Publications by authors named "Sanghoon Jheon"

172 Publications

Synchrotron Radiation-Based Refraction-Contrast Tomographic Images Using X-ray Dark-Field Imaging Optics in Human Lung Adenocarcinoma and Histologic Correlations.

Diagnostics (Basel) 2021 Mar 10;11(3). Epub 2021 Mar 10.

Department of Thoracic and Cardiovascular Surgery, Soonchunhyang University Gumi Hospital, Gumi 39371, Korea.

The aim of this study was to evaluate the clinical implication of synchrotron radiation imaging techniques for human lung adenocarcinoma in comparison with pathologic examination. A refraction-based tomographic imaging technique called the X-ray dark-field imaging (XDFI) method was used to obtain computed tomographic images of human lung adenocarcinoma at the beam line at Photon Factory BL 14B at the High Energy Accelerator Research Organization (KEK) in Tsukuba, Japan. Images of normal lung tissue were also obtained using the same methods and reconstructed as 3D images. Both reconstructed images were compared with pathologic examinations from histologic slides which were made with identical samples. Pulmonary alveolar structure including terminal bronchioles, alveolar sacs, and vasculatures could be identified in synchrotron radiation images of normal lung. Hyperplasia of interstitial tissue and dysplasia of alveolar structures were noticed in images of lung adenocarcinoma. Both synchrotron radiation images were considerably correlated with images from histologic slides. Lepidic patterns of cancer tissue were distinguished from the invasive area in synchrotron radiation images of lung adenocarcinoma. Refraction-contrast tomographic techniques using synchrotron radiation could provide high-resolution images of lung adenocarcinoma which are compatible with those from pathologic examinations.
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http://dx.doi.org/10.3390/diagnostics11030487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999731PMC
March 2021

Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer.

Oncology 2021 Feb 24:1-9. Epub 2021 Feb 24.

Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery.

Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated.

Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00-1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46-0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes.

Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.
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http://dx.doi.org/10.1159/000514131DOI Listing
February 2021

Prognostic significance of tumor spread through air spaces in patients with stage IA part-solid lung adenocarcinoma after sublobar resection.

Lung Cancer 2021 02 5;152:21-26. Epub 2020 Dec 5.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objectives: The purpose of this study was to assess the clinicopathologic implications of tumor spread through air spaces (STAS) in patients with stage IA part-solid lung adenocarcinoma after sublobar resection.

Materials And Methods: Medical records of patients with stage IA part-solid adenocarcinoma who underwent curative pulmonary resection between February 2009 and December 2016 were retrospectively reviewed. The clinicopathological features of STAS and its influence on postoperative recurrence and survival were investigated.

Results: Among the 115 patients with stage IA part-solid adenocarcinoma who underwent wedge resection, 20 (17.4 %) had STAS. The multivariable analysis showed presence of STAS [HR (hazard ratio), 9.447; p = 0.002) and a larger invasive component size (HR, 1.097; p = 0.034) were independent risk factors for recurrence. The 5-year freedom from recurrence rates were 62.4 % and 97.9 % in cases with and without STAS, respectively (p < 0.001), and the 5-year disease-free survival rates were 58.5 % and 97.9 % in cases with and without STAS, respectively (p < 0.001). The presence of STAS was associated with old age (p = 0.030), male gender (p = 0.023), acinar predominant histologic pattern (p = 0.004), presence of micropapillary pattern (p < 0.001), lymphovascular invasion (p < 0.001) and larger invasive component (p < 0.001).

Conclusion: STAS could be an important prognostic factor in patients with stage IA part-solid lung adenocarcinoma after sublobar resection. Effective preoperative evaluation and postoperative surveillance may help improve the outcome of patients with small part-solid nodules, particularly when accompanied by STAS.
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http://dx.doi.org/10.1016/j.lungcan.2020.12.001DOI Listing
February 2021

Effects of Ultralow-Tidal-Volume Ventilation under Veno-Venous Extracorporeal Membrane Oxygenation in a Porcine Model with Ventilator-Induced Lung Injury.

Membranes (Basel) 2020 Nov 28;10(12). Epub 2020 Nov 28.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.

Low-tidal-volume ventilation decreases mortality in acute respiratory distress syndrome (ARDS) patients. This study investigated the effects of ultralow tidal ventilation under veno-venous extracorporeal membrane oxygenator (ECMO) support in pigs with ARDS. Eight pigs were intubated and inoculated with methicillin-resistant through bronchoscopy. Ultralow tidal ventilation (3 mL/kg) under extracorporeal membrane oxygenator (ECMO) support was applied to one group and high tidal ventilation (15 mL/kg) was applied to another group to maintain comparable oxygenation for 12 h without ECMO support. Each group had similar arterial blood gas values and hemodynamic variables at baseline and during the experiment. The high-tidal-volume ventilation group showed a gradual decline in arterial oxygen levels, and repeated ANOVA showed significant differences in oxygenation change over time in the ultralow tidal ventilation group. Inflammatory cytokine levels in the bronchoalveolar lavage fluid and lung ultrasound scores were similar between two groups. Histologic analysis showed that both groups developed pneumonia after 12 h; however, the ultralow tidal ventilation group had a lower lung injury score assessed by the pathologist. We developed the first ultralow-tidal-volume ventilation porcine model under veno-venous ECMO support. The ultralow-tidal-volume ventilation strategy can mitigate mechanical ventilator-associated lung injury.
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http://dx.doi.org/10.3390/membranes10120379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761070PMC
November 2020

Tumor spread through air spaces (STAS): prognostic significance of grading in non-small cell lung cancer.

Mod Pathol 2021 03 16;34(3):549-561. Epub 2020 Nov 16.

Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

Tumor spread through air spaces (STAS) is an invasive pattern of lung cancer that was recently described. In this study, we investigated the association between the extent of STAS and clinicopathological characteristics and patient outcomes in resected non-small cell lung cancers (NSCLCs). STAS has been prospectively described from 2008 and graded its extent with a two-tiered system (STAS I: <2500 μm [one field of ×10 objective lens] from the edge of tumor and STAS II: ≥2500 μm from the edge of tumor) from 2011 in Seoul National University Bundang Hospital. We retrospectively analyzed the correlations between the extent of STAS and clinicopathologic characteristics and prognostic significance in 1869 resected NSCLCs. STAS was observed in 765 cases (40.9%) with 456 STAS I (24.4%) and 309 STAS II (16.5%). STAS was more frequently found in patients with adenocarcinoma (ADC) (than squamous cell carcinoma), pleural invasion, lymphovascular invasion, and/or higher pathologic stage. In ADC, there were significant differences in recurrence free survival (RFS), overall survival (OS), and lung cancer specific survival (LCSS) according to the extent of STAS. In stage IA non-mucinous ADC, multivariate analysis revealed that STAS II was significantly associated with shorter RFS and LCSS (p < 0.001 and p = 0.006, respectively). In addition, STAS II was an independent poor prognostic factor for recurrence in both limited and radical resection groups (p = 0.001 and p = 0.023, respectively). In conclusion, presence of STAS II was an independent poor prognostic factor in stage IA non-mucinous ADC regardless of the extent of resection.
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http://dx.doi.org/10.1038/s41379-020-00709-2DOI Listing
March 2021

The differential prognostic impact of spread through air spaces in early-stage lung adenocarcinoma after lobectomy according to the pT descriptor.

J Thorac Cardiovasc Surg 2020 Oct 7. Epub 2020 Oct 7.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul, Republic of Korea; Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: We evaluated the differential prognostic impact of spread through air spaces (STAS) in early-stage lung adenocarcinoma after lobectomy according to the pT descriptor.

Methods: The study population included 506 patients who underwent lobectomy with mediastinal lymph node dissection for pT1b, pT1c, and pT2a adenocarcinoma between 2011 and 2016. We divided the study population into 2 groups according to STAS status, ie, STAS (+) versus STAS (-), and stratified them according to the pT descriptor. A Cox proportional hazard model and inverse probability of treatment weight-adjusted Kaplan-Meier curves were used to evaluate the prognostic impact of STAS on recurrence-free survival (RFS) and its independency in each stratum.

Results: Multivariable Cox proportional hazard regression analysis demonstrated that in pT1b and pT1c strata, STAS (+) patients had a 7.02-fold and 2.89-fold greater risk of recurrence than STAS (-) patients, respectively. However, in the pT2a stratum, STAS did not affect RFS. And the RFS of the STAS (+) pT1b/c strata was similar to that of the pT2a stratum. In the pT1b/c strata, inverse probability of treatment weighting-adjusted Kaplan-Meier curves also showed that RFS was significantly worse when STAS was present. Furthermore, the risks for locoregional and distant recurrence were both greater when STAS was present.

Conclusions: The presence of STAS increased the risk of recurrence independently from other poor prognostic factors in patients with pT1b/cN0M0 adenocarcinoma who underwent lobectomy, but not in pT2a patients. The presence of STAS in pT1b/cN0M0 adenocarcinoma was associated with a similar risk of recurrence to that of pT2aN0M0 adenocarcinoma.
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http://dx.doi.org/10.1016/j.jtcvs.2020.09.098DOI Listing
October 2020

Comparison of survival outcomes between sublobar resection and lobectomies in early-stage lung adenocarcinoma by propensity score matching analysis.

Indian J Thorac Cardiovasc Surg 2020 Jul 3;36(4):382-387. Epub 2020 Mar 3.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Gyeonggi South Korea.

Background: The aim of this study was to investigate the clinical outcomes of sublobar resections and compare these with those of lobectomies in early-stage lung adenocarcinoma patients.

Methods: We retrospectively reviewed medical records of 871 patients who underwent lobectomies or sublobar resections for early-stage lung adenocarcinomas. Two hundred thirty-five (27.0%) patients underwent sublobar resections (wedge and segmentectomies), and 636 (73.0%) underwent lobectomies. Propensity score matching resulted in 2 groups each with 219 patients. Survival analysis was performed.

Results: Mean age of matched patients was 61.9 (± 10.38, range of 21 to 91) years, mean follow-up period was 50.8 (± 27.57, range of 6.1 to 128.9) months, and mean tumor size was 15.2 (± 6.49, range of 3.0 to 45.0) mm. Overall recurrence rate was 9.4% (41 patients), and it was 8.7% (19 patients) in sublobar resection patients and 9.6% (21 patients) in lobectomy patients. Rates and sites of recurrence were not significantly different between the two surgical groups ( = 0.500 and 0.401, respectively). Overall 5-year survival and recurrence-free survival of sublobar resection patients were 90.6 and 89.5%, respectively, whereas those of lobectomy patients were 91.9 and 88.3%, respectively. No significant differences in overall 5-year survival rate or recurrence-free survival rate were found between the two groups ( = 0.636 and = 0.975, respectively).

Conclusions: Prognosis of early-stage lung adenocarcinoma treated with sublobar resection was not inferior to that treated with lobectomy in carefully selected cases. Further investigations, including randomized controlled trials, are needed to identify the equivalent oncologic efficacy of sublobar resections.
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http://dx.doi.org/10.1007/s12055-019-00897-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525899PMC
July 2020

Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer.

Oncology 2020 13;98(12):897-904. Epub 2020 Aug 13.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC).

Methods: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed.

Results: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54-0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13-4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08-1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10-3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41-1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11-6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17-2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12-6.88, p = 0.03, respectively).

Conclusions: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.
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http://dx.doi.org/10.1159/000509658DOI Listing
December 2020

Predictive Factors for Lymph Node Metastasis in Clinical Stage I Part-Solid Lung Adenocarcinoma.

Ann Thorac Surg 2021 02 9;111(2):456-462. Epub 2020 Jul 9.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea; Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Accurate clinical staging of tumors with a small solid portion is essential for developing an appropriate treatment plan. This study evaluated predictive factors for lymph node (LN) metastasis in patients with clinical stage I part-solid lung adenocarcinoma.

Methods: Medical records of patients with clinical stage I part-solid adenocarcinoma who underwent anatomic pulmonary resection with systematic node evaluation between January 2009 and June 2018 were retrospectively reviewed. To identify predictive factors for LN metastasis, univariate and multivariable logistic regression analyses were performed.

Results: Among the 593 patients in this study, the overall prevalence of LN metastasis was 3.7% (n = 22), which included 3.0% (n = 18) of patients with N1 LN metastasis and 1.5% (n = 9) of patients with N2 LN metastasis. Combined N1 and N2 nodal involvement was observed in 5 patients. Nodal metastasis was not observed in tumors with a solid portion sized 1.1 cm or smaller. The nodal metastasis rates in cT1b, cT1c, and cT2a tumors were 5.5% (13 of 237), 7.1% (6 of 84), and 13.6% (3 of 22), respectively. According to the multivariable analysis, predictive factors included the size of the solid portion (P = .015) and the high maximum standardized uptake value (SUVmax) of the primary tumor (P = .044).

Conclusions: Large solid portion and high SUVmax of the primary tumor were predictive factors of LN metastasis in patients with clinical stage I part-solid lung adenocarcinoma. Systematic LN evaluation should be performed, especially in those who have a large solid portion and high SUVmax of the primary tumor.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.083DOI Listing
February 2021

Correction to: Stepwise Disease Progression Model of Subsolid Lung Adenocarcinoma with Cystic Airspaces.

Ann Surg Oncol 2020 Dec;27(Suppl 3):981-982

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea.

In the original article there are errors in Fig. 3. Following is the corrected figure.
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http://dx.doi.org/10.1245/s10434-020-08840-9DOI Listing
December 2020

Thoracic cancer surgery during the COVID-19 pandemic: a consensus statement from the Thoracic Domain of the Asian Society for Cardiovascular and Thoracic Surgery.

Asian Cardiovasc Thorac Ann 2020 Jul 1;28(6):322-329. Epub 2020 Jul 1.

Department of Thoracic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Objectives: Healthcare resources have been mobilized to combat the COVID-19 pandemic of 2020. The Thoracic Domain of the Asian Society for Cardiovascular and Thoracic Surgery reports a consensus statement on the provision of thoracic cancer surgery during this pandemic.

Methods: A Thoracic Experts Panel was convened by the Society. A consensus on the provision, safety, and setting of thoracic cancer surgery during the pandemic was obtained through a Delphi process.

Results: Responses were received from 26 panel members (96% response rate) from 10 regions across Asia. The Society recommended that elective thoracic cancer surgery services may need to be reduced or postponed if medical resources were needed for COVID-19 patients, especially intensive care unit beds and ventilators. However, thoracic cancer surgery should proceed as normal for all solid tumors, without restrictions based on disease stage, availability of non-surgical treatment options, or patient condition (unless there is a high likelihood of postoperative intensive care unit stay). Aerosol-forming procedures should be avoided intra- and perioperatively. The surgical approach does not make a difference in terms of safety. Services for thoracic cancer patients should be offered only in hospitals that maintain isolation wards for patients with confirmed or suspected COVID-19.

Conclusions: Services for patients with thoracic cancer should be maintained during the COVID-19 pandemic. The position of the Society is that thoracic surgeons have a responsibility to perform good surgical management of thoracic cancer during the pandemic, to advocate for patients' rights to receive it, and to safeguard patients and staff from infection.
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http://dx.doi.org/10.1177/0218492320940162DOI Listing
July 2020

Impact of idiopathic pulmonary fibrosis on recurrence after surgical treatment for stage I-III non-small cell lung cancer.

PLoS One 2020 29;15(6):e0235126. Epub 2020 Jun 29.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.

Background: Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, its effect on recurrence after curative surgery remains unclear.

Objectives: This study aimed to determine the impact of IPF on recurrence-free survival following curative surgical resection of stage I-III non-small cell lung cancer (NSCLC) and investigate the effects of patient and surgical factors on the risk of recurrence.

Methods: We reviewed retrospectively collected data of patients with surgically resected stage I-III NSCLC from two tertiary care hospitals in South Korea. By propensity score matching, patients with IPF (LC with IPF) were matched to those without IPF (LC without IPF).

Results: In total, 3416 patients underwent surgical resection, and 96 were diagnosed with underlying IPF. In the LC with IPF group, 89.6% patients were men, and the average age was 69.7 years. Sublobar resection was performed more frequently in the LC with IPF group than in the LC without IPF group, while the rate of mediastinal lymph node dissection and dissected node number were lower in the former group. The 5-year recurrence-free survival rate was significantly lower in the LC with IPF group (49.2%) than in the LC without IPF group (69.1%; P<0.001). Multivariable Cox regression analysis revealed that IPF and postoperative stage III were independent risk factors for recurrence.

Conclusions: IPF may increase the risk of recurrence after curative surgical treatment for NSCLC. Close surveillance for recurrence is mandatory for patients with underlying IPF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235126PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323957PMC
September 2020

General thoracic surgery services across Asia during the 2020 COVID-19 pandemic.

Asian Cardiovasc Thorac Ann 2020 Jun 12;28(5):243-249. Epub 2020 May 12.

Department of Cardiothoracic Surgery, Seoul National University Bundang Hospital, Bundang, South Korea.

The COVID-19 pandemic of 2020 posed an historic challenge to healthcare systems around the world. Besides mounting a massive response to the viral outbreak, healthcare systems needed to consider provision of clinical services to other patients in need. Surgical services for patients with thoracic disease were maintained to different degrees across various regions of Asia, ranging from significant reductions to near-normal service. Key determinants of robust thoracic surgery service provision included: preexisting plans for an epidemic response, aggressive early action to "flatten the curve", ability to dedicate resources separately to COVID-19 and routine clinical services, prioritization of thoracic surgery, and the volume of COVID-19 cases in that region. The lessons learned can apply to other regions during this pandemic, and to the world, in preparation for the next one.
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http://dx.doi.org/10.1177/0218492320926886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218355PMC
June 2020

Differentiating thymoma from thymic cyst in anterior mediastinal abnormalities smaller than 3 cm.

J Thorac Dis 2020 Apr;12(4):1357-1365

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Gyeonggi-do, Korea.

Background: Computed tomography (CT) screening for lung cancer has led to frequent findings of small anterior mediastinal masses. It is very hard to distinguish small thymomas from thymic cysts. The objective of this study was to develop a clinical model for predicting small thymomas (<3 cm) in asymptomatic patients.

Methods: Patients who underwent thymectomy for anterior mediastinal masses between 2004 and 2016 were included. All preoperative CT scans (pre- and post-enhanced) were retrospectively reviewed. Size, location, contour, shape, presence of calcification, and enhancement [Hounsfield units (HU)] were evaluated. A nomogram was built based on the predictive factors. For external validation, patients undergoing thymectomy in 2017 were enrolled and thymoma prediction was computed using the proposed nomogram.

Results: The study population consisted of 43 patients with thymoma and 57 with thymic cyst. The multivariable analysis identified a lobulated contour and a large difference in HU between post- and pre-enhancement as predictive factors of thymoma. These factors were included in the nomogram, which showed 95% (19/20) power for predicting thymoma after external validation.

Conclusions: This clinical model can be used to predict thymoma in patients with small, asymptomatic thymic abnormalities on CT screening.
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http://dx.doi.org/10.21037/jtd.2020.02.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212157PMC
April 2020

Stepwise Disease Progression Model of Subsolid Lung Adenocarcinoma with Cystic Airspaces.

Ann Surg Oncol 2020 Oct 3;27(11):4394-4403. Epub 2020 May 3.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea.

Objectives: Subsolid lung adenocarcinoma with cystic airspaces (LACA) is a unique manifestation of lung cancer. This study was conducted to establish a radiologic disease progression model of LACA and to explore its association with the clinical course and clinicopathologic features of LACA.

Materials And Methods: Sixty patients with LACA who underwent surgery at our center between 2004 and 2017 were retrospectively reviewed. The morphological changes of LACA over time on 98 serial computed tomography scans from 27 of 60 patients were tracked to establish a radiologic disease progression model. Associations between this model and the clinicopathologic characteristics of LACA were investigated.

Results: The following stepwise progression model of LACA was developed: in phase I, cystic airspaces (CAs) appear in the middle of non-solid nodules; in phase II, the CAs grow; in phase III, a solid component appears on the border of the CAs; and in phase IV, the solid component gradually surrounds the CAs and becomes thicker, and the CAs shrink. In total, 10 (17%), 33 (55%), and 17 (28%) LACA patients were classified as belonging to phases II, III, and IV at the time of surgery, respectively. More advanced phases were associated with higher pathologic T and N staging, lymphovascular invasion, visceral pleural invasion, spread through air spaces, and solid/micropapillary subtype. In the multivariate analysis, our model demonstrated a good discrimination capability for cancer recurrence risk.

Conclusions: The stepwise disease progression model of LACA based on radiologic findings developed in this study represented its natural clinical course and clinicopathologic features well.
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http://dx.doi.org/10.1245/s10434-020-08508-4DOI Listing
October 2020

Conversion surgery after cetuximab or bevacizumab plus FOLFIRI chemotherapy in colorectal cancer patients with liver- and/or lung-limited metastases.

J Cancer Res Clin Oncol 2020 Sep 1;146(9):2399-2410. Epub 2020 May 1.

Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro-173-beon-gil, Seongnam, 13620, Republic of Korea.

Purpose: Some metastatic colorectal cancer (mCRC) patients receive conversion surgery (CS), including metastasectomy after palliative chemotherapy. Although targeted agents significantly improved the outcomes, the clinical outcome of CS in the targeted agent era has not yet been thoroughly investigated.

Methods: We analyzed the clinical data of 96 mCRC patients who initially had unresectable liver- and/or lung-limited metastases and underwent first-line cetuximab or bevacizumab plus FOLFIRI between January 2013 and June 2017.

Results: Liver-limited metastasis was seen in 44 patients (45.8%), lung-limited metastases in 21 patients (21.9%), and both liver and lung metastases in 31 patients (32.3%). Among them, 37 patients (38.5%) received cetuximab, and 59 patients (61.5%) received bevacizumab plus FOLFIRI. Overall response rate was 63.9% and 40.7%, respectively (p = 0.035). After median 8.7 (range 2.5-27.3) months, CS was performed in 11 patients (29.7%) in cetuximab group and 15 patients (25.4%) in bevacizumab group (p = 0.646). Median overall survival has not been reached in R0-resected patients (n = 23), during the median follow-up period of 22.5 (range 9.8-54.5) months. Median disease-free survival was 7.1 (95% CI 2.5-11.7) months: 11.0 (95% CI 3.1-19.0) months in cetuximab group and 3.2 (95% CI 0.0-7.8) months in bevacizumab group (p = 0.422). There was no progression after 18.5 months and disease-free survival reached a plateau at 19.9%.

Conclusions: A substantial proportion of patients could receive CS after cetuximab or bevacizumab plus FOLFIRI chemotherapy. R0-resected patients had excellent overall survival, although 80.1% of them eventually experienced recurrence. Some patients could achieve durable disease-free state.
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http://dx.doi.org/10.1007/s00432-020-03233-7DOI Listing
September 2020

Prognostic stratification of pathological node-negative lung adenocarcinoma by carcinoembryonic antigen level.

Interact Cardiovasc Thorac Surg 2020 06;30(6):820-826

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.

Objectives: Carcinoembryonic antigen (CEA) is a well-known tumour marker for lung adenocarcinoma (AC). This study was conducted to evaluate the clinical characteristics and prognosis of patients with pathological node-negative lung AC who have a high preoperative level of CEA.

Methods: Among 2124 patients with lung AC between 2003 and 2016, 858 patients were enrolled. CEA levels were dichotomized as normal (≤5 ng/ml) or high (>5 ng/ml). According to the levels of CEA between 6 and 12 months after surgery, patients were divided into a normalized and a remained-high group. Propensity score matching was used to compare 80 patients without adjuvant chemotherapy (ACT) with 39 patients with ACT. Kaplan-Meier survival analysis with the log-rank test and Cox proportional hazards regression analysis were performed for recurrence-free survival (RFS) and overall survival (OS).

Results: The multivariable analysis showed that high maximum standardized uptake value and T2 stage were more common in patients with high levels of CEA. The median follow-up period was 52.8 months (range 6-169 months). The 5-year RFS and OS rates were 89.3% and 68.9% and 92.8% and 77.2% in normal patients and patients with high levels of CEA, respectively, with a statistically significant difference. The 5-year RFS was 79.4% and 39.2% in the normalized and remained-high groups after surgery, respectively (P = 0.011). The 5-year RFS and OS rates were 68.9% and 62.2% and 80.1% and 82.9% in patients without and with ACT, respectively. After propensity score matching, RFS was not significantly different between patients without and with ACT (P = 0.500); however, OS was significantly better in patients with ACT than in those without ACT (P = 0.001).

Conclusions: The clinicopathological characteristics, RFS and OS of patients with lung AC might be well discriminated by preoperative CEA levels. In patients with node-negative disease and high CEA levels, those with normalized CEA levels had a significantly better prognosis than those with persistently high CEA levels.
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http://dx.doi.org/10.1093/icvts/ivaa035DOI Listing
June 2020

Do ground-glass opacity-dominant features have prognostic significance in node-negative adenocarcinomas with invasive components of similar sizes?

Eur J Cardiothorac Surg 2020 06;57(6):1189-1194

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.

Objectives: The purpose of this study was to analyse the prognostic significance of the dominant features of ground-glass opacities (GGOs) in part-solid node-negative adenocarcinomas with invasive components of similar sizes.

Methods: From 2004 to 2017, a total of 544 patients with a diagnosis of part-solid pathological node-negative adenocarcinoma with an invasive component <20 mm in size were selected. The enrolled patients were categorized into 2 groups: a GGO-dominant [50% < GGO (%) < 100%, n = 245] group (group 1) and a solid-dominant [0% < GGO (%) ≤ 50%, n = 299] group (group 2). To analyse the prognostic significance of GGO-dominant features, propensity score matching incorporating variables such as age, sex, preoperative pulmonary function, operation methods and size of the solid component was performed.

Results: Propensity score matching produced 92 patients in each group for the prognostic analysis. The mean size of the solid part was 8.8 mm in the GGO-dominant group and 9.0 mm in the solid-dominant group (P = 0.34); the mean size of the total lesion was 22.2 mm in the GGO-dominant group and 14.9 mm in the solid-dominant group (P < 0.001). The 5-year overall survival rates were 96.7% in group 1 and 96.2% in group 2 (P = 0.52), and the 5-year disease-free survival rates were 96.7% in group 1 and 94.3% in group 2 (P = 0.48).

Conclusions: Although the total sizes of the GGO-dominant lesions were larger than those of the solid-dominant lesions, the prognosis of patients with GGO-dominant lesions was not significantly different from that of patients with solid-dominant lesions in node-negative adenocarcinomas with a similar invasive component size <20 mm.
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http://dx.doi.org/10.1093/ejcts/ezaa016DOI Listing
June 2020

Results of low-dose computed tomography as a regular health examination among Chinese hospital employees.

J Thorac Cardiovasc Surg 2020 Sep 14;160(3):824-831.e4. Epub 2019 Nov 14.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Institute of Biomedical Sciences, Fudan University, Shanghai, China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. Electronic address:

Objective: Lung cancer is traditionally more prevalent in the elderly patients, men, and smokers. However, as low-dose computed tomography (LDCT) is increasingly popular, we hypothesized the disease spectrum might change.

Methods: LDCT was performed as a part of regular health examinations in 8392 of 15,686 employees from 6 hospitals in different regions of China in 2012 to 2018. Clinicopathologic characteristics, including age, sex, smoking status, radiologic features, tumor histology, and pathologic stage, were retrospectively analyzed.

Results: LDCT incidentally detected lung cancer (pathologically confirmed) in a total of 179 (2.1%) hospital employees. The lung cancer detection rate was significantly greater in female than male (2.5% vs 1.3%, P = .001) patients. There was also a greater detection rate among nonsmokers than smokers, although statistical significance was not reached (2.2% vs 1.4%, P = .092). The lung cancer detection rate was 1.0% in the "age ≤40 years" group, 2.6% in the "40 < age ≤55 years" group, and 2.9% in the "age >55 years" group (P < .001). Among the hospital employees with lung cancer, 171 (95.5%) presented as ground-glass opacity, 177 (98.9%) were lung adenocarcinoma, 170 (95.0%) were early stage 0/IA, and 177 (98.9%) received curative surgical resection as the initial treatment. After a median follow-up of 38 months, no disease recurrence or death was observed among these patients.

Conclusions: LDCT detected lung cancer in a significant proportion of young, female, and nonsmoking employees. The vast majority of these lung cancers were early stage, with extremely good prognosis.
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http://dx.doi.org/10.1016/j.jtcvs.2019.10.145DOI Listing
September 2020

Endoscopic Vacuum Therapy in the Management of Postoperative Leakage After Esophagectomy.

World J Surg 2020 01;44(1):179-185

Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.

Background: Postoperative leakage after esophagectomy is associated with significant life-threatening complications. Recently, endoscopic vacuum therapy (EVT) was introduced and has been successfully used as a new treatment option. The purpose of this study was to evaluate the safety and efficacy of EVT for the management of postoperative leakage after esophagectomy.

Methods: A total of 22 patients were treated with either intraluminal or intracavitary EVT for the management of postoperative leakage from May 2012 to April 2018. The location of leakage was intrathoracic in 17 patients and cervical in five patients. The outcomes of EVT were analyzed retrospectively.

Results: Complete postoperative leakage closure was achieved in 19 of 22 patients. The median duration of EVT application was 14 days (range 2-103), and a median number of three EVT systems (range 1-14) were used. In 19 patients who were successfully managed with EVT, oral feeding was possible a median of 15 days after the first day of treatment. There were no cases of mortality related to postoperative leakage.

Conclusions: EVT is a well-tolerated and effective therapeutic option for the treatment of various types of postoperative leakage after esophagectomy.
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http://dx.doi.org/10.1007/s00268-019-05228-zDOI Listing
January 2020

Surgical treatment of pulmonary oligorecurrence after curative resection for non-small-cell lung cancer.

Interact Cardiovasc Thorac Surg 2020 01;30(1):18-23

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul, Korea.

Objectives: The most appropriate therapeutic strategy for patients with pulmonary oligorecurrence after curative resection of non-small-cell lung cancer (NSCLC) is unclear; therefore, characterizing the results of various treatments for pulmonary oligorecurrence would be valuable. This study compared the prognosis of operative and non-operative treatment for pulmonary oligorecurrence after complete resection of NSCLC.

Methods: Among 2230 patients from a prospective lung cancer database who underwent surgical resection between 2004 and 2014, 486 patients (22%) experienced recurrence, including 254 with pulmonary recurrence and 102 with pulmonary oligorecurrence (5 or fewer metastatic lesions). Post-recurrence survival (PRS) rates were compared between those who received operative or non-operative treatment, including chemotherapy, radiotherapy, chemoradiotherapy and best supportive care.

Results: Among 102 patients with pulmonary oligorecurrence, 41 patients received operative treatment and 61 received non-operative treatment (34 chemotherapy, 15 radiotherapy, 9 chemoradiotherapy and 3 best supportive care). The patients who received operative treatment were significantly younger at the first operation than those in the non-operative group and had better performance status, lower pathological T stage at the first operation, younger age at recurrence and fewer metastatic lesions. The median PRS was 46.4 months, and the 5-year PRS rates were 67% and 26% in the operative and non-operative groups, respectively. The multivariable analysis revealed that undergoing video-assisted thoracoscopic surgery at the first operation and receiving operative treatment for recurrence were independent prognostic factors for more favourable PRS.

Conclusions: Operative treatment of pulmonary oligorecurrence after curative resection significantly prolonged the PRS in patients who underwent curative resection for NSCLC.
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http://dx.doi.org/10.1093/icvts/ivz221DOI Listing
January 2020

Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery.

Ann Surg Oncol 2019 Oct 16;26(11):3756-3764. Epub 2019 Jul 16.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC.

Methods: Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated.

Results: Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64-0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71-0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (P = 0.02) in tumor tissues.

Conclusions: These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.
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http://dx.doi.org/10.1245/s10434-019-07614-2DOI Listing
October 2019

Effect of sevoflurane-based or propofol-based anaesthesia on the incidence of postoperative acute kidney injury: A retrospective propensity score-matched analysis.

Eur J Anaesthesiol 2019 Sep;36(9):649-655

From the Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam-si (TKO, JK, SH), Department of Anesthesiology and Pain Medicine, College of Medicine, Seoul National University, Seoul (JK, SH), Department of Thoracic Surgery (KK, SJ) and Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam-si, South Korea (EJ).

Background: Propofol may help to protect against ischaemic acute kidney injury (AKI); however, research on this topic is sparse.

Objective: The current study aimed to investigate whether there were differences in the incidence of postoperative AKI after lung resection surgery between patients who received propofol-based total intravenous anaesthesia (TIVA) and those who received sevoflurane-based inhalational anaesthesia.

Design: A retrospective observational study.

Setting: A single tertiary care hospital.

Patients: Medical records of patients aged 19 years or older who underwent curative lung resection surgery for nonsmall cell lung cancer between January 2005 and February 2018 were examined.

Main Outcome Measures: After propensity score matching, the incidence of AKI in the first 3 postoperative days was compared between patients who received propofol and those who received sevoflurane. Logistic regression analyses were also used to investigate whether propofol-based TIVA lowered the risk of postoperative AKI.

Results: The analysis included 2872 patients (1477 in the sevoflurane group and 1395 in the propofol group). After propensity score matching, 661 patients were included in each group; 24 (3.6%) of the 661 patients in the sevoflurane group developed AKI compared with 23 (3.5%) of the 661 patients in the propofol group (95% confidence intervals of difference in incidence -0.019 to 0.022, P = 0.882). The logistic regression analyses revealed that the incidence of AKI was not different in the two groups (odds ratio 0.96, 95% confidence interval 0.53 to 1.71, P = 0.882).

Conclusion: In this retrospective study, no significant difference was found in the incidence of postoperative AKI after lung resection surgery between patients who received propofol-based TIVA and those who received sevoflurane-based inhalational anaesthesia. Considering the methodological limitation of this retrospective study, further studies are required to confirm these results.
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http://dx.doi.org/10.1097/EJA.0000000000001020DOI Listing
September 2019

Perioperative change in neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor in patients with completely resected primary pulmonary sarcomatoid carcinoma.

J Thorac Dis 2019 Mar;11(3):819-826

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: There has been controversy regarding prognostic factors for surgically resected primary pulmonary sarcomatoid carcinoma (PSC). Recently, several studies have shown that neutrophil-to-lymphocyte ratio (NLR) was a prognostic factor for various types of cancers from multiple organs. Therefore, we performed this study to evaluate whether NLR is related to prognosis after complete surgical resection of primary PSC.

Methods: From Oct. 2003 to Sep. 2015, a total of 50 patients underwent surgical resection for primary PSC. After excluding patients with any history of other malignancy and incompletely resected cases, a total of 37 patients were included, and data were retrospectively collected and analyzed. Change in postoperative NLR and the initial NLR (ΔNLR) was calculated from the perioperative complete blood count (CBC) results.

Results: Mean age of the cohort was 62.2±1.9 years, and 31 patients (83.8%) were male. Twenty patients (54.1%) were revealed as pN0. Overall 5-year survival rate was 50.3%. Seventeen patients (45.9%) had locoregional or distant metastases. Univariate survival analysis revealed age >70, ΔNLR >17 as risk factors for overall survival (P=0.009, 0.005) and disease-free survival (P=0.036, 0.018). Multivariate Cox-regression analysis revealed age >70 and ΔNLR >17 as independent risk factors for overall survival and ΔNLR >17 as the only independent risk factor for the disease-free survival.

Conclusions: In patients with completely resected primary PSC, perioperative ΔNLR had a significant effect on the overall survival and disease-free survival. Older age was also an independent risk factor for overall survival.
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http://dx.doi.org/10.21037/jtd.2019.02.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462731PMC
March 2019

Glucose transporter 3 gene variant is associated with survival outcome of patients with non-small cell lung cancer after surgical resection.

Gene 2019 Jun 4;703:58-64. Epub 2019 Apr 4.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Lung Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

This study was conducted to explore whether polymorphisms of glucose transporter 3 (GLUT3) gene affect the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Four single nucleotide polymorphisms (SNPs) in GLUT3 were investigated in a total of 782 patients with NSCLC who underwent curative surgery. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. Among the four SNPs investigated, GLUT3 rs7309332C>T was significantly associated with OS and DFS in multivariate analyses. The SNP was associated with significantly worse OS (adjusted hazard ratio [aHR] = 1.62, 95% confidence interval [CI] = 1.04-2.53, P = 0.03, under recessive model), and worse DFS (aHR = 1.64, 95% CI = 1.18-2.29, P = 0.003, under recessive model). When stratified by tumor histology, the association between the GLUT3 rs7309332C>T and OS/DFS was not limited to either squamous cell carcinoma (SCC) or adenocarcinoma (AC), although the significant association remained only in AC for OS (P = 0.40 for SCC and P = 0.04 for OS) and only in SCC for DFS (P = 0.03 for SCC and P = 0.08 for OS). When AC patients were stratified according to EGFR mutation status, the SNP was significantly associated with DFS in patients with EGFR mutant tumors (aHR = 2.47, 95% CI = 1.15-5.30, P = 0.02, under recessive model), but not in those with EGFR wild-type tumors. This study suggests that genetic variation in GLUT3 may be useful in predicting survival of patients with early stage NSCLC.
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http://dx.doi.org/10.1016/j.gene.2019.04.013DOI Listing
June 2019

Association of perioperative weight-based fluid balance with 30-day mortality and acute kidney injury among patients in the surgical intensive care unit.

J Anesth 2019 06 27;33(3):354-363. Epub 2019 Mar 27.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, 166, Gumi-ro, Bundang-gu, 463-707, Seongnam, South Korea.

Purpose: Perioperative positive fluid balance has negative effects on short-term outcomes, such as surgical complications, although the associations with postoperative mortality remain unclear. This study evaluated the associations of perioperative fluid balance (FB) with 30-day mortality and acute kidney injury (AKI) after postoperative intensive care unit (ICU) admission.

Methods: This retrospective study evaluated data from adult patients who were admitted to the ICU after surgery during 2012-2016. Weight-based cumulative FB (%) was calculated for 3 time periods [postoperative day (POD) 0 (24 h), 0-1 (48 h), and 0-2 (72 h)] and was categorized as positive (≥ 5%), mild to moderate positive (5-10%), severe positive (> 10%), normal (0-5%), or negative (< 0%).

Results: Data from 7896 patients were included in the analysis. The multivariable Cox regression model revealed that increased 30-day mortality was associated with positive FB groups (≥ 5%) compared to normal FB groups (0-5%) during 3 time periods [hazard ratio (HR) on POD 0 (24 h): 1.87, HR on POD 1 (48 h): 1.91, and HR on POD 2 (72 h): 4.62, all P < 0.05]. These trends were more evident in the severe positive FB group across the three time periods. Additionally, similar association was found for incidence of AKI during POD 0-2.

Conclusion: Perioperative cumulative weight-based FB was positively associated with increased postoperative 30-day mortality or postoperative AKI in ICU patients; this association was consistent with the positive FB on POD 0 (24 h), 0-1 (48 h), and 0-2 (72 h).
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http://dx.doi.org/10.1007/s00540-019-02630-8DOI Listing
June 2019

TSC2 genetic variant and prognosis in non-small cell lung cancer after curative surgery.

Thorac Cancer 2019 02 26;10(2):335-340. Epub 2018 Dec 26.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.

This study was conducted to investigate the associations between polymorphisms of genes involved in the LKB1 pathway and the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Twenty-three single nucleotide polymorphisms (SNPs) in the LKB1 pathway were investigated in 782 patients with NSCLC who underwent curative surgery. The association of SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed. Among the 23 SNPs investigated, TSC2 rs30259G > A was associated with significantly worse OS and DFS (adjusted hazard ratio for OS 1.88, 95% confidence interval 1.21-2.91, P = 0.005; adjusted hazard ratio for DFS 1.65, 95% confidence interval 1.15-2.38, P = 0.01, under codominant models, respectively). Subgroup analysis showed that SNPs were significantly associated with survival outcomes in squamous cell carcinoma, ever-smokers, and stage I, but not in adenocarcinoma, never-smokers, and stage II-IIIA. The results suggest that TSC2 rs30259G > A may be useful to predict prognosis in patients with NSCLC, especially squamous cell carcinoma, after curative surgery.
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http://dx.doi.org/10.1111/1759-7714.12951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360237PMC
February 2019

Functional intronic variant of SLC5A10 affects DRG2 expression and survival outcomes of early-stage non-small-cell lung cancer.

Cancer Sci 2018 Dec 7;109(12):3902-3909. Epub 2018 Nov 7.

Department of Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.

RegulomeDB is a new tool that can predict the regulatory function of genetic variants. We applied RegulomeDB in selecting putative functional variants and evaluated the relationship between these variants and survival outcomes of surgically resected non-small-cell lung cancer. Among the 244 variants studied, 14 were associated with overall survival (P < 0.05) in the discovery cohort and one variant (rs2257609 C>T) was replicated in the validation cohort. In the combined analysis, rs2257609 C>T was significantly associated with worse overall and disease-free survival under a dominant model (P = 2 × 10 and P = 0.001, respectively). rs2257609 is located in the SLC5A10 intron, but RegulomeDB predicted that this variant affected DRG2, not SLC5A10 expression. The expression level of SLC5A10 was not different with the rs2257609 genotype. However, DRG2 expression was different according to the rs2257609 genotype (P = 0.03) and was significantly higher in tumor than in non-malignant lung tissues (P = 1 × 10 ). Luciferase assay also showed higher promoter activity of DRG2 in samples with the rs2257609 T allele (P < 0.0001). rs2257609 C>T affected DRG2 expression and, thus, influenced the prognosis of early-stage non-small-cell lung cancer. This study was approved by the Institutional Review Broad of Kyungpook National University of Hospital (Approval No. KNUMC 2014-04-210-003).
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http://dx.doi.org/10.1111/cas.13814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272084PMC
December 2018

Clinical and functional outcomes after curative resection in octogenarians with clinical stage I non-small cell lung cancer.

J Geriatr Oncol 2019 05 16;10(3):436-438. Epub 2018 Sep 16.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Republic of Korea; Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Republic of Korea.

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http://dx.doi.org/10.1016/j.jgo.2018.08.011DOI Listing
May 2019