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BackgroundLactococcus lactis subsp. cremoris (YRC3780), which is isolated from kefir, has been associated with anti-allergic effects in humans. However, it remains unknown whether daily intake of YRC3780 attenuates the response to psychological stress in humans in parallel with changes to the gut microbiome. We examined the fundamental role of YRC3780 in the gut microbiome, stress response, sleep, and mental health in humans.MethodsEffects of daily intake of YRC3780 on the hypothalamic-pituitary-adrenal (HPA) axis response to acute psychological stress were investigated in a double-blind, placebo-controlled clinical trial involving 27 healthy young men (mean age and body mass index: 23.5 years and 21.5 kg/m2) who were randomly assigned to placebo (n = 13) or YRC3780 (n = 14) groups. The HPA axis response to acute psychological stress, the diurnal rhythm of HPA axis activity, and gut microbiome were assessed and compared between the two groups.ResultsThe results showed that daily intake of YRC3780 significantly lowered morning salivary cortisol levels compared with placebo. In addition, salivary cortisol levels following a social stress test significantly decreased +40 min after beginning the TSST in the YRC3780-treated group compared to placebo. There were no significant differences between the two groups in terms of actigraphy-based sleep quality, but the subjective sleep quality and mental health were significantly improved in the YRC3780-treated group compared to placebo.ConclusionsOur study suggests that daily intake of YRC3780 improves the HPA axis response to acute psychological stress, which might be associated with a decrease in morning cortisol levels.

INTRODUCTION:Underwater endoscopic mucosal resection (UEMR) and cold snare polypectomy (CSP) are novel endoscopic procedures for superficial nonampullary duodenal epithelial tumors (SNADET). However, consensus on how to use both procedures appropriately has not been established. In this study, we evaluated treatment outcomes of both procedures, including resectability.METHODS:In this single-center randomized controlled study conducted between January 2020 and June 2022, patients with SNADET ≤12 mm were randomly allocated to UEMR and CSP groups. The primary end point was sufficient vertical R0 resection (SVR0), which was defined as R0 resection including a sufficient submucosal layer. We compared treatment outcomes including SVR0 rate between groups.RESULTS:The SVR0 rate was significantly higher in the UEMR group than in the CSP group (65.6% vs 41.5%, P = 0.01). By contrast, the R0 resection rate was not significantly different between study groups (70.3% vs 61.5%, P = 0.29). The submucosal layer thickness was significantly greater in the UEMR group than in the CSP group (median 546 [range, 309-833] μm vs 69 [0-295] μm, P < 0.01). CSP had a shorter total procedure time (median 12 [range, 8-16] min vs 1 [1-3] min, P < 0.01) and fewer total bleeding events (9.4% vs 1.5%, P = 0.06).DISCUSSION:UEMR has superior vertical resectability compared with CSP, but CSP has a shorter procedure time and fewer bleeding events. Although CSP is preferable for most small SNADET, UEMR should be selected for lesions that cannot be definitively diagnosed as mucosal low-grade neoplasias.

Background and AimsEndoscopic mucosal resection (EMR) and Underwater EMR have been reported as effective endoscopic treatment for superficial duodenal tumor (SDET). However, a notable problem of EMR for SDET is technical difficulty for the lesion with non-lifting sign, and it of UEMR is that en bloc resection rate is relatively low. Therefore, we performed partial submucosal injection combining UEMR (PI-UEMR). The aim of this study is to evaluate feasibility and safety of this technique for duodenal tumor.MethodsThis is a prospective observational study from tertiary care hospital. We performed PI-UEMR in patients with SDET that is 13–20 mm in diameter, or less than 13 mm with technical difficulty for EMR and UEMR from January 2019 to March 2020. Primary outcome was en bloc resection rate. Secondary outcomes were R0 resection rate, mean total procedure time, intra- and post-procedure complication.ResultsThirty patients were included in this study. Mean age was 62 ± 12 years old. Three fourths lesions were located at anal side from major papilla. Median lesion size was 12 mm [IQR 10–16 mm]. Twenty-four cases were taken endoscopic biopsy in prior hospital and observed biopsy scar. En bloc resection rate was 97%. Ro resection rate was 83%. Mean total procedure time was 17 ± 12 min. And there was an only one case of complication, intra-procedure bleeding that was controllable endoscopically.ConclusionsPI-UEMR might be very useful and safe technique of endoscopic resection for SDET including relatively large lesions.

Long-term outcomes after endoscopic resection (ER) provide important information for the treatment of esophageal carcinoma. This study aimed to investigate the rates of survival and metastasis after ER of esophageal carcinoma. From 1995 to 2010, 570 patients with esophageal carcinoma were treated by ER. Of these, the 402 patients with squamous cell carcinoma (280 epithelial (EP) or lamina propria (LPM) cancer, 70 muscularis mucosa (MM) cancer, and 52 submucosal (SM) cancer) were included in our analysis. Seventeen patients had cancer invading into the submucosa up to 0.2 mm (SM1) and 35 patients had cancer invading into the submucosa more than 0.2 mm (SM2). The mean (range) follow-up time was 50 (4-187) months. The 5-year overall survival rates of patients with EP/LPM, MM, and SM cancer were 90.5, 71.1, and 70.8%, respectively (P=0.007). Multivariate analysis identified depth of invasion and age as independent predictors of survival, with hazard ratios of 3.6 for MM cancer and 3.2 for SM cancer compared with EP/LPM cancer, and 1.07 per year of age. The cumulative 5-year metastasis rates in patients with EP/LPM, MM, SM1, and SM2 cancer were 0.4, 8.7, 7.7, and 36.2%, respectively (P<0.001). Multivariate analysis identified depth of invasion as an independent risk factor for metastasis, with hazard ratios of 13.1 for MM, 40.2 for SM1, and 196.3 for SM2 cancer compared with EP/LPM cancer. The cumulative 5-year metastasis rates in patients with mucosal cancer with and without lymphovascular involvement were 46.7 and 0.7%, respectively (P<0.0001). The long-term risk of metastasis after ER was mainly associated with the depth of invasion. This risk should be taken into account when considering the indications for ER.

BackgroundDifferential diagnosis of superficial duodenal epithelial tumors (SDETs) and non-neoplastic lesions (NNLs) in duodenum by endoscopy is difficult. Here, we attempted to distinguish them by magnified endoscopic examination with image-enhanced endoscopy (IEE-ME).MethodsVarious IEE-ME findings of 95 SDETs who underwent endoscopic resection and 58 NNLs who underwent biopsy were retrospectively reviewed.ResultsWhen we compared the IEE-ME findings of SDETs and NNLs, the presence of demarcation line (DL) (97.9% vs. 79.3%, P = 0.0002), white opaque substance (WOS) (84.2% vs. 1.7%, P < 0.0001) and light blue crest (LBC) (93.7% vs. 32.8%, P < 0.0001) and the absence of enlarged marginal epithelium (EME) (98.9% vs. 62.1%, P < 0.0001) were significantly more frequent in SDETs than NNLs. When divided into each superficial structure, it was the most effective to evaluate the combination of WOS and LBC as SDET with open-loop structure (OLS), and the combination of DL and EME as SDET with closed-loop structure (CLS). However, LBC was excluded because of low inter- and intra-observer agreements. Finally, the sensitivity, specificity and accuracy for the diagnosis of SDETs were 88.4%, 98.3% and 92.2%, respectively, and we developed an algorithm for the differential diagnosis of duodenal lesions.ConclusionWe could distinguish SDET from NNL, diagnosed SDET as presence of WOS indicated OLS of superficial structure, and presence of DL and absence of EME indicated CLS of superficial structure.

Previous reports have shown favorable performance of artificial intelligence (AI) systems for diagnosing esophageal squamous cell carcinoma (ESCC) compared with endoscopists. However, these findings don’t reflect performance in clinical situations, as endoscopists classify lesions based on both magnified and non-magnified videos, while AI systems often use only a few magnified narrow band imaging (NBI) still images. We evaluated the performance of the AI system in simulated clinical situations. We used 25,048 images from 1433 superficial ESCC and 4746 images from 410 noncancerous esophagi to construct our AI system. For the validation dataset, we took NBI videos of suspected superficial ESCCs. The AI system diagnosis used one magnified still image taken from each video, while 19 endoscopists used whole videos. We used 147 videos and still images including 83 superficial ESCC and 64 non-ESCC lesions. The accuracy, sensitivity and specificity for the classification of ESCC were, respectively, 80.9% [95% CI 73.6–87.0], 85.5% [76.1–92.3], and 75.0% [62.6–85.0] for the AI system and 69.2% [66.4–72.1], 67.5% [61.4–73.6], and 71.5% [61.9–81.0] for the endoscopists. The AI system correctly classified all ESCCs invading the muscularis mucosa or submucosa and 96.8% of lesions ≥ 20 mm, whereas even the experts diagnosed some of them as non-ESCCs. Our AI system showed higher accuracy for classifying ESCC and non-ESCC than endoscopists. It may provide valuable diagnostic support to endoscopists.

BackgroundSecond cancers in patients with esophageal cancer (EC) are common and have a poor prognosis. We evaluated the incidence of second cancers at different sites by patients’ ages when their index ECs were diagnosed.MethodsThis study included patients who underwent endoscopic resection for superficial EC at our hospital between September 1994 and September 2011. Patients’ data, including sex, age at diagnosis, sequence of cancer incidence, cancer histology, and cancer site, were extracted from the cancer registry.ResultsOf 544 patients, 255 developed second cancers. Simultaneous head and neck cancers (HNCs) and other organ cancers (OCs) were, respectively, present in 15% (80/544) and 9.6% (52/544) of patients; and 30% (162/544) developed metachronous second cancers over a median follow-up period of 79.5 months (range 2–120), including 44 metachronous HNCs and 70 OCs. The cumulative incidence of metachronous HNCs was significantly higher in younger patients (< 60 years) than in older patients (≥ 60 years; P = 0.001), whereas the cumulative incidence of OCs was significantly higher in older patients than in younger patients (P = 0.03).ConclusionsThe incidence of second HNC after index EC was higher in younger-onset patients than in older-onset patients. We suggest that younger patients with EC should be carefully monitored for early detection of second HNC.

BackgroundA standard treatment method for pedunculated duodenal lesions has not yet been established. This study aimed to evaluate the feasibility of endoscopic resection (ER) for pedunculated duodenal lesions, especially for large lesions.MethodsThis study retrospectively reviewed cases of pedunculated duodenal lesions treated with ER at our institute between July 2010 and January 2021. We collected data on the clinical characteristics and treatment outcomes. In addition, the cases were divided based on the treatment provided for the lesion, i.e., the ESD and snare resection groups, and we compared the data between the two groups.ResultsThirty-eight cases were included in this study. The overall en bloc resection rate was 95%. No perforation occurred in any of the cases. There were 10 cases treated with ESD, which were considered difficult to achieve en bloc resection using snare forceps, and 28 cases treated with snare resection. Although the median lesion size was significantly larger in the ESD group than in the snare resection group (27 [range 23–66] vs. 19 [range 6–55] mm, P = 0.0052), treatment outcomes were not significantly different between the two groups. Among the 10 cases treated using ESD, en bloc resection was achieved in all cases, along with specimen retrieval without any perforations, despite the large size of the lesions.ConclusionER could be performed to achieve a high en bloc resection rate without any perforations in pedunculated duodenal lesions, even in extremely large (e.g., ≧ 60 mm) lesions, suggesting that ER is feasible and may be an alternative to surgical resection for large pedunculated duodenal lesions.