1.Clinical Utility of Monitoring Circulating Tumor DNA Using a Targeted Next-generation Sequencing Panel in Patients with Colorectal Cancer
Hyoeun SHIM ; Soobeen HEO ; Jiyu SUN ; Moon Ki CHOI ; Sung Chan PARK ; Chang Won HONG ; Seong Hoon KIM ; Seog-Yun PARK ; Sun-Young KONG ; Ji Yeon BAEK
Annals of Laboratory Medicine 2025;45(4):450-458
Background:
Circulating tumor DNA (ctDNA) profiling from peripheral blood allows relatively noninvasive monitoring of solid tumors; however, its utility post-surgery or chemotherapy in colorectal cancer remains underexplored. We evaluated the clinical implications of a ctDNA next-generation sequencing (NGS) panel post-surgery or chemotherapy in patients with colorectal cancer.
Methods:
We collected samples from 23 patients with colorectal cancer (17 men, median age 65 yrs) at baseline and post-surgery or chemotherapy at the National Cancer Center, Korea, between January 2021 and September 2023. ctDNA was analyzed using an NGS panel including 46 genes, and variant allele frequencies (VAFs) were determined. Followup samples were analyzed using the NGS panel or droplet digital PCR (ddPCR) when probes were available. Clinical status was compared with ctDNA results, and survival was analyzed using a time-dependent Cox model.
Results:
Mutations were identified in 13 out of 14 patients (92.8%) with stage II/III cancer and in all nine patients (100%) with stage IV cancer. Mutations were detected in KRAS (N = 15, 65%), APC (N = 8, 35%), TP53 (N = 7, 30%), PIK3CA (N = 5, 22%), and RET (N = 4, 17%). A 1% increase in KRAS and TP53 VAFs was associated with 48% and 32% increased mortality risk, respectively. Changes in VAF correlated well with clinical findings.
Conclusions
The detection of and an increase in KRAS and TP53 VAFs were associated with poor prognosis. ddPCR-based ctDNA monitoring results were comparable to those obtained with the NGS panel. ctDNA monitoring during treatment is clinically informative in managing colorectal cancer.
2.Systemic Inflammatory Response Following Preoperative Chemoradiotherapy Can Affect Oncologic Outcomes in MSI-H/dMMR Rectal Cancer
Hyukjin CHOI ; Jin Ho BAEK ; An Na SEO ; Su Yeon PARK ; Hye Jin KIM ; Jun Seok PARK ; Gyu Seog CHOI ; Jong Gwang KIM ; Byung Woog KANG
Chonnam Medical Journal 2024;60(2):105-112
Systemic inflammatory response (SIR) is a crucial determinant of disease progression and survival in patients with colorectal cancer. This study investigated the prognostic relevance of changes in the platelet count on survival and the predictive value of changes in the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) on the pathological tumor response to preoperative chemoradiotherapy (CRT) in patients with microsatellite instability-high (MSI-H) rectal cancer. From 2011 to 2022, data of 46 consecutive patients with MSI-H rectal cancer who were treated with preoperative CRT followed by curative surgery at Kyungpook National University Chilgok Hospital (Daegu, South Korea) were retrospectively analyzed. A 235 cut-off value was used to define whether PLR was high or low. Any change in the PLR or NLR was calculated on the basis of subtracting the pre-CRT PLR or NLR from the post-CRT values. Both pre-CRT and post-CRT values of the NLR and PLR were not significantly associated with clinical outcomes. Simple logistic regression analysis showed that a change in the PLR following CRT was not significantly associated with survival outcomes; however, patients who maintained a high change in the PLR following CRT showed significantly better pathologic T-stage. No statistically significant association was noted between changes in the platelet count and clinical outcomes of patients. The results suggested that changes in the PLR following CRT are associated with pathologic T-stage of the group. However, the SIR markers showed no prognostic values on the survival outcomes of the patients with MSI-H/mismatch repair-deficient (dMMR) locally advanced rectal cancer (LARC).
3.Resilience Gap in Gastrointestinal Endoscopy Activity during the COVID-19 Pandemic in South Korea
Hye-Yeon KIM ; Jeong-Ho YANG ; Sun-Seog KWEON
Chonnam Medical Journal 2024;60(3):180-186
This study assessed the impact of distancing measures during the COVID-19 pandemic on cancer diagnostic activities, including gastrointestinal endoscopy (GIE). It analyzed GIE volumes from 2020 to 2022 in comparison to 2018-2019, considering variations in resilience linked to socioeconomic status (SES). The analysis utilized data from the Korean Health Insurance Review and Assessment Services database, covering the entire population and medical facilities. Diagnostic GIE rates (2018-2022) in Gwangju Metropolitan City and Jeonnam province were examined, comparing age-standardized rates (ASRs) by area, gender, and SES. The results indicated a decline in ASRs for colonoscopy and endoscopic gastroduodenoscopy (EGD) in 2020 compared to 2018-2019, followed by an increase in 2021-2022, except for EGD in the medical aid population.SES based and rural-urban disparities were evident in the recovery of GIE rates. The findings suggest that equity-focused strategies are needed to ensure equitable healthcare access among different socioeconomic groups after pandemic.
4.Seroma prevention with topical Abnobaviscum sclerotherapy following excision of giant cervical lipoma
Jun Ho CHOI ; Seung Yeon CHOI ; Jae Ha HWANG ; Kwang Seog KIM ; Sam Yong LEE
Archives of Craniofacial Surgery 2023;24(1):10-17
Background:
Lipomas are common benign tumors of mesenchymal origin that are composed of mature adipocytes. Giant lipomas have a diameter ≥ 10 cm in one or more dimensions or weigh at least 1,000 g. The surgical excision of a giant lipoma requires extensive dissection, increasing the risk of a seroma, which can cause surgical site complications such as wound infection and necrosis. Sclerotherapy with Abnobaviscum (Viscum album extract) is a relatively new technique used to reduce malignant pleural effusion. In this study, we evaluated the effectiveness of prophylactic sclerotherapy using Abnobaviscum to decrease seroma after giant lipoma excision.
Methods:
We conducted a retrospective medical record review of patients who underwent surgical excision for giant lipoma of the neck from January 2019 to December 2022. Sclerotherapy was performed on the first postoperative day in patients who consented to the procedure, and Abnobaviscum was instilled through the existing Hemovac drain. We compared the clinical course between those who underwent postoperative sclerotherapy and those who did not.
Results:
Among the 30 patients who underwent giant lipoma excision, we applied sclerotherapy with Abnobaviscum to 15 patients. The average time from surgery to Hemovac removal was statistically shorter in patients who underwent sclerotherapy (p= 0.004). Furthermore, seroma formation was significantly reduced in patients receiving sclerotherapy (p= 0.003).
Conclusion
In patients undergoing giant lipoma excision, sclerotherapy using Abnobaviscum helps reduce postoperative seroma formation during the initial postoperative period. It can be an excellent method to reduce complications related to seroma and attenuate patients’ postoperative burden.
5.Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas
Seok Jin KIM ; Yeon Jeong KIM ; Sang Eun YOON ; Kyung Ju RYU ; Bon PARK ; Donghyun PARK ; Duck CHO ; Hyun-Young KIM ; Junhun CHO ; Young Hyeh KO ; Woong-Yang PARK ; Won Seog KIM
Cancer Research and Treatment 2023;55(1):291-303
Purpose:
Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL).
Materials and Methods:
After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes.
Results:
Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE.
Conclusion
Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.
6.Comparison of Pharmacodynamics between Tegoprazan and Dexlansoprazole Regarding Nocturnal Acid Breakthrough: A Randomized Crossover Study
Sungpil HAN ; Hee Youn CHOI ; Yo Han KIM ; SeungChan CHOI ; Seokuee KIM ; Ji Yeon NAM ; Bongtae KIM ; Geun Seog SONG ; Hyeong-Seok LIM ; Kyun-Seop BAE
Gut and Liver 2023;17(1):92-99
Background/Aims:
Tegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects.
Methods:
In a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation.
Results:
All 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration–time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing.
Conclusions
All the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.
7.Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
Joo Hyun OH ; Yeon Sil JANG ; Danbee KANG ; Hong Seog KIM ; Eui-Joong KIM ; So-Young PARK ; Cheol-Hyun KIM ; Yang Won MIN ; Dong Kyung CHANG
Gut and Liver 2023;17(1):100-107
Background/Aims:
There is increasing evidence that supplementation with pre- and probiotics appears to have positive effects on irritable bowel syndrome (IBS). The aim of this study was to determine the effects of a new synbiotic formulation on gastrointestinal symptoms in elderly patients with IBS.
Methods:
Sixty-seven IBS patients aged ≥60 years were randomly assigned to either a placebogroup (n=34) or a synbiotic group (n=33). During a 4-week intervention, subjects used a placebo or a synbiotic containing Lactobacillus paracasei DKGF1 and extracts of Opuntia humifusa once a day. Patients were evaluated with the subject global assessment, visual analog scale, and Bristol stool chart. The primary outcome was the overall responder rate and the secondary outcome was the responder rates for abdominal symptom reduction at week 4.
Results:
Overall, responder rates were significantly higher in the synbiotic group (51.5%) than in the placebo group (23.5%) (p=0.017). Abdominal pain (58.8% vs 81.8%) and psychological wellbeing (26.4% vs 60.6%) were noticeably improved in the synbiotic group (p=0.038 and p=0.004, respectively). However, there were no significant differences in gas and bloating symptoms (p=0.88 and p=0.88, respectively). In patients with constipation-dominant and diarrhea-dominant IBS (n=16), the synbiotic significantly improved abdominal pain and defecation symptoms (responder rates for the placebo vs the synbiotic: 22.2% vs 85.7%, p=0.04). There were no adverse events in either group.
Conclusions
The results indicate that this new synbiotic supplement can potentially relieve abdominal symptoms in elderly IBS patients.
8.Isolated unilateral temporalis muscle hypertrophy of unknown etiology: a case report and literature review
Jun Ho CHOI ; Seung Yeon CHOI ; Jae Ha HWANG ; Kwang Seog KIM ; Sam Yong LEE
Archives of Craniofacial Surgery 2023;24(6):278-283
The initial instance of isolated unilateral temporalis muscle hypertrophy (IUTMH) was reported in 1990. Since then, only few cases have been documented. The cause of this condition remains ambiguous; however, it is presumed to be linked to compensatory and stress-induced hypertrophy. We introduce a rare case of the diagnosis and treatment of IUTMH. A 39-year-old woman presented with a steadily enlarging pain-free swelling on the left side of her face, first noticed a month ago. Apart from a hyperthyroidism medication regimen her medical history was unremarkable. She had no history of temporomandibular joint disease, bruxism, surgery, or trauma. However, she complained of having been under substantial stress lately. Contrast-enhanced magnetic resonance imaging revealed asymmetric temporalis muscle hypertrophy. The treatment plan consisted of administering type A botulinum toxin injections into left temporalis muscle, supplemented by lifestyle changes and relaxation techniques. At a follow-up visit 9 months after the injections, the muscle contour was normalized both in physical and in radiologic examinations. While further supportive evidence is needed, it can be anticipated that cosmetic treatment with botulinum toxin, rather than surgical interventions, will become the standard treatment of IUTMH.
9.Effect Modification of Kidney Function on the Non-linear Association Between Serum Calcium Levels and Cardiovascular Mortality in Korean Adults
Jung-Ho YANG ; Sun-Seog KWEON ; Young-Hoon LEE ; Seong-Woo CHOI ; So-Yeon RYU ; Hae-Sung NAM ; Hye-Yeon KIM ; Min-Ho SHIN
Journal of Preventive Medicine and Public Health 2023;56(3):282-290
Objectives:
This study aimed to evaluate the potential interaction between kidney function and the non-linear association between serum calcium levels and cardiovascular disease (CVD) mortality.
Methods:
This study included 8927 participants enrolled in the Dong-gu Study. Albumin-corrected calcium levels were used and categorized into 6 percentile categories: <2.5th, 2.5-25.0th, 25.0-50.0th, 50.0-75.0th, 75.0-97.5th, and >97.5th. Restricted cubic spline analysis was used to examine the non-linear association between calcium levels and CVD mortality. Cox proportional hazard regression was used to estimate hazard ratios (HRs) for CVD mortality according to serum calcium categories. All survival analyses were stratified by the estimated glomerular filtration rate.
Results:
Over a follow-up period of 11.9±2.8 years, 1757 participants died, of whom 219 died from CVD. A U-shaped association between serum calcium and CVD mortality was found, and the association was more evident in the low kidney function group. Compared to the 25.0-50.0th percentile group for serum calcium levels, both low and high serum calcium tended to be associated with CVD mortality (<2.5th: HR, 6.23; 95% confidence interval [CI], 1.16 to 33.56; >97.5th: HR, 2.56; 95% CI, 0.76 to 8.66) in the low kidney function group. In the normal kidney function group, a similar association was found between serum calcium levels and CVD mortality (<2.5th: HR, 1.37; 95% CI, 0.58 to 3.27; >97.5th: HR, 1.65; 95% CI, 0.70 to 3.93).
Conclusions
We found a non-linear association between serum calcium levels and CVD mortality, suggesting that calcium dyshomeostasis may contribute to CVD mortality, and kidney function may modify the association.
10.MR Template‑Based Individual Brain PET Volumes‑of‑Interest Generation Neither Using MR nor Using Spatial Normalization
Seung Yeon SEO ; Jungsu S. OH ; Jinwha CHUNG ; Seog‑Young KIM ; Jae Seung KIM
Nuclear Medicine and Molecular Imaging 2023;57(2):73-85
For more anatomically precise quantitation of mouse brain PET, spatial normalization (SN) of PET onto MR template and subsequent template volumes-of-interest (VOIs)-based analysis are commonly used. Although this leads to dependency on the corresponding MR and the process of SN, routine preclinical/clinical PET images cannot always afford corresponding MR and relevant VOIs. To resolve this issue, we propose a deep learning (DL)-based individual-brain-specific VOIs (i.e., cortex, hippocampus, striatum, thalamus, and cerebellum) directly generated from PET images using the inverse-spatialnormalization (iSN)-based VOI labels and deep convolutional neural network model (deep CNN). Our technique was applied to mutated amyloid precursor protein and presenilin-1 mouse model of Alzheimer’s disease. Eighteen mice underwent T2-weighted MRI and 18 F FDG PET scans before and after the administration of human immunoglobin or antibody-based treatments. To train the CNN, PET images were used as inputs and MR iSN-based target VOIs as labels. Our devised methods achieved decent performance in terms of not only VOI agreements (i.e., Dice similarity coefficient) but also the correlation of mean counts and SUVR, and CNN-based VOIs was highly accordant with ground-truth (the corresponding MR and MR template-based VOIs). Moreover, the performance metrics were comparable to that of VOI generated by MR-based deep CNN. In conclusion, we established a novel quantitative analysis method both MR-less and SN-less fashion to generate individual brain space VOIs using MR template-based VOIs for PET image quantification.

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