1.Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial
Ji-Jung JUNG ; Jong-Ho CHEUN ; Soo-Yeon KIM ; Jiwon KOH ; Jai Min RYU ; Tae-Kyung YOO ; Hee-Chul SHIN ; Sung Gwe AHN ; Seho PARK ; Woosung LIM ; Sang-Eun NAM ; Min Ho PARK ; Ku Sang KIM ; Taewoo KANG ; Jeeyeon LEE ; Hyun Jo YOUN ; Yoo Seok KIM ; Chang Ik YOON ; Hong-Kyu KIM ; Hyeong-Gon MOON ; Wonshik HAN ; Nariya CHO ; Min Kyoon KIM ; Han-Byoel LEE
Journal of Breast Cancer 2024;27(1):61-71
Purpose:
Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies.
Methods
The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuumassisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years.Discussion: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients.
2.Characterization of Glycosyl Inositol Phosphoceramides from Panax ginseng using Nanospray Tandem Mass Spectrometry
So-Hyun KIM ; Ye-Been LEE ; Yoonho JEONG ; Jae-Yeon CHO ; Hyung-Kyoon CHOI
Natural Product Sciences 2024;30(2):103-116
Korean ginseng (Panax ginseng C. A. Meyer) is one of the most popular medicinal herbs in the world. This plant is known to have many health benefits and contain a wide variety of bioactive components. However, the knowledge on its lipid compound is still far from being fully explored. Although glycosyl inositol phosphoceramides (GIPCs) are the main sphingolipids in plant tissues, GIPCs of P. ginseng are unknown. The present study employed nanoESI-MS n , which generated characteristic fragmentation pattern that were used for the structural identification of P. ginseng GIPCs. In addition to detecting a typical mass fragmentation pattern for GIPC in positive ion mode, novel fragmentation correlating with cleavage of the last carbohydrate and fatty acyl chain of the ceramide moiety was identified. In total, 42 GIPC species were detected in P. ginseng. The major P. ginseng GIPC structure was hexose (R 1 )-hexuronic acid-inositol phosphoceramide, with three types of R 1 (amine, N-acetylamine, or hydroxyl). The most intense peak was found at m/z 1136.3 ([M+H] + ion), corresponding to a GIPC (d18:0/h16:0, R 1 = OH). Only three GIPC subtypes showed significantly different levels in five- and six-year-old P. ginseng tap roots.
3.Full-Term Baby with Cerebellar Hemorrhage Referred for Severe Jaundice Occurring within the First 3 Days of Life
In Wook LEE ; Jae Kyoon HWANG ; Ja-Hye AHN ; Hyun Ju LEE ; Chang-Ryul KIM
Neonatal Medicine 2024;31(1):9-15
Cerebellar hemorrhage in full-term infants is a rare condition recently recognized in high-risk newborns requiring intensive care with the availability of advanced neuroimaging techniques. Several aspects such as the incidence, pathophysiology, clinical features, and prognosis of cerebellar hemorrhage in full-term infants remain unknown. We present a case of cerebellar hemorrhage with subdural hemorrhage in a patient hospitalized for jaundice after birth without a history of traumatic delivery, such as breech presentation, prolonged labor or forceps delivery. A full-term female infant weighing 3,100 g at birth, with no complications during delivery, developed jaundice within 48 hours of birth and was admitted for intensive phototherapy in the first 3 days of life with a transcutaneous total bilirubin level of 18.1 mg/dL. Magnetic resonance imaging revealed cerebellar brain lesions with a subdural hemorrhage. At the age of 3 months, the infant exhibited leg rigidity and was referred for rehabilitation. The patient showed signs of improvement during treatment and was generally catching up well with her peers at the age of 9 months. Long-term follow-ups are required to evaluate the consequences on cognitive development, behavior, and motor performance subsequently in life.
4.Whole-Genome and Transcriptome Sequencing Identified NOTCH2 and HES1 as Potential Markers of Response to Imatinib in Desmoid Tumor (Aggressive Fibromatosis): A Phase II Trial Study
Joonha KWON ; Jun Hyeong LEE ; Young Han LEE ; Jeeyun LEE ; Jin-Hee AHN ; Se Hyun KIM ; Seung Hyun KIM ; Tae Il KIM ; Kum-Hee YUN ; Young Suk PARK ; Jeong Eun KIM ; Kyu Sang LEE ; Jung Kyoon CHOI ; Hyo Song KIM
Cancer Research and Treatment 2022;54(4):1240-1255
Purpose:
Desmoid tumor, also known as aggressive fibromatosis, is well-characterized by abnormal Wnt/β-catenin signaling. Various therapeutic options, including imatinib, are available to treat desmoid tumor. However, the molecular mechanism of why imatinib works remains unclear. Here, we describe potential roles of NOTCH2 and HES1 in clinical response to imatinib at genome and transcriptome levels.
Materials and Methods:
We identified somatic mutations in coding and noncoding regions via whole-genome sequencing. To validate the genetic interaction with expression level in desmoid-tumor condition, we utilized large-scale whole-genome sequencing and transcriptome datasets from the Pan-Cancer Analysis of Whole Genomes project. RNA-sequencing was performed using prospective and retrospective cohort samples to evaluate the expressional relevance with clinical response.
Results:
Among 20 patients, four (20%) had a partial response and 14 (66.7%) had stable disease, 11 of which continued for ≥ 1 year. With gene-wise functional analyses, we detected a significant correlation between recurrent NOTCH2 noncoding mutations and clinical response to imatinib. Based on Pan-Cancer Analysis of Whole Genomes data analyses, NOTCH2 mutations affect expression levels particularly in the presence of CTNNB1 missense mutations. By analyzing RNA-sequencing with additional desmoid tumor samples, we found that NOTCH2 expression was significantly correlated with HES1 expression. Interestingly, NOTCH2 had no statistical power to discriminate between responders and non-responders. Instead, HES1 was differentially expressed with statistical significance between responders and non-responders.
Conclusion
Imatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, and an important therapeutic consideration for desmoid tumor.
5.Rapidly Progressive Pericardial Effusion and Cardiac Tamponade in a Term Infant with an Umbilical Venous Catheter: A Case Report
Min-Jung PARK ; Ja-Hye AHN ; Hyun Ju LEE ; Hyun-Kyung PARK ; Jae-Kyoon HWANG ; Chang-Ryul KIM ; Jae Yoon NA
Neonatal Medicine 2022;29(4):135-140
Pericardial effusion (PCE) in neonates has various clinical presentations depending on the amount and speed of fluid accumulation and can cause cardiac tamponade (CT). We report a case of rapidly accumulating PCE and near-fatal CT with an umbilical venous catheter successfully resolved by emergent echo-guided pericardiocentesis in a term infant who had been hospitalized with meconium aspiration syndrome and persistent pulmonary hypertension. This case report suggests that if a patient with an intracardiac umbilical catheter shows sudden cardiopulmonary instability, the possibility of PCE and CT should be considered. Furthermore, if necessary, emergency drainage of the PCE and removal of the umbilical catheter should be immediately performed.
6.Effects of Ponderal Index on Neonatal Mortality and Morbidities in Extremely Premature Infants
Jae Kyoon HWANG ; Ha-Na KANG ; Ja-Hye AHN ; Hyun Ju LEE ; Hyun-Kyung PARK ; Chang-Ryul KIM
Journal of Korean Medical Science 2022;37(24):e198-
Background:
To evaluate how intrauterine stress affects extremely premature infants in terms of intrauterine growth restriction. We hypothesized that extremely premature infants with mildly-low ponderal index (MPI) would have better neonatal outcomes.
Methods:
We selected 2,721 subjects of 23 to 28 weeks of gestation between 2013 and 2015 from Korean Neonatal Network database. They were divided into 4 groups based on ponderal index (PI) percentile; PI ≤ 3rd as severely-low PI (SPI, n = 82), 3rd < PI ≤ 10th as MPI (n = 190), 10th < PI ≤ 90th as adequate PI (API, n = 2,179), and PI > 90th as high PI (HPI, n = 270).
Results:
The mortality in MPI and API groups was comparable (16.3% vs. 16.9%). It was significantly lower than that in the SPI and HPI groups (30.5% and 24.9%, respectively;P = 0.001). The MPI and API groups had better neonatal morbidities compared with the SPI and/or HPI groups, while the MPI group (8.2%) showed a lower incidence of severe intraventricular hemorrhage (IVH) than the other groups (SPI, 21.3%; API, 15.0%; HPI, 19.7%, respectively; P = 0.004). The MPI group had a trend of a bottom in neonatal mortality and morbidities in extremely premature infants.
Conclusion
The MPI and API groups had lower mortality, massive pulmonary hemorrhage, severe bronchopulmonary dysplasia or death, pulmonary hypertension and neonatal seizure rates than the SPI and/or HPI groups, while the MPI group showed a lower incidence of severe IVH than the other groups. We speculate that the lower incidence of neonatal morbidities and mortality in the MPI group indicating mild intrauterine stress might accelerate fetal maturation resulting in better outcomes in extremely premature infants.
7.Effects of Lipopolysaccharide on Oligodendrocyte Differentiation at Different Developmental Stages: an In Vitro Study
Ja-Hye AHN ; Hyun Ju LEE ; Kyeongmi LEE ; Jean LIM ; Jae Kyoon HWANG ; Chang-Ryul KIM ; Hyun A KIM ; Han-Suk KIM ; Hyun-Kyung PARK
Journal of Korean Medical Science 2021;36(49):e332-
Background:
Lipopolysaccharide (LPS) exerts cytotoxic effects on brain cells, especially on those belonging to the oligodendrocyte lineage, in preterm infants. The susceptibility of oligodendrocyte lineage cells to LPS-induced inflammation is dependent on the developmental stage. This study aimed to investigate the effect of LPS on oligodendrocyte lineage cells at different developmental stages in a microglial cell and oligodendrocyte coculture model.
Methods:
The primary cultures of oligodendrocytes and microglia cells were prepared from the forebrains of 2-day-old Sprague–Dawley rats. The oligodendrocyte progenitor cells (OPCs) co-cultured with microglial cells were treated with 0 (control), 0.01, 0.1, and 1 µg/mL LPS at the D3 stage to determine the dose of LPS that impairs oligodendrocyte differentiation. The co-culture was treated with 0.01 µg/mL LPS, which was the lowest dose that did not impair oligodendrocyte differentiation, at the developmental stages D1 (early LPS group), D3 (late LPS group), or D1 and D3 (double LPS group). On day 7 of differentiation, oligodendrocytes were subjected to neural glial antigen 2 (NG2) and myelin basic protein (MBP) immunostaining to examine the number of OPCs and mature oligodendrocytes, respectively.
Results:
LPS dose-dependently decreased the proportion of mature oligodendrocytes (MBP+ cells) relative to the total number of cells. The number of MBP+ cells in the early LPS group was significantly lower than that in the late LPS group. Compared with those in the control group, the MBP+ cell numbers were significantly lower and the NG2+ cell numbers were significantly higher in the double LPS group, which exhibited impaired oligodendrocyte lineage cell development, on day 7 of differentiation.
Conclusion
Repetitive LPS stimulation during development significantly inhibited brain cell development by impairing oligodendrocyte differentiation. In contrast, brain cell development was not affected in the late LPS group. These findings suggest that inflammation at the early developmental stage of oligodendrocytes increases the susceptibility of the preterm brain to inflammation-induced injury.
8.Clinical Characteristics of False-Positive Lymph Node on Chest CT or PET-CT Confirmed by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Lung Cancer.
Jongmin LEE ; Young Kyoon KIM ; Ye Young SEO ; Eun Kyoung CHOI ; Dong Soo LEE ; Yeon Sil KIM ; Sook Hee HONG ; Jin Hyoung KANG ; Kyo Young LEE ; Jae Kil PARK ; Sook Whan SUNG ; Hyun Bin KIM ; Mi Sun PARK ; Hyeon Woo YIM ; Seung Joon KIM
Tuberculosis and Respiratory Diseases 2018;81(4):339-346
BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure to evaluate suspicious lymph node involvement of lung cancer because computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography-CT (PET-CT) have limitations in their sensitivity and specificity. There are a number of benign causes of false positive lymph node such as anthracosis or anthracofibrosis, pneumoconiosis, old or active tuberculosis, interstitial lung disease, and other infectious conditions including pneumonia. The purpose of this study was to evaluate possible causes of false positive lymph node detected in chest CT or PET-CT. METHODS: Two hundred forty-seven patients who were initially diagnosed with lung cancer between May 2009 and December 2012, and underwent EBUS-TBNA to confirm suspicious lymph node involvement by chest CT or PET-CT were analyzed for the study. RESULTS: Of 247 cases, EBUS-TBNA confirmed malignancy in at least one lymph node in 189. The remaining 58 patients whose EBUS-TBNA results were negative were analyzed. Age ≥65, squamous cell carcinoma as the histologic type, and pneumoconiosis were related with false-positive lymph node involvement on imaging studies such as chest CT and PET-CT. CONCLUSION: These findings suggest that lung cancer staging should be done more carefully when a patient has clinically benign lymph node characteristics including older age, squamous cell carcinoma, and benign lung conditions.
Anthracosis
;
Carcinoma, Squamous Cell
;
Electrons
;
Humans
;
Lung Diseases, Interstitial
;
Lung Neoplasms*
;
Lung*
;
Lymph Nodes*
;
Needles*
;
Pneumoconiosis
;
Pneumonia
;
Sensitivity and Specificity
;
Thorax*
;
Tomography, X-Ray Computed*
;
Tuberculosis
9.Quantitative Evaluation of Post-stroke Spasticity Using Neurophysiological and Radiological Tools: A Pilot Study.
Mi Jin HONG ; Jong Bum PARK ; Yung Jin LEE ; Hyeong Tae KIM ; Won Chul LEE ; Cheol Mog HWANG ; Hyun Kyoon LIM ; Dong Hyun LEE
Annals of Rehabilitation Medicine 2018;42(3):384-395
OBJECTIVE: To determine the possibility of a new measurement tool using electromyography and ultrasonography for quantitative spasticity assessment in post-stroke patients. METHODS: Eight hemiplegic stroke patients with ankle plantarflexor spasticity confirmed by a Modified Ashworth Scale (MAS) were enrolled. Spasticity was evaluated using the MAS and Modified Tardieu Scale (MTS). Each subject underwent surface electromyography (sEMG) using the Brain Motor Control Assessment (BMCA) protocol and was compared with a healthy control group. Using ultrasonography, muscle architecture and elasticity index were measured from the medial gastrocnemius muscle (GCM) on the affected and unaffected sides. RESULTS: MAS and MTS revealed significant correlation with sEMG activity. The fascicle length and pennation angle were significantly decreased in the medial GCM on the hemiplegic side compared with the unaffected side. The elasticity index of the spastic medial GCM was significantly increased compared with the unaffected side. The MTS X and R2–R1 values were significantly correlated with the elasticity index in the hemiplegic GCM. The relationship between clinical evaluation tools and both BMCA and sonoelastography was linear, but not statistically significant in the multiple regression analysis. CONCLUSION: The BMCA protocol and ultrasonographic evaluation provide objective assessment of post-stroke spasticity. Further studies are necessary to conduct accurate assessment and treatment of spasticity.
Ankle
;
Brain
;
Elasticity
;
Elasticity Imaging Techniques
;
Electromyography
;
Evaluation Studies as Topic*
;
Humans
;
Muscle Spasticity*
;
Muscle, Skeletal
;
Muscles
;
Pilot Projects*
;
Stroke
;
Ultrasonography
10.Anti-N-methyl-D-aspartate Receptor Encephalitis Caused by a Mature Mediastinal Teratoma
Hyun Jae KIM ; Je Hong MIN ; So Young PARK ; Seungyon KOH ; Jun Young CHOI ; Kyoon HUH
Journal of the Korean Neurological Association 2018;36(2):103-106
An extra-ovarian teratoma has been reported in a few cases of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. A 25-year-old woman presented with psychiatric symptoms. We did not find an ovarian teratoma on initial examination, and her initial simple chest X-ray was normal. We incidentally found an abnormality on follow-up simple chest X-ray and diagnosed an anterior mediastinal teratoma. Therefore, in patients with suspected anti-NMDAR encephalitis, even if simple chest X-ray is normal, chest computed tomography should be performed to investigate a hidden teratoma.
Adult
;
Anti-N-Methyl-D-Aspartate Receptor Encephalitis
;
Encephalitis
;
Female
;
Follow-Up Studies
;
Humans
;
Teratoma
;
Thorax

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