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.

Clinical and Pathologic Supraclavicular Lymph Node Metastases in Esophageal Squamous Cell Carcinoma Treated by Esophagectomy with Three-Field Lymph Node Dissection.

BACKGROUND: This study investigated the survival outcomes for surgically treated esophageal squamous cell carcinoma (ESCC) patients based on clinically suspicious supraclavicular lymph node (SCN) metastasis (cSCN+) and pathologically confirmed SCN metastasis (pSCN+). METHODS: Using an institutional registry between 1994 and 2018, this study retrospectively analyzed 611 patients who received curative-intent esophagectomy with 3-field lymph node dissection for ESCC. The study used computed tomography and positron emission tomography to define cSCN+. RESULTS: Among 611 patients, 24.4% had cSCN+ and 12.2% had pSCN+. The 5-year overall survival (OS) rates were 68.2% for cN0, 43.5% for cN+ without cSCN+, and 30.3% for cN+ with cSCN+ (p = 0.018). Although the univariable analysis showed that cSCN+ was associated with poorer survival than cN0 or cN+ with cSCN- (hazard ratio [HR], 1.818; p < 0.001), the multivariable analysis did not support this finding (HR, 1.281; p = 0.681). The 5-year OS rates were 64.2% for pN0, 41.5% for pN+ without pSCN+, and 25.6% for pN+ with pSCN+ (p = 0.054). Univariable analysis showed an association of pSCN+ with poor OS (HR, 1.830; p < 0.001), but the difference in the multivariable analysis was not significant (HR, 0.912; p = 0.587). CONCLUSIONS: The presence of SCN metastasis did not have a significant impact on the OS of ESCC patients with 3-field lymph node dissection regardless of clinical suspicion or pathologic confirmation.

Distinct Recurrence Pattern and Survival Outcomes of Invasive Mucinous Adenocarcinoma of the Lung: The Potential Role of Local Therapy in Intrapulmonary Spread.

BACKGROUND: Invasive mucinous adenocarcinoma (IMA) is distinct from non-mucinous adenocarcinoma, but studies on recurrent IMA are scarce. Thus, this study aimed to evaluate the recurrence patterns of IMA and the role of pulmonary local therapy (LT) in resectable pulmonary recurrence of IMA. METHODS: The study reviewed 403 patients with surgically resected IMA between 1998 and 2018. The recurrence patterns were categorized as solitary pulmonary recurrence (SPR), multiple pulmonary recurrence (MPR), and extra-pulmonary recurrence (EPR). The clinicopathologic characteristics, overall survival (OS), and post-recurrence survival (PRS) were analyzed according to the recurrence pattern and LT administration. RESULTS: Recurrences were found in 91 (22.6%) patients, including 18 patients with SPR, 37 patients with MPR, and 36 patients with EPR. Compared with the MPR and EPR groups, the SPR group had a longer disease-free interval (32.5 vs. 9.6 vs. 10.1 months, respectively; p < 0.01) and a better OS (5-year OS: 88.5%, 41.5%, and 22.9%, respectively; p < 0.01). In case of resectable pulmonary recurrence, pulmonary LT was administered to 15 patients with SPR and 3 patients with MPR. These patients showed a better 5-year PRS than the other patients with pulmonary recurrence (86.3% vs. 30.4%; p < 0.01). Notably, long-term survival was observed for one patient with MPR undergoing LT and two patients with SPR undergoing a second LT for a second pulmonary recurrence. CONCLUSIONS: In this series, the patients with recurrent IMA showed different prognoses according to the recurrence pattern. The patients with pulmonary recurrence of IMA undergoing LT showed a favorable prognosis, suggesting the potential role of LT for resectable pulmonary recurrence of IMA.

Comparison of the Oncologic Outcomes for Patients with Middle to Lower Esophageal Squamous Cell Carcinoma Undergoing Surgical Treatment Using the Ivor-Lewis or McKeown Operation.

BACKGROUND: The upper mediastinum is the most common metastatic site of esophageal squamous cell carcinoma (ESCC), and complete dissection of this region is important for oncologic reasons. This study aimed to compare the oncologic outcomes and completeness of upper mediastinal dissection for ESCC patients undergoing the Ivor-Lewis (IL) or McKeown (MK) operations. METHODS: Between 2013 and 2018, 680 patients (IL, 433; MK, 247) underwent upfront esophagectomy with two-field lymph node (LN) dissection for mid-to-lower ESCCs. Propensity score-matching (1:1 ratio) was performed to minimize the effects of confounding factors. RESULTS: The mean age was 64.5 ± 8.8 years, and 635 (93.4%) of the patients were male. The median follow-up period was 71.66 months (interquartile range [IQR], 59.60-91.04 months). The IL group had a higher mean age, lower body mass index, higher proportion of advanced T and N, and higher adjuvant therapy rates, but these differences were well-balanced after propensity score-matching. The mean number of dissected LNs at the mediastinum and at the right recurrent laryngeal nerve (RLN) were similar between the two groups after matching, whereas the IL group exhibited a slightly greater number of dissected LNs at the left RLN. Among the matched patients, the IL and MK groups exhibited similar 5-year overall survival (OS: 75.1% vs 78.0%; p = 0.368). The multivariate model showed no differences in OS, disease-free survival, or recurrence-free survival for locoregional, upper mediastinum, or neck between the two groups. CONCLUSIONS: This study suggests that both the IL and MK operations are oncologically feasible for patients with mid-to-lower ESCC.

PD-L1 expression in resected lung adenocarcinoma: prevalence and prognostic significance in relation to the IASLC grading system.

AIMS: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for adjuvant immunotherapy and has been linked to poor differentiation in lung adenocarcinoma. However, its prevalence and prognostic role in the context of the novel histologic grade has not been evaluated. METHODS: We analysed a cohort of 1233 patients with resected lung adenocarcinoma where PD-L1 immunohistochemistry (22C3 assay) was reflexively tested. Tumour PD-L1 expression was correlated with the new standardized International Association for the Study of Lung Cancer (IASLC) histologic grading system (G1, G2, and G3). Clinicopathologic features including patient outcome were analysed. RESULTS: PD-L1 was positive (≥1%) in 7.0%, 23.5%, and 63.0% of G1, G2, and G3 tumours, respectively. PD-L1 positivity was significantly associated with male sex, smoking, and less sublobar resection among patients with G2 tumours, but this association was less pronounced in those with G3 tumours. PD-L1 was an independent risk factor for recurrence (adjusted hazard ratio [HR] = 3.25, 95% confidence intervals [CI] = 1.93-5.48, P < 0.001) and death (adjusted HR = 2.69, 95% CI = 1.13-6.40, P = 0.026) in the G2 group, but not in the G3 group (adjusted HR for recurrence = 0.94, 95% CI = 0.64-1.40, P = 0.778). CONCLUSION: PD-L1 expression differs substantially across IASLC grades and identifies aggressive tumours within the G2 subgroup. This knowledge may be used for both prognostication and designing future studies on adjuvant immunotherapy.

Computed tomography characteristics of cN0 primary non-small cell lung cancer predict occult lymph node metastasis.

RATIONALE: Occult lymph node metastasis (OLNM) is frequently found in patients with resectable non-small cell lung cancer (NSCLC), despite using diagnostic methods recommended by guidelines. OBJECTIVES: To evaluate the risk of OLNM in NSCLC patients using the radiologic characteristics of the primary tumor on computed tomography (CT). METHODS: We retrospectively reviewed clinicopathologic features of 2042 clinical T1-4N0 NSCLC patients undergoing curative intent pulmonary resection. Unique radiological features (i.e., air-bronchogram throughout the whole tumor, heterogeneous ground-glass opacity (GGO), mainly cystic appearance, endobronchial location), percentage of solid portion, and shape of tumor margin were analyzed via a stepwise approach. We used multivariable logistic regression to assess the relationship between OLNM and tumor characteristics. RESULTS: Compared with the other unique features, endobronchial tumors were associated with the highest risk of OLNM (OR = 3.9, 95% confidence interval (CI) = 2.29-6.62), and heterogeneous GGO and mainly cystic tumors were associated with a low risk of OLNM. For tumors without unique features, the percentage of the solid portion was measured, and solid tumors were associated with OLNM (OR = 2.49, 95% CI = 1.86-3.35). Among part-solid tumors with solid proportion > 50%, spiculated margin, and peri-tumoral GGO were associated with OLNM. CONCLUSIONS: The risk of OLNM could be assessed using radiologic characteristics on CT. This could allow us to adequately select optimal candidates for invasive nodal staging procedures (INSPs) and complete systematic lymph node dissection. CLINICAL RELEVANCE STATEMENT: These data may be helpful for clinicians to select appropriate candidates for INSPs and complete surgical systematic lymph node dissection in NSCLC patients. KEY POINTS: Lymph node metastasis status plays a key role in both prognostication and treatment planning. Solid tumors, particularly endobronchial tumors, were associated with occult lymph node metastasis (OLNM). The risk of OLNM can be assessed using radiologic characteristics acquired from CT images.

Metabolic dysfunction-associated steatotic liver disease and risk of esophageal cancer in patients with diabetes mellitus: a nationwide cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with type 2 diabetes and a developing several cancers including esophageal cancer (EC). However, the association between MASLD and EC in diabetic patients has not been investigated. Therefore, we aimed to investigate the relation between MASLD and developing EC in diabetic patients. This was a population-based retrospective cohort study of data from the Korean National Health Insurance Service (NHIS). A total of 1,904,468 subjects diagnosed with diabetes who underwent NHIS-provided health checkups from 2009 to 2012 were included. We constructed a Cox proportional hazard model for the association of fatty liver index (FLI) and the risk of EC stratified by potential confounders. Over a mean follow-up duration of 6.9 years, the incidence of EC was higher in the high (≥60) FLI group compared to the low (<30) FLI group (14.4 vs. 13.7 event per 100,000 person-years). The risk of EC correlated with the degree of FLI, particularly in older (P = 0.002), female (P = 0.033), non-smoking (P = 0.002), and non-drinking patients (P = 0.025). Among obese patients, the risk of EC was not associated with FLI; however, the risk of EC was higher in the high FLI group in non-obese patients. Lean MASLD patients had the highest risk of EC (adjusted hazard ratio 1.78; 95% confidence interval, 1.5-2.13). MASLD was associated with an increased risk of EC in diabetic patients, and lean MASLD has the highest risk. Further studies are required to determine the causal relationship between MASLD and EC.

Prognostic role of pathologic status other than complete response after neoadjuvant therapy followed by surgery in esophageal squamous cell carcinoma.

BACKGROUND: This retrospective study was performed to investigate the survival differences according to the pathologic status after neoadjuvant chemotherapy followed by surgery in esophageal squamous cell carcinoma (ESCC), and to investigate whether current AJCC 8th ypStage can predict survival accurately. METHODS: Data of 563 patients who received neoadjuvant therapy and esophagectomy for ESCC between 1994 and 2018 were retrospectively reviewed. RESULTS: The mean age was 62.00 ± 8.01 years, of which 524 (93.1%) were males. The median follow-up period was 29.12 months. A total of 153 (27.1%) patients showed pathologic complete response (pCR) and 92 (16.3%) patients showed pCR of the primary lesion with residual metastatic lymph nodes (ypT0N +). A total of 196 (35%) and 122 (21.6%) patients showed ypT + N + and ypT + N, respectively. The 5-year overall survival (OS) of each group was 75.1% (CR), 42.4% (ypT + N0), 54.9% (ypT0N +), and 26.1% (ypT + N +); CR patients showed better survival than the other groups, and no survival differences were found in the 5-year OS between ypT + N0 and ypT0N + patients (p = 0.811). In ypStage I, there were survival differences between ypT0N0 and ypTis-2N0 patients, and ypT1N0 (ypStage I) and ypT0N1 (ypStageIIIA) showed similar OS (5-year OS in 49.3% vs. 67.1%, p = 0.623). CONCLUSIONS: pCR offers long-term survival in patients; however, survival significantly declines with the presence of residual primary lesion and nodal metastases.

Validation of the IASLC Residual Tumor Classification in Patients With Stage III-N2 Non-Small Cell Lung Cancer Undergoing Neoadjuvant Chemoradiotherapy Followed By Surgery.

OBJECTIVE: The aim of this study was to validate the International Association for the Study of Lung Cancer (IASLC) residual tumor classification in patients with stage III-N2 non-small cell lung cancer (NSCLC) undergoing neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery. BACKGROUND: As adequate nodal assessment is crucial for determining prognosis in patients with clinical N2 NSCLC undergoing nCCRT followed by surgery, the new classification may have better prognostic implications. METHODS: Using a registry for thoracic cancer surgery at a tertiary hospital in Seoul, Korea, between 2003 and 2019, we analyzed 910 patients with stage III-N2 NSCLC who underwent nCCRT followed by surgery. We classified resections using IASLC criteria: complete (R0), uncertain (R[un]), and incomplete resection (R1/R2). Recurrence and mortality were compared using adjusted subdistribution hazard model and Cox-proportional hazards model, respectively. RESULTS: Of the 96.3% (n = 876) patients who were R0 by Union for International Cancer Control (UICC) criteria, 34.5% (n = 3O2) remained R0 by IASLC criteria and 37.6% (n = 329) and 28% (n = 245) migrated to R(un) and R1, respectively. Most of the migration from UICC-R0 to lASLC-R(un) and IASLC-R1/R2 occurred due to inadequate nodal assessment (85.5%) and extracapsular nodal extension (77.6%), respectively. Compared to R0, the adjusted hazard ratios in R(un) and R1/R2 were 1.20 (95% confidence interval, 0.94-1.52), 1.50 (1.17-1.52) ( P fortrend = .001) for recurrence and 1.18 (0.93-1.51) and 1.51 (1.17-1.96) for death ( P for trend = .002). CONCLUSIONS: The IASLC R classification has prognostic relevance in patients with stage III-N2 NSCLC undergoing nCCRT followed by surgery. The IASLC classification will improve the thoroughness of intraoperative nodal assessment and the completeness of resection.

Impact of interstitial lung abnormalities on postoperative pulmonary complications and survival of lung cancer.

BACKGROUND: Interstitial lung abnormalities (ILAs) are associated with the risk of lung cancer and its mortality. However, the impact of ILA on treatment-related complications and survival in patients who underwent curative surgery is still unknown. RESEARCH QUESTION: This study aimed to evaluate the significance of the presence of computed tomography-diagnosed ILA and histopathologically matched interstitial abnormalities on postoperative pulmonary complications (PPCs) and the long-term survival of patients who underwent surgical treatment for lung cancer. STUDY DESIGN AND METHODS: A matched case-control study was designed to compare PPCs and mortality among 50 patients with ILA, 50 patients with idiopathic pulmonary fibrosis (IPF) and 200 controls. Cases and controls were matched by sex, age, smoking history, tumour location, the extent of surgery, tumour histology and pathological TNM stage. RESULTS: Compared with the control group, the OR of the prevalence of PPCs increased to 9.56 (95% CI 2.85 to 32.1, p<0.001) in the ILA group and 56.50 (95% CI 17.92 to 178.1, p<0.001) in the IPF group. The 5-year overall survival (OS) rates of the control, ILA and IPF groups were 76% (95% CI 71% to 83%), 52% (95% CI 37% to 74%) and 32% (95% CI 19% to 53%), respectively (log-rank p<0.001). Patients with ILA had better 5-year OS than those with IPF (log-rank p=0.046) but had worse 5-year OS than those in the control group (log-rank p=0.002). CONCLUSIONS: The presence of radiological and pathological features of ILA in patients with lung cancer undergoing curative surgery was associated with frequent complications and decreased survival.

Factors Contributing to Successful Transvenous Retrograde Thoracic Duct Cannulation.

PURPOSE: To identify key factors for successful transvenous retrograde cannulation (TVRC) of the thoracic duct. MATERIALS AND METHODS: A total of 47 consecutive patients (62.1 ± 13.2 years; 32 men) who underwent attempted TVRC between July 2016 and July 2021 were included. Reasons for interventions were chylous leakage from the chest (n = 36), abdomen (n = 6), and other sites (n = 5). Patient age, sex, access vein (femoral vs brachial), anatomic classification (presence of dominant channel vs plexiform) of the terminal thoracic duct, and engagement of a diagnostic catheter into the jugulovenous junction were included in the analyses. Anatomic details were evaluated according to catheter-based high-pressure lymphangiography and conventional intranodal lymphangiography. The Firth bias-reduced penalized-likelihood logistic regression model was used to analyze prognostic factors. RESULTS: TVRC was successful in 33 of the 47 patients (70%). In univariate analysis, femoral access, diagnostic catheter engagement, and presence of dominant channel were significant positive prognostic factors (P <.05). In multivariate analysis, diagnostic catheter engagement and presence of dominant channel were significant prognostic factors (P <.05). Diagnostic catheter engagement showed the highest prognostic performance (accuracy = 0.872), followed by presence of a dominant channel. High-pressure catheter-based lymphangiographic findings showed better performance (accuracy, 0.844 vs 0.727) than intranodal lymphangiography to delineate the anatomy of the terminal thoracic duct. CONCLUSIONS: A secure selection of the jugulovenous junction and the presence of a dominant channel in the terminal portion of the thoracic duct were significant prognostic factors for successful TVRC.

Enhanced Recovery After Surgery Program and Opioid Consumption in Pulmonary Resection Surgery: A Retrospective Observational Study.

BACKGROUND: Pulmonary resection surgery causes severe postoperative pain and usually requires opioid-based analgesia, particularly in the early postoperative period. However, the administration of large amounts of opioids is associated with various adverse events. We hypothesized that patients who underwent pulmonary resection under an enhanced recovery after surgery (ERAS) program consumed fewer opioids than patients who received conventional treatment. METHODS: A total of 2147 patients underwent pulmonary resection surgery between August 2019 and December 2020. Two surgeons (25%) at our institution implemented the ERAS program for their patients. After screening, the patients were divided into the ERAS and conventional groups based on the treatment they received. The 2 groups were then compared after the stabilized inverse probability of treatment weighting. The primary end point was the total amount of opioid consumption from surgery to discharge. The secondary end points included daily average and highest pain intensity scores during exertion, opioid-related adverse events, and clinical outcomes, such as length of intensive care unit (ICU) stay, hospital stay, and postoperative complication grade defined by the Clavien-Dindo classification. Additionally, the number of patients discharged without opioids prescription was assessed. RESULTS: Finally, 2120 patients were included in the analysis. The total amount of opioid consumption (median [interquartile range]) after surgery until discharge was lower in the ERAS group (n = 260) than that in the conventional group (n = 1860; morphine milligram equivalents, 44 [16-122] mg vs 208 [146-294] mg; median difference, -143 mg; 95% CI, -154 to -132; P < .001). The number of patients discharged without opioids prescription was higher in the ERAS group (156/260 [60%] vs 329/1860 [18%]; odds ratio, 7.0; 95% CI, 5.3-9.3; P < .001). On operation day, both average pain intensity score during exertion (3.0 ± 1.7 vs 3.5 ± 1.8; mean difference, -0.5; 95% CI, -0.8 to -0.3; P < .001) and the highest pain intensity score during exertion (5.5 ± 2.1 vs 6.4 ± 1.7; mean difference, -0.8; 95% CI, -1.0 to -0.5; P < .001) were lower in the ERAS group than in the conventional group. There were no significant differences in the length of ICU stay, hospital stay, or Clavien-Dindo classification grade. CONCLUSIONS: Patients who underwent pulmonary resection under the ERAS program consumed fewer opioids than those who received conventional management while maintaining no significant differences in clinical outcomes.

Factors associated with failure of cardiopulmonary function recovery after lung cancer surgery.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate the longitudinal changes in cardiopulmonary function (CPF) and identify predictors of cardiopulmonary recovery failure after lung cancer surgery. METHODS: Data was obtained from a prospective CATCH-LUNG cohort study, where patients were divided into two groups based on 6-min walk distance (6MWD) at baseline and 6 months after surgery. CPF recovery failure was defined as a participant whose 6MWD dropped over 50 m from baseline to 6 months after surgery. Patients with a baseline 6MWD less than 400 m were excluded. The analysis was investigated using mixed effects models, and the relative estimates for the predictors were expressed relative risk (RR) and 95% CI using a Poisson regression. RESULTS: Among 419 patients, 24.1% and 17.7% showed failure of CPF recovery at 6 months and 1 year after surgery, respectively. In the multivariable analysis, baseline step count [RR per 1000 steps lower = 1.05 (95% CI, 1.01-1.09)], baseline dyspnoea [RR per 10 points higher = 1.15(1.07-1.23)], decreased FEV1 % predicted from baseline to 2 weeks after surgery [RR per 10% lower = 1.30(1.10-1.53)] and decreased moderate-to-vigorous physical activity (MVPA) from baseline to 2 weeks [RR = 1.95(1.22, 3.11)] or persistent low MVPA at baseline and 2 weeks after surgery [RR = 1.63(1.04, 2.54)] were significant factors for loss of CPF. CONCLUSION: The inability to recover CPF at 6 months after surgery was linked to reduction of lung function and MVPA from baseline to 2 weeks as well as baseline physical activity (PA) and dyspnoea. These results imply that engagement of perioperative PA is necessary to facilitate recovery of CPF after lung cancer surgery.

Role of Recurrent Laryngeal Nerve Lymph Node Dissection in Surgery of Early-Stage Esophageal Squamous Cell Carcinoma.

BACKGROUND: In esophageal cancer surgery, it is difficult to perform thorough dissection of lymph nodes along the recurrent laryngeal nerve (RLN-LN). However, there are limited data regarding the necessity of RLN-LN dissection in surgery for superficial esophageal squamous carcinoma (focused on T1b tumor) and its role in locoregional control and accurate nodal staging. METHODS: Between 2001 and 2016, 567 patients with pT1N0 and 927 patients with cT1N0 squamous cell carcinoma were identified in a prospectively maintained, single institution esophagectomy registry. Sufficient or insufficient RLN-LN assessment group was defined by receiver operating characteristic curve analysis of the number of RLN-LN harvested. To mitigate bias, inverse probability weighting adjustment and several sensitivity analyses were performed. RESULTS: In the pT1N0 cohort, patients with sufficient (≥ 4) harvested RLN-LNs showed significantly superior 5-year recurrence-free survival (89.1% versus 74.8%, log-rank P < 0.001). Patients with insufficient RLN-LN dissection mainly developed locoregional failure at the upper mediastinal or cervical area (87% of total recurred cases). The survival impact of sufficient RLN-LN dissection was more prominent in subsets of upper-middle thoracic tumors or with deep submucosal invasion. In the analysis on cT1N0 cohort, sufficient RLN-LN assessment conferred a 1.5-fold increase in the discovery of positive-nodal disease (19.4% versus 27.8%, P = 0.008). CONCLUSIONS: Adequate RLN-LN dissection during surgery may help reduce the risk of recurrence and enhance the accuracy of nodal staging in early-stage esophageal squamous cell carcinoma. Therefore, meticulous surgical evaluation for this region should not be underrated, particularly in the high-risk subset with lymph node metastasis. Visual Abstract Graphical summary of key study findings. T wo cohorts (pT1 and cT1 ; both mainly comprised T1b ) were analyzed for separate purposes; the former controlled for pathologic stage was primarily analyzed in terms of survival and recurrence hazard, whereas the latter (controlled for clinical was used for stage migration ( and intention to treat analysis. Th e results show the significance of adequate bilateral RLN LN in the surgery for early stage ESCC (particularly those with T1b)T1b), in terms of accurate nodal staging, effective nodal clearance, and reduced regional.

Longitudinal changes in pulmonary function and patient-reported outcomes after lung cancer surgery.

BACKGROUND: Surgery is the mainstay of treatment for non-small cell lung cancer, but the decline in pulmonary function after surgery is noticeable and requires attention. This study aimed to evaluate longitudinal changes in pulmonary function and integrated patient-reported outcomes (PROs) after lung cancer surgery. METHODS: Data were obtained from a prospective cohort study, the Coordinate Approach to Cancer Patients' Health for Lung Cancer. Changes in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) at 2 weeks, 6 months, and 1 year after surgery, and the corresponding modified Medical Research Council (mMRC) dyspnea scale and chronic obstructive lung disease assessment test (CAT) scores were evaluated. Mixed effects model was used to investigate changes in pulmonary function and PROs. RESULTS: Among 620 patients, 477 (76.9%) underwent lobectomy, whereas 120 (19.4%) and 23 (3.7%) were treated with wedge resection/segmentectomy and bilobectomy/pneumonectomy, respectively. Both FVC and FEV1 markedly decreased 2 weeks after surgery and improved thereafter; however, they did not recover to baseline values. The corresponding mMRC dyspnea scale and CAT scores worsened immediately after surgery. The dyspnea scale of the mMRC was still higher, while CAT scores returned to baseline one year after surgery, although breathlessness and lack of energy persisted. Compared to the changes from baseline of FVC and FEV1 in patients who underwent lobectomy, patients who underwent bilobectomy/pneumonectomy showed a greater decrease in FVC and FEV1, while wedge resection/segmentectomy patients had smaller decreases in FVC and FEV1 at 2 weeks, 6 months, and 1 year after surgery. Bilobectomy/pneumonectomy patients had the highest mMRC dyspnea grade among the three groups, but the difference was not statistically significant one year after surgery. CONCLUSIONS: After lung cancer surgery, pulmonary function and PROs noticeably decreased in the immediate post-operative period and improved thereafter, except for dyspnea and lack of energy. Proper information on the timeline of changes in lung function and symptoms following lung cancer surgery could guide patient care approaches after surgery. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03705546; URL: www. CLINICALTRIALS: gov.

Pragmatic role of noncontrast magnetic resonance lymphangiography in postoperative chylothorax or cervical chylous leakage as a diagnostic and preprocedural planning tool.

OBJECTIVES: To define the roles of noncontrast magnetic resonance lymphangiography (MRL) in the management of postoperative chylothorax or cervical chylous leakage. METHODS: A total of 50 consecutive patients underwent noncontrast MRL, intranodal lymphangiography, and thoracic duct embolization between May 2016 and April 2020. Their mean age was 62.6 years ± 10.3 (SD) years, and 35 of the participants were men. Conventional lymphangiographic images were sufficient in quality as a reference for the evaluation of diagnostic accuracy of leakage and location in 35 patients (70%) and for evaluation of anatomic details of the thoracic duct and jugulovenous junction in 34 patients (68%). RESULTS: MRL showed that the sensitivity, specificity, and positive and negative predictive values for leakage detection were 100%, 97.1%, 100%, and 100%, respectively, and the concordance rate was 97.14% (95% confidence interval [CI], 85.08-99.93%; p < .001). Leakage location was concordant between MRL and conventional lymphangiography in 27 patients (77.1%, 27/35). Regarding anatomical details of the thoracic duct, variation of the thoracic duct was missed in 11.7% of patients (4/34). The jugulovenous junction was observed in 91.1% (31/34), and its opening into the central vein was depicted in 76.4% (26/34). The concordance rate was between 76.47 and 91.18. CONCLUSIONS: Noncontrast MRL has a high sensitivity for the detection of postoperative thoracic and cervical chylous leakage but is suboptimal for the localization of the leak and depiction of anatomical details of the thoracic duct. This method is worthy of consideration as either a decision-making or planning tool for subsequent interventions. KEY POINTS: • Noncontrast MRL provides limited resolution images of CLS but has a high sensitivity for the detection of postoperative chylous leakage in the thoracic and neck regions. • Noncontrast MRL is suboptimal for depicting anatomic details in the thoracic duct and jugulovenous junction but can play a role as a decision-making and a planning tool for subsequent lymphatic interventions.

Mortality and lung function decline in patients who develop chronic pulmonary aspergillosis after lung cancer surgery.

BACKGROUND: Lung cancer surgery is reported as a risk factor for chronic pulmonary aspergillosis (CPA). However, limited data are available on its clinical impact. We aimed to determine the effect of developed CPA after lung cancer surgery on mortality and lung function decline. METHODS: We retrospectively identified the development of CPA after lung cancer surgery between 2010 and 2016. The effect of CPA on mortality was evaluated using multivariable Cox proportional hazard analyses. The effect of CPA on lung function decline was evaluated using multiple linear regression analyses. RESULTS: During a median follow-up duration of 5.01 (IQR, 3.41-6.70) years in 6777 patients, 93 developed CPA at a median of 3.01 (IQR, 1.60-4.64) years. The development of CPA did not affect mortality in multivariable analysis. However, the decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were greater in patients with CPA than in those without (FVC, - 71.0 [- 272.9 to - 19.4] vs. - 10.9 [- 82.6 to 57.9] mL/year, p < 0.001; FEV1, - 52.9 [- 192.2 to 3.9] vs. - 20.0 [- 72.6 to 28.6] mL/year, p = 0.010). After adjusting for confounding factors, patients with CPA had greater FVC decline (ß coefficient, - 103.6; 95% CI - 179.2 to - 27.9; p = 0.007) than those without CPA. However, the FEV1 decline (ß coefficient, - 14.4; 95% CI - 72.1 to 43.4; p = 0.626) was not significantly different. CONCLUSION: Although the development of CPA after lung cancer surgery did not increase mortality, the impact on restrictive lung function deterioration was profound.

Female reproductive factors and the risk of lung cancer in postmenopausal women: a nationwide cohort study.

BACKGROUND: Reproductive factors and hormone use in postmenopausal women have been hypothesised to affect the risk of developing lung cancer, but the epidemiological evidence is inconsistent. METHODS: Using the Korean National Health Insurance System database, we identified 4,775,398 postmenopausal women older than 40 years who had undergone both cardiovascular health- and cancer screening between 1 January 2009 and 31 December 2014. Information about reproductive factors was obtained from a self-administered questionnaire. The risk of lung cancer was estimated using Cox proportional hazard regression models. RESULTS: During a median follow-up of 4.4 years, 16,556 women (15,223 non-smokers) were diagnosed with lung cancer. The risk of lung cancer was not significantly influenced by early menarche age (adjusted hazard ratio [aHR] 1.03 for menarche ≥18 vs. ≤14; 95% confidence interval [CI], 0.98-1.09) or late age at menopause (aHR 1.02 for menopause ≥55 vs. <40; 95% CI, 0.91-1.14). Furthermore, the number of children, duration of breastfeeding and use of hormone replacement therapy were not associated with the risk of lung cancer. CONCLUSIONS: No statistically significant association was found between reproductive factors and the risk of lung cancer in postmenopausal Korean women.

PDX models of human lung squamous cell carcinoma: consideration of factors in preclinical and co-clinical applications.

BACKGROUND: Treatment of human lung squamous cell carcinoma (LUSC) using current targeted therapies is limited because of their diverse somatic mutations without any specific dominant driver mutations. These mutational diversities preventing the use of common targeted therapies or the combination of available therapeutic modalities would require a preclinical animal model of this tumor to acquire improved clinical responses. Patient-derived xenograft (PDX) models have been recognized as a potentially useful preclinical model for personalized precision medicine. However, whether the use of LUSC PDX models would be appropriate enough for clinical application is still controversial. METHODS: In the process of developing PDX models from Korean patients with LUSC, the authors investigated the factors influencing the successful initial engraftment of tumors in NOD scid gamma mice and the retainability of the pathological and genomic characteristics of the parental patient tumors in PDX tumors. CONCLUSIONS: The authors have developed 62 LUSC PDX models that retained the pathological and genomic features of parental patient tumors, which could be used in preclinical and co-clinical studies. Trial registration Tumor samples were obtained from 139 patients with LUSC between November 2014 and January 2019. All the patients provided signed informed consents. This study was approved by the institutional review board (IRB) of Samsung Medical Center (2018-03-110).

Impact of diffusing lung capacity before and after neoadjuvant concurrent chemoradiation on postoperative pulmonary complications among patients with stage IIIA/N2 non-small-cell lung cancer.

BACKGROUND AND OBJECTIVE: This study aims to evaluate the impact of diffusing capacity of the lung for carbon monoxide (DLco) before and after neoadjuvant concurrent chemoradiotherapy (CCRT) on postoperative pulmonary complication (PPC) among stage IIIA/N2 non-small-cell lung cancer (NSCLC) patients. METHODS: We retrospectively studied 324 patients with stage IIIA/N2 NSCLC between 2009 and 2016. Patients were classified into 4 groups according to DLco before and after neoadjuvant CCRT; normal-to-normal (NN), normal-to-low (NL), low-to-low (LL), and low-to-very low (LVL). Low DLco and very low DLco were defined as DLco < 80% predicted and DLco < 60% predicted, respectively. RESULTS: On average, DLco was decreased by 12.3% (±10.5) after CCRT. In multivariable-adjusted analyses, the incidence rate ratio (IRR) for any PPC comparing patients with low DLco to those with normal DLco before CCRT was 2.14 (95% confidence interval (CI) = 1.36-3.36). Moreover, the IRR for any PPC was 3.78 (95% CI = 1.68-8.49) in LVL group compared to NN group. The significant change of DLco after neoadjuvant CCRT had an additional impact on PPC, particularly after bilobectomy or pneumonectomy with low baseline DLco. CONCLUSIONS: The DLco before CCRT was significantly associated with risk of PPC, and repeated test of DLco after CCRT would be helpful for risk assessment, particularly in patients with low DLco before neoadjuvant CCRT.