Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Purpose: Only a few Asian studies have discussed the impact of statin intensity on clinical outcomes in patients with peripheral artery disease (PAD). We aimed to investigate the clinical impact of statin intensity in patients with PAD after endovascular revascularization. Materials and Methods: From April 2009 to June 2019, 376 patients with lower extremity PAD treated with endovascular revascularization were enrolled. They were classified into three groups according to statin intensity: no-statin, low-to-moderate intensity (LMI), and high-intensity (HI). The primary outcomes were major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Results: During the 40-month follow-up, MACE occurred less frequently in the HI and LMI groups than the no-statin group (11.4% vs. 16.0% vs. 39%, p<0.001). In adjusted Cox models, the HI group had the fewest MACE [hazard ratio (HR): 0.447; 95% confidence interval (CI): 0.244–0.834; p=0.018] and MALE (HR: 0.360; 95% CI: 0.129–1.006; p=0.051) events, while the LMI group had fewer MACE (HR: 0.571; 95% CI: 0.326–1.0; p=0.050) events than the no-statin group. HI statin therapy was associated with better outcomes in terms of MALE (HR: 0.432; 95% CI: 0.223–0.837; p=0.003) than LMI statin therapy after inverse probability treatment weighting analysis. Conclusion HI and LMI statin use is associated with a significant reduction in MACE events than no-statin use. HI statin use was associated with better MALE outcomes than no-statin or LMI statin use.

Background: Although regular physical activity benefits cardiovascular health, there is a concern that intense exer‑ cise is linked to the promotion of atrial fibrillation (AF) and coronary plaque rupture. However, the impact of physical activity on the outcomes of patients with concomitant AF and coronary artery disease (CAD) remains unclear. This study aimed to evaluate the association with clinical outcomes according to the level of physical activity in patients with concomitant AF and CAD. Methods: We assessed 551 patients with AF and CAD (mean age, 67.1 ± 9.8 years) who completed a self-reported questionnaire for physical activity from 2015 to 2020 in a single tertiary-care hospital. Physical activity levels were con‑ verted into metabolic equivalent of task (MET) per week and categorized to correspond with multiple public health recommendations. We examined the association between physical activity, all-cause mortality, and major adverse cardiac and cerebrovascular events (MACCE). Results: The risks of all-cause mortality (P for linear trend = 0.017) and MACCE (P for linear trend = 0.05) appeared inverse trend with a greater level of physical activity. Compared with inactive patients, patients who met the recom‑ mended target range of physical activity (500–1,000 MET-min/week: unadjusted hazard ratio [HR] = 0.58, 95% confi‑ dence interval [CI] = 0.36–0.99) and highly active patients who exceeded the minimum recommended level (≥ 1,000 MET-min/week: unadjusted HR = 0.47, 95% CI = 0.25–0.88) had a lower risk of all-cause mortality in the unadjusted model; however, these associations did not remain significant after adjusting for the model. There was no evidence of increased risk of all-cause mortality and MACCE at levels of physical activity above the recommended target range, even with vigorous-intensity physical activity exceeding the recommended target range. Conclusions There appears to be an inverse trend between physical activity levels and all-cause mortality and MACCE in patients with concomitant AF and CAD. No excess risk of mortality or MACCE was found at exercise levels above the recommended target range. Further large-scale studies are warranted to create an improved evidence base concerning the effects of physical activity in patients with AF and CAD.

PURPOSE: This study aimed to elucidate which echocardiographic criteria at three time points, for cardiac resynchronization therapy (CRT) response, are accurate in discriminating the hierarchical clinical composite end point (HCCEP). MATERIALS AND METHODS: We included 120 patients (age, 66.1±12.6 years; men, 54.2%) who underwent CRT implantation for heart failure (HF). Echocardiography was performed before and at 3, 6, and 12 months after CRT implantation. The 1-year HCCEP included all-cause mortality, hospitalization for HF, and New York Heart Association functional class for 12 months. CRT response criteria were decrease in left ventricular (LV) end-systolic volume (LVESV) >15%, decrease in LV end-diastolic volume >15%, absolute increase in LV ejection fraction (LVEF) ≥5%, relative increase in LVEF ≥15%, and decrease in mitral regurgitation ≥1 grade. Temporal changes in CRT response rates, accuracy of CRT response criteria at each time and cutoff value for the discrimination of improvement in HCCEP, and agreements with improvement in HCCEP were analyzed. RESULTS: HCCEP improvement rates were 65.8% in total group. In nonischemic group, CRT response rates according to all echocardiographic criteria significantly increased with time. In ischemic group, CRT response rate did not significantly change with time. In total group, ΔLVESV at 6 months (ΔLVESV6) had the most significant accuracy for the discrimination of HCCEP (area under the curve=0.781). The optimal cutoff value of ΔLVESV6 was 13.5% (sensitivity=0.719, specificity=0.719). ΔLVESV6 had fair agreement with HCCEP (κ=0.391, p < 0.001). CONCLUSION: ΔLVESV6 is the most useful echocardiographic CRT response criterion for the prediction of 1-year HCCEP.
Cardiac Resynchronization Therapy* ; Discrimination (Psychology) ; Echocardiography ; Heart ; Heart Failure ; Hospitalization ; Humans ; Male ; Mitral Valve Insufficiency ; Mortality ; Stroke Volume*

PURPOSE: Despite undergoing successful catheter ablation of typical atrial flutter (AFL), patients remain at increased risk for ischemic stroke. However, data on risk prediction tools for the development of stroke after AFL ablation are lacking. This study investigates whether CHA₂DS₂-VASc score is useful for predicting ischemic stroke after successful ablation of typical AFL. MATERIALS AND METHODS: A total of 293 patients (236 men, mean age 56.1±13.5 years) who underwent successful radiofrequency catheter ablation for typical AFL were included in this study. The clinical end point was occurrence of ischemic stroke during follow-up after AFL ablation. RESULTS: During the follow-up period (60.8±45.9 months), ischemic stroke occurred in 18 (6%) patients at a median of 34 months (interquartile range, 13–65 months). CHA₂DS₂-VASc score [hazard ratio 2.104; 95% confidence interval (CI), 1.624–2.726; p < 0.001] was an independent predictor for the occurrence of stroke after AFL ablation. The area under the receiver operating characteristic curve for CHA₂DS₂-VASc score was 0.798 (95% CI, 0.691–0.904). The CHA₂DS₂-VASc score could be used to stratify patients into two groups with different incidences of ischemic stroke (1.6% vs. 14.4%, p < 0.001) at a cutoff value of 2. CONCLUSION: CHA₂DS₂-VASc score is useful in a prediction model for the risk of stroke after catheter ablation of typical AFL.
Aged ; Aged, 80 and over ; Atrial Flutter/*surgery ; Brain Ischemia/epidemiology/*etiology ; Catheter Ablation/*adverse effects ; Female ; Follow-Up Studies ; Humans ; Incidence ; Middle Aged ; Postoperative Complications/*epidemiology ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Risk Assessment/*methods ; Seoul/epidemiology ; Stroke/epidemiology/*etiology ; Treatment Outcome

PURPOSE: The identification of sick sinus syndrome (SSS) in patients with atrial flutter (AFL) is difficult before the termination of AFL. This study investigated the patient characteristics used in predicting a high risk of SSS after AFL ablation. MATERIALS AND METHODS: Out of 339 consecutive patients who had undergone radiofrequency ablation for AFL from 1991 to 2012, 27 (8%) had SSS (SSS group). We compared the clinical characteristics of patients with and without SSS (n=312, no-SSS group). RESULTS: The SSS group was more likely to have a lower body mass index (SSS: 22.5+/-3.2; no-SSS: 24.0+/-3.0 kg/m2; p=0.02), a history of atrial septal defects (ASD; SSS: 19%; no-SSS: 6%; p=0.01), a history of coronary artery bypass graft surgery (CABG; SSS: 11%; no-SSS: 2%; p=0.002), and a longer flutter cycle length (CL; SSS: 262.3+/-39.2; no-SSS: 243.0+/-40; p=0.02) than the no-SSS group. In multivariate analysis, a history of ASD [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.2-11.4, p=0.02] and CABG (7.1, 95% CI 1.5-32.8, p=0.01) as well as longer flutter CL (1.1, 95% CI 1.0-1.2, p=0.04) were independent risk factors for SSS. CONCLUSION: A history of ASD and CABG as well as longer flutter CL increased the risk of SSS after AFL ablation. While half of the patients with SSS after AFL ablation experienced transient SSS, heart failure was associated with irreversible SSS.
Atrial Flutter/physiopathology/*surgery ; Catheter Ablation/*adverse effects ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Risk Factors ; Sick Sinus Syndrome/*etiology/physiopathology ; Treatment Outcome

Thyroglossal duct cyst (TGDC) carcinoma generally shows a favorable prognosis. If metastasis is present latently, it may not threaten the patient's life immediately. It has been shown, however, that larger than 1 cm papillary carcinoma (PC), level VI metastasis to the lymph node (LN), which is the nearest to the thyroid, independently predicts a worse prognosis. In the case presented herein, a 61-year-old female patient was diagnosed with an about 3 cm PC in the TGDC, particularly the columnar variant subtype, one of the aggressive variants. She had occult papillary thyroid microcarcinoma, but no LN metastasis. Even though she underwent the Sistrunk procedure and total thyroidectomy with central compartment neck dissection followed by high-dose radioactive iodine remnant ablation, however, the cancer cells spread to level IV neck LN, and finally to the lung. Therefore, when a patient is diagnosed with an aggressive histologic variant of PC in the TGDC, even without LN metastasis, the invasive surgical approach and close postoperative surveillance are necessary, with consideration of the risk of disease progression. Therefore, if it is possible to stratify the risk for patients, higher-risk patients can be offered a more invasive therapeutic approach.
Carcinoma, Papillary* ; Disease Management ; Disease Progression ; Female ; Humans ; Iodine ; Lung* ; Lymph Nodes ; Middle Aged ; Neck ; Neck Dissection ; Neoplasm Metastasis* ; Prognosis ; Thyroglossal Cyst* ; Thyroid Gland ; Thyroidectomy

With the aging population, more patients who have undergone previous coronary artery bypass grafting (CABG) are surviving long enough to require subsequent aortic valve replacement (AVR). Conventional redo AVR after prior CABG involves resternotomy, dissection and clamping of the patent bypass graft vessel. Favorable results have been reported for AVR following previous CABG; however, the problems of this procedure includes that injury to the patent bypass grafts can result in catastrophic complications. Increasing patient age and comorbidities may increase operative mortality, less invasive percutaneous aortic valve intervention has advanced. However, because there are no sufficient data comparing transcatheter aortic valve intervention with surgical AVR, currently, the surgical approach should still be consider as the standard of treatment for AVR following previous CABG. We report a patient in whom successful conventional AVR was underwent after previous CABG with patent left internal mammary artery.
Aging ; Aortic Valve Stenosis ; Aortic Valve* ; Comorbidity ; Constriction ; Coronary Artery Bypass* ; Coronary Vessels* ; Heart Valve Prosthesis Implantation ; Humans ; Mammary Arteries* ; Mortality ; Transplants

The rearrangement of c-ros oncogene 1 (ROS1) has been recently identified as an important molecular target in non small cell lung cancer (NSCLC). ROS1 rearrangement and epidermal growth factor receptor (EGFR) mutation were mutually exclusive each other in previous studies, and the clinical implication of co-existence of the two genetic alterations has not been determined. We report a case of 46-year-old female never-smoker NSCLC patient whose tumor harbored ROS1 rearrangement and EGFR mutation concomitantly. She had undergone curative surgery for stage IIIA NSCLC, and the recurrence in left pleura and brain occurred at 2 years after the surgery. She received several lines of chemotherapy including docetaxel plus carboplatin, erlotinib, pemetrexed, and gemcitabine. Erlotinib therapy showed a favorable treatment response with progression-free survival of 9.5 months and partial response of tumor on radiologic evaluations. This case represents a successful erlotinib treatment in a NSCLC patient with concurrent ROS1 rearrangement and EGFR mutation.
Adenocarcinoma* ; Brain ; Carboplatin ; Carcinoma, Non-Small-Cell Lung ; Disease-Free Survival ; Drug Therapy ; Female ; Humans ; Lung* ; Middle Aged ; Oncogenes ; Pleura ; Receptor, Epidermal Growth Factor ; Recurrence ; Small Cell Lung Carcinoma ; Erlotinib Hydrochloride ; Pemetrexed