adjunctive therapy for patients with refractory disease or severe complications, but surgical indications and extent of resection remain unclear. We present surgical treatment outcomes for NTMPD and analyzes risk factors for unfavorable outcomes. METHODS: We conducted a retrospective investigation of medical records for patients diagnosed with NTMPD who underwent surgical treatment at Asan Medical Center between 2007 and 2021. We analyzed clinical data including microbiological and surgical outcomes. RESULTS: A total of 71 NTMPD patients underwent thoracic surgery. Negative conversion of acid-fast bacillus (AFB) culture following pulmonary resection was observed in 51 (73.9%) patients. In terms of long-term outcomes, negative conversion was sustained in 38 cases (55.1%). Mortality occurred in 7 patients who underwent pulmonary resections for NTMPD. Statistically significant associations with factors for recurrence or non-negative conversion of AFB culture were found in older age (odds ratio [OR] =1.093, 95% confidence interval [CI]: 1.029-1.161, P = 0.004), male sex (OR = 0.251, 95% CI: 0.071-0.892, P = 0.033), and extensive NTMPD lesions involving three lobes or more (OR = 5.362, 95% CI: 1.315-21.857, P = 0.019). Interstitial lung disease (OR = 13.111, 95% CI: 1.554-110.585, P = 0.018) and pneumonectomy (OR = 19.667, 95% CI: 2.017-191.797, P = 0.018) were statistically significant risk factors for postoperative mortality. CONCLUSION: Pulmonary resection can be an effective adjuvant treatment option for NTMPD patients, with post-operative antibiotic treatment as the primary treatment. Careful patient selection is crucial, considering the associated risk factors and resectability due to complications and recurrence.

Distinguishing thymic cysts from low-risk thymomas via [18F]FDG PET/CT.

BACKGROUND: Thymic cysts are a rare benign disease that needs to be distinguished from low-risk thymoma. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a non-invasive imaging technique used in the differential diagnosis of thymic epithelial tumours, but its usefulness for thymic cysts remains unclear. Our study evaluated the utility of visual findings and quantitative parameters of [18F]FDG PET/CT for differentiating between thymic cysts and low-risk thymomas. METHODS: Patients who underwent preoperative [18F]FDG PET/CT followed by thymectomy for a thymic mass were retrospectively analyzed. The visual [18F]FDG PET/CT findings evaluated were PET visual grade, PET central metabolic defect, and CT shape. The quantitative [18F]FDG PET/CT parameters evaluated were PET maximum standardized uptake value (SUVmax), CT diameter (cm), and CT attenuation in Hounsfield units (HU). Findings and parameters for differentiating thymic cysts from low-risk thymomas were assessed using Pearson's chi-square test, the Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. RESULTS: Seventy patients (18 thymic cysts and 52 low-risk thymomas) were finally included. Visual findings of PET visual grade (P < 0.001) and PET central metabolic defect (P < 0.001) showed significant differences between thymic cysts and low-risk thymomas, but CT shape did not. Among the quantitative parameters, PET SUVmax (P < 0.001), CT diameter (P < 0.001), and CT HU (P = 0.004) showed significant differences. In ROC analysis, PET SUVmax demonstrated the highest area under the curve (AUC) of 0.996 (P < 0.001), with a cut-off of equal to or less than 2.1 having a sensitivity of 100.0% and specificity of 94.2%. The AUC of PET SUVmax was significantly larger than that of CT diameter (P = 0.009) and CT HU (P = 0.004). CONCLUSIONS: Among the [18F]FDG PET/CT parameters examined, low FDG uptake (SUVmax ≤ 2.1, equal to or less than the mediastinum) is a strong diagnostic marker for a thymic cyst. PET visual grade and central metabolic defect are easily accessible findings.

Abrupt Bulla Formation by Visceral Pleural Detachment after Pulmonary Lobectomy: A Case Report.

Pulmonary bullae usually grow slowly and have thin walls. However, we have observed 2 cases of abrupt bulla formation immediately after lobectomy and during surgery. The pathologic findings of what can be called visceral pleural detachment are quite distinctive: these bullae had a broad base connected to the lung, and their walls were thick, including the full extent of visceral pleural and peripheral alveolar tissues, which suggests that the visceral pleura were detached from the distal alveoli. High transpleural pressure might be the key factor in the pathogenesis of this type of bulla, unlike previously known types of bullous lung disease.

Early Outcomes of COVID-19 Lung Transplantation Recipients in Korea: A Single-Center Study.

Background: Coronavirus disease 2019 (COVID-19) has been found to cause life-threatening respiratory failure, which can progress to irreversible lung damage. Lung transplantation can be a life-saving treatment in patients with terminal lung disease (e.g., acute respiratory distress syndrome caused by infection). This study aimed to present the clinical course and results after initial lung transplantation in patients with severe COVID-19 who did not recover even with optimal medical care. Methods: From August 2019 to February 2022, this study enrolled 10 patients with COVID-19 (5 men; median age, 55.7 years) who underwent lung transplantation at a single center in Korea. All patients' characteristics, clinical pathway, overall survival, complications, and operative data were collected and analyzed. Results: Veno-venous extracorporeal membrane oxygenation or an oxygenator in a right ventricular assist device circuit was applied to 90% of the patients, and the median length of extracorporeal life support before operation was 48.5 days. There were no cases of mortality after a median follow-up of 372.8 days (interquartile range, 262.25-489 days). The major complications included the requirement for postoperative extracorporeal membrane oxygenation support in 2 cases (20%), re-transplantation in 1 case (10%), and re-exploration due to bleeding in 2 cases (20%). During the follow-up period, 3 out of 10 patients died. Conclusion: Excellent early outcomes were observed for patients who underwent lung transplantation. Thus, lung transplantation can be an effective and feasible treatment for patients with end-stage lung disease caused by COVID-19.

Prognostic significance of extranodal extension in patients with pathologic N1 non-small cell lung cancer undergoing complete resection.

Background: The prognostic significance of extranodal extension (ENE) remains unclear in patients with pathologic N1 (pN1) non-small-cell lung cancer (NSCLC) undergoing surgery. We evaluated the prognostic impact of ENE in patients with pN1 NSCLC. Methods: From 2004 to 2018, we retrospectively analyzed the data of 862 patients with pN1 NSCLC who underwent lobectomy and more (lobectomy, bilobectomy, pneumonectomy, sleeve lobectomy). According to their resection status and the presence of ENE, patients were classified into R0 without ENE (pure R0) (n=645), R0 with ENE (R0-ENE) (n=130), and incomplete resection (R1/R2) groups (n=87). The primary and secondary endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS), respectively. Results: The prognosis of the R0-ENE group was significantly worse than the pure R0 group for both OS (5-year rate: 51.6% vs. 65.4%, P=0.008) and RFS (44.4% vs. 53.0%, P=0.04). According to the recurrence pattern, a difference of RFS was found only for distant metastasis (55.2% vs. 65.0%, P=0.02). The multivariable Cox analysis revealed that the presence of ENE was a negative prognostic factor in patients who did not undergo adjuvant chemotherapy [hazard ratio (HR) =1.58; 95% confidence interval (CI): 1.06-2.36; P=0.03], but it was not in those with adjuvant chemotherapy (HR =1.20; 95% CI: 0.80-1.81; P=0.38). Conclusions: For patients with pN1 NSCLC, the presence of ENE was a negative prognostic factor for both OS and RFS, regardless of resection status. The negative prognostic effect of ENE was significantly associated with an increase in distant metastasis and was not observed in patients who underwent adjuvant chemotherapy.

Clinical impact of histologic type on survival and recurrence in patients with surgically resected stage II and III non-small cell lung cancer.

OBJECTIVES: This study aimed to investigate the clinical impact of histologic type on the survival and recurrence outcomes of patients with stage II and III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A total of 2155 consecutive adult patients who underwent complete resection of stage II and III NSCLC between 2008 and 2018 were enrolled. The primary endpoints were freedom from recurrence (FFR) and overall survival (OS). The secondary endpoint was the time to lung cancer or non-lung cancer death. RESULTS: Of the 2155 patients, 1436 (66.6 %) had adenocarcinoma (ADC) and 719 (33.4 %) had squamous cell carcinoma (SqCC). Patients with SqCC had better FFR than those with ADC (stage II, p < 0.001; stage III, p < 0.001). Although patients with ADC showed a slightly better OS until 5 years than those with SqCC, the difference was insignificant (stage II, p = 0.292; stage III, p = 0.196). Patients with SqCC had higher rates of non-lung cancer death than patients with ADC (stage II, p < 0.001; stage III, p = 0.039). The time from lung cancer recurrence to death was shorter in patients with SqCC than in those with ADC (stage II, median 13 vs 37 months, p < 0.001; stage III, median 11 vs 26 months, p < 0.001). CONCLUSIONS: In stage II and III NSCLC, ADC had a higher risk of recurrence than SqCC, with no difference in OS. These results were related to significant differences in non-lung cancer mortality and recurrence-to-death time between the two histologic types.

What is the benefit of preserving the superior segment in anatomical thoracoscopic resections of the lower lobe?

Background: The beneficial effect of preserved superior segment (S6) after common basal segmentectomy remains unknown. We aimed to evaluate the effect of preserved superior segment on lung volume and function. Methods: Among 671 segmentectomies and 2,249 lobectomies for clinical stage IA lung cancer between 2004 and 2020, 48 patients who received thoracoscopic common basal segmentectomy were included and compared with 96 patients who received thoracoscopic lower lobectomy after propensity score matching. The variables analyzed were age, sex, comorbidity, smoking history, preoperative forced expiratory volume in one second (FEV1), clinical T stage, histology, and tumor location. Lung volume was assessed using a three-dimensional (3D) computed tomography (CT)-based volumetric method. Results: There were no significant differences between common basal segmentectomy (segmentectomy group) and lower lobectomy (lobectomy group) (4,183.8±1,114.9 versus 3,850.7±1,132.1 mL; P=0.10) in terms of preoperative CT-measured total lung volume. At the immediate postoperative median follow-up period (6.4 months), the reduced percentage of CT-measured total lung volume in the segmentectomy group was significantly larger than that in the lobectomy group (-16.2% versus -6.5%; P=0.004). The percentage of CT-measured contralateral lung volume expansion in the segmentectomy group was significantly smaller than that in the lobectomy group (-0.7% versus +8.9%; P=0.006). At the last median follow-up period (43.1 months), the reduced percentage of CT-measured total lung volume in the segmentectomy group remained larger than that in the lobectomy group (-13.0% versus -3.0%; P=0.01). The reduced percentage of postoperative FEV1 in the segmentectomy group did not differ from that in the lobectomy group (-9.9% versus -11.5%, P=0.63). Conclusions: Preserving the superior segment might not provide beneficial effect on the preservation of postoperative lung volume and function after common basal segmentectomy compared with lower lobectomy.

Surgical outcomes of 500 robot-assisted minimally invasive esophagectomies for esophageal carcinoma.

Background: In 2003, robot-assisted minimally invasive esophagectomy (RAMIE) was first reported to overcome the technical limitations of minimally invasive esophagectomy. RAMIE requires repeated modifications to set up the robotic system, and sufficient experience is required to gain technical proficiency. This study aimed to identify the learning periods and the outcomes of RAMIE for esophageal carcinoma. Methods: We retrospectively reviewed 500 consecutive RAMIE cases for esophageal cancer from December 2008 to February 2021. The learning curve for RAMIE was identified using cumulative sum analysis. Results: In a total of 500 RAMIE patients, the Ivor Lewis and McKeown operation were performed in 267 patients (53.4%) and 192 patients (38.4%), respectively. We classified learning periods into the learning phase (first 50 cases), the developing phase (51-150 case), and the stable phase (151-500 case). The rates of vocal cord palsy (42.0% vs. 28.4%) and anastomotic leakage (10.0% vs. 6.4%) were reduced after the learning phase. The mean total operative time (420 vs. 373 min), the mean length of stay (21.6 vs. 16.7 days), and the rate of anastomotic stricture (27.0% vs. 12.4%) were significantly reduced after reaching stable phase. In the stable phase, the proportion of the Ivor Lewis operation (26.0% vs. 67.1%), neoadjuvant chemoradiation therapy (14.0% vs. 25.7%), and bilateral cervical node dissection cases (12.0% vs. 22.0%) were significantly increased. Conclusions: Fifty procedures might be needed to achieve early proficiency, and extensive experience of more than 150 procedures is needed for quality stabilization.

E3 ligase SOCS3 regulates NOD2 expression by ubiquitin proteasome system in lung cancer progression.

PURPOSE: Despite lung cancer is one of the leading causes of cancer-related deaths, it remains hard to discover effective diagnostic and therapeutic approaches. Moreover, the five-year survival rate is relatively lower than other tumors. So urgent needs for finding a new theranostic target to treat lung cancer effectively. This study aims to present SOCS3 and NOD2 proteins as novel targets for diagnosis and therapy. METHODS: We first confirmed SOCS3 expression level in patients' tissues. Then, we applied knockdown and overexpression of SOCS3 on lung cancer cell lines and performed proliferation, migration, and invasion assay. After that, we found NOD2 is a target of SOCS3 and introduced overexpression of NOD2 to A549 for verifying reduced tumorigenicity of lung cancer cells. RESULTS: We identified protein expression level of SOCS3 was frequently higher in tumor tissues than adjacent normal tissues. Truly, overexpression of SOCS3 promoted proliferation, migration, and invasion capacity of lung cancer cells. We found that SOCS3 interacts with NOD2 and SOCS3 ubiquitinates NOD2 directly. Furthermore, lung cancer tissues with higher SOCS3 expression showed lower NOD2 expression. We confirmed overexpression of NOD2 leads to suppressed tumorigenicity of lung cancer cells, and these effects occurred through MAPK pathway. CONCLUSION: Collectively, our work reveals novel roles of SOCS3 in lung tumorigenesis and proposes SOCS3 as a promising biomarker candidate for therapeutic and diagnostic target for lung cancer.