Medical Centers In Korea Research Articles

Contralateral Low-to-Intermediate Suspicion Nodule Is Not a Contraindication for Lobectomy in Patients with Papillary Thyroid Carcinoma.

Background: The optimal extent of surgery for unilateral papillary thyroid carcinoma (PTC) with contralateral nodules remains unclear. This study evaluated the long-term outcomes in a large cohort of patients with unilateral PTC and contralateral low-to-intermediate suspicious nodules who underwent lobectomy. Methods: This retrospective cohort study included patients with unilateral PTC who underwent lobectomy between January 2016 and December 2017 at Asan Medical Center in Korea. Patients were divided into two groups, those with and without contralateral nodules at the time of lobectomy: the Present group and the Absent group. All contralateral nodules observed at the time of surgery and during follow-up were evaluated. Results: The study cohort consisted of 1761 patients (1879 nodules), including 700 (39.8%) with and 1061 (60.2%) without contralateral nodules. The median size of the contralateral nodules was 0.5 cm. After a median follow-up of 59 months, the median growth of the contralateral nodules in the Present group was 0.1 cm (range, -3.4 to 4.7 cm). Of the contralateral nodules present at the time of lobectomy, 54.7% remained unchanged, decreased in size, or disappeared; whereas 14.8% increased ≥0.3 cm. Of the 700 patients with contralateral nodules, 20 (2.9%) were diagnosed with contralateral PTC. The 5-year contralateral PTC disease-free survival rates in patients with and without contralateral nodules were 98.2% and 99.3% (p = 0.003), respectively, whereas the 5-year recurrence-free survival rates did not differ significantly in these two groups. Of the 39 patients who underwent completion thyroidectomy, 2 (5.1%) experienced permanent hypocalcemia. Conclusions: Lobectomy may be a safe and feasible initial treatment option for patients with unilateral low-risk PTC and contralateral low-to-intermediate suspicious nodules.

Low Muscle and High Fat Percentages Are Associated with Low Natural Killer Cell Activity: A Cross-Sectional Study.

This study aimed to investigate whether body fat and muscle percentages are associated with natural killer cell activity (NKA). This was a cross-sectional study, conducted on 8058 subjects in a medical center in Korea. The association between the muscle and fat percentage tertiles and a low NKA, defined as an interferon-gamma level lower than 500 pg/mL, was assessed. In both men and women, the muscle mass and muscle percentage were significantly low in participants with a low NKA, whereas the fat percentage, white blood cell count, and C-reactive protein (CRP) level were significantly high in those with a low NKA. Compared with the lowest muscle percentage tertile as a reference, the fully adjusted odd ratios (ORs) (95% confidence intervals (CIs)) for a low NKA were significantly lower in T2 (OR: 0.69; 95% CI: 0.55-0.86) and T3 (OR: 0.74; 95% CI: 0.57-0.95) of men, and T3 (OR: 0.76; 95% CI: 0.59-0.99) of women. Compared with the lowest fat percentage tertile as a reference, the fully adjusted OR was significantly higher in T3 of men (OR: 1.31; 95% CI: 1.01-1.69). A high muscle percentage was significantly inversely associated with a low NKA in men and women, whereas a high fat percentage was significantly associated with a low NKA in men.

Association between the triglyceride to high-density lipoprotein cholesterol ratio and the risk of gestational diabetes mellitus: a second analysis based on data from a prospective cohort study.

Although there is strong evidence linking triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to insulin resistance and diabetes mellitus, its clinical importance in pregnant women has not been well determined. This study sought to determine the connection between the TG/HDL-C ratio in the first trimester and the eventual onset of gestational diabetes mellitus (GDM). We performed a secondary analysis of open-access data from a prospective cohort study. This present study included 590 singleton pregnant women at 10-14 weeks who visited the outpatient clinics for prenatal checks and were recorded at Incheon Seoul Women's Hospital and Seoul Metropolitan Government Seoul National University Boramae Medical Center in Korea. A binary logistic regression model, a series of sensitivity analyses, and subgroup analysis were used to examine the relationship between TG/HDL-C ratio and incident GDM. A receiver operating characteristic (ROC) analysis was also conducted to assess the ability of the TG/HDL-C ratio to predict GDM. The mean age of the included individuals was 32.06 ± 3.80 years old. The mean TG/HDL-C ratio was 1.96 ± 1.09. The incidence rate of GDM was 6.27%. After adjustment for potentially confounding variables, TG/HDL-C ratio was positively associated with incident GDM (OR=1.77, 95%CI: 1.32-2.38, P=0.0001). Sensitivity analyses and subgroup analysis demonstrated the validity of the relationship between the TG/HDL-C ratio and GDM. The TG/HDL-C ratio was a good predictor of GDM, with an area under the ROC curve of 0.7863 (95% CI: 0.7090-0.8637). The optimal TG/HDL-C ratio cut-off value for detecting GDM was 2.2684, with a sensitivity of 72.97% and specificity of 75.05%. Our results demonstrate that the elevated TG/HDL-C ratio is related to incident GDM. The TG/HDL-C ratio at 10-14 weeks could help identify pregnant women at risk for GDM and may make it possible for them to receive early and effective treatment to improve their prognosis.

Lateral neck dissection for the treatment of synchronous and metachronous lateral neck metastasis of N1b papillary thyroid cancer.

Metachronous lateral neck recurrence after thyroidectomy for N1b papillary thyroid cancer is accompanied by high morbidity and increased difficulty of reoperation. From the perspective of recurrence, the objective of this study was to compare patients who underwent metachronous lateral neck dissection (mLND) despite initial thyroidectomy and patients who underwent synchronous lateral neck dissection (sLND) for papillary thyroid cancer and analyze the risk factors for recurrence after mLND. This retrospective study involved 1,760 patients who underwent lateral neck dissection for papillary thyroid cancer at the Gangnam Severance Hospital, a tertiary medical center in Korea, from June 2005 to December 2016. The primary outcome was structural recurrence, and secondary outcome measures were risk factors of recurrence in the mLND group. A total of 1,613 patients underwent thyroidectomy and sLND at diagnosis. In 147 patients, thyroidectomy alone was performed at the time of diagnosis, and mLND was performed when recurrence to the lateral neck lymph node was confirmed. During a median follow-up of 102.1 months, 110 (6.3%) patients experienced a recurrence. There was no significant difference in the recurrence between the sLND and mLND groups (6.1% vs 8.2%, P=.32). The period from lateral neck dissection to recurrence was longer in the mLND group than in the sLND group (113.6 ± 39.4 months vs 87.0 ± 33.8 months, respectively, P<.001). Age ≥50 years (adjusted HR=5.209, 95% CI=1.359-19.964; P=.02), tumor size >1.45cm (adjusted HR=4.022, 95% CI=1.036-15.611; P=.04), and lymph node ratio in the lateral compartment (adjusted HR=4.043, 95% CI=1.079-15.148; P=.04) were independent variables predictive of recurrence after mLND. mLND is suitable for treating lateral neck recurrence in patients with N1b papillary thyroid cancer who previously underwent thyroidectomy. Lateral neck recurrence after treatment in patients who underwent mLND was predicted by age, tumor size, and lymph node ratio in the lateral compartment.

Laparoscopic pancreaticoduodenectomy and laparoscopic pancreaticoduodenectomy with robotic reconstruction: single-surgeon experience and technical notes

Despite the increasing number of robotic pancreaticoduodenectomies, laparoscopic pancreaticoduodenectomy (LPD) and LPD with robotic reconstruction (LPD-RR) are still valuable surgical options for minimally invasive pancreaticoduodenectomy (MIPD). This study introduces the surgical techniques, tips, and outcomes of our experience with LPD and LPD-RR.Between March 2014 and July 2021, 122 and 48 patients underwent LPD and LPD-RR respectively, at CHA Bundang Medical Center in Korea. The operative settings, procedures, and trocar placements were identical in both approaches; however, different trocars were used. We introduced our techniques of retraction methods for Kocherization and uncinate process dissection, pancreatic reconstruction, pancreatic division, and protection using the round ligament. The perioperative surgical outcomes of LPD and LPD-RR were compared.Baseline demographics of patients in the LPD and LPD-RR groups were comparable, but the LPD group had older age (65.5 ± 11.6 years vs. 60.0 ± 14.1 years, p = 0.009) and lesser preoperative chemotherapy (15.6% vs. 35.4%, p = 0.008). The proportion of malignant disease was similar (LPD group, 86.1% vs. LPD-RR group, 83.3%; p = 0.759). Perioperative outcomes were also comparable, including operative time, estimated blood loss, clinically relevant postoperative pancreatic fistula (LPD group, 9.0% vs. LPD-RR group, 10.4%; p = 0.684), and major postoperative complication rates (LPD group, 14.8% vs. LPD-RR group, 6.2%; p = 0.082).Both LPD and LPR-RR can be safely performed by experienced surgeons with acceptable surgical outcomes. Further investigations are required to evaluate the objective benefits of robotic surgical systems in MIPD and establish widely acceptable standardized MIPD techniques.

#3619 CKD EPI 2021 EQUATION FOR EGFR HAS GOOD EFFICACY TO PREDICT CLINICAL OUTCOMES IN A LARGE PROSPECTIVE COHORT OF ADULT KOREANS

Abstract Background and Aims A new eGFR equation using serum creatinine (CKD-EPI 2021) without race were developed by Chronic Kidney Disease Epidemiology Collaboration in 2021. We projected the changes of eGFR, CKD prevalence, and incidence of end stage renal disease (ESRD) and mortality in a large prospective cohort of adult Koreans who had voluntary health check-ups, using current (CKD-EPI 2009) and new equation (CKD-EPI 2021). Method We included 112,772 adult participants, aged 18 years or older, who had voluntary routine health check-ups including serum creatinine at three medical centers in Korea from 2003 to 2009. We compared the difference of eGFR and predictability of mortality and ESRD between eGFR values calculated by CKD-EPI 2009 and CKD-EPI 2021. Serum creatinine was expressed as the IDMS-traceable creatinine according to the manufacturer's conversion formula from the original value measured by the alkaline picrate Jaffe kinetic method. The incidence of mortality data was extracted from Statistics Korea and the ESRD data from the ESRD registry of the Korean Society of Nephrology. Results At baseline study, there were 60,723 males (53.8%). Age was 48.9 ± 12.0 years. The value of IDMS-traceable serum creatinine was 0.86 ± 0.21 mg/dl. Levels of eGFR at baseline study were 93.5 ± 15.6 ml/min/1.73 m2 by CKD-EPI2009, and 97.1 ± 15.0 ml/min/1.73 m2 by CKD-EPI2021. Values subtracted eGFRs by CKD-EPI2009 from eGFR by CKD-EPEI2021 were 3.6 ± 1.2 (range: -32.9∼6.1) ml/min/1.73 m2. The difference of eGFR was higher in males compared to females (p&amp;lt;0.001), was the highest in the oldest group among patients aged 18–44 years, 45–64 years, and 65 years or more (p&amp;lt;0.001). Patients with diabetes mellitus (DM) or hypertension showed higher difference of eGFR compared patients without DM or hypertension, respectively (each p&amp;lt;0.001). Patients with eGFR ≥120.0 ml/min/1.73 m2 by CKD-EPI 2009 showed the highest difference between two eGFRs compared to patients with the other values. CKD stage was improved in 11,828 (10.5%) participants using eGFR calculated by CKD-EPI 2021 instead of CKD-EPI 2009, however, only 0.63% of participants with eGFR &amp;lt;60 ml/min/1.73 m2 by CKD-EPI equation was reclassified into eGFR ≥60 ml/min/1.73 m2 by CKD-EPI 2021.During 11.6 ± 2.0 years, 3354 (3.00%) subjects were dead and 151 (0.13%) subjects had end stage renal disease (ESRD) before death. Any eGFR or stage of eGFR was an independent risk factors to ESRD or mortality estimated by Cox's hazard proportional model adjusted by related factors. AUC to estimate renal survival by eGFRs was not different between eGFRs by CKD-EPI2021 and CKD-EPI2009 [0.739 (0.687-0.790) vs 0.740(0.688-0.792), p = 0.170]. p&amp;lt;0.001]. AUC to estimate survival by eGFRs calculated through CKD-EPI equation was slightly higher than that by CKD-EPI2021 equation [0.673(0.664-0.682) vs 0.667(0.658-0.676), p&amp;lt;0.001], however, the difference of AUC was negligible [standard error of AUC difference by two eGFRs; 0.96 (95% CI; 0.006-0.007)]. Conclusion The eGFR calculated by CKD-EPI2021 was higher compared to eGFR calculated by CKD-EPI2009. The power to estimate renal survival was not different between eGFRs by CKD-EPI2021 and CKD-EPI2009.

Effectiveness of Initial Troponin I and Brain Natriuretic Peptide Levels as Biomarkers for Predicting Delayed Neuropsychiatric Sequelae in Patients with CO Poisoning: A Retrospective Multicenter Observational Study.

Delayed neuropsychiatric sequelae (DNS) are a severe complication of carbon monoxide (CO) poisoning, and predicting DNS is difficult. This study aimed to investigate whether cardiac markers can be used as biomarkers to predict DNS occurrence following acute CO poisoning. This was a retrospective observational study that included patients with acute CO poisoning who visited two emergency medical centers in Korea from January 2008 to December 2020. The primary outcome was whether the occurrence of DNS was associated with laboratory results. Of the 1327 patients with CO poisoning, 967 patients were included. Troponin I and BNP were significantly higher in the DNS group. As a result of multivariate logistic regression analysis, it was found that troponin I, mentality, creatine kinase, brain natriuretic peptide, and lactate levels independently influenced DNS occurrence in CO poisoning patients. The adjusted odds ratios for DNS occurrence were 2.12 (95% CI 1.31-3.47, p = 0.002) for troponin I and 2.80 (95% CI 1.81-3.47, p < 0.001) for BNP. Troponin I and BNP might be useful biomarkers for predicting the occurrence of DNS in patients with acute CO poisoning. This finding can help to identify high-risk patients who require close monitoring and early intervention to prevent DNS.

The Risk of Heart Failure Progression in Patients With Patent Foramen Ovale: Differential Risk Associated With Device Closure

A patent foramen ovale (PFO) can unload left atrial pressure via an interatrial shunt. We investigated whether device closure of PFO is associated with a subsequent risk of heart failure (HF), particularly in patients with structural heart disease or atrial fibrillation (AF). We enrolled 4,804 consecutive patients who underwent transesophageal echocardiography at tertiary medical centers in Korea between 2007 and 2019. The primary outcome was the 4-year risk of HF hospitalization. Underlying structural heart disease was determined by echocardiography. A PFO was observed in 981 (20.4%) patients, where 161 underwent device closure. During follow-up (median, 3.5 [1.4-6.4] years), the primary outcome was lower in patients with PFO than in those without (2.6% vs 4.0%; adjusted hazard ratio [aHR], 0.65; 95% CI, 0.45-0.94; P=.021). Among the patients with PFO, the primary outcome was higher in the device closure group than in the no-closure group (5.5% vs 1.2%; aHR, 5.59; 95% CI, 4.26-7.34; P<.001). A consistent result was found in patients with structural heart disease or AF (9.6% vs 3.9%; aHR, 2.55; 95% CI, 1.95-3.33; P<.001), demonstrating an increased risk of the primary outcome proportionate to the number of combined structural abnormalities. However, no significant association was observed between the primary outcome and PFO closure in those without structural heart disease or AF (1.7% vs 1.5%; aHR, 1.22; 95% CI, 0.99-1.50; P=.054). Patients with underlying structural heart disease or AF may be predisposed to symptomatic HF progression after PFO closure. Therefore, careful medical surveillance with optimal risk management is needed in these patients.

Abstract 4405: Tumor mutational burden, as a potential predictive marker for the efficacy of immunotherapy in advanced gastric cancer

Abstract Background: The optimal value of tumor mutational burden (TMB) for predicting treatment response of immunotherapy in advanced gastric cancer (AGC) is still unclear. We aimed to establish the optimal cut-off value of TMB, and evaluate the efficacy of immunotherapy in AGC according to TMB and other markers. Method: From October 1, 2020, to July 27, 2021, at Samsung medical center in Korea, patients with AGC, who received pembrolizumab or nivolumab were included. TMB was measured by next-generation sequencing (NGS)-based assays, and PD-L1 is tested using immune-histochemical assay 22C3 pharmDx. Based on receiver operating characteristic analysis, the cut-point value of TMB was determined as the point where the Youden’s index is maximum. Result: A total of 53 patients were analyzed. The cut-off value of TMB for predicting the overall response of immune checkpoint inhibitors was defined as 13.31 mutations/megabase (mt/mb), with 56% of sensitivity and 95% of specificity. Under this definition of TMB, 7 patients were TMB-high group (≥13.31 mt/mb), while 46 patients were TMB-low group (&amp;lt;13.31 mt/mb). The overall response rate (ORR) had a statistically significant difference between TMB-low (8.7%, n=4/46) and TMB-high patients (71.4%, n=5/7; p=0.001). The progression-free survival (PFS) and overall survival (OS) for 53 patients were 1.93 months (95% CI, 1.600-2.268) and 4.26 months (95% CI, 2.992-5.532). The OS was longer in the TMB-high group with the median of 20.8 months (95% CI, 2.292-39.281) compared to the TMB-low group with the median of 3.31 months (95% CI, 1.604-5.019; p=0.049). The ORR of the patients whose PD-L1 CPS was 1 or above was not different from the patients whose PD-L1 CPS was lower than 1. Conclusion: In this study, the optimal value of TMB for predicting the objective response rate of immunotherapy in AGC was determined as 13.31 mt/mb. TMB-high (≥13.31 mt/mb) was associated with a better objective response rate, and TMB-high patients exhibited better overall survival. TMB has the potential for predicting therapeutic response to immunotherapy in advanced gastric cancer. Citation Format: Jaeyeon Jang, Youngkyung Jeon, Sun Young Jeong, Ye Ji Jung, Daeho Choi, Joohyun Hong, Jeeyun Lee, Won Ki Kang, Seung Tae Kim. Tumor mutational burden, as a potential predictive marker for the efficacy of immunotherapy in advanced gastric cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4405.

Nutritional Status is Associated With Preserved Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease

Malnutrition is a common complication in autosomal dominant polycystic kidney disease (ADPKD). We examined whether nutritional status is associated with the preservation of kidney function, using a cohort of typical ADPKD. We enrolled ambulatory ADPKD patients in 9 tertiary medical centers in Korea from May 2019 to December 2021. We excluded patients who were aged less than 18years, who had known end-stage kidney disease at the time of enrollment, who had a diagnosis of atypical ADPKD, and who were Tolvaptan users. The primary outcome was an estimated glomerular filtration rate (eGFR) decline >3mL/min/1.73m2, based on nutritional status assessed by subjective global assessment (SGA). We also evaluated an eGFR decline >1mL/min/1.73m2, an increase in urine protein-creatinine ratio (UPCR)>0, and an increase in UPCR >0.3 as secondary outcomes, based on SGA after the 1-year follow-up. A logistic regression (LR) model was used to calculate the odds ratio (OR) for the primary outcome. Because there were differences in several baseline variables, such as Mayo classification, serum hemoglobin, serum creatinine, and UPCR between SGA groups, we matched propensity scores. In total, 805 patients were prospectively enrolled. Among them, 236 patients who had 1-year follow-up data and typical imaging findings were analyzed to evaluate the effect of nutritional status on kidney function. SGA was used to assess the nutritional status. The mean age was 45.0±13.3years, and 49.6% of the patients were female. The mean eGFR was 81.9mL/min/1.73m2. Among the 236 patients, 91 (38.6%) experienced a 1-year eGFR decline >3mL/min/1.73m2. When a multivariable LR was applied, SGA 3-6 was identified as a significant factor related to a 1-year eGFR decline >3mL/min/1.73m2 (adjusted OR=1.22 [1.04-1.43]; P=.017). Despite matching propensity scores, the 1-year eGFR decline >3mL/min/1.73m2 was still higher in the SGA 3-6 group regardless of proteinuria. Good nutritional status is associated with better-preserved kidney function in non-obese typical ADPKD patients who do not take Tolvaptan.

Trends in Survival Rates of Non–Small Cell Lung Cancer With Use of Molecular Testing and Targeted Therapy in Korea, 2010-2020

Over the past 10 years, treatment of non-small cell lung cancer (NSCLC) has been continually revolutionized. However, standard clinical trials may not reflect current multiple lines of treatment and corresponding outcomes in a timely manner. To investigate outcomes associated with new treatment of NSCLC in a clinical setting. This cohort study included patients with NSCLC between January 1, 2010, and November 30, 2020, who received any anticancer treatment at Samsung Medical Center in Korea. Data were analyzed from November 2021 through February 2022. Clinical and pathological stage, histology, and major druggable sequence variation, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS1, RET, MET exon 14 skipping, BRAF V600E, KRAS G12C, and NTRK between 2 periods (period I: 2010-2015 vs period II: 2016-2020). The primary outcome was the 3-year survival rate of NSCLC. Secondary outcomes included median overall survival, progression-free survival, and recurrence-free survival. Among 21 978 patients with NSCLC (median [range] age at diagnosis, 64.1 [57.0-71.0] years; 13 624 males [62.0%]), there were 10 110 patients in period I and 11 868 patients in period II; adenocarcinoma (AD) was the predominant histology (7112 patients [70.3%] in period I and 8813 patients [74.3%] in period II). There were 4224 never smokers [41.8%] in period I and 5292 never smokers [44.6%] in period II. Compared with patients in period I, patients during period II were more likely to undergo molecular tests in the AD (5678 patients [79.8%] vs 8631 patients [97.9%]) and non-AD (1612 of 2998 patients [53.8%] and 2719 of 3055 patients [89.0%]) groups. In patients with AD in period I, 3-year survival rates were 92.8% (95% CI, 91.8%-93.7%), 72.4% (95% CI, 68.3%-76.8%), 56.7% (95% CI, 53.4%-60.2%), and 28.7% (95% CI, 27.0%-30.4%) for stage I, II, III, and IV, respectively. In period II, 3-year survival rates of patients with AD were 95.1% (95% CI, 94.4%-95.9%), 82.5% (95% CI, 79.1%-86.1%), 65.1% (95% CI, 61.8%-68.6%), and 42.4% (95% CI, 40.3%-44.7%) for each stage, respectively. In patients without AD, 3-year survival rates were 72.0% (95% CI, 68.8%-75.3%), 60.0% (95% CI, 56.2%-64.1%), 38.9% (95% CI, 35.6%-42.5%), and 9.7% (95% CI, 7.9%-12.1%) for each stage in period I. In period II, the 3-year survival rates of patients without AD were 79.3% (95% CI, 76.3%-82.4%), 67.3% (95% CI, 62.8%-72.1%), 48.2% (95% CI, 44.5%-52.3%), and 18.1% (95% CI, 15.1%-21.6%) for each stage. In this cohort study of 10 years of clinical data, survival outcomes were improved across all stages, with larger increases in patients with stage III to IV disease. The incidence of never-smokers and the use of molecular testing increased.

Lymphatic Embolization versus Sclerotherapy for Symptomatic Post-operative Pelvic Lymphocele (LESPOL): A Randomized Pilot Study

This study was performed to compare clinical outcomes of lymphatic n-butyl cyanoacrylate (NBCA) embolization and ethanol sclerotherapy in patients with symptomatic postoperative pelvic lymphoceles. This prospective, open-label, randomized, and controlled trial took place at two medical centers in Korea. Patients ≥ 18 years old with symptomatic postoperative pelvic lymphoceles were randomly assigned (1:1) to one of two study arms: embolization or sclerotherapy. A target of 44 patients was set for each group to assess clinical outcomes. The trial began in August 2018 but ended as a pilot study in February 2020. Problematic patient enrollment precluded full population recruitment, only 11 patients (embolization, 5; sclerotherapy, 6) eventually participating. Clinical success and drainage tube removal rates were 100% in both arms. To achieve clinical success, significantly more procedures were needed in the sclerotherapy group than in the embolization group (4.5 ± 1.23 vs 2.0 ± 1.00; p < 0.001). The time to achieve daily drainage reduction thresholds (< 20 mL or < 20% of initial daily drainage) was also less in the sclerotherapy (vs embolization) group but fell short of statistical significance (4.8 ± 2.63 days vs 7.0 ± 3.67 days; p = 0.267). No significant adverse events or recurring symptomatic lymphoceles were evident at 3-month follow-up visits. Both NBCA embolization and ethanol sclerotherapy might be safe and effective in treating symptomatic postoperative pelvic lymphoceles, showing no significant difference in clinical outcomes. In a future randomized prospective study, it is essential to establish better inclusion criteria to selectively include intractable lymphoceles to find out the difference in the outcome between the two treatments. Trial registration: The study is registered as KCT0003078 at the Clinical Research Information Service ( http://cris.nih.go.kr ). Registered April 2, 2018.

Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study

ObjectiveThe purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor (TKI) as the first-line therapy for patients with metastatic renal cell carcinoma (mRCC) in terms of overall survival (OS), progression-free survival (PFS), and rates of discontinuation and adverse effects during the treatment period. MethodsThis is a retrospective, nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017. We focused on patients at either “favorable” or “intermediate” risk according to the International mRCC Database Consortium criteria, and they were followed up (median 335 days). Finally, a total of 1409 patients were selected as the study population. We generated a Cox proportional hazard model adjusted for covariates, and the different therapy schemes were statistically tested in terms of OS as well as PFS. In addition, frequencies of discontinuation and adverse events were compared among the therapy schemes. ResultsOf the primary patterns of treatment sequences (24 sequences), “sunitinib–pazopanib” and “sunitinib–everolimus–immunotherapy” showed the most beneficial results in both OS and PFS with significantly lower hazards than “sunitinib”, which is the most commonly treated agent in Korea. Considering that the “TKI–TKI” structure showed relatively higher discontinuation rates with higher adverse effects, the overall beneficial sequence would be “sunitinib–everolimus–immunotherapy”. ConclusionAmong several sequential therapy starting with TKIs, “sunitinib–everolimus– immunotherapy” was found to be the best scheme for mRCC patients with “favorable” or “intermediate” risks.

Tumor mutational burden as a potential predictive marker for the efficacy of immunotherapy in advanced gastric cancer.

324 Background: Tumor mutational burden (TMB) is known as an independent predictive factor in predicting treatment response of immunotherapy. We aimed to evaluate the efficacy of immunotherapy in advanced gastric cancer (AGC) according to TMB and other markers. Methods: The patients with AGC, aged ≥ 18, who received pembrolizumab or nivolumab from October 1, 2020, to July 27, 2021, at Samsung medical center in Korea, were analyzed retrospectively. TMB was measured by next-generation sequencing-based assays, and PD-L1 is tested using immunohistochemical assay 22C3 pharmDx. Referring to the results of previous studies, TMB-high was defined as 14.31 mutations/megabase (mt/Mb) or above. Results: A total of 54 AGC patients who were treated with immunotherapy, pembrolizumab or nivolumab, were analyzed. Seven patients were TMB-high, and 47 patients were TMB-low. Compared to TMB-low group, TMB-high group showed higher overall response rate (ORR) (42.9% vs 6.4%, p=0.023), and disease control rate (66.7% vs. 22.9%; p=0.033). The median OS was longer in the TMB-high group with 22.4 months (95% CI, 19.738-25.115), while the TMB-low group with 3.6 months (95% CI, 2.109-5.104; p=0.020). In addition to TMB, microsatellite status was statistically significantly associated with the efficacy of immunotherapy in AGC. Microsatellite instability group had better ORR (n=3/4, 75%) compared to microsatellite stable group (n=4/50, 8.0%; p=0.005). Other than that, the ORR of the patients whose PD-L1 CPS was 1 or above did not differ from the patients whose PD-L1 CPS was lower than 1. Although there was no statistical significance, among TMB-low patients, PD-L1 CPS ≥1 group numerically exhibited a higher overall response rate (13.0% vs 4.0%; p=0.338). Conclusions: In our analysis, the cut-off value of TMB was set to 14.31mb/Mt, and TMB-high was associated with the better ORR and OS of immunotherapy in AGC. TMB could be a potential predicting marker for a therapeutic response of immunotherapy in AGC.[Table: see text]

Machine Learning-Based Mortality Prediction Model for Critically Ill Cancer Patients Admitted to the Intensive Care Unit (CanICU).

Although cancer patients are increasingly admitted to the intensive care unit (ICU) for cancer- or treatment-related complications, improved mortality prediction remains a big challenge. This study describes a new ML-based mortality prediction model for critically ill cancer patients admitted to ICU. We developed CanICU, a machine learning-based 28-day mortality prediction model for adult cancer patients admitted to ICU from Medical Information Mart for Intensive Care (MIMIC) database in the USA (n = 766), Yonsei Cancer Center (YCC, n = 3571), and Samsung Medical Center in Korea (SMC, n = 2563) from 2 January 2008 to 31 December 2017. The accuracy of CanICU was measured using sensitivity, specificity, and area under the receiver operating curve (AUROC). A total of 6900 patients were included, with a 28-day mortality of 10.2%/12.7%/36.6% and a 1-year mortality of 30.0%/36.6%/58.5% in the YCC, SMC, and MIMIC-III cohort. Nine clinical and laboratory factors were used to construct the classifier using a random forest machine-learning algorithm. CanICU had 96% sensitivity/73% specificity with the area under the receiver operating characteristic (AUROC) of 0.94 for 28-day, showing better performance than current prognostic models, including the Acute Physiology and Chronic Health Evaluation (APACHE) or Sequential Organ Failure Assessment (SOFA) score. Application of CanICU in two external data sets across the countries yielded 79-89% sensitivity, 58-59% specificity, and 0.75-0.78 AUROC for 28-day mortality. The CanICU score was also correlated with one-year mortality with 88-93% specificity. CanICU offers improved performance for predicting mortality in critically ill cancer patients admitted to ICU. A user-friendly online implementation is available and should be valuable for better mortality risk stratification to allocate ICU care for cancer patients.

The Optimal Tumor Mutational Burden Cutoff Value as a Novel Marker for Predicting the Efficacy of Programmed Cell Death-1 Checkpoint Inhibitors in Advanced Gastric Cancer.

The optimal tumor mutational burden (TMB) value for predicting treatment response to programmed cell death-1 (PD-1) checkpoint inhibitors in advanced gastric cancer (AGC) remains unclear. We aimed to investigate the optimal TMB cutoff value that could predict the efficacy of PD-1 checkpoint inhibitors in AGC. Patients with AGC who received pembrolizumab or nivolumab between October 1, 2020, and July 27, 2021, at Samsung Medical Center in Korea were retrospectively analyzed. The TMB levels were measured using a next-generation sequencing assay. Based on receiver operating characteristic curve analysis, the TMB cutoff value was determined. A total 53 patients were analyzed. The TMB cutoff value for predicting the overall response rate (ORR) to PD-1 checkpoint inhibitors was defined as 13.31 mutations per megabase (mt/Mb) with 56% sensitivity and 95% specificity. Based on this definition, 7 (13.2%) patients were TMB-high (TMB-H). The ORR differed between the TMB-low (TMB-L) and TMB-H (8.7% vs. 71.4%, P=0.001). The progression-free survival and overall survival (OS) for 53 patients were 1.93 (95% confidence interval [CI], 1.600-2.268) and 4.26 months (95% CI, 2.992-5.532). The median OS was longer in the TMB-H (20.8 months; 95% CI, 2.292-39.281) than in the TMB-L (3.31 months; 95% CI, 1.604-5.019; P=0.049). The TMB cutoff value for predicting treatment response in AGC patients who received PD-1 checkpoint inhibitor monotherapy as salvage treatment was 13.31 mt/Mb. When applying the programmed death ligand-1 status to TMB-H, patients who would benefit from PD-1 checkpoint inhibitors can be selected.

Seroprevalence of Varicella-Zoster Virus and Measles among Healthcare Workers in a Tertiary Medical Center in Korea.

Measles and varicella still occur in the general population despite the widespread vaccination against them, and healthcare workers (HCWs) are still at risk of exposure to these diseases. Here, we evaluated the seroprevalence of measles and varicella-zoster virus (VZV) in HCWs and the trend of seroprevalence according to age, birth year, and occupational group. The serostatuses of measles and VZV of HCWs during new employee medical examinations between October 2015 and October 2021 were included. Thereafter, the trends of seroprevalence according to age, birth year, and occupational groups were evaluated. Overall, 2070 and 1827 HCWs were evaluated for VZV and measles serostatus, respectively. The seroprevalences of VZV and measles were 91% (1884/2070) and 70% (1284/1827), respectively. Younger HCWs had a significantly lower seroprevalence of measles (p = 0.02, age) and VZV (p = 0.003, birth year and p &lt; 0.001, age). The seroprevalence of measles and VZV was significantly higher among doctors and nursing assistants than among nurses and other HCWs (p &lt; 0.001 in both). In conclusion, the seroprevalence of measles and VZV significantly decreased in younger HCWs. Additionally, monitoring the serostatus of measles and VZV and the immunization of susceptible HCWs are required to prepare and control infectious diseases in healthcare facilities.

Abstract 9538: Impact of Device Closure on Heart Failure Progression in Patients With Patent Foramen Ovale

Background: Patent foramen ovale (PFO) can unload left atrial pressure via interatrial shunt. We evaluated whether device occlusion of PFO is associated with subsequent risk of heart failure (HF). Methods: We enrolled 4,804 consecutive patients (median age: 68 years, 62.4% male) who underwent transesophageal echocardiography at tertiary medical centers in Korea between 2007 and 2019. The primary outcome was the 4-year risk of HF. The independent association of PFO closure with HF was evaluated using the Cox regression hazard model after multivariate adjustment for demographics, clinical risk factors, and echocardiographic parameters. Additional subgroup analysis was performed according to the presence structural heart disease defined as left ventricular (LV) ejection fraction &lt; 55%, left atrial (LA) size &gt; 35ml or LA volume ≥ 40ml/m 2 , LV mass index ≥ 115g/m 2 , E/e' ≥ 15, or presence of atrial fibrillation. Results: In total, PFO was observed in 981 (20.4%) patients, where 161 (16.4%) of them underwent device closure. Patients with PFO showed a lower risk of HF than those without (2.6 vs. 4.0%, adjusted hazard ratio [HR]: 0.65, 95% confidence interval [CI] 0.45-0.94, p=0.021). PFO closure group showed a significantly higher risk of HF than no closure group (5.5 vs. 1.2%, adjusted HR: 5.59, 95% CI 4.26-7.34, p&lt;0.001) (Figure). In subgroup analysis, PFO closure was significantly associated with HF risk in patients with underlying structural heart disease (9.6 vs. 3.9%, adjusted HR: 2.55, 95% CI 1.95-3.33, p&lt;0.001), demonstrating an increasing trend in proportion to the number of structural abnormalities. However, PFO closure showed no significant association with HF risk in patients without structural heart disease (1.7 vs. 1.5%, adjusted HR: 1.22, 95% CI 0.99-1.50, p=0.054). Conclusion: PFO closure may increase the risk of HF. Therefore, careful patient selection is needed, especially among those with underlying structural heart disease.

Real-World Safety and Clinical Outcomes of Macitentan in Asian Patients with Pulmonary Arterial Hypertension: A Prospective Multicenter Study.

Macitentan is approved for treating pulmonary arterial hypertension. However, the real-world evidence of macitentan use is limited. Therefore, we evaluated the safety and clinical outcomes of macitentan use in clinical practice under a post-marketing surveillance. Patients with pulmonary arterial hypertension receiving macitentan treatment were prospectively and consecutively enrolled from 2014 to 2020 at 50 medical centers in Korea. Safety and clinical outcomes were monitored from baseline to the nearest timepoint of 24 weeks after macitentan initiation. The adverse events and adverse drug reactions were identified. Changes in the World Health Organization functional class were assessed as the primary clinical outcome, which was used to estimate the final effectiveness (both improved and maintained). Factors associated with safety and final effectiveness were identified. Among 474 patients enrolled in the study, 467 and 440 were included in the safety and clinical outcome analyses, respectively. Dyspnea, nasopharyngitis, and worsening pulmonary arterial hypertension were the most frequent adverse events with incidences of 5%, 3%, and 3%, respectively. The final effectiveness rate was 93%. Older age (adjusted odds ratio [aOR] = 1.021, p = 0.003) and higher level (III vs II) of baseline World Health Organization functional class (aOR = 1.784; p = 0.022) were significantly associated with a higher adverse event occurrence. Younger age (aOR = 0.947; p = 0.001) and shorter disease duration (aOR = 0.991; p = 0.010) were significantly associated with positive final effectiveness. This real-world study demonstrated the safety and clinical outcomes of macitentan use in Korean patients with pulmonary arterial hypertension. Macitentan was well tolerated and significantly effective with no new safety concerns during the 24 weeks.

Clinical Characteristics of Elderly People with Osteoporotic Vertebral Compression Fracture Based on a 12-Year Single-Center Experience in Korea.

In an aging human population, osteoporotic vertebral compression fracture (OVCF) frequently occurs. We conducted this retrospective study to analyze the clinical characteristics of elderly people with OVCF who underwent percutaneous vertebroplasty or kyphoplasty over a 12-year period at a single medical center in Korea. Between 2007 and 2019, A total of 868 patients (n = 868) were treated at our institution. We assessed 600 of these patients as eligible for study purposes and divided them into three groups: Group A (spine and hip T-scores ≤-2.5; n = 332); Group B (spine T-scores ≤-2.5; n = 189); and Group C (hip T-scores ≤-2.5; n = 79). The baseline characteristics of the patients included age, sex, body mass index (BMI), past history of steroid use, alcohol consumption, use of osteoporosis therapy, smoking, and treatment for OVCF. We compared these characteristics between the three groups. We found that the mean patient age was significantly higher in Group A, compared with Group B, and significantly lower in Group B, compared with Group C. We also found significant differences in the male-to-female ratio and mean body mass index between the three groups. In conclusion, we suggest that special attention should be paid to factors closely associated with spine and hip T-scores when evaluating elderly people with OVCF and determining appropriate treatment.