Eicosapentaenoic Acid and the Outcomes in Older Patients Undergoing Atrial Fibrillation Ablation.

BACKGROUND: A lower serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio (EPA/AA) level correlates with cardiovascular events. Nevertheless, elevated serum EPA levels increase the risk of new-onset atrial fibrillation (AF) in older patients. The relationship between the EPA/AA and outcomes post-AF ablation remains unclear. This study investigated the impact of the EPA/AA on AF recurrence and cardiovascular events after AF ablation in older patients. METHODS AND RESULTS: This retrospective cohort study examined consecutive patients with AF aged ≥65 years who underwent a first-time AF ablation. We compared the 3-year AF recurrence and 5-year major adverse cardiovascular event (MACE) rates between patients divided into high and low EPA/AA levels defined as above and below the median EPA/AA value before ablation. MACE was defined as heart failure hospitalizations, strokes, coronary artery disease, major bleeding, and cardiovascular death. Among the 673 included patients, the median EPA/AA value was 0.35. Compared with the low EPA/AA group, the high EPA/AA group had a significantly higher cumulative incidence of AF recurrence (39.3% versus 27.6%; log-rank P=0.004) and lower cumulative incidence of MACE (13.8% versus 25.5%, log-rank P=0.021). A high EPA/AA level was determined as an independent predictor of AF recurrence (hazard ratio [HR], 1.75 95% CI, 1.24-2.49; P=0.002) and MACE (HR, 0.60 [95% CI, 0.36-0.99]; P=0.046). CONCLUSIONS: The EPA/AA was associated with AF recurrence and MACE after ablation in patients with AF aged ≥65 years.

Pre-procedural Stratification by the Endothelial Function in Patients with Heart Failure Undergoing Atrial Fibrillation Ablation.

BACKGROUND: Endothelial dysfunction (ED), a well-established risk marker of cardiovascular events, is associated with heart failure (HF) and atrial fibrillation (AF). Its relationship with cardiovascular events in patients with HF undergoing AF ablation remains unclear. We aimed to elucidate the association between ED and the outcomes after AF ablation in patients with HF. METHODS: This prospective cohort study included patients with HF who underwent an endothelial function assessment using the peripheral vascular reactive hyperemia index (RHI) before first-time AF ablation. We defined AF recurrence according to the following types: the conventional form (AF≥30 seconds) and persistent form (requiring cardioversion). An RHI<2.1 indicated ED. Those with and without ED were compared in terms of the 3-year incidence of AF recurrence and cardiovascular events after AF ablation. RESULTS: Among 421 patients with HF (69 ± 9 years and 38% females), 343 (81.5%) had ED. Although the incidence of the conventional form of AF recurrence was similar between the groups, that of the persistent form was significantly higher in the ED group (25.7% vs. 15.3%, log-rank P = 0.028). The ED group also had a significantly higher rate of cardiovascular events (14.8% vs. 3.6%, log-rank P = 0.028). Pre-procedural ED was identified as an independent predictor of a persistent form of AF recurrence (adjusted hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.05-5.07, P = 0.037) and that of cardiovascular events (adjusted HR 4.21, 95% CI 1.02-17.5, P = 0.048), respectively. CONCLUSIONS: The endothelial function assessment enabled the risk stratification of clinically problematic outcomes after AF ablation in patients with HF.

Serial changes in the trends of direct oral anticoagulant use and incidence of thromboembolisms and major bleeding events in very old patients with non-valvular atrial fibrillation.

Aims: Direct oral anticoagulants (DOACs) have become the first-line antithrombotic therapy in patients with non-valvular atrial fibrillation (NVAF). During this period, the incidence of thromboembolisms and major bleeding events has decreased. However, no studies have shown a correlation between them, and even fewer data are available on older patients. Therefore, we evaluated the serial changes in oral anticoagulant (OAC) use and the correlation between DOAC use and the incidence of adverse events among very old patients with NVAF. Methods and results: We conducted a historical cohort study in 1320 consecutive patients with NVAF aged ≥80 years who received medical treatment for AF from March 2011 to February 2021. We analysed the temporal trends regarding patients using OACs, including the DOAC prescription rate and incidence of adverse events. Over the last decade, the number of patients using OACs has increased from 228 to approximately 600 person-years. The DOAC prescription rate has significantly increased (4-90%, P < 0.001). The age of the patients and proportion of patients with a HASBLED score ≥3 significantly increased (84 ± 4 to 86 ± 4 years, 16-25%, P < 0.001, respectively). The composite incidence of thromboembolisms and major bleeding events significantly decreased (7.02-3.30 events/100 person-years, P < 0.001). Conclusion: The incidence of thromboembolisms and major bleeding events might be inversely correlated with the increase in the DOAC prescription rate in patients with NVAF aged ≥80 years.

Cardiovascular events and death after catheter ablation in very old patients with nonvalvular atrial fibrillation.

BACKGROUND: Catheter ablation of atrial fibrillation (AF) is recommended for selected older patients. However, the preventive effects of AF ablation on cardiovascular events and death remain unclear, especially in older patients. This study aimed to investigate the impact of AF ablation on the incidence of cardiovascular events and death in very old nonvalvular AF (NVAF) patients. METHODS: We conducted a prospective cohort study of consecutive patients with NVAF aged ≥80 years and using direct oral anticoagulants (DOACs). We defined cardiovascular events as acute heart failure (AHF), strokes and systemic embolisms (SSEs), acute coronary syndrome (ACS), and sudden cardiac death (SCD) and cardiovascular death as AHF/SSE/ACS-related death and SCD. We compared the 3-year incidence of cardiovascular events and death between the patients who underwent AF ablation (Ablation group) and those who received medical therapy only (Medication group). RESULTS: Among the 782 NVAF patients using DOACs, propensity score matching provided 208 patients in each group. The Ablation group had a significantly lower 3-year incidence of cardiovascular events and death than the Medication group: cardiovascular events, 24 (13.2%) vs. 43 (23.3%), log-rank P = 0.009 and hazard ratio (HR) 0.52 (95% confidence interval (CI) 0.32-0.86) and cardiovascular deaths, 5 (3.0%) vs. 15 (7.8%), log-rank P = 0.019 and HR 0.32 (95% CI 0.16-0.88). CONCLUSIONS: In very old NVAF patients using DOACs, those who underwent AF ablation had a lower incidence of both cardiovascular events and death than those who received medical therapy only.

Prognostic Impact of the Early Use of Tolvaptan in Elderly Patients with Acute Decompensated Heart Failure.

The number of elderly patients with acute decompensated heart failure (ADHF) is increasing, and it is often difficult to treat. This study aimed to evaluate the efficacy and safety of using tolvaptan early after hospitalization in elderly patients with ADHF and the prognosis one year after hospitalization. This study enrolled 185 patients with ADHF who were admitted for the first time. Tolvaptan was administered within 24 h after admission. These patients were assigned to two groups: over 80 years old (n = 109) and under 80 years old (n = 76). There were no significant differences between the two groups in the occurrence of MACCE within one year (25% vs. 20%, p = 0.59). All-cause mortality was significantly higher in the over-80 group (12% vs. 2%, p = 0.01). There were no significant differences in the incidence of worsening renal failure (11% vs. 7%, p = 0.46) and hypernatremia (5% vs. 9%, p = 1.0), and in the duration of hospitalization (19.2 days vs. 18.8 days, p = 0.8). Tolvaptan might be effective and safe in elderly patients with ADHF, and there was no difference in the incidence of MACCE within one year.

MRI safety for leave-on powdered hair thickeners under 1.5-T and 3.0-T MRI: measurement of deflection force, MRI artifact, and evaluation of preexamination screening.

This study aimed to clarify the magnetic resonance imaging (MRI) compatibility of leave-on powdered hair thickeners by evaluating the displacement force and image artifacts of commercially available leave-on powdered hair thickeners on MRI devices and their response to metal and ferromagnetic detectors. Thirteen types of leave-on powdered hair thickeners were studied: nine hair thickener and four foundation types. MRI systems of 1.5 T and 3.0 T were used. Deflection angles and MR image artifacts according to ASTM F2052 and F2119 were evaluated. Handheld metal and ferromagnetic detectors were used to investigate whether hair thickeners could be detected in screening before MRI examinations. The hair thickener type had a deflection angle of 0°, whereas the foundation type had a deflection angle of 90°, indicating a strong physical effect. Significant image artifacts appeared only on the foundation type. The foundation type reacted at distances of less than 10 cm only with a ferromagnetic detector. Foundation-type leave-on powdered hair thickeners containing magnetic substances exhibited strong physical effects and produced significant image artifacts, and those can only be detected by screening with a ferromagnetic detector.

Relationship Between Endothelial Dysfunction and the Outcomes After Atrial Fibrillation Ablation.

Background Endothelial dysfunction (ED) is associated with cardiovascular events in patients with atrial fibrillation (AF). However, the utility of ED as a prognostic marker after AF ablation supplementary to the CHA2DS2-VASc score is unclear. This study aimed to investigate the relationship between ED and 5-year cardiovascular events in patients undergoing AF ablation. Methods and Results We conducted a prospective cohort study of patients who underwent a first-time AF ablation and for whom the endothelial function was assessed by the peripheral vascular reactive hyperemia index (RHI) before ablation. We defined ED as an RHI of <2.1. Cardiovascular events included strokes, heart failure requiring hospitalization, arteriosclerotic disease requiring treatment, venous thromboses, and ventricular arrhythmias or sudden cardiac death. We compared the 5-year incidence of cardiovascular events after AF ablation between those with and without ED. Among the 1040 patients who were enrolled, 829 (79.7%) had ED, and the RHI value was found to be associated with the CHA2DS2-VASc score (P=0.004). The 5-year incidence of cardiovascular events was higher among patients with ED than those without ED (98 [11.8%] versus 13 [6.2%]; log-rank P=0.014). We found ED to be an independent predictor of cardiovascular events after AF ablation (hazard ratio [HR], 1.91 [95% CI, 1.04-3.50]; P=0.036) along with a CHA2DS2-VASc score of ≥2 (≥3 for women) (HR, 3.68 [95% CI, 1.89-7.15]; P<0.001). Conclusions The prevalence of ED among patients with AF was high. Assessing the endothelial function could enable the risk stratification of cardiovascular events after AF ablation.

Effect of Direct Slow Pathway Capture Mapping-Guided Ablation on Typical Atrioventricular Nodal Re-Entrant Tachycardia.

BACKGROUND: Direct slow pathway capture (DSPC) mapping is a novel electrophysiological technique for detecting antegrade slow pathway input sites. However, the effect of DSPC mapping-guided ablation on atrioventricular nodal re-entrant tachycardia (AVNRT) is unknown. OBJECTIVES: This study aimed to evaluate the efficacy and safety of DSPC mapping-guided ablation in typical AVNRT patients. METHODS: A multicenter retrospective study was conducted in 301 consecutive typical AVNRT patients. The outcomes in patients who underwent DSPC mapping-guided ablation (DSPC group) and those who underwent conventional anatomical ablation (conventional group) were compared. The conventional group was established before introducing DSPC mapping-guided ablation. Positive DSPC sites were defined as sites with a return cycle atrioventricular prolongation of ≥20 ms with high-output (10-20 V) pacing during tachycardia or the last paced beat of the atrial extrastimulation. RESULTS: Among 116 patients in the DSPC group, 102 (88%) had positive DSPC sites, and 86 (74%) had a successful ablation at that site. Of the remaining 30 patients, 27 had a successful anatomical ablation. The DSPC group had a significantly lower frequency of radiofrequency applications and shorter total application time than the conventional group (median: 5.5 [IQR: 3-11] times vs 9 [IQR: 5-15] times, and 168 [IQR: 108-266] seconds vs 244 [IQR: 158-391] seconds, respectively; P < 0.01). Moreover, the DSPC group had a numerically lower incidence of permanent pacemaker implantations and AVNRT recurrences than the conventional group (0% vs 1.6%; P = 0.17, and 1.7% vs 3.2%; P = 0.43, respectively). CONCLUSIONS: DSPC mapping-guided ablation was associated with a lower operative time, which can reduce the risk of AV conduction injury in typical AVNRT.

P-wave terminal force in lead V1 and outcomes in patients with persistent atrial fibrillation undergoing catheter ablation.

AIMS: The P-wave terminal force in electrocardiogram lead V1 (PTFV1) correlates with outcomes in patients with paroxysmal atrial fibrillation (AF). Nevertheless, the correlation between the PTFV1 and outcomes after AF ablation in patients with persistent AF remains unclear. This study aimed to determine whether the PTFV1 at 3 months after AF ablation could predict AF recurrence and cardiovascular events in patients with persistent AF. METHODS: This historical cohort study examined 453 consecutive patients with persistent AF who underwent a first-time AF ablation. We measured the PTFV1 at 3 months after the ablation. An abnormal PTF was defined as a ≥4 mVms depression. The 3-year incidence of AF recurrence and composite cardiovascular events, including strokes, heart failure hospitalizations, and cardiovascular death, were compared between the abnormal and normal PTF groups. RESULTS: Among 434 enrolled patients, 101 had an abnormal, and 333 normal PTF at 3 months after AF ablation. Compared with the normal PTF group, the abnormal PTF group had a significantly higher incidence of AF recurrence (52.6% vs 28.1%, log-rank P < .001) and cardiovascular events (13.7% vs 2.6%, log-rank P = .005). After adjusting for the risk factors, an abnormal PTF was established as an independent predictor of AF recurrence (hazard ratio [HR] 2.12, 95% confidence interval [CI]: 1.44-3.13, P < .001) and cardiovascular events (HR 3.26, 95% CI: 1.19-8.97, P = .022). CONCLUSIONS: The PTFV1 at 3 months after AF ablation could be a valuable noninvasive predictor of both AF recurrence and cardiovascular events in patients with persistent AF.

Myeloid-associated differentiation marker is an essential host factor for human parechovirus PeV-A3 entry.

Human parechovirus (PeV-A) is an RNA virus that belongs to the family Picornaviridae and it is currently classified into 19 genotypes. PeV-As usually cause mild illness in children and adults. Among the genotypes, PeV-A3 can cause severe diseases in neonates and young infants, resulting in neurological sequelae and death. In this study, we identify the human myeloid-associated differentiation marker (MYADM) as an essential host factor for the entry of six PeV-As (PeV-A1 to PeV-A6), including PeV-A3. The infection of six PeV-As (PeV-A1 to PeV-A6) to human cells is abolished by knocking out the expression of MYADM. Hamster BHK-21 cells are resistant to PeV-A infection, but the expression of human MYADM in BHK-21 confers PeV-A infection and viral production. Furthermore, VP0 capsid protein of PeV-A3 interacts with one extracellular domain of human MYADM on the cell membrane of BHK-21. The identification of MYADM as an essential entry factor for PeV-As infection is expected to advance our understanding of the pathogenesis of PeV-As.

[Epithelioid Hemangioendothelioma of the Upper Mediastinum:Report of a Case].

A 81-year-old woman was referred to our hospital for neck discomfort. Chest computed tomography (CT) showed a tumor in the upper mediastinum. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed the mild accumulation in the tumor. Percutaneous biopsy was performed and epithelioid hemangioendothelioma was suspected, and the surgical treatment was performed. The histological study showed polygonal and irregular cells with nuclear atypia in myxoma-like substrate compatible with epithelioid hemangioendothelioma.

Electron-atom Compton profiles due to the intramolecular motions of the H and D atoms in HD.

We report an atomic momentum spectroscopy (AMS) experiment on HD, performed at a scattering angle of 135° and at an incident electron energy of 2.0 keV. The electron-atom Compton profiles due to the intramolecular motions of the H and D atoms in HD were obtained. The two Compton profiles are shown to be identical with each other in both shape and intensity, proving that the experimental responses of the intramolecular atomic motions are disentangled from the effect of molecular translational motion. It is also shown that the Compton profiles are in agreement with associated quantum chemistry-based calculations, indicating that the large momentum transfer limit is achieved under the experimental conditions. These observations demonstrate the ability of AMS not only to map the intramolecular motion of each atom with different masses but also to perform elemental composition analysis of a molecular system.

Theoretical Study of Valence Shell Excitation by Electron Impact in CCl4.

This paper reports a theoretical study of valence shell excitation in CCl4 by high-energy electron impact. Generalized oscillator strengths are calculated for the molecule at the equation-of-motion coupled-cluster singles and doubles level. To elucidate the influence of nuclear dynamics on electron excitation cross-sections, the effects of molecular vibration are included in the calculation. Based on a comparison with recent experimental data, several reassignments of spectral features are made, and it is found that excitations from the Cl 3p nonbonding orbitals to σ* antibonding orbitals, 7a1 and 8t2, play dominant roles below the excitation energy of ∼9 eV. Furthermore, the calculations reveal that distortion of the molecular structure due to the asymmetric stretching vibration significantly affects the valence excitations at small momentum transfers, where contributions from dipole transitions are dominant. It indicates that vibrational effects have a considerable influence on Cl formation in the photolysis of CCl4.

[Primary Pericardial Malignant Mesothelioma:Report of a Case].

A 67-year-old woman was referred to our hospital for cough and fever. Chest computed tomography (CT) showed some masses showing slightly enhanced effect in the pericardium. FDG-PET showed the accumulation of FDG in the masses. Thoracoscopic surgical biopsy was performed to establish the diagnosis. The histological study showed proliferation of short spindle-shaped cells surrounded by lymphocyte, and the spindle cells were immunohistochemically positive for cytokeratin AE1/AE3, WT-1, D2-40, CAM5.2, intelectin-1 and negative for CEA, TTF-1, napsin A, claudin-4, calretinin, MUC4, PAX8, CD30. These findings were compatible with epithelial pericardial malignant mesothelioma.

Impact of direct oral anticoagulant use on mortality in very old patients with non-valvular atrial fibrillation.

BACKGROUND: the efficacy and safety of direct oral anticoagulants (DOACs) compared with that of warfarin in very old patients with non-valvular atrial fibrillation (NVAF) have been reported in terms of thromboembolisms and bleeding. However, the association of DOAC use and mortality in such patients remains unclear. OBJECTIVES: this study aimed to investigate the incidence of mortality, as well as thromboembolisms and major bleeding, in very old patients with NVAF using DOACs as compared with warfarin. METHODS: we conducted a single-centre historical cohort study of consecutive patients with NVAF aged ≥80 years who used oral anticoagulants. We compared the 5-year outcomes (all-cause mortality, thromboembolism, major bleeding and intracranial haemorrhage) between the DOAC and Warfarin groups. RESULTS: of 1,676 patients with atrial fibrillation aged 80 years and over, 1,208 with NVAF were included. Propensity score matching provided 461 patients in each group, and the risk of all-cause mortality, thromboembolisms, major bleeding and intracranial haemorrhages was significantly lower in the DOAC group than Warfarin group (hazard ratio [95% confidence interval] for DOAC use, 0.68 [0.54-0.87], 0.31 [0.19-0.53], 0.56 [0.36-0.88], 0.23 [0.10-0.56], log-rank P = 0.002, P < 0.001, P = 0.010, P < 0.001). The mortality rate within 1 year after major bleeding was significantly lower in the DOAC group than Warfarin group (14% versus 38%, P = 0.03), however, that after a thromboembolism was similar between the two groups (33% versus 35%). CONCLUSION: patients with NVAF aged ≥80 years and using DOACs had a lower mortality than those using warfarin.

Asymptotic behavior of the electron-atom Compton profile due to the intramolecular H-atom motion in H2.

We report the asymptotic behavior of the electron-atom Compton profile due to the intramolecular H-atom motion in H2. The experiment has been performed at a scattering angle of 135° and at incident electron energies from 1.0 to 2.2 keV, thus covering a momentum transfer (K) range from 15.8 to 23.5 a.u. It is shown that with the increase in K, the Compton profile changes in shape and becomes more symmetric. Furthermore, it is found that the experiment reaches the limit of sufficiently large K at an incident electron energy of 2.0 keV, where the plane-wave impulse approximation is applicable to directly relate the Compton profile to the momentum distribution of the H atom.

Effect of Early Initiation of Evolocumab on Lipoprotein(a) in Patients with Acute Myocardial Infarction: Sub-Analysis of a Randomized Controlled Trial.

Elevated circulating lipoprotein(a) levels are associated with an increased risk of cardiovascular events. We reported that early initiation of evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in addition to a statin substantially reduced the lipoprotein(a) levels in patients with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PCI). This sub-analysis sought to investigate the effect of evolocumab on lipoprotein(a) based on baseline lipoprotein(a) levels and characteristics. This study was a prespecified analysis of a randomized controlled trial that enrolled 102 patients who underwent primary PCI for AMI. Patients received pitavastatin (2 mg/day) alone or pitavastatin and evolocumab 140 mg subcutaneously within 24 h and 2 weeks after the index PCI. The evolocumab group showed significantly suppressed lipoprotein(a) levels in patients with baseline lipoprotein(a) levels of ≤10 mg/dL, 10 < lipoprotein(a) ≤ 20 mg/dL, and >20 mg/dL compared with the control group, as well as similar reductions in lipoprotein(a) levels in all patient subgroups. Among these subgroups, evolocumab tended to show more favorable effects in patients with diabetes mellitus. In AMI patients, early initiation of evolocumab therapy within 24 h of primary PCI suppressed the increase in lipoprotein(a) levels within 4 weeks, regardless of baseline levels and characteristics.

HIF-1α stimulates the progression of oesophageal squamous cell carcinoma by activating the Wnt/ß-catenin signalling pathway.

BACKGROUND: This study aimed to clarify the significance of the crosstalk between hypoxia-inducible factor-1α (HIF-1α) and the Wnt/ß-catenin pathway in oesophageal squamous cell carcinoma (ESCC). METHODS: The oncogenic role of HIF-1α in ESCC was investigated using in vitro and in vivo assays. The clinicopathological significance of HIF-1α, ß-catenin and TCF4/TCF7L2 in ESCC were evaluated using quantitative real-time PCR and immunohistochemistry. RESULTS: The expression level of HIF-1α, ß-catenin, and TCF4/TCF7L2 in T.Tn and TE1 cell lines were elevated under hypoxia in vitro. HIF-1α knockdown suppressed proliferation, migration/invasion and epithelial-mesenchymal transition (EMT) progression, induced G0/G1 cell cycle arrest, promoted apoptosis and inhibited 5-fluorouracil chemoresistance in vitro. In vivo assays showed that HIF-1α is essential in maintaining tumour growth, angiogenesis, and 5-fluorouracil chemoresistance. Mechanically, we identified the complex between HIF-1α and ß-catenin, HIF-1α can directly bind to the promoter region of TCF4/TCF7L2. The mRNA level of HIF-1α, ß-catenin and TCF4/TCF7L2 were increased in ESCC tumour tissues compared to the corresponding non-tumour tissues. High levels of HIF-1α and TCF4/TCF7L2 expression were correlated with aggressive phenotypes and poor prognosis in ESCC patients. CONCLUSIONS: HIF-1α serves as an oncogenic transcriptional factor in ESCC, probably by directly targeting TCF4/TCF7L2 and activating the Wnt/ß-catenin pathway.

SIRT1 Expression Is a Promising Prognostic Biomarker in Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

Background/Aim: Several articles have assessed the prognostic significance of the expression of sirtuin 1 (SIRT1) in esophageal squamous cell carcinoma (ESCC). However, evidence in this field is insufficient. Thus, we conducted a meta-analysis to investigate the prognostic and clinical impact of SIRT1 expression in ESCC. Materials and Methods: We searched the PubMed, Cochrane Library, and Web of Science databases for articles on the expression of SIRT1 and clinicopathological features in patients with ESCC. A meta-analysis was conducted. Results: Four studies with 429 patients were included. The meta-analysis revealed a significant relationship between the high expression of SIRT1 and higher T-stage (odds ratio=2.39. 95% confidence interval=1.12-5.13, p=0.02), more advanced TNM stage (odds ratio=2.35. 95% confidence interval=1.20-4.60, p=0.01), and a poor overall survival (hazard ratio=1.90, 95% confidence interval=1.45-2.47, p<0.00001). Conclusion: SIRT1 expression may be a promising prognostic biomarker for patients with ESCC.

Metformin-Induced Heat Shock Protein Family A Member 6 Is a Promising Biomarker of Esophageal Squamous Cell Carcinoma.

INTRODUCTION: Antidiabetic drug metformin exerts various antitumor effects on different cancers. Esophageal squamous cell carcinoma (ESCC) is an intractable digestive organ cancer and new treatment strategy is required. In this study, we performed a comprehensive gene expression analysis of ESCC cell lines treated with metformin, which provided helpful information on the antitumor effects of metformin in ESCC. Next, we selected a promising gene among them and examined its effects on ESCC properties. METHODS: We examined metformin-induced mRNA expression changes in two human ESCC cell lines by performing next-generation sequencing (NGS) and pathway analysis. Heat shock protein family A (Hsp70) member 6 (HSPA6) expression in surgical specimens obtained from 83 ESCC patients who underwent curative operations was evaluated immunohistochemically and analyzed. RESULTS: Metformin upregulated mRNA expression of the many genes, including HSPA6, a cancer immune-related gene, and inhibited mRNA expression of the other many genes. Pathway analysis indicated major canonical pathways and upstream regulators related to metformin. The result indicated HSPA6 as a promising biomarker. HSPA6 expression correlated with disease-free survival (DFS) of the patients with all stage ESCC (p = 0.021), especially with stage I/II ESCC (p < 0.001). With stage III, low HSPA6 expression was not associated with poor DFS (p = 0.918). Multivariate analysis indicated that independent low HSPA6 expression was an independent poor prognostic factor of stage I/II ESCC (p < 0.001). However, HSPA6 expression did not correlate with the clinicopathological characteristics, including age, sex, tumor depth, lymph node metastasis, tumor stage, and tumor markers of the patients with stage I/II ESCC. CONCLUSIONS: This NGS analysis detected prospective candidate genes, including HSPA6. Our results indicate that HSPA6 is a promising biomarker of the recurrence risk of stage I/II ESCC. Further studies on HSPA6 would lead to better treatment.