1.Development of an Instrument for Slit-lamp Examination of Donor Corneas in Preservation Medium
Ga Hee NAM ; Da Ran KIM ; Young Chae YOON ; Soon Won YANG ; Woong Joo WHANG ; Yong-Soo BYUN ; Hyung Bin HWANG ; Kyung Sun NA ; Hyun Soo LEE ; So Hyang CHUNG ; Eun Chul KIM ; Yang Kyung CHO ; Hyun Seung KIM ; Ho Sik HWANG
Journal of the Korean Ophthalmological Society 2024;65(2):108-116
Purpose:
To evaluate the effectiveness of an instrument devised for slit-lamp examination of donor corneas suspended in preservation medium.
Methods:
The study examined two donor corneas received at Yeouido St. Mary's Hospital in February 2023 and March 2023. The instrument has three main components: a plastic holder to hold the preservation medium bottle, a cube with a mirror for reflecting the slit beam, and a stand to attach the device to the slit-lamp. Using the instrument, the donor corneas were examined via slit-lamp: microscopy with the endothelium facing upward and downward. Specular microscopy and anterior segment optical coherence tomography (OCT) were also performed on the preserved donor corneas.
Results:
Slit-lamp examination of donor corneas in preservation medium using the instrument showed overall corneal buttoning and optical sections of the donor cornea. Using specular reflection and retroillumination, the endothelial layer was partially visible. However, specular microscopy and anterior segment OCT could not examine the donor cornea in preservation medium using the instrument.
Conclusions
The devised instrument facilitates slit-lamp examination of donor corneas in preservation medium, enabling a qualitative assessment of donor corneas before corneal transplantation surgery.
2.A Case of Moyamoya Disease in Morning Glory Syndrome
Jun Chul BYUN ; Se Youp LEE ; Soon Young CHO
Journal of the Korean Ophthalmological Society 2024;65(3):257-260
Purpose:
We report a diagnosis of Moyamoya disease based on brain magnetic resonance imaging (MRI) and brain magnetic resonance angiography (MRA) performed in a child diagnosed with morning glory syndrome.Case summary: A 6-year-old boy visited the hospital with a chief complaint of exodeviation of his left eye that started at 1 year of age. The corrected visual acuity was 20/30 in the right eye and 20/400 in the left. The Krimsky test showed exotropia of 35 prism diopters (PD) for near vision and 30 PD for distance. Fundus photography showed an enlarged optic disc with funnel-shaped excavation in the left eye. With a diagnosis of morning glory syndrome accompanied by exotropia, the patient underwent brain MRI and brain MRA. The patient had no neurological symptoms such as headache and muscle weakness. Moyamoya disease was diagnosed, as brain MRI and MRA showed tiny tortuous vessels forming collateral vessels from the lenticulostriatal arteries, left posterior cerebral artery, and left middle meningeal artery, which originated from the external carotid artery.
Conclusions
Moyamoya disease can occur in children with morning glory disease. Brain MRI and MRA can help to diagnose Moyamoya disease. Caution is needed because transient ischemic attack, cerebral infarction, and cerebral hemorrhage may occur in patients with Moyamoya disease.
3.Noninferiority Outcomes of Besifovir Compared to Tenofovir Alafenamide in Treatment-Naïve Patients with Chronic Hepatitis B
Tae Hyung KIM ; Ji Hoon KIM ; Hyung Joon YIM ; Yeon Seok SEO ; Sun Young YIM ; Young-Sun LEE ; Young Kul JUNG ; Jong Eun YEON ; Soon Ho UM ; Kwan Soo BYUN
Gut and Liver 2024;18(2):305-315
Background/Aims:
Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB).However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB.
Methods:
We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes.
Results:
A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (–0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15.
Conclusions
BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.
4.Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09)
Jieun LEE ; Keun Seok LEE ; Sung Hoon SIM ; Heejung CHAE ; Joohyuk SOHN ; Gun Min KIM ; Kyung-Hee LEE ; Su Hwan KANG ; Kyung Hae JUNG ; Jae-ho JEONG ; Jae Ho BYUN ; Su-Jin KOH ; Kyoung Eun LEE ; Seungtaek LIM ; Hee Jun KIM ; Hye Sung WON ; Hyung Soon PARK ; Guk Jin LEE ; Soojung HONG ; Sun Kyung BAEK ; Soon Il LEE ; Moon Young CHOI ; In Sook WOO
Cancer Research and Treatment 2023;55(1):123-135
Purpose:
The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.
Materials and Methods:
We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.
Results:
The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).
Conclusion
Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.
5.A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation
Guk Jin LEE ; Hyunho KIM ; Sung Shim CHO ; Hyung Soon PARK ; Ho Jung AN ; In Sook WOO ; Jae Ho BYUN ; Ji Hyung HONG ; Yoon Ho KO ; Der Sheng SUN ; Hye Sung WON ; Jong Youl JIN ; Ji Chan PARK ; In-Ho KIM ; Sang Young ROH ; Byoung Yong SHIM
Journal of Gastric Cancer 2023;23(2):315-327
Purpose:
Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy.
Materials and Methods:
Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level.
Results:
Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020).
Conclusions
After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.
6.Novel Method Measuring Conjunctival Microvascular Blood Flow Velocity by Zoom-lens, Ultra-high-speed Camera Attached Slit-lamp Biomicroscope
Hyo Sin KIM ; Da Ran KIM ; Young Chae YOON ; Soon Won YANG ; Young Sik YOO ; Woong Joo WHANG ; Yong-Soo BYUN ; Hyung Bin HWANG ; Kyung Sun NA ; Hyun Soo LEE ; So Hyang CHUNG ; Eun Chul KIM ; Yang Kyung CHO ; Hyun Seung KIM ; Ho Sik HWANG
Journal of the Korean Ophthalmological Society 2023;64(11):1001-1008
Purpose:
To introduce an intuitive method for measuring conjunctival microvascular blood flow velocity by imaging bulbar conjunctival microvessels using a slit-lamp biomicroscope equipped with a zoom lens and an ultra-high-speed camera.
Methods:
After obtaining consent from 10 patients (1 male, 9 females) who visited Yeouido St. Mary’s Hospital from August 21, 2020, to June 12, 2021, the patients were examined under a slit lamp microscope equipped with an ultra-high-speed camera and zoom lens. The blood flow in the conjunctival microvessels was photographed. The captured images were analyzed with ImageJ software to measure the blood flow velocity in the conjunctival microvessels, and we investigated whether the blood flow velocity correlated with the vessel diameter and age.
Results:
The median age of the subjects was 49.0 years. The mean conjunctival blood flow velocity in 53 microvessels was 0.786 ± 0.468 mm/s. The median conjunctival microvascular diameter was 7.06 μm (interquartile range 5.84 to 9.23 μm). The conjunctival microvascular diameter and blood flow velocity were not significantly correlated (Spearman’s p = 0.177), and the subjects’ age and conjunctival microvascular blood flow velocity were also not correlated (Spearman’s p = 0.669).
Conclusions
In this study, the blood flow velocity in the bulbar conjunctival microvessels could be measured easily by means of image analysis using a slit-lamp microscope equipped with an ultra-high-speed camera with a zoom lens.
7.Assessment for Macular Thickness after Uncomplicated Phacoemulsification Using Optical Coherence Tomography
Byung-Jin KIM ; Ye Jin AHN ; Hye-Young OH ; Soon Il CHOI ; Young-Sik YOO ; Woong-Joo WHANG ; Yong-Soo BYUN ; Mee-yon LEE ; Choun-Ki JOO
Korean Journal of Ophthalmology 2022;36(4):296-305
Purpose:
Macular edema including cystoid macular edema is one of the main causes of unfavorable visual outcomes after cataract surgery. The macular thickness and the occurrence of macular edema after uncomplicated cataract surgery was evaluated using optical coherence tomography (OCT) in this study.
Methods:
Macular map images were taken by OCT before surgery and at 1 week, 1 month, and 2 months postsurgery. The subjects were classified into two groups (group 1, patients with no macular edema; group 2, patients with macular edema). Group 2 was defined as increase in central macular thickness (CMT) by 30% compared with that before surgery. The risk factors for macular edema were evaluated. Group 2 was divided into two subgroups: subclinical macular edema (group 2A) and cystoid macular edema (group 2B) and they were assessed in terms of the clinical course of best-corrected visual acuity and CMT.
Results:
A total of 376 patients were enrolled in this study, of which 36 (9.57%, group 2) showed macular edema measured by OCT after the surgery. Univariate analysis for group 1 and 2 revealed that intracameral injection of epinephrine during phacoemulsification was associated with the development of macular edema. In group 2, five patients (1.33%) developed cystoid macular edema. Statistically significant differences in the clinical course of CMT were observed at 2 months (201.2 ± 23.1, 250.0 ± 29.8, and 371.0 ± 160.3 in group 1, group 2A, and group 2B, respectively; p < 0.001) and 1 month postoperatively (198.5 ± 23.6, 237.8 ± 40.9, and 314.0 ± 104.5 in group 1, group 2A, and group 2B, respectively; p < 0.001). Group 2B required additional treatment and eventually achieved best-corrected visual acuity of >0.2 with CMT in the normal range.
Conclusions
The intracameral injection of epinephrine may cause macular edema after uncomplicated cataract surgery. Examination of CMT using OCT is recommended for the early detection of macular edema.
8.Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models
Seong Hee KANG ; Hyung Joon YIM ; Ji-won HWANG ; Mi-jung KIM ; Young-Sun LEE ; Young Kul JUNG ; Hyungshin YIM ; Baek-Hui KIM ; Hae-Chul PARK ; Yeon Seok SEO ; Ji Hoon KIM ; Jong Eun YEON ; Soon Ho UM ; Kwan Soo BYUN
The Korean Journal of Internal Medicine 2022;37(4):745-756
Background/Aims:
Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects.
Methods:
The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis.
Results:
The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2.
Conclusions
The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.
9.Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer
Hyunseung OH ; Soon Gu KIM ; Sung Uk BAE ; Sang Jun BYUN ; Shin KIM ; Jae-Ho LEE ; Ilseon HWANG ; Sun Young KWON ; Hye Won LEE
Journal of Pathology and Translational Medicine 2022;56(1):40-47
Background:
Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT).
Methods:
A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens.
Results:
We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression.
Conclusions
This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.
10.Comparison of Sorafenib versus Hepatic Arterial Infusion Chemotherapy-Based Treatment for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis
Young Eun AHN ; Sang Jun SUH ; Hyung Joon YIM ; Yeon Seok SEO ; Eileen L. YOON ; Tae Hyung KIM ; Young Sun LEE ; Sun Young YIM ; Hae Rim KIM ; Seong Hee KANG ; Young Kul JUNG ; Ji Hoon KIM ; Jong Eun YEON ; Soon Ho UM ; Kwan Soo BYUN
Gut and Liver 2021;15(2):284-294
Background/Aims:
Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT.
Methods:
Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR).
Results:
Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030).
Conclusions
HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.

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