Clinicopathological Features of Early Gastric Cancer Complicated by Autoimmune Gastritis.

INTRODUCTION: In the post-Helicobacter pylori era, autoimmune gastritis (AIG) is attracting increasing attention as an origin of gastric cancer. Here, we performed clinicopathological examination of gastric cancer complicating AIG treated in our hospital. METHODS: Eighty-six early gastric cancer lesions complicating AIG in 50 patients were treated by endoscopic submucosal dissection (ESD) at our hospital in 2008-2022. Their clinicopathological characteristics were compared with those of a control group comprising 2,978 early gastric cancer lesions (excluding lesions in the remnant stomach after surgery) in 2,278 patients treated by ESD during the same period. RESULTS: Mean age was significantly higher in the AIG group than in the control group (74.7 years vs. 70.9 years; p < 0.01). In the respective groups, the occurrence rate of synchronous/metachronous lesions was 38.0% and 20.4% (p < 0.01), the ratio of longitudinal cancer locations (upper/middle/lower third [U/M/L]) was 27/32/27 and 518/993/1,467 (p < 0.01), the ratio of circumferential cancer locations (lesser curvature/greater curvature/anterior wall/posterior wall) was 25/31/12/18 and 1,259/587/475/657 (p < 0.01), the ratio of major macroscopic types (I/IIa/IIb/IIc) was 13/38/5/30 and 65/881/220/1,812 (p < 0.01). The rates of multiple gastric cancer and cancers in the U region, at the greater curvature, and of protruding types were significantly higher in the AIG group. CONCLUSION: The occurrence rate of multiple gastric cancer was significantly higher in gastric cancer complicating AIG (approximately 40%), and compared with the control group, the proportions of cancers at the U region, at the greater curvature, and of protruding types were significantly higher.

RyR2-targeting therapy prevents left ventricular remodeling and ventricular tachycardia in post-infarction heart failure.

BACKGROUND: Dantrolene binds to the Leu601-Cys620 region of the N-terminal domain of cardiac ryanodine receptor (RyR2), which corresponds to the Leu590-Cys609 region of the skeletal ryanodine receptor, and suppresses diastolic Ca2+ leakage through RyR2. OBJECTIVE: We investigated whether the chronic administration of dantrolene prevented left ventricular (LV) remodeling and ventricular tachycardia (VT) after myocardial infarction (MI) by the same mechanism with the mutation V3599K of RyR2, which indicated that the inhibition of diastolic Ca2+ leakage occurred by enhancing the binding affinity of calmodulin (CaM) to RyR2. METHODS AND RESULTS: A left anterior descending coronary artery ligation MI model was developed in mice. Wild-type (WT) were divided into four groups: sham-operated mice (WT-Sham), sham-operated mice treated with dantrolene (WT-Sham-DAN), MI mice (WT-MI), and MI mice treated with dantrolene (WT-MI-DAN). Homozygous V3599K RyR2 knock-in (KI) mice were divided into two groups: sham-operated mice (KI-Sham) and MI mice (KI-MI). The mice were followed for 12 weeks. Survival was significantly higher in the WT-MI-DAN (73%) and KI-MI groups (70%) than the WT-MI group (40%). Echocardiography, pathological tissue, and epinephrine-induced VT studies showed that LV remodeling and VT were prevented in the WT-MI-DAN and KI-MI groups compared to the WT-MI group. An increase in diastolic Ca2+ spark frequency and a decrease in the binding affinity of CaM to the RyR2 were observed at 12 weeks after MI in the WT-MI group, although significant improvements in these values were observed in the WT-MI-DAN and KI-MI groups. CONCLUSIONS: Pharmacological or genetic stabilization of RyR2 tetrameric structure improves survival after MI by suppressing LV remodeling and proarrhythmia.

Long-term outcome of cervical lymph node metastasis in superficial pharyngeal squamous cell carcinoma after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Superficial pharyngeal squamous cell carcinoma (PSCC) has received increasing attention as a therapeutic target in the GI field with recent innovations in endoscopic submucosal dissection (ESD). However, there are currently no defined criteria for the application of ESD to superficial PSCC. One of the problems encountered during follow-up after ESD is cervical lymph node metastasis (LNM). Identifying the clinicopathologic predictors of cervical LNM can help to provide a basis for the refinement of therapeutic strategies for superficial PSCC. METHODS: The risk of cervical LNM was evaluated in 331 patients with superficial PSCC who underwent initial ESD between 2008 and 2021. Since tumor size, rather than depth, is the dominant factor in the current TNM classification for PSCC, the correlation between tumor size and thickness was investigated. RESULTS: The median follow-up period was 4.8 years. The cumulative 5-year cervical LNM rate was 6.1%. Multivariate Cox proportional hazards regression analysis identified tumor thickness ≥1000 µm and lymphatic invasion as significant independent predictors. Among 204 cases with subepithelial invasion, both factors were also revealed to be significant independent predictors, suggesting that tumor thickness was superior to tumor size in predicting cervical LNM. Despite the positive correlation between tumor thickness and size, there was noticeable variability in the values (R = .20), and the current staging was inadequate to identify groups at high risk for cervical LNM. CONCLUSIONS: Tumor thickness and lymphatic invasion are validated as significant independent predictors for cervical LNM and can be useful indicators to optimize the therapeutic strategies for superficial PSCC.

Safety of Cold Snare Polypectomy during Continuous Use of Antithrombotic Drugs for Delayed Post-Polypectomy Bleeding: A Pilot Study.

BACKGROUND: Cold snare polypectomy is a high-risk endoscopic procedure with a low delayed post-polypectomy bleeding rate. However, it is unclear whether delayed post-polypectomy bleeding rates increase during continuous antithrombotic treatment. This study aimed to determine the safety of cold snare polypectomy during continuous antithrombotic treatment. METHODS: This single-center, retrospective cohort study enrolled patients who underwent cold snare polypectomy during antithrombotic treatment between January 2015 and December 2021. Patients were divided into continuation and withdrawal groups based on whether they continued with antithrombotic drugs or not. Propensity score matching was performed using age, sex, Charlson comorbidity index, hospitalization, scheduled treatment, type of antithrombotic drugs used, multiple medications used, indication for antithrombotic drugs, and gastrointestinal endoscopist qualifications. The delayed polypectomy bleeding rates were compared between the groups. Delayed polypectomy bleeding was defined as the presence of blood in stools and requiring endoscopic treatment or a decrease in hemoglobin level by 2 g/dL or more. RESULTS: The continuation and withdrawal groups included 134 and 294 patients, respectively. Delayed polypectomy bleeding was observed in 2 patients (1.5%) and 1 patient (0.3%) in the continuation and withdrawal groups, respectively (p = 0.23), before propensity score matching, with no significant difference. After propensity score matching, delayed polypectomy bleeding was observed in 1 patient (0.9%) in the continuation group but not in the withdrawal group, with no significant difference. CONCLUSION: Cold snare polypectomy during continuous antithrombotic treatment did not significantly increase delayed post-polypectomy bleeding rates. Therefore, this procedure may be safe during continuous antithrombotic treatment.

Metachronous Multiple Gastric Cancer Discovered as Endoscopic Curability C2 during Regular Follow-Up after Gastric Endoscopic Submucosal Dissection.

INTRODUCTION: The objective of this study was to clarify characteristics of metachronous endoscopic curability C2 (eCura C2) cancer during post-endoscopic submucosal dissection (ESD) follow-up. METHODS: Of 4,355 gastric lesions treated by ESD at our hospital during 2005-2021, 657 were metachronous. After excluding lesions found ≥2 years since the prior examination or in the gastric remnant, the remaining 515 were analyzed. Study 1: We compared 35 eCura C2 cancers and 480 eCura A-C1 cancers. Study 2: Endoscopic findings of the 35 lesions were examined to determine why they had been missed. RESULTS: Mean tumor size was larger (34.0 mm vs. 12.1 mm, p < 0.01) and the proportions of mixed-type and poorly differentiated cancers were higher (highly:mixed:poorly, 34.3:57.1:8.6 vs. 94.2:5.0:0.8, p < 0.01) in the eCura C2 group. Study 2: At the prior examination, 4 lesions were noticed but considered benign, 2 lacked sufficient imaging, 19 were detectable on imaging but missed, and 10 were not detectable on imaging. Over half the lesions that were detectable but missed at the prior examination were in the lesser curvature, many being type IIa-IIb lesions with color similar to the background mucosa. All lesions not detectable on imaging at the prior examination were mixed-type or poorly differentiated type. DISCUSSION: Metachronous cancer detected as eCura C2 cancers was significantly larger, and a significantly higher proportion was mixed-type or poorly differentiated cancers, compared with eCura A-C1 cancers. Possible reasons why these lesions were missed include rapid progression of mixed-type and poorly differentiated cancers, and poor recognition that lesions showing only slight color changes may be present at the lesser curvature.

Risk Assessment of Side Branch Compromise After Coronary Bifurcation Stenting　- A Substudy of the 3D-OCT Bifurcation Registry.

BACKGROUND: Side branch (SB) occlusion during bifurcation stenting is a serious complication. This study aimed to predict SB compromise (SBC) using optical coherence tomography (OCT).Methods and Results: Among the 168 patients who enrolled in the 3D-OCT Bifurcation Registry, 111 bifurcation lesions were analyzed to develop an OCT risk score for predicting SBC. SBC was defined as worsening of angiographic SB ostial stenosis (≥90%) immediately after stenting. On the basis of OCT before stenting, geometric parameters (SB diameter [SBd], length from proximal branching point to carina tip [BP-CT length], and distance of the polygon of confluence [dPOC]) and 3-dimensional bifurcation types (parallel or perpendicular) were evaluated. SBC occurred in 36 (32%) lesions. The parallel-type bifurcation was significantly more frequent in lesions with SBC. The receiver operating characteristic curve indicated SBd ≤1.77 mm (area under the curve [AUC]=0.73, sensitivity 64%, specificity 75%), BP-CT length ≤1.8 mm (AUC=0.83, sensitivity 86%, specificity 68%), and dPOC ≤3.96 mm (AUC=0.68, sensitivity 63%, specificity 69%) as the best cut-off values for predicting SBC. To create the OCT risk score, we assigned 1 point to each of these factors. As the score increased, the frequency of SBC increased significantly (Score 0, 0%; Score 1, 8.7%; Score 2, 28%; Score 3, 58%; Score 4, 85%; P<0.0001). CONCLUSIONS: Prediction of SBC using OCT is feasible with high probability.

Prasugrel Monotherapy After Percutaneous Coronary Intervention With Biodegradable-Polymer Platinum-Chromium Everolimus Eluting Stent for Japanese Patients With Chronic Coronary Syndrome (ASET-JAPAN).

BACKGROUND: P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) has not been tested in East Asian patients, so in this study we aimed to assess the safety and feasibility of reduced dose (3.75 mg/day) prasugrel monotherapy in Japanese patients presenting with chronic coronary syndrome (CCS).Methods and Results: ASET-JAPAN is a prospective, multicenter, single-arm pilot study that completed enrolment of 206 patients from 12 Japanese centers in September 2022. Patients with native de-novo coronary lesions and a SYNTAX score <23 were treated exclusively with biodegradable-polymer platinum-chromium everolimus-eluting stent(s). Patients were loaded with standard dual antiplatelet therapy (DAPT) and following successful PCI and optimal stent deployment, they received low-dose prasugrel (3.75 mg/day) monotherapy for 3 months. The primary ischemic endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5. At 3-month follow-up, there were no primary bleeding or ischemic events, or any stent thrombosis. CONCLUSIONS: This pilot study showed the safety and feasibility of prasugrel monotherapy in selected low-risk Japanese patients with CCS. This "aspirin-free" strategy may be a safe alternative to traditional DAPT following PCI.

Diagnostic Performance of Endoscopic Ultrasonography with Water-Filled Balloon Method for Superficial Esophageal Squamous Cell Carcinoma.

BACKGROUND: Endoscopic ultrasonography (EUS) is a commonly used tool for preoperative depth diagnosis of superficial esophageal squamous cell carcinoma (ESCC). Probing EUS using the water-filled balloon method is a simple and safe examination. AIM: The aim of this study was to clarify the diagnostic performance of EUS with the water-filled balloon method for superficial ESCC compared to magnifying narrow-band imaging (ME-NBI). METHODS: We retrospectively examined 403 lesions in 393 consecutive patients diagnosed with ESCC and evaluated them with ME-NBI and EUS. Clinicopathological findings were collected, and the accuracy of the preoperative diagnosis was compared between ME-NBI and EUS-B. EUS examiners were not blinded to prior ME-NBI results, and EUS results may have been influenced by ME-NBI results. RESULTS: The pathological tumor depth of the EP/LPM in 152 lesions, MM/SM1 in 130 lesions, and deep submucosa (SM2/SM3) in 121 lesions was examined. The proportion of total lesions with an accurate diagnosis was significantly higher in EUS than in ME-NBI (67.7% versus 62.0%, P = 0.015). When analyzed by clinical depth diagnosis using ME-NBI, the proportion of lesions with an accurate diagnosis was significantly higher for EUS in MM/SM1 (55.7% versus 46.1%, P = 0.033). The sensitivity was significantly higher in EUS for SM2/SM3 lesions (76.0% versus 54.5%, P < 0.001). The accuracy and specificity of EUS, which differentiate MM/SM1 from EP/LPM or SM2/SM3, were significantly higher than those of ME-NBI. The median endoscopic ultrasonography procedure time was approximately 6.5 min. CONCLUSIONS: EUS with the water-filled balloon method is a safe and straightforward method that can be performed on lesions clinically diagnosed as MM/SM1 using ME-NBI. We retrospectively reviewed lesions in patients diagnosed with ESCC and evaluated them using magnifying endoscopy with narrow-band imaging (ME-NBI) and endoscopic ultrasound using the water-filled balloon method (EUS-B). We conclude that EUS-B can increase the diagnostic accuracy.

Dantrolene reduces platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell proliferation and neointimal formation following vascular injury in mice.

Dantrolene is a ryanodine receptor blocker that is used clinically for treatment of malignant hyperthermia. This study was conducted using murine aortic vascular smooth muscle cells (MOVAS) and a mouse arterial injury model to investigate the inhibitory effect of dantrolene on smooth muscle cell proliferation and migration. We investigated whether dantrolene suppressed platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell proliferation and migration in vitro. The effect of dantrolene on smooth muscle phenotype was evaluated using immunostaining. In addition, smooth muscle cell proliferation and phenotype switching were tested by applying dantrolene around blood vessels using a mouse arterial injury model. Dantrolene inhibited PDGF-induced cell proliferation and migration of MOVAS. Dantrolene also inhibited the switch from contractile to synthetic phenotype both in vitro and in vivo. Dantrolene is effective at inhibiting vascular smooth muscle cell proliferation, migration, and neointimal formation following arterial injury in mice.

Endoplasmic reticulum stress promotes nuclear translocation of calmodulin, which activates phenotypic switching of vascular smooth muscle cells.

BACKGROUND AND AIMS: Increased endoplasmic reticulum (ER) stress is strongly associated with the phenotypic switching of vascular smooth muscle cells (VSMCs) in atherosclerosis. Depletion of the ER Ca2+ content is one of the leading causes of increased ER stress in VSMCs. The ryanodine receptor (RyR) is a major Ca2+ release channel in the sarcoplasmic reticulum membrane. Calmodulin (CaM), which binds to RyR (CaM-RyR), stabilizes the closed state of RyR in the resting state in normal cells. Defective CaM-RyR interactions can cause abnormal Ca2+ leakage through RyR, resulting in decreased Ca2+ content, indicating that defective CaM-RyR interactions may be a cause of increased ER stress. Herein, we used a mouse VSMCs to assess whether CaM-RyR plays a pivotal role in VSMCs phenotypic switching, which is caused by ER stress, and whether dantrolene, which enhances the binding affinity of CaM to RyR, affects VSMCs phenotypic switching. METHODS AND RESULTS: Tunicamycin was used to mimic ER stress in vitro. Tunicamycin-induced ER stress caused CaM to dissociate from the RyR and translocate to the nucleus, which stimulated phenotypic switching through the activation of MEF2 and KLF5. Dantrolene suppressed tunicamycin-induced apoptosis, ER stress (restoring ER Ca2+ content), and phenotypic switching of VSMCs. Suramin, which directly unbinds CaM from RyR, promoted nuclear CaM accumulation with parallel VSMCs phenotypic switching, and dantrolene prevented these effects. CONCLUSIONS: We observed that ER stress causes CaM translocation to the nucleus and drives the phenotypic switching of VSMCs. Thus, restoration of the binding affinity of CaM to RyR may be a therapeutic target for atherosclerosis.

Effect of proximal optimization technique on coronary bifurcation stent failure: Insights from the multicenter randomized PROPOT trial.

OBJECTIVE: We investigated the effect of proximal optimization technique (POT) on coronary bifurcation stent failure (BSF) in cross-over stenting by comparing with the kissing balloon technique (KBT) in a multicenter randomized PROPOT trial. BACKGROUND: POT is recommended due to increased certainty for optimal stent expansion and side branch (SB) wiring. METHODS: We randomized 120 patients treated with crossover stenting into the POT group, which was followed by SB dilation (SBD), and the KBT group. Finally, 52 and 57 patients were analyzed by optical coherence tomography before SBD and at the final procedure, respectively. Composite BSF was defined as a maximal malapposition distance of >400 µm, or malapposed and SB-jailed strut rates of >5.95% and >21.4%, respectively. RESULTS: Composite BSF before SBD in the POT and KBT groups was observed in 29% and 26% of patients, respectively. In the POT group, differences in stent volumetric index between the proximal and distal bifurcation (odds ratio [OR] 60.35, 95% confidential interval [CI] 0.13-0.93, p = 0.036) and between the proximal bifurcation and bifurcation core (OR: 3.68, 95% CI: 1.01-13.40, p = 0.048) were identified as independent risk factors. Composite BSF at final in 27% and 32%, and unplanned additional procedures in 38% and 25% were observed, respectively. Composite BSF before SBD was a risk factor for the former (OR: 6.33, 95% CI: 1.10-36.50, p = 0.039) and the latter (OR: 6.43, 95% CI: 1.25-33.10, p = 0.026) in the POT group. CONCLUSION: POT did not result in a favorable trend in BSF. Insufficient expansion of the bifurcation core after POT was associated with BSF.

Effect of Helicobacter pylori infection on malignancy of undifferentiated-type gastric cancer.

BACKGROUND: Although almost all cases of gastric cancer are caused by Helicobacter pylori (HP) infection, there are some rare exceptions. Furthermore, the clinicopathological characteristics of gastric cancer may differ depending on HP infection status. This study aimed to determine the clinicopathological characteristics of undifferentiated-type gastric cancer (UD-GC) according to HP status. METHODS: The study involved 83 patients with UD-GC who were selected from 1559 patients with gastric cancer who underwent endoscopic resection at our hospital and whose HP infection status was confirmed. Clinicopathological characteristics were evaluated according to HP status (eradicated, n = 28; infected, n = 32; not infected, n = 23). RESULTS: In patients without HP infection, UD-GCs were < 20 mm and intramucosal with no vascular invasion. In patients with eradicated HP, there was no correlation between development of UD-GC and time since eradication. Nine of twelve patients with a tumor detected ≥ 5 years after eradication had undergone yearly endoscopy. Submucosal invasion was observed in two of four patients and lymphovascular invasion in three of four patients whose UD-GC was detected ≥ 10 years after eradication. There was no significant between-group difference in the frequency of lesions with invasion into the submucosal layer or deeper (14.3%, 10.5%, and 0% in the UD-E, UD-I, and UD-U groups, respectively). CONCLUSION: The clinicopathological characteristics of UD-GC were similar between HP-infected patients and HP-eradicated patients. Three of four patients with eradicated HP whose UD-GC developed ≥ 10 years after eradication were not eligible for endoscopic treatment and required additional surgery resection. In contrast, UD-GC was curable by endoscopic resection in all patients without HP infection.

Early and Long-Term Outcomes of Transcatheter Aortic Valve Replacement for Selected Nonagenarians in Japan.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly being performed in very elderly patients, although its efficacy and validity remain unclear. This study evaluated real-world TAVI outcomes in Japanese nonagenarians with severe aortic stenosis.Methods and Results: This single-center study retrospectively assessed the early and long-term clinical outcomes of TAVI in nonagenarians (n=35) and in patients aged <90 years (group Y; n=171). There were no in-hospital deaths in either group. The device success rate and early safety were comparable between the 2 groups. The 5-year rates of freedom from cardiac events and deaths were equivalent in both groups. The cumulative survival rate at 5 years was non-significantly lower in nonagenarians (32.6% in nonagenarians vs. 57.5% in patients aged <90 years, P=0.49). There were no differences in the 5-year survival between nonagenarians after TAVI and the sex- and age-matched populations (P=0.18). The Cox regression model revealed that lower hemoglobin levels were associated with all-cause mortality (P=0.02), and age ≥90 years was not associated with all-cause mortality. CONCLUSIONS: The early and long-term clinical outcomes of TAVI for selected Japanese nonagenarians were comparable to those in patients aged <90 years. Nonagenarians who underwent TAVI achieved an acceptable prognosis compared to the sex- and age-matched population; thus, TAVI appears to be effective for treating aortic stenosis in Japanese nonagenarians.

Serial changes in the quantitative flow ratio in patients with intermediate residual stenosis after percutaneous coronary intervention.

A beneficial surrogate marker for evaluating the effect of medical therapy is warranted to avoid deferred lesion revascularization. Similar to coronary artery imaging for monitoring the effects of medical therapy by analyzing plaque regression and stabilization, we hypothesized that evaluation of serial changes in the quantitative flow ratio (QFR) would serve as a surrogate marker of the effects of medical therapy against deferred lesion revascularization. Here, we investigated serial changes in QFR over time after percutaneous coronary intervention in patients who underwent medical therapy as a secondary prevention. Patients with intermediate stenosis in an untreated vessel observed at the baseline (BL) coronary angiography and follow-up (FU) coronary angiography performed 6-18 months after BL angiography were screened in 2 centers. A total of 52 patients were able to analyze both BL and FU QFR. The median QFR was 0.83 (IQR, 0.69, 0.89) at BL and 0.80 (IQR, 0.70, 0.86) at FU. The number of positive ΔQFR and negative ΔQFR were 21 and 31, respectively. The median ΔQFR was 0.05 (IQR, 0.03, 0.09) in positive ΔQFR and - 0.05 (IQR, - 0.07, - 0.03) in negative ΔQFR (p < 0.0001). Univariate and multivariate analyses revealed that LDL-C at FU predicted improvement in the QFR (OR 0.95, 95% confidence interval [0.91, 0.98], P = 0.001). Assessment of serial changes in the QFR may serve as a surrogate marker for the effects of medical therapy in patients with residual intermediate coronary stenosis.

Comprehensive risk evaluation for metachronous carcinogenesis after endoscopic submucosal dissection of superficial pharyngeal squamous cell carcinoma.

BACKGROUND: Pharyngeal squamous cell carcinoma (PSCC) is associated with a high likelihood of metachronous carcinogenesis, which is known to have a poor prognosis. This study aimed to identify comprehensive risk evaluation indicators for metachronous carcinogenesis after endoscopic submucosal dissection (ESD) of superficial PSCC. METHODS: The risk of metachronous carcinogenesis was evaluated in 144 patients with superficial PSCC (with no history of PSCC or esophageal squamous cell carcinoma) who underwent initial ESD from 2008 to 2020. Multiple lugol-voiding lesions (LVLs) in the background pharyngeal and esophageal epithelium were evaluated as endoscopic indicators. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score was analyzed as a serum marker. RESULTS: The median follow-up period was 4.3 years. The coincidence rate for pharyngeal and esophageal LVL grade was 55%. The cumulative 3-year metachronous PSCC rate was 18.9%. The cumulative 3-year second metachronous PSCC rate was 43.9%. Forward stepwise multivariate Cox proportional hazards regression analysis identified pharyngeal LVL grade and a lower HALP score as significant independent predictors. Pharyngeal LVL grade was superior to esophageal LVL grade as a predictor of metachronous PSCC. A lower HALP score was significantly associated with younger age in forward stepwise multivariate logistic regression analysis. CONCLUSIONS: Patients with a history of superficial PSCC remain at risk for metachronous carcinogenesis over time, and long-term follow-up is imperative. Comprehensive evaluation of endoscopic features with a novel serum marker, namely, the HALP score, can help predict metachronous carcinogenesis.

Trends Over Time in the Incidences of ST-Segment Elevation Myocardial Infarction and Non-ST-Segment Elevation Myocardial Infarction During the Past Decade in a Rural Japanese High-Aged Population.

BACKGROUND: In developed countries, the incidence of non-ST-segment elevation myocardial infarction (NSTEMI) has outpaced that of ST-segment elevation myocardial infarction (STEMI). However, whether this trend is observed in Japan, in which the aging of society is rapidly progressing, remains to be elucidated.Methods and Results:This study retrospectively investigated the trends over time in the incidence of acute coronary syndrome (ACS) between August 2009 and July 2019 at 2 institutions in Izumo City (in rural Japan), which has an elderly population. Crude and age-sex-adjusted incidences of total ACS, STEMI, and non-ST-segment elevation-ACS (NSTE-ACS; including NSTEMI and unstable angina pectoris) were calculated for each year. In the total population, factors associated with the development of NSTEMI were evaluated by multivariate analysis. In total, 1,087 patients were enrolled. The age-adjusted incidence of NSTE-ACS in male patients aged ≥75 years showed a significantly increasing trend. The proportion of NSTEMI per total ACS cases showed a significantly increasing trend over the entire study period. In the multivariate analysis, pre-development use of ≥3 medications for comorbidities was associated with the development of NSTEMI, independent of high-sensitivity cardiac troponin assay use. CONCLUSIONS: This study demonstrated an increasing trend in the incidence of NSTEMI in a rural high-aged Japanese population. In addition to the widespread use of high-sensitivity cardiac troponin assays, early medication use for comorbidities might have contributed to this trend.

Association Between Atrial High-Rate Episodes and Ischemic/Major Bleeding Events in Patients With a Cardiac Implantable Electronic Device　- A 10-Year, Single-Center Historical Cohort Study.

BACKGROUND: An association between atrial high-rate episode (AHRE) and stroke has been reported, although data for the Asian population are limited. This study aimed to investigate the role of AHRE in ischemic and major bleeding events in patients who underwent a cardiac implantable electronic device (CIED) procedure.Methods and Results:This single-center historical cohort study included 710 patients (age: 78±11 years, 374 women) who underwent a CIED-related procedure between October 2009 and September 2019 at Shimane Prefectural Central Hospital (median follow-up period: 4.5 [2.5, 7] years, 3439 person-years). Based on the maximum AHRE burden, patients were divided into: (1) <6 min; (2) ≥6 min to 24-h; and (3) ≥24-h groups. The cumulative incidence of ischemic (ischemic stroke, systemic embolism, and transient ischemic attack) and major bleeding (≥3 Bleeding Academic Research Consortium bleeding criteria) events after the procedure were compared. Uni- and multivariate analyses were performed to identify factors associated with these events. The incidence of both events increased with the rising AHRE burden, being significantly higher in the ≥24-h group than in the <6 min group. Multivariate analysis found age ≥85 years to be the only independent factor associated with both events. CONCLUSIONS: Longer AHRE duration is associated with a high number of major bleeding and ischemic events. Monitoring these bleeding risks is mandatory when clinicians are considering anticoagulation therapy for such patients.

Effectiveness of Chemoradiotherapy for Metachronous Esophageal Squamous Cell Carcinoma.

INTRODUCTION: Multiple Lugol-voiding lesions (LVLs) in the esophagus increase the risk of synchronous and metachronous development of esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) following endoscopic submucosal dissection (ESD) may reduce the incidence of metachronous ESCC, but few studies have investigated this. Therefore, we retrospectively examined the effect of CRT on metachronous ESCC and multiple esophageal dysplasias visible as multiple LVLs. METHODS: This study reviewed 146 patients who underwent esophageal ESD and were determined pathologically to have noncurative resection. They were divided into 2 groups: those who received additional CRT (CRT group; n = 64) and those without additional treatment (control group; n = 82). Incidence of metachronous ESCC was analyzed using propensity scores to adjust for patient characteristics. The number of multiple LVLs was also examined. RESULTS: The CRT group was significantly younger than the control group (mean 66.6 vs. 70.6 years, p = 0.011), had significantly deeper tumor invasion (p = 0.013), and had a significantly higher rate of lymphovascular invasion (47.8 vs. 12.2%, p < 0.001). The CRT group also had a significantly higher improvement rate of multiple LVLs (58.1 vs. 2.0%, p < 0.001). The LVLs after CRT had a distinctive irregular crack-shaped appearance. Metachronous ESCC was found in 7 patients (10.9%) in the CRT group and in 17 patients (20.7%) in the control group (p = 0.113). In propensity score-adjusted logistic regression analysis, the odds ratio for metachronous ESCC in the CRT group was 0.316 (p = 0.023). The occurrence rate was significantly lower in the CRT group than in the control group. DISCUSSION/CONCLUSION: CRT may be effective in preventing metachronous ESCC.

Metachronous carcinogenesis of superficial esophagus squamous cell carcinoma after endoscopic submucosal dissection: incidence and risk stratification during long-term observation.

BACKGROUND: This study aimed to reveal long-term outcomes, such as incidence of metachronous esophageal and head and neck squamous cell carcinomas and overall survival rate, through long-term observation of patients with esophageal carcinoma post-endoscopic submucosal dissection. METHODS: Risk of metachronous carcinogenesis was evaluated in 88 patients with intramucosal esophageal carcinoma (without history of metachronous esophageal or head and neck squamous cell carcinomas) who underwent endoscopic submucosal dissection from 2007 to 2008 and were endoscopically observed for > 3 years. Histologically, the papillary vessel is defined as the clock gear-like structure composed of capillaries directly penetrating the epithelium (starting from the lamina propria) and covering at least two-thirds of it, around which the tumor cells are arranged in a spiral pattern. RESULTS: Median endoscopic follow-up period was 11.0 years. Cumulative 2-, 5-, and 10-year metachronous esophageal carcinoma rates were 11.4%, 20.6%, and 39.3%, respectively. Stepwise multivariate Cox proportional hazard regression analysis identified multiple Lugol-voiding lesions (LVLs) as the single significant independent predictor. Cumulative 2-, 5-, and 10-year metachronous head and neck squamous cell carcinoma rates were 6.9%, 10.4%, and 19.6%, respectively. Stepwise multivariate Cox proportional hazard regression analysis identified multiple LVLs, Brinkman index, papillary vessel, and younger age as significant predictive factors. Overall post-endoscopic submucosal dissection survival rates were 98.8% and 87.5% at 5 and 10 years, respectively. CONCLUSION: Patients with a history of esophageal carcinoma remain at risk for metachronous carcinogenesis even > 5 years after endoscopic submucosal dissection. Thus, long-term follow-up is important.

Long-Term Outcomes of Absorb Bioresorbable Vascular Scaffold vs. Everolimus-Eluting Metallic Stent　- A Randomized Comparison Through 5 Years in Japan.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) are promising alternatives to metallic drug-eluting stents (DES) in percutaneous coronary interventions. Absorb BVS was comparable to XIENCE (DES) for patient- and device-oriented composite endpoints through 1 year post-procedure. Mid-term results showed increased rates of device-oriented events with Absorb. The objective of this study was to evaluate the long-term safety and effectiveness of Absorb BVS compared with XIENCE metallic DES when implanted in patients in Japan with de novo coronary artery lesions.Methods and Results:ABSORB Japan randomized 400 patients into either Absorb (n=266) or XIENCE (n=134) treatment arm. Through 5-year follow-up, the composite endpoints of DMR (death, myocardial infarction [MI], and all revascularization), target vessel failure (TVF), major adverse cardiac events (MACE), target lesion failure (TLF), and cardiac death/all MI were evaluated. Individual endpoints included death, MI, coronary revascularization, and scaffold/stent thrombosis. There were no significant differences in the composite or individual endpoint outcomes between the Absorb and XIENCE arms through 5 years or between 3 and 5 years. Numerically lower TVF, MACE, and all MI rates were observed for the Absorb vs. XIENCE arm after 3 years. No scaffold/stent thrombosis was reported beyond 3 years. Post-procedure imaging subgroups showed comparable event rates. CONCLUSIONS: Following resorption of the scaffold, between 3 and 5 years post-procedure, the Absorb BVS performed comparably to XIENCE in all patient- and device-oriented endpoints (ClinicalTrials.gov, #NCT01844284).