1.Clinical Outcomes of Surgery after Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Ductal Adenocarcinoma
Yoo Na LEE ; Min Kyu SUNG ; Dae Wook HWANG ; Yejong PARK ; Bong Jun KWAK ; Woohyung LEE ; Ki Byung SONG ; Jae Hoon LEE ; Changhoon YOO ; Kyu-Pyo KIM ; Heung-Moon CHANG ; Baek-Yeol RYOO ; Song Cheol KIM
Cancer Research and Treatment 2024;56(4):1240-1251
Purpose:
Clinical outcomes of surgery after neoadjuvant chemotherapy have not been investigated for locally advanced pancreatic cancer (LAPC), despite well-established outcomes in borderline resectable pancreatic cancer (BRPC). This study aimed to investigate the clinical outcomes of patients with LAPC who underwent curative resection following neoadjuvant chemotherapy.
Materials and Methods:
We retrospectively reviewed the records of patients diagnosed with pancreatic adenocarcinoma between January 2017 and December 2020.
Results:
Among 1,358 patients, 260 underwent surgery following neoadjuvant chemotherapy. Among 356 LAPC patients, 98 (27.5%) and 147 (35.1%) of 418 BRPC patients underwent surgery after neoadjuvant chemotherapy. Compared to resectable pancreatic cancer (resectable PC) with upfront surgery, both LAPC and BRPC exhibited higher rates of venous resection (28.6% vs. 49.0% vs. 4.0%), arterial resection (30.6% vs. 6.8% vs. 0.5%) and greater estimated blood loss (260.5 vs. 213.1 vs. 70.4 mL). However, hospital stay, readmission rates, and postoperative pancreatic fistula rates (grade B or C) did not differ significantly between LAPC, BRPC, and resectable PC. Overall and relapse-free survival did not differ significantly between LAPC and BRPC patients. The median overall survival was 37.3 months for LAPC and 37.0 months for BRPC. The median relapse-free survival was 22.7 months for LAPC and 26.0 months for BRPC.
Conclusion
Overall survival time and postoperative complications in LAPC patients who underwent curative resection following neoadjuvant chemotherapy showed similar results to those of BRPC patients. Further research is needed to identify specific sub-populations of LAPC patients who benefit most from conversion surgery and to minimize postoperative complications.
2.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
3.Microbiologic pattern and clinical outcome of non-ICU-acquired pneumonia: Korean HAP registry analysis
Jin Ho JANG ; Hye Ju YEO ; Taehwa KIM ; Woo Hyun CHO ; Kyung Hoon MIN ; Sang-Bum HONG ; Ae-Rin BAEK ; Hyun-Kyung LEE ; Changhwan KIM ; Youjin CHANG ; Hye Kyeong PARK ; Jee Youn OH ; Heung Bum LEE ; Soohyun BAE ; Jae Young MOON ; Kwang Ha YOO ; Hyun-Il GIL ; Kyeongman JEON ;
The Korean Journal of Internal Medicine 2023;38(3):450-450
4.Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX
So Heun LEE ; Dae Wook HWANG ; Changhoon YOO ; Kyu-pyo KIM ; Sora KANG ; Jae Ho JEONG ; Dongwook OH ; Tae Jun SONG ; Sang Soo LEE ; Do Hyun PARK ; Dong Wan SEO ; Jin-hong PARK ; Ki Byung SONG ; Jae Hoon LEE ; Woohyung LEE ; Yejong PARK ; Bong Jun KWAK ; Heung-Moon CHANG ; Baek-Yeol RYOO ; Song Cheol KIM
Cancer Research and Treatment 2023;55(3):956-968
Purpose:
The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population.
Materials and Methods:
This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status.
Results:
Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]).
Conclusion
Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.
5.Novel Genome-Wide Interactions Mediated via BOLL and EDNRA Polymorphisms in Intracranial Aneurysm
Eun Pyo HONG ; Dong Hyuk YOUN ; Bong Jun KIM ; Jae Jun LEE ; Sehyeon NAM ; Hyojong YOO ; Heung Cheol KIM ; Jong Kook RHIM ; Jeong Jin PARK ; Jin Pyeong JEON
Journal of Korean Neurosurgical Society 2023;66(4):409-417
Objective:
: The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort.
Methods:
: Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors.
Results:
: Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene.
Conclusion
: BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.
6.Empiric Anti-Pseudomonal β-Lactam Monotherapy Versus Fluoroquinolone Combination Therapy in Patients With Hospital-Acquired Pneumonia: A Multicenter Cohort Study With Propensity Score Matching
Moon Seong BAEK ; Ae-Rin BAEK ; Sang-Bum HONG ; Soohyun BAE ; Hye Kyeong PARK ; Changhwan KIM ; Hyun-Kyung LEE ; Woo Hyun CHO ; Jin Hyoung KIM ; Youjin CHANG ; Heung Bum LEE ; Hyun-Il GIL ; Beomsu SHIN ; Kwang Ha YOO ; Jae Young MOON ; Jee Youn OH ; Kyung Hoon MIN ; Kyeongman JEON ;
Journal of Korean Medical Science 2023;38(41):e353-
Background:
There is insufficient data on the benefits of empiric antibiotic combinations for hospital-acquired pneumonia (HAP). We aimed to investigate whether empiric antipseudomonal combination therapy with fluoroquinolones decreases mortality in patients with HAP.
Methods:
This multicenter, retrospective cohort study included adult patients admitted to 16 tertiary and general hospitals in Korea between January 1 and December 31, 2019.Patients with risk factors for combination therapy were divided into anti-pseudomonal non-carbapenem β-lactam monotherapy and fluoroquinolone combination therapy groups.Primary outcome was 30-day mortality. Propensity score matching (PSM) was used to reduce selection bias.
Results:
In total, 631 patients with HAP were enrolled. Monotherapy was prescribed in 54.7% (n = 345) of the patients, and combination therapy was prescribed in 45.3% (n = 286).There was no significant difference in 30-day mortality between the two groups (16.8% vs.18.2%, P = 0.729) or even after the PSM (17.5% vs. 18.2%, P = 0.913). After the PSM, adjusted hazard ratio for 30-day mortality from the combination therapy was 1.646 (95% confidence interval, 0.782–3.461; P = 0.189) in the Cox proportional hazards model. Moreover, there was no significant difference in the appropriateness of initial empiric antibiotics between the two groups (55.0% vs. 56.8%, P = 0.898). The proportion of multidrug-resistant (MDR) pathogens was high in both groups.
Conclusion
Empiric anti-pseudomonal fluoroquinolone combination therapy showed no survival benefit compared to β-lactam monotherapy in patients with HAP. Caution is needed regarding the routine combination of fluoroquinolones in the empiric treatment of HAP patients with a high risk of MDR.
7.Microbiologic pattern and clinical outcome of non-ICU-acquired pneumonia: Korean HAP registry analysis
Jin Ho JANG ; Hye Ju YEO ; Taehwa KIM ; Woo Hyun CHO ; Kyung Hoon MIN ; Sang-Bum HONG ; Ae-Rin BAEK ; Hyun-Kyung LEE ; Changhwan KIM ; Youjin CHANG ; Hye Kyeong PARK ; Jee Youn OH ; Heung Bum LEE ; Soohyun BAE ; Jae Young MOON ; Kwang Ha YOO ; Hyun-Il GIL ; Kyeongman JEON ;
The Korean Journal of Internal Medicine 2022;37(4):800-810
Background/Aims:
Most studies on hospital-acquired pneumonia (HAP) have been conducted in intensive care unit (ICU) settings. This study aimed to investigate the microbiological and clinical characteristics of non-ICU-acquired pneumonia (NIAP) and to identify the factors affecting clinical outcomes in Korea.
Methods:
This multicenter retrospective cohort study was conducted in patients admitted to 13 tertiary hospitals between July 1, 2019 and December 31, 2019. Patients diagnosed with NIAP were included in this study. To assess the prognostic factors of NIAP, the study population was classified into treatment success and failure groups.
Results:
Of 526 patients with HAP, 379 were diagnosed with NIAP. Overall, the identified causative pathogen rate was 34.6% in the study population. Among the isolated organisms (n = 113), gram-negative bacilli were common pathogens (n = 91), such as Pseudomonas aeruginosa (n = 25), Acinetobacter baumannii (n = 23), and Klebsiella pneumoniae (n = 21). The multidrug resistance rates of A. baumannii, P. aeruginosa, and K. pneumoniae were 91.3%, 76.0%, and 57.1%, respectively. Treatment failure was significantly associated with K. pneumoniae (odds ratio [OR], 3.50; 95% confidence interval [CI], 1.35 to 9.05; p = 0.010), respiratory viruses (OR, 3.81; 95% CI, 1.34 to 10.82; p = 0.012), hematological malignancies (OR, 3.54; 95% CI, 1.57 to 8.00; p = 0.002), and adjunctive corticosteroid treatment (OR, 2.40; 95% CI, 1.27 to 4.52; p = 0.007).
Conclusions
The causative pathogens of NIAP in Korea are predominantly gram-negative bacilli with a high rate of multidrug resistance. These were not different from the common pathogens of ICU-acquired pneumonia.
8.Characteristics, Management, and Clinical Outcomes of Patients with Hospital-Acquired and Ventilator-Associated Pneumonia: A Multicenter Cohort Study in Korea
Ryoung-Eun KO ; Kyung Hoon MIN ; Sang-Bum HONG ; Ae-Rin BAEK ; Hyun-Kyung LEE ; Woo Hyun CHO ; Changhwan KIM ; Youjin CHANG ; Sung-Soon LEE ; Jee Youn OH ; Heung Bum LEE ; Soohyun BAE ; Jae Young MOON ; Kwang Ha YOO ; Kyeongman JEON ;
Tuberculosis and Respiratory Diseases 2021;84(4):317-325
Background:
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are significant public health issues in the world, but the epidemiological data pertaining to HAP/VAP is limited in Korea. The objective of this study was to investigate the characteristics, management, and clinical outcomes of HAP/VAP in Korea.
Methods:
This study is a multicenter retrospective cohort study. In total, 206,372 adult patients, who were hospitalized at one of the 13 participating tertiary hospitals in Korea, were screened for eligibility during the six-month study period. Among them, we included patients who were diagnosed with HAP/VAP based on the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) definition for HAP/VAP.
Results:
Using the IDSA/ATS diagnostic criteria, 526 patients were identified as HAP/VAP patients. Among them, 27.9% were diagnosed at the intensive care unit (ICU). The cohort of patients had a median age of 71.0 (range from 62.0 to 79.0) years. Most of the patients had a high risk of aspiration (63.3%). The pathogen involved was identified in 211 patients (40.1%). Furthermore, multidrug resistant (MDR) pathogens were isolated in 138 patients; the most common MDR pathogen was Acinetobacter baumannii. During hospitalization, 107 patients with HAP (28.2%) had to be admitted to the ICU for additional care. The hospital mortality rate was 28.1% in the cohort of this study. Among the 378 patients who survived, 54.2% were discharged and sent back home, while 45.8% were transferred to other hospitals or facilities.
Conclusion
This study found that the prevalence of HAP/VAP in adult hospitalized patients in Korea was 2.54/1,000 patients. In tertiary hospitals in Korea, patients with HAP/VAP were elderly and had a risk of aspiration, so they were often referred to step-down centers.
9.Characteristics, Management, and Clinical Outcomes of Patients with Hospital-Acquired and Ventilator-Associated Pneumonia: A Multicenter Cohort Study in Korea
Ryoung-Eun KO ; Kyung Hoon MIN ; Sang-Bum HONG ; Ae-Rin BAEK ; Hyun-Kyung LEE ; Woo Hyun CHO ; Changhwan KIM ; Youjin CHANG ; Sung-Soon LEE ; Jee Youn OH ; Heung Bum LEE ; Soohyun BAE ; Jae Young MOON ; Kwang Ha YOO ; Kyeongman JEON ;
Tuberculosis and Respiratory Diseases 2021;84(4):317-325
Background:
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are significant public health issues in the world, but the epidemiological data pertaining to HAP/VAP is limited in Korea. The objective of this study was to investigate the characteristics, management, and clinical outcomes of HAP/VAP in Korea.
Methods:
This study is a multicenter retrospective cohort study. In total, 206,372 adult patients, who were hospitalized at one of the 13 participating tertiary hospitals in Korea, were screened for eligibility during the six-month study period. Among them, we included patients who were diagnosed with HAP/VAP based on the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) definition for HAP/VAP.
Results:
Using the IDSA/ATS diagnostic criteria, 526 patients were identified as HAP/VAP patients. Among them, 27.9% were diagnosed at the intensive care unit (ICU). The cohort of patients had a median age of 71.0 (range from 62.0 to 79.0) years. Most of the patients had a high risk of aspiration (63.3%). The pathogen involved was identified in 211 patients (40.1%). Furthermore, multidrug resistant (MDR) pathogens were isolated in 138 patients; the most common MDR pathogen was Acinetobacter baumannii. During hospitalization, 107 patients with HAP (28.2%) had to be admitted to the ICU for additional care. The hospital mortality rate was 28.1% in the cohort of this study. Among the 378 patients who survived, 54.2% were discharged and sent back home, while 45.8% were transferred to other hospitals or facilities.
Conclusion
This study found that the prevalence of HAP/VAP in adult hospitalized patients in Korea was 2.54/1,000 patients. In tertiary hospitals in Korea, patients with HAP/VAP were elderly and had a risk of aspiration, so they were often referred to step-down centers.
10.Adjuvant Chemotherapy for Resected Ampulla of Vater Carcinoma: Retrospective Analysis of 646 Patients
Jwa Hoon KIM ; Jae Ho JEONG ; Baek-Yeol RYOO ; Kyu-pyo KIM ; Heung-Moon CHANG ; Dongwook OH ; Tae Jun SONG ; Sang Soo LEE ; Dong Wan SEO ; Sung Koo LEE ; Myung-Hwan KIM ; Yejong PARK ; Jae Woo KWON ; Dae Wook HWANG ; Jae Hoon LEE ; Woohyung LEE ; Song Cheol KIM ; Changhoon YOO ; Ki Byung SONG
Cancer Research and Treatment 2021;53(2):424-435
Purpose:
This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma.
Materials and Methods:
Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed.
Results:
The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111).
Conclusion
AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.

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