1.Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-analysis Based on Individual Patient-Level Data of Randomized Trials
Jaewon HYUNG ; Minsu KANG ; Ilhwan KIM ; Kyu-pyo KIM ; Baek-Yeol RYOO ; Jaekyung CHEON ; Hyewon RYU ; Ji Sung LEE ; Ji-Won KIM ; In Sil CHOI ; Jin Hyun PARK ; Ghassan K. ABOU-ALFA ; Jin Won KIM ; Changhoon YOO
Cancer Research and Treatment 2025;57(2):519-527
Purpose:
While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head.
Materials and Methods:
We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens.
Results:
A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy.
Conclusion
Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.
2.Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-analysis Based on Individual Patient-Level Data of Randomized Trials
Jaewon HYUNG ; Minsu KANG ; Ilhwan KIM ; Kyu-pyo KIM ; Baek-Yeol RYOO ; Jaekyung CHEON ; Hyewon RYU ; Ji Sung LEE ; Ji-Won KIM ; In Sil CHOI ; Jin Hyun PARK ; Ghassan K. ABOU-ALFA ; Jin Won KIM ; Changhoon YOO
Cancer Research and Treatment 2025;57(2):519-527
Purpose:
While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head.
Materials and Methods:
We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens.
Results:
A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy.
Conclusion
Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.
3.Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-analysis Based on Individual Patient-Level Data of Randomized Trials
Jaewon HYUNG ; Minsu KANG ; Ilhwan KIM ; Kyu-pyo KIM ; Baek-Yeol RYOO ; Jaekyung CHEON ; Hyewon RYU ; Ji Sung LEE ; Ji-Won KIM ; In Sil CHOI ; Jin Hyun PARK ; Ghassan K. ABOU-ALFA ; Jin Won KIM ; Changhoon YOO
Cancer Research and Treatment 2025;57(2):519-527
Purpose:
While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head.
Materials and Methods:
We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens.
Results:
A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy.
Conclusion
Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.
4.Mucosa-Associated Lymphoid Tissue Lymphoma of the Labial Minor Salivary Glands: Case Report
Jung Eun LEE ; Dawool HAN ; Hyun Sil KIM ; Chena LEE ; YounJung PARK ; Jeong-Seung KWON
Journal of Oral Medicine and Pain 2024;49(1):22-27
A 74-year-old female presented with a complaint of dry mouth, continuous spontaneous burning sensation in the tongue, and asymptomatic submucosal soft tissue mass on both sides of the lower labial mucosa. She refused to undergo total excision of the mass due to concern about the possibility of complications such as nerve damage because of the large size of the mass. As her clinical features and magnetic resonance imaging indicated the possibility of Sjögren’s syndrome, a biopsy of the minor salivary gland of the right lower lip was performed. Consequently, she was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma. Although the patient had typical signs and symptoms of Sjögren’s syndrome, the histopathological result of MALT lymphoma made it impossible to determine whether the patient had a history of Sjögren’s syndrome. For patients with risk factors for MALT lymphoma, such as Sjögren’s syndrome, a biopsy of the labial minor salivary gland with immunohistochemical staining can be helpful in the diagnosis of not only Sjögren’s syndrome but also MALT lymphoma.
5.Reconstruction of a deformed umbilicus with a keloid using a single triangular incision line: a case report
Archives of Aesthetic Plastic Surgery 2024;30(2):78-81
A common goal in reconstructing the umbilicus is to achieve an aesthetically pleasing result. This single-subject study demonstrates the outcome of managing an umbilical keloid scar using a single excisional line. A patient presented with a large, oval keloid scar at the center of his abdomen. The scar, measuring 4×3 cm in diameter, was deformed to the extent that it completely obscured the umbilicus. The patient frequently experienced intermittent inflammation at the site of the scar. We planned a triangular incision around the keloid. The umbilical keloid was excised and reconstructed using a flap anchored along the lower edge of the triangle. The triangular flap was elevated and the deep dermis of its cephalic portion was attached to the linea alba. The remainder of the flap was sutured at the center to create a conical shape. Eleven months post-procedure, the umbilicus maintained an aesthetically pleasing appearance with proper depth, superior hooding, and a concave shape without protrusion. An advantage of this straightforward surgical method is that it allows for simultaneous resection and reconstruction without the need for additional flap design. This method is expected to be a useful option for reconstructing umbilical keloids the size of a fully developed umbilicus.
6.Diagnostic Utility of Whole Genome Sequencing After Negative Karyotyping/Chromosomal Microarray in Infants Born With Multiple Congenital Anomalies
Misun YANG ; Jee Ah KIM ; Heui Seung JO ; Jong-Ho PARK ; So Yoon AHN ; Se In SUNG ; Won Soon PARK ; Hye-Won CHO ; Jeong-Min KIM ; Mi-Hyun PARK ; Hyun-Young PARK ; Ja-Hyun JANG ; Yun Sil CHANG
Journal of Korean Medical Science 2024;39(36):e250-
Background:
Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA.
Methods:
In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping.The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trioWGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group. Results: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants.There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants.
Conclusion
This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS.
7.Current Status of Public Long-term Care Insurance Services and Future Perspective: A Questionnaire Survey and National Health Insurance Service Data of South Korea
Eun Hyang SONG ; Yeon Sil MOON ; Jung Hyun PARK ; Byung Euk JOO ; Ho Seong HAN ; Chan-Nyoung LEE ; Hyun Jeong HAN ; Jae Moon KIM
Journal of the Korean Neurological Association 2024;42(1):1-12
The continuing growth of population aged 65 years and above, the socioeconomic burden of long-term care insurance has consistently increased. This study aimed to review the current system and efficiently develop long-term care insurance services according to changes in socioeconomic situations. First, a 21 items questionnaire survey was conducted from August 16 to August 31, 2022, for all members of the Korean Neurological Association. The survey was divided into seven areas, and individualized results were analyzed. Second, cumulative data on long-term care insurance services were collected and analyzed from July 1, 2008 to December 31, 2021, for the National Health Insurance system, and the results were summarized. In the survey, approximately 21% of the neurologists answered a web-based questionnaire survey on current doctors’ referral slips for long-term insurance services. Most (94%) had doctor referral slips for long-term insurance services. However, the authors estimated that doctors’ referral slips did not sufficiently affect the grading of longterm insurance services. The long-term care insurance services data according to several categories were classified and then, we statistically analyzed the socioeconomic burden of long-term insurance. Those cumulative data showed a gradual increase in the recipient number, diversity of geriatric diseases, and socioeconomic burden. We suggested that it is necessary for the government and academic society to continue to cooperate to develop the long-term care insurance systems for elderly.
8.Unenhanced Breast MRI With Diffusion-Weighted Imaging for Breast Cancer Detection: Effects of Training on Performance and Agreement of Subspecialty Radiologists
Yeon Soo KIM ; Su Hyun LEE ; Soo-Yeon KIM ; Eun Sil KIM ; Ah Reum PARK ; Jung Min CHANG ; Vivian Youngjean PARK ; Jung Hyun YOON ; Bong Joo KANG ; Bo La YUN ; Tae Hee KIM ; Eun Sook KO ; A Jung CHU ; Jin You KIM ; Inyoung YOUN ; Eun Young CHAE ; Woo Jung CHOI ; Hee Jeong KIM ; Soo Hee KANG ; Su Min HA ; Woo Kyung MOON
Korean Journal of Radiology 2024;25(1):11-23
Objective:
To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI).
Materials and Methods:
A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm 2 was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive.The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC).
Results:
Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4–79.9), 90.8% (95% CI: 85.6–94.2), and 83.5% (95% CI: 78.6–87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8–97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9–89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1–79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52–0.63) before training and 0.68 (95% CI: 0.62–0.74) after training, with a difference of 0.11 (95% CI: 0.02–0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69–0.74) before training and 0.79 (95% CI: 0.76–0.80) after training (P = 0.002).
Conclusion
Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.
9.Quality Improvement Project to Reduce Admission Hypothermia of Preterm Infants Born at Less than 32 Weeks or 1,500 g
Hanna KIM ; Jieun HWANG ; Chan KIM ; Seung Hyun KIM ; Misun YANG ; So Yoon AHN ; Se In SUNG ; Yun Sil CHANG
Neonatal Medicine 2024;31(2):38-46
Purpose:
Hypothermia upon admission to the neonatal intensive care unit (NICU) contributes significantly to various neonatal complications, particularly in preterm infants. This study aimed to assess the impact of quality improvement (QI) interventions, including using plastic bags and head caps, and adjusting delivery room temperatures, on improving the admission body temperature and reducing hypothermia in infants born at less than 32 weeks or weighing 1,500 g.
Methods:
This study retrospectively analyzed the medical records of infants born at less than 32 weeks or weighing 1,500 g who admitted to the NICU at Samsung Medical Center from January 2022 to February 2024. The QI program that was initiated in April 2023 focused on managing admission temperatures using plastic bags and head caps, and maintaining delivery room temperatures at ≥25 °C. The admission temperature and short-term outcomes pre- and post-QI were compared.
Results:
In a study of 270 patients, implementing QI initiatives significantly raised the admission temperature from 36.2±0.5 to 36.4±0.4 °C (p<0.01), particularly impacting infants weighing ≥1,000 g, in whom mild hypothermia occurrences dropped from 76.3% to 43.9% (p<0.01). This improvement in temperature management significantly decreased both mild and severe hypothermia rates post-QI. Additionally, implementing all three initiatives was more effective than when two or fewer initiatives were implemented.
Conclusion
Simple and cost-effective QI interventions can increase admission temperatures and decrease hypothermia in neonates. Further research is essential to explore the long-term outcomes and develop effective hypothermia management strategies in neonatal care.
10.Clinical Characteristics of Hypospadias and Its Association with Very Low Birth Weight Infants with Small for Gestational Age
Seon Nyo KIM ; Seung Hyun KIM ; Chan KIM ; Hanna KIM ; Jieun HWANG ; Misun YANG ; So Yoon AHN ; Se In SUNG ; Yun Sil CHANG ; Hyeseon KIM
Neonatal Medicine 2024;31(2):17-23
Purpose:
To investigate the risk factors associated with hypospadias in very low birth weight (VLBW) infants (VLBWIs).
Methods:
We retrospectively analyzed 729 infants born at ≥24 weeks of gestational age and weighing <1,500 g from January 2012 to December 2022. We assessed the prevalence of hypospadias by birth weight percentiles and also compared the demographics and placental histopathology of the infants with hypospadias (n=52) and those without hypospadias (n=677).
Results:
Of the 729 patients analysed, hypospadias was recorded in 26 (20.3%), 14 (26.9%), and 12 (2.5%) infants in the <3rd, ≥3rd–<10th, and ≥10th–<90th percentiles, respectively. Of all of the patients with hypospadias, 50% had birth weights <3rd percentile (p<0.001). The hypospadias group demonstrated a longer mean gestational age (30.1 weeks vs. 27.9 weeks, p<0.001), lower incidence of maternal pregnancy-induced hypertension (48.1% vs. 17.3%, p<0.001), lower incidence of premature rupture of membrane (11.5% vs. 27.1%, p=0.013), lower acute chorioamniotic maternal response (9.1% vs. 35.2%, p<0.001), and higher maternal underperfusion (95.5% vs. 71.9%, p<0.001).
Conclusion
The frequency of hypospadias was found to be the highest among VBLWIs <3rd percentile, who were severely small for their gestational age (SGA). Additionally, the incidence increased with a decreasing birth weight. Physical examination is necessary at birth for VLBWIs classified as SGA. Moreover, the data on the incidence of hypospadias among VLBWIs in neonatal intensive care units can assist in tracking counseling from the prenatal to the postnatal period for patients born <3rd percentile.

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