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The incidence of duodenal tumors (DTs) is increasing. However, the mechanisms underlying its development remain unclear. Environmental factors, including the microbiome and bile acids (BAs), are believed to influence tumor development. Therefore, we conducted a single-center, prospective, observational study to investigate the potential differences between patients with DTs and healthy controls (HCs) based on these factors. In addition, the BAs in the duodenal fluid were measured using liquid chromatography-tandem mass spectrometry. We recruited 41 patients and performed 16S rRNA-seq. There was no difference in the observed ASVs or PCoA plot of Bray-Curtis dissimilarity between the DTs and HCs. The lithocholic acid concentration was significantly lower in the DT group than in the control group. The ratio of CDCA to LCA was significantly higher in patients with DTs. No significant differences in microbiota were observed between DTs and HCs. In patients with DTs, the lithocholic acid concentration in duodenal was significantly lower than in HCs.
Subject(s)
Bile Acids and Salts , Duodenal Neoplasms , Duodenum , Gastrointestinal Microbiome , RNA, Ribosomal, 16S , Humans , Male , Bile Acids and Salts/metabolism , Female , Prospective Studies , Middle Aged , Duodenal Neoplasms/microbiology , Duodenal Neoplasms/metabolism , Duodenum/metabolism , Duodenum/microbiology , Aged , RNA, Ribosomal, 16S/genetics , Adult , Lithocholic Acid/metabolism , Microbiota , Case-Control StudiesABSTRACT
Water pressure method (WPM) is useful for colorectal endoscopic submucosal dissection (ESD), characterized not only by underwater conditions but also by active water pressure via the waterjet function. However, the extension of the colorectum by injecting excess water and contaminating the operative field by stool and bleeding have been issues. This study aimed to evaluate the feasibility of a novel perfusion system using a continuous liquid-suction catheter attachment (CLCA) in colorectal ESD with WPM. We retrospectively reviewed cases in which the perfusion system was used in colorectal ESD with WPM between August 2022 and September 2023. We evaluated clinical characteristics, treatment outcomes, volume of injection by the waterjet function, volume of suction by the endoscope and CLCA, and concentration of floating matter in the operative field over time. Thirty-one cases were enrolled. The median lesion size was 30 (range, 15-100) mm. In all cases, en bloc resection was achieved without perforation. The median injection volume was 2312 (range, 1234-13,866) g. The median suction volumes by the endoscope and CLCA were 918 (range, 141-3162) and 1147 (range, 254-11,222) g, respectively. The median concentration of floating matter in the operative field (measured in 15 cases) was 15.3 (range, 7.3-112) mg/mL when the endoscope arrived at the lesion and 8.0 (range, 3.2-16) mg/mL after endoscopically washing at the beginning of the ESD. It ranged from 7.6 to 13.4 mg/dL every 20 min during ESD. This perfusion system could prevent the extension of the lumen and maintain a good field of view in colorectal ESD with WPM.
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BACKGROUNDS AND AIMS: The Mayo endoscopic subscore (MES) is the most popular endoscopic disease activity measure of ulcerative colitis (UC). Artificial intelligence (AI)-assisted colonoscopy is expected to reduce diagnostic variability among endoscopists. However, no study has been conducted to ascertain whether AI-based MES assignments can help predict clinical relapse, nor has AI been verified to improve the diagnostic performance of non-specialists. METHODS: This open-label, prospective cohort study enrolled 110 patients with UC in clinical remission. The AI algorithm was developed using 74713 images from 898 patients who underwent colonoscopy at three centers. Patients were followed up after colonoscopy for 12 months, and clinical relapse was defined as a partial Mayo score >2. A multi-video, multi-reader analysis involving 124 videos was conducted to determine whether the AI system reduced the diagnostic variability among six non-specialists. RESULTS: The clinical relapse rate for patients with AI-based MES = 1 (24.5% [12/49]) was significantly higher (log-rank test, P = 0.01) than that for patients with AI-based MES = 0 (3.2% [1/31]). Relapse occurred during the 12-month follow-up period in 16.2% (13/80) of patients with AI-based MES = 0 or 1 and 50.0% (10/20) of those with AI-based MES = 2 or 3 (log-rank test, P = 0.03). Using AI resulted in better inter- and intra-observer reproducibility than endoscopists alone. CONCLUSIONS: Colonoscopy using the AI-based MES system can stratify the risk of clinical relapse in patients with UC and improve the diagnostic performance of non-specialists.
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Background/Aims: Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features. Methods: This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component. Results: Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%). Conclusions: This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.
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BACKGROUND: The relationship between primary sclerosing cholangitis (PSC) and biliary bile acids (BAs) remains unclear. Although a few studies have compared PSC biliary BAs with other diseases, they did not exclude the influence of cholestasis, which affects the composition of BAs. We compared biliary BAs and microbiota among patients with PSC, controls without cholestasis, and controls with cholestasis, based on the hypothesis that alterations in BAs underlie the pathophysiology of PSC. METHODS: Bile samples were obtained using endoscopic retrograde cholangiopancreatography from patients with PSC (n = 14), non-hepato-pancreato-biliary patients without cholestasis (n = 15), and patients with cholestasis (n = 13). RESULTS: The BA profiles showed that patients with PSC and cholestasis controls had significantly lower secondary BAs than non-cholestasis controls, as expected, whereas the ratio of cholic acid/chenodeoxycholic acid in patients with PSC was significantly lower despite cholestasis, and the ratio of (cholic acid + deoxycholic acid)/(chenodeoxycholic acid + lithocholic acid) in patients with PSC was significantly lower than that in the controls with or without cholestasis. The BA ratio in the bile of patients with PSC showed a similar trend in the serum. Moreover, there were correlations between the alteration of BAs and clinical data that differed from those of the cholestasis controls. Biliary microbiota did not differ among the groups. CONCLUSIONS: Patients with PSC showed characteristic biliary and serum BA compositions that were different from those in other groups. These findings suggest that the BA synthesis system in patients with PSC differs from that in controls and patients with other cholestatic diseases. Our approach to assessing BAs provides insights into the pathophysiology of PSC.
Subject(s)
Bile Acids and Salts , Cholangitis, Sclerosing , Cholestasis , Cholangitis, Sclerosing/blood , Cholangitis, Sclerosing/microbiology , Humans , Male , Bile Acids and Salts/blood , Bile Acids and Salts/analysis , Bile Acids and Salts/metabolism , Female , Middle Aged , Adult , Cholestasis/blood , Cholestasis/microbiology , Cholangiopancreatography, Endoscopic Retrograde , Case-Control Studies , Aged , Bile Ducts/microbiology , Bile/metabolism , Bile/microbiology , Chenodeoxycholic Acid/analysis , Cholic Acid/analysis , Cholic Acid/bloodABSTRACT
Objective: This study aimed to evaluate the use of video capsule endoscopy (VCE) in patients with obscure gastrointestinal bleeding (OGIB), compare cases of overt and occult OGIB, assess the rates of balloon-assisted enteroscopy (BAE) interventions and rebleeding, and identify predictive markers of positive VCE findings. Methods: Medical records of 430 patients who underwent VCE for OGIB between 2004 and 2022 were analyzed. Occult OGIB was defined as IDA or positive fecal occult blood, whereas overt OGIB was defined as clinically imperceptible bleeding. We retrospectively analyzed demographics, VCE findings based on Saurin classification (P0, P1, and P2), outcome of BAE interventions, and rebleeding rates. Results: A total of 253 patients with overt OGIB and 177 with occult OGIB were included. P1 findings were predominant in both groups, with a similar distribution. The percentage of patients receiving conservative therapy was higher in P1 than in P2 for both overt and occult OGIB. BAE was more frequently performed in P2 than in P1 VCE (83.0% vs. 35.3% in overt OGIB, 84.4% vs. 24.4% in occult OGIB). The percentage of positive findings and intervention in total BAE performed patients were comparable in P1 and P2 of overt OGIB, whereas these percentages in P2 were more than P1 of occult OGIB. Conclusion: VCE effectively identified OGIB lesions requiring intervention, particularly occult OGIB lesions, potentially reducing unnecessary BAE. Rebleeding rates varied according to the VCE findings, emphasizing the importance of follow-up in high-risk patients.
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Background and study aims Superficial pharyngeal cancers can be cured with transoral surgery (TOS), which preserves organ function and quality of life. Pharyngeal endoscopic submucosal dissection (ESD) is challenging to perform because of limited maneuverability and complex anatomical features. The water pressure method (WPM) is useful for natural traction techniques during ESD and is potentially useful for pharyngeal ESD. This study aimed to investigate the short-term outcomes of WPM-ESD for pharyngeal lesions. Patients and methods Therapeutic outcomes of patients who underwent WPM-ESD for pharyngeal lesions at Keio University between May 2019 and February 2022 were retrospectively analyzed. Results Twenty-one pharyngeal lesions treated with WPM-ESD were analyzed. Three lesions were located in the oropharynx and 18 in the hypopharynx. All ESD procedures were performed under general anesthesia. The endoscopic en bloc resection rate was 100%. The median procedure time was 15 minutes (range 4-45 minutes). All patients were successfully extubated on the day of ESD. No serious adverse events (AEs) related to WPM-ESDs were observed. None of the patients required nasogastric intubation, percutaneous endoscopic gastrostomy, or tracheotomy. The median fasting time and hospital stay were 2 days (range 2-5 days) and 6 days (range 6-10 days), respectively. All the histological results indicated squamous cell carcinoma. The complete histologic resection rate was 76.2%. Conclusions WPM-ESD achieved a high en bloc resection rate and short procedure time without serious AEs. Thus, it may be a useful treatment for pharyngeal lesions.
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BACKGROUND: Endoscopic healing is generally defined as Mayo endoscopic subscore (MES) ≤1 in ulcerative colitis (UC). However, patients with an MES of 1 are at higher relapse risk than those with an MES of 0. This study evaluated the therapeutic efficacy of proactive dose escalation of oral 5-aminosalicylic acid (5-ASA) in UC patients with an MES of 1. METHODS: An open-label, randomized controlled trial was conducted in 5 hospitals between 2018 and 2022. Ulcerative colitis patients in clinical remission under oral 5-ASA therapy and diagnosed as having an MESâ ofâ 1 were enrolled. Patients receiving maintenance therapy other than 5-ASA and immunomodulator were excluded. Patients were randomly assigned in a 1:1 ratio to receive either a dose-escalated (intervention) or constant dose (control) of 5-ASA. Concomitant immunomodulator was used as the stratification factor in the randomization. The primary end point was relapse within 1 year. The subgroup analysis was stratified for the use of immunomodulators. RESULTS: The full analysis set included 79 patients (39 intervention and 40 control). Immunomodulators were used in 20 (25.3%) patients. Relapse was less in the intervention group (15.4%) than the control group (37.5%; P = .026). In the subgroup with concomitant immunomodulators, relapse was also less in the intervention group (10.0%) than the control group (70.0%; P = .020). In patients without immunomodulators, the difference was not significant between 2 groups (intervention, 17.2%; control, 26.7%; P = .53). CONCLUSIONS: Dose escalation of 5-ASA reduced relapse within 1 year in UC patients in clinical remission with an MES of 1.
Dose escalation of 5-aminosalicylic acid for ulcerative colitis reduced relapse rate in patients in clinical remission with a Mayo endoscopic subscore of 1. The therapeutic efficacy was more evident in those whom immunomodulators were used.
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Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.
Subject(s)
Colitis, Ulcerative , Drugs, Chinese Herbal , Humans , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Indigo Carmine , Retrospective Studies , Drugs, Chinese Herbal/pharmacology , RecurrenceABSTRACT
BACKGROUND: Research on whether gastrointestinal symptoms correlate with the severity of Coronavirus Disease 2019 (COVID-19) has been inconclusive. This study aimed to clarify any associations between gastrointestinal symptoms and the prognosis of COVID-19. METHODS: We collected data from the Japanese nationwide registry for COVID-19 to conduct a retrospective cohort study. Data from 3498 Japanese COVID-19 patients, diagnosed at 74 facilities between February 2020 and August 2022, were analyzed in this study. Hospitalized patients were followed up until discharge or transfer to another hospital. Outpatients were observed until the end of treatment. Associations between gastrointestinal symptoms and clinical outcomes were investigated using multivariable-adjusted logistic regression models. RESULTS: The prevalence of diarrhea, nausea/vomiting, abdominal pain, and melena were 16.6% (581/3498), 8.9% (311/3498), 3.5% (121/3498), and 0.7% (23/3498), respectively. In the univariable analysis, admission to intensive care unit (ICU) and requirement for mechanical ventilation were less common in patients with diarrhea than those without (ICU, 15.7% vs. 20.6% (p = 0.006); mechanical ventilation, 7.9% vs. 11.4% (p = 0.013)). In the multivariable-adjusted analysis, diarrhea was associated with lower likelihood of ICU admission (adjusted odds ratio (aOR), 0.70; 95% confidence interval (CI), 0.53-0.92) and mechanical ventilation (aOR, 0.61; 95% CI, 0.42-0.89). Similar results were obtained in a sensitivity analysis with another logistic regression model that adjusted for 14 possible covariates with diarrhea (ICU; aOR, 0.70; 95% CI, 0.53-0.93; mechanical ventilation; aOR 0.62; 95% CI, 0.42-0.92). CONCLUSIONS: Diarrhea was associated with better clinical outcomes in COVID-19 patients.
Subject(s)
COVID-19 , Gastrointestinal Diseases , Humans , COVID-19/complications , COVID-19/epidemiology , SARS-CoV-2 , Retrospective Studies , Japan/epidemiology , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Diarrhea/epidemiology , Diarrhea/etiology , Patient Acuity , RegistriesABSTRACT
Patients with a long history of ulcerative colitis (UC) are at risk of developing a significant complication known as UC-associated neoplasia (UCAN). To reduce the risk of UCAN and the associated mortality, the current guidelines recommend initiating surveillance colonoscopy 8-10 years after confirmation of UC diagnosis. In recent years, advancements in endoscopic diagnostic technologies, including magnifying and image-enhancing techniques, have allowed for the production of high-contrast images that emphasize mucosal structures, vascular patterns, and color tones. Recently, image-enhanced endoscopy technologies have become available and offer the potential to improve the qualitative endoscopic assessment of UCAN. The use of high-definition chromoendoscopy enables the evaluation of subtle mucosal patterns in the colon. Magnifying narrow-band imaging facilitates the visualization of mucosal vascular structures. Texture and color enhancement imaging processes structure, color tone, and brightness aspects more appropriately, whereas linked color imaging optimizes the emphasis on mucosal and vascular redness. Both techniques are expected to excel in the depiction of subtle color variations and mucosal changes characteristic of UCAN. This article provides an overview of the current status and future challenges regarding the use of various image-enhanced endoscopy techniques in the diagnosis of UCAN.
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OBJECTIVES: Despite recent advances in endoscopic equipment and diagnostic techniques, early detection of ulcerative colitis-associated neoplasia (UCAN) remains difficult because of the complex background of the inflamed mucosa of ulcerative colitis and the morphologic diversity of the lesions. We aimed to describe the main diagnostic patterns for UCAN in our cohort, including lateral extension surrounding flat lesions. METHODS: Sixty-three lesions in 61 patients with flat-type dysplasia that were imaged with dye chromoendoscopy (DCE) were included in this analysis. These DCE images were analyzed to clarify the dye-chromoendoscopic imaging characteristics of flat dysplasia, and the lesions were broadly classified into dysplastic and nondysplastic mucosal patterns. RESULTS: Dysplastic mucosal patterns were classified into two types: small round patterns with round to roundish structures, and mesh patterns with intricate mesh-like structures. Lesions with a nondysplastic mucosal pattern were divided into two major types: a ripple-like type and a gyrus-like type. Of note, 35 lesions (55.6%) had a small round pattern, and 51 lesions (80.9%) had some type of mesh pattern. About 70% of lesions with small round patterns and 49% of lesions with mesh patterns were diagnosed as high-grade dysplasia or carcinoma, while about 30% of lesions with small round patterns and 51% of lesions with mesh patterns were diagnosed as low-grade dysplasia. CONCLUSION: When a characteristic mucosal pattern, such as a small round or mesh pattern, is found by DCE, the possibility of UCAN should be considered.
Subject(s)
Colitis, Ulcerative , Humans , Colitis, Ulcerative/diagnostic imaging , Colitis, Ulcerative/pathology , Indigo Carmine , Colonoscopy/methods , Carmine , HyperplasiaABSTRACT
OBJECTIVES: Although endoscopic submucosal dissection (ESD) training is important, quantitative assessments have not been established. This study aimed to explore a novel quantitative assessment system by analyzing an electrical surgical unit (ESU). METHODS: This was an ex vivo study. Step one: to identify the novel efficiency indicators, 20 endoscopists performed one ESD each, and we analyzed correlations between their resection speed and electrical status. Step two: to identify the novel precision indicators, three experts and three novices performed one ESD each, and we compared the stability of the electrical status. Step three: three novices in step two performed 19 additional ESDs, and we analyzed the learning curve using novel indicators. RESULTS: Step one: the percentage of total activation time (AT) of ESU in the procedure time (ß coefficient, 0.80; P < 0.01) and AT required for submucosal dissection (ß coefficient, -0.57; P < 0.01) were significantly correlated with the resection speed. Step two: coefficient of variation of the AT per one pulse (0.16 [range, 0.13-0.17] vs. 0.26 [range, 0.20-0.41], P = 0.049) and coefficient of variation of the peak electric power per pulse during mucosal incision (0.14 [range, 0.080-0.15] vs. 0.25 [range, 0.24-0.28], P = 0.049) were significantly lower in the experts than in the novices. Regarding the learning curve, the percentage of total AT of ESU in the procedure time and AT required for submucosal dissection had a trend of improvement. CONCLUSION: Novel indicators identified by analyzing ESU enable quantitative assessment for endoscopist's skill.
Subject(s)
Endoscopic Mucosal Resection , Animals , Endoscopic Mucosal Resection/methods , Gastric Mucosa/surgery , Models, Animal , Dissection/methods , Learning CurveABSTRACT
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.
Subject(s)
Duodenal Neoplasms , Endoscopic Mucosal Resection , Humans , Endoscopic Mucosal Resection/methods , Male , Female , Middle Aged , Duodenal Neoplasms/surgery , Duodenal Neoplasms/pathology , Aged , Treatment Outcome , Adult , Intestinal Mucosa/surgery , Intestinal Mucosa/pathology , Intestinal Polyps/surgery , Intestinal Polyps/pathology , Duodenoscopy/methods , Aged, 80 and overABSTRACT
OBJECTIVES: Fever and increased inflammatory responses sometimes occur following endoscopic resection (ER). However, the differences in causes according to the organ are scarcely understood, and several modified ER techniques have been proposed. Therefore, we conducted a comprehensive prospective study to investigate the cause of fever and increased inflammatory response across multiple organs after ER. METHODS: We included patients who underwent gastrointestinal endoscopic submucosal dissection (ESD) and duodenal endoscopic mucosal resection at our hospital between January 2020 and April 2022. Primary endpoints were fever and increased C-reactive protein (CRP) levels following ER. The secondary endpoints were risk factors for aspiration pneumonia. Blood tests and radiography were performed on the day after ER, and computed tomography was performed if the cause was unknown. RESULTS: Among the 822 patients included, aspiration pneumonia was the most common cause of fever and increased CRP levels after ER of the upper gastrointestinal tract (esophagus, 53%; stomach, 48%; and duodenum, 71%). Post-ER coagulation syndrome was most common after colorectal ESD (38%). On multivariate logistic regression analysis, lesions located in the esophagus (odds ratio [OR] 3.57; P < 0.001) and an amount of irrigation liquid of ≥1 L (OR 3.71; P = 0.003) were independent risk factors for aspiration pneumonia. CONCLUSIONS: Aspiration pneumonia was the most common cause of fever after upper gastrointestinal ER and post-ER coagulation syndrome following colorectal ESD. Lesions in the esophagus and an amount of irrigation liquid of ≥1 L were independent risk factors for aspiration pneumonia.
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OBJECTIVES: Existing endoscopic scores for ulcerative colitis (UC) objectively categorize disease severity based on the presence or absence of endoscopic findings; therefore, it may not reflect the range of clinical severity within each category. However, inflammatory bowel disease (IBD) expert endoscopists categorize the severity and diagnose the overall impression of the degree of inflammation. This study aimed to develop an artificial intelligence (AI) system that can accurately represent the assessment of the endoscopic severity of UC by IBD expert endoscopists. METHODS: A ranking-convolutional neural network (ranking-CNN) was trained using comparative information on the UC severity of 13,826 pairs of endoscopic images created by IBD expert endoscopists. Using the trained ranking-CNN, the UC Endoscopic Gradation Scale (UCEGS) was used to express severity. Correlation coefficients were calculated to ensure that there were no inconsistencies in assessments of severity made using UCEGS diagnosed by the AI and the Mayo Endoscopic Subscore, and the correlation coefficients of the mean for test images assessed using UCEGS by four IBD expert endoscopists and the AI. RESULTS: Spearman's correlation coefficient between the UCEGS diagnosed by AI and Mayo Endoscopic Subscore was approximately 0.89. The correlation coefficients between IBD expert endoscopists and the AI of the evaluation results were all higher than 0.95 (P < 0.01). CONCLUSIONS: The AI developed here can diagnose UC severity endoscopically similar to IBD expert endoscopists.
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BACKGROUND & AIMS: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression. METHODS: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model. RESULTS: The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains. CONCLUSIONS: D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.
Subject(s)
Cholangitis , Colitis, Ulcerative , Colitis , Inflammatory Bowel Diseases , Humans , Animals , Mice , Amino Acids , Proteobacteria , Escherichia coli , Inflammatory Bowel Diseases/drug therapy , Colitis/chemically induced , Colitis/drug therapy , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Alanine , Cholangitis/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic useABSTRACT
Intestinal intraepithelial lymphocytes (IELs) reside in the gut epithelial layer, where they help in maintaining intestinal homeostasis. Peripheral CD4+ T cells can develop into CD4+CD8αα+ IELs upon arrival at the gut epithelium via the lamina propria (LP). Although this specific differentiation of T cells is well established, the mechanisms preventing it from occurring in the LP remain unclear. Here, we show that chemokine receptor 9 (CCR9) expression is low in epithelial CD4+CD8αα+ IELs, but CCR9 deficiency results in CD4+CD8αα+ over-differentiation in both the epithelium and the LP. Single-cell RNA sequencing shows an enriched precursor cell cluster for CD4+CD8αα+ IELs in Ccr9-/- mice. CD4+ T cells isolated from the epithelium of Ccr9-/- mice also display increased expression of Cbfß2, and the genomic occupancy modification of Cbfß2 expression reveals its important function in CD4+CD8αα+ differentiation. These results implicate a link between CCR9 downregulation and Cbfb2 splicing upregulation to enhance CD4+CD8αα+ IEL differentiation.
Subject(s)
Intraepithelial Lymphocytes , Receptors, CCR , Animals , Mice , Cell Differentiation , Down-Regulation , Epithelium , Up-Regulation , Receptors, CCR/metabolismABSTRACT
BACKGROUND AND AIM: Multiple duodenal polyposis associated with familial adenomatous polyposis (FAP) is a high risk of duodenal cancer development. We evaluated the feasibility of intensive endoscopic resection that is a comprehensive treatment strategy combining multiple kinds of endoscopic treatments. METHODS: This is a retrospective observational study. From January 2012 to July 2022, a total of 28 consecutive patients in FAP who underwent endoscopic resection for multiple duodenal polyposis more than twice were included. Various endoscopic treatments, such as cold polypectomy (CP), endoscopic mucosal resection (EMR), underwater EMR (UEMR), endoscopic submucosal dissection (ESD), and endoscopic papillectomy (EP), were applied depending on lesions size and location. We evaluated individual information from patients' medical records, including patient characteristics, lesion characteristics, details of endoscopic treatment, pathologic findings, and Spigelman index (SI). We compared the differences in the number of treatments and observation periods with and without SI decrease. RESULTS: A total of 1040 lesions were removed by 138 sessions of endoscopic resections. The median follow-up period was 3.2 years. At the beginning of the endoscopic intervention, median SI was 9 (6-11) and the proportion of Spigelman stage (SS) IV was 61%. Repeated endoscopic treatments finally reduced SI in 26 patients (93%), and the proportion of SS IV significantly decreased to 13% with every endoscopic treatment. The mean SI change was -4.2 points per year (95% confidence interval: -0.6 to -5.9). There were no patients required surgical duodenectomy during the follow-up period. CONCLUSION: Intensive resection has a potential of downstaging duodenal lesions associated with FAP.
Subject(s)
Adenomatous Polyposis Coli , Adenomatous Polyps , Duodenal Neoplasms , Humans , Adenomatous Polyposis Coli/complications , Adenomatous Polyposis Coli/surgery , Duodenum/surgery , Duodenum/pathology , Endoscopy , Duodenal Neoplasms/complications , Duodenal Neoplasms/surgery , Duodenal Neoplasms/pathology , Retrospective StudiesABSTRACT
Background and study aims Colorectal endoscopic submucosal dissection (ESD) remains challenging for novice endoscopists. Not only the underwater conditions but also active use of water pressure with the water pressure method (WPM) can help widen the submucosal layer. This study aimed to clarify the usefulness of WPM in colorectal ESD, especially for novice endoscopists. Methods This study was ex vivo and enrolled three novices. Each endoscopist performed conventional ESD (C-ESD) and ESD with WPM (WPM-ESD) 10 times on an excised bovine rectum. The treatment outcomes were compared between the two groups. Results Median procedure time was significantly shorter in the WPM-ESD group than in the C-ESD group (54 minutes, interquartile range [IQR] 42-67 vs. 45 minutes, IQR 34-55, P = 0.035). Although no significant difference in the activation time of electrical surgical unit (ESU) during the procedure was noted, the interval time during the procedure at which the ESU was not activated was significantly shorter in the WPM-ESD group (52 minutes, IQR 40-65 vs. 42 minutes, IQR 32-52, P = 0.030) than in the C-ESD group. Moreover, the time required for the endoscope to enter the submucosa was significantly shorter in the WPM-ESD group than in the C-ESD group (8.0 minutes, IQR 6.0-10 vs. 5.0 minutes, IQR 3.0-6.0, P < 0.001). Conclusions The present study reveals that the WPM method significantly shortens the procedure times for novices in colorectal ESD, especially the interval time, which refers to the time spent creating the field of view, and the time required for the endoscope to enter the submucosa.