Publications by authors named "Young Mog Shim"

297 Publications

Metformin Reduces Histone H3K4me3 at the Promoter Regions of Positive Cell Cycle Regulatory Genes in Lung Cancer Cells.

Cancers (Basel) 2021 Feb 10;13(4). Epub 2021 Feb 10.

Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.

This study aimed at understanding the effect of metformin on histone H3 methylation, DNA methylation, and chromatin accessibility in lung cancer cells. Metformin significantly reduced H3K4me3 level at the promoters of positive cell cycle regulatory genes such as CCNB2, CDK1, CDK6, and E2F8. Eighty-eight genes involved in cell cycle showed reduced H3K4me3 levels in response to metformin, and 27% of them showed mRNA downregulation. Metformin suppressed the expression of H3K4 methyltransferases MLL1, MLL2, and WDR82. The siRNA-mediated knockdown of MLL2 significantly downregulated global H3K4me3 level and inhibited lung cancer cell proliferation. MLL2 overexpression was found in 14 (33%) of 42 NSCLC patients, and a Cox proportional hazards analysis showed that recurrence-free survival of lung adenocarcinoma patients with MLL2 overexpression was approximately 1.32 (95% CI = 1.08-4.72; = 0.02) times poorer than in those without it. Metformin showed little effect on DNA methylation and chromatin accessibility at the promoter regions of cell cycle regulatory genes. The present study suggests that metformin reduces H3K4me3 levels at the promoters of positive cell cycle regulatory genes through MLL2 downregulation in lung cancer cells. Additionally, MLL2 may be a potential therapeutic target for reducing the recurrence of lung adenocarcinoma.
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http://dx.doi.org/10.3390/cancers13040739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916663PMC
February 2021

Prognostic Significance of Metabolic Parameters by F-FDG PET/CT in Thymic Epithelial Tumors.

Cancers (Basel) 2021 Feb 9;13(4). Epub 2021 Feb 9.

Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Background: Imaging tumor FDG avidity could complement prognostic implication in thymic epithelial tumors. We thus investigated the prognostic value of volume-based F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/CT parameters in thymic epithelial tumors with other clinical prognostic factors.

Methods: This is a retrospective study that included 83 patients who were diagnosed with thymic epithelial tumors and underwent pretreatment F-FDG PET/CT. PET parameters, including maximum and average standardized uptake values (SUV, SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured with a threshold of SUV 2.5. Univariate and multivariate analysis of PET parameters and clinicopathologic variables for time-to-progression was performed by using a Cox proportional hazard regression model.

Results: There were 21 low-risk thymomas (25.3%), 27 high-risk thymomas (32.5%), and 35 thymic carcinomas (42.2%). Recurrence or disease progression occurred in 24 patients (28.9%). On univariate analysis, Masaoka stage ( < 0.001); histologic types ( = 0.009); treatment modality ( = 0.001); and SUV, SUV, MTV, and TLG (all < 0.001) were significant prognostic factors. SUV ( < 0.001) and Masaoka stage ( = 0.001) were independent prognostic factors on multivariate analysis.

Conclusion: SUV and Masaoka stage are independent prognostic factors in thymic epithelial tumors.
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http://dx.doi.org/10.3390/cancers13040712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916204PMC
February 2021

Thoracoscopic Vs Open Surgery Following Neoadjuvant Chemoradiation for Clinical N2 Lung Cancer.

Semin Thorac Cardiovasc Surg 2021 Jan 12. Epub 2021 Jan 12.

Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

We evaluated the feasibility of video-assisted thoracoscopic surgery (VATS) following neoadjuvant concurrent chemoradiotherapy (nCCRT) for N2 non-small-cell lung cancer (NSCLC). We retrospectively reviewed patients with clinical N2 NSCLC who underwent lobectomy and lymph node dissection after nCCRT. The patients were matched using a propensity score based on age, sex, pulmonary function test, histologic type, clinical T factor, and method of N-staging. A total of 385 patients were enrolled between June 2012 and July 2017 (35 VATS, 350 open). After propensity matching (31 VATS, 112 open), the VATS group showed a significantly lower major complication rate (≥ grade II Clavien-Dindo classification; 9.7% vs 30.4%, P = 0.036). No significant differences were found between 2 group of 5-year survival rates (77.1% for the VATS group, 59.9% for the open group; P = 0.276) and recurrence-free survival rates (66.3% for the VATS group, 54.6% for the open group; P = 0.354). In multivariable analysis, VATS did not affect overall survival and recurrence-free survival. VATS was comparable to open thoracotomy in patients with clinical N2 NSCLC after nCCRT without compromising oncologic efficacy.
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http://dx.doi.org/10.1053/j.semtcvs.2021.01.002DOI Listing
January 2021

The role of postoperative radiotherapy in stage II and III thymoma: a Korean multicenter database study.

J Thorac Dis 2020 Nov;12(11):6680-6689

Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Complete resection is a standard treatment for patients with Masaoka-Koga stages II and III thymoma, however the role of postoperative radiotherapy (PORT) is controversial. We analyzed data collected from 4 Korean hospitals to determine the effectiveness of PORT in stage II and III thymoma patients.

Methods: Between January 2000 and December 2013, 1,663 patients underwent surgery for thymic tumors at the 4 hospitals. Among them, 668 patients (527 with stage II and 141 with stage III) were investigated, among whom, 443 received PORT (335 with stage II and 108 with stage III). Propensity score matching (PSM) was performed, and 404 patients (346 with stage II and 58 with stage III) were selected.

Results: Perioperative characteristics were similar in the PORT and non-PORT groups after PSM. On survival analysis of stage II patients, the PORT and non-PORT groups showed no difference in either 5-year recurrence-free survival (RFS) (96.3% 96.6%, P=0.622) or 5-year overall survival (OS) (94.6% 93.8%, P=0.839). However, among stage III patients, the PORT group showed significantly better 5-year RFS (75.7% 50.1%, P=0.040) and 5-year OS (86.5% 54.7%, P=0.001). On multivariate Cox regression analysis, PORT was a significant positive prognostic factor in terms of both RFS (P=0.005) and OS (P=0.004) in patients with stage III thymomas, but not in those with stage II disease (P=0.987 and 0.968, respectively).

Conclusions: PORT improved the RFS and OS in stage III thymoma patients, but showed no survival benefit in stage II patients.
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http://dx.doi.org/10.21037/jtd-20-1713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711424PMC
November 2020

Prognostic impact of lymph node ratio in patients with pT1-2N1M0 non-small cell lung cancer.

J Thorac Dis 2020 Oct;12(10):5552-5560

Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: This study evaluated the lymph node ratio (LNR) defined as the ratio of the number of metastatic lymph nodes to the number of dissected lymph nodes as a prognostic factor for survival in patients with pT1-2N1M0 non-small cell lung cancer (NSCLC).

Methods: We retrospectively reviewed 413 patients with pathologic T1-2N1M0 NSCLC after complete surgical resection and mediastinal LN dissection between January 2004 and December 2012. The cut-off value for LNR was determined using χ tests, which were calculated using Cox proportional hazards regression model. Based on this model, the optimal cut-off value for LNR was 0.1.

Results: The study included 337 males and 76 females with a mean age of 62 years (range, 34-83 years). Patients with a high LNR (≥0.1) were more likely to be female and have more adenocarcinomas compared with patients with a low LNR (<0.1). The overall survival (OS) and disease-free survival (DFS) rates were significantly worse in the high LNR group than the low LNR group (OS, 55.4% 69.8%, respectively P=0.003; DFS, 33.2% 61.7%, P<0.001). In the multivariate analysis, a high LNR was associated with significantly worse OS [adjusted hazard ratio (aHR), 2.69; 95% confidence interval (CI), 1.74-4.17] and DFS (aHR, 2.41; 95% CI, 1.57-3.68).

Conclusions: LNR is an independent prognostic factor for survival in patients with pT1-2N1M0 NSCLC. These findings may provide useful prognostic information to allow the selection of patients for more aggressive postoperative therapy or follow-up strategies.
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http://dx.doi.org/10.21037/jtd-20-1611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656357PMC
October 2020

Long-term outcomes of video-assisted thoracoscopic lobectomy for clinical N1 non-small cell lung cancer: A propensity score-weighted comparison with open thoracotomy.

Lung Cancer 2020 12 29;150:201-208. Epub 2020 Oct 29.

Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Objectives: Although the video-assisted thoracic surgery (VATS) approach has been accepted as a safe and effective alternative to lobectomy, its advantage remains unclear in advanced-stage lung cancer. This study is aimed to evaluate the feasibility and long-term outcomes of VATS in lung cancer with clinical N1 (cN1) disease.

Materials And Methods: We retrospectively reviewed the records of 1149 consecutive patients who underwent lobectomy for cN1 disease from 2006 to 2016. Perioperative outcomes and long-term survival rates were compared using a propensity score-based inverse probability of treatment weighting (IPTW) technique.

Results: We performed VATS and open thoracotomy for 500 and 649 patients, respectively. All preoperative characteristics became similar between the two groups after IPTW adjustment. Compared to thoracotomy, VATS was associated with shorter hospitalization (7.7 days vs. 9.2 days, p < 0.001), earlier adjuvant chemotherapy (41.7 days vs. 46.6 days, p = 0.028), similar complete resection rates (95.2 % vs. 94.0 %, p = 0.583), and equivalent dissected lymph nodes (27.5 vs. 27.8, p = 0.704). On IPTW-adjusted analysis, overall survival (OS) (59.4 % vs. 60.3 %, p = 0.588) and recurrence-free survival (RFS) (59.2 % vs. 56.9 %, p = 0.651) at 5 years were also similar between the two groups. Multivariable Cox analysis revealed that VATS was not a significant prognostic factor for cN1 disease (p = 0.764 for OS and p = 0.879 for RFS).

Conclusions: VATS lobectomy is feasible for patients with cN1 disease, providing comparable perioperative outcomes, oncologic efficacy, and long-term outcomes as open thoracotomy.
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http://dx.doi.org/10.1016/j.lungcan.2020.10.014DOI Listing
December 2020

Incidence and Risk Factors of Chronic Pulmonary Aspergillosis Development during Long-Term Follow-Up after Lung Cancer Surgery.

J Fungi (Basel) 2020 Nov 9;6(4). Epub 2020 Nov 9.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro 81, Gangnam-gu, Seoul 06351, Korea.

Lung resection surgery for non-small-cell lung cancer (NSCLC) is reportedly a risk factor for developing chronic pulmonary aspergillosis (CPA). However, limited data are available regarding the development of CPA during long-term follow-up after lung cancer surgery. This study aimed to investigate the cumulative incidence and clinical factors associated with CPA development after lung cancer surgery. We retrospectively analyzed 3423 patients with NSCLC who (1) underwent surgical resection and (2) did not have CPA at the time of surgery between January 2010 and December 2013. The diagnosis of CPA was based on clinical symptoms, serological or microbiological evidences, compatible radiological findings, and exclusion of alternative diagnoses. The cumulative incidence of CPA and overall survival (OS) were estimated using the Kaplan-Meier method, and a multivariable Cox proportional hazard analysis was performed to identify factors associated with CPA development. Patients were followed-up for a median of 5.83 years with a 72.3% 5-year OS rate. Fifty-six patients developed CPA at a median of 2.68 years after surgery, with cumulative incidences of 0.4%, 1.1%, 1.6%, and 3.5% at 1, 3, 5, and 10 years, respectively. Lower body mass index (BMI), smoking, underlying interstitial lung disease, thoracotomy, development of postoperative pulmonary complications 30 days after surgery, and treatment with both chemotherapy and radiotherapy were independently associated with CPA development. The cumulative incidence of CPA after surgery was 3.5% at 10 years and showed a steadily increasing trend during long-term follow-up. Therefore, increased awareness regarding CPA development is needed especially in patients with risk factors.
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http://dx.doi.org/10.3390/jof6040271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712970PMC
November 2020

Treatment modality and outcomes among early-stage non-small cell lung cancer patients with COPD: a cohort study.

J Thorac Dis 2020 Sep;12(9):4651-4660

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background: While there is an increasing number of early-stage non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), there are no specific clinical guidelines for treating them. This study aims to evaluate different treatment modalities and corresponding clinical outcomes among early-stage NSCLC patients with COPD.

Methods: We retrospectively reviewed 692 patients with stage I and II NSCLC and COPD from January 2012 to June 2014. Patients were categorized into four groups according to primary treatment modality: surgery only group (n=442), surgery with adjuvant treatment group (n=157), radiotherapy (RT) group (n=48), and supportive care (SC)-only group (n=45).

Results: Overall, mortality rate was the highest in the SC-only group (35.7 deaths per 100 person-years), followed by RT group (21.5 deaths per 100 person-years), surgery with adjuvant treatment group (8.9 deaths per 100 person-years) and surgery only group (7.2 deaths per 100 person-years). The adjusted hazard ratios (HR) for all-cause mortality compared to the surgery only group were 1.18 (95% CI, 0.84-1.67) in surgery with adjuvant treatment group, 1.61 (95% CI, 1.01-2.57) in RT group and 3.23 (95% CI, 1.99-5.23) in SC-only group.

Conclusions: Surgical resection should be considered as the first choice for early-stage NSCLC with COPD. Despite poor lung function or general patient condition, RT rather than SC can be an alternative option if surgery is not feasible. A multi-disciplinary approach and active communication between patients and physicians might be helpful for adequate decision-making regarding treatment for patients with early-stage NSCLC and COPD.
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http://dx.doi.org/10.21037/jtd-20-667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578486PMC
September 2020

Conditional Survival of Patients Who Underwent Curative Resection for Esophageal Squamous Cell Carcinoma.

Ann Surg 2020 Oct 19. Epub 2020 Oct 19.

Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Objective: To analyze conditional survival estimates of patients with esophageal cancer who underwent curative resection.

Summary Background Data: Conditional survival reflects dynamic prognosis updated to the current status and is a more relevant indicator for current healthcare and life decisions.

Methods: This study included 1,883 patients who underwent complete resection for esophageal squamous cell carcinoma at a tertiary cancer center from 1994 to 2016. We calculated 5-year (5Y) conditional overall survival (COS), conditional recurrence-free survival (CRFS), and conditional relative survival (CRS) estimates from diagnosis to 5 years of survival.

Results: The 5Y COS, CRFS, and CRS increased from 63.7%, 65.2%, and 70.2% at diagnosis to 75.8%, 91.9%, and 86.4 at 5 years after diagnosis, respectively. While there were large differences with different stages (stage I, II, III) at diagnosis (81.2%, 64.9%, and 37.3% for COS; 85.1, 65.1%, and 67.9% for CRFS; 89.2%, 72.1%, and 41.1% for CRS), the gap decreased with time; rates were similar after 5 years (77.1%, 75.7%, and 72.6% for COS; 91.7%, 90.6%, and 94.5% for CRFS, and 89.3%, 85.4%, and 78.3% in CRS, respectively). The 5Y COS, CRFS, and CRS were persistently lower in older patients even after 5 years.

Conclusions: Conditional survival estimates generally increase over time, and the largest improvements were observed for patients with advanced stage. Availability of updated prognosis at various time points allows clinicians to better guide their patients. Our results also imply substantial residual risk of recurrence and sustained excess mortality compared to the general population even after 5 years.
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http://dx.doi.org/10.1097/SLA.0000000000004473DOI Listing
October 2020

Association between Sarcopenia and Physical Function among Preoperative Lung Cancer Patients.

J Pers Med 2020 Oct 13;10(4). Epub 2020 Oct 13.

Department of Family Medicine & Supportive Care Center, Samsung Medical Center, Seoul 06351, Korea.

We aimed to investigate the prevalence of sarcopenia using new diagnostic criteria and association of sarcopenia with cardiopulmonary function and physical activity (PA) in preoperative lung cancer patients. The data of 614 patients were obtained from the CATCH-LUNG cohort study. Patients were classified into three groups-normal ( = 520), pre-sarcopenia ( = 60, low skeletal muscle mass index only), and sarcopenia ( = 34, low SMI and strength). Cardiopulmonary function was measured using the 6-min walk test (6MWT), and PA was objectively measured using a wearable device. The adjusted odds ratio (aOR) for a <400-m distance in 6MWT was 3.52 (95% confidence interval (CI) 1.34-9.21) and 6.63 (95% CI 2.25-19.60) in the pre-sarcopenia and sarcopenia groups, respectively, compared to that in the normal group. The aOR (95% CI) for <5000 steps/day was 1.64 (0.65-4.16) and 4.20 (1.55-11.38) in the pre-sarcopenia and sarcopenia groups, respectively, compared to that in the normal group. In conclusion, the prevalence of pre-sarcopenia and sarcopenia was 9.8% and 5.5%, respectively, among preoperative lung cancer patients. Cardiopulmonary function and physical activity were significantly lower in the pre-sarcopenia and sarcopenia groups than in the normal group. Patients with sarcopenia had more robust findings, suggesting the importance of muscle strength and mass.
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http://dx.doi.org/10.3390/jpm10040166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712435PMC
October 2020

Negative Effect of Reduced NME1 Expression on Recurrence-Free Survival in Early Stage Non-Small Cell Lung Cancer.

J Clin Med 2020 Sep 23;9(10). Epub 2020 Sep 23.

Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.

This study aimed to understand whether the effect of non-metastatic cells 1 (NME1) on recurrence-free survival (RFS) in early stage non-small cell lung cancer (NSCLC) can be modified by β-catenin overexpression and cisplatin-based adjuvant chemotherapy. Expression levels of NME1 and β-catenin were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 425 early stage NSCLC patients. Reduced NME1 expression was found in 39% of samples. The median duration of follow-up was 56 months, and recurrence was found in 186 (44%) of 425 patients. The negative effect of reduced NME1 expression on RFS was worsened by cisplatin-based adjuvant chemotherapy (adjusted hazard ratio = 3.26, 95% CI = 1.16-9.17, = 0.03). β-catenin overexpression exacerbated the effect of reduced NME1 expression on RFS and the negative effect was greater when receiving cisplatin-based adjuvant chemotherapy: among patients treated with cisplatin-based adjuvant chemotherapy, hazard ratios of patients with reduced NME1 expression increased from 5.59 (95% confidence interval (CI) = 0.62-50.91, = 0.13) to 15.52 (95% CI = 2.94-82.38, = 0.001) by β-catenin overexpression, after adjusting for confounding factors. In conclusion, the present study suggests that cisplatin-based adjuvant chemotherapy needs to be carefully applied to early stage NSCLC patients with overexpressed β-catenin in combination with reduced NME1 expression.
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http://dx.doi.org/10.3390/jcm9103067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598190PMC
September 2020

Spread through air spaces (STAS) in invasive mucinous adenocarcinoma of the lung: Incidence, prognostic impact, and prediction based on clinicoradiologic factors.

Thorac Cancer 2020 11 25;11(11):3145-3154. Epub 2020 Sep 25.

Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background: Spread through air spaces (STAS) has recently been demonstrated to exhibit a negative impact on lung adenocarcinoma prognosis. However, most of these studies investigated STAS in nonmucinous adenocarcinoma. Here, we investigated the incidence of STAS in invasive mucinous adenocarcinoma (IMA) of the lung and evaluated whether tumor STAS was a risk factor of disease recurrence in IMA. We also examined clinicoradiologic factors in patients with IMA harboring STAS.

Methods: We reviewed pathologic specimens and imaging characteristics of primary tumors from 132 consecutive patients who underwent surgical resection for IMA to evaluate STAS. Patients with and without STAS were compared with respect to clinical characteristics as well as computed tomography (CT) imaging using logistic regression. The relationships between all variables including STAS and survival were analyzed.

Results: Among a total of 132 patients, full pathologic specimens were available for 119 patients, and STAS was observed in 86 (72.3%). IMA patients with STAS were significantly associated with older age, presence of lobulated and spiculated margins on CT scan (P = 0.009, P = 0.006, and P = 0.027). In multivariate analysis for overall survival (OS), STAS was a borderline independent poor prognostic predictor (P = 0.028). Older age, history of smoking, higher T stage, presence of lymph node metastasis, and consolidative morphologic type remained independent predictors for OS.

Conclusions: STAS was associated with reduced OS and was a borderline independent poor prognostic factor in IMA. IMA with STAS was associated with older age and presence of lobulated and spiculated margins on CT scan.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Compared with other subtypes, IMA shows a higher incidence of STAS, which is an independent poor prognostic predictor even in IMA. Lobulated and spiculated margins on CT are associated with STAS.

What This Study Adds: Considering that STAS can carry the potential for aerogenous metastasis, predicting STAS using preoperative surrogate CT imaging is desirable to avoid limited resection.
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http://dx.doi.org/10.1111/1759-7714.13632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606017PMC
November 2020

Utility of positron emission-computed tomography for predicting pathological response in resectable oesophageal squamous cell carcinoma after neoadjuvant chemoradiation.

Eur J Cardiothorac Surg 2020 11;58(5):1019-1026

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea.

Objectives: For patients with locally advanced oesophageal cancer, improved complete pathological response after neoadjuvant chemoradiation (nCRT) and the detrimental effects on the quality of life related to oesophagectomy have led to the need for a reliable method to select patients who have achieved complete pathological response and do not need surgery. The reliability of 18F-fluorodeoxyglucose positron emission-computed tomography (PET-CT) for predicting the pathological response after nCRT was evaluated.

Methods: Patients with locally advanced oesophageal cancer who were treated with nCRT and oesophagectomy from July 2010 to February 2017 were analysed. On the post-nCRT PET-CT, a complete metabolic response was defined as all tumourous lesions demonstrating maximum standardized uptake value (SUVmax) ≤2.5. To minimize the effect of radiation-induced oesophagitis, complete metabolic response was also defined as no viable lesion distinguishable from the background with diffuse uptake. The sensitivity, specificity, positive predictive value and negative predictive value were analysed for SUVmax, [X]ΔSUVmax and %ΔSUVmax.

Results: A total of 158 patients with oesophageal squamous cell carcinoma were analysed. The rate of complete pathological response was 27.8%, and that of complete metabolic response was 7.6%. The sensitivity, specificity, positive predictive value and negative predictive value based on SUVmax ≤2.5 and visual normalization were 95%, 14%, 74% and 50%, respectively. Analysis for [X]ΔSUVmax and %ΔSUVmax using the optimal cut-off values determined by the receiver operating characteristic curves did not show an improved predictive efficacy.

Conclusions: PET-CT is not a reliable tool for predicting pathological response. Patients diagnosed with resectable oesophageal cancer who underwent neoadjuvant therapy should not be exempt from surgery based on PET-CT results.
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http://dx.doi.org/10.1093/ejcts/ezaa181DOI Listing
November 2020

A return-to-work intervention protocol directed at cancer patients (self-assessment, tailored information & lifestyle management for returning to work among cancer patients, START): A multi-center, randomized controlled trial.

Contemp Clin Trials Commun 2020 Sep 12;19:100633. Epub 2020 Aug 12.

Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.

Purpose: This study describes the protocol for the design and evaluation of a self-assessment based educational program supporting cancer patients' return-to-work (RTW), prior to its complete and ongoing implementation.

Methods: We designed a multi-center, randomized controlled trial with three follow-up points. The study population (N = 239) includes recently diagnosed cancer patients who plan to receive active treatment at two university hospitals in Korea. A pre-test is conducted at the point of enrollment for both groups. The intervention group receives a leaflet clarifying misconceptions about RTW and is shown a video clip of patient interviews concerning RTW. The control group receives a booklet about cancer and nutrition, and is not provided with further intervention. After active treatment, the intervention group receives a one-time, face-to-face education session with an oncology nurse. Following the education session, both groups receive three follow-up phone calls. The first follow-up call occurs at the end of intervention and at the end of active treatment for intervention and control groups, respectively. The next two follow-up calls will be conducted one month and a year following the post-test. The primary outcome is whether the patient has RTW or has plans to RTW, and the secondary outcome is knowledge of RTW.

Results: As of April 2020, 239 patients have been enrolled in the trial. Statistical analyses will be conducted upon trial completion in December 2020.

Discussion: We hypothesize that the provision of RTW education near diagnosis will not only enhance patients' intentions to RTW, but also effectively encourage them to RTW.
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http://dx.doi.org/10.1016/j.conctc.2020.100633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451719PMC
September 2020

Esophageal Cancer: Overcome the Hurdles and Reach for the Cure.

Korean J Thorac Cardiovasc Surg 2020 Aug;53(4):151

Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.5090/kjtcs.2020.53.4.151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409888PMC
August 2020

Tumor size as a prognostic factor in limited-stage thymic epithelial tumors: A multicenter analysis.

J Thorac Cardiovasc Surg 2020 May 27. Epub 2020 May 27.

Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objective: The prognostic significance of tumor size in thymic epithelial tumors (TETs) has not been fully evaluated. We aimed to clarify the prognostic value of tumor size in limited-stage and advanced-stage TETs.

Methods: Clinical records of patients with completely resected TETs were retrospectively collected from 4 tertiary centers between January 2000 and February 2013. Information on the Masaoka-Koga stage was available for 1215 patients (M-K group), and 433 patients were classified according to the eighth edition of the Tumor-Node-Metastasis staging system (TNM group). Limited-stage and advanced-stage TETs were defined according to whether they were confined within the surrounding fatty tissues without invasion. The optimal cutoff value was selected using a maximally selected log-rank statistic.

Results: The median tumor size was 6.0 ± 2.8 cm in the M-K group and 6.5 ± 3.0 cm in the TNM group. In the multivariable analysis, tumor size had a significant effect on both overall survival (P = .003) and recurrence-free survival (P < .001) for limited-stage tumors (M-K stage I or II or TNM stage I), but not for advanced-stage tumors (M-K stage III or IV or TNM stage II-IV; P = .349 for overall survival and P = .439 for recurrence-free survival). The optimal cutoff value for tumor size was >5.5 cm for both overall survival and recurrence-free survival in limited-stage TETs.

Conclusions: Tumor size is an independent prognostic factor in patients with completely resected limited-stage TETs and a cutoff value >5.5 cm might help clinicians enact proper treatment strategies and surveillance.
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http://dx.doi.org/10.1016/j.jtcvs.2020.05.048DOI Listing
May 2020

Adjuvant therapy in stage IIIA-N2 non-small cell lung cancer after neoadjuvant concurrent chemoradiotherapy followed by surgery.

J Thorac Dis 2020 May;12(5):2602-2613

Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: This study aimed to determine whether adjuvant therapy improves survival in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) after neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery.

Methods: We retrospectively reviewed 467 consecutive patients with stage IIIA-N2 NSCLC who received neoadjuvant CCRT followed by surgery between 2004 and 2013. From these, we identified 398 eligible patients and their clinical outcomes were compared according to whether adjuvant therapy was provided.

Results: In total, 296 patients (74%) received adjuvant therapy consisting of chemotherapy alone (n=71) radiotherapy alone (n=118) and both chemotherapy and radiotherapy (n=107). Adjuvant therapy was not given to remaining 102 patients. Patients who receiving adjuvant therapy were significantly younger (P=0.001), and predominantly male (P=0.014) compared to patients who did not receive adjuvant therapy. Regarding to the pathologic response, the adjuvant therapy group had a significantly poor pathologic response. However, the 5-year overall survival (OS) rate did not significantly differ between the groups (adjuvant therapy group, 52.9%; no adjuvant therapy group, 54.9%; P=0.369). After adjusting for age, sex, type of operation, cell type and yp stage, adjuvant therapy was significantly associated with better OS (hazard ratio =0.59; 95% CI, 0.38-0.92; P=0.019) and disease free survival (hazard ratio =0.62; 95% CI, 0.44-0.87; P=0.006).

Conclusions: Our data indicate that adjuvant therapy is more often given to patients with poor pathologic findings. Adjuvant treatment after trimodal therapy is a significant predictor of survival after adjustment of clinical variables.
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http://dx.doi.org/10.21037/jtd.2020.03.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330356PMC
May 2020

The major effects of health-related quality of life on 5-year survival prediction among lung cancer survivors: applications of machine learning.

Sci Rep 2020 07 1;10(1):10693. Epub 2020 Jul 1.

Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Korea.

The primary goal of this study was to evaluate the major roles of health-related quality of life (HRQOL) in a 5-year lung cancer survival prediction model using machine learning techniques (MLTs). The predictive performances of the models were compared with data from 809 survivors who underwent lung cancer surgery. Each of the modeling technique was applied to two feature sets: feature set 1 included clinical and sociodemographic variables, and feature set 2 added HRQOL factors to the variables from feature set 1. One of each developed prediction model was trained with the decision tree (DT), logistic regression (LR), bagging, random forest (RF), and adaptive boosting (AdaBoost) methods, and then, the best algorithm for modeling was determined. The models' performances were compared using fivefold cross-validation. For feature set 1, there were no significant differences in model accuracies (ranging from 0.647 to 0.713). Among the models in feature set 2, the AdaBoost and RF models outperformed the other prognostic models [area under the curve (AUC) = 0.850, 0.898, 0.981, 0.966, and 0.949 for the DT, LR, bagging, RF and AdaBoost models, respectively] in the test set. Overall, 5-year disease-free lung cancer survival prediction models with MLTs that included HRQOL as well as clinical variables improved predictive performance.
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http://dx.doi.org/10.1038/s41598-020-67604-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329866PMC
July 2020

Clinicopathological Significance of in Non-Small Cell Lung Cancer.

J Clin Med 2020 Jun 2;9(6). Epub 2020 Jun 2.

Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.

This study aimed to understand the clinicopathological significance of runt-related transcription factor 1 () in non-small cell lung cancer (NSCLC). The methylation and mRNA levels of in NSCLC were determined using the Infinium HumanMethylation450 BeadChip and the HumanHT-12 expression BeadChip. RUNX1 protein levels were analyzed using immunohistochemistry of formalin-fixed paraffin-embedded tissues from 409 NSCLC patients. Three CpGs (cg04228935, cg11498607, and cg05000748) in the CpG island of showed significantly different methylation levels (Bonferroni corrected < 0.05) between tumor and matched normal tissues obtained from 42 NSCLC patients. Methylation levels of the CpGs in the tumor tissues were inversely related to mRNA levels of . A logistic regression model based on cg04228935 showed the best performance in predicting NSCLCs in a test dataset (N = 28) with the area under the receiver operating characteristic (ROC) curve (AUC) of 0.96 (95% confidence interval (CI) = 0.81-0.99). The expression of RUNX1 was reduced in 125 (31%) of 409 patients. Adenocarcinoma patients with reduced RUNX1 expression showed 1.97-fold (95% confidence interval = 1.16-3.44, = 0.01) higher hazard ratio for death than those without. In conclusion, the present study suggests that abnormal methylation of may be a valuable biomarker for detection of NSCLC regardless of race. And, reduced RUNX1 expression may be a prognostic indicator of poor overall survival in lung adenocarcinoma.
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http://dx.doi.org/10.3390/jcm9061694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356912PMC
June 2020

Efficacy of health coaching and a web-based program on physical activity, weight, and distress management among cancer survivors: A multi-centered randomised controlled trial.

Psychooncology 2020 07 23;29(7):1105-1114. Epub 2020 Apr 23.

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Objectives: To investigate the efficacy of health coaching and a web-based program on survivor physical activity (PA), weight, and distress management among stomach, colon, lung and breast cancer patients.

Methods: This randomised, controlled, 1-year trial conducted in five hospitals recruited cancer survivors within 2 months of completing primary cancer treatment who had not met ≥1 of these behavioural goals: (i) conducting moderate PA for at least 150 minutes/week or strenuous exercise for over 75 minutes per week or, in the case of lung cancer patients, low or moderate intensity exercise for over 12.5 MET per week, (ii) maintaining normal weight, and (iii) attaining a score >72 in the Post Traumatic Growth Inventory (PTGI). Participants were randomly assigned to one of three groups: the control group, a web-only group, or a health coaching + web group. The primary endpoint was based on a composite of PA, weight, and PTGI score at 12 months.

Results: Patients in the health coaching + web group (difference = 6.6%, P = .010) and the web-only group (difference = 5.9%, P = .031) had greater overall improvements across the three-outcome composite than the control group. The health coaching + web group had greater overall improvement in PTGI (difference = 12.6%; P < .001) than the control group, but not in PA and weight.

Conclusion: The web-based program, with or without health coaching, may improve health behaviours including PA, weight, and distress management among cancer survivors within 2 months of completing primary cancer treatment. The web-based program with health coaching was mainly effective for reducing psychological distress.
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http://dx.doi.org/10.1002/pon.5394DOI Listing
July 2020

Prognostic Impact of Sarcopenia and Skeletal Muscle Loss During Neoadjuvant Chemoradiotherapy in Esophageal Cancer.

Cancers (Basel) 2020 Apr 10;12(4). Epub 2020 Apr 10.

Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Backgrounds: The relationship between sarcopenia, characterized by loss of muscle mass and strength, and survival outcomes of esophageal cancer is controversial. This study aimed to assess the effect of sarcopenia and skeletal muscle loss on overall survival (OS) and recurrence-free survival (RFS) of esophageal cancer patients.

Methods: We retrospectively collected the medical records of 248 male patients diagnosed with squamous cell esophageal cancer and who underwent neoadjuvant chemoradiotherapy (NACRT) followed by surgery. We measured the cross-sectional area of the skeletal muscle at the L3 vertebra level using computed tomography images and calculated the skeletal muscle index (SMI). Sarcopenia was defined as SMI <52.4 cm/m, and excessive muscle loss was defined as SMI change <-10.0%/50 days during NACRT. Moreover, laboratory test results, such as albumin, prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) before and after NACRT, were collected.

Results: In the univariable Cox analysis, pre- ( = 0.689) and post-radiotherapy (RT) sarcopenia ( = 0.669) were not associated with OS. However, excessive muscle loss had a significant association with OS in both the univariable and multivariable analyses (all = 0.001). Excessive muscle loss was also related to RFS in both the univariable ( = 0.011) and multivariable ( = 0.022) Cox analysis. Patients with excessive muscle loss had significantly lower levels of post-RT albumin ( < 0.001) and PNI ( < 0.001), higher levels of post-RT NLR ( = 0.031) and PLR ( = 0.071), larger decrease in albumin ( < 0.001) and PNI ( < 0.001) after NACRT, and larger increase in NLR ( = 0.051) and PLR ( = 0.088) after NACRT than in those with non-excessive muscle loss.

Conclusion: Excessive muscle loss rather than pre- and post-RT sarcopenia was a significant prognostic factor for OS and RFS, and it was also related to nutritional and inflammatory markers.
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http://dx.doi.org/10.3390/cancers12040925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226603PMC
April 2020

Clinical outcomes of microscopic residual disease after bronchial sleeve resection for non-small cell lung cancer.

J Thorac Cardiovasc Surg 2020 Feb 29. Epub 2020 Feb 29.

Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea. Electronic address:

Objectives: To evaluate the significance of microscopic residual disease (MRD) at the bronchial resection margin after bronchial sleeve resection in non-small cell lung cancer.

Methods: We retrospectively reviewed 536 consecutive patients who underwent bronchial sleeve resection between 1995 and 2015. Clinical outcomes, including recurrence and long-term survival, were analyzed according to the bronchial resection margin status (R0 = complete resection and R1 = microscopic residual tumor).

Results: Forty patients (7.5%) were identified to have MRD. During a 52.4-month follow-up (range, 0.1-261.0 months), there was no significant difference in 5-year overall survival (61.8% vs 61.5%; P = .550) and 5-year recurrence-free survival (53.7% vs 59.0%; P = .390) between groups R1 and R0. Multivariable cox regression analysis demonstrated that the margin status (group R1) was not associated with significantly decreased overall survival and recurrence-free survival. In group R1, 3 patients (7.5%) showed locoregional recurrence, including 1 patient (2.5%) with anastomotic recurrence. There were no significant differences between both groups in anastomotic recurrence (2.5% vs 2.6%; P = 1.000), locoregional recurrence (7.5% vs 12.7%; P = .476), and distant recurrence (25.0% vs 23.2%; P = .947) rates. Subgroup analysis of group R1 revealed a significant trend toward an increasing recurrence rate as the pathological extent of MRD advanced toward invasive extramucosal carcinoma (P for trend = .015).

Conclusions: In our experience of bronchial sleeve resection, the oncologic outcome of MRD was not jeopardized. Furthermore, the pathological extent of MRD might be helpful for recurrence prediction and treatment planning.
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http://dx.doi.org/10.1016/j.jtcvs.2020.02.079DOI Listing
February 2020

Chronic obstructive pulmonary disease and lung cancer incidence in never smokers: a cohort study.

Thorax 2020 06 2;75(6):506-509. Epub 2020 Apr 2.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

There has been limited evidence for the association between chronic obstructive pulmonary disease (COPD) and the incidence of lung cancer among never smokers. We aimed to estimate the risk of lung cancer incidence in never smokers with COPD, and to compare it with the risk associated with smoking. This cohort study involved 338 548 subjects, 40 to 84 years of age with no history of lung cancer at baseline, enrolled in the National Health Insurance Service National Sample Cohort. During 2 355 005 person-years of follow-up (median follow-up 7.0 years), 1834 participants developed lung cancer. Compared with never smokers without COPD, the fully-adjusted hazard ratios (95% CI) for lung cancer in never smokers with COPD, ever smokers without COPD, and ever smokers with COPD were 2.67 (2.09 to 3.40), 1.97 (1.75 to 2.21), and 6.19 (5.04 to 7.61), respectively. In this large national cohort study, COPD was also a strong independent risk factor for lung cancer incidence in never smokers, implying that COPD patients are at high risk of lung cancer, irrespective of smoking status.
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http://dx.doi.org/10.1136/thoraxjnl-2019-213732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279186PMC
June 2020

Surgically Resected Esophageal Squamous Cell Carcinoma: Patient Survival and Clinicopathological Prognostic Factors.

Sci Rep 2020 03 19;10(1):5077. Epub 2020 Mar 19.

Division of Hemato-oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), Seoul, South Korea.

We aimed to report patients' survival after surgical resection of eSCC and to ascertain the clinical, imaging, and pathological factors related to patient prognosis. This retrospective study included 435 patients with eSCC of
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http://dx.doi.org/10.1038/s41598-020-62028-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081270PMC
March 2020

Seasonal Variation in Physical Activity among Preoperative Patients with Lung Cancer Determined Using a Wearable Device.

J Clin Med 2020 Jan 27;9(2). Epub 2020 Jan 27.

Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul 06351, Korea.

We aim to examine how season and temperature levels affect physical activity using a wearable device among patients scheduled to undergo surgical resection of lung cancer. Physical activity (PA) data from the wearable device were analyzed by seasons for 555 preoperative lung cancer patients from the CATCH-LUNG cohort study. The seasons were divided into spring, summer, autumn, and winter using the study enrollment date before surgery. The overall mean (SD) age was 61.1 (8.9) years, and the mean (SD) daily steps at each season were 11,438 (5922), 11,147 (5065), 10,404 (4403), and 8548 (4293), respectively. In the fully-adjusted models, patients in the winter season had 27.04% fewer daily steps (95% CI = -36.68%, -15.93%) and 35.22% less time spent performing moderate to vigorous physical activity (MVPA) compared to patients in the spring. The proportion of participants with over 8000 steps and duration of MVPA were significantly lower in the winter than the spring. In particular, daily steps had a negative linear association with wind chill temperature in patients who lived in Seoul. In conclusion, PA was significantly lower in the winter and it was more robust in patients who had a low cardiorespiratory function.
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http://dx.doi.org/10.3390/jcm9020349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073689PMC
January 2020

Prognostic Value of 6-Min Walk Test to Predict Postoperative Cardiopulmonary Complications in Patients With Non-small Cell Lung Cancer.

Chest 2020 Jun 25;157(6):1665-1673. Epub 2020 Jan 25.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address:

Background: The risk stratification value of the 6-min walk test (6MWT) to decide the feasibility of surgical resection is not well elucidated in patients with non-small cell lung cancer (NSCLC) and moderately decreased lung function.

Objective: This study aimed to determine the role of the 6MWT in predicting postoperative cardiopulmonary complications in patients with NSCLC who underwent lobectomy and had moderately decreased lung function.

Methods: The data were obtained from a prospective cohort study called Coordinate Approach to Cancer Patient's Health for Lung Cancer (CATCH-LUNG). Patients who underwent lobectomy for NSCLC were classified into two groups according to predicted postoperative pulmonary function (low-risk group or moderate-risk group); each group was then further classified into short-distance (< 400 m) or long-distance (≥ 400 m) groups according to a 6-min walk distance. The main end point of this study was the incidence of postoperative cardiopulmonary complications occurring within the first 30 postoperative days. A multivariable logistic regression model was used to compare the postoperative cardiopulmonary complications among the four groups.

Results: The adjusted ORs for any postoperative pulmonary complications, postoperative cardiac complications, and postoperative cardiopulmonary complications in patients with moderate-risk/short-distance relative to those with low-risk/long-distance were 10.26 (95% CI, 2.37-44.36), 5.65 (95% CI, 1.39-22.90), and 7.84 (95% CI, 2.24-27.46), respectively. However, these complications were not different between the patients with moderate-risk/long-term distance and those with low-risk/long-distance. Among patients in the moderate-risk group, those in the short-distance group had a significantly higher risk of postoperative cardiopulmonary complications compared with those in the long-distance group (adjusted OR, 4.95; 95% CI, 1.37-17.93).

Conclusions: Patients with NSCLC with moderate-risk/short-distance were at greater risk of developing postoperative cardiopulmonary complications; it may be feasible, however, for patients with NSCLC and moderate-risk/long-distance to undergo lobectomy compared with those with low-risk/long-distance. Our study suggests that the 6MWT could provide additional information in identifying optimal candidates for lung resection surgery of NSCLC.

Trial Registry: ClinicalTrials.gov; No.: NCT03705546; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2019.12.039DOI Listing
June 2020

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.

Respir Res 2020 Jan 10;21(1):13. Epub 2020 Jan 10.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

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.
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http://dx.doi.org/10.1186/s12931-019-1254-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954564PMC
January 2020

High CD3 and ICOS and low TIM-3 expression predict favourable survival in resected oesophageal squamous cell carcinoma.

Sci Rep 2019 12 27;9(1):20197. Epub 2019 Dec 27.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

With the increasing oncological potential of immunotherapy, several immune checkpoint modulators are being investigated. The value of immune markers, including programmed cell death ligand-1, programmed cell death-1 (PD-1), inducible co-stimulator (ICOS), lymphocyte activation gene-3, T-cell immunoglobulin, and mucin-dominant containing-3 (TIM-3), is not well known. Using tissue microarrays of 396 patients who underwent surgery for oesophageal squamous cell carcinoma (ESCC), infiltrated T-cell subsets (CD3, CD8, and Foxp3) and checkpoint protein expression were scored. With a median follow-up of 24.8 months, CD3 TIL subsets (50.0%) had longer median recurrence-free survival (RFS, 55.0 vs 21.4 months) and overall survival (OS, 77.7 vs 35.8 months). Patients with high ICOS expression (46.5%) had longer median RFS (53.9 vs 25.3 months) and OS (88.8 vs 36.9 months). For PD-1, RFS (hazard ratio [HR] 0.67) and OS (HR 0.66) were significantly longer in the high-expression group (45.2%). In the multivariate analysis, high TIM-3 expression (50.8%) had a significant relationship with shorter RFS (HR = 1.52) and OS (HR = 1.60). High CD3 TIL and T-cell ICOS expression were associated with favourable prognosis, whereas high TIM-3 expression suggested a poor prognosis. Our findings may confer new insights to improve ESCC outcomes beyond the application of PD-1 blockade.
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http://dx.doi.org/10.1038/s41598-019-56828-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934772PMC
December 2019

Predictors of post-thymectomy long-term neurological remission in thymomatous myasthenia gravis: an analysis from a multi-institutional database.

Eur J Cardiothorac Surg 2020 05;57(5):867-873

Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objectives: Thymectomy is the treatment of choice for thymomatous myasthenia gravis (MG) for both oncological and neurological aspects. However, only a few studies comprising small numbers of patients have investigated post-thymectomy neurological outcomes. We examined post-thymectomy long-term neurological outcomes and predictors of thymomatous MG using a multi-institutional database.

Methods: In total, 193 patients (47.3 ± 12.0 years; male:female = 90:103) with surgically resected thymomatous MG between 2000 and 2013 were included. Complete stable remission (CSR) and composite neurological remission (CNR), defined as the achievement of CSR and pharmacological remission after thymectomy, were evaluated. Predictors for CSR and CNR were examined by Cox regression analysis.

Results: The median duration between MG and thymectomy was 3.1 months. In addition, 161 patients (83.4%) had symptoms less than Myasthenia Gravis Foundation of America clinical classification III. All patients underwent an extended thymectomy; there were no perioperative deaths. The 10-year cumulative probability of CSR and CNR was 36.9% and 69.1%, respectively. Mild preoperative symptoms were a significant predictor for CSR (P = 0.040), and a large tumour was a predictor for CNR (P < 0.001). Patients with a large tumour were associated with early MG onset and no steroid treatment. Surgical methods, thymoma stage and histological subtypes were not associated with long-term neurological remission.

Conclusions: Large tumour size and preoperative mild symptoms were predictors for long-term neurological outcome in thymomatous MG. Considering that patients with early onset of MG and no immunosuppressive treatment tend to have large tumours, early surgical intervention for patients with thymomatous MG having mild symptoms might be beneficial for controlling neurological outcomes.
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http://dx.doi.org/10.1093/ejcts/ezz334DOI Listing
May 2020

Nomogram for prediction of lymph node metastasis in patients with superficial esophageal squamous cell carcinoma.

J Gastroenterol Hepatol 2020 Jun 15;35(6):1009-1015. Epub 2019 Dec 15.

Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background And Aim: Knowledge of lymph node metastasis (LNM) status is crucial to determine whether patients with superficial esophageal squamous cell carcinoma (ESCC) can be cured with endoscopic resection alone, without the need for additional esophagectomy. The present study aimed to identify predictive factors and develop a prediction model for LNM in patients with superficial ESCC.

Methods: Clinicopathologic data from 501 patients with superficial ESCC treated with radical esophagectomy were reviewed. Stepwise logistic regression analysis determined the predictors of LNM. Using these predictors, a nomogram for predicting the risk of LNM was constructed and internally validated using a bootstrap resampling method.

Results: LNM rates of tumors invading the lamina propria, muscularis mucosa, and SM1 layers were 3.7%, 15.5%, and 40.7%, respectively. Deep tumor invasion depth, moderately or poorly differentiated histology, and lymphovascular invasion were independent predictors of LNM. ESCC with muscularis mucosa and SM1 invasion had odds ratios of 3.635 and 11.834, respectively, compared with that for ESCC confined to the lamina propria. Large tumor size (>2.0 cm) and presence of tumor budding showed borderline significance for LNM prediction. These five variables were incorporated into a nomogram. A constructed nomogram showed good calibration and good discrimination with an area under the receiver-operating characteristic curve (area under the curve [AUC]) of 0.812. After bootstrapping, AUC was 0.811.

Conclusions: We developed a nomogram that can facilitate individualized prediction of risk of LNM in patients with superficial ESCC. This model can aid in decision-making for the need for additional esophagectomy after endoscopic resection for superficial ESCC.
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http://dx.doi.org/10.1111/jgh.14915DOI Listing
June 2020