Chat agents respond more empathetically by using hearsay experience.

As the responses of chat dialogue systems have become more natural, the empathy skill of dialogue systems has become an important new issue. In text-based chat dialogue systems, the definition of empathy is not precise, and how to design the kind of utterance that improves the user's impression of receiving empathy is not clear since the main method used is to imitate utterances and dialogues that humans consider empathetic. In this study, we focus on the necessity of grasping an agent as an experienceable Other, which is considered the most important factor when empathy is performed by an agent, and propose an utterance design that directly conveys the fact that the agent can experience and feel empathy through text. Our system has an experience database including the system's pseudo-experience and feelings to show empathetic feelings. Then, the system understands the user's experiences and empathizes with the user on the basis of the system's experience database, in line with the dialogue content. As a result of developing and evaluating several systems with different ways of conveying the aforementioned rationale, we found that conveying the rationale as a hearsay experience improved the user's impression of receiving empathy more than conveying it as the system's own experience. Moreover, an exhaustive evaluation shows that our empathetic utterance design using hearsay experience is effective to improve the user's impression about the system's cognitive empathy.

Asymmetric communication: cognitive models of humans toward an android robot.

In the development of dialogue systems for android robots, the goal is to achieve human-like communication. However, subtle differences between android robots and humans are noticeable, leading even human-like android robots to be perceived differently. Understanding how humans accept android robots and optimizing their behavior is crucial. Generally, human customers have various expectations and anxieties when interacting with a robotic salesclerk instead of a human. Asymmetric communication arises when android robots treat customers like humans while customers treat robots as machines. Focusing on human-robot interaction in a tourist guide scenario, In this paper, we propose an asymmetric communication strategy that does not use estimation technology for preference information, but instead performs changing the agent's character in order to pretend to tailor to the customer. In line with this, we prepared an experimental method to evaluate asymmetric communication strategies, using video clips to simulate dialogues. Participants completed questionnaires without prior knowledge of whether the salesclerk was human-like or robotic. The method allowed us to assess how participants treated the salesclerk and the effectiveness of the asymmetric communication strategy. Additionally, during our demonstration in a dialogue robot competition, 29 visitors had a positive impression of the android robot's asymmetric communication strategy and reported a high level of satisfaction with the dialogue.

Temporary improvement of cognitive and behavioral scales for Dementia elderly by Shiritori word game with a dialogue robot: A pilot study.

Communication therapies based on conversations with caregivers, such as reminiscence therapy and music therapy, have been proposed to delay the progression of dementia. Although these therapies have been reported to improve the cognitive and behavioral functions of elderly people suffering from dementia, caregivers do not have enough time to spend on administering such communication therapies, especially in Japan where the workforce of caregivers is inadequate. Consequently, the progression of dementia in the elderly and the accompanying increased burden on caregivers has become a social problem. While the automation of communication therapy using robots and virtual agents has been proposed, the accuracy of both speech recognition and dialogue control is still insufficient to improve the cognitive and behavioral functions of the dementia elderly. In this study, we examine the effect of a Japanese word-chain game (Shiritori game) with an interactive robot and that of music listening on the maintenance and improvement of cognitive and behavioral scales [Mini-Mental State Examination (MMSE) and Dementia Behavior Disturbance scale (DBD)] of the dementia elderly. These activities can provide linguistic and phonetic stimuli, and they are simpler to implement than conventional daily conversation. The results of our Wizard-of-Oz-based experiments show that the cognitive and behavioral function scores of the elderly who periodically played the Shiritori game with an interactive robot were significantly improved over the elderly in a control group. On the other hand, no such effect was observed with the music listening stimuli. Our further experiments showed that, in the Shiritori intervention group, there was a ceiling on the increase in MMSE. The lower the MMSE before participating in the experiment, the greater the increase. Furthermore, greater improvement in DBD was observed when the participants actively played the Shiritori game. Since the Shiritori game is relatively easy to automate, our findings show the potential benefits of automating dementia therapies to maintain cognitive and behavioral functions.

[Ulcerative colitis complicated by multiple aseptic subcutaneous abscesses: a case report].

A woman in her 40s, previously diagnosed with ulcerative colitis (UC), presented with anterior chest pain. A CT scan of her chest and skin examination showed no abnormal findings. She was initially managed with antibacterial agents, but her chest pain worsened, she developed a fever, and there was an overall deterioration of her general condition. A repeat CT scan found abscesses on the anterior surface of her sternum and gluteal region, and colonoscopy found worsening UC lesions. Her multiple subcutaneous abscesses were aseptic, and she was diagnosed with pyoderma gangrenosum (PG), an extraintestinal manifestation of UC. Steroid treatment was initiated and her overall condition as well as her subcutaneous abscesses improved rapidly. There are only a few case reports of PG without skin manifestation but only subcutaneous aseptic abscesses. However, subcutaneous abscesses may progress to PG with skin ulcers if initial treatment is delayed. Even with non-specific clinical features, prompt diagnosis of relapsed UC with potential extraintestinal manifestations must be considered. This is a rare case and aims to highlight the importance of early diagnosis and treatment of PG, which is an extraintestinal manifestation of relapsed UC.

Different Impact of Resting Heart Rate on Adverse Events in Paroxysmal and Sustained Atrial Fibrillation　- The Fushimi AF Registry.

BACKGROUND: Heart rate (HR) is an important factor in atrial fibrillation (AF); however, it remains unclear whether the impact of HR differs between paroxysmal AF and sustained (persistent and permanent) AF.Methods and Results:The association of resting HR during AF with adverse events (composite of all-cause death, hospitalization for heart failure, stroke/systemic embolisms, myocardial infarction, and arrhythmic events) in 1,064 paroxysmal and 1,610 sustained AF patients from the Fushimi AF Registry were investigated. These patients were divided into 4 groups based on their resting HR; ≥110 beats/min (bpm), 80-109 bpm, 60-79 bpm, and <60 bpm. The number of patients in each group was 486, 400, 172, and 22 for paroxysmal AF, and 205, 734, 645, and 71 for sustained AF, respectively. Among patients with sustained AF, a HR ≥110 bpm was associated with a higher incidence of adverse events at 1 year and during the entire follow up (median of 1,833 days) (hazard ratio [95% confidence interval] compared with a HR of 60-79 bpm: 1.90 [1.31-2.72] at 1 year, 1.38 [1.10-1.72] during the entire follow up). Patients with a HR <60 bpm showed higher incidence of adverse events at 1 year; however, the incidence of adverse events did not differ among all HR groups of paroxysmal AF. CONCLUSIONS: Baseline HR was associated with adverse events in sustained AF, but not in paroxysmal AF.

Development of Ion Mobility Spectrometry with Novel Atmospheric Electron Emission Ionization for Field Detection of Gaseous and Blister Chemical Warfare Agents.

Drift tube ion mobility spectrometry with a novel atmospheric electron emission (AEE) source was developed for determination of gaseous and blister chemical warfare agents (CWAs) in negative mode. The AEE source was fabricated from an aluminum substrate electrode covered with 1 µm silver nanoparticle-dispersed silicone resin and a thin gold layer. This structure enabled stable tunneling electron emission upon the application of more than 11 V potential under atmospheric pressure. The reactant ion peak (RIP) was observed for the reduced mobility constant ( K0) of 2.18 and optimized at the charging voltage of 20 V. This RIP was assigned to O2- by using a mass spectrometer. Hydrogen cyanide was detected as a peak ( K0 = 2.47) that was discriminatively separated from the RIP (resolution = 1.4), with a limit of detection (LOD) of 0.057 mg/m3, and assigned to CN- and OCN-. Phosgene was detected as a peak ( K0 = 2.36; resolution = 1.2; and LOD = 0.6 mg/m3), which was assigned to Cl-. Lewisite 1 was detected as two peaks ( K0 = 1.68 and 1.34; LOD = 12 and 15 mg/m3). The K0 = 1.68 peak was ascribed to a mixture of adducts of molecules or the product of hydrolysis with oxygen or chloride. Cyanogen chloride, chlorine, and sulfur mustard were also well detected. The detection performance with the AEE source was compared with those under corona discharge and 63Ni ionizations. The advantage of the AEE source is the simple RIP pattern (only O2-), and the characteristic marker ions contribute to the discriminative CWAs detection.

Effect of geometrical configuration of reactor on a ZrP nano-dispersion process using ultrasonic irradiation.

This study investigated the position of ultrasonic irradiation source and reactor geometry on fragmentation rate of a layered compound, α-zirconium phosphate (α-ZrP). By numerically solving the acoustic pressure distribution using COMSOL Multiphysics®, it is clarified the mechanism whereby the operating factors influenced the α-ZrP dispersion to make a suggestion of guideline of the process design method. Two vessels made of glass with a flat-bottom and a spherical-bottom, respectively, were used. Although the flat-bottom vessel at lower horn position showed the best performance of fragmentation, the region of high acoustic pressure field in the flat bottom vessel sharply narrowed and the transmittance became prominently low. On the other hand, no significant difference of the transmittance value in the spherical bottom vessel between the cases of low and high horn positions could be observed and the spherical bottom vessel was robust for the horn position. These results suggest that not only the magnitude of acoustic pressure but also the size of high acoustic pressure region is also an important factor and a spherical bottom vessel is one of suitable shape which gives large size of high acoustic pressure region regardless of the horn position.

Middle ear mucosal regeneration by tissue-engineered cell sheet transplantation.

The recurrence of cholesteatoma after surgical treatment often occurs as a result of poor mucosal regeneration in the middle ear cavity and mastoid cavity and changes, such as granulation tissue formation, which impair gas exchange in the middle ear cavity. Conventional tympanoplasty often results in a lack of mucosal regeneration in the resected area of the mastoid cavity. In particular, mucosal regeneration in a poorly pneumatized mastoid cavity is extremely difficult. If the middle ear mucosa can be preserved or rapid postoperative regeneration of mucosa on the exposed bone surface can be achieved after middle ear surgery, the results of surgical treatment for otitis media, including cholesteatoma, can potentially be improved and the physiological function of the middle ear can be recovered. To overcome these limitations, we developed a novel treatment method combining tympanoplasty and autologous nasal mucosal epithelial cell sheet transplantation for postoperative regeneration of the middle ear mucosa. In clinical research, we endoscopically removed an approximately 10 × 10 mm2 piece of nasal mucosal tissue. Tissue-engineered autologous nasal mucosal epithelial cell sheets were fabricated by culturing the harvested cells in an aseptic environment in a good manufacturing practice-compliant cell processing facility. The cultivated cell sheets were transplanted, during tympanoplasty, onto the exposed bony surface of the attic of the tympanic and mastoid cavities where the mucosa had been lost. We performed this procedure on four patients with middle ear cholesteatoma and one patient with adhesive otitis media. All patients showed favorable postoperative course with no adverse events or complications and the patients' hearing ability post-transplantation remained good.

Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial.

AIMS: Substantial portion of early arrhythmia recurrence after catheter ablation for atrial fibrillation (AF) is considered to be due to irritability in left atrium (LA) from the ablation procedure. We sought to evaluate whether 90-day use of antiarrhythmic drug (AAD) following AF ablation could reduce the incidence of early arrhythmia recurrence and thereby promote reverse remodelling of LA, leading to improved long-term clinical outcomes. METHODS AND RESULTS: A total of 2038 patients who had undergone radiofrequency catheter ablation for paroxysmal, persistent, or long-lasting AF were randomly assigned to either 90-day use of Vaughan Williams class I or III AAD (1016 patients) or control (1022 patients) group. The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of class I or III AAD at 1 year, following the treatment period of 90 days post ablation. Patients assigned to AAD were associated with significantly higher event-free rate from recurrent atrial tachyarrhythmias when compared with the control group during the treatment period of 90 days [59.0 and 52.1%, respectively; adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.73-0.96; P = 0.01]. However, there was no significant difference in the 1-year event-free rates from the primary endpoint between the groups (69.5 and 67.8%, respectively; adjusted HR 0.93; 95% CI 0.79-1.09; P = 0.38). CONCLUSION: Short-term use of AAD for 90 days following AF ablation reduced the incidence of recurrent atrial tachyarrhythmias during the treatment period, but it did not lead to improved clinical outcomes at the later phase.

Brush biopsy of human oral mucosal epithelial cells as a quality control of the cell source for fabrication of transplantable epithelial cell sheets for regenerative medicine.

Autologous oral mucosal epithelial cell sheets have been used for treating epithelial defects such as cornea and esophagus. The cell source of patients' oral mucosal epithelial cell sheet should be examined in normality because it has individual difference. In this study, oral mucosal epithelial cells were less invasively collected by brush biopsy from the buccal, gingival, labial, and palate mucosa of four healthy volunteer donors without anesthesia, and analyzed the keratin expressions by western blotting and the obtained results were compared with those by immunohistochemistry of each of the native tissues. All of the oral mucosal epithelial cells expressed keratin 4 (K4) and K13, which were mucosal stratified squamous epithelial cell markers. K1 and K10, keratinized epithelial cell markers, were also detected in keratinized tissues such as gingival and palate mucosa. The markers of epithelial basal cells such as p63 and K15 were not detected by brush biopsy-western blotting. Although this method does not include basal layers of oral mucosa, protein expressions of upper layer of lesion area are different from normal. Therefore, brush biopsy-western blotting was extremely less invasive and would contribute to quality control of the fabrication of autologous oral mucosal epithelial cell sheets.

Adenosine triphosphate-guided pulmonary vein isolation for atrial fibrillation: the UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate (UNDER-ATP) trial.

AIMS: Most of recurrent atrial tachyarrhythmias after pulmonary vein isolation (PVI) for atrial fibrillation (AF) are due to reconnection of PVs. The aim of the present study was to evaluate whether elimination of adenosine triphosphate (ATP)-induced dormant PV conduction by additional energy applications during the first ablation procedure could reduce the incidence of recurrent atrial tachyarrhythmias. METHODS AND RESULTS: We randomly assigned 2113 patients with paroxysmal, persistent, or long-lasting AF to either ATP-guided PVI (1112 patients) or conventional PVI (1001 patients). The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of Vaughan Williams class I or III antiarrhythmic drugs at 1 year with the blanking period of 90 days post ablation. Among patients assigned to ATP-guided PVI, 0.4 mg/kg body weight of ATP provoked dormant PV conduction in 307 patients (27.6%). Additional radiofrequency energy applications successfully eliminated dormant conduction in 302 patients (98.4%). At 1 year, 68.7% of patients in the ATP-guided PVI group and 67.1% of patients in the conventional PVI group were free from the primary endpoint, with no significant difference (adjusted hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.74-1.09; P = 0.25). The results were consistent across all the prespecified subgroups. Also, there was no significant difference in the 1-year event-free rates from repeat ablation for any atrial tachyarrhythmia between the groups (adjusted HR 0.83; 95% CI 0.65-1.08; P = 0.16). CONCLUSION: In the catheter ablation for AF, we found no significant reduction in the 1-year incidence of recurrent atrial tachyarrhythmias by ATP-guided PVI compared with conventional PVI.

Non-Triple Helical Form of Type IV Collagen α1 Chain.

Type IV collagen with a triple-helical structure composed of three α chains is a major component of basement membrane. Previously, we reported that non-triple helical form of type IV collagen α1 chain (NTHα1(IV)) was isolated from human placenta and the culture media of human cells. In the present study, we report on the localization of NTH α1(IV) with a monoclonal antibody #370, exclusively reactive for the nascent chain, in the rabbit tissues. The staining was found on the basement membrane of blood vessels, of endomysium, of nerve, and of kidney but not on epithelial basement membrane. In a rabbit angiogenic model, #370 antibody staining was exclusively observed in neovascular tip region of endothelial cells, where no staining with anti-type IV collagen antibody was seen. Distinct localizations suggest that NTHα1(IV) is produced and stably deposited in endothelial cells and the surroundings under physiological conditions with some physiological roles in relation to the dynamics of vascular system.

Remodeling of epithelial cells and basement membranes in a corneal deficiency model with long-term follow-up.

The ocular surface consists of the cornea, conjunctiva, and the limbus that is located in the transitional zone between the cornea and conjunctiva. The corneal epithelial cells are generated through the mitosis of corneal epithelial stem cells in the limbus. This study investigated a rabbit corneal deficiency model prepared by the surgical removal of the corneal and limbal epithelia, which express cytokeratin 12 (K12). After the surgery, K13-expressing conjunctival epithelium migrated onto the corneal surface and completely covered the surface, leading to neovascularization and corneal opacification. However, at 24 and 48 weeks after the surgery, K12-expressing cornea-like cells reappeared on the model ocular surface. These cells formed an island surrounded by invaded conjunctiva and were isolated from the limbus. Interestingly, in the 24-week model surface, α1(IV) and α2(IV) collagen chains, which are normally found in the basement membrane of the native limbus and conjunctiva, and not in the cornea, were continuously deposited throughout the entire basement membrane, including the basement membrane under cornea-like cells. By contrast, in the 48-week model surface, α1(IV) and α2(IV) collagen chains were absent from the basement membrane beneath the central part of cornea-like cells and were localized below the invaded conjunctiva and the transitional zone between cornea-like cells and the invaded conjunctiva, which had similar distribution to the native ocular basement membrane. Moreover, K12, K14, p63, vimentin, and α1(IV) and α2(IV) collagen chains, which are colocalized in the native limbus, were all present at the transitional zone of the 48-week model surface. Therefore, a limbus-like structure appeared to be reconstructed on the surface of the 48-week model as a stem cell niche. This study should aid in the understanding of human corneal deficiency, the correlation between the epithelial cell phenotype and the composition of the basement membrane, and the epithelial stem cell niche.

The effect of transplantation of nasal mucosal epithelial cell sheets after middle ear surgery in a rabbit model.

Postoperative regeneration of the middle ear mucosa and pneumatization of the middle ear cavity are of great importance after middle ear surgery. This study developed a new method to transplant autologous nasal mucosal epithelial cell sheets into the damaged middle ear cavity. The aim of this study was to evaluate postoperative healing after the transplantation of the cell sheets. Rabbit nasal mucosal epithelial cell sheets were fabricated on a temperature-responsive culture dish, and transplanted into the damaged middle ear of rabbit, which was surgically created. The healing of middle ears was evaluated by histology and X-ray computed tomography after transplantation. Functional evaluation was performed by measuring the maximum middle ear total pressure reflecting a trans-mucosal gas exchange function. Two control groups were used: the normal control group and the mucosa-eliminated control group. Transplantation of cell sheets suppressed the bone hyperplasia and the narrowing of pneumatic space in the middle ear cavity compared with the mucosa-eliminated control group. The mucosal gas exchange function was also better in the cell sheet-transplanted group. Nasal mucosal epithelial cell sheet was confirmed to be useful as an effective graft material after middle ear surgery and hopefully become a novel therapy in the future.

Maintenance and distribution of epithelial stem/progenitor cells after corneal reconstruction using oral mucosal epithelial cell sheets.

We assessed the maintenance and distribution of epithelial stem/progenitor cells after corneal reconstruction using tissue-engineered oral mucosal cell sheets in a rat model. Oral mucosal biopsy specimens were excised from green fluorescent protein (GFP) rats and enzymatically treated with Dispase II. These cells were cultured on inserts with mitomycin C-treated NIH/3T3 cells, and the resulting cell sheets were harvested. These tissue-engineered cell sheets from GFP rats were transplanted onto the eyes of a nude rat limbal stem cell deficiency model. Eight weeks after surgery, ocular surfaces were completely covered by the epithelium with GFP-positive cells. Transplanted corneas expressed p63 in the basal layers and K14 in all epithelial layers. Epithelial cells harvested from the central and peripheral areas of reconstructed corneas were isolated for a colony-forming assay, which showed that the colony-forming efficiency of the peripheral epithelial cells was significantly higher than that of the central epithelial cells 8 weeks after corneal reconstruction. Thus, in this rat model, the peripheral cornea could maintain more stem/progenitor cells than the central cornea after corneal reconstruction using oral mucosal epithelial cell sheets.

A case of cap polyposis remission by betamethasone enema after antibiotics therapy including Helicobacter pylori eradication.

We report the case of a 58-year-old woman who was referred to our hospital due to frequent bloody mucus diarrhea. She was diagnosed with cap polyposis based on typical endoscopic and histological findings. Colonoscopy revealed multiple, reddish, mucus-capped polypoid lesions from the rectum to the sigmoid colon. A pathological examination revealed that the polyps were covered by erosive and inflamed granulation tissue with decreased crypt cells. Laboratory data indicated positive values for Helicobacter pylori immunoglobulin G antibody and hypoproteinemia. Metronidazole, H. pylori eradication, and levofloxacin therapies were not effective; however, the subsequent administration of betamethasone enema dramatically improved the clinical symptoms and endoscopic findings. The hypoproteinemia was normalized after the therapy. The dose of the betamethasone enema was tapered gradually, and no recurrence was observed 6 months after discontinuation of the treatment. This case suggests that betamethasone enema may be considered as the second treatment choice for cap polyposis patients after H. pylori eradication, metronidazole or levofloxacin therapy.

Evidence of the survival of ectopically transplanted oral mucosal epithelial stem cells after repeated wounding of cornea.

Tissue engineering has become an essential tool in the development of regenerative medicine. We have developed cell sheet-based techniques for use in regenerative medicine that have already been successfully used in clinical applications. Native corneal epithelium is produced from limbal stem cells located in the transition zone between the cornea and the bulbar conjunctiva. Limbal stem cell deficiency (LSCD) is a severe defect of the limbal stem cells leading to vision loss due to conjunctival epithelial invasion and neovascularization. Rabbit LSCD models were treated with transplantable autologous oral mucosal epithelial cell (OEC) sheets fabricated on temperature-responsive cell culture surfaces, after which, the ocular surfaces were clear and smooth with no observable defects. The central part of the reconstructed ocular surface was scraped and wounded, after which proliferating epithelial cells covered the scraped area within a few days. The ocular surfaces were clear and smooth even after repeated scrapings and consisted of only OECs or heterogeneously mixed with corneal epithelial cells. This study demonstrates that transplanted cell sheets containing oral mucosal epithelial stem cells could reconstruct the ocular surface to maintain cornea homeostasis; moreover, they provide an ideal microenvironment to support the proliferation of remaining native limbal stem cells.

Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder.

BACKGROUND: N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the ß1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT2 gallbladder carcinoma with simple in vitro experiments. METHODS: Ninety patients with pT2 gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA. RESULTS: Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis. CONCLUSIONS: GnT-V expression in the subserosal layer of pT2 gallbladder carcinoma is correlated with the aggressiveness of the disease.

Risk factors for submucosal and lymphovascular invasion in gastric cancer looking indicative for endoscopic submucosal dissection.

BACKGROUND: Submucosal and lymphovascular (SM/LV) invasions of early gastric cancer (EGC) are difficult to diagnose accurately prior to endoscopic submucosal dissection (ESD), and are occasionally found in resected specimens, requiring additional gastrectomy and lymph node dissection. We performed a retrospective study to determine the risk factors for SM/LV invasions. METHODS: We analyzed clinicopathological data (age, sex, cancer location, gross morphology, multifocality, tumor size, histological differentiation, depth of invasion, and the presence or absence of lymphovascular invasion) in patients receiving ESD between 2007 and 2012 and presenting with EGC of 2.0 cm or smaller in size, a differentiated-type adenocarcinoma, and without ulceration. RESULTS: Of 208 lesions consecutively resected by ESD, 143 lesions in 132 patients were included in this study. Submucosal and lymphovascular invasions were detected in 16 lesions. Multivariate analysis revealed three independent risk factors for SM/LV invasions: dominant histology of moderately-differentiated or papillary adenocarcinoma, gross type of 0-IIa + IIc or IIc + IIa, and tumor size of ≥1.5 cm. Lesions exhibiting more than two of these three risk factors were associated with having a 47 % increased incidence of SM/LV invasion (odds ratio 15; 95 % confidence interval 4.6-49.0; P < 0.0001). CONCLUSIONS: Moderately-differentiated or papillary adenocarcinoma, 0-IIa + IIc or IIc + IIa, and a tumor size of ≥1.5 cm were identified as independent risk factors for SM/LV invasion among EGCs which appeared to be an endoscopically good indication for ESD. Careful surveillances including endoscopic ultrasonography or enhanced computed tomography might be needed for high risk patients before ESD.