1.JAK2 Loss Arising From Tumor-SpreadThrough-Air-Spaces (STAS) Promotes Tumor Progression by Suppressing CD8+ T Cells in Lung Adenocarcinoma:A Machine Learning Approach
Soohwan CHOI ; Hyung Suk KIM ; Kyueng-Whan MIN ; Yung-Kyun NOH ; Jeong-Yeon LEE ; Ji-Yong MOON ; Un Suk JUNG ; Mi Jung KWON ; Dong-Hoon KIM ; Byoung Kwan SON ; Jung Soo PYO ; Sun Kyun RO
Journal of Korean Medical Science 2024;39(2):e16-
Background:
Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates.
Methods:
This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis.
Results:
The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression.
Conclusion
In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.
2.Nodal Outcomes of Uniportal versus Multiportal Video-Assisted Thoracoscopic Surgery for Clinical Stage I Lung Cancer
Jung Suk CHOI ; Jiyun LEE ; Young Kyu MOON ; Seok Whan MOON ; Jae Kil PARK ; Mi Hyoung MOON
The Korean Journal of Thoracic and Cardiovascular Surgery 2020;53(3):104-113
Background:
Accurate intraoperative assessment of mediastinal lymph nodes is a critical aspect of lung cancer surgery. The efficacy and potential for upstaging implicit in these dissections must therefore be revisited in the current era of uniportal video-assisted thoracoscopic surgery (VATS).
Methods:
A retrospective study was conducted in which 544 patients with stage I (T1abc–T2a, N0, M0) primary lung cancer were analyzed. To assess risk factors for nodal upstaging and to limit any imbalance imposed by surgical choices, we constructed an inverse probability of treatment-weighted (IPTW) logistic regression model (in addition to non-weighted logistic models). We also evaluated risk factors for early locoregional recurrence using IPTW logistic regression analysis.
Results:
In the comparison of uniportal and multiportal VATS, the resected lymph node count (14.03±8.02 vs. 14.41±7.41, respectively; p=0.48) and rate of nodal upstaging (6.5% vs. 8.7%, respectively; p=0.51) appeared similar. Predictors of nodal upstaging included tumor size (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.12–2.70), carcinoembryonic antigen level (OR, 1.11; 95% CI, 1.04–1.18), and histologically confirmed pleural invasion (OR, 3.97; 95% CI, 1.89–8.34). The risk factors for locoregional recurrence within 1 year were found to be number of resected N2 nodes, age, and nodal upstaging.
Conclusion
Uniportal and multiportal VATS appear similar with regard to accuracy and thoroughness, showing no significant difference in the extent of nodal dissection.
3.Impact of Sarcopenia on Early Postoperative Complications in Early-Stage Non–Small-Cell Lung Cancer
Jiyun LEE ; Seok Whan MOON ; Jung Suk CHOI ; Kwanyong HYUN ; Young Kyu MOON ; Mi Hyoung MOON
The Korean Journal of Thoracic and Cardiovascular Surgery 2020;53(3):93-103
Background:
Risk assessment for pulmonary resection in patients with early-stage non– small-cell lung cancer (NSCLC) is important for minimizing postoperative morbidity. Depletion of skeletal muscle mass is closely associated with impaired nutritional status and limited physical ability. We evaluated the relationship between skeletal muscle depletion and early postoperative complications in patients with early-stage NSCLC.
Methods:
Patients who underwent curative lung resection between 2016 and 2018 and who were diagnosed with pathological stage I/II NSCLC were included, and their records were retrospectively analyzed. The psoas volume index (PVI, cm3/m3) was calculated based on computed tomography images from routine preoperative positron emission tomography- computed tomography. Early postoperative complications, defined as those occurring within 90 days of surgery, were compared between the lowest sex-specific quartile for PVI and the remaining quartiles.
Results:
A strong correlation was found between the volume and the cross-sectional area of the psoas muscle (R2=0.816). The overall rate of complications was 57.6% among patients with a low PVI and 32.8% among those with a normal-to-high PVI. The most common complication was prolonged air leak (low PVI, 16.9%; normal-to-high PVI, 9.6%), followed by pneumonia (low PVI, 13.6%; normal-to-high PVI, 7.9%) and recurrent pleural effusion (low PVI, 11.9%; normal-to-high PVI, 6.8%). The predictors of overall complications were low PVI (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07–4.09; p=0.03), low hemoglobin level (OR, 0.686; 95% CI, 0.54–0.87; p=0.002), and smoking history (OR, 3.93; 95% CI, 2.03–7.58; p<0.001).
Conclusion
Low PVI was associated with a higher rate of early postoperative complications in patients with early-stage NSCLC.
4.Effects of vitamin D supplements in patients with chronic hepatitis C: a randomized, multi-center, open label study
Jae Yoon JEONG ; Dae Won JUN ; Sol Ji PARK ; Joo Hyun SOHN ; Sang Gyune KIM ; Se Whan LEE ; Soung Won JEONG ; Moon Young KIM ; Won KIM ; Jae-Jun SHIM ; Hyoung Su KIM ; Ki Tae SUK ; Sang Bong AHN
The Korean Journal of Internal Medicine 2020;35(5):1074-1083
Background/Aims:
We aimed to assess the role of vitamin D supplementation in the response to pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC).
Methods:
Our study was a multi-center, randomized controlled trial in 11 hospitals. CHC patients were randomly assigned (1:1) to two groups namely, PEGIFN-α plus RBV (control group) or PEG-IFN-α plus RBV + vitamin D (800 IU daily) (vitamin D group). The primary end-point was the rate of sustained virologic response (SVR).
Results:
One hundred forty eight CHC patients were randomly assigned to two groups. Seventy-one patients received the PEG-IFN-α plus RBV and 77 patients received the PEG-IFN-α plus RBV + vitamin D. A total of 105 patients completed the study (control group, 47 vs. vitamin D group, 58). Baseline characteristics were mostly similar in both the groups. There was a modest but non-significant increase in SVR in the vitamin D group compared to the control group with the intention to treat analysis (64.0% vs. 49.3 %, p = 0.071) as well as in the per protocol analysis (control group vs. vitamin D group: 74.5% vs. 84.5%, p = 0.202). Fifty-two patients (73.2%) in the control group and 63 patients (81.8%) in the vitamin D group experienced at least one adverse event. The drop-out rate due to adverseeffects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111).
Conclusions
Vitamin D supplement did not increase SVR in treatment naïve patients with CHC irrespective of genotype.
5.Preliminary results of entire pleural intensity-modulated radiotherapy in a neoadjuvant setting for resectable malignant mesothelioma
Ji Hyun HONG ; Hyo Chun LEE ; Kyu Hye CHOI ; Seok Whan MOON ; Kyung Soo KIM ; Suk Hee HONG ; Ju Young HONG ; Yeon Sil KIM ;
Radiation Oncology Journal 2019;37(2):101-109
PURPOSE: The purpose of this study is to evaluate the safety and efficacy of the multimodality treatment with neoadjuvant intensity-modulated radiotherapy (IMRT) for resectable clinical T1-3N0-1M0 malignant pleural mesothelioma (MPM). MATERIALS AND METHODS: A total of eleven patients who received neoadjuvant chemotherapy and radiotherapy between March 2016 and June 2018 were reviewed. Patients received 25 Gy in 5 fractions to entire ipsilateral hemithorax with helical tomotherapy. RESULTS: All of patients were men with a median age of 56 years. Epithelioid subtype was found in 10 patients. All patients received neoadjuvant chemotherapy with pemetrexed-cisplatin regimen. Ten patients (90.9%) completed 25 Gy/5 fractions and one (9.0%) completed 20 Gy/4 fractions of radiotherapy. IMRT was well tolerated with only one acute grade 3 radiation pneumonitis. Surgery was performed 1 week (median, 8 days; range, 1 to 15 days) after completing IMRT. Extrapleural pneumonectomy was performed in 4 patients (36.3%), extended pleurectomy/decortication in 2 (18.2%) and pleurectomy/decortications in 5 (63.6%). There was no grade 3+ surgical complication except two deaths after EPP in 1 month. Based on operative findings and pathologic staging, adjuvant chemotherapy was delivered in 7 patients (63.6%), and 2 (18.2%) were decided to add adjuvant radiotherapy. After a median follow-up of 14.6 months (range, 2.8 to 30 months), there were 3 local recurrence (33.3%) and 1 distant metastasis (11.1%). CONCLUSION: Neoadjuvant entire pleural IMRT can be delivered with a favorable radiation complication. An optimal strategy has to be made in resectable MPM patients who would benefit from neoadjuvant radiation and surgery. Further studies are needed to look at long-term outcomes.
Chemotherapy, Adjuvant
;
Combined Modality Therapy
;
Drug Therapy
;
Follow-Up Studies
;
Humans
;
Male
;
Mesothelioma
;
Neoadjuvant Therapy
;
Neoplasm Metastasis
;
Pneumonectomy
;
Radiation Pneumonitis
;
Radiotherapy
;
Radiotherapy, Adjuvant
;
Radiotherapy, Intensity-Modulated
;
Recurrence
6.A 2-Week Steroid Trial for Differentiating Isolated IgG4-Related Sclerosing Cholangitis from Cholangiocarcinoma.
Bho Hyeon LEE ; Sung Hoon MOON ; Kyueng Whan MIN ; Ji Won PARK ; Hyun LIM ; Sung Eun KIM ; Ho Suk KANG ; Jong Hyeok KIM
Korean Journal of Pancreas and Biliary Tract 2018;23(3):127-133
Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is rare disease which is steroid-responsive and often associated with IgG4 related systemic disease such as autoimmune pancreatitis. It is characterized by increased serum IgG4 and IgG4-positive lymphoplasmacytic infiltration in bile ducts. It is often difficult to distinguish IgG4-SC to hilar cholangiocarcinoma if it manifests as an isolated bile duct. We report a case of 79-year-old woman with IgG4-SC which was difficult to distinguish hilar cholangiocarcinoma due to similar clinical and radiologic findings, showing good therapeutic effect after a 2-week steroid trial.
Aged
;
Bile Ducts
;
Cholangiocarcinoma*
;
Cholangitis, Sclerosing*
;
Female
;
Humans
;
Immunoglobulin G
;
Immunoglobulins
;
Klatskin Tumor
;
Pancreatitis
;
Rare Diseases
7.Characteristics and Trends of Published Adult Hip Research over the Last Decade.
Hong Suk KWAK ; Pil Whan YOON ; Moon Seok PARK ; Jeong Joon YOO ; Hee Joong KIM
Yonsei Medical Journal 2015;56(1):132-138
PURPOSE: We designed this study to demonstrate recent trends in the proportion of adult hip research in orthopedics, to identify countries leading the adult hip research, and to evaluate the relationship between the economic power of the countries and their contributions. MATERIALS AND METHODS: Studies published in seven select orthopedic journals were retrieved from PubMed. Among them, we determined the number of adult hip studies. The countries-of-origin of adult hip studies, and the economic power of the countries were investigated. RESULTS: A total of 7218 orthopedic publications and 1993 (27.6%) addressed adult hip research were identified. Adult hip studies increased from 313 (23.7%) in 2000 to 555 (27.9%) in 2011. Twenty-five countries accounted for 97.6% of the total number of adult hip studies, and gross domestic product correlated with publication volume (Spearman's rho, 0.723; p=0.000). CONCLUSION: Researchers from a limited number of developed countries have published their studies in the adult hip discipline.
Adult
;
Geography
;
Hip/*physiology
;
Humans
;
PubMed
;
Publications/*trends
;
Research/*trends
8.Surgical Resection for Lung Metastases from Colorectal Cancer.
Hyung Jin KIM ; Bong Hyeon KYE ; Jae Im LEE ; Sang Chul LEE ; Yoon Suk LEE ; In Kyu LEE ; Won Kyung KANG ; Hyeon Min CHO ; Seok Whan MOON ; Seong Taek OH
Journal of the Korean Society of Coloproctology 2010;26(5):354-358
PURPOSE: The lung is the second most common site of metastasis from colorectal cancer. Of all patients who undergo a curative resection for colorectal cancer, 10% to 15% will develop lung metastasis. As a hepatic resection of colorectal liver metastases results in improved survival, many reports have suggested that a pulmonary resection of a colorectal lung metastasis would also improve survival. The aim of this study was to analyze the postoperative outcomes of and the prognostic factors for a surgical resection of a lung metastasis. METHODS: Between August 1997 and March 2006, 27 patients underwent surgical resections for colorectal lung metastases at Seoul St. Mary's hospital. A retrospective review of patients' characteristics and various tumor factors was performed. RESULTS: The mean interval between colorectal resection and lung metastasis was 24.0 +/- 15.1 months. The overall 3- and 5-year survival rates were 76.5% and 22.2%, respectively. The mean follow-up after pulmonary resection was 39.5 +/- 21.6 months (range, 3.3 to 115 months). Except for the existence of hilar-lymph-node metastasis (P < 0.001), no risk factors that we studied were statistically significant. Two patients had hilar-lymph-node metastasis. They survived for only for 3.3- and 11.6-months, respectively. CONCLUSION: In our study, we found that a pulmonary resection for metastases from colorectal cancer may improve survival in selected patients.
Colorectal Neoplasms
;
Follow-Up Studies
;
Humans
;
Liver
;
Lung
;
Neoplasm Metastasis
;
ortho-Aminobenzoates
;
Retrospective Studies
;
Risk Factors
;
Survival Rate
9.A Nationwide Survey of Lymphangioleiomyomatosis in Korea: Recent Increase in Newly Diagnosed Patients.
Hye Yun PARK ; Hae Seong NAM ; Man Pyo CHUNG ; Sung Hwan JEONG ; Yu Jin KIM ; Seung Ick CHA ; Young Whan KIM ; Jong Sun PARK ; Soo Taek UH ; Choon Sik PARK ; Moo Suk PARK ; Ji Ae MOON ; Kyung Soo JUNG ; Yang Jin JEGAL ; Dong Soon KIM ; Jin Woo SONG ; Ho Kee YUM ; Young Bum PARK
Journal of Korean Medical Science 2010;25(8):1182-1186
In 2007, the Korean Interstitial Lung Disease Society had collected clinical data of patients who have diagnosed as Lymphangioleiomyomatosis (LAM) since 1990 through nationwide survey, which showed that LAM patients had increased sharply after 2004. The present study was performed to show the clinical features of Korean patients with LAM, and to establish the reason for the recent increase in the diagnosis. All 63 patients were women and the mean age at diagnosis was 36 yr. The most common presenting symptom was dyspnea and 8 patients had tuberous sclerosis complex. The survival rate at 5 yr after diagnosis was 84%. Compared with patients diagnosed after 2004 (n=34), the patients diagnosed before 2004 (n=29) complained with dyspnea more (P=0.016) and had lower FEV1% predicted (P=0.003), and DLco% predicted (P=0.042). The higher proportion of patients diagnosed after 2004 showed the normal chest radiography, and they were detected by routine chest CT screening (P=0.016). This study showed that clinical features of Korean patients with LAM were not different from those reported elsewhere. It is concluded that the reason for the increase of newly diagnosed patients is the result of increase in detection of the early stage LAM by the widespread use of chest CT screening.
Adult
;
Aged
;
Early Diagnosis
;
Female
;
Humans
;
Lung Neoplasms/*diagnosis/mortality/radiography
;
Lymphangioleiomyomatosis/*diagnosis/mortality/radiography
;
Middle Aged
;
Republic of Korea
;
Respiratory Function Tests
;
Survival Rate
;
Tomography, X-Ray Computed
10.Clinical Characteristics of Inguinal Hernia in Children on Peritoneal Dialysis.
Hee Kyung PARK ; Kyu Whan JUNG ; Suk Bae MOON ; Sung Eun JUNG ; Kwi Won PARK
Journal of the Korean Association of Pediatric Surgeons 2009;15(2):141-148
Peritoneal dialysis (PD) has been utilized for the children with end stage renal disease. Nevertheless, it is thought to promote inguinal hernia by increasing intraabdominal pressure. To investigate the clinical characteristics of inguinal hernia in children on PD, 155 cases of PD in children between January 1996 and June 2007 at Seoul National University Children's Hospital were reviewed retrospectively. Inguinal hernia developed in 16 cases (10.3%, M:F=8:8). Hernia occurrence was not correlated to age. Eleven cases (69%) of inguinal hernia developed in first 6 months after initiation of PD. All inguinal hernias were surgically repaired. No complications occurred related to inguinal hernia or surgery. Recurrent hernia developed in 1 patient (6.3%) of 2 cases who had PD postoperatively on the day of surgery. In conclusion, inguinal hernia developed more frequently with children on PD than general population (3.5~5%). The rate of hernia development was highest within the first 6 months following initiation of PD. After repair of hernia, we recommend to discontinue PD immediate postoperatively to prevent recurrence.
Child
;
Hernia
;
Hernia, Inguinal
;
Humans
;
Kidney Failure, Chronic
;
Peritoneal Dialysis
;
Retrospective Studies

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