Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms.

BACKGROUND AND AIM: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk. METHODS: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. RESULTS: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). CONCLUSIONS: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase eta.

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy. Depletion of TUG1 increased sensitivity to cisplatin in the OVCA cell lines, SKOV3 and KURAMOCHI. Combination therapy of cisplatin with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system effectively relieved the tumor burden in xenograft mouse models. Mechanistically, TUG1 acts as a competing endogenous RNA by downregulating miR-4687-3p and miR-6088, both of which target DNA polymerase eta (POLH), an enzyme required for translesion DNA synthesis. Overexpression of POLH reversed the effect of TUG1 depletion on cisplatin-induced cytotoxicity. Our data suggest that TUG1 upregulation allows OVCA to tolerate DNA damage via upregulation of POLH; this provides a strong rationale for targeting TUG1 to overcome cisplatin resistance in OVCA.

Post-intensive care syndrome: Recent advances and future directions.

Post-intensive care syndrome comprises physical, cognitive, and mental impairments in patients treated in an intensive care unit (ICU). It occurs either during the ICU stay or following ICU discharge and is related to the patients' long-term prognosis. The same concept also applies to pediatric patients, and it can greatly affect the mental status of family members. In the 10 years since post-intensive care syndrome was first proposed, research has greatly expanded. Here, we summarize the recent evidence on post-intensive care syndrome regarding its pathophysiology, epidemiology, assessment, risk factors, prevention, and treatments. We highlight new topics, future directions, and strategies to overcome post-intensive care syndrome among people treated in an ICU. Clinical and basic research are still needed to elucidate the mechanistic insights and to discover therapeutic targets and new interventions for post-intensive care syndrome.

Astrocyte-induced mGluR1 activates human lung cancer brain metastasis via glutamate-dependent stabilization of EGFR.

There are limited methods to stably analyze the interactions between cancer cells and glial cells in vitro, which hinders our molecular understanding. Here, we develop a simple and stable culture method of mouse glial cells, termed mixed-glial culture on/in soft substrate (MGS), which serves well as a platform to study cancer-glia interactions. Using this method, we find that human lung cancer cells become overly dependent on metabotropic glutamate receptor 1 (mGluR1) signaling in the brain microenvironment. Mechanistically, interactions with astrocytes induce mGluR1 in cancer cells through the Wnt-5a/prickle planar cell polarity protein 1 (PRICKLE1)/RE1 silencing transcription factor (REST) axis. Induced mGluR1 directly interacts with and stabilizes the epidermal growth factor receptor (EGFR) in a glutamate-dependent manner, and these cells then become responsive to mGluR1 inhibition. Our results highlight increased dependence on mGluR1 signaling as an adaptive strategy and vulnerability of human lung cancer brain metastasis.

Association of Contrast Extravasation Grade With Massive Transfusion in Pediatric Blunt Liver and Spleen Injuries: A Multicenter Retrospective Cohort Study.

BACKGROUND: This study aimed to assess whether the grade of contrast extravasation (CE) on CT scans was associated with massive transfusion (MT) requirements in pediatric blunt liver and/or spleen injuries (BLSI). METHODS: This multicenter retrospective cohort study included pediatric patients (≤16 years old) who sustained BLSI between 2008 and 2019. MT was defined as transfusion of all blood products ≥40 mL/kg within the first 24 h of admission. Associations between CE and MT requirements were assessed using multivariate logistic regression analysis with cluster-adjusted robust standard errors to calculate the adjusted odds ratio (AOR). RESULTS: A total of 1407 children (median age: 9 years) from 83 institutions were included in the analysis. Overall, 199 patients (14 %) received MT. CT on admission revealed that 54 patients (3.8 %) had CE within the subcapsular hematoma, 100 patients (7.1 %) had intraparenchymal CE, and 86 patients (6.1 %) had CE into the peritoneal cavity among the overall cohort. Multivariate analysis, adjusted for age, sex, age-adjusted shock index, injury severity, and laboratory and imaging factors, showed that intraparenchymal CE and CE into the peritoneal cavity were significantly associated with the need for MT (AOR: 2.50; 95 % CI, 1.50-4.16 and AOR: 4.98; 95 % CI, 2.75-9.02, respectively both p < 0.001). The latter significant association persisted in the subgroup of patients with spleen and liver injuries. CONCLUSION: Active CE into the free peritoneal cavity on admission CT was independently associated with a greater probability of receiving MT in pediatric BLSI. The CE grade may help clinicians plan blood transfusion strategies. LEVEL OF EVIDENCE: Level 4; Therapeutic/Care management.

Challenges hindering emergency physicians; involvement in multicenter collaborative studies in Japan: A nationwide survey analysis.

Aim: Multicenter collaborative research accelerates patient recruitment and strengthens evidence. Nevertheless, the factors influencing emergency and critical care physicians' involvement in such research in Japan remain unclear. Methods: A nationwide web-based survey conducted in early 2023 targeted emergency physicians working a minimum of 3 days per week in Japan. The survey descriptively assessed their backgrounds, work and research environments, experiences, and perceived impediments and motivators for multicenter research. Results: Of the 387 respondents, 348 were included in the study, yielding a 5.1% response rate. Women comprised 11% of the participants; 33% worked in university hospitals, 65% served in both emergency departments and intensive care units, and 54% did shift work. Only 12% had designated research time during working hours, with a median of 1 hour per week (interquartile range 0-5 h), including time outside of work. While 73% had participated in multicenter research, 58% noted barriers to participation. The key obstacles were excessive data entry (72%), meeting time constraints (59%), ethical review at each facility (50%), and unique sample collection, such as bronchoalveolar lavage specimens or pathological tissues (51%). The major incentives were networking (70%), data sets reuse (65%), feedback on research results (63%), and recognition from academic societies (63%). Financial rewards were not highly prioritized (38%). Conclusions: While valuing clinical research, emergency physicians face barriers, especially data entry burden and limited research time. Networking and sharing research findings motivate them. These insights can guide strategies to enhance collaborative research in emergency and critical care in Japan.

Defining super-enhancers by highly ranked histone H4 multi-acetylation levels identifies transcription factors associated with glioblastoma stem-like properties.

BACKGROUND: Super-enhancers (SEs), which activate genes involved in cell-type specificity, have mainly been defined as genomic regions with top-ranked enrichment(s) of histone H3 with acetylated K27 (H3K27ac) and/or transcription coactivator(s) including a bromodomain and extra-terminal domain (BET) family protein, BRD4. However, BRD4 preferentially binds to multi-acetylated histone H4, typically with acetylated K5 and K8 (H4K5acK8ac), leading us to hypothesize that SEs should be defined by high H4K5acK8ac enrichment at least as well as by that of H3K27ac. RESULTS: Here, we conducted genome-wide profiling of H4K5acK8ac and H3K27ac, BRD4 binding, and the transcriptome by using a BET inhibitor, JQ1, in three human glial cell lines. When SEs were defined as having the top ranks for H4K5acK8ac or H3K27ac signal, 43% of H4K5acK8ac-ranked SEs were distinct from H3K27ac-ranked SEs in a glioblastoma stem-like cell (GSC) line. CRISPR-Cas9-mediated deletion of the H4K5acK8ac-preferred SEs associated with MYCN and NFIC decreased the stem-like properties in GSCs. CONCLUSIONS: Collectively, our data highlights H4K5acK8ac's utility for identifying genes regulating cell-type specificity.

TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation.

Oncogene-induced DNA replication stress (RS) and consequent pathogenic R-loop formation are known to impede S phase progression. Nonetheless, cancer cells continuously proliferate under such high-stressed conditions through incompletely understood mechanisms. Here, we report taurine upregulated gene 1 (TUG1) long noncoding RNA (lncRNA), which is highly expressed in many types of cancers, as an important regulator of intrinsic R-loop in cancer cells. Under RS conditions, TUG1 is rapidly upregulated via activation of the ATR-CHK1 signaling pathway, interacts with RPA and DHX9, and engages in resolving R-loops at certain loci, particularly at the CA repeat microsatellite loci. Depletion of TUG1 leads to overabundant R-loops and enhanced RS, leading to substantial inhibition of tumor growth. Our data reveal a role of TUG1 as molecule important for resolving R-loop accumulation in cancer cells and suggest targeting TUG1 as a potent therapeutic approach for cancer treatment.

Burnout among Japanese emergency medicine physicians: A multicentric questionnaire study.

Objective: Burnout negatively affects the wellness and performance of emergency physicians (EPs). This study aimed to clarify the actual prevalence of burnout and its associated factors among Japanese EPs. Methods: We conducted a cross-sectional questionnaire study of selected 27 Japanese emergency departments (EDs). We examined the Maslach Burnout Inventory-Human Services Survey score and its associations with ED-level- and EP-level factors in a multivariable analysis. Results: A total of 267 EPs (81.9%) completed survey. Of these, 43 EPs (16.1%) scored severe emotional exhaustion (EE), 53 (19.8%) scored severe depersonalization (DP), and 179 (67.0%) scored severe personal accomplishment (PA), and 24 (8.9%) scored severely in all three domains. In our multivariable analysis, emergency medical service centers were associated with severe PA scores (odds ratio [OR], 10.56; 95% confidence interval [CI], 1.78-62.66; p = 0.009). A 3 to 6 hour-sleep period was associated with severe EE scores (OR, 2.04; 95% CI, 1.04-3.98; p = 0.036), and EPs in their 20s were associated with severe DP scores (OR, 7.37; 95% CI, 1.41-38.38; p = 0.018). Conclusion: Our results suggest that 8.9% of Japanese EPs are in higher degrees of burnout. In particular, Japanese EPs scored more severely on PA. To avoid burnout in Japanese EPs, it is important to improve the working environment by ensuring more than 6 h of sleep, providing more support for young EPs, and taking effective action to combat low EP self-esteem.

Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts.

Retrograde menstruation is a widely accepted cause of endometriosis. However, not all women who experience retrograde menstruation develop endometriosis, and the mechanisms underlying these observations are not yet understood. Here, we demonstrated a pathogenic role of Fusobacterium in the formation of ovarian endometriosis. In a cohort of women, 64% of patients with endometriosis but <10% of controls were found to have Fusobacterium infiltration in the endometrium. Immunohistochemical and biochemical analyses revealed that activated transforming growth factor-ß (TGF-ß) signaling resulting from Fusobacterium infection of endometrial cells led to the transition from quiescent fibroblasts to transgelin (TAGLN)-positive myofibroblasts, which gained the ability to proliferate, adhere, and migrate in vitro. Fusobacterium inoculation in a syngeneic mouse model of endometriosis resulted in a marked increase in TAGLN-positive myofibroblasts and increased number and weight of endometriotic lesions. Furthermore, antibiotic treatment largely prevented establishment of endometriosis and reduced the number and weight of established endometriotic lesions in the mouse model. Our data support a mechanism for the pathogenesis of endometriosis via Fusobacterium infection and suggest that eradication of this bacterium could be an approach to treat endometriosis.

Physical and chemical properties of PM1 in Delhi: A comparison between clean and polluted days.

Considering the significance of PM1 aerosol in assessing health impacts of air pollution, an extensive analysis of PM1 samples collected at an urban site in Delhi is presented in this study. Overall, PM1 contributed to about 50 % of PM2.5 mass which is alarming especially in Delhi where particle mass loadings are usually higher than prescribed limits. Major portion of PM1 consisted of organic matter (OM) that formed nearly 47 % of PM1 mass. Elemental carbon (EC) contributed to about 13 % of PM1 mass, whereas SO42- (16 %), NH4+ (10 %), NO3- (4 %) and Cl- (3 %) were the major inorganic ions present. Sampling was performed in two distinctive campaign periods (in terms of meteorological conditions and heating (fire) activities), during the year 2019, each spanning two-week time, i.e. (i) September 3rd-16th (clean days), and (ii) November 22nd-December 5th (polluted days). Additionally, PM2.5 and black carbon (BC) were measured simultaneously for subsequent analysis. The 24-h averaged mean concentrations of PM2.5 and BC during clean days (polluted days) were 70.6 ± 26.9 and 3.9 ± 1.0 µg m-3 (196 ± 104 and 7.6 ± 4.1 µg m-3), respectively, which were systematically lower (higher) than that of the annual mean (taken from studies conducted at same site in 2019) of 142 and 5.7 µg m-3, respectively. Changes in characteristic ratios (i.e., organic carbon (OC)/elemental carbon (EC) and K+/EC) of chemical species detected in PM1 show an increase in biomass emissions during polluted days. Increase in biomass emission can be attributed to increase in heating practices (burning of biofuels such as wood logs, straw, and cow-dung cake) in- and around- Delhi because of fall in temperature during second campaign. Furthermore, a significant increase in NO3- fraction of PM1 is observed during second campaign which shows fog processing of NOX due to conducive meteorological conditions in winters. Also, comparatively stronger correlation of NO3- with K+ during second campaign (r = 0.98 as compared to r = 0.5 during first campaign) suggests the increased heating practices to be a contributing factor for increased fraction of NO3- in PM1. We observed that during polluted days, meteorological parameters such as dispersion rate also played a major role in intensifying the impact of increased local emissions due to heating activities. Apart from this, change in the direction of regional emission transport to study site and the topology of Delhi are the possible reasons for the elevated pollution level, especially PM1 during winter in Delhi. This study also suggests that black carbon measurement techniques used in current study (optical absorbance with heated inlet and evolved carbon techniques) can be used as reference techniques to determine the site-specific calibration constant of optical photometers for urban aerosol.

Use of preoperative contrast-enhanced computed tomography in damage control strategy for blunt liver injury: A case report.

For patients with unstable abdominal trauma unresponsive to initial transfusion, the damage control strategy includes prompt hemostasis by open surgery and packing. Recently, a hybrid treatment that combines packing and transcatheter arterial embolization as a damage control strategy was reported to be effective; however, the indications and techniques are yet to be established. A 25-year-old male patient who was in shock due to severe liver injury after a traffic accident was brought to our emergency room by emergency services. After initial resuscitation, including resuscitative endovascular balloon occlusion of the aorta and blood transfusion, preoperative contrast-enhanced computed tomography indicated grade IV liver injury with active bleeding from the right hepatic artery. Damage control strategy with packing and subsequent transcatheter arterial embolization was determined to be useful. During treatment, bile leakage was observed. An endoscopic nasobiliary drainage tube was inserted, and the patient was treated conservatively. He was discharged on day 83 of hospitalization. Although using preoperative contrast-enhanced computed tomography before damage control surgery remains controversial, it can provide useful information to determine damage control strategy, including morphological evaluation of the injured area and the presence of active bleeding.

Heat stroke management during the COVID-19 pandemic: Recommendations from the experts in Japan (2nd edition).

Both coronavirus disease 2019 (COVID-19) and heat stroke have symptoms of fever or hyperthermia and the difficulty in distinguishing them could lead to a strain on emergency medical care. To mitigate the potential confusion that could arise from actions for preventing both COVID-19 spread and heat stroke, particularly in the context of record-breaking summer season temperatures, this work offers new knowledge and evidence that address concerns regarding indoor ventilation and indoor temperatures, mask wearing and heat stroke risk, and the isolation of older adults. Specifically, the current work is the second edition to the previously published guidance for handling heat stroke during the COVID-19 pandemic, prepared by the "Working group on heat stroke medical care during the COVID-19 epidemic," composed of members from four organizations in different medical and related fields. The group was established by the Japanese Association for Acute Medicine Heatstroke and Hypothermia Surveillance Committee. This second edition includes new knowledge, and conventional evidence gleaned from a primary selection of 60 articles from MEDLINE, one article from Cochrane, 13 articles from Ichushi, and a secondary/final selection of 56 articles. This work summarizes the contents that have been clarified in the prevention and treatment of infectious diseases and heat stroke to provide guidance for the prevention, diagnosis, and treatment of heat stroke during the COVID-19 pandemic.

Rapid detection of the MYD88 L265P mutation for pre- and intra-operative diagnosis of primary central nervous system lymphoma.

The myeloid differentiation primary response gene 88 (MYD88) L265P mutation is a disease-specific mutation of primary central nervous system lymphoma (PCNSL) among the central nervous system tumors. Accordingly, this mutation is considered a reliable diagnostic molecular marker of PCNSL. As the intra-operative diagnosis of PCNSL is sometimes difficult to achieve using histological examinations alone, intra-operative detection of the MYD88 L265P mutation could be effective for the accurate diagnosis of PCNSL. Herein, we aimed to develop a novel rapid genotyping system (GeneSoC) using real-time polymerase chain reaction (PCR) based on microfluidic thermal cycling technology. This real-time PCR system shortened the analysis time, which enabled the detection of the MYD88 L265P mutation within 15 min. Rapid detection of the MYD88 L265P mutation was performed intra-operatively using GeneSoC in 24 consecutive cases with suspected malignant brain tumors, including 10 cases with suspected PCNSL before surgery. The MYD88 L265P mutation was detected in eight cases in which tumors were pathologically diagnosed as PCNSL after the operation, while wild-type MYD88 was detected in 16 cases. Although two of the 16 cases with wild-type MYD88 were pathologically diagnosed as PCNSL after the operation, MYD88 L265P could be detected in all eight PCNSL cases harboring MYD88 L265P. The MYD88 L265P mutation could also be detected using cell-free DNA derived from the cerebrospinal fluid of two PCNSL cases. Detection of the MYD88 L265P mutation using GeneSoC might not only improve the accuracy of intra-operative diagnosis of PCNSL but also help the future pre-operative diagnosis through liquid biopsy of cerebrospinal fluid.

Smoking history and severe atrophic gastritis assessed by pepsinogen are risk factors for the prevalence of synchronous gastric cancers in patients with gastric endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND: No studies have evaluated the relationship between lifestyle and synchronous gastric cancers (SGCs) in patients with endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs). Using data from the Tohoku gastrointestinal (GI) study, we aimed to identify factors associated with SGCs. METHODS: Tohoku GI study is a multicenter prospective cohort study investigating the relationship between lifestyle and metachronous gastric cancers. Patients who had a schedule to undergo ESD for primary EGCs were enrolled. We used logistic regression analysis to examine the relationship of 15 candidate factors, including lifestyle, with the prevalence of SGCs in this study. RESULTS: Of 850 patients between 2016 and 2019, 16.0% (136 patients) had SGCs. In multivariate analysis, smoking history (odds ratio [OR], 1.93; p = 0.048) and severe atrophic gastritis assessed by pepsinogen (OR, 1.92; p = 0.004) were risk factors for the prevalence of SGCs. Regarding smoking, current smoking (OR, 2.33; p = 0.021), but not former smoking (OR, 1.76; p = 0.098), was a significant risk factor for its prevalence. In the stratified analysis, severe atrophic gastritis assessed by pepsinogen was a risk factor in patients without Helicobacter pylori (H. pylori) eradication (OR, 2.10; p = 0.002), but not a risk factor in those with H. pylori eradication (OR, 0.75; p = 0.737). CONCLUSION: Smoking history was a risk factor for the prevalence of SGCs in patients with ESD for EGCs, and severe atrophic gastritis assessed by pepsinogen was also a risk factor when H. pylori was not eradicated.

Treatment strategy after noncurative endoscopic resection for early gastric cancers in patients aged ≥ 85 years: a multicenter retrospective study in a highly aged area of Japan.

BACKGROUND: The guidelines recommend additional gastrectomy after noncurative endoscopic resection for early gastric cancers (EGCs). However, no additional treatment might be acceptable in some patients aged ≥ 85 years. We aimed to identify this patient group using the data in a highly aged area. METHODS: We enrolled patients aged ≥ 85 years after noncurative endoscopic resection for EGCs at 30 institutions of the Tohoku district in Japan between 2002 and 2017. Treatment selection and prognosis after noncurative endoscopic resection were investigated. Fourteen candidates were evaluated using the Cox model to identify risk factors for poor overall survival (OS) in patients with no additional treatment. RESULTS: Of 1065 patients aged ≥ 85 years, 143 underwent noncurative endoscopic resection. Despite the guidelines' recommendation, 88.8% of them underwent no additional treatment. The 5-year OS rates in those with additional gastrectomy and those with no additional treatment were 63.1 and 65.2%, respectively. Multivariate analysis showed independent risk factors for poor OS in patients with no additional treatment were the high-risk category in the eCura system (hazard ratio [HR], 2.91), Charlson comorbidity index (CCI) ≥ 3 (HR, 2.78), and male (HR, 2.04). In patients with no additional treatment, nongastric cancer-specific survival was low (69.0% in 5 years), whereas disease-specific survival rates were very high in the low- and intermediate-risk categories of the eCura system (100.0 and 97.1%, respectively, in 5 years). CONCLUSIONS: No additional treatment may be acceptable in the low- and intermediate-risk categories of the eCura system in patients aged ≥ 85 years with noncurative endoscopic resection for EGCs.

Long non-coding RNA lnc-CHAF1B-3 promotes renal interstitial fibrosis by regulating EMT-related genes in renal proximal tubular cells.

Renal interstitial fibrosis (RIF) is a common pathological manifestation of chronic kidney diseases. Epithelial-mesenchymal transition (EMT) of tubular epithelial cells is considered a major cause of RIF. Although long non-coding RNAs (lncRNAs) are reportedly involved in various pathophysiological processes, the roles and underlying molecular mechanisms of lncRNAs in the progression of RIF are poorly understood. In this study, we investigated the function of lncRNAs in RIF. Microarray assays showed that expression of the lncRNA lnc-CHAF1B-3 (also called claudin 14 antisense RNA 1) was significantly upregulated in human renal proximal tubular cells by both transforming growth factor-ß1 (TGF-ß1) and hypoxic stimulation, accompanied with increased expression of EMT-related genes. Knockdown of lnc-CHAF1B-3 significantly suppressed TGF-ß1-induced upregulated expression of collagen type I alpha 1, cadherin-2, plasminogen activator inhibitor-1, snail family transcriptional repressor I (SNAI1) and SNAI2. Quantitative reverse transcriptase PCR analyses of paraffin-embedded kidney biopsy samples from IgA nephropathy patients revealed lnc-CHAF1B-3 expression was correlated positively with urinary protein levels and correlated negatively with estimated glomerular filtration rate. In situ hybridization demonstrated that lnc-CHAF1B-3 is expressed only in proximal tubules. These findings suggest lnc-CHAF1B-3 affects the progression of RIF by regulating EMT-related signaling. Thus, lnc-CHAF1B-3 is a potential target in the treatment of RIF.

Prognostic Benefit of Additional Treatment After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Although additional treatment is considered for patients with esophageal squamous cell carcinoma (ESCC) invading into the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic submucosal dissection (ESD), the actual benefits of this method remain to be elucidated. AIMS: We aimed to evaluate the prognostic benefits of additional treatment in such patients. METHODS: Between 2006 and 2017, we enrolled patients with pT1a-MM/pT1b-SM ESCC after ESD at 21 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were compared between the additional treatment and follow-up groups after propensity score matching, to reduce the bias of baseline characteristics. A subgroup analysis was performed according to the pathological findings: category A, pT1a-MM but negative for lymphovascular invasion (LVI) and vertical margin (VM); category B, tumor invasion into the submucosa ≤ 200 µm but negative for LVI and VM; category C, others. RESULTS: Of 593 patients with pT1a-MM/pT1b-SM ESCC after ESD, 101 matched pairs were extracted after propensity score matching. The OSs were similar between the additional treatment and follow-up groups (80.6% vs. 78.6% in 5 years; P = 0.972). In a subgroup analysis, the OS in the additional treatment group was significantly lower than that in the follow-up group (65.7% vs. 95.2% in 5 years; P = 0.037) in category A, whereas OS did not significantly differ in category C (76.8% vs. 69.5% in 5 years; P = 0.360). CONCLUSIONS: Additional treatment after ESD in patients with pT1a-MM/pT1b-SM ESCC was not associated with an improved prognosis.