1.Effector Function Characteristics of Exhausted CD8+ T-Cell in Microsatellite Stable and Unstable Gastric Cancer
Dong-Seok HAN ; Yoonjin KWAK ; Seungho LEE ; Soo Kyung NAM ; Seong-Ho KONG ; Do Joong PARK ; Hyuk-Joon LEE ; Nak-Jung KWON ; Hye Seung LEE ; Han-Kwang YANG
Cancer Research and Treatment 2024;56(4):1146-1163
Purpose:
Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability–high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors, presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential.
Materials and Methods:
We explored the molecular characteristics of CD8+ T-cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis.
Results:
In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T cell and natural killer T cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The interferon γ (IFN-γ) signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer.
Conclusion
Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.
2.The size of pelvic hematoma can be a predictive factor for angioembolization in hemodynamically unstable pelvic trauma
Hak Jae LEE ; Hyo Keun NO ; Nak Joon CHOI ; Hyun Woo SUN ; Jae Suk LEE ; Yoon Joong JUNG ; Suk Kyung HONG
Annals of Surgical Treatment and Research 2020;98(3):146-152
PURPOSE:
Unstable pelvic fracture with bleeding can be fatal, with a mortality rate of up to 40%. Therefore, early detection and treatment are important in unstable pelvic trauma. We investigated the early predictive factors for possible embolization in patients with hemodynamically unstable pelvic trauma.
METHODS:
From January 2011 to December 2013, 46 patients with shock arrived at a single hospital within 24 hours after injury. Of them, 44 patients underwent CT scan after initial resuscitation, except for 2 who were dead on arrival. Nine patients with other organ injuries were excluded. Seventeen patients underwent embolization. A single radiologist measured the width (longest length in axial view) and length (longest length in coronal view) of pelvic hematoma on CT scans. Demographic, clinical, and radiological data were reviewed retrospectively.
RESULTS:
Among 35 patients with hemodynamically unstable pelvic fracture, 22 (62.9%) were men. Width (P = 0.002) and length (P = 0.006) of hematoma on CT scans were significantly different between the embolization and nonembolization groups. The predictors of embolization were width of pelvic hematoma (odds ratio [OR], 1.07; P = 0.028) and female sex (OR, 10.83; P = 0.031). The cutoff value was 3.35 cm. More embolization was performed (OR, 12.00; P = 0.003) and higher mortality was observed in patients with hematoma width >3.35 cm (OR, 4.96; P = 0.048).
CONCLUSION
Patients with hemodynamically unstable pelvic trauma have a high mortality rate. CT is useful for the initial identification of the need for embolization among these patients. The width of pelvic hematoma can predict possible embolization in patients with unstable pelvic trauma.
3.Clinical Outcomes of Diffuse Axonal Injury According to Radiological Grade
Hak Jae LEE ; Hyun Woo SUN ; Jae Seok LEE ; Nak Joon CHOI ; Yoon Joong JUNG ; Suk Kyung HONG
Journal of the Korean Society of Traumatology 2018;31(2):51-57
PURPOSE:
Patients with diffuse axonal injury experience various disabilities and have a high cost of treatment. Recent researches have revealed the underlying mechanism and pathogenesis of diffuse axonal injury. This study aimed to investigate the correlation between the radiological grading of diffuse axonal injury and the clinical outcomes of patients.
METHODS:
From January 2011 to December 2016, among 294 patients with traumatic brain injury, 44 patients underwent magnetic resonance imaging (MRI). A total of 18 patients were enrolled in this study except for other cerebral injuries, such as cerebral hemorrhage or hypoxic brain damage. Demographic data, clinical data, and radiological findings were retrospectively reviewed. The grading of diffuse axonal injury was analyzed based on patient's MRI findings.
RESULTS:
For the most severe diffuse axonal injury patients, prolonged intensive care unit (ICU) stay (p=0.035), hospital stay (p=0.012), and prolonged mechanical ventilation (p=0.030) were observed. However, there was no significant difference in healthcare-associated infection rates between MRI grading (p=0.123). Massive transfusion, initial hemoglobin and lactate levels, and MRI gradings were found to be highly significant in predicting the duration of unconsciousness.
CONCLUSIONS
This study showed that patients with high grade diffuse axonal injury have prolonged ICU stays and significantly longer hospital stays. Deteriorated mental patients with high energy injuries should be evaluated to identify diffuse axonal injuries by using an appropriate imaging tool, such as MRI. It will be important to predict the duration of consciousness recovery using MRI scans.
4.Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers.
Ha Youn LEE ; Se Hoon LEE ; Jae Kyung WON ; Dong Soo LEE ; Nak Jung KWON ; Sun Mi CHOI ; Jinwoo LEE ; Chang Hoon LEE ; Sang Min LEE ; Jae Joon YIM ; Chul Gyu YOO ; Young Whan KIM ; Sung Koo HAN ; Young Sik PARK
Journal of Korean Medical Science 2017;32(3):415-420
Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations. Fifty cancer-related genes in never-smokers were compared to those in ever-smokers. Of 379 lung SCC patients, 19 (5.0%) were never-smokers. The median age of these 19 patients was 67 years (interquartile range 57–73 years), and 10 of these patients were women (52.5%). The incidence rates of stage I, II, III, and IV disease in this group were 26.4%, 5.3%, 31.6%, and 36.8%, respectively, and sequencing was performed successfully in 14 cases. In the 26 lung SCC tumor samples (12 from never-smokers and 14 from ever-smokers) sequenced using personal genome machine, the most common mutations were in TP53 (75.0%), RAS (66.7%), and STK11 (33.3%), but mutations were also found in EGFR, KIT, and PTEN. The distribution of hotspot mutations in never-smokers was similar to that in ever-smokers. There was no significant difference in overall survival between the 2 groups. The 50 hotspot mutations of lung SCC in never-smokers were similar to those of ever-smokers.
Carcinoma, Squamous Cell*
;
Epithelial Cells*
;
Female
;
Genome
;
Humans
;
Incidence
;
Lung Neoplasms
;
Lung*
;
Medical Records
;
Retrospective Studies
;
Risk Factors
;
Seoul
;
Smoke
;
Smoking
5.Neurocognitive Outcome in Survivors of Childhood Acute Lymphoblastic Leukemia: Experience at a Tertiary Care Hospital in Korea.
Seong Joon KIM ; Min Hyun PARK ; Jae Wook LEE ; Nak Gyun CHUNG ; Bin CHO ; In Goo LEE ; Seung Yun CHUNG
Journal of Korean Medical Science 2015;30(4):463-469
This study was conducted to investigate long-term neurocognitive outcomes and to determine associated risk factors in a cohort of Korean survivors of childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL were compared with 42 healthy controls on measures of a neurocognitive test battery. We analysed potential risk factors (cranial irradiation, sex, age at diagnosis, elapsed time from diagnosis, and ALL risk group) on neurocognitive outcomes. ALL patients had lower, but non-significant full-scale intelligence quotient (FSIQ, 107.2 +/- 12.2 vs. 111.7 +/- 10.2), verbal intelligence quotient (VIQ, 107.7 +/- 13.6 vs. 112.2 +/- 11.4), and performance intelligence quotient (PIQ, 106.3 +/- 14.2 vs. 110.1 +/- 10.7) scores than healthy controls. However, patients treated with cranial irradiation performed significantly lower on FSIQ (102.2 +/- 8.1), VIQ (103.3 +/- 11.7), and PIQ (101.4 +/- 13.2) compared to non-irradiated patients and healthy controls. ALL patients also had poor attention, concentration, and executive functions. Among ALL survivors, cranial irradiation was a risk factor for poor FSIQ, being male was a risk factor for poor PIQ, and younger age was a risk factor for poor attention. Therefore, the delayed cognitive effects of ALL treatment and its impact on quality of life require continuing monitoring and management.
Adolescent
;
Age Factors
;
Child
;
*Cognition
;
Female
;
Humans
;
Intelligence
;
Male
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality/*psychology
;
*Survivors
;
Tertiary Healthcare
6.Comparison of Two Sedation Protocols for Postoperative Intensive Care Unit Care after Head and Neck Reconstructive Surgery: Midazolam/Morphine versus Remifentanil Sedation.
Nak Joon LEE ; Jeon Yeob JANG ; Sung Yong CHOI ; Ki Nam PARK ; Chung Hwan BAEK ; Jun Seo PARK ; Sook Hyun PARK ; Han Sin JEONG
Korean Journal of Otolaryngology - Head and Neck Surgery 2014;57(3):172-177
BACKGROUND AND OBJECTIVES: In head and neck reconstructive surgery, the stability of vital signs is important for patient recovery and flap outcome. We aimed to determine the better sedation protocol by comparing two protocols, namaely, midazolam/morphine (MM)-based and remifentanil (RF)-based sedation protocols, in the immediate postoperative settings of head and neck reconstructive surgery. SUBJECTS AND METHOD: We retrospectively reviewed the medical data of patients who underwent reconstructive surgery after the ablation of head and neck cancer involving MM sedation (n=34) or RF sedation (n=28). Parameters related to vital signs, flap outcomes, occurrence of delirium, length of stay and nursing burden were compared between the groups. RESULTS: The length of stay at the intensive care unit and flap outcomes were similar in the two groups. However, blood pressure as measured by frequency of variation was more stable in the RF group than in the MM group. In addition, the number of medical calls from the attending nurse due to the fluctuation of vital signs was less in the RF group than in the MM group. CONCLUSION: RF-based sedation for the postoperative intensive care unit care after head and neck reconstructive surgery is more effective in cases where vital signs are less stable. This type of sedation may decrease the nursing burden for these patients.
Blood Pressure
;
Delirium
;
Free Tissue Flaps
;
Head and Neck Neoplasms
;
Head*
;
Humans
;
Intensive Care Units*
;
Critical Care*
;
Length of Stay
;
Neck*
;
Nursing
;
Postoperative Care
;
Retrospective Studies
;
Vital Signs
7.Evaluation of Lymph Nodes in Patients with Concurrent Papillary Thyroid Carcinoma and Cervical Tuberculous Lymphadenitis.
Eun Wook CHUNG ; Young Soo CHANG ; Jungbok LEE ; Sung Yong CHOI ; Nak Joon LEE ; Yoon Kyoung SO ; Han Sin JEONG
Korean Journal of Otolaryngology - Head and Neck Surgery 2012;55(9):571-577
BACKGROUND AND OBJECTIVES: To determine the diagnostic clues to differentiate tuberculous lymph node infection from nodal metastasis in patients with both papillary thyroid carcinoma and cervical tuberculous lymphadenitis. SUBJECTS AND METHOD: We retrospectively reviewed 11 patients suffering concurrently from papillary thyroid carcinomas with cervical tuberculous lymphadenitis. Nine of the 11 patients underwent preoperative neck ultrasonography (US) and seven CT scans. Using the surgical pathology as the reference standards, the results of the preoperative diagnostic tools were re-evaluated according to lymph node level-based analysis. US and CT features were also compared between metastatic nodes and tuberculous lymphadenitis. RESULTS: Preoperative CT could localize the involved lymph node levels and differentiate tuberculous infection from metastasis of thyroid carcinoma in only two of seven patients. The site of the involved lymph nodes, the presence of pulmonary tuberculosis, and the tumor volume of the thyroid carcinoma were the clues to diagnose the lymph node status. However, in five of seven cases, CT could not differentiate tuberculosis from metastasis in the lymph nodes. The morphological characteristics of lymph nodes seen on CT and US did not differ between tuberculous infection and metastasis of papillary thyroid carcinomas. CONCLUSION: Pre-operative CT or US does not provide differential information about lymph node status between tuberculous infection and metastasis in patients with concurrent papillary thyroid carcinomas and cervical tuberculous lymphadenitis. Rather, clinical characteristics such as the site of the involved lymph nodes, the primary tumor burden, and the associated clinical features can help the physician differentiate between them.
Carcinoma
;
Humans
;
Lymph Nodes
;
Lymphatic Metastasis
;
Neck
;
Neoplasm Metastasis
;
Pathology, Surgical
;
Retrospective Studies
;
Stress, Psychological
;
Thyroid Gland
;
Thyroid Neoplasms
;
Tuberculosis
;
Tuberculosis, Lymph Node
;
Tuberculosis, Pulmonary
;
Tumor Burden
8.Clinical and hematologic manifestations in patients with Diamond Blackfan anemia in Korea.
Soon Ki KIM ; Hyo Seop AHN ; Hee Jo BACK ; Bin CHO ; Eun Jin CHOI ; Nak Gyun CHUNG ; Pyoung Han HWANG ; Dae Chul JEOUNG ; Hyung Jin KANG ; Hyery KIM ; Kyung Nam KO ; Hong Hoe KOO ; Hoon KOOK ; Kwang Chul LEE ; Ho Joon LIM ; Young Tak LIM ; Chuhl Joo LYU ; Jun Eun PARK ; Kyung Duk PARK ; Sang Kyu PARK ; Kyung Ha RYU ; Jong Jin SEO ; Hee Young SHIN ; Ki Woong SUNG ; Eun Sun YOO
Korean Journal of Hematology 2012;47(2):131-135
BACKGROUND: Diamond Blackfan anemia (DBA), characterized by impaired red cell production, is a rare condition that is usually symptomatic in early infancy. The purpose of this study was to assess nationwide experiences of DBA encountered over a period of 20 years. METHODS: The medical records of 56 patients diagnosed with DBA were retrospectively reviewed from November 1984 to July 2010. Fifteen institutions, including 13 university hospitals, participated in this study. RESULTS: The male-to-female ratio of patients with DBA was 1.67:1. The median age of diagnosis was 4 months, and 74.1% were diagnosed before 1 year of age. From 2000 to 2009, annual incidence was 6.6 cases per million. Excluding growth retardation, 38.2% showed congenital defects: thumb deformities, ptosis, coarctation of aorta, ventricular septal defect, strabismus, etc. The mean hemoglobin concentration was 5.1+/-1.9 g/dL, mean corpuscular volume was 93.4+/-11.6 fL, and mean number of reticulocytes was 19,700/mm3. The mean cellularity of bone marrow was 75%, with myeloid:erythroid ratio of 20.4:1. After remission, 48.9% of patients did not need further steroids. Five patients with DBA who received hematopoietic transplantation have survived. Cancer developed in 2 cases (3.6%). CONCLUSION: The incidence of DBA is similar to data already published, but our study had a male predilection. Although all patients responded to initial treatment with steroids, about half needed further steroids after remission. It is necessary to collect further data, including information regarding management pathways, from nationwide DBA registries, along with data on molecular analyses.
Anemia
;
Anemia, Diamond-Blackfan
;
Aortic Coarctation
;
Bone Marrow
;
Congenital Abnormalities
;
Diamond
;
Erythrocyte Indices
;
Heart Septal Defects, Ventricular
;
Hemoglobins
;
Hospitals, University
;
Humans
;
Incidence
;
Korea
;
Male
;
Medical Records
;
Registries
;
Reticulocytes
;
Retrospective Studies
;
Steroids
;
Strabismus
;
Thumb
;
Transplants
9.Preoperative Evaluation of the Facial Artery Using Facial Angio Computed Tomography.
Joo Hak KIM ; Nak Heon KANG ; In Ho LEE ; Young Joon SEO ; Ho Jik YANG ; Seung Han SONG ; Sang Ha OH
Journal of the Korean Society of Plastic and Reconstructive Surgeons 2011;38(6):719-724
PURPOSE: Previous studies of the facial artery have shown significant anatomical variability in this region. The vascular anatomy of the region is considered unreliable in predicting the ideal pedicle. Preoperative imaging has been suggested as a means of improving preoperative awareness, with Doppler ultrasound as useful tools. Multi-detector row angiographic computed tomography (angio CT) is a significant improvement, providing non- invasive operator-independent details of the vascular anatomy. This tool was used to perform an in vivo anatomical study of the facial artery, demonstrating the usefulness of facial angio CT in planning the facial reconstruction. METHODS: Eleven consecutive patients underwent facial angio CT of the facial vasculature with the anatomical details of the facial artery assessed. RESULTS: Facial angio CT could demonstrate the size and course of the facial vasculature, particularly the facial artery. CONCLUSION: The vascular anatomy of the facial artery is highly variable, and thus there is a role for preoperative imaging. Facial angio CT can demonstrate cases where there is an aberrant or non-preferred anatomy, or select the method of a facial reconstruction.
Arteries
;
Humans
10.Clinical Investigation of Bacteremia in Children with Hemato-Oncologic Diseases.
Eun Young KO ; Hyun ju KANG ; Hyo Jin KWON ; Ui Yoon CHOI ; Jae Wook LEE ; Dong Gun LEE ; Yeon Joon PARK ; Nak Gyun CHUNG ; Bin CHO ; Hack Ki KIM ; Jin Han KANG
Infection and Chemotherapy 2011;43(2):191-197
BACKGROUND: The purpose of this study was to determine the spectrum of locally prevalent pathogens and their susceptibility patterns responsible for bacteremia in pediatric hemato-oncologic patients for empiric antimicrobial therapy. MATERIALS AND METHODS: A one-year retrospective study of pediatric hematooncologic patients with bacteremia in Seoul St. Mary's Hospital, the Catholic University of Korea, from April 2009 to March 2010 was conducted using previous medical records. The findings were compared with our previous data obtained from 2004 to 2006. RESULTS: Sixty-five episodes of bacteremia were recorded in 41 patients. Of them, 55 (84.6%) occurred in neutropenic and 10 (15.4%) in non-neutropenic patients. Gram-positive organisms were more commonly isolated than Gram-negative organisms (56.9% vs. 41.5%) in the following order: viridans streptococci (23.1%), Klebsiella pneumoniae (21.6%), coagulase-negative staphylococci (12.3%), Staphylococcus aureus (7.7%), Enterococcus faecium (7.7%). Susceptibility rates of viridans streptococci to penicillin, cefotaxime and vancomycin were 33.3%, 60% and 100%, and those of Enterobacteriaceae to amikacin, ceftazidime, piperacillin/ tazobactam and meropenem were 94.7%, 73.7%, 78.9%, and 100%, respectively. Compared to our previous data, infection still contributed towards a major fraction of mortality and morbidity in the management of patients with cancer. No differences in mortality rate were observed between isolated organisms from bacteremia. CONCLUSIONS: Gram-positive organisms were more prevalent than Gram-negative organisms in our population. The monitoring of causative agents and antimicrobial resistance should be considered in therapeutic strategies of pediatric hemato-oncologic infection.
Amikacin
;
Bacteremia
;
Cefotaxime
;
Ceftazidime
;
Child
;
Enterobacteriaceae
;
Enterococcus faecium
;
Humans
;
Klebsiella pneumoniae
;
Korea
;
Medical Records
;
Neutropenia
;
Penicillanic Acid
;
Penicillins
;
Retrospective Studies
;
Staphylococcus aureus
;
Thienamycins
;
Vancomycin
;
Viridans Streptococci

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