1.Analysis of Clinical Characteristics and Post-Treatment Prognosis of Eosinophilic and Neutrophilic Chronic Rhinosinusitis With Nasal Polyps in Korean Patients
Chae-Young KIM ; Kwang-Hyun BYUN ; Jun-Sang BAE ; Eun-Hee KIM ; Shin-Hyuk YOO ; Ji-Hun MO
Korean Journal of Otolaryngology - Head and Neck Surgery 2024;67(6):328-335
Background and Objectives:
The aim of this study was to examine the clinical characteristics and prognosis of chronic rhinosinusitis with nasal polyps (CRSwNP) following endoscopic sinus surgery (ESS), focusing on distinct histological endotypes characterized by eosinophil and neutrophil infiltration.Subjects and Method A total of 207 patients diagnosed with CRSwNP who underwent ESS between August 2014 and September 2018 were included in the study. Patients were categorized into different groups based on eosinophil and neutrophil counts in the tissues. The demographic data, Lund-Mackay score, Lund-Kennedy (L-K) endoscopic score, Sino-Nasal Outcome Test-22 and Kaplan-Meier estimation were analyzed according to different histologic endotypes.
Results:
The histologic types were divided into four groups: the eosinophilic polyp (EP)+ neutrophlic polyp (NP) group, the EP group, the NP group, and the nonEP+nonNP group. Among the groups, the highest level of inflammation (L-K score, p<0.05) was observed in the EP+NP group, and the worst prognosis was observed in the EP+NP group according to the results of the Kaplan-Meier analysis (p<0.001).
Conclusion
Compared to non-neutrophil-infiltration polyps, neutrophil infiltration was associated with worse outcome when it was accompanied with eosinophilic infiltration. This discovery underlines how crucial it is to take neutrophils in nasal polyps into account in order to better understand their clinical behavior and maybe design customized treatments for better patient outcomes.
2.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.
3.Characteristics of Hyaluronic Acid and Its Use in Ocular Surface Diseases Including Dry Eye
Jinu KIM ; Jae Woong KOH ; Hyuk Jin CHOI ; Yong-Soo BYUN ; Ji Won JUNG ; Sang-Mok LEE
Journal of the Korean Ophthalmological Society 2023;64(2):170-183
Hyaluronic acid (HA) is a polysaccharide found in the extracellular matrix of the epithelial, nervous, and connective tissues of vertebrates. It is widely used in the treatment of ocular surface diseases (OSDs), including dry eye, due to its high water-retaining capacity, viscoelasticity, and role as a signaling molecule in inflammation and wound healing. This paper reviews the physicochemical and biological properties of HA related to the treatment of OSDs and the results of published preclinical studies, clinical trials, and meta-analyses on the effects of HA eye drops on the tear film, the mechanism of action of HA eye drops, and its clinical effects and adverse events in OSDs, such as corneal/conjunctival epithelial defects, dry eye, and postoperative dry eye. This review should help inform clinical judgments by providing clinical evidence and precautions on the use of HA eye drops in OSDs, including dry eye.
4.Nuclear Factor Erythroid 2-Related Factor 2/Kelch-Like ECH-Associated Protein 1 as a Predictor of Prognosis and Radiotherapy Resistance in Patients With Locally Advanced Rectal Cancer: A Prospective Analysis
Ji Min PARK ; Shin KIM ; Sung Uk BAE ; Sang Jun BYUN ; Incheol SEO ; Hye Won LEE
Journal of Korean Medical Science 2023;38(26):e200-
Background:
The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/ Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC).
Methods:
In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed.
Results:
The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity.
Conclusion
CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance.The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.
5.Comparison of the Optimized Intraocular Lens Constants Calculated by Automated and Manifest Refraction for Korean
Youngsub EOM ; Dong Hui LIM ; Dong Hyun KIM ; Yong-Soo BYUN ; Kyung Sun NA ; Seong-Jae KIM ; Chang Rae RHO ; So-Hyang CHUNG ; Ji Eun LEE ; Kyong Jin CHO ; Tae-Young CHUNG ; Eun Chul KIM ; Young Joo SHIN ; Sang-Mok LEE ; Yang Kyung CHO ; Kyung Chul YOON ; In-Cheon YOU ; Byung Yi KO ; Hong Kyun KIM ; Jong Suk SONG ; Do Hyung LEE
Journal of the Korean Ophthalmological Society 2022;63(9):747-753
Purpose:
To derive the optimized intraocular lens (IOL) constants from automated and manifest refraction after cataract surgery in Korean patients, and to evaluate whether there is a difference in optimized IOL constants according to the refraction method.
Methods:
This retrospective multicenter cohort study enrolled 4,103 eyes of 4,103 patients who underwent phacoemulsification and in-the-bag IOL implantation at 18 institutes. Optimized IOL constants for the SRK/T, Holladay, Hoffer Q, and Haigis formulas were calculated via autorefraction or manifest refraction of samples using the same biometry and IOL. The IOL constants derived from autorefraction and manifest refraction were compared.
Results:
Of the 4,103 eyes, the majority (62.9%) were measured with an IOLMaster 500 followed by an IOLMaster 700 (15.2%). A total of 33 types of IOLs were used, and the Tecnis ZCB00 was the most frequently used (53.0%). There was no statistically significant difference in IOL constants derived from autorefraction and manifest refraction when IOL constants were optimized with a large number of study subjects. On the other hand, optimized IOL constants derived from autorefraction were significantly smaller than those from manifest refraction when the number of subjects was small.
Conclusions
It became possible to use the IOL constants optimized from Koreans to calculate the IOL power. However, if the IOL constant is optimized using autorefraction in a small sample group, the IOL constant tends to be small, which may lead to refractive error after surgery.
6.Real-World Clinical Data of Palbociclib in Asian Metastatic Breast Cancer Patients: Experiences from Eight Institutions
Jieun LEE ; Hyung Soon PARK ; Hye Sung WON ; Ji Hyun YANG ; Hee Yeon LEE ; In Sook WOO ; Kabsoo SHIN ; Ji Hyung HONG ; Young Joon YANG ; Sang Hoon CHUN ; Jae Ho BYUN
Cancer Research and Treatment 2021;53(2):409-423
Purpose:
Use of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib.
Materials and Methods:
Between April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2–negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed.
Results:
Median age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0-1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%).
Conclusion
To our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.
7.Comparison of Clinical Outcomes of Borderline Resectable Pancreatic Cancer According to the Neoadjuvant Chemo-Regimens: Gemcitabine versus FOLFIRINOX
Yoo Jin CHOI ; Yoonhyeong BYUN ; Jae Seung KANG ; Hyeong Seok KIM ; Youngmin HAN ; Hongbeom KIM ; Wooil KWON ; Do-Youn OH ; Woo Hyun PAIK ; Sang Hyub LEE ; Ji Kon RYU ; Yong-Tae KIM ; Kyungbun LEE ; Haeryoung KIM ; Eui Kyu CHIE ; Jin-Young JANG
Gut and Liver 2021;15(3):466-475
Background/Aims:
Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC.
Methods:
In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment.
Results:
For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p<0.001). The 2- and 5-year survival rates (YSRs) were significantly higher after FOLFIRINOX (2YSR, 72.2%; 5YSR, 46.0%) than after gemcitabine (2YSR, 58.4%; 5YSR, 19.1%; p=0.041). The margin negative rate was comparable (gemcitabine, 94.1%; FOLFIRINOX, 92.4%; p=0.753), and the tumor size change in percentage showed only a marginal difference (gemcitabine, 20.5%; FOLFIRINOX, 29.0%; p=0.069). Notably, the metastatic recurrence rate was significantly lower in the FOLFIRINOX group (n=20, 52.6%) than in the gemcitabine group (n=22, 78.6%; p=0.001). The rate of adverse events after chemotherapy was significantly higher with FOLFIRINOX than with gemcitabine (43.9%, 20.6%, respectively; p=0.037).
Conclusions
FOLFIRINOX provided more clinical and oncological benefit than gemcitabine, with significantly higher overall survival and lower cumulative recurrence rates in BRPC. However, since FOLFIRINOX causes more adverse effects, the regimen should be individualized based on patient’s general condition and clinical status.
8.Change in the Recurrence Pattern and Predictors over Time after Complete Cure of Hepatocellular Carcinoma
Han Ah LEE ; Young-Sun LEE ; Beom Kyung KIM ; Young Kul JUNG ; Seung Up KIM ; Jun Yong PARK ; Ji Hoon KIM ; Hyunggin AN ; Do Young KIM ; Hyung Joon YIM ; Sang Hoon AHN ; Jong Eun YEON ; Kwan Soo BYUN ; Kwang-Hyub HAN ; Soon Ho UM ; Yeon Seok SEO
Gut and Liver 2021;15(3):420-429
Background/Aims:
We investigated changes in recurrence rates and significant recurrence predictors over time after complete cure of hepatocellular carcinoma (HCC).
Methods:
A total of 1,491 patients with first-time diagnosis of Barcelona Clinic Liver Cancer stage A HCC, completely cured by treatment between 2007 and 2016, were recruited from two Korean tertiary institutes.
Results:
The mean age of the population (1,144 men and 347 women) was 58.6 years. Of the total population, 914 patients (61.3%) had liver cirrhosis. Nine-hundred and forty-one (63.1%) and 550 (36.9%) patients were treated with surgical resection and radiofrequency ablation (RFA), respectively. One-year cumulative incidences of HCC recurrence were 14.3%, 9.9%, and 5.1% from the time of treatment, 3 years after treatment, and 5 years after treatment, respectively. Upon multivariate analysis, multiple tumors, maximal tumor size ≥3 cm, and high Model for End-Stage Liver Disease scores were independently associated with increased HCC recurrence risk from the time of treatment and 1 and 2 years after curative treatment (all p<0.05, except for maxi-mal tumor size ≥3 cm for recurrence 2 years after treatment). Meanwhile, liver cirrhosis and RFA were independently associated with the increased HCC recurrence risk for almost all time points (liver cirrhosis: all p<0.05; RFA: all p<0.005 except for recurrence from 5 years after treatment).
Conclusions
The recurrence rate of HCC after curative treatment gradually decreased over time. Two years after treatment, when tumor-related factors lose their prognostic implications, may be used as a cutoff to define the boundary between early and late recurrence of HCC.
9.Real-World Clinical Data of Palbociclib in Asian Metastatic Breast Cancer Patients: Experiences from Eight Institutions
Jieun LEE ; Hyung Soon PARK ; Hye Sung WON ; Ji Hyun YANG ; Hee Yeon LEE ; In Sook WOO ; Kabsoo SHIN ; Ji Hyung HONG ; Young Joon YANG ; Sang Hoon CHUN ; Jae Ho BYUN
Cancer Research and Treatment 2021;53(2):409-423
Purpose:
Use of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib.
Materials and Methods:
Between April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2–negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed.
Results:
Median age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0-1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%).
Conclusion
To our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.
10.Comparison of Clinical Outcomes of Borderline Resectable Pancreatic Cancer According to the Neoadjuvant Chemo-Regimens: Gemcitabine versus FOLFIRINOX
Yoo Jin CHOI ; Yoonhyeong BYUN ; Jae Seung KANG ; Hyeong Seok KIM ; Youngmin HAN ; Hongbeom KIM ; Wooil KWON ; Do-Youn OH ; Woo Hyun PAIK ; Sang Hyub LEE ; Ji Kon RYU ; Yong-Tae KIM ; Kyungbun LEE ; Haeryoung KIM ; Eui Kyu CHIE ; Jin-Young JANG
Gut and Liver 2021;15(3):466-475
Background/Aims:
Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC.
Methods:
In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment.
Results:
For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p<0.001). The 2- and 5-year survival rates (YSRs) were significantly higher after FOLFIRINOX (2YSR, 72.2%; 5YSR, 46.0%) than after gemcitabine (2YSR, 58.4%; 5YSR, 19.1%; p=0.041). The margin negative rate was comparable (gemcitabine, 94.1%; FOLFIRINOX, 92.4%; p=0.753), and the tumor size change in percentage showed only a marginal difference (gemcitabine, 20.5%; FOLFIRINOX, 29.0%; p=0.069). Notably, the metastatic recurrence rate was significantly lower in the FOLFIRINOX group (n=20, 52.6%) than in the gemcitabine group (n=22, 78.6%; p=0.001). The rate of adverse events after chemotherapy was significantly higher with FOLFIRINOX than with gemcitabine (43.9%, 20.6%, respectively; p=0.037).
Conclusions
FOLFIRINOX provided more clinical and oncological benefit than gemcitabine, with significantly higher overall survival and lower cumulative recurrence rates in BRPC. However, since FOLFIRINOX causes more adverse effects, the regimen should be individualized based on patient’s general condition and clinical status.

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