Prognostic Implications of Selective Dissection of Left Lower Paratracheal Lymph Nodes in Patients with Left-Sided Non-Small Cell Lung Cancer.

Background: This study aimed to examine the clinical implications of selective station 4L lymph node dissection (S4L-LND) on survival in non-small cell lung cancer (NSCLC) and to evaluate its potential advantages. Methods: We enrolled patients with primary left-sided NSCLC who underwent upfront video-assisted thoracoscopic surgery with R0 resection including lobectomy and segmentectomy, with or without S4L-LND, at our institution between January 2007 and December 2021. Following 1:1 propensity score matching (PSM), we compared overall survival (OS) and recurrence-free survival (RFS) between patients with and without S4L-LND. Results: The study included 2,601 patients, of whom 1,126 underwent S4L-LND and 1,475 did not. PSM yielded 1,036 patient pairs. Among those who underwent S4L-LND, 87 (7.7%) exhibited S4L-LN involvement. Neither OS (p=0.12) nor RFS (p=0.24) differed significantly between matched patients with and without S4L-LND. In patients with S4L-LN involvement, metastases were more common in the left upper lobe (LUL) than in the left lower lobe (LLL) (3.6% vs. 2.0%, p=0.061). Metastasis became significantly more frequent with more advanced clinical N (cN) stage (cN0, 2.3%; cN1, 5.8%; cN2, 32.6%; p<0.001). Multivariate logistic regression analysis revealed that cN stage and tumor location were independently associated with S4L-LN involvement (p<0.001 for both). Conclusion: OS and RFS did not differ significantly between matched patients with and without S4L-LND. Among participants with S4L-LN involvement, metastases occurred more frequently in the LUL than the LLL, and their incidence increased significantly with more advanced cN stage. Thus, patients with LUL or advanced cN lung cancers may benefit from S4L-LND.

Risk prediction of multiple-station N2 metastasis in patients with upfront surgery for clinical single-station N2 non-small cell lung cancer.

To investigate long-term outcomes and develop a risk model for pathological multi-station N2 (pN2b) in patients who underwent upfront surgery for clinical single-station N2 (cN2a) non-small cell lung cancer (NSCLC). From 2006 to 2018, 547 patients who had upfront surgery for suspected cN2a NSCLC underwent analysis. A risk model for predicting pN2b metastasis was developed using preoperative clinical variables via multivariable logistic analysis. Among 547 clinical cN2a NSCLC patients, 118 (21.6%), 58 (10.6%), and 371 (67.8%) had pN0, pN1, and pN2. Among 371 pN2 NSCLC patients, 77 (20.8%), 165 (44.5%), and 129 (34.7%) had pN2a1, pN2a2, and pN2b. The 5-year overall survival rates for pN2a1 and pN2a2 were significantly higher than for pN2b (p = 0.041). Histologic type (p < 0.001), age ≤ 50 years (p < 0.001), preoperatively confirmed N2 metastasis (p < 0.001), and clinical stage IIIB (vs. IIIA) (p = 0.003) were independent risk factors for pN2b metastasis. The risk scoring system based on this model demonstrated good discriminant ability for pN2b disease (area under receiver operating characteristic: 0.779). In cN2a NSCLC patients, those with multiple N2 metastases indicate worse prognosis than those with a single N2 metastasis. Our risk scoring system effectively predicts pN2b in these patients.

Surgical prognosis of lung invasive mucinous and non-mucinous adenocarcinoma: Propensity score matched analysis.

OBJECTIVES: Invasive mucinous adenocarcinoma exhibits distinct prognostic outcomes compared to nonmucinous adenocarcinoma. This study investigated and compared the clinical outcomes and prognostic factors of invasive mucinous and nonmucinous adenocarcinoma patients. METHODS: This retrospective study included patients who underwent curative surgery for adenocarcinoma between 2011 and 2021. Patient characteristics were balanced using propensity score matching. Cumulative incidence was analysed to evaluate cancer recurrence incidence, and the Kaplan-Meier method was used to calculate overall survival for each group. RESULTS: A total of 6,101 patients were included. After matching, the nonmucinous group and mucinous groups comprised 798 and 408 patients, respectively. The patients in the mucinous group had a lower recurrence incidence than those in the nonmucinous group (p = 0.014). The recurrence incidence in the mucinous group was between those of grades 1 (p = 0.011) and 2 (p = 0.012) and the overall survival rates were comparable to those of grades 2 (p = 0.6) and 3 (p = 0.2). Multivariable analysis revealed that the maximal standardised uptake value (HR: 1.13, p = 0.11) and progressed pathological stages (pStage II, HR: 3.9, p = 0.028; pStage III, HR: 8.33, p = 0.038) served as adverse prognostic factors for the mucinous group. CONCLUSIONS: Patients with mucinous adenocarcinoma demonstrated lower recurrence incidence and similar overall survival rates compared to those with nonmucinous adenocarcinoma. The recurrence incidence of mucinous adenocarcinoma was between those of International Association for the Study of Lung Cancer grades 1 and 2, with the overall survival rates comparable to those of grades 2 and 3.

TIPRL Regulates Stemness and Survival in Lung Cancer Stem Cells through CaMKK2-CaMK4-CREB Feedback Loop Activation.

Frequent recurrence and metastasis caused by cancer stem cells (CSCs) are major challenges in lung cancer treatment. Therefore, identifying and characterizing specific CSC targets are crucial for the success of prospective targeted therapies. In this study, it is found that upregulated TOR Signaling Pathway Regulator-Like (TIPRL) in lung CSCs causes sustained activation of the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) signaling pathway by binding to CaMKK2, thereby maintaining stemness and survival. CaMKK2-mediated activation of CaM kinase 4 (CaMK4) leads to phosphorylation of cAMP response element-binding protein (CREB) at Ser129 and Ser133, which is necessary for its maximum activation and the downstream constitutive expression of its target genes (Bcl2 and HMG20A). TIPRL depletion sensitizes lung CSCs to afatinib-induced cell death and reduces distal metastasis of lung cancer in vivo. It is determined that CREB activates the transcription of TIPRL in lung CSCs. The positive feedback loop consisting of CREB and TIPRL induces the sustained activation of the CaMKK2-CaMK4-CREB axis as a driving force and upregulates the expression of stemness- and survival-related genes, promoting tumorigenesis in patients with lung cancer. Thus, TIPRL and the CaMKK2 signaling axis may be promising targets for overcoming drug resistance and reducing metastasis in lung cancer.

Differences in the Prognostic Impact between Single-zone and Multi-zone N2 Node Metastasis in Patients with Station-based Multiple N2 Non-Small Cell Lung Cancer.

Purpose: The International Association for the Study of Lung Cancer suggest further subdivision of pathologic N (pN) stage in non-small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups. Materials and Methods: This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal. Results: Among 996 eligible patients, 211 (21.2%), 394 (39.6%) and 391 (39.4) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT stage, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio 0.67, 95% confidence interval 0.49-0.90, p<0.009) and was comparable to that of N2a2 disease (1.12, 0.83-1.49, p=0.46). Conclusion: Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.

Recurrence Dynamics of Pathological N2 Non-small Cell Lung Cancer Based on IASLC Residual Tumor Descriptor.

Purpose: This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC). Materials and Methods: From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared. Results: In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96-1.46) and 1.58 (1.31-1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease. Conclusion: The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.

Management for recurrent laryngeal nerve paralysis following oesophagectomy for oesophageal cancer: thoracic surgeon perspective.

Background: Recurrent laryngeal nerve (RLN) paralysis following oesophagectomy may increase postoperative morbidity and mortality. However, clinical studies on this complication are uncommon. The aim of this study was to report the clinical course of patients with RLN paralysis following oesophageal cancer surgery. Methods: We retrospectively examined patients who underwent oesophagectomy for oesophageal carcinoma at Asan Medical Center between January 2013 and November 2018. We enrolled 189 patients with RLN paralysis confirmed using laryngoscopy in this study. Results: Of the 189 patients, 22 patients had bilateral RLN paralysis, and 167 patients had unilateral RLN paralysis. Every patient received oral feeding rehabilitation, and 145 (76.7%) patients received hyaluronic acid injection laryngoplasty. During the postoperative period, 21 (11.1%) patients experienced aspiration pneumonia and recovered. One patient died of severe pulmonary complication. Twenty-four (12.7%) patients underwent feeding jejunotomy, while 11 (5.9%) patients underwent tracheostomy. In total, 173 (91.5%) patients were discharged with oral nutrition, and the median time to begin oral diet was 9 days. Statistical analysis using logistic regression revealed that only the advanced T stage affected nerve recovery. More than 50% of the patients showed nerve recovery within 6 months, and 165 (87.9%) patients fully or partially recovered during the observation period. Conclusions: RLN paralysis following oesophagectomy in oesophageal carcinoma is a predictable complication. In patients with RLN paralysis, early detection and intervention through multidisciplinary cooperation are required, and the incidence of postoperative complications can be reduced by implementing the appropriate management.

Prognostic Value of Preoperative N Subcategories in Patients with Stage IIIA N2 Non-Small Cell Lung Cancer.

Purpose To evaluate the preoperative risk factors in patients with pathologic IIIA N2 non-small cell lung cancer (NSCLC) who underwent upfront surgery and to evaluate the prognostic value of new N subcategories. Materials and Methods Patients with pathologic stage IIIA N2 NSCLC who underwent upfront surgery in a single tertiary center from January 2015 to April 2021 were retrospectively reviewed. Each patient's clinical N (cN) was assigned to one of six subcategories (cN0, cN1a, cN1b, cN2a1, cN2a2, and cN2b) based on recently proposed N descriptors. Cox regression analysis was used to identify the significant prognostic factors for recurrence-free survival (RFS) and overall survival (OS). Results A total of 366 patients (mean age ± SD, 62.0 years ± 10.1; 202 male patients [55%]) were analyzed. The recurrence rate was 55% (203 of 366 patients) over a median follow-up of 37.3 months. Multivariable analysis demonstrated that cN (hazard ratios [HRs] for cN1 and cN2b compared with cN0, 1.66 [95% CI: 1.11, 2.48] and 2.11 [95% CI: 1.32, 3.38], respectively) and maximum lymph node (LN) size at N1 station (≥12 mm; HR, 1.62 [95% CI: 1.15, 2.29]), in addition to clinical T category (HR, 1.51 [95% CI: 1.14, 1.99]), were independent prognostic factors for RFS. For OS, clinical N subcategories (cN1, cN2a2, and cN2b vs cN0; HRs, 1.91 [95% CI: 1.11, 3.27], 1.89 [95% CI: 1.13, 2.18], and 2.02 [95% CI: 1.07, 3.80], respectively) and LN size at N1 station (HR, 1.75 [95% CI: 1.12, 2.71]) were independent prognostic factors. For clinical N1, OS was further stratified according to LN size (log-rank test, P < .001). Conclusion Assessing the proposed N subcategories by reporting single versus multistation involvement of N2 disease and maximum size of metastatic LN, reflecting metastatic burden, at preoperative CT may offer useful prognostic information for planning optimal treatment strategies. Keywords: CT, Lung, Staging, Non-Small Cell Lung Cancer Supplemental material is available for this article. ©RSNA, 2024.

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.

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.

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.

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.

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.

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.

Pre-operative clonal hematopoiesis is related to adverse outcome in lung cancer after adjuvant therapy.

BACKGROUND: Clonal hematopoiesis (CH) frequently progresses after chemotherapy or radiotherapy. We evaluated the clinical impact of preoperative CH on the survival outcomes of patients with non-small cell lung cancer (NSCLC) who underwent surgical resection followed by adjuvant therapy. METHODS: A total of 415 consecutive patients with NSCLC who underwent surgery followed by adjuvant therapy from 2011 to 2017 were analyzed. CH status was evaluated using targeted deep sequencing of blood samples collected before surgery. To minimize the possible selection bias between the two groups according to CH status, a propensity score matching (PSM) was adopted. Early-stage patients were further analyzed with additional matched cohort of patients who did not receive adjuvant therapy. RESULTS: CH was detected in 21% (86/415) of patients with NSCLC before adjuvant therapy. Patients with CH mutations had worse overall survival (OS) than those without (hazard ratio [95% confidence interval] = 1.56 [1.07-2.28], p = 0.020), which remained significant after the multivariable analysis (1.58 [1.08-2.32], p = 0.019). Of note, the presence of CH was associated with non-cancer mortality (p = 0.042) and mortality of unknown origin (p = 0.018). In patients with stage IIB NSCLC, there was a significant interaction on OS between CH and adjuvant therapy after the adjustment with several cofactors through the multivariable analysis (HR 1.19, 95% CI 1.00-1.1.41, p = 0.041). CONCLUSIONS: In resected NSCLC, existence of preoperative CH might amplify CH-related adverse outcomes through adjuvant treatments, resulting in poor survival results.

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.

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.

[18F]fluorodeoxyglucose positron emission tomography/computed tomography characteristics of primary mediastinal germ cell tumors.

Primary mediastinal germ cell tumor (MGCT) is an uncommon tumor. Although it has histology similar to that of gonadal germ cell tumor (GCT), the prognosis for MGCT is generally worse than that for gonadal GCT. We performed visual assessment and quantitative analysis of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) for MGCTs. A total of 35 MGCT patients (age = 33.1 ± 16.8 years, F:M = 16:19) who underwent preoperative PET/CT were retrospectively reviewed. The pathologic diagnosis of MGCTs identified 24 mature teratomas, 4 seminomas, 5 yolk sac tumors, and 2 mixed germ cell tumors. Visual assessment was performed by categorizing the uptake intensity, distribution, and contour of primary MGCTs. Quantitative parameters including the maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter were compared between benign and malignant MGCTs. On visual assessment, the uptake intensity was the only significant parameter for differentiating between benign and malignant MGCTs (p = 0.040). In quantitative analysis, the SUVmax (p < 0.001), TBR (p < 0.001), MTV (p = 0.033), and TLG (p < 0.001) showed significantly higher values for malignant MGCTs compared with benign MGCTs. In receiver operating characteristic (ROC) curve analysis of these quantitative parameters, the SUVmax had the highest area under the curve (AUC) (AUC = 0.947, p < 0.001). Furthermore, the SUVmax could differentiate between seminomas and nonseminomatous germ cell tumors (p = 0.042) and reflect serum alpha fetoprotein (AFP) levels (p = 0.012). The visual uptake intensity and SUVmax on [18F]FDG PET/CT showed discriminative ability for benign and malignant MGCTs. Moreover, the SUVmax may associate with AFP levels.

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.

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.